PMID-sentid	Pub_year	Sent_text	compound_name	comp_offset	prot_official_name	organism	prot_offset
24717679-0	2014	Involvement of catalase in the protective benefits of metformin in mice with oxidative liver injury.	Metformin	54-63	catalase	Mus musculus	15-23
24915260-15	2014	CONCLUSIONS AND RELEVANCE: Among patients with diabetes who were receiving metformin, the addition of insulin vs a sulfonylurea was associated with an increased risk of a composite of nonfatal cardiovascular outcomes and all-cause mortality.	Metformin	75-84	insulin	Homo sapiens	102-109
24915260-0	2014	Association between intensification of metformin treatment with insulin vs sulfonylureas and cardiovascular events and all-cause mortality among patients with diabetes.	Metformin	39-48	insulin	Homo sapiens	64-71
24915260-2	2014	OBJECTIVE: To compare time to acute myocardial infarction (AMI), stroke, or death in a cohort of metformin initiators who added insulin or a sulfonylurea.	Metformin	97-106	insulin	Homo sapiens	128-135
24792694-3	2014	Under these conditions, the migration time of metformin is 35s and the LOD is 0.3 muM.	Metformin	46-55	latexin	Homo sapiens	82-85
24717679-6	2014	In addition, metformin treatment dose-dependently enhanced the activities of catalase (CAT) and decreased CCl4-induced elevation of hepatic H2O2 levels, but it had no obvious effects on the protein level of CAT.	Metformin	13-22	catalase	Mus musculus	77-85
24717679-6	2014	In addition, metformin treatment dose-dependently enhanced the activities of catalase (CAT) and decreased CCl4-induced elevation of hepatic H2O2 levels, but it had no obvious effects on the protein level of CAT.	Metformin	13-22	catalase	Mus musculus	87-90
24717679-8	2014	A molecular docking analysis indicated that metformin might interact with CAT via hydrogen bonds.	Metformin	44-53	catalase	Mus musculus	74-77
24896641-0	2014	Metformin attenuates palmitate-induced endoplasmic reticulum stress, serine phosphorylation of IRS-1 and apoptosis in rat insulinoma cells.	Metformin	0-9	insulin receptor substrate 1	Rattus norvegicus	95-100
24717679-9	2014	These data suggested that metformin effectively alleviated CCl4-induced oxidative liver injury in mice and these hepatoprotective effects might be associated with CAT.	Metformin	26-35	catalase	Mus musculus	163-166
24899137-7	2014	The primary objective of the METFORMIN study is to determine the effect of adding metformin treatment to lifestyle intervention in reducing BMI in obese adolescents with insulin resistance.	Metformin	29-38	insulin	Homo sapiens	170-177
25333031-2	2014	Metformin is one of the longest established oral insulin sensitising agents.	Metformin	0-9	insulin	Homo sapiens	49-56
24899137-7	2014	The primary objective of the METFORMIN study is to determine the effect of adding metformin treatment to lifestyle intervention in reducing BMI in obese adolescents with insulin resistance.	Metformin	82-91	insulin	Homo sapiens	170-177
24627290-10	2014	Co-therapy of gemigliptin and metformin showed additional effects by increasing plasma active GLP-1 concentrations and lowering serum glucose levels.	Metformin	30-39	glucagon	Homo sapiens	94-99
24837407-3	2014	The combination of vildagliptin with the biguanide metformin is of particular interest because of its complementary mode of action, addressing insulin resistance, alpha- and beta cell function in the islet of the pancreas.	Metformin	51-60	insulin	Homo sapiens	143-150
24683044-7	2014	Modulation by metformin of 42 of 1281 pulmonary microRNAs in smoke-free mice highlighted a variety of mechanisms, including modulation of AMPK, stress response, inflammation, NFkappaB, Tlr9, Tgf, p53, cell cycle, apoptosis, antioxidant pathways, Ras, Myc, Dicer, angiogenesis, stem cell recruitment, and angiogenesis.	Metformin	14-23	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	175-183
24129850-4	2014	In the current study, we showed that activation of AMPK by metformin caused decrease of AR protein level through suppression of AR mRNA expression and promotion of AR protein degradation, demonstrating that AMPK activation is upstream of AR downregulation.	Metformin	59-68	androgen receptor	Homo sapiens	88-90
24129850-4	2014	In the current study, we showed that activation of AMPK by metformin caused decrease of AR protein level through suppression of AR mRNA expression and promotion of AR protein degradation, demonstrating that AMPK activation is upstream of AR downregulation.	Metformin	59-68	androgen receptor	Homo sapiens	128-130
24129850-4	2014	In the current study, we showed that activation of AMPK by metformin caused decrease of AR protein level through suppression of AR mRNA expression and promotion of AR protein degradation, demonstrating that AMPK activation is upstream of AR downregulation.	Metformin	59-68	androgen receptor	Homo sapiens	128-130
24129850-4	2014	In the current study, we showed that activation of AMPK by metformin caused decrease of AR protein level through suppression of AR mRNA expression and promotion of AR protein degradation, demonstrating that AMPK activation is upstream of AR downregulation.	Metformin	59-68	androgen receptor	Homo sapiens	128-130
24129850-5	2014	We also showed that inhibition of AR function by an anti-androgen or its siRNA enhanced AMPK activation and growth inhibition whereas overexpression of AR delayed AMPK activation and increased prostate cancer cellular resistance to metformin treatment, suggesting that AR suppresses AMPK signaling-mediated growth inhibition in a feedback mechanism.	Metformin	232-241	androgen receptor	Homo sapiens	152-154
24129850-5	2014	We also showed that inhibition of AR function by an anti-androgen or its siRNA enhanced AMPK activation and growth inhibition whereas overexpression of AR delayed AMPK activation and increased prostate cancer cellular resistance to metformin treatment, suggesting that AR suppresses AMPK signaling-mediated growth inhibition in a feedback mechanism.	Metformin	232-241	androgen receptor	Homo sapiens	152-154
24674102-4	2014	We present a case of long term metformin use resulting in vitamin B12 deficiency.	Metformin	31-40	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	66-69
24943970-0	2014	The relationship between anticancer effect of metformin and the transcriptional regulation of certain genes (CHOP, CAV-1, HO-1, SGK-1 and Par-4) on MCF-7 cell line.	Metformin	46-55	DNA damage inducible transcript 3	Homo sapiens	109-113
24943970-0	2014	The relationship between anticancer effect of metformin and the transcriptional regulation of certain genes (CHOP, CAV-1, HO-1, SGK-1 and Par-4) on MCF-7 cell line.	Metformin	46-55	caveolin 1	Homo sapiens	115-120
24943970-3	2014	It is suggested that metformin has an anticancer and antiproliferative effect and affects the apoptosis by activating the AMPK and inhibiting the mammalian target of rapamycin (mTOR).	Metformin	21-30	mechanistic target of rapamycin kinase	Homo sapiens	146-175
24943970-3	2014	It is suggested that metformin has an anticancer and antiproliferative effect and affects the apoptosis by activating the AMPK and inhibiting the mammalian target of rapamycin (mTOR).	Metformin	21-30	mechanistic target of rapamycin kinase	Homo sapiens	177-181
24972480-7	2014	Logistic regression models were developed to explore the association between B12 deficiency and metformin dose.	Metformin	96-105	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	77-80
24639469-3	2014	Our previous studies have shown that phosphorylation of CBP at S436 is important for the regulation of hepatic glucose production by metformin.	Metformin	133-142	CREB binding protein	Homo sapiens	56-59
24639469-5	2014	These data suggests that CBP phosphorylation in WBCs may be used as a biomarker of metformin action in the liver.	Metformin	83-92	CREB binding protein	Homo sapiens	25-28
24972480-13	2014	It was observed that OP who consumed high doses of metformin had 1.9 times the risk of B12 deficiency (OR: 1.9; 95%CI: 1,08- 3,30).	Metformin	51-60	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	87-90
24972480-14	2014	CONCLUSION: These results show a strong association between high doses of metformin and low levels of vitamin B12 in diabetic elderly.	Metformin	74-83	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	110-113
24997826-0	2014	Effect of piglitazone and metformin on retinol-binding protein-4 and adiponectin in patients with type 2 diabetes mellitus complicated with non-alcohol fatty acid liver diseases.	Metformin	26-35	adiponectin, C1Q and collagen domain containing	Homo sapiens	69-80
24788596-5	2014	Furthermore, metformin sensitized ICC cells to certain chemotherapeutic agents, such as sorafenib, 5-fluorouracil and As2O3 by targeting the AMPK/mTOR/HIF-1alpha/MRP1 pathway and ERK.	Metformin	13-22	ATP binding cassette subfamily C member 1	Homo sapiens	162-166
24788596-5	2014	Furthermore, metformin sensitized ICC cells to certain chemotherapeutic agents, such as sorafenib, 5-fluorouracil and As2O3 by targeting the AMPK/mTOR/HIF-1alpha/MRP1 pathway and ERK.	Metformin	13-22	mitogen-activated protein kinase 1	Homo sapiens	179-182
24905518-0	2014	Metformin affects macrophages" phenotype and improves the activity of glutathione peroxidase, superoxide dismutase, catalase and decreases malondialdehyde concentration in a partially AMPK-independent manner in LPS-stimulated human monocytes/macrophages.	Metformin	0-9	catalase	Homo sapiens	116-124
24504677-3	2014	The biomolecular characteristics of tumors, such as appropriate expression of organic cation transporters or genetic alterations including p53, K-ras, LKB1, and PI3K may impact metformin"s anticancer efficiency.	Metformin	177-186	tumor protein p53	Homo sapiens	139-142
24788596-5	2014	Furthermore, metformin sensitized ICC cells to certain chemotherapeutic agents, such as sorafenib, 5-fluorouracil and As2O3 by targeting the AMPK/mTOR/HIF-1alpha/MRP1 pathway and ERK.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	146-150
24788596-5	2014	Furthermore, metformin sensitized ICC cells to certain chemotherapeutic agents, such as sorafenib, 5-fluorouracil and As2O3 by targeting the AMPK/mTOR/HIF-1alpha/MRP1 pathway and ERK.	Metformin	13-22	hypoxia inducible factor 1 subunit alpha	Homo sapiens	151-161
24844651-6	2014	gamma-H2AX, as an indicator of DSBs, had significantly more foci per cell in the group treated with metformin and radiation compared to groups treated with metformin or irradiation, respectively.	Metformin	100-109	H2A.X variant histone	Mus musculus	0-10
24844651-6	2014	gamma-H2AX, as an indicator of DSBs, had significantly more foci per cell in the group treated with metformin and radiation compared to groups treated with metformin or irradiation, respectively.	Metformin	156-165	H2A.X variant histone	Mus musculus	0-10
24844651-8	2014	In addition, the reduced phosphorylation of DNA-PKcs caused by EGFR/PI3K/Akt down-regulation is essential for metformin to induce radiosensitivity in prostate cancer cells.	Metformin	110-119	thymoma viral proto-oncogene 1	Mus musculus	73-76
24644001-0	2014	Metformin sensitizes EGFR-TKI-resistant human lung cancer cells in vitro and in vivo through inhibition of IL-6 signaling and EMT reversal.	Metformin	0-9	epidermal growth factor receptor	Homo sapiens	21-25
24858012-0	2014	Metformin induces apoptosis and cell cycle arrest mediated by oxidative stress, AMPK and FOXO3a in MCF-7 breast cancer cells.	Metformin	0-9	forkhead box O3	Homo sapiens	89-95
24858012-8	2014	In MCF-7 cells metformin decreased the activation of IRbeta, Akt and ERK1/2, increased p-AMPK, FOXO3a, p27, Bax and cleaved caspase-3, and decreased phosphorylation of p70S6K and Bcl-2 protein expression.	Metformin	15-24	AKT serine/threonine kinase 1	Homo sapiens	61-64
24858012-8	2014	In MCF-7 cells metformin decreased the activation of IRbeta, Akt and ERK1/2, increased p-AMPK, FOXO3a, p27, Bax and cleaved caspase-3, and decreased phosphorylation of p70S6K and Bcl-2 protein expression.	Metformin	15-24	mitogen-activated protein kinase 3	Homo sapiens	69-75
24858012-8	2014	In MCF-7 cells metformin decreased the activation of IRbeta, Akt and ERK1/2, increased p-AMPK, FOXO3a, p27, Bax and cleaved caspase-3, and decreased phosphorylation of p70S6K and Bcl-2 protein expression.	Metformin	15-24	forkhead box O3	Homo sapiens	95-101
24858012-8	2014	In MCF-7 cells metformin decreased the activation of IRbeta, Akt and ERK1/2, increased p-AMPK, FOXO3a, p27, Bax and cleaved caspase-3, and decreased phosphorylation of p70S6K and Bcl-2 protein expression.	Metformin	15-24	BCL2 associated X, apoptosis regulator	Homo sapiens	108-111
24858012-8	2014	In MCF-7 cells metformin decreased the activation of IRbeta, Akt and ERK1/2, increased p-AMPK, FOXO3a, p27, Bax and cleaved caspase-3, and decreased phosphorylation of p70S6K and Bcl-2 protein expression.	Metformin	15-24	BCL2 apoptosis regulator	Homo sapiens	179-184
24858012-10	2014	In the presence of metformin, treating with SOD and catalase improved cell viability.	Metformin	19-28	superoxide dismutase 1	Homo sapiens	44-47
24858012-10	2014	In the presence of metformin, treating with SOD and catalase improved cell viability.	Metformin	19-28	catalase	Homo sapiens	52-60
24858012-11	2014	Treatment with metformin resulted in an increase in p-p38 MAPK, catalase, MnSOD and Cu/Zn SOD protein expression.	Metformin	15-24	mitogen-activated protein kinase 3	Homo sapiens	58-62
24858012-11	2014	Treatment with metformin resulted in an increase in p-p38 MAPK, catalase, MnSOD and Cu/Zn SOD protein expression.	Metformin	15-24	catalase	Homo sapiens	64-72
24858012-11	2014	Treatment with metformin resulted in an increase in p-p38 MAPK, catalase, MnSOD and Cu/Zn SOD protein expression.	Metformin	15-24	superoxide dismutase 1	Homo sapiens	76-79
24858012-12	2014	These results show that metformin has an antiproliferative effect associated with cell cycle arrest and apoptosis, which is mediated by oxidative stress, as well as AMPK and FOXO3a activation.	Metformin	24-33	forkhead box O3	Homo sapiens	174-180
24644001-7	2014	Metformin reversed EMT and decreased IL-6 signaling activation in TKI-resistant cells, while adding IL-6 to those cells bypassed the anti-TKI-resistance effect of metformin.	Metformin	163-172	interleukin 6	Homo sapiens	100-104
24644001-8	2014	Furthermore, overexpression or addition of IL-6 to TKI-sensitive cells induced TKI resistance, which could be overcome by metformin.	Metformin	122-131	interleukin 6	Homo sapiens	43-47
24644001-9	2014	Finally, metformin-based combinatorial therapy effectively blocked tumor growth in xenografts with TKI-resistant cancer cells, which was associated with decreased IL-6 secretion and expression, EMT reversal, and decreased IL-6-signaling activation in vivo.	Metformin	9-18	interleukin 6	Homo sapiens	163-167
24644001-9	2014	Finally, metformin-based combinatorial therapy effectively blocked tumor growth in xenografts with TKI-resistant cancer cells, which was associated with decreased IL-6 secretion and expression, EMT reversal, and decreased IL-6-signaling activation in vivo.	Metformin	9-18	interleukin 6	Homo sapiens	222-226
24644001-10	2014	CONCLUSION: Metformin, generally considered nontoxic and remarkably inexpensive, might be used in combination with TKIs in patients with non-small cell lung cancer, harboring EGFR mutations to overcome TKI resistance and prolong survival.	Metformin	12-21	epidermal growth factor receptor	Homo sapiens	175-179
24644001-0	2014	Metformin sensitizes EGFR-TKI-resistant human lung cancer cells in vitro and in vivo through inhibition of IL-6 signaling and EMT reversal.	Metformin	0-9	interleukin 6	Homo sapiens	107-111
24644001-4	2014	This study aims to investigate the effect of metformin on sensitizing EGFR-TKI-resistant human lung cancer cells in vitro and in vivo through inhibition of IL-6 signaling and EMT reversal.	Metformin	45-54	epidermal growth factor receptor	Homo sapiens	70-74
24682417-5	2014	Confirmation of insulin-mediated effects, independent of body mass index, also supports the potential benefit of adjuvant metformin therapy.	Metformin	122-131	insulin	Homo sapiens	16-23
24644001-4	2014	This study aims to investigate the effect of metformin on sensitizing EGFR-TKI-resistant human lung cancer cells in vitro and in vivo through inhibition of IL-6 signaling and EMT reversal.	Metformin	45-54	interleukin 6	Homo sapiens	156-160
24644001-7	2014	Metformin reversed EMT and decreased IL-6 signaling activation in TKI-resistant cells, while adding IL-6 to those cells bypassed the anti-TKI-resistance effect of metformin.	Metformin	0-9	interleukin 6	Homo sapiens	37-41
24843020-5	2014	Metformin also reduced hypoxic activation of hypoxia-inducible factor 1 (HIF-1).	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	45-71
24735537-0	2014	Differential AMPK phosphorylation by glucagon and metformin regulates insulin signaling in human hepatic cells.	Metformin	50-59	insulin	Homo sapiens	70-77
24843020-5	2014	Metformin also reduced hypoxic activation of hypoxia-inducible factor 1 (HIF-1).	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	73-78
24671882-5	2014	In cultured bovine granulosa cells, INSULIN, IGF1, and two insulin sensitizers-metformin and rosiglitazone-increased rarres2 mRNA expression whereas they decreased cmklr1, gpr1, and cclr2 mRNA expression.	Metformin	79-88	retinoic acid receptor responder 2	Bos taurus	117-124
24810045-0	2014	Metformin lowers Ser-129 phosphorylated alpha-synuclein levels via mTOR-dependent protein phosphatase 2A activation.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	67-71
24810045-6	2014	On the other hand, metformin-induced phospho-Ser129 alpha-synuclein reduction was consistently associated with inhibition of mammalian target of rapamycin (mTOR) and activation of protein phosphatase 2A (PP2A).	Metformin	19-28	mechanistic target of rapamycin kinase	Homo sapiens	125-154
24810045-6	2014	On the other hand, metformin-induced phospho-Ser129 alpha-synuclein reduction was consistently associated with inhibition of mammalian target of rapamycin (mTOR) and activation of protein phosphatase 2A (PP2A).	Metformin	19-28	mechanistic target of rapamycin kinase	Homo sapiens	156-160
24446492-4	2014	For instance, the derivatives of cannabis and an anti-diabetic agent, metformin, both are able to inhibit ERK, which is commonly activated in TC cells.	Metformin	70-79	mitogen-activated protein kinase 1	Homo sapiens	106-109
29159083-1	2014	Aim: To evaluate the efficacy/safety of canagliflozin twice daily (BID) compared with placebo in patients with type 2 diabetes mellitus (T2DM) on metformin.	Metformin	146-155	BH3 interacting domain death agonist	Homo sapiens	67-70
24217938-1	2014	PURPOSE: The aim of the present study is to assess the impact of adding oral metformin to insulin therapy in pregnant women with insulin-resistant diabetes mellitus.	Metformin	77-86	insulin	Homo sapiens	90-97
24428821-6	2014	Metformin also increased PGC-1alpha in human primary hepatocytes; this effect of metformin was abolished by AMPK inhibitor compound C and sirtuin 1 siRNA.	Metformin	0-9	PPARG coactivator 1 alpha	Homo sapiens	25-35
24671882-5	2014	In cultured bovine granulosa cells, INSULIN, IGF1, and two insulin sensitizers-metformin and rosiglitazone-increased rarres2 mRNA expression whereas they decreased cmklr1, gpr1, and cclr2 mRNA expression.	Metformin	79-88	chemerin chemokine-like receptor 1	Bos taurus	164-170
24428821-6	2014	Metformin also increased PGC-1alpha in human primary hepatocytes; this effect of metformin was abolished by AMPK inhibitor compound C and sirtuin 1 siRNA.	Metformin	81-90	PPARG coactivator 1 alpha	Homo sapiens	25-35
24428821-10	2014	Metformin down-regulated several key transcription factors that mediate the effect of PGC-1alpha on gluconeogenic genes including Kruppel-like factor 15, forkhead box protein O1 and hepatocyte NF 4alpha, whereas it increased nuclear respiratory factor 1, which is involved in PGC-1alpha-mediated regulation of mitochondrial proteins.	Metformin	0-9	nuclear respiratory factor 1	Mus musculus	225-253
24940426-2	2014	The mechanism of action of metformin involves regulation of the adenosine monophosphate-activated protein kinase/mammalian target of rapamycin signaling pathway, which is implicated in the control of protein synthesis and cell proliferation.	Metformin	27-36	mechanistic target of rapamycin kinase	Homo sapiens	113-142
24419232-5	2014	Gene expression profiling of human umbilical vein endothelial cells revealed a paradoxical modulation of several angiogenesis-associated genes and proteins by metformin, with short-term induction of vascular endothelial growth factor (VEGF), cyclooxygenase 2 and CXC chemokine receptor 4 at the messenger RNA level and downregulation of ADAMTS1.	Metformin	159-168	vascular endothelial growth factor A	Homo sapiens	199-233
24419232-5	2014	Gene expression profiling of human umbilical vein endothelial cells revealed a paradoxical modulation of several angiogenesis-associated genes and proteins by metformin, with short-term induction of vascular endothelial growth factor (VEGF), cyclooxygenase 2 and CXC chemokine receptor 4 at the messenger RNA level and downregulation of ADAMTS1.	Metformin	159-168	vascular endothelial growth factor A	Homo sapiens	235-239
24419232-5	2014	Gene expression profiling of human umbilical vein endothelial cells revealed a paradoxical modulation of several angiogenesis-associated genes and proteins by metformin, with short-term induction of vascular endothelial growth factor (VEGF), cyclooxygenase 2 and CXC chemokine receptor 4 at the messenger RNA level and downregulation of ADAMTS1.	Metformin	159-168	prostaglandin-endoperoxide synthase 2	Homo sapiens	242-258
24419232-8	2014	Metformin inhibits VEGF-dependent activation of extracellular signal-regulated kinase 1/2, and the inhibition of AMPK activity abrogates this event.	Metformin	0-9	vascular endothelial growth factor A	Homo sapiens	19-23
24419232-8	2014	Metformin inhibits VEGF-dependent activation of extracellular signal-regulated kinase 1/2, and the inhibition of AMPK activity abrogates this event.	Metformin	0-9	mitogen-activated protein kinase 3	Homo sapiens	48-89
24580044-5	2014	Several studies have indicated that metformin, as an insulin sensitizer, effectively improves NAFLD and its related metabolic status.	Metformin	36-45	insulin	Homo sapiens	53-60
24940426-8	2014	Furthermore, the caspase-3 levels in the metformin-treated T98G cells were higher than those in the control cells.	Metformin	41-50	caspase 3	Homo sapiens	17-26
24940437-8	2014	Therefore, the administration of metformin and pioglitazone in patients with T2DM may improve insulin function, reduce the role of IR and improve endothelial function.	Metformin	33-42	insulin	Homo sapiens	94-101
24517721-7	2014	Serum MDA, ET-1, HOMA and sdLDL-C levels decreased and PON1 activity and NO levels increased significantly after the metformin treatment.	Metformin	117-126	endothelin 1	Homo sapiens	11-15
24517721-7	2014	Serum MDA, ET-1, HOMA and sdLDL-C levels decreased and PON1 activity and NO levels increased significantly after the metformin treatment.	Metformin	117-126	paraoxonase 1	Homo sapiens	55-59
24517721-9	2014	Metformin seemed to decrease oxidative stress and improve insulin resistance, dyslipidemia and endothelial dysfunction in PCOS patients.	Metformin	0-9	insulin	Homo sapiens	58-65
24671665-11	2014	Early basal insulin treatment in patients insufficiently controlled with metformin is efficient, safe and convenient.	Metformin	73-82	insulin	Homo sapiens	12-19
24561578-7	2014	The activators of the AMPK/Akt pathway, adiponectin, AICAR, and metformin, attenuated superoxide generation, TRAF3IP2 expression, and oxLDL/TRAF3IP2-mediated EC death.	Metformin	64-73	AKT serine/threonine kinase 1	Homo sapiens	27-30
24606093-1	2014	CONTEXT: Although metformin is widely used to improve insulin resistance in women with polycystic ovary syndrome (PCOS), its mechanism of action is complex, with inconsistent effects on insulin sensitivity and variability in treatment response.	Metformin	18-27	insulin	Homo sapiens	54-61
24606093-2	2014	OBJECTIVE: The aim of the study was to delineate the effect of metformin on glucose and insulin parameters, determine additional treatment outcomes, and predict patients with PCOS who will respond to treatment.	Metformin	63-72	insulin	Homo sapiens	88-95
24236897-1	2014	AIMS: Given that sleep disorders are known to be related to insulin resistance, and metformin has favourable effects on insulin resistance and on ventilatory drive, we sought to determine whether metformin therapy was related to sleep variables in a group of patients with Type 2 diabetes.	Metformin	84-93	insulin	Homo sapiens	120-127
23999197-8	2014	Accordingly, the improvement of insulin sensitivity with surgery-induced weight loss (+51%, P=0.01) and metformin (+42%, P=0.02) led to increased adipose p53.	Metformin	104-113	insulin	Homo sapiens	32-39
23999197-8	2014	Accordingly, the improvement of insulin sensitivity with surgery-induced weight loss (+51%, P=0.01) and metformin (+42%, P=0.02) led to increased adipose p53.	Metformin	104-113	tumor protein p53	Homo sapiens	154-157
24789104-0	2014	Metformin inhibits the IL-6-induced epithelial-mesenchymal transition and lung adenocarcinoma growth and metastasis.	Metformin	0-9	interleukin 6	Mus musculus	23-27
26327840-3	2014	The aim of this study was to verify indications for metformin use in obese women based on metabolic and anthropometric parameters assessed by dual-X-ray absorptiometry (DXA), to establish the degree of insulin resistance and its correlations.	Metformin	52-61	insulin	Homo sapiens	202-209
24789104-8	2014	Importantly, metformin inhibited tumor growth and distant metastases in tumor-bearing nude mice and reversed IL-6-induced EMT both in vitro and in vivo.	Metformin	13-22	interleukin 6	Mus musculus	109-113
24789104-9	2014	Furthermore, we found that blockade of STAT3 phosphorylation might be the underlying mechanism of metformin inhibition of IL-6-induced EMT.	Metformin	98-107	signal transducer and activator of transcription 3	Mus musculus	39-44
24789104-9	2014	Furthermore, we found that blockade of STAT3 phosphorylation might be the underlying mechanism of metformin inhibition of IL-6-induced EMT.	Metformin	98-107	interleukin 6	Mus musculus	122-126
24789104-11	2014	We found that metformin could inhibit IL-6-induced EMT possibly by blocking STAT3 phosphorylation.	Metformin	14-23	interleukin 6	Mus musculus	38-42
24789104-11	2014	We found that metformin could inhibit IL-6-induced EMT possibly by blocking STAT3 phosphorylation.	Metformin	14-23	signal transducer and activator of transcription 3	Mus musculus	76-81
24799988-5	2014	Metformin improves insulin sensitivity and serum alanine transaminase and aspartate transaminase (ALT/AST) levels in the majority of subjects; however, it has no significant effect on liver histology.	Metformin	0-9	insulin	Homo sapiens	19-26
24799988-5	2014	Metformin improves insulin sensitivity and serum alanine transaminase and aspartate transaminase (ALT/AST) levels in the majority of subjects; however, it has no significant effect on liver histology.	Metformin	0-9	solute carrier family 17 member 5	Homo sapiens	98-105
24699248-10	2014	GSK263 had no effect on active or total GLP-1 or GIP, but co-dosing with metformin increased post-prandial total GLP-1, with little effect on active GLP-1.	Metformin	73-82	glucagon	Homo sapiens	113-118
24756098-5	2014	The aim of this study was to investigate whether exercise training and/or metformin improve glucose homeostasis and albuminuria and downregulate renal ADAM17 and ACE2 shedding in db/db mice.	Metformin	74-83	a disintegrin and metallopeptidase domain 17	Mus musculus	151-157
24756098-5	2014	The aim of this study was to investigate whether exercise training and/or metformin improve glucose homeostasis and albuminuria and downregulate renal ADAM17 and ACE2 shedding in db/db mice.	Metformin	74-83	angiotensin I converting enzyme (peptidyl-dipeptidase A) 2	Mus musculus	162-166
24756098-12	2014	In conclusion, exercise training alone and in combination with metformin prevented shedding of renal ACE2 by decreasing ADAM17 protein.	Metformin	63-72	angiotensin I converting enzyme (peptidyl-dipeptidase A) 2	Mus musculus	101-105
24756098-12	2014	In conclusion, exercise training alone and in combination with metformin prevented shedding of renal ACE2 by decreasing ADAM17 protein.	Metformin	63-72	a disintegrin and metallopeptidase domain 17	Mus musculus	120-126
24764656-13	2014	New players in mTOR signaling pathway, such as non-steroidal anti-inflammatory drug and metformin with therapeutic potentials are also discussed here.	Metformin	88-97	mechanistic target of rapamycin kinase	Homo sapiens	15-19
24762064-0	2014	Beneficial effects of pioglitazone and metformin in murine model of polycystic ovaries via improvement of chemerin gene up-regulation.	Metformin	39-48	retinoic acid receptor responder (tazarotene induced) 2	Mus musculus	106-114
24595965-3	2014	Whether metformin treatment in pregnant PCOS women affects maternal and fetal insulin concentrations at birth is not clarified.	Metformin	8-17	insulin	Homo sapiens	78-85
24595965-4	2014	OBJECTIVES: To investigate the possible effect of metformin on insulin concentrations in umbilical cord blood and the possible association between maternal and fetal insulin concentrations.	Metformin	50-59	insulin	Homo sapiens	63-70
24595965-9	2014	RESULTS: At delivery women randomized to metformin had lower insulin concentrations than those randomized to placebo (259+-209 vs 361+-261 pmol/l; P=0.020).	Metformin	41-50	insulin	Homo sapiens	61-68
24595965-13	2014	CONCLUSIONS: In PCOS, metformin treatment during pregnancy resulted in lower maternal insulin concentrations at delivery.	Metformin	22-31	insulin	Homo sapiens	86-93
24699248-10	2014	GSK263 had no effect on active or total GLP-1 or GIP, but co-dosing with metformin increased post-prandial total GLP-1, with little effect on active GLP-1.	Metformin	73-82	glucagon	Homo sapiens	113-118
24482374-0	2014	Metformin protects endothelial function in diet-induced obese mice by inhibition of endoplasmic reticulum stress through 5" adenosine monophosphate-activated protein kinase-peroxisome proliferator-activated receptor delta pathway.	Metformin	0-9	peroxisome proliferator activator receptor delta	Mus musculus	173-221
24482374-3	2014	We aim to investigate whether PPARdelta is crucial for metformin in ameliorating ER stress and endothelial dysfunction induced by high-fat diet.	Metformin	55-64	peroxisome proliferator activator receptor delta	Mus musculus	30-39
24482374-8	2014	These effects of high-fat diet were reversed by oral treatment with metformin in diet-induced obese PPARdelta wild-type mice but not in diet-induced obese PPARdelta knockout littermates.	Metformin	68-77	peroxisome proliferator activator receptor delta	Mus musculus	100-109
24482374-10	2014	Effects of metformin were abolished by cotreatment of GSK0660 (PPARdelta antagonist), whereas effects of GW1516 were unaffected by compound C (AMPK inhibitor).	Metformin	11-20	peroxisome proliferator activator receptor delta	Mus musculus	63-72
24482374-11	2014	CONCLUSIONS: Metformin restores endothelial function through inhibiting ER stress and oxidative stress and increasing NO bioavailability on activation of AMPK/PPARdelta pathway in obese diabetic mice.	Metformin	13-22	peroxisome proliferator activator receptor delta	Mus musculus	159-168
24462282-9	2014	CONCLUSIONS: Our results show that the functional, biochemical and ultrastructural abnormalities observed in human islet cells exposed to glucotoxic condition can be significantly prevented by metformin, further highlighting a direct beneficial effect of this drug on the insulin secreting human pancreatic beta cells.	Metformin	193-202	insulin	Homo sapiens	272-279
24534455-10	2014	Moreover, both statins and metformin are known to inhibit mTOR via AMPK activation so that they would fully exploit the beneficial effects of mTOR inhibition in atherosclerosis.	Metformin	27-36	mechanistic target of rapamycin kinase	Homo sapiens	58-62
24534455-10	2014	Moreover, both statins and metformin are known to inhibit mTOR via AMPK activation so that they would fully exploit the beneficial effects of mTOR inhibition in atherosclerosis.	Metformin	27-36	mechanistic target of rapamycin kinase	Homo sapiens	142-146
24520038-0	2014	Repurposing of metformin and aspirin by targeting AMPK-mTOR and inflammation for pancreatic cancer prevention and treatment.	Metformin	15-24	mechanistic target of rapamycin kinase	Homo sapiens	55-59
24520038-6	2014	For metformin, the most important mechanism may involve the inhibition of mTOR signaling via AMP-activated protein kinase (AMPK)-dependent and -independent pathways.	Metformin	4-13	mechanistic target of rapamycin kinase	Homo sapiens	74-78
23848509-0	2014	Respiratory effects of insulin sensitisation with metformin: a prospective observational study.	Metformin	50-59	insulin	Homo sapiens	23-30
23848509-2	2014	We aimed to assess whether treatment with metformin, an oral insulin-sensitising agent, improved lung function or symptoms in individuals with COPD and glucose intolerance.	Metformin	42-51	insulin	Homo sapiens	61-68
24612291-5	2014	RESULTS: Patients who used metformin showed a lower incidence of gastric cancer than those who did not use metformin, in insulin non-users (P = 0.047, log-rank test).	Metformin	27-36	insulin	Homo sapiens	121-128
24612291-7	2014	In insulin non-users, the adjusted hazard ratio (AHR) for metformin use was 0.73 (95% confidential interval [CI], 0.53-1.01) with borderline statistical significance (P = 0.059).	Metformin	58-67	insulin	Homo sapiens	3-10
24480115-0	2014	Metformin modulates PI3K and GLUT4 expression and Akt/PKB phosphorylation in human endometrial stromal cells after stimulation with androgen and insulin.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	50-53
24437490-5	2014	In the AR(+) LNCaP prostate cancer cells, we found that metformin inhibits androgen-induced CRE activity and IGF-IR gene transcription.	Metformin	56-65	androgen receptor	Homo sapiens	7-9
24437490-9	2014	Moreover, metformin blocked membrane-initiated signals of AR to the mammalian target of rapamycin/p70S6Kinase pathway by inhibiting AR phosphorylation and its association with c-Src.	Metformin	10-19	androgen receptor	Homo sapiens	58-60
24437490-9	2014	Moreover, metformin blocked membrane-initiated signals of AR to the mammalian target of rapamycin/p70S6Kinase pathway by inhibiting AR phosphorylation and its association with c-Src.	Metformin	10-19	mechanistic target of rapamycin kinase	Homo sapiens	68-97
24437490-9	2014	Moreover, metformin blocked membrane-initiated signals of AR to the mammalian target of rapamycin/p70S6Kinase pathway by inhibiting AR phosphorylation and its association with c-Src.	Metformin	10-19	androgen receptor	Homo sapiens	132-134
24437490-9	2014	Moreover, metformin blocked membrane-initiated signals of AR to the mammalian target of rapamycin/p70S6Kinase pathway by inhibiting AR phosphorylation and its association with c-Src.	Metformin	10-19	SRC proto-oncogene, non-receptor tyrosine kinase	Homo sapiens	176-181
24437490-11	2014	By inhibiting androgen-dependent IGF-IR up-regulation, metformin reduced IGF-I-mediated proliferation of LNCaP cells.	Metformin	55-64	insulin like growth factor 1	Homo sapiens	33-38
24437490-12	2014	These results indicate that, in prostate cancer cells, metformin inhibits IGF-I-mediated biological effects by disrupting membrane-initiated AR action responsible for IGF-IR up-regulation and suggest that metformin could represent a useful adjunct to the classical antiandrogen therapy.	Metformin	55-64	insulin like growth factor 1	Homo sapiens	74-79
24437490-12	2014	These results indicate that, in prostate cancer cells, metformin inhibits IGF-I-mediated biological effects by disrupting membrane-initiated AR action responsible for IGF-IR up-regulation and suggest that metformin could represent a useful adjunct to the classical antiandrogen therapy.	Metformin	55-64	androgen receptor	Homo sapiens	141-143
24437490-12	2014	These results indicate that, in prostate cancer cells, metformin inhibits IGF-I-mediated biological effects by disrupting membrane-initiated AR action responsible for IGF-IR up-regulation and suggest that metformin could represent a useful adjunct to the classical antiandrogen therapy.	Metformin	205-214	insulin like growth factor 1	Homo sapiens	74-79
24480115-0	2014	Metformin modulates PI3K and GLUT4 expression and Akt/PKB phosphorylation in human endometrial stromal cells after stimulation with androgen and insulin.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	54-57
24480115-0	2014	Metformin modulates PI3K and GLUT4 expression and Akt/PKB phosphorylation in human endometrial stromal cells after stimulation with androgen and insulin.	Metformin	0-9	insulin	Homo sapiens	145-152
24480115-1	2014	OBJECTIVE: To assess the effect of metformin on expression of Akt, ERK, PI3K and GLUT4, proteins associated with the growth factor signaling cascade, in human endometrial stromal cells after stimulation with androgen and insulin.	Metformin	35-44	AKT serine/threonine kinase 1	Homo sapiens	62-65
24480115-1	2014	OBJECTIVE: To assess the effect of metformin on expression of Akt, ERK, PI3K and GLUT4, proteins associated with the growth factor signaling cascade, in human endometrial stromal cells after stimulation with androgen and insulin.	Metformin	35-44	mitogen-activated protein kinase 1	Homo sapiens	67-70
24480115-4	2014	RESULTS: PI3K and GLUT4 expression were increased in the insulin-treated group and further attenuated when metformin was added.	Metformin	107-116	insulin	Homo sapiens	57-64
24480115-5	2014	The ERK protein was not affected, whereas the Akt phosphorylation was significantly decreased by the action of metformin.	Metformin	111-120	AKT serine/threonine kinase 1	Homo sapiens	46-49
24480115-6	2014	CONCLUSION: Metformin affects human endometrial stromal cells by acting on proteins related to growth factors, usually increasing their expression when combined with insulin.	Metformin	12-21	insulin	Homo sapiens	166-173
24480115-7	2014	Akt phosphorylation was inhibited by metformin, possibly due to its anti-proliferative action.	Metformin	37-46	AKT serine/threonine kinase 1	Homo sapiens	0-3
24444314-2	2014	In this study, we elucidated the anti-hypertrophic action of metformin, specifically, the role of the AMPK/eNOS/p53 pathway.	Metformin	61-70	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	102-106
24420540-2	2014	Although metformin is a known activator of AMPK, it is unclear whether its cardioprotection acts independently of an AMPKalpha2-dependent pathway.	Metformin	9-18	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	43-47
24420540-5	2014	Administration of metformin was equally effective in attenuating transverse aortic constriction-induced LV remodeling in both wild-type and AMPKalpha2 knockout mice, as evidenced by reduced LV and lung weights, a preserved LV ejection fraction, and reduced phosphorylation of mammalian target of rapamycin (p-mTOR(Ser2448)) and its downstream target p-p70S6K(Thr389).	Metformin	18-27	mechanistic target of rapamycin kinase	Homo sapiens	276-305
24420540-5	2014	Administration of metformin was equally effective in attenuating transverse aortic constriction-induced LV remodeling in both wild-type and AMPKalpha2 knockout mice, as evidenced by reduced LV and lung weights, a preserved LV ejection fraction, and reduced phosphorylation of mammalian target of rapamycin (p-mTOR(Ser2448)) and its downstream target p-p70S6K(Thr389).	Metformin	18-27	mechanistic target of rapamycin kinase	Homo sapiens	309-313
24680596-0	2014	CGRRF1 as a novel biomarker of tissue response to metformin in the context of obesity.	Metformin	50-59	cell growth regulator with ring finger domain 1	Homo sapiens	0-6
24680596-4	2014	We identified CGRRF1 (cell growth regulator with ring finger domain 1) as a novel metformin-responsive gene and characterized its possible role in endometrial cancer prevention.	Metformin	82-91	cell growth regulator with ring finger domain 1	Homo sapiens	14-20
24680596-4	2014	We identified CGRRF1 (cell growth regulator with ring finger domain 1) as a novel metformin-responsive gene and characterized its possible role in endometrial cancer prevention.	Metformin	82-91	cell growth regulator with ring finger domain 1	Homo sapiens	22-69
24680596-10	2014	CONCLUSION: CGRRF1 represents a novel, reproducible tissue marker of metformin response in the obese endometrium.	Metformin	69-78	cell growth regulator with ring finger domain 1	Homo sapiens	12-18
24444314-4	2014	Results showed that treatment with metformin significantly attenuated AngII-induced cell hypertrophy and death.	Metformin	35-44	angiotensinogen	Rattus norvegicus	70-75
24444314-5	2014	Metformin attenuated AngII-induced activation (cleavage) of caspase 3, Bcl-2 down-regulation and p53 up-regulation.	Metformin	0-9	angiotensinogen	Rattus norvegicus	21-26
24444314-5	2014	Metformin attenuated AngII-induced activation (cleavage) of caspase 3, Bcl-2 down-regulation and p53 up-regulation.	Metformin	0-9	BCL2, apoptosis regulator	Rattus norvegicus	71-76
24444314-8	2014	The AMPK inhibitor, compound C, prevented AT1R down-regulation, indicating that metformin mediated its effects via AMPK activation.	Metformin	80-89	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	4-8
24444314-8	2014	The AMPK inhibitor, compound C, prevented AT1R down-regulation, indicating that metformin mediated its effects via AMPK activation.	Metformin	80-89	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	115-119
24444314-10	2014	Thus, this study demonstrates that the anti-hypertrophic effects of metformin are associated with AMPK-induced AT1R down-regulation and prevention of mitochondrial dysfunction through the SIRT1/eNOS/p53 pathway.	Metformin	68-77	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	98-102
24444314-10	2014	Thus, this study demonstrates that the anti-hypertrophic effects of metformin are associated with AMPK-induced AT1R down-regulation and prevention of mitochondrial dysfunction through the SIRT1/eNOS/p53 pathway.	Metformin	68-77	sirtuin 1	Rattus norvegicus	188-193
24612549-0	2014	Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma.	Metformin	0-9	estrogen receptor 1	Homo sapiens	65-67
24329524-1	2014	WHAT IS KNOWN AND OBJECTIVE: There are acknowledged benefits to continuing metformin when initiating insulin, but there appears to be growing concern over the role of sulphonylureas and thiazolidinediones when used in combination with insulin.	Metformin	75-84	insulin	Homo sapiens	101-108
24684803-2	2014	Though basal insulin with metformin or sulfonylurea is an effective therapy, it cannot reduce postprandial glycemia without the risk of hypoglycemia.	Metformin	26-35	insulin	Homo sapiens	13-20
24297263-7	2014	In addition, metformin inhibited the activation of caspase-3 and levels of poly-ADP-ribose polymerase (PARP).	Metformin	13-22	caspase 3	Homo sapiens	51-60
24297263-7	2014	In addition, metformin inhibited the activation of caspase-3 and levels of poly-ADP-ribose polymerase (PARP).	Metformin	13-22	poly(ADP-ribose) polymerase 1	Homo sapiens	75-101
24297263-7	2014	In addition, metformin inhibited the activation of caspase-3 and levels of poly-ADP-ribose polymerase (PARP).	Metformin	13-22	poly(ADP-ribose) polymerase 1	Homo sapiens	103-107
24638078-10	2014	Additionally, in bone marrow-derived macrophages, metformin treatment partially blunted the effects of lipopolysaccharide on inducing the phosphorylation of JNK1 and nuclear factor kappa B (NF-kappaB) p65 and on increasing the mRNA levels of proinflammatory cytokines.	Metformin	50-59	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	166-188
24638078-10	2014	Additionally, in bone marrow-derived macrophages, metformin treatment partially blunted the effects of lipopolysaccharide on inducing the phosphorylation of JNK1 and nuclear factor kappa B (NF-kappaB) p65 and on increasing the mRNA levels of proinflammatory cytokines.	Metformin	50-59	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	190-199
24612549-8	2014	Moreover, metformin enhanced tamoxifen-mediated inhibition of proliferation, DNA replication activity, colony formation, soft-agar colony formation, and induction of apoptosis in ER-positive breast cancer cells.	Metformin	10-19	estrogen receptor 1	Homo sapiens	179-181
24612549-9	2014	In addition, these tamoxifen-induced effects that were enhanced by metformin may be involved in the bax/bcl-2 apoptotic pathway and the AMPK/mTOR/p70S6 growth pathway.	Metformin	67-76	BCL2 associated X, apoptosis regulator	Homo sapiens	100-103
24612502-3	2014	This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer.	Metformin	134-143	estrogen receptor 1	Homo sapiens	186-203
24612502-3	2014	This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer.	Metformin	134-143	estrogen receptor 1	Homo sapiens	205-207
24612549-9	2014	In addition, these tamoxifen-induced effects that were enhanced by metformin may be involved in the bax/bcl-2 apoptotic pathway and the AMPK/mTOR/p70S6 growth pathway.	Metformin	67-76	BCL2 apoptosis regulator	Homo sapiens	104-109
24612502-9	2014	DISCUSSION: This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer.	Metformin	80-89	estrogen receptor 1	Homo sapiens	136-138
24612549-9	2014	In addition, these tamoxifen-induced effects that were enhanced by metformin may be involved in the bax/bcl-2 apoptotic pathway and the AMPK/mTOR/p70S6 growth pathway.	Metformin	67-76	mechanistic target of rapamycin kinase	Homo sapiens	141-145
24612549-11	2014	CONCLUSION: The present work shows that metformin and tamoxifen additively inhibited the growth and augmented the apoptosis of ER-positive breast cancer cells.	Metformin	40-49	estrogen receptor 1	Homo sapiens	127-129
23685372-7	2014	Metformin 500 mg bid was initiated and increased to 1 g bid after 1 week.	Metformin	0-9	BH3 interacting domain death agonist	Homo sapiens	17-20
24662793-4	2014	However, some of the biological responses to metformin (e.g. the release of cytokines and the expression of arginase I or PGC-1alpha) are not limited to AMPK activation but also are mediated by AMPK-independent mechanisms.	Metformin	45-54	PPARG coactivator 1 alpha	Homo sapiens	122-132
23685372-9	2014	The cobiotic bid was added on the 9th day of metformin treatment, and after 2 days, his FBS dropped to 175 mg/dl.	Metformin	45-54	BH3 interacting domain death agonist	Homo sapiens	13-16
24317794-8	2014	In individual SNP analyses, Gly482Ser (rs8192678, PPARGC1A) was associated with accumulation of subcutaneous adiposity and worsening insulin resistance at 1 year (both p < 0.05), while rs2970852 (PPARGC1A) modified the effects of metformin on triacylglycerol levels (p(interaction) = 0.04).	Metformin	233-242	PPARG coactivator 1 alpha	Homo sapiens	50-58
24106875-1	2014	BACKGROUND: Insulin and incretin agents (dipeptidyl peptidase-4 inhibitors [DPP4is] and glucagon-like peptide-1 receptor agonists [GLP1 RAs]) are second-line treatment options in patients with type 2 diabetes (T2D) not achieving glycemic targets with metformin.	Metformin	251-260	insulin	Homo sapiens	12-19
24270984-0	2014	Metformin lowers plasma triglycerides by promoting VLDL-triglyceride clearance by brown adipose tissue in mice.	Metformin	0-9	CD320 antigen	Mus musculus	51-55
24270984-2	2014	Besides its well-characterized antihyperglycemic properties, metformin also lowers plasma VLDL triglyceride (TG).	Metformin	61-70	CD320 antigen	Mus musculus	90-94
24270984-4	2014	We found that metformin markedly lowered plasma total cholesterol and TG levels, an effect mostly due to a decrease in VLDL-TG, whereas HDL was slightly increased.	Metformin	14-23	CD320 antigen	Mus musculus	119-123
24270984-8	2014	Furthermore, therapeutic concentrations of metformin increased AMPK and HSL activities and promoted lipolysis in T37i differentiated brown adipocytes.	Metformin	43-52	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	63-67
24270984-9	2014	Collectively, our results identify BAT as an important player in the TG-lowering effect of metformin by enhancing VLDL-TG uptake, intracellular TG lipolysis, and subsequent mitochondrial fatty acid oxidation.	Metformin	91-100	CD320 antigen	Mus musculus	114-118
24461109-10	2014	On day 7, compared with pasireotide alone, the decrease in serum insulin was attenuated with nateglinide, metformin, liraglutide and vildagliptin co-administration (levels were 3%, 6%, 34% and 71% higher, respectively).	Metformin	106-115	insulin	Homo sapiens	65-72
24361375-3	2014	In this study, we showed that antidiabetes drugs rosiglitazone and metformin inhibit NPC cell growth through reducing the expression of integrin-linked kinase (ILK).	Metformin	67-76	integrin linked kinase	Homo sapiens	136-158
24361375-3	2014	In this study, we showed that antidiabetes drugs rosiglitazone and metformin inhibit NPC cell growth through reducing the expression of integrin-linked kinase (ILK).	Metformin	67-76	integrin linked kinase	Homo sapiens	160-163
24361375-4	2014	Blockade of PPARgamma and AMPKalpha overcame the effects of rosiglitazone and metformin on ILK protein.	Metformin	78-87	peroxisome proliferator activated receptor gamma	Homo sapiens	12-21
24361375-4	2014	Blockade of PPARgamma and AMPKalpha overcame the effects of rosiglitazone and metformin on ILK protein.	Metformin	78-87	integrin linked kinase	Homo sapiens	91-94
24361375-5	2014	Importantly, overexpression of ILK abrogated the effect of rosiglitazone and metformin on NPC cell growth.	Metformin	77-86	integrin linked kinase	Homo sapiens	31-34
24361375-8	2014	Chromatin immunoprecipitation (ChIP) assay showed that rosiglitazone induced AP-2alpha, while metformin reduced Sp1 protein binding to the DNA sequences in the ILK gene promoter.	Metformin	94-103	integrin linked kinase	Homo sapiens	160-163
24361375-10	2014	Collectively, we show that rosiglitazone and metformin inhibit ILK gene expression through PPARgamma- and AMPKalpha-dependent signaling pathways that are involved in the regulation of AP-2alpha and Sp1 protein expressions.	Metformin	45-54	integrin linked kinase	Homo sapiens	63-66
24361375-10	2014	Collectively, we show that rosiglitazone and metformin inhibit ILK gene expression through PPARgamma- and AMPKalpha-dependent signaling pathways that are involved in the regulation of AP-2alpha and Sp1 protein expressions.	Metformin	45-54	peroxisome proliferator activated receptor gamma	Homo sapiens	91-100
24361375-12	2014	The cross-talk of PPARgamma and AMPKalpha signaling enhances the synergistic effects of rosiglitazone and metformin.	Metformin	106-115	peroxisome proliferator activated receptor gamma	Homo sapiens	18-27
24362725-10	2014	Of particular importance, we found that metformin treatment downregulated Srebp-1c promoter activity, decreased the specific binding of SREBP-1c to Irs-1 promoter and upregulated Irs-1 promoter activity in PA-cultured L6 cells.	Metformin	40-49	insulin receptor substrate 1	Rattus norvegicus	148-153
24362725-10	2014	Of particular importance, we found that metformin treatment downregulated Srebp-1c promoter activity, decreased the specific binding of SREBP-1c to Irs-1 promoter and upregulated Irs-1 promoter activity in PA-cultured L6 cells.	Metformin	40-49	insulin receptor substrate 1	Rattus norvegicus	179-184
24505341-6	2014	Importantly, metformin was preferentially cytotoxic to CD44(high)/CD24(low) cells of MCF-7 cells and, CD44(high)/CD24(high) cells of MIA PaCa-2 cells, which are known to be cancer stem cells (CSCs) of MCF-7 cells and MIA PaCa-2 cells, respectively.	Metformin	13-22	CD24 molecule	Homo sapiens	66-70
24485344-3	2014	Metformin use was associated with improved CD4 recovery (p=0.034).	Metformin	0-9	CD4 molecule	Homo sapiens	43-46
24716225-10	2014	Metformin attenuated IkappaBalpha phosphorylation and NF-kappaB DNA-binding activity.	Metformin	0-9	nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha	Mus musculus	21-33
24716225-10	2014	Metformin attenuated IkappaBalpha phosphorylation and NF-kappaB DNA-binding activity.	Metformin	0-9	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	54-63
24716225-13	2014	Metformin significantly attenuated the severity of colitis in IL-10-/- mice, induced AMPK activity in intestinal epithelial cells, and inhibited the development of colitic cancer in mice.	Metformin	0-9	interleukin 10	Mus musculus	62-67
24716225-14	2014	CONCLUSIONS: These results indicate that metformin suppresses NF-kappaB activation in intestinal epithelial cells and ameliorates murine colitis and colitis-associated tumorigenesis in mice, suggesting that metformin could be a potential therapeutic agent for the treatment of inflammatory bowel disease.	Metformin	41-50	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	62-71
24435937-5	2014	Protective effects of metformin may be modulated via activating the AMP activated protein kinase (AMPK).	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	68-96
24435937-5	2014	Protective effects of metformin may be modulated via activating the AMP activated protein kinase (AMPK).	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	98-102
24435937-8	2014	Besides, inhibition of AMPK by compound c showed that metformin resulted in apoptosis attenuation via AMPK activation.	Metformin	54-63	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	23-27
24435937-8	2014	Besides, inhibition of AMPK by compound c showed that metformin resulted in apoptosis attenuation via AMPK activation.	Metformin	54-63	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	102-106
24435937-9	2014	Interestingly, AMPK activation was also involved in the induction of mitochondrial biogenesis proteins using metformin, inhibition of AMPK by compound c reversed such effect, further supporting the role of AMPK upstream of mitochondrial biogenesis proteins.	Metformin	109-118	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	15-19
24435937-9	2014	Interestingly, AMPK activation was also involved in the induction of mitochondrial biogenesis proteins using metformin, inhibition of AMPK by compound c reversed such effect, further supporting the role of AMPK upstream of mitochondrial biogenesis proteins.	Metformin	109-118	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	134-138
24435937-9	2014	Interestingly, AMPK activation was also involved in the induction of mitochondrial biogenesis proteins using metformin, inhibition of AMPK by compound c reversed such effect, further supporting the role of AMPK upstream of mitochondrial biogenesis proteins.	Metformin	109-118	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	134-138
24435937-10	2014	In summary, Metformin pretreatment is able to modulate mitochondrial biogenesis and apoptotic cell death pathways through AMPK activation in the context of global cerebral ischemia, conducting the outcome towards neuroprotection.	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	122-126
24577086-0	2014	Metformin promotes autophagy and apoptosis in esophageal squamous cell carcinoma by downregulating Stat3 signaling.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	99-104
24577086-8	2014	Mechanistically, signal transducer and activator of transcription 3 (Stat3) and its downstream target Bcl-2 was inactivated by metformin treatment.	Metformin	127-136	signal transducer and activator of transcription 3	Homo sapiens	17-67
24577086-8	2014	Mechanistically, signal transducer and activator of transcription 3 (Stat3) and its downstream target Bcl-2 was inactivated by metformin treatment.	Metformin	127-136	signal transducer and activator of transcription 3	Homo sapiens	69-74
24577086-8	2014	Mechanistically, signal transducer and activator of transcription 3 (Stat3) and its downstream target Bcl-2 was inactivated by metformin treatment.	Metformin	127-136	BCL2 apoptosis regulator	Homo sapiens	102-107
24577086-9	2014	Accordingly, small interfering RNA (siRNA)-mediated Stat3 knockdown enhanced metformin-induced autophagy and apoptosis, and concomitantly enhanced the inhibitory effect of metformin on cell viability.	Metformin	77-86	signal transducer and activator of transcription 3	Homo sapiens	52-57
24577086-9	2014	Accordingly, small interfering RNA (siRNA)-mediated Stat3 knockdown enhanced metformin-induced autophagy and apoptosis, and concomitantly enhanced the inhibitory effect of metformin on cell viability.	Metformin	172-181	signal transducer and activator of transcription 3	Homo sapiens	52-57
24577086-10	2014	Similarly, the Bcl-2 proto-oncogene, an inhibitor of both apoptosis and autophagy, was repressed by metformin.	Metformin	100-109	BCL2 apoptosis regulator	Homo sapiens	15-20
24577086-11	2014	Ectopic expression of Bcl-2 protected cells from metformin-mediated autophagy and apoptosis.	Metformin	49-58	BCL2 apoptosis regulator	Homo sapiens	22-27
24577086-12	2014	In vivo, metformin downregulated Stat3 activity and Bcl-2 expression, induced apoptosis and autophagy, and inhibited tumor growth.	Metformin	9-18	signal transducer and activator of transcription 3	Homo sapiens	33-38
24577086-12	2014	In vivo, metformin downregulated Stat3 activity and Bcl-2 expression, induced apoptosis and autophagy, and inhibited tumor growth.	Metformin	9-18	BCL2 apoptosis regulator	Homo sapiens	52-57
24577086-13	2014	Together, inactivation of Stat3-Bcl-2 pathway contributes to metformin-induced growth inhibition of ESCC by facilitating crosstalk between apoptosis and autophagy.	Metformin	61-70	signal transducer and activator of transcription 3	Homo sapiens	26-31
24577086-13	2014	Together, inactivation of Stat3-Bcl-2 pathway contributes to metformin-induced growth inhibition of ESCC by facilitating crosstalk between apoptosis and autophagy.	Metformin	61-70	BCL2 apoptosis regulator	Homo sapiens	32-37
24531544-0	2014	Metformin interferes with bile acid homeostasis through AMPK-FXR crosstalk.	Metformin	0-9	nuclear receptor subfamily 1, group H, member 4	Mus musculus	61-64
24531544-7	2014	Furthermore, treatment with AMPK activators, including the antidiabetic biguanide metformin, inhibited FXR agonist induction of FXR target genes in mouse liver and intestine.	Metformin	82-91	nuclear receptor subfamily 1, group H, member 4	Mus musculus	103-106
24531544-7	2014	Furthermore, treatment with AMPK activators, including the antidiabetic biguanide metformin, inhibited FXR agonist induction of FXR target genes in mouse liver and intestine.	Metformin	82-91	nuclear receptor subfamily 1, group H, member 4	Mus musculus	128-131
24531544-8	2014	In a mouse model of intrahepatic cholestasis, metformin treatment induced FXR phosphorylation, perturbed bile acid homeostasis, and worsened liver injury.	Metformin	46-55	nuclear receptor subfamily 1, group H, member 4	Mus musculus	74-77
24393785-8	2014	Metformin might influence tumourigenesis, both indirectly, through the systemic reduction of insulin levels, and directly, via the induction of energetic stress; however, these effects require further investigation.	Metformin	0-9	insulin	Homo sapiens	93-100
24505341-8	2014	Metformin has been reported to activate AMPK, thereby suppressing mTOR, which plays an important role for protein synthesis, cell cycle progression, and cell survival.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	66-70
24505341-10	2014	Furthermore, hyperthermia potentiated the effect of metformin to activate AMPK and inactivate mTOR and S6K.	Metformin	52-61	mechanistic target of rapamycin kinase	Homo sapiens	94-98
24505341-11	2014	Cell proliferation was markedly suppressed by metformin or combination of metformin and hyperthermia, which could be attributed to activation of AMPK leading to inactivation of mTOR.	Metformin	46-55	mechanistic target of rapamycin kinase	Homo sapiens	177-181
24505341-11	2014	Cell proliferation was markedly suppressed by metformin or combination of metformin and hyperthermia, which could be attributed to activation of AMPK leading to inactivation of mTOR.	Metformin	74-83	mechanistic target of rapamycin kinase	Homo sapiens	177-181
24322659-0	2014	Metformin selectively targets tumor-initiating cells in ErbB2-overexpressing breast cancer models.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	56-61
24285728-5	2014	Finally, forcing glycolysis by metformin treatment augments this response and the efficacy of MCT1 inhibitors, suggesting an attractive combination therapy for MYC/MCT1-expressing malignancies.	Metformin	31-40	solute carrier family 16 member 1	Homo sapiens	164-168
24322659-11	2014	Our results, especially the in vivo data, provide fundamental support for developing metformin-mediated preventive strategies targeting ErbB2-associated carcinogenesis.	Metformin	85-94	erb-b2 receptor tyrosine kinase 2	Homo sapiens	136-141
24322659-6	2014	We report here for the first time that systemic administration of metformin selectively inhibits CD61(high)/CD49f(high) subpopulation, a group of tumor-initiating cells (TIC) of mouse mammary tumor virus (MMTV)-ErbB2 mammary tumors, in preneoplastic mammary glands.	Metformin	66-75	erb-b2 receptor tyrosine kinase 2	Homo sapiens	211-216
24322659-7	2014	Metformin also inhibited CD61(high)/CD49f(high) subpopulation in MMTV-ErbB2 tumor-derived cells, which was correlated with their compromised tumor initiation/development in a syngeneic tumor graft model.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	70-75
24322659-8	2014	Molecular analysis indicated that metformin induced downregulation of ErbB2 and EGFR expression and inhibited the phosphorylation of ErbB family members, insulin-like growth factor-1R, AKT, mTOR, and STAT3 in vivo.	Metformin	34-43	erb-b2 receptor tyrosine kinase 2	Homo sapiens	70-75
24322659-8	2014	Molecular analysis indicated that metformin induced downregulation of ErbB2 and EGFR expression and inhibited the phosphorylation of ErbB family members, insulin-like growth factor-1R, AKT, mTOR, and STAT3 in vivo.	Metformin	34-43	epidermal growth factor receptor	Homo sapiens	80-84
24322659-8	2014	Molecular analysis indicated that metformin induced downregulation of ErbB2 and EGFR expression and inhibited the phosphorylation of ErbB family members, insulin-like growth factor-1R, AKT, mTOR, and STAT3 in vivo.	Metformin	34-43	epidermal growth factor receptor	Homo sapiens	70-74
24322659-8	2014	Molecular analysis indicated that metformin induced downregulation of ErbB2 and EGFR expression and inhibited the phosphorylation of ErbB family members, insulin-like growth factor-1R, AKT, mTOR, and STAT3 in vivo.	Metformin	34-43	AKT serine/threonine kinase 1	Homo sapiens	154-188
24322659-8	2014	Molecular analysis indicated that metformin induced downregulation of ErbB2 and EGFR expression and inhibited the phosphorylation of ErbB family members, insulin-like growth factor-1R, AKT, mTOR, and STAT3 in vivo.	Metformin	34-43	mechanistic target of rapamycin kinase	Homo sapiens	190-194
24322659-8	2014	Molecular analysis indicated that metformin induced downregulation of ErbB2 and EGFR expression and inhibited the phosphorylation of ErbB family members, insulin-like growth factor-1R, AKT, mTOR, and STAT3 in vivo.	Metformin	34-43	signal transducer and activator of transcription 3	Homo sapiens	200-205
24322659-9	2014	In vitro data indicate that low doses of metformin inhibited the self-renewal/proliferation of cancer stem cells (CSC)/TICs in ErbB2-overexpressing breast cancer cells.	Metformin	41-50	erb-b2 receptor tyrosine kinase 2	Homo sapiens	127-132
24322659-10	2014	We further demonstrated that the expression and activation of ErbB2 were preferentially increased in CSC/TIC-enriched tumorsphere cells, which promoted their self-renewal/proliferation and rendered them more sensitive to metformin.	Metformin	221-230	erb-b2 receptor tyrosine kinase 2	Homo sapiens	62-67
23668534-2	2014	Metformin, which attenuates insulin resistance, has been recommended as the first-line antidiabetic medication.	Metformin	0-9	insulin	Homo sapiens	28-35
24186866-0	2014	Effects of sitagliptin and metformin treatment on incretin hormone and insulin secretory responses to oral and "isoglycemic" intravenous glucose.	Metformin	27-36	insulin	Homo sapiens	71-78
24186866-1	2014	Dipeptidyl peptidase-4 (DPP-4) inhibitors prevent degradation of incretin hormones (glucagon-like peptide 1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]), whereas metformin may increase GLP-1 levels.	Metformin	181-190	gastric inhibitory polypeptide	Homo sapiens	166-169
24186866-3	2014	Fasting total GLP-1 was significantly increased by metformin and not changed by sitagliptin.	Metformin	51-60	glucagon	Homo sapiens	14-19
23668534-5	2014	Moreover, recent studies have suggested that metformin enhances the biological effect of GLP-1 by increasing GLP-1 secretion, suppressing activity of DPP-4 and upregulating the expression of GLP-1 receptor in pancreatic beta-cells.	Metformin	45-54	glucagon	Homo sapiens	89-94
23668534-5	2014	Moreover, recent studies have suggested that metformin enhances the biological effect of GLP-1 by increasing GLP-1 secretion, suppressing activity of DPP-4 and upregulating the expression of GLP-1 receptor in pancreatic beta-cells.	Metformin	45-54	glucagon	Homo sapiens	109-114
24485398-12	2014	CONCLUSIONS: Even after long duration of diabetes, addition of glimepiride to insulin and metformin can be effective in lowering HbA1c and/or reducing the need for exogenous insulin.	Metformin	90-99	insulin	Homo sapiens	174-181
29872460-2	2014	The objective of this study was to analyse efficacy and hypoglycaemia outcomes in people with type 2 diabetes receiving insulin glargine (IG) with metformin (MET), sulphonylurea (SU) or MET+SU.	Metformin	147-156	insulin	Homo sapiens	120-127
24261663-7	2014	KEY RESULTS: Metformin (50 muM) decreased mRNA and protein levels of GLUT1, GLUT3, MCT4 and PFK 1 but did not affect LDH mRNA or protein levels.	Metformin	13-22	latexin	Homo sapiens	27-30
29872461-2	2014	More recently, several clinical trials have confirmed resveratrol"s potential to substantially enhance the therapeutic effects of the pharmaceutical metformin hydrochloride, particularly related to glucose management, insulin sensitivity and cardioprotection.	Metformin	149-172	insulin	Homo sapiens	218-225
24396411-0	2014	Metformin inhibits proliferation of human keratinocytes through a mechanism associated with activation of the MAPK signaling pathway.	Metformin	0-9	mitogen-activated protein kinase 3	Homo sapiens	110-114
24251799-7	2014	Lifestyle modifications and metformin produced comparable changes in adiponectin levels, which were not associated with changes in BF, HbA1c, glucose and regional fat depots.	Metformin	28-37	adiponectin, C1Q and collagen domain containing	Homo sapiens	69-80
24251799-10	2014	CONCLUSIONS: In postmenopausal women with newly diagnosed T2DM, lifestyle modifications alone or combined with metformin produced comparable changes in adiponectin levels.	Metformin	111-120	adiponectin, C1Q and collagen domain containing	Homo sapiens	152-163
24396411-11	2014	In conclusion, metformin treatment upregulated the levels of p-AMPK and p-ERK1/2 in HaCaT cells, and significantly inhibited HaCaT cell proliferation in vitro by a mechanism associated with activation of the mitogen-activated protein kinase signaling pathway.	Metformin	15-24	mitogen-activated protein kinase 3	Homo sapiens	74-80
24231192-0	2014	Ferritin heavy chain as main mediator of preventive effect of metformin against mitochondrial damage induced by doxorubicin in cardiomyocytes.	Metformin	62-71	ferritin heavy chain 1	Rattus norvegicus	0-20
24622715-15	2014	Patients taking metformin had lower HbA1c, insulin, HOMA-IR, and tissue plasminogen activator compared with those taking placebo, but there were no significant differences for total cholesterol, HDL-cholesterol, non-HDL-cholesterol, triglycerides, high sensitivity C-reactive protein, or fasting glucose.	Metformin	16-25	insulin	Homo sapiens	43-50
24231192-2	2014	Metformin (MET) has been seen to have a protective effect against the oxidative stress induced by DOX in cardiomyocytes through its modulation of ferritin heavy chain (FHC), the main iron-storage protein.	Metformin	0-9	ferritin heavy chain 1	Rattus norvegicus	146-166
24231192-2	2014	Metformin (MET) has been seen to have a protective effect against the oxidative stress induced by DOX in cardiomyocytes through its modulation of ferritin heavy chain (FHC), the main iron-storage protein.	Metformin	0-9	ferritin heavy chain 1	Rattus norvegicus	168-171
24281385-9	2014	Nitric oxide donor sodium nitroprusside was more potent in inducing relaxation in cav-1(-/-) than in WT, and metformin reversed this effect.	Metformin	109-118	caveolin 1	Homo sapiens	82-87
24622715-15	2014	Patients taking metformin had lower HbA1c, insulin, HOMA-IR, and tissue plasminogen activator compared with those taking placebo, but there were no significant differences for total cholesterol, HDL-cholesterol, non-HDL-cholesterol, triglycerides, high sensitivity C-reactive protein, or fasting glucose.	Metformin	16-25	C-reactive protein	Homo sapiens	265-283
24474794-9	2014	Metformin directly inhibited mTOR by enhancing PRAS40"s association with RAPTOR, whereas AICAR blocked the cell cycle through proteasomal degradation of the G2M phosphatase cdc25c.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	29-33
24589588-9	2014	Metformin caused an initial up-regulation followed by a down-regulation of GRP78 expression in KB cells and increased the expression of activated caspase-3.	Metformin	0-9	heat shock protein family A (Hsp70) member 5	Homo sapiens	75-80
24589588-9	2014	Metformin caused an initial up-regulation followed by a down-regulation of GRP78 expression in KB cells and increased the expression of activated caspase-3.	Metformin	0-9	caspase 3	Homo sapiens	146-155
24569407-1	2014	AIM: Anti-Mullerian hormone (AMG) reduction in women with hyperinsulinemia in therapy with metformin suggests that metformin affects the level of AMH and ovulatory dysfunction through insulin-mediated mechanisms.	Metformin	91-100	insulin	Homo sapiens	63-70
24569407-1	2014	AIM: Anti-Mullerian hormone (AMG) reduction in women with hyperinsulinemia in therapy with metformin suggests that metformin affects the level of AMH and ovulatory dysfunction through insulin-mediated mechanisms.	Metformin	115-124	insulin	Homo sapiens	63-70
24474794-9	2014	Metformin directly inhibited mTOR by enhancing PRAS40"s association with RAPTOR, whereas AICAR blocked the cell cycle through proteasomal degradation of the G2M phosphatase cdc25c.	Metformin	0-9	AKT1 substrate 1	Homo sapiens	47-53
24513020-11	2014	Moreover, oral chronic administration of metformin significantly attenuated the haloperidol-induced increase of malondialdehyde and nitrite, as well as the deficit of glutathione and catalase.	Metformin	41-50	catalase	Mus musculus	167-191
24484909-0	2014	Metformin anti-tumor effect via disruption of the MID1 translational regulator complex and AR downregulation in prostate cancer cells.	Metformin	0-9	midline 1	Homo sapiens	50-54
24484909-9	2014	The inhibitory effect of metformin was mimicked by disruption of the MID1-alpha4/PP2A protein complex by siRNA knockdown of MID1 or alpha4 whereas AMPK activation was not required.	Metformin	25-34	midline 1	Homo sapiens	69-73
24484909-9	2014	The inhibitory effect of metformin was mimicked by disruption of the MID1-alpha4/PP2A protein complex by siRNA knockdown of MID1 or alpha4 whereas AMPK activation was not required.	Metformin	25-34	midline 1	Homo sapiens	124-128
24302004-7	2014	Activation of AMPK by metformin inhibited mTORC1-STAT3 signaling, thereby preventing excess amino acid-impaired insulin signaling.	Metformin	22-31	signal transducer and activator of transcription 3	Homo sapiens	49-54
24302004-7	2014	Activation of AMPK by metformin inhibited mTORC1-STAT3 signaling, thereby preventing excess amino acid-impaired insulin signaling.	Metformin	22-31	insulin	Homo sapiens	112-119
24302004-9	2014	Chronic administration of either metformin or rapamycin inhibited the HPD-activated mTORC1/STAT3/Notch1 signaling pathway and prevented hepatic insulin resistance.	Metformin	33-42	signal transducer and activator of transcription 3	Homo sapiens	91-96
24302004-9	2014	Chronic administration of either metformin or rapamycin inhibited the HPD-activated mTORC1/STAT3/Notch1 signaling pathway and prevented hepatic insulin resistance.	Metformin	33-42	notch receptor 1	Homo sapiens	97-103
24257750-11	2014	These data provide a novel mechanism of action for metformin involving improvement of systemic insulin sensitivity through the regulation of SeP production and suggest an additional approach to the development of anti-diabetic drugs.	Metformin	51-60	selenoprotein P	Homo sapiens	141-144
24563672-0	2014	Combination of Diane-35 and Metformin to Treat Early Endometrial Carcinoma in PCOS Women with Insulin Resistance.	Metformin	28-37	insulin	Homo sapiens	94-101
24563672-3	2014	The aim of the study was to describe and discuss cases of PCOS and insulin resistance (IR) women with early endometrial carcinoma while being co-treated with Diane-35 and metformin.	Metformin	171-180	insulin	Homo sapiens	67-74
24257750-0	2014	Metformin suppresses expression of the selenoprotein P gene via an AMP-activated kinase (AMPK)/FoxO3a pathway in H4IIEC3 hepatocytes.	Metformin	0-9	selenoprotein P	Homo sapiens	39-54
24257750-0	2014	Metformin suppresses expression of the selenoprotein P gene via an AMP-activated kinase (AMPK)/FoxO3a pathway in H4IIEC3 hepatocytes.	Metformin	0-9	forkhead box O3	Homo sapiens	95-101
24257750-3	2014	The present findings demonstrate that metformin suppresses SEPP1 expression by activating AMP-activated kinase (AMPK) and subsequently inactivating FoxO3a in H4IIEC3 hepatocytes.	Metformin	38-47	selenoprotein P	Homo sapiens	59-64
24257750-3	2014	The present findings demonstrate that metformin suppresses SEPP1 expression by activating AMP-activated kinase (AMPK) and subsequently inactivating FoxO3a in H4IIEC3 hepatocytes.	Metformin	38-47	forkhead box O3	Homo sapiens	148-154
24257750-4	2014	Treatment with metformin reduced SEPP1 promoter activity in a concentration- and time-dependent manner; this effect was cancelled by co-administration of an AMPK inhibitor.	Metformin	15-24	selenoprotein P	Homo sapiens	33-38
24257750-6	2014	Computational analysis of transcription factor binding sites conserved among the species resulted in identification of the FoxO-binding site in the metformin-response element of the SEPP1 promoter.	Metformin	148-157	selenoprotein P	Homo sapiens	182-187
24257750-7	2014	A luciferase reporter assay showed that metformin suppresses Forkhead-response element activity, and a ChIP assay revealed that metformin decreases binding of FoxO3a, a direct target of AMPK, to the SEPP1 promoter.	Metformin	40-49	selenoprotein P	Homo sapiens	199-204
24257750-7	2014	A luciferase reporter assay showed that metformin suppresses Forkhead-response element activity, and a ChIP assay revealed that metformin decreases binding of FoxO3a, a direct target of AMPK, to the SEPP1 promoter.	Metformin	128-137	forkhead box O3	Homo sapiens	159-165
24257750-7	2014	A luciferase reporter assay showed that metformin suppresses Forkhead-response element activity, and a ChIP assay revealed that metformin decreases binding of FoxO3a, a direct target of AMPK, to the SEPP1 promoter.	Metformin	128-137	selenoprotein P	Homo sapiens	199-204
24257750-8	2014	Transfection with siRNAs for Foxo3a, but not for Foxo1, cancelled metformin-induced luciferase activity suppression of the metformin-response element of the SEPP1 promoter.	Metformin	66-75	forkhead box O3	Homo sapiens	29-35
24257750-8	2014	Transfection with siRNAs for Foxo3a, but not for Foxo1, cancelled metformin-induced luciferase activity suppression of the metformin-response element of the SEPP1 promoter.	Metformin	66-75	selenoprotein P	Homo sapiens	157-162
24257750-8	2014	Transfection with siRNAs for Foxo3a, but not for Foxo1, cancelled metformin-induced luciferase activity suppression of the metformin-response element of the SEPP1 promoter.	Metformin	123-132	forkhead box O3	Homo sapiens	29-35
24257750-8	2014	Transfection with siRNAs for Foxo3a, but not for Foxo1, cancelled metformin-induced luciferase activity suppression of the metformin-response element of the SEPP1 promoter.	Metformin	123-132	selenoprotein P	Homo sapiens	157-162
24257750-9	2014	The overexpression of FoxO3a stimulated SEPP1 promoter activity and rescued the suppressive effect of metformin.	Metformin	102-111	forkhead box O3	Homo sapiens	22-28
24857149-2	2014	Metformin, an oral antidiabetic drug, improves insulin resistance and has been associated with reduced cancer incidence and cancer mortality.	Metformin	0-9	insulin	Homo sapiens	47-54
24857149-0	2014	Hype versus hope: metformin and vitamin D as anticancer agents.	Metformin	18-27	FIC domain protein adenylyltransferase	Homo sapiens	0-4
24385405-6	2014	Previous studies have supported the beneficial effects of metformin in reduction of body weight, improvement of insulin resistance, prevention of complications related to diabetes and chemo-preventive benefits in reducing hepatocellular carcinoma.	Metformin	58-67	insulin	Homo sapiens	112-119
24935589-9	2014	In the present study, with an increasing concentration of metformin, the expression of MMP-9 was downregulated whereas that of E-cadherin was significantly upregulated.	Metformin	58-67	cadherin 1	Homo sapiens	127-137
24935589-0	2014	Cisplatin combined with metformin inhibits migration and invasion of human nasopharyngeal carcinoma cells by regulating E-cadherin and MMP-9.	Metformin	24-33	cadherin 1	Homo sapiens	120-130
24716971-4	2014	MATERIALS AND METHODS: Breast cancer cell lines from luminal A, luminal B, ErbB2 and triple-negative molecular subtypes were treated with a pharmacological concentration of metformin (2mM) at a glucose concentration of 5.5mM.	Metformin	173-182	erb-b2 receptor tyrosine kinase 2	Homo sapiens	75-80
24791887-1	2014	BACKGROUND: The renoprotective mechanisms of adenosine monophosphate (AMP)-activated protein kinase (AMPK) agonist - metformin have not been stated clearly.	Metformin	117-126	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	101-105
24762600-9	2014	Metformin increased the expression of SIRT3 (1.5-fold) and SOD2 (2-fold) while down regulating NF-kappaB p65 (1.5-fold) and JNK1 (1.5-fold).	Metformin	0-9	synaptotagmin 1	Rattus norvegicus	105-108
24762600-10	2014	Knockdown of SIRT3 (P < 0.05) reversed the metformin-induced decreases in NF-kappaB p65 and JNK1 and the metformin-induced increase in SOD2 (P < 0.05).	Metformin	46-55	synaptotagmin 1	Rattus norvegicus	87-90
24791887-11	2014	Conlusion Metformin can suppress the expression of NF-kappaB, MCP-1, ICAM-1 and TGF-beta1 of glomerular MCs induced by high glucose via AMPK activation, which may partly contribute to its reno-protection.	Metformin	10-19	transforming growth factor, beta 1	Rattus norvegicus	80-89
24791887-11	2014	Conlusion Metformin can suppress the expression of NF-kappaB, MCP-1, ICAM-1 and TGF-beta1 of glomerular MCs induced by high glucose via AMPK activation, which may partly contribute to its reno-protection.	Metformin	10-19	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	136-140
24791887-2	2014	We hypothesized that metformin may ameliorate inflammation via AMPK interaction with critical inflammatory cytokines.	Metformin	21-30	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	63-67
24791887-9	2014	Both genes and protein expression of NF-kappaB, MCP-1, ICAM-1, TGF-beta1 of MCs induced by high glucose were markedly reduced after metformin treatment in a dose-dependent manner (P < 0.05).	Metformin	132-141	transforming growth factor, beta 1	Rattus norvegicus	63-72
24791887-10	2014	The expression of p-AMPK increased with the rising of metformin concentration, presenting the opposite trend, while the level of total-AMPK protein was unchanged with exposure to HG or metformin.	Metformin	54-63	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	20-24
23983188-8	2014	Mouse embryonic stem cells were used as a cell culture model of embryonic neuroepithelium to study metformin effects on AMPK and Pax3 expression.	Metformin	99-108	paired box 3	Mus musculus	129-133
24135389-0	2014	Metformin, but not rosiglitazone, attenuates the increasing plasma levels of a new cardiovascular marker, fibulin-1, in patients with type 2 diabetes.	Metformin	0-9	fibulin 1	Homo sapiens	106-115
24135389-3	2014	We hypothesized that metformin would influence the increased level of plasma fibulin-1 in diabetes.	Metformin	21-30	fibulin 1	Homo sapiens	77-86
24135389-6	2014	RESULTS Plasma fibulin-1 increased in all groups throughout the 2-year period; however, the increase was strongly attenuated among patients treated with metformin.	Metformin	153-162	fibulin 1	Homo sapiens	15-24
24135389-7	2014	A highly significant difference was observed when the mean change in plasma fibulin-1 was compared between metformin- and non-metformin-treated individuals both at 18 and 24 months of treatment, but rosiglitazone had no effect.	Metformin	107-116	fibulin 1	Homo sapiens	76-85
24135389-7	2014	A highly significant difference was observed when the mean change in plasma fibulin-1 was compared between metformin- and non-metformin-treated individuals both at 18 and 24 months of treatment, but rosiglitazone had no effect.	Metformin	126-135	fibulin 1	Homo sapiens	76-85
24135389-9	2014	CONCLUSIONS Metformin attenuates the increase in plasma fibulin-1 concentrations in T2D, independently of glycemic effects.	Metformin	12-21	fibulin 1	Homo sapiens	56-65
24135389-10	2014	Changes in fibulin-1 may reflect an important element in diabetic arteriopathy that can be influenced by metformin.	Metformin	105-114	fibulin 1	Homo sapiens	11-20
24992778-1	2014	OBJECTIVE: The aim of this study was to observe clinical curative effects of combination application of dimethylbiguanide and pioglitazone and single application of pioglitazone in patients with polycystic ovarian syndrome (PCOS) complicated with insulin resistance (IR).	Metformin	104-121	insulin	Homo sapiens	247-254
24992778-9	2014	CONCLUSION: The combination of dimethylbiguanide and pioglitazone was more effective for the treatment of PCOS complicated with IR than simple pioglitazone; chronic inflammation occurrence was possibly one of reasons for insulin sensitivity reduction of patients with PCOS.	Metformin	31-48	insulin	Homo sapiens	221-228
24078137-10	2014	VGLUT1, which is responsible for loading glutamate into synaptic vesicles, was found to be differentially abundant in db/db mice and was not normalised by metformin.	Metformin	155-164	solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 7	Mus musculus	0-6
23983188-11	2014	However, metformin increased activated AMPK and inhibited Pax3 expression by mouse embryonic stem cells.	Metformin	9-18	paired box 3	Mus musculus	58-62
24549596-9	2014	Plasma proinsulin and androstenedione levels decreased after metformin treatment only in obese PCOS women.	Metformin	61-70	insulin	Homo sapiens	7-17
24478399-8	2014	Metformin (but not placebo) led to significant changes in circulating miR-192 (49.5%; P = 0.022), miR-140-5p (-15.8%; P = 0.004), and miR-222 (-47.2%; P = 0.03), in parallel to decreased fasting glucose and HbA1c.	Metformin	0-9	microRNA 192	Homo sapiens	70-77
24183733-5	2014	Metformin is an insulin sensitising agent which is safe, widely available and currently licensed for type-2 diabetes.	Metformin	0-9	insulin	Homo sapiens	16-23
25069836-3	2014	Metformin is a first-line drug in the treatment of overweight and obese type 2 diabetic patients, offering a selective pathophysiological approach by its effect on insulin resistance.	Metformin	0-9	insulin	Homo sapiens	164-171
25069836-9	2014	Because of the suggested benefits for the treatment of insulin resistance in many clinical conditions, besides type 2 diabetes, the prospective exists that more indications for metformin treatment are becoming a reality.	Metformin	177-186	insulin	Homo sapiens	55-62
24289822-8	2014	Patients with pronounced insulin resistance might need Metformin, and Glitazones need more studies.	Metformin	55-64	insulin	Homo sapiens	25-32
24549596-11	2014	Proinsulin level decreases due to metformin treatment.	Metformin	34-43	insulin	Homo sapiens	0-10
26464852-0	2014	p21(WAF1/CIP1) Expression is Differentially Regulated by Metformin and Rapamycin.	Metformin	57-66	cyclin dependent kinase inhibitor 1A	Homo sapiens	0-3
26464852-0	2014	p21(WAF1/CIP1) Expression is Differentially Regulated by Metformin and Rapamycin.	Metformin	57-66	cyclin dependent kinase inhibitor 1A	Homo sapiens	4-8
26464852-0	2014	p21(WAF1/CIP1) Expression is Differentially Regulated by Metformin and Rapamycin.	Metformin	57-66	cyclin dependent kinase inhibitor 1A	Homo sapiens	9-13
26464852-4	2014	Here we investigated the effect of metformin and rapamycin on mTOR-related phenotypes in cell lines of epithelial origin.	Metformin	35-44	mechanistic target of rapamycin kinase	Homo sapiens	62-66
26464852-5	2014	This study reports that metformin inhibits high glucose-induced p21 expression.	Metformin	24-33	cyclin dependent kinase inhibitor 1A	Homo sapiens	64-67
26464852-8	2014	However, the inhibition of the mTOR pathway by rapamycin did not have a negative effect on p21 expression, suggesting that metformin regulates p21 upstream of mTOR.	Metformin	123-132	mechanistic target of rapamycin kinase	Homo sapiens	31-35
26464852-8	2014	However, the inhibition of the mTOR pathway by rapamycin did not have a negative effect on p21 expression, suggesting that metformin regulates p21 upstream of mTOR.	Metformin	123-132	cyclin dependent kinase inhibitor 1A	Homo sapiens	143-146
26464852-8	2014	However, the inhibition of the mTOR pathway by rapamycin did not have a negative effect on p21 expression, suggesting that metformin regulates p21 upstream of mTOR.	Metformin	123-132	mechanistic target of rapamycin kinase	Homo sapiens	159-163
24577463-3	2014	No study has yet reported a protective cognitive effect of metformin, an insulin-sensitizing biguanide widely used in diabetic patients.	Metformin	59-68	insulin	Homo sapiens	73-80
24603137-0	2014	Human granulosa cells: insulin and insulin-like growth factor-1 receptors and aromatase expression modulation by metformin.	Metformin	113-122	insulin like growth factor 1	Homo sapiens	35-63
24603137-0	2014	Human granulosa cells: insulin and insulin-like growth factor-1 receptors and aromatase expression modulation by metformin.	Metformin	113-122	cytochrome P450 family 19 subfamily A member 1	Homo sapiens	78-87
24603137-3	2014	The aim of this study was to evaluate gene and protein expression of an insulin receptor (IR), insulin-like growth factor-1 (IGF1) receptor (IGF1R) and aromatase in granulosa cells treated with metformin and insulin.	Metformin	194-203	cytochrome P450 family 19 subfamily A member 1	Homo sapiens	152-161
24603137-3	2014	The aim of this study was to evaluate gene and protein expression of an insulin receptor (IR), insulin-like growth factor-1 (IGF1) receptor (IGF1R) and aromatase in granulosa cells treated with metformin and insulin.	Metformin	194-203	insulin	Homo sapiens	72-79
24603137-7	2014	Aromatase mRNA expression was significantly reduced in metformin-incubated cells following stimulation with insulin for 30 min.	Metformin	55-64	cytochrome P450 family 19 subfamily A member 1	Homo sapiens	0-9
24603137-7	2014	Aromatase mRNA expression was significantly reduced in metformin-incubated cells following stimulation with insulin for 30 min.	Metformin	55-64	insulin	Homo sapiens	108-115
24603137-9	2014	CONCLUSION: A direct effect of metformin on the gene expression of IGF1R, IR and aromatase was observed.	Metformin	31-40	cytochrome P450 family 19 subfamily A member 1	Homo sapiens	81-90
24750786-3	2014	Metformin exerts anticancer effects by primarily blocking the pivotal LKB1/AMPK/mTOR/S6K1 pathway-dependent cell growth, induces selective lethal effects on GSC by impairing the GSC-initiating spherogenesis and inhibits the proliferation of CD133+ cells, while having a low or null effect on differentiated glioblastoma cells and normal human stem cells.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	80-84
24750786-4	2014	Metformin and ATO induce autophagy and apoptosis in glioma cells by inhibiting and stimulating the PI3K/Akt and the mitogen-activated protein kinase pathways, respectively.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	104-107
24750786-6	2014	In this regard, metformin acts via activation of the AMPK-FOXO3 axis, whereas ATO blocks the interleukin 6-induced promotion of STAT3 phosphorylation.	Metformin	16-25	forkhead box O3	Homo sapiens	58-63
24243637-9	2014	Treatment of adipocyte fractions or SGBS adipocytes with metformin or acetylsalicylic acid, which target C/EBPbeta and NF-kappaB/RelA signaling, attenuated the IL-1alpha induction of 11beta-HSD1 (P<=.002).	Metformin	57-66	nuclear factor kappa B subunit 1	Homo sapiens	119-128
24243637-9	2014	Treatment of adipocyte fractions or SGBS adipocytes with metformin or acetylsalicylic acid, which target C/EBPbeta and NF-kappaB/RelA signaling, attenuated the IL-1alpha induction of 11beta-HSD1 (P<=.002).	Metformin	57-66	hydroxysteroid 11-beta dehydrogenase 1	Homo sapiens	183-194
24243637-11	2014	These molecules/signaling pathways are, therefore, potential targets for drugs, including metformin and acetylsalicylic acid, to prevent/decreased up-regulation of 11beta-HSD1 in human obese/metabolic syndrome adipose tissue.	Metformin	90-99	hydroxysteroid 11-beta dehydrogenase 1	Homo sapiens	164-175
24296614-3	2014	Hyperglycemia was determined without any clinical sign and metformin was started for steroid-induced insulin resistance.	Metformin	59-68	insulin	Homo sapiens	101-108
24812633-11	2014	Metformin attenuated the suppression on proliferation with increased expression of Col I, OCN, and OPG, meanwhile suppressing MMP1 and MMP2.	Metformin	0-9	bone gamma-carboxyglutamate protein	Homo sapiens	90-93
24812633-13	2014	Metformin attenuated the downregulation of ALP completely at day 6, partly at day 12, but not at day 18.	Metformin	0-9	alkaline phosphatase, placental	Homo sapiens	43-46
23893676-9	2014	Within the PWS group, responders to metformin had higher 2-h glucose levels on OGTT (7.48 mmol/L vs. 4.235 mmol/L; p=0.003) and higher fasting insulin levels (116 pmol/L vs. 53.5 pmol/L; p=0.04).	Metformin	36-45	insulin	Homo sapiens	143-150
25763406-3	2014	Insulin resistance (IR) plays a pivotal role in the pathogenesis of both PCOS and GDM, representing an important therapeutic target, with metformin being the most widely prescribed insulin-sensitizing antidiabetic drug.	Metformin	138-147	insulin	Homo sapiens	0-7
25763406-3	2014	Insulin resistance (IR) plays a pivotal role in the pathogenesis of both PCOS and GDM, representing an important therapeutic target, with metformin being the most widely prescribed insulin-sensitizing antidiabetic drug.	Metformin	138-147	insulin	Homo sapiens	181-188
23981104-6	2014	RESULTS: Metformin significantly reduced levels of vWF, sVCAM-1, t-PA, PAI-1, CRP and sICAM-1, which, except for CRP, remained significant after adjustment for baseline differences in age, sex, smoking and severity of previous cardiovascular (CV) disease.	Metformin	9-18	von Willebrand factor	Homo sapiens	51-54
23981104-6	2014	RESULTS: Metformin significantly reduced levels of vWF, sVCAM-1, t-PA, PAI-1, CRP and sICAM-1, which, except for CRP, remained significant after adjustment for baseline differences in age, sex, smoking and severity of previous cardiovascular (CV) disease.	Metformin	9-18	plasminogen activator, tissue type	Homo sapiens	65-69
23981104-6	2014	RESULTS: Metformin significantly reduced levels of vWF, sVCAM-1, t-PA, PAI-1, CRP and sICAM-1, which, except for CRP, remained significant after adjustment for baseline differences in age, sex, smoking and severity of previous cardiovascular (CV) disease.	Metformin	9-18	C-reactive protein	Homo sapiens	78-81
23981104-6	2014	RESULTS: Metformin significantly reduced levels of vWF, sVCAM-1, t-PA, PAI-1, CRP and sICAM-1, which, except for CRP, remained significant after adjustment for baseline differences in age, sex, smoking and severity of previous cardiovascular (CV) disease.	Metformin	9-18	C-reactive protein	Homo sapiens	113-116
23981104-8	2014	The improvements in vWf and sVCAM-1 statistically explained about 34% of the reduction in the risk of CV morbidity and mortality associated with metformin treatment in this study.	Metformin	145-154	von Willebrand factor	Homo sapiens	20-23
23981104-9	2014	CONCLUSIONS: Metformin is associated with improvement in some (vWF and sVCAM-1) but not all markers of endothelial function, which may explain why it is associated with a decreased risk of CV disease in type 2 diabetes.	Metformin	13-22	von Willebrand factor	Homo sapiens	63-66
24829699-2	2014	Metformin is an oral hypoglycemic agent which improves insulin resistance.	Metformin	0-9	insulin	Homo sapiens	55-62
25726246-6	2014	Peripheral insulin resistance was also enhanced and the GP in charge decided to discontinue the dosing of metformin as a result.	Metformin	106-115	insulin	Homo sapiens	11-18
25308229-0	2014	[Sulphonylurea derivatives or insulin with metformin?].	Metformin	43-52	insulin	Homo sapiens	30-37
24190973-8	2014	The activation of p53 through AMPK-mediated MDMX phosphorylation and inactivation was further confirmed by using cell and animal model systems with two AMPK activators, metformin and salicylate (the active form of aspirin).	Metformin	169-178	tumor protein p53	Homo sapiens	18-21
26351208-2	2014	Adenosine 5"-monophosphate-activated protein kinase (AMPK) activators such as metformin have similar actions in keeping with the TSC2/1 pathway linking activation of AMPK to inhibition of mTOR.	Metformin	78-87	mechanistic target of rapamycin kinase	Homo sapiens	188-192
24351837-5	2013	Further experiments revealed that metformin activated AMP-activated protein kinase (AMPK) and suppressed mammalian target of rapamycin (mTOR), the central regulator of protein synthesis and cell growth.	Metformin	34-43	mechanistic target of rapamycin kinase	Homo sapiens	105-134
24357397-0	2014	Metformin reduces TGF-beta1-induced extracellular matrix production in nasal polyp-derived fibroblasts.	Metformin	0-9	transforming growth factor beta 1	Homo sapiens	18-27
24357397-3	2014	The purposes of this study were to investigate the effect of metformin on TGF-beta1-induced myofibroblast differentiation (alpha-smooth muscle actin [alpha-SMA]) and extracellular matrix (ECM) production and to determine the underlying mechanism of the action of metformin in nasal polyp-derived fibroblasts (NPDFs).	Metformin	61-70	transforming growth factor beta 1	Homo sapiens	74-83
24357397-3	2014	The purposes of this study were to investigate the effect of metformin on TGF-beta1-induced myofibroblast differentiation (alpha-smooth muscle actin [alpha-SMA]) and extracellular matrix (ECM) production and to determine the underlying mechanism of the action of metformin in nasal polyp-derived fibroblasts (NPDFs).	Metformin	263-272	transforming growth factor beta 1	Homo sapiens	74-83
24357397-10	2014	RESULTS: In TGF-beta1-induced NPDFs, metformin inhibited the expression of alpha-SMA and fibronectin, as confirmed by both RT-PCR and Western blot analysis.	Metformin	37-46	transforming growth factor beta 1	Homo sapiens	12-21
24357397-10	2014	RESULTS: In TGF-beta1-induced NPDFs, metformin inhibited the expression of alpha-SMA and fibronectin, as confirmed by both RT-PCR and Western blot analysis.	Metformin	37-46	fibronectin 1	Homo sapiens	89-100
24357397-11	2014	Metformin increased the phosphorylation of AMPK and the expression levels of alpha-SMA and fibronectin.	Metformin	0-9	fibronectin 1	Homo sapiens	91-102
24357397-13	2014	Metformin inhibited TGF-beta1-induced phosphorylation of Smad2/3.	Metformin	0-9	transforming growth factor beta 1	Homo sapiens	20-29
24357397-14	2014	CONCLUSIONS: This study showed that metformin inhibits TGF-beta1-induced myofibroblast differentiation and ECM production in NPDFs via the Smad2/3 pathway.	Metformin	36-45	transforming growth factor beta 1	Homo sapiens	55-64
24351837-5	2013	Further experiments revealed that metformin activated AMP-activated protein kinase (AMPK) and suppressed mammalian target of rapamycin (mTOR), the central regulator of protein synthesis and cell growth.	Metformin	34-43	mechanistic target of rapamycin kinase	Homo sapiens	136-140
24351837-6	2013	Moreover, daily treatment of metformin led to a substantial inhibition of tumor growth in a xenograft model with concomitant decrease in the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and p-mTOR.	Metformin	29-38	mechanistic target of rapamycin kinase	Homo sapiens	214-218
24097562-6	2013	AMPK stimulation using N1-(alpha-d-ribofuranosyl)-5-aminoimidizole-4-carboxamide or metformin decreased the LPS-induced increase in permeability, as determined by filtration coefficient (Kf) measurements, and resolved edema as indicated by decreased wet-to-dry ratios.	Metformin	84-93	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	0-4
24107633-9	2013	Mechanisms of metformin action at normal vs. high glucose overlapped but were not identical; for example, metformin reduced IGF-1R expression in both the HER2+ SK-BR-3 and TNBC MDA-MB-468 cell lines more significantly at 5, as compared with 10 mmol/L glucose.	Metformin	14-23	erb-b2 receptor tyrosine kinase 2	Homo sapiens	154-158
24107633-9	2013	Mechanisms of metformin action at normal vs. high glucose overlapped but were not identical; for example, metformin reduced IGF-1R expression in both the HER2+ SK-BR-3 and TNBC MDA-MB-468 cell lines more significantly at 5, as compared with 10 mmol/L glucose.	Metformin	106-115	erb-b2 receptor tyrosine kinase 2	Homo sapiens	154-158
24321717-10	2013	Total plasma GIP was higher in the pre-lunch period (p=0.05), but not in the post-lunch period (p=0.95), with metformin compared with placebo.	Metformin	110-119	gastric inhibitory polypeptide	Homo sapiens	13-16
23974492-6	2013	As a result, protein abundance of p27, p57 and PTEN were increased in cells exposed to metformin.	Metformin	87-96	cyclin dependent kinase inhibitor 1C	Homo sapiens	39-42
23803693-2	2013	Several metformin-induced responses and genes are similar to those observed after knockdown of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 by RNA interference, and we hypothesized that the mechanism of action of metformin in pancreatic cancer cells was due, in part, to downregulation of Sp transcription factors.	Metformin	8-17	Sp3 transcription factor	Homo sapiens	147-150
23803693-2	2013	Several metformin-induced responses and genes are similar to those observed after knockdown of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 by RNA interference, and we hypothesized that the mechanism of action of metformin in pancreatic cancer cells was due, in part, to downregulation of Sp transcription factors.	Metformin	232-241	Sp3 transcription factor	Homo sapiens	147-150
23803693-3	2013	Treatment of Panc1, L3.6pL and Panc28 pancreatic cancer cells with metformin downregulated Sp1, Sp3 and Sp4 proteins and several pro-oncogenic Sp-regulated genes including bcl-2, survivin, cyclin D1, vascular endothelial growth factor and its receptor, and fatty acid synthase.	Metformin	67-76	Sp3 transcription factor	Homo sapiens	96-99
23803693-3	2013	Treatment of Panc1, L3.6pL and Panc28 pancreatic cancer cells with metformin downregulated Sp1, Sp3 and Sp4 proteins and several pro-oncogenic Sp-regulated genes including bcl-2, survivin, cyclin D1, vascular endothelial growth factor and its receptor, and fatty acid synthase.	Metformin	67-76	BCL2 apoptosis regulator	Homo sapiens	172-177
23803693-4	2013	Metformin induced proteasome-dependent degradation of Sps in L3.6pL and Panc28 cells, whereas in Panc1 cells metformin decreased microRNA-27a and induced the Sp repressor, ZBTB10, and disruption of miR-27a:ZBTB10 by metformin was phosphatase dependent.	Metformin	0-9	microRNA 27a	Homo sapiens	198-205
23803693-4	2013	Metformin induced proteasome-dependent degradation of Sps in L3.6pL and Panc28 cells, whereas in Panc1 cells metformin decreased microRNA-27a and induced the Sp repressor, ZBTB10, and disruption of miR-27a:ZBTB10 by metformin was phosphatase dependent.	Metformin	109-118	microRNA 27a	Homo sapiens	198-205
23803693-5	2013	Metformin also inhibited pancreatic tumor growth and downregulated Sp1, Sp3 and Sp4 in tumors in an orthotopic model where L3.6pL cells were injected directly into the pancreas.	Metformin	0-9	Sp3 transcription factor	Homo sapiens	72-75
24145224-6	2013	The leading metformin response S-marker in combined group of DM2 patients was the CC variant of OCT1-R61C polymorphism of organic cation transporter protein 1 gene.	Metformin	12-21	solute carrier family 22 member 1	Homo sapiens	96-100
24321717-12	2013	Metformin, independent of exercise, significantly increased total plasma GLP-1 and GIP concentrations in these patients.	Metformin	0-9	gastric inhibitory polypeptide	Homo sapiens	83-86
24466358-2	2013	The initial reluctance to use metformin in these patients has given way to a broader acceptance after clinical trials and meta-analyses have revealed that some of the insulin-sensitizing agents lead to adverse cardiovascular events.	Metformin	30-39	insulin	Homo sapiens	167-174
24465050-8	2013	Levels of serum total cholesterol (P = 0.004), triglycerides (P = 0.014), and adiponectin (P = 0.001) took a favorable turn after metformin treatment.	Metformin	130-139	adiponectin, C1Q and collagen domain containing	Homo sapiens	78-89
24053326-8	2013	Furthermore, inactivation of Akt, blockade of ROS generation and independence of activations of AMPK and MAPK by metformin were also observed.	Metformin	113-122	mitogen-activated protein kinase 1	Mus musculus	105-109
24267731-2	2013	Metformin might reduce cancer growth through direct antiproliferative effects or through indirect mechanisms, particularly the reduction of insulin.	Metformin	0-9	insulin	Homo sapiens	140-147
24053326-0	2013	Blockade of reactive oxygen species and Akt activation is critical for anti-inflammation and growth inhibition of metformin in phosphatase and tensin homolog-deficient RAW264.7 cells.	Metformin	114-123	thymoma viral proto-oncogene 1	Mus musculus	40-43
24053326-3	2013	OBJECTIVE: We aimed to investigate the possible mechanisms of how PTEN regulates metformin against cell growth and inflammation.	Metformin	81-90	phosphatase and tensin homolog	Mus musculus	66-70
23657947-7	2013	Glipizide plus metformin significantly increased fasting insulin [2.33, 95 % CI (1.94, 2.73)].	Metformin	15-24	insulin	Homo sapiens	57-64
24152681-0	2013	Metformin increases the novel adipokine cartonectin/CTRP3 in women with polycystic ovary syndrome.	Metformin	0-9	C1q and TNF related 3	Homo sapiens	40-51
24152681-0	2013	Metformin increases the novel adipokine cartonectin/CTRP3 in women with polycystic ovary syndrome.	Metformin	0-9	C1q and TNF related 3	Homo sapiens	52-57
24152681-9	2013	After 6 months of metformin treatment, there was an associated increase in serum cartonectin (P < .05).	Metformin	18-27	C1q and TNF related 3	Homo sapiens	81-92
24152681-11	2013	Finally, cartonectin protein production and secretion into conditioned media were significantly increased by metformin in control human omental AT explants (P < .05).	Metformin	109-118	C1q and TNF related 3	Homo sapiens	9-20
24152681-13	2013	Metformin treatment increases serum cartonectin levels in these women and in omental AT explants.	Metformin	0-9	C1q and TNF related 3	Homo sapiens	36-47
24053326-10	2013	Moreover, metformin affected PTEN-deficient cells dependent of inhibition of ROS production and Akt activation against enlarged inflammatory mediators and/or cell growth in shPTEN cells.	Metformin	10-19	phosphatase and tensin homolog	Mus musculus	29-33
24053326-10	2013	Moreover, metformin affected PTEN-deficient cells dependent of inhibition of ROS production and Akt activation against enlarged inflammatory mediators and/or cell growth in shPTEN cells.	Metformin	10-19	thymoma viral proto-oncogene 1	Mus musculus	96-99
23953891-7	2013	Following metformin, which decreased glucose and insulin in only the IR subjects, 4 BCAA/AAAs increased in the IR subjects at or below P=0.05, and none changed in the IS subjects.	Metformin	10-19	AT-rich interaction domain 4B	Homo sapiens	84-88
23875783-0	2013	Role of adiponectin and its receptor in prediction of reproductive outcome of metformin treatment in patients with polycystic ovarian syndrome.	Metformin	78-87	adiponectin, C1Q and collagen domain containing	Homo sapiens	8-19
23875783-1	2013	AIMS: The aim of this study was to examine the effect of metformin on serum adiponectin and adiponectin receptor-1 (AdipoR1) and evaluate their role in prediction of ovulation in patients with polycystic ovarian syndrome (PCOS).	Metformin	57-66	adiponectin, C1Q and collagen domain containing	Homo sapiens	76-87
24094981-0	2013	Resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin.	Metformin	121-130	insulin	Homo sapiens	54-61
24094981-2	2013	As the first-line medication, metformin is commonly used for MS to reduce insulin resistance.	Metformin	30-39	insulin	Homo sapiens	74-81
24094981-8	2013	Here, we hypothesized that resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin.	Metformin	148-157	insulin	Homo sapiens	81-88
24094981-9	2013	This hypothesis could explain why rosiglitazone is superior to metformin in enhancement of insulin sensitivity.	Metformin	63-72	insulin	Homo sapiens	91-98
23875783-7	2013	Group 1 showed post-metformin higher adiponectin and AdipoR1 (P = 0.01) and lower HOMA-IR (P = 0.006) and T (P = 0.001) compared to pre-treatment levels.	Metformin	20-29	adiponectin, C1Q and collagen domain containing	Homo sapiens	37-48
23875783-8	2013	Post-metformin ovulatory patients had higher adiponectin and AdipoR1 and lower HOMA-IR and T compared to anovulatory patients.	Metformin	5-14	adiponectin, C1Q and collagen domain containing	Homo sapiens	45-56
23875783-10	2013	CONCLUSIONS: Metformin treatment enhances both adiponectin activity and insulin sensitivity, resulting in a less hyperandrogenic state in patients with PCOS.	Metformin	13-22	adiponectin, C1Q and collagen domain containing	Homo sapiens	47-58
23875783-10	2013	CONCLUSIONS: Metformin treatment enhances both adiponectin activity and insulin sensitivity, resulting in a less hyperandrogenic state in patients with PCOS.	Metformin	13-22	insulin	Homo sapiens	72-79
24138903-0	2013	Inhibition of p38 MAPK-dependent MutS homologue-2 (MSH2) expression by metformin enhances gefitinib-induced cytotoxicity in human squamous lung cancer cells.	Metformin	71-80	mitogen-activated protein kinase 14	Homo sapiens	14-17
24138903-14	2013	Transient expression of MKK6E or HA-p38 MAPK vector could abrogate metformin and gefitinib-induced synergistic cytotoxic effect in H520 and H1703 cells.	Metformin	67-76	mitogen-activated protein kinase kinase 6	Homo sapiens	24-29
24138903-14	2013	Transient expression of MKK6E or HA-p38 MAPK vector could abrogate metformin and gefitinib-induced synergistic cytotoxic effect in H520 and H1703 cells.	Metformin	67-76	mitogen-activated protein kinase 14	Homo sapiens	36-39
23953891-9	2013	CONCLUSIONS: BCAA/AAAs changed acutely during glipizide and metformin administration, and the magnitude and direction of change differed by the insulin resistance status of the individual and the intervention.	Metformin	60-69	AT-rich interaction domain 4B	Homo sapiens	13-17
24466367-9	2013	These results suggest that biologic effects of metformin are mediated through decreased CSC markers cluster of differentiation 44 (CD44 and CD133), aldehyde dehydrogenase isoform 1 (ALDH1), and epithelial cell adhesion molecule (EPCAM) and modulation of the mTOR signaling pathway.	Metformin	47-56	epithelial cell adhesion molecule	Mus musculus	194-227
24309653-0	2013	Metformin trims fats to restore insulin sensitivity.	Metformin	0-9	insulin	Homo sapiens	32-39
23690338-6	2013	Interestingly, a statistically significant decrease in CD4(+)CD28(null) frequency occurred after 6 months of DRSP/EE-metformin (median 3-1.5; P < .01).	Metformin	117-126	CD4 molecule	Homo sapiens	55-58
24466367-9	2013	These results suggest that biologic effects of metformin are mediated through decreased CSC markers cluster of differentiation 44 (CD44 and CD133), aldehyde dehydrogenase isoform 1 (ALDH1), and epithelial cell adhesion molecule (EPCAM) and modulation of the mTOR signaling pathway.	Metformin	47-56	epithelial cell adhesion molecule	Mus musculus	229-234
24157825-2	2013	We determined whether metformin induced a modulation of apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) overall and by insulin resistance status in a presurgical trial.	Metformin	22-31	insulin	Homo sapiens	154-161
24403860-7	2013	Activation of AMPK by metformin triggered a growth inhibitory signal but also increased BCA2 protein levels, which correlated with AKT activation and could be curbed by an AMPK inhibitor, suggesting a potential feedback mechanism from pAMPKalpha1 to pAkt to BCA2.	Metformin	22-31	AKT serine/threonine kinase 1	Homo sapiens	131-134
24403860-8	2013	Finally, BCA2 siRNA, or inhibition of its upstream stabilizing kinase AKT, increased the growth inhibitory effect of metformin in multiple breast cancer cell lines, supporting the conclusion that BCA2 weakens metformin"s efficacy.	Metformin	117-126	AKT serine/threonine kinase 1	Homo sapiens	70-73
24403860-8	2013	Finally, BCA2 siRNA, or inhibition of its upstream stabilizing kinase AKT, increased the growth inhibitory effect of metformin in multiple breast cancer cell lines, supporting the conclusion that BCA2 weakens metformin"s efficacy.	Metformin	209-218	AKT serine/threonine kinase 1	Homo sapiens	70-73
24157825-7	2013	In the 59 women without insulin resistance (HOMA index<2.8) ,there was a higher level of TUNEL at surgery on metformin vs placebo (median difference on metformin +4%, IQR: 2-14 vs +2%, IQR: 0-7 on placebo), whereas an opposite trend was found in the 28 women with insulin resistance (median difference on metformin +2%, IQR: 0-6, vs +5%, IQR: 0-15 on placebo, P-interaction=0.1).	Metformin	112-121	insulin	Homo sapiens	267-274
24157825-10	2013	Our findings provide additional evidence for a dual effect of metformin on BC growth according to insulin resistance status.	Metformin	62-71	insulin	Homo sapiens	98-105
24240433-0	2013	Direct inhibition of hexokinase activity by metformin at least partially impairs glucose metabolism and tumor growth in experimental breast cancer.	Metformin	44-53	hexokinase 1	Homo sapiens	21-31
24189526-4	2013	Antidiabetic biguanides such as metformin, which reduce hyperglycemia and hyperinsulinemia by decreasing insulin resistance, extend lifespan, and inhibit carcinogenesis in rodents.	Metformin	32-41	insulin	Homo sapiens	79-86
24240433-2	2013	In the present study, we demonstrate that metformin directly inhibits the enzymatic function of hexokinase (HK) I and II in a cell line of triple-negative breast cancer (MDA-MB-231).	Metformin	42-51	hexokinase 1	Homo sapiens	96-113
24240433-8	2013	Taken together, our results strongly suggest that HK inhibition contributes to metformin therapeutic and preventive potential in breast cancer.	Metformin	79-88	hexokinase 1	Homo sapiens	50-52
24091934-7	2013	Although LPS diminished AMPK phosphorylation, metformin or AICAR was able to partially decrease the effects of LPS/toll-like receptor 4 (TLR4) engagement on downstream signaling events, particularly LPS-induced IkappaBalpha degradation.	Metformin	46-55	toll-like receptor 4	Mus musculus	111-114
23786328-1	2013	Metformin is not only a widely used oral antidiabetic drug, which acts as an insulin sensitizer and suppressor of hepatic gluconeogenesis, but it also exhibits antitumor properties.	Metformin	0-9	insulin	Homo sapiens	77-84
24091934-7	2013	Although LPS diminished AMPK phosphorylation, metformin or AICAR was able to partially decrease the effects of LPS/toll-like receptor 4 (TLR4) engagement on downstream signaling events, particularly LPS-induced IkappaBalpha degradation.	Metformin	46-55	nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha	Mus musculus	211-223
24091934-7	2013	Although LPS diminished AMPK phosphorylation, metformin or AICAR was able to partially decrease the effects of LPS/toll-like receptor 4 (TLR4) engagement on downstream signaling events, particularly LPS-induced IkappaBalpha degradation.	Metformin	46-55	toll-like receptor 4	Mus musculus	111-135
24091934-7	2013	Although LPS diminished AMPK phosphorylation, metformin or AICAR was able to partially decrease the effects of LPS/toll-like receptor 4 (TLR4) engagement on downstream signaling events, particularly LPS-induced IkappaBalpha degradation.	Metformin	46-55	toll-like receptor 4	Mus musculus	137-141
23933835-9	2013	In addition, whereas aPKC inhibition diminished gluconeogenic enzyme levels in the absence and presence of insulin in hepatocytes from both non-diabetic and diabetic donors, metformin and AICAR increased gluconeogenic enzyme levels in hepatocytes from non-diabetic individuals, but nevertheless diminished gluconeogenic enzyme levels in insulin-treated hepatocytes from diabetic donors.	Metformin	174-183	insulin	Homo sapiens	337-344
24209692-4	2013	We identified multiple rare variants in KSR2 that disrupt signaling through the Raf-MEKERK pathway and impair cellular fatty acid oxidation and glucose oxidation in transfected cells; effects that can be ameliorated by the commonly prescribed antidiabetic drug, metformin.	Metformin	262-271	kinase suppressor of ras 2	Homo sapiens	40-44
24219188-6	2013	A prescription medication inventory was used to determine use of insulin sensitizers (metformin and thiazolidinedione).	Metformin	86-95	insulin	Homo sapiens	65-72
24282458-2	2013	We sought to determine what effect metformin had on recurrence and cancer-specific survival (CSS) rates of patients with clinically localized pT2 and pT3 renal cell carcinoma (RCC) following radical or partial nephrectomy.	Metformin	35-44	zinc finger protein 135	Homo sapiens	150-153
24089540-9	2013	Metformin monotherapy also was associated with lower mortality (HR, 0.73; 95% CI, 0.54-0.99; P < 0.05), whereas no other monotherapies or combination therapies were significantly associated with POE or all-cause mortality compared with insulin as monotherapy.	Metformin	0-9	insulin	Homo sapiens	239-246
24089540-10	2013	CONCLUSIONS: In obese patients with type 2 diabetes and high risk of cardiovascular disease, monotherapy with metformin or diet-only treatment was associated with lower risk of cardiovascular events than treatment with insulin.	Metformin	110-119	insulin	Homo sapiens	219-226
23982736-0	2013	Low concentration of metformin induces a p53-dependent senescence in hepatoma cells via activation of the AMPK pathway.	Metformin	21-30	tumor protein p53	Homo sapiens	41-44
23982736-8	2013	In addition, p53 siRNA transfection attenuated metformin-induced SA-beta-gal staining.	Metformin	47-56	tumor protein p53	Homo sapiens	13-16
23982736-9	2013	Intriguingly, co-expression of SIRT1 and p53 dramatically reduced the levels of Ac-p53, however, low doses of metformin treatment partially reversed the effect of SIRT1 on p53 acetylation and elevated SA-beta-gal activity.	Metformin	110-119	tumor protein p53	Homo sapiens	83-86
23982736-9	2013	Intriguingly, co-expression of SIRT1 and p53 dramatically reduced the levels of Ac-p53, however, low doses of metformin treatment partially reversed the effect of SIRT1 on p53 acetylation and elevated SA-beta-gal activity.	Metformin	110-119	tumor protein p53	Homo sapiens	83-86
23982736-10	2013	These observations indicate that activation of the AMPK pathway promotes senescence in hepatoma cells exposed to low concentrations of metformin in a p53-dependent manner.	Metformin	135-144	tumor protein p53	Homo sapiens	150-153
23831117-14	2013	Further, the SNARK kinase inhibitor metformin suppressed both HCV replication and SNARK-mediated enhancement of TGF-beta signaling.	Metformin	36-45	transforming growth factor beta 1	Homo sapiens	112-120
23568147-0	2013	Mitochondrial energetic and AKT status mediate metabolic effects and apoptosis of metformin in human leukemic cells.	Metformin	82-91	AKT serine/threonine kinase 1	Homo sapiens	28-31
24269881-7	2013	Metformin limited (p<0.05) ceramide"s effects on insulin signaling, senescence, and cell cycle regulation.	Metformin	0-9	insulin	Homo sapiens	52-59
23568147-8	2013	Importantly, leukemic cells with high basal AKT phosphorylation, glucose consumption or glycolysis exhibit a markedly reduced induction of the Pasteur effect in response to metformin and are resistant to metformin-induced apoptosis.	Metformin	173-182	AKT serine/threonine kinase 1	Homo sapiens	44-47
23568147-8	2013	Importantly, leukemic cells with high basal AKT phosphorylation, glucose consumption or glycolysis exhibit a markedly reduced induction of the Pasteur effect in response to metformin and are resistant to metformin-induced apoptosis.	Metformin	204-213	AKT serine/threonine kinase 1	Homo sapiens	44-47
23568147-9	2013	Accordingly, glucose starvation or treatment with deoxyglucose or an AKT inhibitor induces sensitivity to metformin.	Metformin	106-115	AKT serine/threonine kinase 1	Homo sapiens	69-72
23568147-10	2013	Overall, metformin elicits reprogramming of intermediary metabolism leading to inhibition of cell proliferation in all leukemic cells and apoptosis only in leukemic cells responding to metformin with AKT phosphorylation and a strong Pasteur effect.	Metformin	9-18	AKT serine/threonine kinase 1	Homo sapiens	200-203
23879830-5	2013	Inhibition of endothelin-1 (ET-1) signaling produced 20% dilation and eliminated the difference between metformin-treated and untreated OLETF rats in insulin-induced dilation of SFA.	Metformin	104-113	endothelin 1	Rattus norvegicus	14-26
23568147-10	2013	Overall, metformin elicits reprogramming of intermediary metabolism leading to inhibition of cell proliferation in all leukemic cells and apoptosis only in leukemic cells responding to metformin with AKT phosphorylation and a strong Pasteur effect.	Metformin	185-194	AKT serine/threonine kinase 1	Homo sapiens	200-203
24041694-0	2013	Metformin-induced inhibition of the mitochondrial respiratory chain increases FGF21 expression via ATF4 activation.	Metformin	0-9	fibroblast growth factor 21	Homo sapiens	78-83
24136225-0	2013	FoxO1 controls lysosomal acid lipase in adipocytes: implication of lipophagy during nutrient restriction and metformin treatment.	Metformin	109-118	forkhead box O1	Homo sapiens	0-5
24157941-0	2013	Adiponectin and metformin additively attenuate IL1beta-induced malignant potential of colon cancer.	Metformin	16-25	interleukin 1 beta	Homo sapiens	47-54
24204674-10	2013	In obese mice, greater levels of eotaxin, TNF-alpha and NOx, together with increased iNOS protein expression were observed, all of which were normalized by metformin.	Metformin	156-165	chemokine (C-C motif) ligand 11	Mus musculus	33-40
24204674-10	2013	In obese mice, greater levels of eotaxin, TNF-alpha and NOx, together with increased iNOS protein expression were observed, all of which were normalized by metformin.	Metformin	156-165	tumor necrosis factor	Mus musculus	42-51
24204674-10	2013	In obese mice, greater levels of eotaxin, TNF-alpha and NOx, together with increased iNOS protein expression were observed, all of which were normalized by metformin.	Metformin	156-165	nitric oxide synthase 2, inducible	Mus musculus	85-89
24204674-11	2013	In addition, metformin nearly abrogated the binding of NF-kappaB subunit p65 to the iNOS promoter gene in lung tissue of obese mice.	Metformin	13-22	nitric oxide synthase 2, inducible	Mus musculus	84-88
24204674-14	2013	In conclusion, metformin inhibits the TNF-alpha-induced inflammatory signaling and NF-kappaB-mediated iNOS expression in lung tissue of obese mice.	Metformin	15-24	tumor necrosis factor	Mus musculus	38-47
24204674-14	2013	In conclusion, metformin inhibits the TNF-alpha-induced inflammatory signaling and NF-kappaB-mediated iNOS expression in lung tissue of obese mice.	Metformin	15-24	nitric oxide synthase 2, inducible	Mus musculus	102-106
24041694-6	2013	Importantly, inhibition of mitochondrial complex I activity by metformin resulted in FGF21 induction through PKR-like ER kinase (PERK)-eukaryotic translation factor 2alpha (eIF2alpha)-activating transcription factor 4 (ATF4).	Metformin	63-72	fibroblast growth factor 21	Homo sapiens	85-90
24041694-7	2013	We showed that metformin activated ATF4 and increased FGF21 expression in the livers of mice, which led to increased serum levels of FGF21.	Metformin	15-24	activating transcription factor 4	Mus musculus	35-39
24041694-8	2013	We also found that serum FGF21 level was increased in human subjects with T2D after metformin therapy for 6 months.	Metformin	84-93	fibroblast growth factor 21	Homo sapiens	25-30
24041694-9	2013	In conclusion, our results indicate that metformin induced expression of FGF21 through an ATF4-dependent mechanism by inhibiting mitochondrial respiration independently of AMPK.	Metformin	41-50	fibroblast growth factor 21	Homo sapiens	73-78
24041694-10	2013	Therefore, FGF21 induction by metformin might explain a portion of the beneficial metabolic effects of metformin.	Metformin	30-39	fibroblast growth factor 21	Homo sapiens	11-16
24041694-10	2013	Therefore, FGF21 induction by metformin might explain a portion of the beneficial metabolic effects of metformin.	Metformin	103-112	fibroblast growth factor 21	Homo sapiens	11-16
23942093-10	2013	Mechanistically, metformin/AMPK activation inhibited NF-kappaB signaling through upregulation of IkappaBalpha.	Metformin	17-26	NFKB inhibitor alpha	Homo sapiens	97-109
23942093-11	2013	Activation of NF-kappaB signaling by ectopic expression of P65 or overexpression of an undegradable mutant form of IkappaBalpha attenuated the anticancer effects of metformin.	Metformin	165-174	NFKB inhibitor alpha	Homo sapiens	115-127
24319557-7	2013	Patients who responded to metformin treatment had significantly lower mean SHBG levels compared to those who did not (0.88+0.32vs.	Metformin	26-35	sex hormone binding globulin	Homo sapiens	75-79
23991629-0	2013	Short-term continuous subcutaneous insulin infusion combined with insulin sensitizers rosiglitazone, metformin, or antioxidant alpha-lipoic acid in patients with newly diagnosed type 2 diabetes mellitus.	Metformin	101-110	insulin	Homo sapiens	66-73
23991629-7	2013	The metformin group achieved euglycemia in a shorter time (2.6 +- 1.3 vs. 3.7 +- 1.8 days, P=0.020) with less daily insulin dosage and was more powerful in lowering total cholesterol, increasing AIR and HOMA beta-cell function, whereas reduction of IMCL in the soleus was more obvious in the rosiglitazone group but not in the metformin group.	Metformin	4-13	insulin	Homo sapiens	116-123
23979954-12	2013	CONCLUSION: ILS and metformin treatment have favorable effects on lipoprotein subfractions that are primarily mediated by intervention-related changes in insulin resistance, BMI, and adiponectin.	Metformin	20-29	insulin	Homo sapiens	154-161
24025223-3	2013	In female rat aortic smooth muscle cells (RASMCs), we observed that metformin significantly alleviated beta-glycerophosphate-induced Ca deposition and alkaline phosphatase activity, corresponding with reduced expression of some specific genes in osteoblast-like cells, including Runx2 and bone morphogenetic protein-2, and positive effects on alpha-actin expression, a specific marker of smooth muscle cells.	Metformin	68-77	RUNX family transcription factor 2	Rattus norvegicus	279-284
23979954-12	2013	CONCLUSION: ILS and metformin treatment have favorable effects on lipoprotein subfractions that are primarily mediated by intervention-related changes in insulin resistance, BMI, and adiponectin.	Metformin	20-29	adiponectin, C1Q and collagen domain containing	Homo sapiens	183-194
23873119-1	2013	OBJECTIVE: The aim of this study was to determine the association between the renal clearance (CL(renal)) of metformin in healthy Caucasian volunteers and the single-nucleotide polymorphism (SNP) c.808G>T (rs316019) in OCT2 as well as the relevance of the gene-gene interactions between this SNP and (a) the promoter SNP g.-66T>C (rs2252281) in MATE1 and (b) the OCT1 reduced-function diplotypes.	Metformin	109-118	solute carrier family 22 member 1	Homo sapiens	369-373
24346380-9	2013	Spearman"s rank correlation between cumulative metformin use and B12 level was calculated.	Metformin	47-56	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	65-68
24346380-11	2013	RESULTS: Mean serum B12 levels was significantly lower in metformin exposed group (n=84) compared with nonmetformin exposed group (n=52) (410+-230.7 versus 549.2+-244.7, P=0.0011).	Metformin	58-67	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	20-23
24346380-15	2013	There was significant negative correlation between cumulative metformin dose and vitamin B12 level (r=-0.68, P<0.0001).	Metformin	62-71	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	89-92
23922447-11	2013	It remains to be determined whether genetic variants, disease conditions, or drugs that affect HNF1 activity may affect the pharmacokinetics and efficacy of OCT1-transported drugs such as morphine, tropisetron, ondansetron, tramadol, and metformin.	Metformin	238-247	HNF1 homeobox A	Homo sapiens	95-99
23922447-11	2013	It remains to be determined whether genetic variants, disease conditions, or drugs that affect HNF1 activity may affect the pharmacokinetics and efficacy of OCT1-transported drugs such as morphine, tropisetron, ondansetron, tramadol, and metformin.	Metformin	238-247	solute carrier family 22 member 1	Homo sapiens	157-161
23794020-3	2013	These results have drawn attention to the mechanisms underlying metformin"s anti-cancer effects, which may include triggering of the AMP-activated protein kinase (AMPK) pathway, resulting in vulnerability to an energy crisis (leading to cell death under conditions of nutrient deprivation) and a reduction in circulating insulin/IGF-1 levels.	Metformin	64-73	insulin	Homo sapiens	321-328
23794020-3	2013	These results have drawn attention to the mechanisms underlying metformin"s anti-cancer effects, which may include triggering of the AMP-activated protein kinase (AMPK) pathway, resulting in vulnerability to an energy crisis (leading to cell death under conditions of nutrient deprivation) and a reduction in circulating insulin/IGF-1 levels.	Metformin	64-73	insulin like growth factor 1	Homo sapiens	329-334
23999444-5	2013	With respect to indirect mechanisms, it will be important to determine whether recently demonstrated metformin-induced changes in levels of candidate systemic mediators such as insulin or inflammatory cytokines are of sufficient magnitude to achieve therapeutic benefit.	Metformin	101-110	insulin	Homo sapiens	177-184
24011132-11	2013	The vasoactive factors: COX-2 and NOS were increased in the ovaries of the OHSS group (P<0.05 and P<0.01) and metformin normalized their expression (P<0.05); suggesting that metformin has a role preventing the increased in vascular permeability caused by the syndrome.	Metformin	183-192	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	24-29
24011132-13	2013	These effects of metformin are mediated by inhibiting the increased of the vasoactive molecules: VEGF, COX-2 and partially NOS.	Metformin	17-26	vascular endothelial growth factor A	Homo sapiens	97-101
24011132-13	2013	These effects of metformin are mediated by inhibiting the increased of the vasoactive molecules: VEGF, COX-2 and partially NOS.	Metformin	17-26	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	103-108
24023727-0	2013	Metformin inhibits angiotensin II-induced differentiation of cardiac fibroblasts into myofibroblasts.	Metformin	0-9	angiotensinogen	Rattus norvegicus	19-33
24023727-6	2013	Ang II stimulation induced the differentiation of cardiac fibroblasts into myofibroblasts, as indicated by increased expression of alpha-smooth muscle actin (alpha-SMA) and collagen types I and III, and this effect of Ang II was inhibited by pretreatment of cardiac fibroblasts with metformin.	Metformin	283-292	angiotensinogen	Rattus norvegicus	0-6
24023727-6	2013	Ang II stimulation induced the differentiation of cardiac fibroblasts into myofibroblasts, as indicated by increased expression of alpha-smooth muscle actin (alpha-SMA) and collagen types I and III, and this effect of Ang II was inhibited by pretreatment of cardiac fibroblasts with metformin.	Metformin	283-292	angiotensinogen	Rattus norvegicus	218-224
24023727-7	2013	Metformin also decreased Ang II-induced reactive oxygen species (ROS) generation in cardiac fibroblasts via inhibiting the activation of the PKC-NADPH oxidase pathway.	Metformin	0-9	angiotensinogen	Rattus norvegicus	25-31
24023727-9	2013	These data indicate that metformin inhibits Ang II-induced myofibroblast differentiation by suppressing ROS generation via the inhibition of the PKC-NADPH oxidase pathway in adult rat cardiac fibroblasts.	Metformin	25-34	angiotensinogen	Rattus norvegicus	44-50
23845075-8	2013	Metformin activates 5-adenosine monophosphate-activated protein kinase (AMPK), that has growth inhibition effects on human cancer cell lines via inhibition of its downstream target mammalian target of rapamycin (mTOR), and decreases the expression of Livin, a protein involved in both cell proliferation and survivalexpressed at high level in neoplastic cell.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	181-210
23845075-8	2013	Metformin activates 5-adenosine monophosphate-activated protein kinase (AMPK), that has growth inhibition effects on human cancer cell lines via inhibition of its downstream target mammalian target of rapamycin (mTOR), and decreases the expression of Livin, a protein involved in both cell proliferation and survivalexpressed at high level in neoplastic cell.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	212-216
23809765-5	2013	Recent studies seem to indicate that drugs commonly used in diabetes patients such as metformin, thiazolidinediones, GLP-1 agonists, DPP-4 inhibitors, insulin, statins and ACE inhibitors may increase EPC number and improve EPC function.	Metformin	86-95	insulin	Homo sapiens	151-158
23809765-5	2013	Recent studies seem to indicate that drugs commonly used in diabetes patients such as metformin, thiazolidinediones, GLP-1 agonists, DPP-4 inhibitors, insulin, statins and ACE inhibitors may increase EPC number and improve EPC function.	Metformin	86-95	angiotensin I converting enzyme	Homo sapiens	172-175
24378094-10	2013	Western blotting results revealed that the expression of CD133, phosphorylated Akt and the Bcl-2/Bax ratio were downregulated, and PTEN was upregulated in the Huh-7 cells after treated with 25 mmol/L metformin for 48 hrs.	Metformin	200-209	BCL2 apoptosis regulator	Homo sapiens	91-96
25206548-0	2013	Metformin inhibits food intake and neuropeptide Y gene expression in the hypothalamus.	Metformin	0-9	neuropeptide Y	Rattus norvegicus	35-49
25206548-4	2013	A reduction of neuropeptide Y expression and induction of AMP-activated protein kinase phosphorylation in the hypothalamus were also observed 4 hours after metformin administration, which could be reversed by compound C, a commonly-used antagonist of AMP-activated protein kinase.	Metformin	156-165	neuropeptide Y	Rattus norvegicus	15-29
25206548-6	2013	Our findings suggest that under normal physiological conditions, central regulation of appetite by metformin is related to a decrease in neuropeptide Y gene expres-sion, and that the activation of AMP-activated protein kinase may simply be a response to the anorexigenic effect of metformin.	Metformin	99-108	neuropeptide Y	Rattus norvegicus	137-151
23666872-0	2013	Involvement of carnitine/organic cation transporter OCTN1/SLC22A4 in gastrointestinal absorption of metformin.	Metformin	100-109	solute carrier family 22 (organic cation transporter), member 4	Mus musculus	52-57
23891275-9	2013	FRAP concentrations increased significantly with metformin (p=0.012).	Metformin	49-58	mechanistic target of rapamycin kinase	Homo sapiens	0-4
23666872-0	2013	Involvement of carnitine/organic cation transporter OCTN1/SLC22A4 in gastrointestinal absorption of metformin.	Metformin	100-109	solute carrier family 22 (organic cation transporter), member 4	Mus musculus	58-65
23666872-2	2013	Here, we examined the role of carnitine/organic cation transporter OCTN1/SLC22A4, which is localized on apical membranes of small intestine in mice and humans, in metformin absorption.	Metformin	163-172	solute carrier family 22 (organic cation transporter), member 4	Mus musculus	67-72
23666872-2	2013	Here, we examined the role of carnitine/organic cation transporter OCTN1/SLC22A4, which is localized on apical membranes of small intestine in mice and humans, in metformin absorption.	Metformin	163-172	solute carrier family 22 (organic cation transporter), member 4	Mus musculus	73-80
23666872-3	2013	The maximum plasma concentration (Cmax ) after oral administration of metformin (50 mg/kg) in octn1 gene knockout mice (octn1 (-/-) ) was higher than that in wild-type mice, with only a minimal difference in terminal half-life, but Cmax in octn1(-/-) mice given a higher dose (175 mg/kg) was lower than that in wild-type mice.	Metformin	70-79	solute carrier family 22 (organic cation transporter), member 4	Mus musculus	94-99
23666872-3	2013	The maximum plasma concentration (Cmax ) after oral administration of metformin (50 mg/kg) in octn1 gene knockout mice (octn1 (-/-) ) was higher than that in wild-type mice, with only a minimal difference in terminal half-life, but Cmax in octn1(-/-) mice given a higher dose (175 mg/kg) was lower than that in wild-type mice.	Metformin	70-79	solute carrier family 22 (organic cation transporter), member 4	Mus musculus	120-125
23666872-3	2013	The maximum plasma concentration (Cmax ) after oral administration of metformin (50 mg/kg) in octn1 gene knockout mice (octn1 (-/-) ) was higher than that in wild-type mice, with only a minimal difference in terminal half-life, but Cmax in octn1(-/-) mice given a higher dose (175 mg/kg) was lower than that in wild-type mice.	Metformin	70-79	solute carrier family 22 (organic cation transporter), member 4	Mus musculus	120-125
23666872-5	2013	OCTN1-mediated uptake of metformin was observed in human embryonic kidney 293 cells transfected with mouse OCTN1 gene, but much lower than the uptake of the typical substrate [(3) H]ergothioneine (ERGO).	Metformin	25-34	solute carrier family 22 (organic cation transporter), member 4	Mus musculus	107-112
23666872-6	2013	In particular, the distribution volume for OCTN1-mediated uptake increased markedly and then tended to decrease as the metformin concentration was increased.	Metformin	119-128	solute carrier family 22 (organic cation transporter), member 4	Mus musculus	43-48
23666872-8	2013	Overall, the present findings suggest that OCTN1 transports metformin and may be involved in its oral absorption in small intestine.	Metformin	60-69	solute carrier family 22 (organic cation transporter), member 4	Mus musculus	43-48
23660512-7	2013	RESULTS: Compared to placebo, both ILS and metformin significantly reduced LDL-C and raised HDL-C among HT users, changes partially explained by change in estradiol and testosterone but independent of changes in waist circumference and 1/fasting insulin.	Metformin	43-52	insulin	Homo sapiens	246-253
23889981-0	2013	Metformin treatment improves erectile function in an angiotensin II model of erectile dysfunction.	Metformin	0-9	angiotensinogen	Rattus norvegicus	53-67
23846817-4	2013	OBJECTIVE: The aim of this study was to investigate metformin"s interaction with the FSH/cAMP/protein kinase A pathway, which is the primary signaling pathway controlling CYP19A1 (aromatase) expression in the ovary.	Metformin	52-61	cytochrome P450 family 19 subfamily A member 1	Homo sapiens	171-178
23986086-0	2013	Dietary restriction-resistant human tumors harboring the PIK3CA-activating mutation H1047R are sensitive to metformin.	Metformin	108-117	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	57-63
23891087-8	2013	Loss of AMPK sensitized cells to the anti-proliferative effects of metformin, while loss of p53 promoted both the growth inhibitory and toxic effects of metformin.	Metformin	153-162	tumor protein p53	Homo sapiens	92-95
23986086-3	2013	The anti-diabetic drug metformin is a stereotypical DR mimetic that exerts its anti-cancer activity through a dual mechanism involving insulin-related (systemic) and mTOR-related (cell-autonomous) effects.	Metformin	23-32	insulin	Homo sapiens	135-142
23986086-3	2013	The anti-diabetic drug metformin is a stereotypical DR mimetic that exerts its anti-cancer activity through a dual mechanism involving insulin-related (systemic) and mTOR-related (cell-autonomous) effects.	Metformin	23-32	mechanistic target of rapamycin kinase	Homo sapiens	166-170
23986086-12	2013	Thus, metformin can no longer be considered as a bona fide DR mimetic, at least in terms of anti-cancer activity, because tumors harboring the insulin-unresponsive, DR-resistant, PIK3CA-activating mutation H1047R remain sensitive to the anti-tumoral effects of the drug.	Metformin	6-15	insulin	Homo sapiens	143-150
23986086-12	2013	Thus, metformin can no longer be considered as a bona fide DR mimetic, at least in terms of anti-cancer activity, because tumors harboring the insulin-unresponsive, DR-resistant, PIK3CA-activating mutation H1047R remain sensitive to the anti-tumoral effects of the drug.	Metformin	6-15	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	179-185
23986086-13	2013	Given the high prevalence of PIK3CA mutations in human carcinomas and the emerging role of PIK3CA mutation status in the treatment selection process, these findings might have a significant impact on the design of future trials evaluating the potential of combining metformin with targeted therapy.	Metformin	266-275	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	29-35
23891087-0	2013	Contributions of AMPK and p53 dependent signaling to radiation response in the presence of metformin.	Metformin	91-100	tumor protein p53	Homo sapiens	26-29
23891087-2	2013	Metformin activates AMPK that in turn can launch a p53-dependent metabolic checkpoint.	Metformin	0-9	tumor protein p53	Homo sapiens	51-54
23889981-4	2013	AIM: The goal of this study was to test the hypothesis that AngII induces ED by means of increased corpus cavernosum contraction, and that metformin treatment will reverse ED in AngII-treated rats.	Metformin	139-148	angiotensinogen	Rattus norvegicus	178-183
23889981-6	2013	Animals were then treated with metformin or vehicle during the last week of AngII infusion.	Metformin	31-40	angiotensinogen	Rattus norvegicus	76-81
23889981-9	2013	Metformin treatment improved erectile function in the AngII-treated rats by reversing the increased contraction and decreased relaxation.	Metformin	0-9	angiotensinogen	Rattus norvegicus	54-59
23889981-11	2013	CONCLUSIONS: Metformin treatment increased eNOS phosphorylation and improved erectile function in AngII hypertensive rats by reestablishing normal cavernosal smooth muscle tone.	Metformin	13-22	angiotensinogen	Rattus norvegicus	98-103
23891087-4	2013	Since radiation-induced signaling also involves AMPK and p53, we investigated their importance in mediating responses to metformin and radiation.	Metformin	121-130	tumor protein p53	Homo sapiens	57-60
23891087-10	2013	CONCLUSIONS: The anti-proliferative activity of metformin may confer benefit in combination with radiotherapy, and this benefit is intensified upon loss of AMPK or p53 signaling.	Metformin	48-57	tumor protein p53	Homo sapiens	164-167
23707609-10	2013	These results highlight the Raf-ERK-Nrf2 axis as a new molecular target in anticancer therapy in response to metformin treatment.	Metformin	109-118	mitogen-activated protein kinase 1	Homo sapiens	32-35
24180199-6	2013	Metformin may exert its anti-cancer activity by a direct effect (insulin) and an indirect effect (AMPK and mTOR).	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	107-111
23707609-10	2013	These results highlight the Raf-ERK-Nrf2 axis as a new molecular target in anticancer therapy in response to metformin treatment.	Metformin	109-118	NFE2 like bZIP transcription factor 2	Homo sapiens	36-40
23707609-0	2013	Metformin inhibits heme oxygenase-1 expression in cancer cells through inactivation of Raf-ERK-Nrf2 signaling and AMPK-independent pathways.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	91-94
23707609-0	2013	Metformin inhibits heme oxygenase-1 expression in cancer cells through inactivation of Raf-ERK-Nrf2 signaling and AMPK-independent pathways.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	95-99
23707609-6	2013	Metformin also markedly reduced Nrf2 mRNA and protein levels in whole cell lysates and suppressed tert-butylhydroquinone (tBHQ)-induced Nrf2 protein stability and antioxidant response element (ARE)-luciferase activity in HepG2 cells.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	32-36
23707609-6	2013	Metformin also markedly reduced Nrf2 mRNA and protein levels in whole cell lysates and suppressed tert-butylhydroquinone (tBHQ)-induced Nrf2 protein stability and antioxidant response element (ARE)-luciferase activity in HepG2 cells.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	136-140
23707609-7	2013	We also found that metformin regulation of Nrf2 expression is mediated by a Keap1-independent mechanism and that metformin significantly attenuated Raf-ERK signaling to suppress Nrf2 expression in cancer cells.	Metformin	19-28	NFE2 like bZIP transcription factor 2	Homo sapiens	43-47
23707609-7	2013	We also found that metformin regulation of Nrf2 expression is mediated by a Keap1-independent mechanism and that metformin significantly attenuated Raf-ERK signaling to suppress Nrf2 expression in cancer cells.	Metformin	19-28	kelch like ECH associated protein 1	Homo sapiens	76-81
23707609-7	2013	We also found that metformin regulation of Nrf2 expression is mediated by a Keap1-independent mechanism and that metformin significantly attenuated Raf-ERK signaling to suppress Nrf2 expression in cancer cells.	Metformin	113-122	mitogen-activated protein kinase 1	Homo sapiens	152-155
23707609-7	2013	We also found that metformin regulation of Nrf2 expression is mediated by a Keap1-independent mechanism and that metformin significantly attenuated Raf-ERK signaling to suppress Nrf2 expression in cancer cells.	Metformin	113-122	NFE2 like bZIP transcription factor 2	Homo sapiens	178-182
24004910-3	2013	Patients" sera were analyzed before and 5 h after a defined test meal at intervals of 30 min.The sulfonylurea/metformin group exhibited the highest basal levels of active TGF-beta (31.50 +- 3.58 ng/ml).	Metformin	110-119	transforming growth factor beta 1	Homo sapiens	171-179
23904524-0	2013	Metformin inhibits growth of eutopic stromal cells from adenomyotic endometrium via AMPK activation and subsequent inhibition of AKT phosphorylation: a possible role in the treatment of adenomyosis.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	129-132
23904524-12	2013	The inhibitory effects of metformin on AKT activation (p-AKT/AKT) were more pronounced in A-ESCs from the secretory phase (3.2-fold inhibition vs control) than in those from the proliferation phase (2.3-fold inhibition vs control).	Metformin	26-35	AKT serine/threonine kinase 1	Homo sapiens	39-42
23904524-12	2013	The inhibitory effects of metformin on AKT activation (p-AKT/AKT) were more pronounced in A-ESCs from the secretory phase (3.2-fold inhibition vs control) than in those from the proliferation phase (2.3-fold inhibition vs control).	Metformin	26-35	AKT serine/threonine kinase 1	Homo sapiens	57-60
23904524-12	2013	The inhibitory effects of metformin on AKT activation (p-AKT/AKT) were more pronounced in A-ESCs from the secretory phase (3.2-fold inhibition vs control) than in those from the proliferation phase (2.3-fold inhibition vs control).	Metformin	26-35	AKT serine/threonine kinase 1	Homo sapiens	57-60
23904524-14	2013	Metformin inhibits cell growth via AMPK activation and subsequent inhibition of PI3K/AKT signaling in A-ESCs, particularly during the secretory phase, suggesting a greater effect of metformin on A-ESCs from secretory phase.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	85-88
24071688-0	2013	[Effect of metformin on the expression of SIRT1 and UCP2 in rat liver of type 2 diabetes mellitus and nonalcoholic fatty liver].	Metformin	11-20	sirtuin 1	Rattus norvegicus	42-47
24071688-1	2013	OBJECTIVE: To observe the effect of metformin on the expression of SIRT1 and UCP2 in rat liver of type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD), and discuss the pathogenesis of T2DM with NAFLD, and the treatment with and possible mechanism of metformin.	Metformin	36-45	sirtuin 1	Rattus norvegicus	67-72
24071688-10	2013	After the metformin treatment, the expression of SIRT1 was higher than in group MC (P<0.05), and the expression of UCP2 was lower than in group MC (P<0.05).	Metformin	10-19	sirtuin 1	Rattus norvegicus	49-54
24071688-13	2013	Metformin can increase the expression of SIRT1 and reduce the expression of UCP2, with negative correlation between the expression of SIRT1 and UCP2.	Metformin	0-9	sirtuin 1	Rattus norvegicus	41-46
24071688-13	2013	Metformin can increase the expression of SIRT1 and reduce the expression of UCP2, with negative correlation between the expression of SIRT1 and UCP2.	Metformin	0-9	sirtuin 1	Rattus norvegicus	134-139
24009772-3	2013	Metformin activated AMPK, down-regulated the unfolded protein response (UPR) demonstrated by significant decrease in the main UPR regulator GRP78, and led to UPR-mediated cell death via up-regulation of the ER stress/UPR cell death mediators IRE1alpha and CHOP.	Metformin	0-9	heat shock protein family A (Hsp70) member 5	Homo sapiens	140-145
24009772-3	2013	Metformin activated AMPK, down-regulated the unfolded protein response (UPR) demonstrated by significant decrease in the main UPR regulator GRP78, and led to UPR-mediated cell death via up-regulation of the ER stress/UPR cell death mediators IRE1alpha and CHOP.	Metformin	0-9	DNA damage inducible transcript 3	Homo sapiens	256-260
24009772-4	2013	Using shRNA, we demonstrate that metformin-induced apoptosis is AMPK-dependent since AMPK knock-down rescued ALL cells, which correlated with down-regulation of IRE1alpha and CHOP and restoration of the UPR/GRP78 function.	Metformin	33-42	DNA damage inducible transcript 3	Homo sapiens	175-179
24009772-4	2013	Using shRNA, we demonstrate that metformin-induced apoptosis is AMPK-dependent since AMPK knock-down rescued ALL cells, which correlated with down-regulation of IRE1alpha and CHOP and restoration of the UPR/GRP78 function.	Metformin	33-42	heat shock protein family A (Hsp70) member 5	Homo sapiens	207-212
24009772-5	2013	Additionally rapamycin, a known inhibitor of mTOR-dependent protein synthesis, rescued cells from metformin-induced apoptosis and down-regulated CHOP expression.	Metformin	98-107	mechanistic target of rapamycin kinase	Homo sapiens	45-49
24009772-6	2013	Finally, metformin induced PIM-2 kinase activity and co-treatment of ALL cells with a PIM-1/2 kinase inhibitor plus metformin synergistically increased cell death, suggesting a buffering role for PIM-2 in metformin"s cytotoxicity.	Metformin	9-18	Pim-1 proto-oncogene, serine/threonine kinase	Homo sapiens	27-30
24009772-7	2013	Similar synergism was seen with agents targeting Akt in combination with metformin, supporting our original postulate that AMPK and Akt exert opposite regulatory roles on UPR activity in ALL.	Metformin	73-82	AKT serine/threonine kinase 1	Homo sapiens	132-135
24004910-4	2013	The glargine/metformin group had active TGF-beta levels (24.98 +- 1.90 ng/ml) that were comparable to those of the healthy participants (22.12 +- 2.34 ng/ml).	Metformin	13-22	transforming growth factor beta 1	Homo sapiens	40-48
24004910-5	2013	The lowest basal levels of active TGF-beta were detected in the DPP-4i/metformin group (12.28 +- 0.84 ng/ml).	Metformin	71-80	transforming growth factor beta 1	Homo sapiens	34-42
24004910-9	2013	Active TGF-beta levels in the DPP-4i/metformin group did not change significantly after the test meal.	Metformin	37-46	transforming growth factor beta 1	Homo sapiens	7-15
24004910-13	2013	Our results suggest that glargine/metformin and DPP4i/metformin treatment may more effectively reduce active TGF-beta serum levels than the sulfonylurea/metformin treatment.	Metformin	34-43	transforming growth factor beta 1	Homo sapiens	109-117
24004910-13	2013	Our results suggest that glargine/metformin and DPP4i/metformin treatment may more effectively reduce active TGF-beta serum levels than the sulfonylurea/metformin treatment.	Metformin	54-63	transforming growth factor beta 1	Homo sapiens	109-117
24004910-13	2013	Our results suggest that glargine/metformin and DPP4i/metformin treatment may more effectively reduce active TGF-beta serum levels than the sulfonylurea/metformin treatment.	Metformin	54-63	transforming growth factor beta 1	Homo sapiens	109-117
23961326-11	2013	CONCLUSION: In Asian patients inadequately controlled with insulin (with or without concomitant metformin), insulin-vildagliptin combination treatment significantly reduced HbA1c compared with placebo, without an increase in risk of hypoglycemia or weight gain.	Metformin	96-105	insulin	Homo sapiens	108-115
23526220-12	2013	Thus, metformin helps to overcome tumor drug resistance by targeting STAT3.	Metformin	6-15	signal transducer and activator of transcription 3	Homo sapiens	69-74
23659985-11	2013	Maternal metformin did not impact maternal markers but significantly decreased diet-induced TNF-alpha and chemokine (C-C motif) ligand 2 in the fetal plasma.	Metformin	9-18	tumor necrosis factor	Rattus norvegicus	92-101
23659985-12	2013	Finally, metformin dose-dependently reduced TNF-alpha-induced IL-6 and IkappaBalpha levels in cultured placental JAR cells.	Metformin	9-18	tumor necrosis factor	Homo sapiens	44-53
23659985-12	2013	Finally, metformin dose-dependently reduced TNF-alpha-induced IL-6 and IkappaBalpha levels in cultured placental JAR cells.	Metformin	9-18	interleukin 6	Homo sapiens	62-66
23659985-12	2013	Finally, metformin dose-dependently reduced TNF-alpha-induced IL-6 and IkappaBalpha levels in cultured placental JAR cells.	Metformin	9-18	NFKB inhibitor alpha	Homo sapiens	71-83
23659985-14	2013	Similarly, metformin treatment of a placental cell line suppressed TNF-alpha-induced IL-6 levels by NFkappaB inhibitor.	Metformin	11-20	tumor necrosis factor	Rattus norvegicus	67-76
23659985-14	2013	Similarly, metformin treatment of a placental cell line suppressed TNF-alpha-induced IL-6 levels by NFkappaB inhibitor.	Metformin	11-20	interleukin 6	Rattus norvegicus	85-89
23951244-11	2013	The protective effect of metformin is dependent on an intact PI3-kinase/Akt pathway, but does not require AMPK/mTOR-signaling.	Metformin	25-34	AKT serine/threonine kinase 1	Rattus norvegicus	72-75
23526220-0	2013	Metformin enhances cisplatin cytotoxicity by suppressing signal transducer and activator of transcription-3 activity independently of the liver kinase B1-AMP-activated protein kinase pathway.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	57-107
23526220-5	2013	A STAT3 inhibitor (JSI-124) enhanced the cisplatin sensitivity in AS2 cells, whereas metformin inhibited STAT3 phosphorylation and enhanced cisplatin cytotoxicity.	Metformin	85-94	signal transducer and activator of transcription 3	Homo sapiens	105-110
23526220-8	2013	Metformin also inhibited cisplatin-induced ROS production and autocrine IL-6 secretion in AS2 cells.	Metformin	0-9	interleukin 6	Homo sapiens	72-76
23988170-15	2013	The metformin therapy significantly improved insulin resistance, imbalance of endocrine hormones, hirsutism and menstrual cyclicity in women with PCOS.	Metformin	4-13	insulin	Homo sapiens	45-52
23526220-9	2013	Both mechanisms contributed to the ability of metformin to suppress STAT3 activation in cancer cells, which resulted in the decreased secretion of vascular endothelial growth factor by cancer cells.	Metformin	46-55	signal transducer and activator of transcription 3	Homo sapiens	68-73
23526220-9	2013	Both mechanisms contributed to the ability of metformin to suppress STAT3 activation in cancer cells, which resulted in the decreased secretion of vascular endothelial growth factor by cancer cells.	Metformin	46-55	vascular endothelial growth factor A	Homo sapiens	147-181
23526220-11	2013	This is the first study to demonstrate that metformin suppresses STAT3 activation via LKB1-AMPK-mTOR-independent but ROS-related and autocrine IL-6 production-related pathways.	Metformin	44-53	signal transducer and activator of transcription 3	Homo sapiens	65-70
23526220-11	2013	This is the first study to demonstrate that metformin suppresses STAT3 activation via LKB1-AMPK-mTOR-independent but ROS-related and autocrine IL-6 production-related pathways.	Metformin	44-53	mechanistic target of rapamycin kinase	Homo sapiens	96-100
23526220-11	2013	This is the first study to demonstrate that metformin suppresses STAT3 activation via LKB1-AMPK-mTOR-independent but ROS-related and autocrine IL-6 production-related pathways.	Metformin	44-53	interleukin 6	Homo sapiens	143-147
23988170-4	2013	Metformin treatment after 6 and 12 months significantly reduced weight, BMI, waist circumference, insulin and HOMA-IR (p=0.000) with high differences of variances within repeated measurements.	Metformin	0-9	insulin	Homo sapiens	98-105
23988170-16	2013	The most important predictors for duration of metformin treatment in PCOS women were testosterone, progesterone, FSH, CRP and presence of anovulation.	Metformin	46-55	C-reactive protein	Homo sapiens	118-121
23408390-3	2013	Metformin, which represses mTOR signaling by activating adenosine monophosphate-activated protein kinase, has been shown to decrease liver carcinogenesis in population studies.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	27-31
23595973-0	2013	Metformin augments the levels of molecules that regulate the expression of the insulin-dependent glucose transporter GLUT4 in the endometria of hyperinsulinemic PCOS patients.	Metformin	0-9	insulin	Homo sapiens	79-86
23595973-1	2013	STUDY QUESTION: Does treatment with the insulin sensitizer metformin modify the levels and activation of proteins related to the expression of the insulin-dependent glucose transporter (GLUT4), such as adenosine monophosphate-activated protein kinase (AMPK) and myocyte enhancer factor 2A (MEF2A), in endometria from hyperinsulinemic hyperandrogenemic polycystic ovary syndrome (PCOS h-Ins) patients?	Metformin	59-68	insulin	Homo sapiens	40-47
23595973-1	2013	STUDY QUESTION: Does treatment with the insulin sensitizer metformin modify the levels and activation of proteins related to the expression of the insulin-dependent glucose transporter (GLUT4), such as adenosine monophosphate-activated protein kinase (AMPK) and myocyte enhancer factor 2A (MEF2A), in endometria from hyperinsulinemic hyperandrogenemic polycystic ovary syndrome (PCOS h-Ins) patients?	Metformin	59-68	insulin	Homo sapiens	147-154
23595973-18	2013	WIDER IMPLICATIONS OF THE FINDINGS: Since the insulin sensitizer metformin increases the expression of the GLUT4, it may improve endometrial physiology in PCOS patients and, therefore, promote better reproductive outcomes.	Metformin	65-74	insulin	Homo sapiens	46-53
23595973-19	2013	These results suggest that in PCOS patients, metformin may act directly at the endometrial level and decrease insulin resistance condition by increasing the expression of GLUT4 and, in this way, indirectly restore endometrial function.	Metformin	45-54	insulin	Homo sapiens	110-117
23880192-1	2013	OBJECTIVES: Metformin impairs endothelialization of drug eluting stents (DES) due to convergent signaling at the mammalian target of rapamycin (mTOR) pathway.	Metformin	12-21	mechanistic target of rapamycin kinase	Homo sapiens	113-142
23880192-1	2013	OBJECTIVES: Metformin impairs endothelialization of drug eluting stents (DES) due to convergent signaling at the mammalian target of rapamycin (mTOR) pathway.	Metformin	12-21	mechanistic target of rapamycin kinase	Homo sapiens	144-148
24009539-0	2013	Metformin Down-regulates TNF-alpha Secretion via Suppression of Scavenger Receptors in Macrophages.	Metformin	0-9	tumor necrosis factor	Mus musculus	25-34
24009539-5	2013	Metformin reduced the production of NO, PGE2 and pro-inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) through down-regulation of NF-kappaB translocation in macrophages in a dose-dependent manner.	Metformin	0-9	interleukin 1 beta	Mus musculus	77-85
24009539-5	2013	Metformin reduced the production of NO, PGE2 and pro-inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) through down-regulation of NF-kappaB translocation in macrophages in a dose-dependent manner.	Metformin	0-9	interleukin 6	Mus musculus	87-91
24009539-5	2013	Metformin reduced the production of NO, PGE2 and pro-inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) through down-regulation of NF-kappaB translocation in macrophages in a dose-dependent manner.	Metformin	0-9	tumor necrosis factor	Mus musculus	96-105
24009539-6	2013	On the other hand, the protein expressions of anti-inflammatory cytokines, IL-4 and IL-10, were enhanced or maintained by metformin.	Metformin	122-131	interleukin 10	Mus musculus	84-89
24009539-7	2013	Also, metformin suppressed secretion of TNF-alpha and reduced the protein and mRNA expression of TNF-alpha in obese mice as well as in macrophages.	Metformin	6-15	tumor necrosis factor	Mus musculus	40-49
24009539-7	2013	Also, metformin suppressed secretion of TNF-alpha and reduced the protein and mRNA expression of TNF-alpha in obese mice as well as in macrophages.	Metformin	6-15	tumor necrosis factor	Mus musculus	97-106
24009539-9	2013	These results suggest that metformin may attenuate inflammatory responses by suppressing the production of TNF-alpha and the expressions of scavenger receptors.	Metformin	27-36	tumor necrosis factor	Mus musculus	107-116
23751310-6	2013	We postulate that even a few-month treatment with metformin results in the decrease of vitamin B12 and folate.	Metformin	50-59	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	95-98
23751310-7	2013	However, supplementation of vitamin B12 rather than the combination of vitamin B12 and folate might be profitable based on the mechanism of metformin on vitamins in patients with type 2 diabetes.	Metformin	140-149	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	36-39
23751310-0	2013	Adverse effect of metformin therapy on serum vitamin B12 and folate: short-term treatment causes disadvantages?	Metformin	18-27	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	53-56
23751310-3	2013	Recent observational studies, however, have demonstrated that long-term metformin therapy increases the probability of vitamin B12 and folate deficiency, and might contribute to the progression of diabetic peripheral neuropathy.	Metformin	72-81	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	127-130
23751310-4	2013	Despite metformin is widely used and extensively studied, randomized controlled trials performed to explore the effects of metformin on vitamin B12 and folate are limited.	Metformin	123-132	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	144-147
23438101-3	2013	OBJECTIVE: To assess the effect of metformin (Met) or omega-3 (omega-3) polyunsaturated fatty acids (PUFA) on the homeostasis model assessment-estimated insulin resistance (HOMA-IR) index, lipid profile, and body mass index (BMI) of obese children.	Metformin	35-44	insulin	Homo sapiens	153-160
24051942-4	2013	It has been demonstrated that by reducing hyperinsulinemia, in particular with the administration of metformin, insulin-lowering agents might improve endocrine and reproductive abnormalities in PCOS patients.	Metformin	101-110	insulin	Homo sapiens	47-54
23624033-8	2013	Metformin is the most commonly prescribed insulin sensitizer in PCOS.	Metformin	0-9	insulin	Homo sapiens	42-49
23562376-0	2013	Transfer of metformin across the rat placenta is mediated by organic cation transporter 3 (OCT3/SLC22A3) and multidrug and toxin extrusion 1 (MATE1/SLC47A1) protein.	Metformin	12-21	solute carrier family 47 member 1	Rattus norvegicus	109-140
23562376-0	2013	Transfer of metformin across the rat placenta is mediated by organic cation transporter 3 (OCT3/SLC22A3) and multidrug and toxin extrusion 1 (MATE1/SLC47A1) protein.	Metformin	12-21	solute carrier family 47 member 1	Rattus norvegicus	142-147
23562376-0	2013	Transfer of metformin across the rat placenta is mediated by organic cation transporter 3 (OCT3/SLC22A3) and multidrug and toxin extrusion 1 (MATE1/SLC47A1) protein.	Metformin	12-21	solute carrier family 47 member 1	Rattus norvegicus	148-155
23562376-2	2013	Since metformin is a substrate of both OCT3 and MATE1, in this study we used the model of dually perfused rat placenta to investigate the role of these transporters in metformin passage across the placenta.	Metformin	6-15	solute carrier family 47 member 1	Rattus norvegicus	48-53
23562376-5	2013	Furthermore, we observed that the oppositely directed H(+)-gradient can drive the secretion of metformin from placenta to maternal circulation, confirming apical efflux of metformin from trophoblast by MATE1.	Metformin	172-181	solute carrier family 47 member 1	Rattus norvegicus	202-207
23562376-6	2013	In conclusion, we suggest an important role of OCT3 and MATE1 in the transplacental transfer of metformin.	Metformin	96-105	solute carrier family 47 member 1	Rattus norvegicus	56-61
23922888-5	2013	Flow cytometric analysis showed that metformin treatment markedly reduced the number of tumor-initiating epithelial cell adhesion molecule (EpCAM)(+) HCC cells.	Metformin	37-46	epithelial cell adhesion molecule	Homo sapiens	105-138
23922888-5	2013	Flow cytometric analysis showed that metformin treatment markedly reduced the number of tumor-initiating epithelial cell adhesion molecule (EpCAM)(+) HCC cells.	Metformin	37-46	epithelial cell adhesion molecule	Homo sapiens	140-145
23922888-6	2013	Non-adherent sphere formation assays of EpCAM(+) cells showed that metformin impaired not only their sphere-forming ability, but also their self-renewal capability.	Metformin	67-76	epithelial cell adhesion molecule	Homo sapiens	40-45
23922888-7	2013	Consistent with this, immunostaining of spheres revealed that metformin significantly decreased the number of component cells positive for hepatic stem cell markers such as EpCAM and alpha-fetoprotein.	Metformin	62-71	epithelial cell adhesion molecule	Homo sapiens	173-178
23922888-7	2013	Consistent with this, immunostaining of spheres revealed that metformin significantly decreased the number of component cells positive for hepatic stem cell markers such as EpCAM and alpha-fetoprotein.	Metformin	62-71	alpha fetoprotein	Homo sapiens	183-200
23922888-9	2013	Notably, the administration of metformin but not sorafenib decreased the number of EpCAM(+) cells and impaired their self-renewal capability.	Metformin	31-40	epithelial cell adhesion molecule	Homo sapiens	83-88
23922888-10	2013	As reported, metformin activated AMP-activated protein kinase (AMPK) through phosphorylation; however its inhibitory effect on the mammalian target of rapamycin (mTOR) pathway did not necessarily correlate with its anti-tumor activity toward EpCAM(+) tumor-initiating HCC cells.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	131-160
23922888-10	2013	As reported, metformin activated AMP-activated protein kinase (AMPK) through phosphorylation; however its inhibitory effect on the mammalian target of rapamycin (mTOR) pathway did not necessarily correlate with its anti-tumor activity toward EpCAM(+) tumor-initiating HCC cells.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	162-166
23922888-10	2013	As reported, metformin activated AMP-activated protein kinase (AMPK) through phosphorylation; however its inhibitory effect on the mammalian target of rapamycin (mTOR) pathway did not necessarily correlate with its anti-tumor activity toward EpCAM(+) tumor-initiating HCC cells.	Metformin	13-22	epithelial cell adhesion molecule	Homo sapiens	242-247
23922888-11	2013	These results indicate that metformin is a promising therapeutic agent for the elimination of tumor-initiating HCC cells and suggest as-yet-unknown functions other than its inhibitory effect on the AMPK/mTOR pathway.	Metformin	28-37	mechanistic target of rapamycin kinase	Homo sapiens	203-207
23744726-12	2013	We observed a significant correlation between M value increase, an index of insulin sensitivity, and a decrease in inflammatory parameters in the exenatide plus metformin group.	Metformin	161-170	insulin	Homo sapiens	76-83
23624033-9	2013	Available randomized controlled trials suggest that metformin improves insulin resistance without any effect on body mass index, fasting glucose or lipid levels.	Metformin	52-61	insulin	Homo sapiens	71-78
23865839-5	2013	Metformin is an insulin sensitising agent which is known to improve vascular health outcomes in type 2 diabetes (T2D) and other individuals with insulin resistance.	Metformin	0-9	insulin	Homo sapiens	16-23
23936124-9	2013	AMPK activation by metformin completely reversed the inhibitory effect of glucose on Nampt-Sirt1-PGC-1 alpha and Rev-erb alpha.	Metformin	19-28	nicotinamide phosphoribosyltransferase	Mus musculus	85-90
23865839-5	2013	Metformin is an insulin sensitising agent which is known to improve vascular health outcomes in type 2 diabetes (T2D) and other individuals with insulin resistance.	Metformin	0-9	insulin	Homo sapiens	145-152
23620435-6	2013	Moreover, metformin administration activated AMPK and reduced both ER stress and apoptosis in ISO-induced rat heart failure in vivo.	Metformin	10-19	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	45-49
23524173-1	2013	OBJECTIVE: To evaluate glycemic control in women receiving metformin or insulin for gestational diabetes, and to identify factors predicting the need for supplemental insulin in women initially treated with metformin.	Metformin	207-216	insulin	Homo sapiens	167-174
23524173-8	2013	Twelve women in the metformin group (26.08%) required supplemental insulin for glycemic control.	Metformin	20-29	insulin	Homo sapiens	67-74
23524173-11	2013	Logistic regression analysis showed that gestational age at diagnosis and mean pretreatment glucose level were predictors of the need for supplemental insulin therapy in women initially treated with metformin.	Metformin	199-208	insulin	Homo sapiens	151-158
23362830-4	2013	Metformin treatment decreased cellular TP and ERCC1 protein and mRNA levels by down-regulating phosphorylated MEK1/2-ERK1/2 protein levels in a dose- and time-dependent manner.	Metformin	0-9	mitogen-activated protein kinase 3	Homo sapiens	117-123
23849162-14	2013	Insulin-resistance linked ovarian hyperandrogenism could also contribute to decreased fertility, and the two patients became pregnant after initiation of insulin-sensitizers (metformin).	Metformin	175-184	insulin	Homo sapiens	0-7
23849162-14	2013	Insulin-resistance linked ovarian hyperandrogenism could also contribute to decreased fertility, and the two patients became pregnant after initiation of insulin-sensitizers (metformin).	Metformin	175-184	insulin	Homo sapiens	154-161
23695170-5	2013	Treatment with metformin as single agent, however, induced an activation and phosphorylation of mitogen-activated protein kinase (MAPK) through an increased C-RAF/B-RAF heterodimerization.	Metformin	15-24	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	163-168
23695170-6	2013	The inhibition of EGFR phosphorylation and of downstream signaling by adding gefitinib to metformin treatment abrogated this phenomenon and induced a strong apoptotic effect in vitro and in vivo.	Metformin	90-99	epidermal growth factor receptor	Homo sapiens	18-22
23557757-7	2013	RESULT(S): We found that insulin-resistant PCOS patients [1] had greater limbic activation during an emotion task than controls (n = 5); [2] trended toward decreased positive affect and increased trait anxiety; [3] after metformin treatment, had limbic activation that no longer differed from controls; and [4] had positive correlations between fMRI limbic activation during emotional processing and mu-opioid binding potential.	Metformin	221-230	insulin	Homo sapiens	25-32
23350795-9	2013	CONCLUSIONS: These findings confirm low rates of clinically important hypoglycaemia using this method, and suggest that higher risk of hypoglycaemia may be suspected when patients needing insulin are younger, less obese and taking metformin and a sulphonylurea, and especially when A1c levels <=7.0% are attained with glargine dosage <=0.4 units/kg.	Metformin	231-240	insulin	Homo sapiens	188-195
24121378-2	2013	Metformin is an insulin sensitizer acting in the liver and the peripheral tissues that ameliorates the metabolic and reproductive defects in PCOS.	Metformin	0-9	insulin	Homo sapiens	16-23
23632475-4	2013	Metformin (i) activated the ataxia telengiectasia-mutated (ATM)-AMPK-p53/p21(cip1) and inhibited the Akt-mammalian target of rapamycin (mTOR)-eIF4E-binding protein 1 (4EBP1) pathways, (ii) induced G1 cycle arrest and (iii) enhanced apoptosis.	Metformin	0-9	tumor protein p53	Homo sapiens	69-72
23607966-5	2013	The clinically available adenosine monophosphate-activated protein kinase activator, metformin, which is an antidiabetic drug, prevents rapamycin-induced ERK activation and the development of mechanical hypersensitivity and spontaneous pain.	Metformin	85-94	mitogen-activated protein kinase 1	Homo sapiens	154-157
23624419-5	2013	Vildagliptin+metformin were more effective than placebo+metformin in reducing body weight and BMI, glycemic control, HOMA-IR, glucagon and insulin resistance measurements.	Metformin	13-22	insulin	Homo sapiens	139-146
23624419-7	2013	We also recorded a significant correlation between M value increase and the decrease of vaspin, visfatin, and omentin-1 obtained with vildagliptin+metformin.	Metformin	147-156	serpin family A member 12	Homo sapiens	88-94
23521863-0	2013	Metformin inhibits the senescence-associated secretory phenotype by interfering with IKK/NF-kappaB activation.	Metformin	0-9	nuclear factor kappa B subunit 1	Homo sapiens	89-98
23521863-3	2013	Bioinformatic analysis of genes downregulated by metformin suggests that the drug blocks the activity of the transcription factor NF-kappaB.	Metformin	49-58	nuclear factor kappa B subunit 1	Homo sapiens	130-139
23521863-4	2013	In agreement, metformin prevented the translocation of NF-kappaB to the nucleus and inhibited the phosphorylation of IkappaB and IKKalpha/beta, events required for activation of the NF-kappaB pathway.	Metformin	14-23	nuclear factor kappa B subunit 1	Homo sapiens	55-64
23521863-4	2013	In agreement, metformin prevented the translocation of NF-kappaB to the nucleus and inhibited the phosphorylation of IkappaB and IKKalpha/beta, events required for activation of the NF-kappaB pathway.	Metformin	14-23	nuclear factor kappa B subunit 1	Homo sapiens	182-191
23521863-5	2013	These effects were not dependent on AMPK activation or on the context of cellular senescence, as metformin inhibited the NF-kappaB pathway stimulated by lipopolysaccharide (LPS) in ampk null fibroblasts and in macrophages.	Metformin	97-106	nuclear factor kappa B subunit 1	Homo sapiens	121-130
23582785-8	2013	The Km values for metformin and phenformin were 235 and 37.4 muM, with CL(int) (V(max)/K(m)) values of 71.9x10-3 muL/min per oocyte and 209x10-3 muL/min per oocyte, respectively.	Metformin	18-27	latexin	Homo sapiens	61-64
23384119-8	2013	Addition of Vildagliptin to ongoing Metformin treatment reconstitutes the disproportionality of the proinsulin to insulin secretion from the beta cell.	Metformin	36-45	insulin	Homo sapiens	100-110
23384119-8	2013	Addition of Vildagliptin to ongoing Metformin treatment reconstitutes the disproportionality of the proinsulin to insulin secretion from the beta cell.	Metformin	36-45	insulin	Homo sapiens	103-110
23611575-2	2013	The administration of metformin reduced pain intensity from 9/10 to 3/10 and favorably affected the profile of inflammatory cytokines (i.e., TNF a, IL-1beta, IL-6, and IL-10), adipokines (i.e., adiponectin, leptin, and resistin), and beta-endorphin.	Metformin	22-31	tumor necrosis factor	Homo sapiens	141-146
23611575-2	2013	The administration of metformin reduced pain intensity from 9/10 to 3/10 and favorably affected the profile of inflammatory cytokines (i.e., TNF a, IL-1beta, IL-6, and IL-10), adipokines (i.e., adiponectin, leptin, and resistin), and beta-endorphin.	Metformin	22-31	interleukin 1 beta	Homo sapiens	148-156
23611575-2	2013	The administration of metformin reduced pain intensity from 9/10 to 3/10 and favorably affected the profile of inflammatory cytokines (i.e., TNF a, IL-1beta, IL-6, and IL-10), adipokines (i.e., adiponectin, leptin, and resistin), and beta-endorphin.	Metformin	22-31	interleukin 6	Homo sapiens	158-162
23611575-2	2013	The administration of metformin reduced pain intensity from 9/10 to 3/10 and favorably affected the profile of inflammatory cytokines (i.e., TNF a, IL-1beta, IL-6, and IL-10), adipokines (i.e., adiponectin, leptin, and resistin), and beta-endorphin.	Metformin	22-31	adiponectin, C1Q and collagen domain containing	Homo sapiens	194-205
23611575-2	2013	The administration of metformin reduced pain intensity from 9/10 to 3/10 and favorably affected the profile of inflammatory cytokines (i.e., TNF a, IL-1beta, IL-6, and IL-10), adipokines (i.e., adiponectin, leptin, and resistin), and beta-endorphin.	Metformin	22-31	proopiomelanocortin	Homo sapiens	234-248
23808735-6	2013	Insulin therapy with respect to the positive outcomes of study with insulin analogs moved up to the second line in algorithm therapy, immediately after metformin therapy and change of life style.	Metformin	152-161	insulin	Homo sapiens	0-7
23808735-6	2013	Insulin therapy with respect to the positive outcomes of study with insulin analogs moved up to the second line in algorithm therapy, immediately after metformin therapy and change of life style.	Metformin	152-161	insulin	Homo sapiens	68-75
21945710-7	2013	Insulin resistance was confirmed by HOMA-IR index and metformin-treated group presented reduction of insulin levels at week 22.	Metformin	54-63	insulin	Homo sapiens	0-7
21945710-7	2013	Insulin resistance was confirmed by HOMA-IR index and metformin-treated group presented reduction of insulin levels at week 22.	Metformin	54-63	insulin	Homo sapiens	101-108
21945710-11	2013	Metformin treatment was able to reduce insulin resistance and attenuated this adverse cardiac and vascular remodeling.	Metformin	0-9	insulin	Homo sapiens	39-46
23462329-7	2013	Metformin administration also caused a significant reduction in the phosphorylation of ribosomal S6 protein and ERK in these xenografts.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	112-115
23381014-7	2013	Meta-analysis of observational studies showed a 50% reduction in HCC incidence with metformin use (n=8 studies; OR 0.50, 95% CI 0.34-0.73), 62% and 161% increase in HCC incidence with sulfonylurea (n=8 studies; OR 1.62, 95% CI 1.16-2.24) or insulin use (n=7; OR 2.61, 95% CI 1.46-4.65), respectively.	Metformin	84-93	insulin	Homo sapiens	241-248
23315599-0	2013	How metformin acts in PCOS pregnant women: insights into insulin secretion and peripheral action at each trimester of gestation.	Metformin	4-13	insulin	Homo sapiens	57-64
23315599-9	2013	Insulin secretion was significantly higher during the first trimester in patients with an early failure of metformin treatment.	Metformin	107-116	insulin	Homo sapiens	0-7
22751115-7	2013	AMPK activation by its activators AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) and metformin (N",N"-dimethylbiguanide), the most widely used antidiabetic drug, increased the expression of XPC and UVB-induced DNA repair in mouse skin, normal human epidermal keratinocytes, and AMPK wild-type (WT) cells but not in AMPK-deficient cells, indicating an AMPK-dependent mechanism.	Metformin	92-101	xeroderma pigmentosum, complementation group C	Mus musculus	197-200
22751115-7	2013	AMPK activation by its activators AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) and metformin (N",N"-dimethylbiguanide), the most widely used antidiabetic drug, increased the expression of XPC and UVB-induced DNA repair in mouse skin, normal human epidermal keratinocytes, and AMPK wild-type (WT) cells but not in AMPK-deficient cells, indicating an AMPK-dependent mechanism.	Metformin	109-126	xeroderma pigmentosum, complementation group C	Mus musculus	197-200
22751115-9	2013	Furthermore, AMPK deletion increased extracellular signal-regulated kinase (ERK) activation and cell proliferation, whereas AICAR and metformin inhibited ERK activation and cell proliferation in keratinocytes, mouse skin, AMPK WT and AMPK-deficient cells, suggesting an AMPK-independent mechanism.	Metformin	134-143	mitogen-activated protein kinase 1	Mus musculus	154-157
23632475-4	2013	Metformin (i) activated the ataxia telengiectasia-mutated (ATM)-AMPK-p53/p21(cip1) and inhibited the Akt-mammalian target of rapamycin (mTOR)-eIF4E-binding protein 1 (4EBP1) pathways, (ii) induced G1 cycle arrest and (iii) enhanced apoptosis.	Metformin	0-9	cyclin dependent kinase inhibitor 1A	Homo sapiens	73-76
23632475-4	2013	Metformin (i) activated the ataxia telengiectasia-mutated (ATM)-AMPK-p53/p21(cip1) and inhibited the Akt-mammalian target of rapamycin (mTOR)-eIF4E-binding protein 1 (4EBP1) pathways, (ii) induced G1 cycle arrest and (iii) enhanced apoptosis.	Metformin	0-9	cyclin dependent kinase inhibitor 1A	Homo sapiens	77-81
23632475-4	2013	Metformin (i) activated the ataxia telengiectasia-mutated (ATM)-AMPK-p53/p21(cip1) and inhibited the Akt-mammalian target of rapamycin (mTOR)-eIF4E-binding protein 1 (4EBP1) pathways, (ii) induced G1 cycle arrest and (iii) enhanced apoptosis.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	101-134
23632475-4	2013	Metformin (i) activated the ataxia telengiectasia-mutated (ATM)-AMPK-p53/p21(cip1) and inhibited the Akt-mammalian target of rapamycin (mTOR)-eIF4E-binding protein 1 (4EBP1) pathways, (ii) induced G1 cycle arrest and (iii) enhanced apoptosis.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	136-140
23168250-9	2013	Metformin treatment was associated with a lower total serum vitamin B12, but a comparable RBC-B12 and a slightly lower MMA and better methylation index.	Metformin	0-9	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	68-71
23679951-2	2013	It improves peripheral and liver sensitivity to insulin, reduces basal hepatic glucose production, increases insulin-stimulated uptake and utilization of glucose by peripheral tissues, decreases hunger and causes weight reduction.Recently, much attention has been made toward the possible kidney protective efficacy of metformin.	Metformin	319-328	insulin	Homo sapiens	109-116
23663483-9	2013	The anti-proliferative actions of metformin were associated with an activation of AMP-activated protein kinase AMPKThr172 together with an inhibition of the insulin/insulin-like growth factor-I (IGF-I) receptor activation and downstream signalling mediators IRS-1 and phosphorylated Akt.	Metformin	34-43	insulin like growth factor 1	Homo sapiens	157-193
23663483-9	2013	The anti-proliferative actions of metformin were associated with an activation of AMP-activated protein kinase AMPKThr172 together with an inhibition of the insulin/insulin-like growth factor-I (IGF-I) receptor activation and downstream signalling mediators IRS-1 and phosphorylated Akt.	Metformin	34-43	AKT serine/threonine kinase 1	Homo sapiens	283-286
23663483-10	2013	Furthermore, exposure to metformin during normal glucose conditions led to increased apoptosis as measured by poly(ADP-ribose) polymerase (PARP) cleavage.	Metformin	25-34	poly(ADP-ribose) polymerase 1	Homo sapiens	110-137
23663483-10	2013	Furthermore, exposure to metformin during normal glucose conditions led to increased apoptosis as measured by poly(ADP-ribose) polymerase (PARP) cleavage.	Metformin	25-34	poly(ADP-ribose) polymerase 1	Homo sapiens	139-143
23663483-11	2013	In contrast, exposure to high glucose levels promoted a more robust IGF-I response and Akt activation which correlated to stimulated AMPKSer485 phosphorylation and impaired AMPKThr172 phosphorylation, resulting in reduced anti-proliferative and apoptotic effects by metformin.	Metformin	266-275	insulin like growth factor 1	Homo sapiens	68-73
23663483-12	2013	CONCLUSION: Our results indicate that metformin has direct anti-tumour activities in pancreatic cancer cells involving AMPKThr172 activation and suppression of the insulin/IGF signalling pathways.	Metformin	38-47	insulin	Homo sapiens	164-171
23663483-13	2013	However, hyperglycaemic conditions enhance the insulin/IGF-I responses resulting in an altered AMPK activation profile and prevent metformin from fully switching off the growth promoting signals in pancreatic cancer cells.	Metformin	131-140	insulin like growth factor 1	Homo sapiens	55-60
23402786-0	2013	Metformin increases liver accumulation of vitamin B12 - an experimental study in rats.	Metformin	0-9	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	50-53
23402786-1	2013	AIMS/HYPOTHESIS: Patients treated with metformin exhibit low levels of plasma vitamin B12 (B12), and are considered at risk for developing B12 deficiency.	Metformin	39-48	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	86-89
23402786-1	2013	AIMS/HYPOTHESIS: Patients treated with metformin exhibit low levels of plasma vitamin B12 (B12), and are considered at risk for developing B12 deficiency.	Metformin	39-48	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	91-94
23402786-1	2013	AIMS/HYPOTHESIS: Patients treated with metformin exhibit low levels of plasma vitamin B12 (B12), and are considered at risk for developing B12 deficiency.	Metformin	39-48	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	91-94
23402786-2	2013	In this study, we investigated the effect of metformin treatment on B12 uptake and distribution in rats.	Metformin	45-54	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	68-71
23402786-5	2013	RESULTS: Three weeks of metformin treatment reduced plasma B12 by 22% or 289 [47-383] pmol/L (median and [range]) (p = 0.001), while no effect was observed on unsaturated B12-binding capacity.	Metformin	24-33	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	59-62
23402786-5	2013	RESULTS: Three weeks of metformin treatment reduced plasma B12 by 22% or 289 [47-383] pmol/L (median and [range]) (p = 0.001), while no effect was observed on unsaturated B12-binding capacity.	Metformin	24-33	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	171-174
23402786-6	2013	Compared with controls, the amount of B12 in the liver was 36% (p = 0.007) higher in metformin-treated rats, while the B12 content in the kidney was 34% (p = 0.013) lower.	Metformin	85-94	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	38-41
23402786-6	2013	Compared with controls, the amount of B12 in the liver was 36% (p = 0.007) higher in metformin-treated rats, while the B12 content in the kidney was 34% (p = 0.013) lower.	Metformin	85-94	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	119-122
23402786-8	2013	CONCLUSIONS/INTERPRETATION: These results show that metformin treatment increases liver accumulation of B12, thereby resulting in decreases in circulating B12 and kidney accumulation of the vitamin.	Metformin	52-61	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	104-107
23402786-8	2013	CONCLUSIONS/INTERPRETATION: These results show that metformin treatment increases liver accumulation of B12, thereby resulting in decreases in circulating B12 and kidney accumulation of the vitamin.	Metformin	52-61	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	155-158
23402786-9	2013	Our data questions whether the low plasma B12 observed in patients treated with metformin reflects impaired B12 status, and rather suggests altered tissue distribution and metabolism of the vitamin.	Metformin	80-89	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	42-45
23225247-0	2013	Metformin inhibits advanced glycation end products (AGEs)-induced growth and VEGF expression in MCF-7 breast cancer cells by suppressing AGEs receptor expression via AMP-activated protein kinase.	Metformin	0-9	vascular endothelial growth factor A	Homo sapiens	77-81
23225247-4	2013	We examined here whether and how metformin could block the AGEs-induced growth and vascular endothelial growth factor (VEGF) expression in MCF-7 breast cancer cells.	Metformin	33-42	vascular endothelial growth factor A	Homo sapiens	83-117
23225247-4	2013	We examined here whether and how metformin could block the AGEs-induced growth and vascular endothelial growth factor (VEGF) expression in MCF-7 breast cancer cells.	Metformin	33-42	vascular endothelial growth factor A	Homo sapiens	119-123
23225247-8	2013	Furthermore, metformin at 0.01 mM completely suppressed the AGEs-induced upregulation of RAGE and VEGF mRNA levels in MCF-7 cells.	Metformin	13-22	vascular endothelial growth factor A	Homo sapiens	98-102
23225247-9	2013	An inhibitor of AMP-activated protein kinase, compound C significantly blocked the growth-inhibitory and RAGE and VEGF suppressing effects of metformin in AGEs-exposed MCF-7 cells.	Metformin	142-151	vascular endothelial growth factor A	Homo sapiens	114-118
23225247-10	2013	Our present study suggests that metformin could inhibit the AGEs-induced growth and VEGF expression in MCF-7 breast cancer cells by suppressing RAGE gene expression via AMP-activated protein kinase pathway.	Metformin	32-41	vascular endothelial growth factor A	Homo sapiens	84-88
23686371-5	2013	We observed an association between G6P accumulation, mTOR activation, endoplasmic reticulum (ER) stress, and impaired contractile function, all of which were prevented by pretreating animals with rapamycin (mTOR inhibition) or metformin (AMPK activation).	Metformin	227-236	mechanistic target of rapamycin kinase	Homo sapiens	53-57
23667692-8	2013	Metformin was associated with a reduction of phospho-Erk and phospho-mTOR independent of Akt and AMPK phosphorylation.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	69-73
24843658-5	2013	For instance, metformin, an insulin sensitizer, reportedly has a potential anticancer effect.	Metformin	14-23	insulin	Homo sapiens	28-35
23566618-2	2013	Numerous epidemiological cohort and case-control studies showed that type 2 diabetes is a risk factor for cancer and that metformin therapy is associated with a significant reduction in the incidence of cancer and cancer-related death when compared to other glucose-lowering agents (sulfonylureas, insulin).	Metformin	122-131	insulin	Homo sapiens	298-305
23557965-8	2013	RESULTS: Metformin attenuated both arthritis scores and bone destruction in CAIA mice, decreased the serum levels of the pro-inflammatory cytokines, TNF-alpha and IL-1, and reduced the number of RORgammat+CD4+ T cells in the ALNs.	Metformin	9-18	tumor necrosis factor	Mus musculus	149-158
23557965-10	2013	Metformin treatment of normal cells cultured in Th17-differentiation-inducing conditions decreased the number of RORgammat-expressing CD4+ cells in a dose-dependent manner and downregulated STAT3 phosphorylation via the AMPK pathway.	Metformin	0-9	signal transducer and activator of transcription 3	Mus musculus	190-195
23168250-9	2013	Metformin treatment was associated with a lower total serum vitamin B12, but a comparable RBC-B12 and a slightly lower MMA and better methylation index.	Metformin	0-9	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	94-97
23168250-11	2013	Metformin treatment was associated with low serum vitamin B12 and improved intracellular vitamin B12 metabolism despite low serum vitamin B12.	Metformin	0-9	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	58-61
23168250-11	2013	Metformin treatment was associated with low serum vitamin B12 and improved intracellular vitamin B12 metabolism despite low serum vitamin B12.	Metformin	0-9	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	97-100
23168250-11	2013	Metformin treatment was associated with low serum vitamin B12 and improved intracellular vitamin B12 metabolism despite low serum vitamin B12.	Metformin	0-9	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	97-100
23523792-0	2013	Metformin induces up-regulation of blood-brain barrier functions by activating AMP-activated protein kinase in rat brain microvascular endothelial cells.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	79-107
23748512-8	2013	When necessary, drug intervention, described in this article as the MGI (metformin, glucagon-like peptide-1 receptor agonist, and insulin) approach, should begin with metformin and progress to the early addition of glucagon-like peptide-1 receptor agonists because of their weight loss potential and ability to target multiple pathophysiologic defects in patients with T2DM.	Metformin	167-176	insulin	Homo sapiens	130-137
23748512-10	2013	Long-acting insulin should be initiated if glycemic control is not achieved with metformin and glucagon-like peptide-1 receptor agonist combination therapy, focusing on long-acting insulin analogs that induce the least weight gain and have the lowest hypoglycemic risk.	Metformin	81-90	insulin	Homo sapiens	12-19
23523792-5	2013	These effects of metformin were blocked by compound C, an inhibitor of AMP-activated protein kinase (AMPK).	Metformin	17-26	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	71-99
23523792-5	2013	These effects of metformin were blocked by compound C, an inhibitor of AMP-activated protein kinase (AMPK).	Metformin	17-26	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	101-105
23523792-7	2013	These findings indicate that metformin induces up-regulation of BBB functions via AMPK activation.	Metformin	29-38	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	82-86
23620761-0	2013	Metformin downregulates the insulin/IGF-I signaling pathway and inhibits different uterine serous carcinoma (USC) cells proliferation and migration in p53-dependent or -independent manners.	Metformin	0-9	insulin	Homo sapiens	28-35
23620761-0	2013	Metformin downregulates the insulin/IGF-I signaling pathway and inhibits different uterine serous carcinoma (USC) cells proliferation and migration in p53-dependent or -independent manners.	Metformin	0-9	insulin like growth factor 1	Homo sapiens	36-41
23228442-3	2013	Metformin has also been reported to inhibit mTORC1 independent of AMPK through p53-dependent regulated in development and DNA damage responses 1 (REDD1) or by inhibiting Rag GTPases.	Metformin	0-9	DNA-damage-inducible transcript 4	Mus musculus	146-151
23620761-0	2013	Metformin downregulates the insulin/IGF-I signaling pathway and inhibits different uterine serous carcinoma (USC) cells proliferation and migration in p53-dependent or -independent manners.	Metformin	0-9	tumor protein p53	Homo sapiens	151-154
23620761-7	2013	Given the cross-talk between the insulin and IGF signaling pathways, the aim of this study was to examine the hypothesis that the anti-proliferative actions of metformin in uterine serous carcinoma (USC) are potentially mediated via suppression of the IGF-I receptor (IGF-IR) pathway.	Metformin	160-169	insulin	Homo sapiens	33-40
23620761-8	2013	Our results show that metformin interacts with the IGF pathway, and induces apoptosis and inhibition of proliferation and migration of USC cell lines with both wild type and mutant p53.	Metformin	22-31	tumor protein p53	Homo sapiens	181-184
23417334-1	2013	This study investigated the effects of genetic polymorphisms in organic cation transporter (OCT) genes, such as OCT1-3, OCTN1, MATE1, and MATE2-K, on metformin pharmacokinetics.	Metformin	150-159	solute carrier family 22 member 1	Homo sapiens	112-118
23713537-1	2013	Metformin attenuates the higher insulin sensitivity that occurs with exercise training.	Metformin	0-9	insulin	Homo sapiens	32-39
22963881-10	2013	Comparing the two groups in a final multivariate model, AOPP, FRAP, and AGE levels changed more significantly in metformin compared with lifestyle modification alone (p = 0.007, p < 0.001 and p < 0.001 respectively).	Metformin	113-122	mechanistic target of rapamycin kinase	Homo sapiens	62-66
23205962-2	2013	The Metformin in Gestational Diabetes (MiG) trial reported similar pregnancy outcomes for metformin versus insulin; however, supplemental insulin was required in 46% of women on metformin.	Metformin	178-187	insulin	Homo sapiens	138-145
23223177-4	2013	Conversely, activation of AMPK by metformin stimulated JNK1-Bcl-2 signaling and disrupted the Beclin1-Bcl-2 complex.	Metformin	34-43	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	26-30
23223177-4	2013	Conversely, activation of AMPK by metformin stimulated JNK1-Bcl-2 signaling and disrupted the Beclin1-Bcl-2 complex.	Metformin	34-43	B cell leukemia/lymphoma 2	Mus musculus	60-65
23223177-4	2013	Conversely, activation of AMPK by metformin stimulated JNK1-Bcl-2 signaling and disrupted the Beclin1-Bcl-2 complex.	Metformin	34-43	B cell leukemia/lymphoma 2	Mus musculus	102-107
23223177-7	2013	Finally, chronic administration of metformin in diabetic mice restored cardiac autophagy by activating JNK1-Bcl-2 pathways and dissociating Beclin1 and Bcl-2.	Metformin	35-44	B cell leukemia/lymphoma 2	Mus musculus	108-113
23223177-7	2013	Finally, chronic administration of metformin in diabetic mice restored cardiac autophagy by activating JNK1-Bcl-2 pathways and dissociating Beclin1 and Bcl-2.	Metformin	35-44	B cell leukemia/lymphoma 2	Mus musculus	152-157
22773548-9	2013	Cell line studies showed that metformin inhibits hepatocyte proliferation and induces cell cycle arrest at G0/G1 phase via AMP-activated protein kinase and its upstream kinase LKB1 to upregulate p21/Cip1 and p27/Kip1 and downregulate cyclin D1 in a dose-dependent manner, but independent of p53.	Metformin	30-39	cyclin dependent kinase inhibitor 1A	Homo sapiens	199-203
23000260-6	2013	The silencing of FHC expression with siRNAs inhibited the ability of metformin to protect cardiomyocytes from doxorubicin-induced damage, in terms of the percentage of cell viability, the levels of reactive oxygen species, and the activity of antioxidant enzymes (catalase, glutathione peroxidase, and superoxide dismutase).	Metformin	69-78	catalase	Mus musculus	264-272
23000260-7	2013	In addition, metformin induced the activation of NF-kappaB in HL-1 cells, whereas preincubation with SN50, an inhibitor of NF-kappaB, blocked the upregulation of the FHC and the protective effect mediated by metformin.	Metformin	13-22	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	49-58
23000260-7	2013	In addition, metformin induced the activation of NF-kappaB in HL-1 cells, whereas preincubation with SN50, an inhibitor of NF-kappaB, blocked the upregulation of the FHC and the protective effect mediated by metformin.	Metformin	208-217	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	123-132
23000260-8	2013	Taken together, these results provide new knowledge on the protective actions of metformin against doxorubicin-induced cardiotoxicity by identifying FHC and NF-kappaB as the major mediators of this beneficial effect.	Metformin	81-90	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	157-166
22773548-9	2013	Cell line studies showed that metformin inhibits hepatocyte proliferation and induces cell cycle arrest at G0/G1 phase via AMP-activated protein kinase and its upstream kinase LKB1 to upregulate p21/Cip1 and p27/Kip1 and downregulate cyclin D1 in a dose-dependent manner, but independent of p53.	Metformin	30-39	tumor protein p53	Homo sapiens	291-294
23279603-1	2013	AIM: The aim of the present study was to investigate the efficacy of Metformin compared with a hypocaloric diet on C-reactive protein (CRP) level and markers of insulin resistance in obese and overweight women with polycystic ovary syndrome (PCOS).	Metformin	69-78	insulin	Homo sapiens	161-168
23171036-4	2013	We also followed up a subset of male patients with HIV and hepatitis C virus (HCV) coinfection (n = 47) who were not receiving antiviral treatment and for whom metformin was prescribed for insulin resistance, which tends to have a higher incidence and severity in coinfected patients.	Metformin	160-169	insulin	Homo sapiens	189-196
23171036-7	2013	Treatment with metformin in HIV and HCV coinfected patients was well tolerated and significantly increased the sensitivity of peripheral tissues to insulin.	Metformin	15-24	insulin	Homo sapiens	148-155
23171036-8	2013	The minor allele (C) of the rs11212617 variant was associated with treatment success and may affect the course of insulin resistance in response to metformin (odds ratio 1.21; 95% confidence interval 1.07-1.39; P = 0.005).	Metformin	148-157	insulin	Homo sapiens	114-121
23171036-10	2013	CONCLUSIONS: We provide novel data suggesting that identification of the ATM rs11212617 variant may be important in assessing the glycaemic response to metformin treatment for insulin resistance in HIV-infected patients.	Metformin	152-161	insulin	Homo sapiens	176-183
23225237-0	2013	Gender-dependent effects of metformin on vaspin and adiponectin in type 2 diabetes patients: a randomized clinical trial.	Metformin	28-37	serpin family A member 12	Homo sapiens	41-47
23225237-0	2013	Gender-dependent effects of metformin on vaspin and adiponectin in type 2 diabetes patients: a randomized clinical trial.	Metformin	28-37	adiponectin, C1Q and collagen domain containing	Homo sapiens	52-63
23225237-1	2013	The aim of the study was to assess the effects of metformin on serum concentrations of vaspin and adiponectin in diabetes.	Metformin	50-59	serpin family A member 12	Homo sapiens	87-93
23225237-1	2013	The aim of the study was to assess the effects of metformin on serum concentrations of vaspin and adiponectin in diabetes.	Metformin	50-59	adiponectin, C1Q and collagen domain containing	Homo sapiens	98-109
23225237-8	2013	Vaspin dropped significantly after 3-month metformin therapy only in women (1.36 vs. 0.98, p=0.003 in women and 1.31 vs. 1.20, p=0.335 in men).	Metformin	43-52	serpin family A member 12	Homo sapiens	0-6
23225237-10	2013	Comparing case and control groups, metformin decreased vaspin levels more significantly than lifestyle modification in the final multivariate model after controlling for potential confounders only in women (p=0.002) but not men (p=0.896).	Metformin	35-44	serpin family A member 12	Homo sapiens	55-61
23225237-12	2013	Our findings suggest that metformin therapy reduces vaspin concentration in a gender-specific manner.	Metformin	26-35	serpin family A member 12	Homo sapiens	52-58
23680741-3	2013	While the rationale to keep metformin with insulin is strong (mostly as an insulin-sparing agent to limit weight gain), the evidence is less clear for other OADs.	Metformin	28-37	insulin	Homo sapiens	43-50
23680741-3	2013	While the rationale to keep metformin with insulin is strong (mostly as an insulin-sparing agent to limit weight gain), the evidence is less clear for other OADs.	Metformin	28-37	insulin	Homo sapiens	75-82
23279603-0	2013	Effect of metformin compared with hypocaloric diet on serum C-reactive protein level and insulin resistance in obese and overweight women with polycystic ovary syndrome.	Metformin	10-19	C-reactive protein	Homo sapiens	60-78
23279603-1	2013	AIM: The aim of the present study was to investigate the efficacy of Metformin compared with a hypocaloric diet on C-reactive protein (CRP) level and markers of insulin resistance in obese and overweight women with polycystic ovary syndrome (PCOS).	Metformin	69-78	C-reactive protein	Homo sapiens	115-133
23279603-1	2013	AIM: The aim of the present study was to investigate the efficacy of Metformin compared with a hypocaloric diet on C-reactive protein (CRP) level and markers of insulin resistance in obese and overweight women with polycystic ovary syndrome (PCOS).	Metformin	69-78	C-reactive protein	Homo sapiens	135-138
23279603-5	2013	Serum concentration of hs-CRP significantly decreased in both the Metformin (5.29 +- 2.50 vs 3.81 +- 1.99, P = 0.008) and diet groups (6.08 +- 2.14 vs 4.27 +- 1.60, P = 0.004).	Metformin	66-75	C-reactive protein	Homo sapiens	26-29
23279603-9	2013	CONCLUSIONS: Although weight reduction has equal efficacy with Metformin in decreasing serum hs-CRP levels, it was significantly more effective in improving insulin resistance in obese and overweight PCOS women.	Metformin	63-72	C-reactive protein	Homo sapiens	96-99
23608322-9	2013	Metformin and weight reduction therapy resulted in a significant decrease in the fasting insulin, glucose/insulin ratio and HOMA-IR.	Metformin	0-9	insulin	Homo sapiens	89-96
23608322-10	2013	Metformin and weight reduction therapy resulted in a significant decrease in the lipid parameters, testosterone, LH/FSH ratio, SHBG, and prolactin levels.	Metformin	0-9	sex hormone binding globulin	Homo sapiens	127-131
23608322-14	2013	Metformin and weight reduction therapy decreased also hyperandrogenism and insulin resistance.	Metformin	0-9	insulin	Homo sapiens	75-82
23449430-0	2013	Metformin impairs vascular endothelial recovery after stent placement in the setting of locally eluted mammalian target of rapamycin inhibitors via S6 kinase-dependent inhibition of cell proliferation.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	103-132
23755710-2	2013	Metformin, the first choice oral glucose-lowering agent, is classically contraindicated in case of chronic kidney disease of stages 3-5 (creatinine clearance < 60 ml/min/1.73 m2), because of a risk of accumulation of the biguanide that may lead to lactic acidosis.	Metformin	0-9	CD59 molecule (CD59 blood group)	Homo sapiens	169-174
23531341-0	2013	Proteomic and functional annotation analysis of injured peripheral nerves reveals ApoE as a protein upregulated by injury that is modulated by metformin treatment.	Metformin	143-152	apolipoprotein E	Rattus norvegicus	82-86
23531341-8	2013	With these methods, we identified apolipoprotein E (ApoE) as a protein profoundly increased by PNI and further increased by PNI and metformin.	Metformin	132-141	apolipoprotein E	Rattus norvegicus	34-50
23531341-8	2013	With these methods, we identified apolipoprotein E (ApoE) as a protein profoundly increased by PNI and further increased by PNI and metformin.	Metformin	132-141	apolipoprotein E	Rattus norvegicus	52-56
23531341-10	2013	Furthermore, we show that 7-day treatment with metformin in naive mice leads to an increase in ApoE expression in the sciatic nerve.	Metformin	47-56	apolipoprotein E	Mus musculus	95-99
23531341-12	2013	Our data identify a key association of ApoE with PNI that is regulated by metformin treatment.	Metformin	74-83	apolipoprotein E	Rattus norvegicus	39-43
23531341-13	2013	We conclude from the known functions of ApoE in the nervous system that ApoE may be an intrinsic factor linked to nerve regeneration after PNI, an effect that is further enhanced by metformin treatment.	Metformin	182-191	apolipoprotein E	Rattus norvegicus	40-44
23531341-13	2013	We conclude from the known functions of ApoE in the nervous system that ApoE may be an intrinsic factor linked to nerve regeneration after PNI, an effect that is further enhanced by metformin treatment.	Metformin	182-191	apolipoprotein E	Rattus norvegicus	72-76
23510106-3	2013	In a paper published in Proceedings of the National Academy of Sciences of the United States of America, Hirsch and colleagues show that metformin interferes with a signaling pathway, mediated by the transcription factor NF-kappaB, which drives cell transformation and is required for the maintenance of cancer stem cells.	Metformin	137-146	nuclear factor kappa B subunit 1	Homo sapiens	221-230
23020608-1	2013	A randomized study characterizing metformin patients needing additional insulin.	Metformin	34-43	insulin	Homo sapiens	72-79
23020608-3	2013	Furthermore, we aimed to characterize metformin-treated patients needing additional insulin to achieve prespecified glucose targets.	Metformin	38-47	insulin	Homo sapiens	84-91
23020608-7	2013	Only 23 (20.9%) of the 110 patients in the metformin group needed additional insulin.	Metformin	43-52	insulin	Homo sapiens	77-84
23194004-6	2013	Metformin treatment, lead to a significant decrease in serum insulin (p = 0.0132) and testosterone (p = 0.0017) levels.	Metformin	0-9	insulin	Homo sapiens	61-68
23674518-4	2013	We also studied the effect of metformin therapy on the CRP-leptin correlation in patients with newly diagnosed diabetes.	Metformin	30-39	C-reactive protein	Homo sapiens	55-58
23674518-11	2013	This is the first report demonstrating the restorative role of metformin on the leptin-CRP correlation in patients with newly diagnosed diabetes.	Metformin	63-72	C-reactive protein	Homo sapiens	87-90
22861817-3	2013	As organic cation transporters (OCT) belonging to the solute carrier 22A gene family, including OCT-1, OCT-2, and OCT-3, mediate metformin uptake and activity, it is critical to define what role they play in the antineoplastic activity of metformin.	Metformin	129-138	solute carrier family 22 member 1	Homo sapiens	96-101
22861817-3	2013	As organic cation transporters (OCT) belonging to the solute carrier 22A gene family, including OCT-1, OCT-2, and OCT-3, mediate metformin uptake and activity, it is critical to define what role they play in the antineoplastic activity of metformin.	Metformin	239-248	solute carrier family 22 member 1	Homo sapiens	96-101
23280877-5	2013	In vivo kidney uptake clearances of benzylpenicillin and metformin, which are typical substrates for renal organic anion transporters Oat1 and Oat3 and organic cation transporters Oct1 and Oct2, respectively, were evaluated.	Metformin	57-66	POU class 2 homeobox 2	Rattus norvegicus	189-193
22850868-9	2013	Metformin also countered the JNK2 activation evoked by lipotoxicity.	Metformin	0-9	mitogen-activated protein kinase 9	Mus musculus	29-33
22850868-11	2013	CONCLUSION: This study demonstrates that metformin protects against lipoapoptosis (possibly by blocking JNK2 activation), and enhances GLP-1 secretion from GLP-1-producing cells in vitro.	Metformin	41-50	mitogen-activated protein kinase 9	Mus musculus	104-108
23631252-2	2013	Insulin sensitizers such as metformin and pioglitazone reduce peripheral insulin resistance, whereas dipeptidyl peptidase-4(DPP-4) inhibitors augment postprandial insulin secretion and inhibit glucagon secretion.	Metformin	28-37	insulin	Homo sapiens	0-7
23160726-5	2013	Metformin-imeglimin also significantly improved FPG and the proinsulin/insulin ratio from baseline (-0.91 mg/dL and -7.5, respectively) compared with metformin-placebo (0.36 mg/dL and 11.81).	Metformin	0-9	insulin	Homo sapiens	60-70
23160726-5	2013	Metformin-imeglimin also significantly improved FPG and the proinsulin/insulin ratio from baseline (-0.91 mg/dL and -7.5, respectively) compared with metformin-placebo (0.36 mg/dL and 11.81).	Metformin	0-9	insulin	Homo sapiens	63-70
23631252-2	2013	Insulin sensitizers such as metformin and pioglitazone reduce peripheral insulin resistance, whereas dipeptidyl peptidase-4(DPP-4) inhibitors augment postprandial insulin secretion and inhibit glucagon secretion.	Metformin	28-37	insulin	Homo sapiens	73-80
23228696-8	2013	Finally, expression of constitutive activate MKK6 or HA-p38 MAPK vectors in lung cancer cells was able to abrogate ERCC1 downregulation by metformin and paclitaxel as well as cell viability and DNA repair capacity.	Metformin	139-148	mitogen-activated protein kinase kinase 6	Homo sapiens	45-49
23228696-9	2013	Overall, our results suggest that inhibition of the p38 MAPK signaling by metformin coupled with paclitaxel therapy in human NSCLC cells may be a clinically useful combination, which however will require further validation.	Metformin	74-83	mitogen-activated protein kinase 14	Homo sapiens	52-55
23359066-3	2013	METHODS AND RESULTS: The primary objective of this study was to evaluate the effect on C-reactive protein (CRP) after a 16-week treatment period with either pioglitazone or metformin.	Metformin	173-182	C-reactive protein	Homo sapiens	87-105
23382195-5	2013	Our results show that AMPK activation with treatment of 5-aminoimidazole-4-carboxamide ribonucleotide, metformin, or pulsatile shear stress induces PARP-1 dissociation from the Bcl-6 intron 1, increases Bcl-6 expression, and inhibits expression of inflammatory mediators.	Metformin	103-112	poly(ADP-ribose) polymerase 1	Homo sapiens	148-154
23228696-0	2013	Metformin-mediated downregulation of p38 mitogen-activated protein kinase-dependent excision repair cross-complementing 1 decreases DNA repair capacity and sensitizes human lung cancer cells to paclitaxel.	Metformin	0-9	mitogen-activated protein kinase 14	Homo sapiens	37-40
23228696-7	2013	Furthermore, metformin was able to not only decrease the paclitaxel-induced p38 MAPK-mediated ERCC1 expression, but also augment the cytotoxic effect induced by paclitaxel.	Metformin	13-22	mitogen-activated protein kinase 14	Homo sapiens	76-79
23415113-2	2013	In this setting, metformin, an old and widely accepted first line agent, stands out not only for its antihyperglycemic properties but also for its effects beyond glycemic control such as improvements in endothelial dysfunction, hemostasis and oxidative stress, insulin resistance, lipid profiles, and fat redistribution.	Metformin	17-26	insulin	Homo sapiens	261-268
23359066-3	2013	METHODS AND RESULTS: The primary objective of this study was to evaluate the effect on C-reactive protein (CRP) after a 16-week treatment period with either pioglitazone or metformin.	Metformin	173-182	C-reactive protein	Homo sapiens	107-110
22721394-6	2013	As metformin may act as an anticancer drug through inhibition of mTOR, it might have greater benefice than suggested by insulin lowering alone.	Metformin	3-12	mechanistic target of rapamycin kinase	Homo sapiens	65-69
28609031-6	2013	In addition, the company cited the combination therapy of metformin plus other DPP-4 inhibitors as an alternative comparator therapy, namely for patients who cannot be treated with sulfonylurea or for whom sulfonylurea is unsuitable, but insulin therapy is not yet indicated.	Metformin	58-67	insulin	Homo sapiens	238-245
23169238-7	2013	Metformin, a PRKAA agonist, inhibited HCV replication not only by activating PRKAA as previously reported, but also by activating AKT independently of the autophagy pathway.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	130-133
23192487-2	2013	Interestingly, metformin was previously shown to increase the expression of PGC-1alpha a key controller of energy metabolism in skeletal muscle, which is down-regulated in diabetic conditions.	Metformin	15-24	PPARG coactivator 1 alpha	Homo sapiens	76-86
23292119-8	2013	However, the HER-2 positive rate tended to be lower in the metformin-treated subgroup than in the nonmetformin-treated subgroup (P = 0.002).	Metformin	59-68	erb-b2 receptor tyrosine kinase 2	Homo sapiens	13-18
22714800-8	2013	In particular, 10(-7 )M Ang II reduced phospho-AMPKalpha significantly and continuously at 6, 24, and 48 h. AMPK activators, metformin and 5-aminoimidazole-4-carboxamide-1beta-riboside, restored the suppressed AMPKalpha (Thr172) phosphorylation.	Metformin	125-134	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	24-30
23022130-6	2013	Furthermore, the incretin therapies can be combined with metformin, which is usually continued when basal insulin is introduced in type 2 diabetes.	Metformin	57-66	insulin	Homo sapiens	106-113
23192487-3	2013	We hypothesized that chronic treatment with metformin could protect the aged, diabetic heart against ischemia-reperfusion injury (IRI) by up-regulating PGC-1alpha and improving the impaired functionality of diabetic mitochondria.	Metformin	44-53	PPARG coactivator 1 alpha	Homo sapiens	152-162
23192487-6	2013	In contrast with the diabetic non-treated hearts, the diabetic hearts treated with metformin showed more organized and elongated mitochondria and demonstrated a significant increase in phosphorylated AMPK and in PGC-1alpha expression.	Metformin	83-92	PPARG coactivator 1 alpha	Homo sapiens	212-222
23229592-10	2013	Metformin inhibited the growth of three ESCC cell lines, and this inhibition may have involved reductions in cyclin D1, Cdk4 and Cdk6.	Metformin	0-9	cyclin dependent kinase 6	Homo sapiens	129-133
22946682-8	2013	Metformin reduces the metabolic syndrome, lowers insulin and testosterone levels in postmenopausal women, and it is a potent inhibitor of endometrial cancer cell proliferation.	Metformin	0-9	insulin	Homo sapiens	49-56
22882994-2	2013	The aim of this study was to investigate possible associations of the variants in genes encoding organic cationic transporters-solute carrier family 22, members A1, A2 (SLC22A1, SLC22A2) and solute carrier family 47, member A1 (SLC47A1) with response to metformin in type 2 diabetes.	Metformin	254-263	solute carrier family 22 member 1	Homo sapiens	169-176
21676631-8	2013	Further study revealed metformin induced the activation of AMP-activated protein kinase (AMPK), and inhibited mammalian target of rapamycin (mTOR), which is a central regulator of protein synthesis and cell growth, and negatively regulated by AMPK.	Metformin	23-32	mechanistic target of rapamycin kinase	Homo sapiens	110-139
23395946-6	2013	Furthermore, gene expression arrays revealed that metformin caused expression of stress markers DDIT3, CYP1A1,and GDF-15 and a concomitant reduction in PTGS1 expression.	Metformin	50-59	DNA damage inducible transcript 3	Homo sapiens	96-101
23395946-6	2013	Furthermore, gene expression arrays revealed that metformin caused expression of stress markers DDIT3, CYP1A1,and GDF-15 and a concomitant reduction in PTGS1 expression.	Metformin	50-59	prostaglandin-endoperoxide synthase 1	Homo sapiens	152-157
23287574-12	2013	These responses were paralleled by increased pAMPK availability and by reduced expression of TXNIP messenger RNA in colonic enterocytes exposed to prolonged metformin treatment.	Metformin	157-166	thioredoxin interacting protein	Mus musculus	93-98
23287574-15	2013	Accordingly, the increased bowel glucose metabolism reflects a biologic response to chronic metformin treatment characterized by increased levels of pAMPK and reduced levels of TXNIP.	Metformin	92-101	thioredoxin interacting protein	Mus musculus	177-182
23412023-4	2013	It has been demonstrated that by reducing hyperinsulinemia, in particular with the administration of metformin, insulin-lowering agents might improve endocrine and reproductive abnormalities in PCOS patients.	Metformin	101-110	insulin	Homo sapiens	47-54
21676631-8	2013	Further study revealed metformin induced the activation of AMP-activated protein kinase (AMPK), and inhibited mammalian target of rapamycin (mTOR), which is a central regulator of protein synthesis and cell growth, and negatively regulated by AMPK.	Metformin	23-32	mechanistic target of rapamycin kinase	Homo sapiens	141-145
23303309-3	2013	Also key to better understanding is why and how the anti-diabetic drug metformin (the world"s most prescribed pharmaceutical product) preferentially kills oxidant-deficient mesenchymal p53(- -) cells.	Metformin	71-80	tumor protein p53	Homo sapiens	185-188
23277563-2	2013	In a Src-inducible model of cellular transformation, metformin inhibits the earliest known step in the process, activation of the inflammatory transcription factor NF-kappaB.	Metformin	53-62	SRC proto-oncogene, non-receptor tyrosine kinase	Homo sapiens	5-8
23277563-2	2013	In a Src-inducible model of cellular transformation, metformin inhibits the earliest known step in the process, activation of the inflammatory transcription factor NF-kappaB.	Metformin	53-62	nuclear factor kappa B subunit 1	Homo sapiens	164-173
23277563-5	2013	The antitransformation effect of metformin can be bypassed by overexpression of Lin28B or IL1beta, downstream targets of NF-kappaB.	Metformin	33-42	lin-28 homolog B	Homo sapiens	80-86
23277563-5	2013	The antitransformation effect of metformin can be bypassed by overexpression of Lin28B or IL1beta, downstream targets of NF-kappaB.	Metformin	33-42	interleukin 1 beta	Homo sapiens	90-97
23277563-5	2013	The antitransformation effect of metformin can be bypassed by overexpression of Lin28B or IL1beta, downstream targets of NF-kappaB.	Metformin	33-42	nuclear factor kappa B subunit 1	Homo sapiens	121-130
23277563-6	2013	Metformin preferentially inhibits nuclear translocation of NF-kappaB and phosphorylation of STAT3 in cancer stem cells compared with non-stem cancer cells in the same population.	Metformin	0-9	nuclear factor kappa B subunit 1	Homo sapiens	59-68
23277563-6	2013	Metformin preferentially inhibits nuclear translocation of NF-kappaB and phosphorylation of STAT3 in cancer stem cells compared with non-stem cancer cells in the same population.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	92-97
23714455-5	2013	Further, the use of metformin, a diabetes medication that reduces insulin levels, has been epidemiologically associated with reduced breast cancer risk among patients with diabetes, and a recent observational study found a higher rate of pathologic complete responses among patients with diabetes and breast cancer who were using metformin.	Metformin	20-29	insulin	Homo sapiens	66-73
23103561-8	2013	The increase in angiogenesis by Metformin is abolished by pretreatment with AMPK inhibitor, Compound C. Expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor beta (PDGFbeta) are decreased in IPH-PAEC compared with control PAEC and were not altered by Metformin.	Metformin	288-297	platelet-derived growth factor subunit B	Ovis aries	201-209
23103561-8	2013	The increase in angiogenesis by Metformin is abolished by pretreatment with AMPK inhibitor, Compound C. Expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor beta (PDGFbeta) are decreased in IPH-PAEC compared with control PAEC and were not altered by Metformin.	Metformin	32-41	platelet-derived growth factor subunit B	Ovis aries	201-209
24335168-4	2013	Treatment with metformin was also associated with activation of AMP kinase and inhibition of mTOR/p70S6K/pS6 signaling in both cells.	Metformin	15-24	mechanistic target of rapamycin kinase	Homo sapiens	93-97
23984399-2	2013	Thus, downregulation of SLC22A1, which encodes the organic cation transporter type 1 (OCT1), may affect the response of healthy hepatocytes and liver cancer cells to cationic drugs, such as metformin and sorafenib, respectively.	Metformin	190-199	solute carrier family 22 member 1	Homo sapiens	24-31
23984399-2	2013	Thus, downregulation of SLC22A1, which encodes the organic cation transporter type 1 (OCT1), may affect the response of healthy hepatocytes and liver cancer cells to cationic drugs, such as metformin and sorafenib, respectively.	Metformin	190-199	solute carrier family 22 member 1	Homo sapiens	51-84
23984399-2	2013	Thus, downregulation of SLC22A1, which encodes the organic cation transporter type 1 (OCT1), may affect the response of healthy hepatocytes and liver cancer cells to cationic drugs, such as metformin and sorafenib, respectively.	Metformin	190-199	solute carrier family 22 member 1	Homo sapiens	86-90
24335168-6	2013	In addition, we found USP7, a positive regulator of tumor suppressor p53, as a new molecular target of metformin.	Metformin	103-112	tumor protein p53	Homo sapiens	69-72
24069859-0	2013	Insulin resistance assessment in patients with polycystic ovary syndrome using different diagnostic criteria--impact of metformin treatment.	Metformin	120-129	insulin	Homo sapiens	0-7
24069859-10	2013	Metformin therapy was associated with improvement in insulin sensitivity in HOMA-IR and G120/I120 defined insulin resistant patients.	Metformin	0-9	insulin	Homo sapiens	53-60
24069859-10	2013	Metformin therapy was associated with improvement in insulin sensitivity in HOMA-IR and G120/I120 defined insulin resistant patients.	Metformin	0-9	insulin	Homo sapiens	106-113
24069859-13	2013	Metformin treatment significantly improves insulin sensitivity in insulin resistant patients.	Metformin	0-9	insulin	Homo sapiens	43-50
24069859-13	2013	Metformin treatment significantly improves insulin sensitivity in insulin resistant patients.	Metformin	0-9	insulin	Homo sapiens	66-73
24009856-5	2013	Metformin decreased both MHC class I and class II-restricted presentation of OVA and suppressed the expression of both MHC molecules and co-stimulatory factors such as CD54, CD80, and CD86 in DCs, but did not affect the phagocytic activity toward exogenous OVA.	Metformin	0-9	CD80 antigen	Mus musculus	174-178
24009856-5	2013	Metformin decreased both MHC class I and class II-restricted presentation of OVA and suppressed the expression of both MHC molecules and co-stimulatory factors such as CD54, CD80, and CD86 in DCs, but did not affect the phagocytic activity toward exogenous OVA.	Metformin	0-9	CD86 antigen	Mus musculus	184-188
23255107-0	2013	Metformin selectively affects human glioblastoma tumor-initiating cell viability: A role for metformin-induced inhibition of Akt.	Metformin	93-102	AKT serine/threonine kinase 1	Homo sapiens	125-128
23255107-8	2013	Metformin effects in tumor-initiating cell-enriched cultures were associated with a powerful inhibition of Akt-dependent cell survival pathway, while this pathway was not affected in differentiated cells.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	107-110
23394085-9	2013	Strategies considering the system in its complex are encouraged and, in this context, drugs aimed at reducing circulating insulin levels, such as metformin, should receive attention as potential anti-cancer agents.	Metformin	146-155	insulin	Homo sapiens	122-129
23378779-13	2013	Similarly, a fall in C-reactive protein and adenosine deaminase levels was greater in patients taking metformin with garlic than in patients taking only metformin.	Metformin	102-111	C-reactive protein	Homo sapiens	21-39
23378779-13	2013	Similarly, a fall in C-reactive protein and adenosine deaminase levels was greater in patients taking metformin with garlic than in patients taking only metformin.	Metformin	153-162	C-reactive protein	Homo sapiens	21-39
24018893-1	2013	Aim of the study was to clarify the relationship between metformin-induced vitamin B12 (B12) deficiency, hyperhomocysteinemia and vascular complications in patients with type 2 diabetes.	Metformin	57-66	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	83-86
23873427-0	2013	Changes of plasma fibroblast growth factor-21 (FGF-21) in oral glucose tolerance test and effects of metformin on FGF-21 levels in type 2 diabetes mellitus.	Metformin	101-110	fibroblast growth factor 21	Homo sapiens	114-120
23873427-1	2013	INTRODUCTION: The objectives of our study were to investigate whether fibroblast growth factor-21 (FGF-21) is involved in short-term regulation of glucose and the change of FGF-21 after metformin use in diabetic subjects.	Metformin	186-195	fibroblast growth factor 21	Homo sapiens	173-179
23873427-8	2013	Administration of metformin for nT2DM resulted in a significant decrease in both glucose and FGF-21 at all OGTT times and in insulin at 60 min and 180 min, indicative of a decrease in HOMA-IR.	Metformin	18-27	fibroblast growth factor 21	Homo sapiens	93-99
23873427-10	2013	FGF-21 may participate in the processing of metformin, improving glucose and insulin sensitivity.	Metformin	44-53	fibroblast growth factor 21	Homo sapiens	0-6
23086037-6	2013	Finally, 2 months of therapy with the antidiabetic drug metformin significantly inhibited the maturation of IL-1beta in MDMs from patients with type 2 diabetes through AMP-activated protein kinase (AMPK) activation.	Metformin	56-65	interleukin 1 beta	Homo sapiens	108-116
23086037-7	2013	Taken together, these data suggest that NLRP3 inflammasome activation is elevated in myeloid cells from type 2 diabetic patients and that antidiabetic treatment with metformin contributes to modulation of inflammasome activation in type 2 diabetes.	Metformin	166-175	NLR family pyrin domain containing 3	Homo sapiens	40-45
24018893-1	2013	Aim of the study was to clarify the relationship between metformin-induced vitamin B12 (B12) deficiency, hyperhomocysteinemia and vascular complications in patients with type 2 diabetes.	Metformin	57-66	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	88-91
24018893-3	2013	Firstly, B12 status was analyzed in 62 consecutive metformin-treated patients.	Metformin	51-60	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	9-12
24018893-5	2013	Among the 62 consecutive metformin-treated patients, B12 was deficient (<150 pmol/L) in 8 (13%) and borderline-deficient (150-220 pmol/L) in 18 (29%): the larger the metformin dosage, the lower the B12 (P=0.02, Spearman"s rho=-0.30).	Metformin	25-34	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	53-56
24018893-6	2013	There were independent correlations between metformin use and B12 lowering (P=0.02, r = -0.25), and B12 lowering and elevation of homocysteine (P<0.01, r=-0.34).	Metformin	44-53	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	62-65
24018893-9	2013	Correlation between B12 and homocysteine was stronger in metformin-treated (P<0.01, r=-0.48) than non-metformin-treated (P=0.04, r=-0.38) patients.	Metformin	57-66	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	20-23
24018893-9	2013	Correlation between B12 and homocysteine was stronger in metformin-treated (P<0.01, r=-0.48) than non-metformin-treated (P=0.04, r=-0.38) patients.	Metformin	105-114	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	20-23
24018893-11	2013	Metformin-induced B12 lowering in diabetes was associated with elevation of homocysteine, and hyperhomocysteinemia was independently related to retinopathy.	Metformin	0-9	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	18-21
24018893-12	2013	Metformin-induced B12 deficiency was correctable with B12 supplementation.	Metformin	0-9	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	18-21
23147210-3	2013	In this study we aimed to examine the effectiveness of metformin as a weight reducing drug in obese and overweight patients with regard to their degree of insulin resistance.	Metformin	55-64	insulin	Homo sapiens	155-162
24186599-2	2013	While this paper briefly summarises the current state of knowledge on PCOS, its main aim is to remind the reader about the effectiveness of metformin in women with PCOS in controlling glycaemia, increasing tissue sensitivity to insulin and affecting endothelial function, vascular inflammation, lipid profile and other risk factors of atherosclerosis, which suggests its cardioprotective effects.	Metformin	140-149	insulin	Homo sapiens	228-235
23147210-12	2013	CONCLUSION: Metformin is an effective drug to reduce weight in a naturalistic outpatient setting in insulin sensitive and insulin resistant overweight and obese patients.	Metformin	12-21	insulin	Homo sapiens	100-107
23147210-12	2013	CONCLUSION: Metformin is an effective drug to reduce weight in a naturalistic outpatient setting in insulin sensitive and insulin resistant overweight and obese patients.	Metformin	12-21	insulin	Homo sapiens	122-129
23589723-5	2013	Furthermore, cotreatment of CB-PIC and metformin enhanced the inhibition of HIF1 alpha and Akt/mTOR and the activation of AMPK alpha and pACC in hypoxic SW620 cells.	Metformin	39-48	hypoxia inducible factor 1 subunit alpha	Homo sapiens	76-86
22835064-8	2013	Western blotting analysis demonstrated that metformin induced phosphorylation of AMPK and the inhibitory effect was attenuated with AMPK inhibitor, compound C. In parallel, treatment with metformin decreased phosphorylation of S6 protein.	Metformin	44-53	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	81-85
22835064-8	2013	Western blotting analysis demonstrated that metformin induced phosphorylation of AMPK and the inhibitory effect was attenuated with AMPK inhibitor, compound C. In parallel, treatment with metformin decreased phosphorylation of S6 protein.	Metformin	44-53	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	132-136
22835064-8	2013	Western blotting analysis demonstrated that metformin induced phosphorylation of AMPK and the inhibitory effect was attenuated with AMPK inhibitor, compound C. In parallel, treatment with metformin decreased phosphorylation of S6 protein.	Metformin	188-197	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	81-85
22835064-8	2013	Western blotting analysis demonstrated that metformin induced phosphorylation of AMPK and the inhibitory effect was attenuated with AMPK inhibitor, compound C. In parallel, treatment with metformin decreased phosphorylation of S6 protein.	Metformin	188-197	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	132-136
23589723-5	2013	Furthermore, cotreatment of CB-PIC and metformin enhanced the inhibition of HIF1 alpha and Akt/mTOR and the activation of AMPK alpha and pACC in hypoxic SW620 cells.	Metformin	39-48	AKT serine/threonine kinase 1	Homo sapiens	91-94
23589723-5	2013	Furthermore, cotreatment of CB-PIC and metformin enhanced the inhibition of HIF1 alpha and Akt/mTOR and the activation of AMPK alpha and pACC in hypoxic SW620 cells.	Metformin	39-48	mechanistic target of rapamycin kinase	Homo sapiens	95-99
23296512-7	2013	After the addition of metformin to continuous subcutaneous insulin infusion in the therapy of DM, an improvement in metabolic control was observed.	Metformin	22-31	insulin	Homo sapiens	59-66
23296512-8	2013	Due to the possible mechanism of insulin resistance which is associated with impaired insulin receptors after HSCT procedure, metformin with insulin appears to be effective in the treatment of this type of diabetes.	Metformin	126-135	insulin	Homo sapiens	33-40
23296512-8	2013	Due to the possible mechanism of insulin resistance which is associated with impaired insulin receptors after HSCT procedure, metformin with insulin appears to be effective in the treatment of this type of diabetes.	Metformin	126-135	insulin	Homo sapiens	86-93
24324494-5	2013	SLC22A1, SLC47A1, and ATM gene variants were repeatedly associated with the response to metformin.	Metformin	88-97	solute carrier family 22 member 1	Homo sapiens	0-7
24088749-7	2013	Regarding inflammatory biomarkers, sitagliptin + metformin more effectively reduced the levels of resistin, vaspin and omentin-1 than placebo + metformin.	Metformin	49-58	serpin family A member 12	Homo sapiens	108-114
23899569-7	2013	Concomitantly, fasting insulin resistance improved after metformin therapy.	Metformin	57-66	insulin	Homo sapiens	23-30
23899569-9	2013	CONCLUSIONS: Short-term metformin treatment appears to moderately affect weight reduction in severely obese children and adolescents, with a concomitant improvement in fasting insulin sensitivity.	Metformin	24-33	insulin	Homo sapiens	176-183
24280743-7	2013	One group received metformin (850 mg bid) and the other group received a placebo.	Metformin	19-28	BH3 interacting domain death agonist	Homo sapiens	37-40
25098041-10	2013	RESULTS: After 3 and 6 months of Metformin therapy, significant reduction in biochemical parameters was observed such as fasting glucose, insulin and leptin.	Metformin	33-42	insulin	Homo sapiens	138-145
23899569-3	2013	A systematic review was performed to evaluate the effectiveness of metformin in reducing weight and ameliorating insulin resistance in obese nondiabetic children.	Metformin	67-76	insulin	Homo sapiens	113-120
24288442-0	2013	Metformin inhibits expression and secretion of PEDF in adipocyte and hepatocyte via promoting AMPK phosphorylation.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	94-98
23613388-0	2013	Metformin inhibits proliferation and promotes apoptosis of HER2 positive breast cancer cells by downregulating HSP90.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	59-63
23613388-1	2013	PURPOSE: To investigate the effects and the possible molecular mechanisms of metformin on HER2 positive breast cancer cells.	Metformin	77-86	erb-b2 receptor tyrosine kinase 2	Homo sapiens	90-94
23613388-2	2013	METHODS: SK-BR-3 HER2 positive breast cancer cells were treated with different concentrations of metformin.	Metformin	97-106	erb-b2 receptor tyrosine kinase 2	Homo sapiens	17-21
23613388-9	2013	CONCLUSION: Metformin can inhibit the proliferation and promote apoptosis of HER2 positive breast cancer cells,which is maybe related to inhibition of HSP90.	Metformin	12-21	erb-b2 receptor tyrosine kinase 2	Homo sapiens	77-81
24292754-6	2013	Although one case is insufficient to draw firm conclusions, this report suggests that metformin is a therapeutic choice for SPIDDM when the insulin secretion capacity is maintained.	Metformin	86-95	insulin	Homo sapiens	140-147
24288442-8	2013	Metformin stimulated AMPK phosphorylation in fat and liver of the obese rats, while in vitro, when combined with AMPK inhibitor, the effect of metformin on PEDF was abrogated.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	21-25
24288442-8	2013	Metformin stimulated AMPK phosphorylation in fat and liver of the obese rats, while in vitro, when combined with AMPK inhibitor, the effect of metformin on PEDF was abrogated.	Metformin	143-152	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	113-117
24288442-9	2013	CONCLUSIONS: Metformin inhibits the expression and secretion of PEDF in fat and liver via promoting AMPK phosphorylation, which is closely associated with IR improvement.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	100-104
23744427-6	2013	RESULTS: Beyond improving glucose homeostasis, metformin reduced plasma C-reactive protein levels and lymphocyte release of tumor necrosis factor-alpha and interferon-gamma, as well as tended to reduce interleukin-2 release and plasma intercellular adhesion molecule-1.	Metformin	47-56	interferon gamma	Homo sapiens	156-172
22841520-5	2013	RESULTS: Compared to placebo, metformin reduced monocyte release of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, monocyte chemoattractant protein-1 and interleukin-8, as well as decreased plasma C-reactive protein levels, which were accompanied by an improvement in insulin sensitivity.	Metformin	30-39	tumor necrosis factor	Homo sapiens	68-95
22841520-5	2013	RESULTS: Compared to placebo, metformin reduced monocyte release of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, monocyte chemoattractant protein-1 and interleukin-8, as well as decreased plasma C-reactive protein levels, which were accompanied by an improvement in insulin sensitivity.	Metformin	30-39	interleukin 1 beta	Homo sapiens	97-114
22841520-5	2013	RESULTS: Compared to placebo, metformin reduced monocyte release of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, monocyte chemoattractant protein-1 and interleukin-8, as well as decreased plasma C-reactive protein levels, which were accompanied by an improvement in insulin sensitivity.	Metformin	30-39	interleukin 6	Homo sapiens	116-129
22841520-5	2013	RESULTS: Compared to placebo, metformin reduced monocyte release of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, monocyte chemoattractant protein-1 and interleukin-8, as well as decreased plasma C-reactive protein levels, which were accompanied by an improvement in insulin sensitivity.	Metformin	30-39	C-X-C motif chemokine ligand 8	Homo sapiens	170-183
22841520-5	2013	RESULTS: Compared to placebo, metformin reduced monocyte release of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, monocyte chemoattractant protein-1 and interleukin-8, as well as decreased plasma C-reactive protein levels, which were accompanied by an improvement in insulin sensitivity.	Metformin	30-39	C-reactive protein	Homo sapiens	213-231
23563040-3	2013	RESULTS: Twelve-week treatment with fenofibrate and metformin reduced plasma levels of fibrinogen and PAI-1 and tended to change the other hemostatic markers measured, as well as improved insulin sensitivity.	Metformin	52-61	fibrinogen beta chain	Homo sapiens	87-97
24399727-6	2013	RESULTS: Metformin treatment reduced plasma C-reactive protein levels and monocyte release of tumor necrosis factor-alpha and interleukin-6, as well as tended to reduce monocyte release of interleukin-1beta and monocyte chemoattractant protein-1, which was accompanied by an improvement in insulin sensitivity.	Metformin	9-18	C-reactive protein	Homo sapiens	44-62
24399727-6	2013	RESULTS: Metformin treatment reduced plasma C-reactive protein levels and monocyte release of tumor necrosis factor-alpha and interleukin-6, as well as tended to reduce monocyte release of interleukin-1beta and monocyte chemoattractant protein-1, which was accompanied by an improvement in insulin sensitivity.	Metformin	9-18	interleukin 6	Homo sapiens	126-139
24399727-6	2013	RESULTS: Metformin treatment reduced plasma C-reactive protein levels and monocyte release of tumor necrosis factor-alpha and interleukin-6, as well as tended to reduce monocyte release of interleukin-1beta and monocyte chemoattractant protein-1, which was accompanied by an improvement in insulin sensitivity.	Metformin	9-18	interleukin 1 beta	Homo sapiens	189-206
24399729-1	2013	BACKGROUND: Organic cation transporter 1 (OCT1, SLC22A1) is a membrane transporter that is important for therapeutic effect of the antidiabetic drug metformin.	Metformin	149-158	solute carrier family 22 member 1	Homo sapiens	12-40
24399729-1	2013	BACKGROUND: Organic cation transporter 1 (OCT1, SLC22A1) is a membrane transporter that is important for therapeutic effect of the antidiabetic drug metformin.	Metformin	149-158	solute carrier family 22 member 1	Homo sapiens	42-46
24399729-1	2013	BACKGROUND: Organic cation transporter 1 (OCT1, SLC22A1) is a membrane transporter that is important for therapeutic effect of the antidiabetic drug metformin.	Metformin	149-158	solute carrier family 22 member 1	Homo sapiens	48-55
23457588-6	2013	At the end of the study, two doses of metformin or vehicle were given acutely to mice at the age of 20 weeks, and Insig-1 and GLUT4 mRNA expressions in liver and fat tissue were analysed using qRT-PCR.	Metformin	38-47	insulin induced gene 1	Mus musculus	114-121
23437362-0	2013	Different patterns of Akt and ERK feedback activation in response to rapamycin, active-site mTOR inhibitors and metformin in pancreatic cancer cells.	Metformin	112-121	AKT serine/threonine kinase 1	Homo sapiens	22-25
23457588-6	2013	At the end of the study, two doses of metformin or vehicle were given acutely to mice at the age of 20 weeks, and Insig-1 and GLUT4 mRNA expressions in liver and fat tissue were analysed using qRT-PCR.	Metformin	38-47	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	126-131
23457588-11	2013	Moreover, the expression of GLUT4 mRNA was down-regulated in epididymal fat in male offspring prenatally exposed to metformin.	Metformin	116-125	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	28-33
23457588-12	2013	Based on the microarray and subsequent qRT-PCR analyses, the expression of Insig-1 was changed in the liver of neonatal mice exposed to metformin prenatally.	Metformin	136-145	insulin induced gene 1	Mus musculus	75-82
23457588-13	2013	Furthermore, metformin up-regulated the expression of Insig-1 later in development.	Metformin	13-22	insulin induced gene 1	Mus musculus	54-61
23437362-9	2013	Metformin induced a more pronounced inhibition of proliferation than either KU63794 or rapamycin while, the active-site mTOR inhibitor was more effective than rapamycin.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	120-124
23437362-10	2013	Thus, the effects of metformin on Akt and ERK activation are strikingly different from allosteric or active-site mTOR inhibitors in PDAC cells, though all these agents potently inhibited the mTORC1/S6K axis.	Metformin	21-30	AKT serine/threonine kinase 1	Homo sapiens	34-37
23928867-11	2013	CONCLUSIONS: Addition of metformin to intensive insulin therapy in young obese patients with type 1 diabetes results in a significant reduction of glycated LDL levels.	Metformin	25-34	insulin	Homo sapiens	48-55
23879009-7	2013	It can therefore be concluded that metformin as an inhibitor of mTOR may be a factor that suppresses tumor development.	Metformin	35-44	mechanistic target of rapamycin kinase	Homo sapiens	64-68
23879009-13	2013	Metformin has antiproliferative properties; reduces the VEGF levels, causing a reduction in tumor vasculature; causes an increase in progesterone receptor, which increases the response to hormonal therapy; inhibits the expression of glyoxalase I, mediating resistance to chemotherapy; decreases in the concentration of human telomerase; reduces the activity of Akt and Erk kinases, key regulators of metabolism and progression of tumors and also inhibits the formation of metastases.	Metformin	0-9	vascular endothelial growth factor A	Homo sapiens	56-60
23879009-13	2013	Metformin has antiproliferative properties; reduces the VEGF levels, causing a reduction in tumor vasculature; causes an increase in progesterone receptor, which increases the response to hormonal therapy; inhibits the expression of glyoxalase I, mediating resistance to chemotherapy; decreases in the concentration of human telomerase; reduces the activity of Akt and Erk kinases, key regulators of metabolism and progression of tumors and also inhibits the formation of metastases.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	361-364
23879009-13	2013	Metformin has antiproliferative properties; reduces the VEGF levels, causing a reduction in tumor vasculature; causes an increase in progesterone receptor, which increases the response to hormonal therapy; inhibits the expression of glyoxalase I, mediating resistance to chemotherapy; decreases in the concentration of human telomerase; reduces the activity of Akt and Erk kinases, key regulators of metabolism and progression of tumors and also inhibits the formation of metastases.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	369-372
23797762-4	2013	Here we show that metformin impairs the enzymatic function of HKI and II in Calu-1 cells.	Metformin	18-27	hexokinase 1	Homo sapiens	62-72
24259985-15	2013	CONCLUSION: The results of this observational study show that insulin glargine, when added to a fixed-dose combination of metformin and a DPP-4 inhibitor, resulted in a significant and clinically relevant improvement of glycemic control.	Metformin	122-131	insulin	Homo sapiens	62-69
24448252-5	2013	Drugs that directly reduce insulin resistance (pioglitazone and metformin) are also associated with lesser but still significant decreases in MACE.	Metformin	64-73	insulin	Homo sapiens	27-34
22960565-0	2012	Proteomic analysis of liver mitochondria of apolipoprotein E knockout mice treated with metformin.	Metformin	88-97	apolipoprotein E	Mus musculus	44-60
22960565-5	2012	Thus, we used a proteomic approach to investigate the effect of metformin on liver mitochondria of apolipoprotein E knockout (apoE(-/-)) mice, an animal model of NAFLD.	Metformin	64-73	apolipoprotein E	Mus musculus	99-115
22960565-6	2012	Two-dimensional electrophoresis coupled with mass spectrometry was applied to study the changes in liver mitochondrial protein expression in 6-month old metformin-treated apoE(-/-) mice as compared to non-treated animals.	Metformin	153-162	apolipoprotein E	Mus musculus	171-175
23041647-11	2012	Fibronectin and collagen expression was diminished by metformin through AMPKalpha1 activation in cultured fibroblasts.	Metformin	54-63	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	72-82
23135276-9	2012	Moreover, AMPK knockdown attenuated metformin-induced Cbl/CAP multicomplex formation, which is critical for GLUT4 translocation.	Metformin	36-45	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	108-113
23135276-10	2012	A colorimetric absorbance assay demonstrated that metformin-induced translocation of GLUT4 was suppressed in CAP or Cbl knockdown cells.	Metformin	50-59	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	85-90
23135276-12	2012	In summary, these results demonstrate that metformin modulates GLUT4 translocation by regulating Cbl and CAP signals via AMPK.	Metformin	43-52	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	63-68
23135276-0	2012	Metformin regulates glucose transporter 4 (GLUT4) translocation through AMP-activated protein kinase (AMPK)-mediated Cbl/CAP signaling in 3T3-L1 preadipocyte cells.	Metformin	0-9	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	20-41
23135276-0	2012	Metformin regulates glucose transporter 4 (GLUT4) translocation through AMP-activated protein kinase (AMPK)-mediated Cbl/CAP signaling in 3T3-L1 preadipocyte cells.	Metformin	0-9	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	43-48
23135276-1	2012	Metformin is a leading oral anti-diabetes mellitus medication and is known to stimulate GLUT4 translocation.	Metformin	0-9	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	88-93
23525940-1	2012	The gerosuppressant metformin operates as an efficient inhibitor of the mTOR/S6K1 gerogenic pathway due to its ability to ultimately activate the energy-sensor AMPK.	Metformin	20-29	mechanistic target of rapamycin kinase	Homo sapiens	72-76
20455069-4	2012	Some authors suggest that Metformin has no direct inhibitory effect on DPP-4 activity and that Metformin and the other biguanides enhance GLP-1 secretion; others suggest a possible role of Metformin in the inhibition of the DPP-4 activity.	Metformin	95-104	glucagon	Homo sapiens	138-143
20455069-4	2012	Some authors suggest that Metformin has no direct inhibitory effect on DPP-4 activity and that Metformin and the other biguanides enhance GLP-1 secretion; others suggest a possible role of Metformin in the inhibition of the DPP-4 activity.	Metformin	95-104	glucagon	Homo sapiens	138-143
23141431-0	2012	Metformin enhances the action of insulin on porcine granulosa-lutein cells in vitro.	Metformin	0-9	insulin	Homo sapiens	33-40
23184570-8	2012	As a result, a linagliptin/metformin fixed-dose combination offers the potential to address multiple defects of type 2 diabetes pathophysiology (pancreatic islet dysfunction, insulin resistance, increased hepatic glucose output), and most importantly, in the context of a safe, efficacious, flexible, and convenient therapeutic regimen.	Metformin	27-36	insulin	Homo sapiens	175-182
23107042-5	2012	Metformin, but not placebo, administered to simvastatin-treated IFG subjects reduced plasma levels of C-reactive protein, soluble intercellular adhesion molecule-1, as well as lymphocyte release of interleukin-2, interferon-gamma and tumor necrosis factor-alpha, which was accompanied by the improvement in insulin sensitivity and a reduction in free fatty acid levels.	Metformin	0-9	C-reactive protein	Homo sapiens	102-120
23107042-5	2012	Metformin, but not placebo, administered to simvastatin-treated IFG subjects reduced plasma levels of C-reactive protein, soluble intercellular adhesion molecule-1, as well as lymphocyte release of interleukin-2, interferon-gamma and tumor necrosis factor-alpha, which was accompanied by the improvement in insulin sensitivity and a reduction in free fatty acid levels.	Metformin	0-9	interleukin 2	Homo sapiens	198-211
23107042-5	2012	Metformin, but not placebo, administered to simvastatin-treated IFG subjects reduced plasma levels of C-reactive protein, soluble intercellular adhesion molecule-1, as well as lymphocyte release of interleukin-2, interferon-gamma and tumor necrosis factor-alpha, which was accompanied by the improvement in insulin sensitivity and a reduction in free fatty acid levels.	Metformin	0-9	interferon gamma	Homo sapiens	213-261
23141431-9	2012	In conclusion, we examined the activity of metformin and insulin on pGLS in vitro and metformin enhanced the action of insulin on the intracellular signaling pathways.	Metformin	43-52	insulin	Homo sapiens	119-126
23141431-9	2012	In conclusion, we examined the activity of metformin and insulin on pGLS in vitro and metformin enhanced the action of insulin on the intracellular signaling pathways.	Metformin	86-95	insulin	Homo sapiens	119-126
23141431-2	2012	Metformin increases insulin-stimulated glucose uptake and has direct effects on ovarian steroidogenesis in humans.	Metformin	0-9	insulin	Homo sapiens	20-27
23141431-6	2012	Metformin with insulin significantly increased mRNA expressions of INSR, IGF-1R, and IRS-1, while metformin alone had no significant effect.	Metformin	0-9	insulin	Homo sapiens	15-22
23141431-7	2012	And metformin with insulin had the significant effect on the protein activity (activation and phosphorylation) of downstream targets of INSR signaling pathway.	Metformin	4-13	insulin	Homo sapiens	19-26
23141431-8	2012	Metformin with insulin significantly elicited an induction of luciferase activity in the transfection of AP-1 and NF-kappaBreporter, while metformin alone did not.	Metformin	0-9	insulin	Homo sapiens	15-22
23141431-8	2012	Metformin with insulin significantly elicited an induction of luciferase activity in the transfection of AP-1 and NF-kappaBreporter, while metformin alone did not.	Metformin	0-9	JunB proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	105-109
23141431-8	2012	Metformin with insulin significantly elicited an induction of luciferase activity in the transfection of AP-1 and NF-kappaBreporter, while metformin alone did not.	Metformin	139-148	JunB proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	105-109
22968630-3	2012	Our data showed that the metformin pretreatment strikingly enhanced insulin-stimulated glucose uptake through increasing GLUT4 translocation to the PM in NYGGF4 overexpression adipocytes.	Metformin	25-34	insulin	Homo sapiens	68-75
22563947-3	2012	Metformin has beneficial effects on insulin resistance and endothelial functions.	Metformin	0-9	insulin	Homo sapiens	36-43
23068960-7	2012	The neonates of metformin group had less rate of birth weight centile >90 than insulin group (RR: 0.5, 95% CI: 0.3-0.9, P=0.012).	Metformin	16-25	insulin	Homo sapiens	82-89
22540883-5	2012	RESULTS: Exenatide + metformin gave a greater decrease in body weight, glycaemic control, fasting plasma proinsulin and insulin and their ratio, homeostasis model assessment for insulin resistance (HOMA-IR), and glucagon values and a greater increase in C-peptide levels, homeostasis model assessment beta-cell function index (HOMA-beta) and adiponectin compared with placebo + metformin.	Metformin	21-30	insulin	Homo sapiens	105-115
22540883-5	2012	RESULTS: Exenatide + metformin gave a greater decrease in body weight, glycaemic control, fasting plasma proinsulin and insulin and their ratio, homeostasis model assessment for insulin resistance (HOMA-IR), and glucagon values and a greater increase in C-peptide levels, homeostasis model assessment beta-cell function index (HOMA-beta) and adiponectin compared with placebo + metformin.	Metformin	21-30	insulin	Homo sapiens	108-115
22540883-5	2012	RESULTS: Exenatide + metformin gave a greater decrease in body weight, glycaemic control, fasting plasma proinsulin and insulin and their ratio, homeostasis model assessment for insulin resistance (HOMA-IR), and glucagon values and a greater increase in C-peptide levels, homeostasis model assessment beta-cell function index (HOMA-beta) and adiponectin compared with placebo + metformin.	Metformin	21-30	insulin	Homo sapiens	120-127
22540883-5	2012	RESULTS: Exenatide + metformin gave a greater decrease in body weight, glycaemic control, fasting plasma proinsulin and insulin and their ratio, homeostasis model assessment for insulin resistance (HOMA-IR), and glucagon values and a greater increase in C-peptide levels, homeostasis model assessment beta-cell function index (HOMA-beta) and adiponectin compared with placebo + metformin.	Metformin	21-30	insulin	Homo sapiens	254-263
22540883-5	2012	RESULTS: Exenatide + metformin gave a greater decrease in body weight, glycaemic control, fasting plasma proinsulin and insulin and their ratio, homeostasis model assessment for insulin resistance (HOMA-IR), and glucagon values and a greater increase in C-peptide levels, homeostasis model assessment beta-cell function index (HOMA-beta) and adiponectin compared with placebo + metformin.	Metformin	21-30	adiponectin, C1Q and collagen domain containing	Homo sapiens	342-353
22540883-7	2012	Exenatide + metformin gave a greater increase in M value (+34%), and disposition index (+55%) compared with placebo + metformin; first (+21%) and second phase (+34%) C-peptide response to glucose and C-peptide response to arginine (+25%) were also improved by exenatide + metformin treatment, but not by placebo + metformin.	Metformin	12-21	insulin	Homo sapiens	166-175
22540883-7	2012	Exenatide + metformin gave a greater increase in M value (+34%), and disposition index (+55%) compared with placebo + metformin; first (+21%) and second phase (+34%) C-peptide response to glucose and C-peptide response to arginine (+25%) were also improved by exenatide + metformin treatment, but not by placebo + metformin.	Metformin	12-21	insulin	Homo sapiens	200-209
23122726-0	2012	Short-term treatment with metformin suppresses toll like receptors (TLRs) activity in isoproterenol-induced myocardial infarction in rat: are AMPK and TLRs connected?	Metformin	26-35	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	142-146
23122726-2	2012	The activation of AMPK by metformin prevents cardiac remodeling after myocardial infarction (MI).	Metformin	26-35	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	18-22
23122726-8	2012	Further, metformin reduced TLR-dependent inflammatory cytokines as indexed by reduced myocardial levels of TNFalpha (maximum 68%; P<0.001) and IL6 (maximum 84%; P<0.001) as well as by reduced myocardial MPO activity (25%; P<0.01).	Metformin	9-18	tumor necrosis factor	Rattus norvegicus	107-115
23122726-8	2012	Further, metformin reduced TLR-dependent inflammatory cytokines as indexed by reduced myocardial levels of TNFalpha (maximum 68%; P<0.001) and IL6 (maximum 84%; P<0.001) as well as by reduced myocardial MPO activity (25%; P<0.01).	Metformin	9-18	interleukin 6	Rattus norvegicus	146-149
23122726-9	2012	It was found that the level of phosphorylated AMPK was significantly upregulated by 165% (P<0.001) when treated with 100 mg/kg of metformin, but not with 25 and 50mg/kg.	Metformin	133-142	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	46-50
23122726-11	2012	These results suggest that AMPK activation by metformin and the subsequent suppression of TLRs activity could be considered as a target in protecting the infarcted heart, which may indicate a link between AMPK and TLRs.	Metformin	46-55	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	27-31
23122726-11	2012	These results suggest that AMPK activation by metformin and the subsequent suppression of TLRs activity could be considered as a target in protecting the infarcted heart, which may indicate a link between AMPK and TLRs.	Metformin	46-55	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	205-209
22968630-6	2012	Our data also showed that metformin increased the expressions of PGC1-alpha, NRF-1, and TFAM, which were reduced in the NYGGF4 overexpression adipocytes.	Metformin	26-35	PPARG coactivator 1 alpha	Homo sapiens	65-75
22968630-6	2012	Our data also showed that metformin increased the expressions of PGC1-alpha, NRF-1, and TFAM, which were reduced in the NYGGF4 overexpression adipocytes.	Metformin	26-35	transcription factor A, mitochondrial	Homo sapiens	88-92
22968630-7	2012	These results suggest that NYGGF4 plays a role in IR and its effects on IR could be reversed by metformin through activating IRS-1/PI3K/Akt and AMPK-PGC1-alpha pathways.	Metformin	96-105	AKT serine/threonine kinase 1	Homo sapiens	136-139
22968630-7	2012	These results suggest that NYGGF4 plays a role in IR and its effects on IR could be reversed by metformin through activating IRS-1/PI3K/Akt and AMPK-PGC1-alpha pathways.	Metformin	96-105	PPARG coactivator 1 alpha	Homo sapiens	149-159
22968630-4	2012	NYGGF4 overexpression resulted in significant inhibition of tyrosine phosphorylation of IRS-1 and serine phosphorylation of Akt, whereas incubation with metformin strongly activated IRS-1 and Akt phosphorylation in NYGGF4 overexpression adipocytes.	Metformin	153-162	AKT serine/threonine kinase 1	Homo sapiens	192-195
23185203-3	2012	If metformin use during pregnancy and the lactation period is supported by few data, it could be indicated for women with polycystic ovary syndrome, since it could diminish circulating androgens and insulin resistance, thus ameliorating the ovulation rate.	Metformin	3-12	insulin	Homo sapiens	199-206
23173578-9	2012	Various drugs have been reported to induce FGF21, including peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists such as fenofibrate, the histone deacetylase inhibitor sodium butyrate, and adenosine monophosphate (AMP) kinase activators metformin and 5-amino-1-beta-D-ribofuranosyl-imidazole-4-carboxamide (AICAR).	Metformin	254-263	fibroblast growth factor 21	Homo sapiens	43-48
23257425-7	2012	MEK/ERK signaling pathway may be one of the molecular mechanisms of metformin on NB4 cells.	Metformin	68-77	mitogen-activated protein kinase kinase 7	Homo sapiens	0-3
23257425-7	2012	MEK/ERK signaling pathway may be one of the molecular mechanisms of metformin on NB4 cells.	Metformin	68-77	mitogen-activated protein kinase 1	Homo sapiens	4-7
23285665-4	2012	It was found that ACE inhibitors (apo-perindox, prinvil, gopten) caused a significant decrease in the activity of pepsin, while indapen (a diuretic) and glucophage (an antidiabetic drug) increased the activity of this enzyme.	Metformin	153-163	angiotensin I converting enzyme	Homo sapiens	18-21
23151022-10	2012	Metformin induced an apparent cell cycle arrest at the G0/G1 phase, which was accompanied by an obvious activation of the AMP kinase pathway and a strongly decreased activation of mammalian target of rapamycin and S6 kinase.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	180-209
23151022-11	2012	Metformin treatment led to a remarkable decrease of cyclin D1, cyclin-dependent kinase (CDK) 4 and CDK6 protein levels and phosphorylation of retinoblastoma protein, but did not affect p21 or p27 protein expression in OSCC cells.	Metformin	0-9	cyclin dependent kinase 6	Homo sapiens	99-103
23151022-11	2012	Metformin treatment led to a remarkable decrease of cyclin D1, cyclin-dependent kinase (CDK) 4 and CDK6 protein levels and phosphorylation of retinoblastoma protein, but did not affect p21 or p27 protein expression in OSCC cells.	Metformin	0-9	dynactin subunit 6	Homo sapiens	192-195
23151022-12	2012	In addition, metformin induced apoptosis in OSCC cells, significantly down-regulating the anti-apoptotic proteins Bcl-2 and Bcl-xL and up-regulating the pro-apoptotic protein Bax.	Metformin	13-22	BCL2 apoptosis regulator	Homo sapiens	114-119
23151022-12	2012	In addition, metformin induced apoptosis in OSCC cells, significantly down-regulating the anti-apoptotic proteins Bcl-2 and Bcl-xL and up-regulating the pro-apoptotic protein Bax.	Metformin	13-22	BCL2 like 1	Homo sapiens	124-130
23151022-12	2012	In addition, metformin induced apoptosis in OSCC cells, significantly down-regulating the anti-apoptotic proteins Bcl-2 and Bcl-xL and up-regulating the pro-apoptotic protein Bax.	Metformin	13-22	BCL2 associated X, apoptosis regulator	Homo sapiens	175-178
23076984-13	2012	The likelihood of initiating insulin was higher in subjects initiated with sulfonylurea than with metformin (adjusted odds ratio 1.82, 95% confidence interval [CI] 1.40-2.38; P < 0.001).	Metformin	98-107	insulin	Homo sapiens	29-36
22968146-6	2012	The effect of metformin on liver and muscle metabolism was similar leading to AMPK activation either by liver kinase B1 (LKB1) and/or other kinases in the muscle.	Metformin	14-23	serine/threonine kinase 11	Mus musculus	104-119
22968146-6	2012	The effect of metformin on liver and muscle metabolism was similar leading to AMPK activation either by liver kinase B1 (LKB1) and/or other kinases in the muscle.	Metformin	14-23	serine/threonine kinase 11	Mus musculus	121-125
23054099-0	2012	Effects of metformin on insulin resistance in heart failure.	Metformin	11-20	insulin	Gallus gallus	24-31
22811314-1	2012	BACKGROUND: Metformin is a drug used in the treatment of diabetes and of some disorders related to insulin resistance, such as polycystic ovary syndrome.	Metformin	12-21	insulin	Homo sapiens	99-106
23078974-2	2012	Currently available oral antidiabetic drugs (OADs) attempt to correct the underlying pathophysiological dysfunctions leading to T2DM: insulin resistance for the insulin sensitizers (metformin and thiazolidinediones), and impaired insulin secretion for the insulin secretagogues (sulfonylureas, glinides and more recently incretin mimetics).	Metformin	182-191	insulin	Homo sapiens	134-141
22740509-0	2012	The effect of metformin on insulin resistance and exercise parameters in patients with heart failure.	Metformin	14-23	insulin	Homo sapiens	27-34
23653852-10	2012	Metformin at concentrations of 0.5-3 mM significantly (P<0.001) inhibited VEGF mRNA expression and endothelial cell migration.	Metformin	0-9	vascular endothelial growth factor A	Homo sapiens	77-81
23197693-0	2012	Glioma-initiating cell elimination by metformin activation of FOXO3 via AMPK.	Metformin	38-47	forkhead box O3	Homo sapiens	62-67
23677182-0	2012	[Effect of metformin on the expression of tumor necrosis factor-alpha, Toll like receptors 2/4 and C reactive protein in obese type-2 diabetic patients].	Metformin	11-20	tumor necrosis factor	Homo sapiens	42-69
23677182-0	2012	[Effect of metformin on the expression of tumor necrosis factor-alpha, Toll like receptors 2/4 and C reactive protein in obese type-2 diabetic patients].	Metformin	11-20	toll like receptor 2	Homo sapiens	71-94
23677182-0	2012	[Effect of metformin on the expression of tumor necrosis factor-alpha, Toll like receptors 2/4 and C reactive protein in obese type-2 diabetic patients].	Metformin	11-20	C-reactive protein	Homo sapiens	99-117
23677182-9	2012	Participants receiving metformin had lower levels of hsCRP and lower mRNA relative abundance of TNF-alpha and TLR 2/4.	Metformin	23-32	tumor necrosis factor	Homo sapiens	96-105
23677182-9	2012	Participants receiving metformin had lower levels of hsCRP and lower mRNA relative abundance of TNF-alpha and TLR 2/4.	Metformin	23-32	toll like receptor 2	Homo sapiens	110-117
23677182-11	2012	CONCLUSIONS: Obese diabetic patients treated with metformin had lower levels of hsCRP expression of TNF-alpha and TLR 2/4, than their counterparts not receiving the drug.	Metformin	50-59	tumor necrosis factor	Homo sapiens	100-109
23677182-11	2012	CONCLUSIONS: Obese diabetic patients treated with metformin had lower levels of hsCRP expression of TNF-alpha and TLR 2/4, than their counterparts not receiving the drug.	Metformin	50-59	toll like receptor 2	Homo sapiens	114-121
23162655-7	2012	The action of metformin was mediated through the upregulation of its main signaling molecule, the adenosine monophosphate-activated protein kinase (AMPK), as well as through the downregulation of the signal transducer and activator of transcription 3 (STAT3) and the Akt/PKB serine/threonine protein kinase.	Metformin	14-23	signal transducer and activator of transcription 3	Homo sapiens	200-250
23162655-7	2012	The action of metformin was mediated through the upregulation of its main signaling molecule, the adenosine monophosphate-activated protein kinase (AMPK), as well as through the downregulation of the signal transducer and activator of transcription 3 (STAT3) and the Akt/PKB serine/threonine protein kinase.	Metformin	14-23	signal transducer and activator of transcription 3	Homo sapiens	252-257
23162655-7	2012	The action of metformin was mediated through the upregulation of its main signaling molecule, the adenosine monophosphate-activated protein kinase (AMPK), as well as through the downregulation of the signal transducer and activator of transcription 3 (STAT3) and the Akt/PKB serine/threonine protein kinase.	Metformin	14-23	AKT serine/threonine kinase 1	Homo sapiens	267-306
23197693-5	2012	Furthermore, metformin promoted FOXO3 activation and differentiation via AMP-activated protein kinase (AMPK) activation, which was sensitive to extracellular glucose availability.	Metformin	13-22	forkhead box O3	Homo sapiens	32-37
23197693-3	2012	Here we identified metformin, an antidiabetic agent, as a therapeutic activator of FOXO3.	Metformin	19-28	forkhead box O3	Homo sapiens	83-88
22933030-1	2012	Metformin may exert anti-cancer effects through indirect (insulin-mediated) or direct (insulin-independent) mechanisms.	Metformin	0-9	insulin	Homo sapiens	58-65
22342903-2	2012	Adiponectin expression levels and multimerization are down-regulated in obesity and up-regulated by insulin sensitizers such as thiazolidinediones (TZDs), metformin, sulfonylurea and resveratrol (RSV).	Metformin	155-164	adiponectin, C1Q and collagen domain containing	Homo sapiens	0-11
22933030-1	2012	Metformin may exert anti-cancer effects through indirect (insulin-mediated) or direct (insulin-independent) mechanisms.	Metformin	0-9	insulin	Homo sapiens	87-94
22698918-0	2012	Metformin inhibits growth hormone-mediated hepatic PDK4 gene expression through induction of orphan nuclear receptor small heterodimer partner.	Metformin	0-9	pyruvate dehydrogenase kinase, isoenzyme 4	Mus musculus	51-55
22682949-1	2012	AIMS: To evaluate the impact on glycemic control, insulin resistance, and insulin secretion of sitagliptin+metformin compared to metformin in type 2 diabetic patients.	Metformin	107-116	insulin	Homo sapiens	74-81
22682949-6	2012	Sitagliptin+metformin, but not placebo+metformin, decreased FPPr, FPPR/FPI ratio, and increased C-peptide values, even if no differences between the groups were recorded.	Metformin	12-21	insulin	Homo sapiens	96-105
22682949-7	2012	Sitaglitin+metformin gave also a greater increase of HOMA-beta, M value, C-peptide response to arginine and disposition index compared to placebo+metformin group.	Metformin	11-20	insulin	Homo sapiens	73-82
22658895-9	2012	Secondary analysis revealed that molar insulin-to-C-peptide ratio (I/C) > 0.175 (a surrogate measure of exogenous insulin usage) was associated with decreased overall survival, complete remission duration and progression-free survival (PFS), whereas metformin and/or thiazolidinedione usage were associated with increased PFS.	Metformin	253-262	insulin	Homo sapiens	39-46
22658895-9	2012	Secondary analysis revealed that molar insulin-to-C-peptide ratio (I/C) > 0.175 (a surrogate measure of exogenous insulin usage) was associated with decreased overall survival, complete remission duration and progression-free survival (PFS), whereas metformin and/or thiazolidinedione usage were associated with increased PFS.	Metformin	253-262	insulin	Homo sapiens	117-124
22698918-8	2012	In primary hepatocytes, dominant-negative mutant-AMPK and SHP knockdown prevented the inhibitory effect of metformin on GH-stimulated PDK4 expression.	Metformin	107-116	pyruvate dehydrogenase kinase, isoenzyme 4	Mus musculus	134-138
22698918-2	2012	Because inhibition of the pyruvate dehydrogenase complex (PDC) by pyruvate dehydrogenase kinase 4 (PDK4) conserves substrates for gluconeogenesis, we tested whether GH increases PDK4 expression in liver by a signaling pathway sensitive to inhibition by metformin.	Metformin	253-262	pyruvate dehydrogenase kinase, isoenzyme 4	Mus musculus	99-103
22698918-10	2012	Metformin inhibits GH-induced PDK4 expression and metabolites via an AMPK-SHP-dependent pathway.	Metformin	0-9	pyruvate dehydrogenase kinase, isoenzyme 4	Mus musculus	30-34
22698918-5	2012	Metformin inhibited the induction of PDK4 expression by GH via a pathway dependent on AMP-activated protein kinase (AMPK) and SHP induction.	Metformin	0-9	pyruvate dehydrogenase kinase, isoenzyme 4	Mus musculus	37-41
22698918-7	2012	Metformin decreased GH-mediated induction of PDK4 expression and metabolites in wild-type but not in SHP-null mice.	Metformin	0-9	pyruvate dehydrogenase kinase, isoenzyme 4	Mus musculus	45-49
22475072-1	2012	BACKGROUND: Metformin (an insulin sensitizer) and spironolactone (an antiandrogen) are both used for treatment of polycystic ovary syndrome.	Metformin	12-21	insulin	Homo sapiens	26-33
22735790-7	2012	Analyzing the expression status and the integrity of LKB1-AMPK-mTOR signaling, we found that cervical cancer cells sensitive to metformin were LKB1 intact and exerted an integral AMPK-mTOR signaling response after the treatment.	Metformin	128-137	mechanistic target of rapamycin kinase	Homo sapiens	63-67
22735790-7	2012	Analyzing the expression status and the integrity of LKB1-AMPK-mTOR signaling, we found that cervical cancer cells sensitive to metformin were LKB1 intact and exerted an integral AMPK-mTOR signaling response after the treatment.	Metformin	128-137	mechanistic target of rapamycin kinase	Homo sapiens	184-188
22467055-6	2012	IEC6 rat intestinal epithelial cells treated with AGE showed increased RAGE expression, which was inhibited by treatment with metformin or losartan.	Metformin	126-135	advanced glycosylation end product-specific receptor	Rattus norvegicus	71-75
22467055-7	2012	In the AOM-injected rat colon cancer model, the levels of RAGE and AGE, and the multiplicity of ACF and carcinomas, in Group L + G rats were suppressed by treatment with metformin or losartan.	Metformin	170-179	advanced glycosylation end product-specific receptor	Rattus norvegicus	58-62
24082557-1	2012	OBJECTIVES: To evaluate the effect of metformin and pioglitazone on insulin resistance, ovulation and hyperandrogenism in women with PCOS.	Metformin	38-47	insulin	Homo sapiens	68-75
22786777-4	2012	WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Since the insulin-sensitizing agents came into use in the management of PCOS, metformin has shown a positive benefits-risks ratio.	Metformin	118-127	insulin	Homo sapiens	50-57
22786777-19	2012	GENERALIZABILITY TO OTHER POPULATIONS: The paradigm of using the minimum effective dose of metformin could be pursued in other pathological conditions characterized by insulin resistance.	Metformin	91-100	insulin	Homo sapiens	168-175
22475072-7	2012	There was a significant reduction in the 1 and 2 h glucose and insulin levels with metformin therapy in those with AGT.	Metformin	83-92	insulin	Homo sapiens	63-70
22582808-5	2012	In contrast, Sfrp5 mRNA expression in mature adipose was increased by 34 and 19% upon treatment with rosiglitazone and metformin respectively, whereas Sfrp5 protein secretion was increased by 10 and 6%, correspondingly.	Metformin	119-128	secreted frizzled related protein 5	Homo sapiens	13-18
22926251-4	2012	Ongoing translational research should be useful in guiding design of clinical trials, not only to evaluate metformin at conventional antidiabetic doses, where reduction of elevated insulin levels may contribute to antineoplastic activity for certain subsets of patients, but also to explore more aggressive dosing of biguanides, which may lead to reprogramming of energy metabolism in a manner that could provide important opportunities for synthetic lethality through rational drug combinations or in the context of genetic lesions associated with hypersensitivity to energetic stress.	Metformin	107-116	insulin	Homo sapiens	181-188
22770998-0	2012	Recommendations for diagnosis and management of metformin-induced vitamin B12 (Cbl) deficiency.	Metformin	48-57	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	74-77
22770998-1	2012	Metformin treatment is a known pharmacological cause of vitamin B12 (Cbl) deficiency with controversial responsible mechanisms.	Metformin	0-9	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	64-67
22778212-0	2012	Metformin inhibits human androgen production by regulating steroidogenic enzymes HSD3B2 and CYP17A1 and complex I activity of the respiratory chain.	Metformin	0-9	hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2	Homo sapiens	81-87
22778212-6	2012	Similar to in vivo situation, metformin inhibited androgen production in NCI cells by decreasing HSD3B2 expression and CYP17A1 and HSD3B2 activities.	Metformin	30-39	hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2	Homo sapiens	97-103
22778212-6	2012	Similar to in vivo situation, metformin inhibited androgen production in NCI cells by decreasing HSD3B2 expression and CYP17A1 and HSD3B2 activities.	Metformin	30-39	hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2	Homo sapiens	131-137
22778212-11	2012	In conclusion, metformin inhibits androgen production by mechanisms targeting HSD3B2 and CYP17-lyase.	Metformin	15-24	hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2	Homo sapiens	78-84
22898050-11	2012	Metformin suppressed COX-2 and iNOS mRNA and protein expression dose dependently.	Metformin	0-9	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	21-26
22898050-11	2012	Metformin suppressed COX-2 and iNOS mRNA and protein expression dose dependently.	Metformin	0-9	nitric oxide synthase 2	Homo sapiens	31-35
22582808-8	2012	Up-regulation of Sfrp5 expression and secretion in adipocytes may be one crucial mechanism by which rosiglitazone and metformin improve insulin sensitivity.	Metformin	118-127	secreted frizzled related protein 5	Homo sapiens	17-22
22582808-8	2012	Up-regulation of Sfrp5 expression and secretion in adipocytes may be one crucial mechanism by which rosiglitazone and metformin improve insulin sensitivity.	Metformin	118-127	insulin	Homo sapiens	136-143
25246913-12	2012	Metformin caused a significant decrease in weight (p=0.027), insulin level (p=0.043), and insulin resistance (p=0.048).	Metformin	0-9	insulin	Homo sapiens	61-68
25246913-12	2012	Metformin caused a significant decrease in weight (p=0.027), insulin level (p=0.043), and insulin resistance (p=0.048).	Metformin	0-9	insulin	Homo sapiens	90-97
22735389-0	2012	Association of genetic variation in the organic cation transporters OCT1, OCT2 and multidrug and toxin extrusion 1 transporter protein genes with the gastrointestinal side effects and lower BMI in metformin-treated type 2 diabetes patients.	Metformin	197-206	solute carrier family 22 member 1	Homo sapiens	68-72
22524458-8	2012	Metformin caused cell cycle arrest in HCC cells, which resulted in caspase-3 activation.	Metformin	0-9	caspase 3	Homo sapiens	67-76
22540890-0	2012	Metformin, an antidiabetic agent reduces growth of cutaneous squamous cell carcinoma by targeting mTOR signaling pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	98-102
22540890-5	2012	The mechanism by which metformin manifests antitumor effects appears to be dependent on the inhibition of nuclear factor kappa B (NFkB) and mTOR signaling pathways.	Metformin	23-32	mechanistic target of rapamycin kinase	Homo sapiens	140-144
22540890-10	2012	These results suggest that metformin blocks SCC growth by dampening NFkB and mTOR signaling pathways.	Metformin	27-36	mechanistic target of rapamycin kinase	Homo sapiens	77-81
22735389-2	2012	So far, the number of polymorphisms in SLC22A1, SLC22A2, and SLC47A1 genes coding for organic cation transporter 1 (OCT1), OCT2, and multidrug and toxin extrusion transporter 1 (MATE1) metformin transporters have been described in association with the efficacy of metformin.	Metformin	185-194	solute carrier family 22 member 1	Homo sapiens	39-46
22735389-2	2012	So far, the number of polymorphisms in SLC22A1, SLC22A2, and SLC47A1 genes coding for organic cation transporter 1 (OCT1), OCT2, and multidrug and toxin extrusion transporter 1 (MATE1) metformin transporters have been described in association with the efficacy of metformin.	Metformin	185-194	solute carrier family 22 member 1	Homo sapiens	86-114
22735389-2	2012	So far, the number of polymorphisms in SLC22A1, SLC22A2, and SLC47A1 genes coding for organic cation transporter 1 (OCT1), OCT2, and multidrug and toxin extrusion transporter 1 (MATE1) metformin transporters have been described in association with the efficacy of metformin.	Metformin	185-194	solute carrier family 22 member 1	Homo sapiens	116-120
22735389-7	2012	CONCLUSION: Two genetic variations in OCT1 that are in strong linkage disequilibrium may predispose toward an increased prevalence of the side effects of metformin in patients with T2D.	Metformin	154-163	solute carrier family 22 member 1	Homo sapiens	38-42
22486277-5	2012	RESULTS: The area under the curve (AUC(0-6 h) ) for active glucagon-like peptide 1 was significantly higher on metformin (pre-metformin 1750.8 +- 640 pmol l(-1) min(-1) vs. post-metformin 2718.8 +- 1182.3 pmol l(-1) min(-1) ; P=0.01).	Metformin	111-120	glucagon	Homo sapiens	59-82
22809961-5	2012	Under glucose withdrawal stress, metformin supplementation circumvented the ability of oncogenes (e.g., HER2) to protect breast cancer cells from glucose-deprivation apoptosis.	Metformin	33-42	erb-b2 receptor tyrosine kinase 2	Homo sapiens	104-108
23087748-11	2012	Changes in AST and ALT in silymarin group were demonstrated more than that in other groups and the average difference between changes was significant between silymarin and metformin groups.	Metformin	172-181	solute carrier family 17 member 5	Homo sapiens	11-14
22424822-1	2012	The objective was to determine the effect of metformin on the concentrations of resistin and other markers of insulin resistance or inflammation (C-reactive protein, cytokines, body weight, HbA1c, among others) in minors with glucose intolerance.	Metformin	45-54	insulin	Homo sapiens	110-117
22711171-9	2012	Among patients treated with metformin, BMI decreased by a mean of 0.93 and the insulin resistance index by 2.04.	Metformin	28-37	insulin	Homo sapiens	79-86
22711171-12	2012	CONCLUSIONS: Metformin was effective in reversing antipsychotic-induced adverse events, including restoration of menstruation, promotion of weight loss, and improvement in insulin resistance in female patients with schizophrenia.	Metformin	13-22	insulin	Homo sapiens	172-179
22561086-0	2012	A potential mechanism of metformin-mediated regulation of glucose homeostasis: inhibition of Thioredoxin-interacting protein (Txnip) gene expression.	Metformin	25-34	thioredoxin interacting protein	Homo sapiens	93-124
22561086-0	2012	A potential mechanism of metformin-mediated regulation of glucose homeostasis: inhibition of Thioredoxin-interacting protein (Txnip) gene expression.	Metformin	25-34	thioredoxin interacting protein	Homo sapiens	126-131
22561086-5	2012	In the present study, we report that Txnip mRNA as well as protein expression in cultured cells is markedly reduced upon metformin administration.	Metformin	121-130	thioredoxin interacting protein	Homo sapiens	37-42
22561086-6	2012	The binding of Mondo:MLX to the Txnip gene promoter is reduced, suggesting that the transcription of the Txnip gene is repressed by metformin.	Metformin	132-141	thioredoxin interacting protein	Homo sapiens	32-37
22561086-6	2012	The binding of Mondo:MLX to the Txnip gene promoter is reduced, suggesting that the transcription of the Txnip gene is repressed by metformin.	Metformin	132-141	thioredoxin interacting protein	Homo sapiens	105-110
22561086-7	2012	Moreover, we show that the effect of metformin on Txnip gene transcription is due to the inhibition of mitochondrial complex I and increased glycolysis, and is partially mediated by the AMP activated kinase (AMPK).	Metformin	37-46	thioredoxin interacting protein	Homo sapiens	50-55
22561086-8	2012	These observations prompt us to propose that the novel action of metformin on the Txnip gene expression may contribute to its therapeutic effects in the treatment of type II diabetes.	Metformin	65-74	thioredoxin interacting protein	Homo sapiens	82-87
22329512-7	2012	Pancreatic superoxide dismutase, catalase and glutathione peroxidase were significantly increased in Gl-PS and metformin groups.	Metformin	111-120	catalase	Rattus norvegicus	33-41
22329512-9	2012	The mRNA expressions of Bcl-2 and PDX-1 in pancreas were up-regulated, but Bax, iNOS and Casp-3 down-regulated in Gl- PS and metformin groups compared to diabetic control group.	Metformin	125-134	BCL2, apoptosis regulator	Rattus norvegicus	24-29
22329512-9	2012	The mRNA expressions of Bcl-2 and PDX-1 in pancreas were up-regulated, but Bax, iNOS and Casp-3 down-regulated in Gl- PS and metformin groups compared to diabetic control group.	Metformin	125-134	nitric oxide synthase 2	Rattus norvegicus	80-84
22688336-10	2012	TNFRI combined with the antidiabetic agent, metformin, improved DBD beyond that achieved with metformin alone, suggesting that therapies targeting TNF-alpha may have utility in reversing the secondary urologic complications of type 2 diabetes.	Metformin	44-53	tumor necrosis factor	Homo sapiens	147-156
22486277-5	2012	RESULTS: The area under the curve (AUC(0-6 h) ) for active glucagon-like peptide 1 was significantly higher on metformin (pre-metformin 1750.8 +- 640 pmol l(-1) min(-1) vs. post-metformin 2718.8 +- 1182.3 pmol l(-1) min(-1) ; P=0.01).	Metformin	126-135	glucagon	Homo sapiens	59-82
22486277-5	2012	RESULTS: The area under the curve (AUC(0-6 h) ) for active glucagon-like peptide 1 was significantly higher on metformin (pre-metformin 1750.8 +- 640 pmol l(-1) min(-1) vs. post-metformin 2718.8 +- 1182.3 pmol l(-1) min(-1) ; P=0.01).	Metformin	126-135	glucagon	Homo sapiens	59-82
22486277-7	2012	CONCLUSION: Three months or more of metformin monotherapy in obese patients with Type 2 diabetes was associated with increased postprandial active glucagon-like peptide 1 levels.	Metformin	36-45	glucagon	Homo sapiens	147-170
22622058-0	2012	Cardiopulmonary and endothelial effects of metformin treatment in an insulin resistant population.	Metformin	43-52	insulin	Homo sapiens	69-76
22827994-8	2012	Compared to no medication, pretreatment with metformin was associated with a 2.9-fold reduction in ultrafiltration coefficient, a 2.5-fold reduction in pulmonary edema formation, lower protein concentration in BALF, lower ACE activity in BALF, and fewer histological lesions upon challenge of the lung preparation with injurious ventilation.	Metformin	45-54	angiotensin I converting enzyme	Homo sapiens	222-225
22564993-9	2012	CONCLUSION: Metformin before surgery did not significantly affect Ki-67 overall, but showed significantly different effects according to insulin resistance, particularly in luminal B tumors.	Metformin	12-21	insulin	Homo sapiens	137-144
22378745-0	2012	A novel inverse relationship between metformin-triggered AMPK-SIRT1 signaling and p53 protein abundance in high glucose-exposed HepG2 cells.	Metformin	37-46	tumor protein p53	Homo sapiens	82-85
22442140-1	2012	Focus on "A novel inverse relationship between metformin-triggered AMPK-SIRT1 signaling and p53 protein abundance in high glucose-exposed HepG2 cells".	Metformin	47-56	tumor protein p53	Homo sapiens	92-95
23019799-1	2012	The aim of this multicentre and observational study was to evaluate in a real life setting glycated haemoglobin A1(c), (HbA1c) as well as body weight outcomes in patients with type 2 diabetes in whom insulin was initiated after unsatisfactory response to exenatide, combined with maximal dosages of metformin and a sulfonylurea.	Metformin	299-308	insulin	Homo sapiens	200-207
22378745-5	2012	Metformin induced activation of AMPK and SIRT1 and decreased p53 protein abundance.	Metformin	0-9	tumor protein p53	Homo sapiens	61-64
22378745-8	2012	In addition, overexpression of p53 decreased SIRT1 gene expression and protein abundance, as well as AMPK activity in metformin-treated cells.	Metformin	118-127	tumor protein p53	Homo sapiens	31-34
22112968-0	2012	Metformin and thiazolidinediones are associated with improved breast cancer-specific survival of diabetic women with HER2+ breast cancer.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	117-121
22608319-7	2012	RESULT(S): Metformin inhibited insulin-induced ovarian T-I cell proliferation and the up-regulation of the cell cycle regulatory proteins, cyclin D3 and CDK4.	Metformin	11-20	cyclin D3	Rattus norvegicus	139-148
22608319-7	2012	RESULT(S): Metformin inhibited insulin-induced ovarian T-I cell proliferation and the up-regulation of the cell cycle regulatory proteins, cyclin D3 and CDK4.	Metformin	11-20	cyclin-dependent kinase 4	Rattus norvegicus	153-157
22892913-8	2012	Metformin caused lower insulin and pro-insulin levels and higher glucagon levels and increased systolic carotid diameter and blood flow.	Metformin	0-9	insulin	Homo sapiens	23-30
22892913-8	2012	Metformin caused lower insulin and pro-insulin levels and higher glucagon levels and increased systolic carotid diameter and blood flow.	Metformin	0-9	insulin	Homo sapiens	39-46
22892913-11	2012	Metformin afforded more protection against macrovascular diabetes complications, increased systolic carotid artery diameter and total and systolic blood flow, and decreased insulin levels.	Metformin	0-9	insulin	Homo sapiens	173-180
22112968-8	2012	CONCLUSIONS: Thiazolidinediones and metformin users are associated with better clinical outcomes than nonusers in diabetics with stage>=2 HER2+ breast cancer.	Metformin	36-45	erb-b2 receptor tyrosine kinase 2	Homo sapiens	141-145
22525206-11	2012	CONCLUSIONS: Metformin has no effect on blood pressure and blood glucose levels, but it does reduce total cholesterol, abdominal obesity and C-reactive protein levels in obese hypertensive patients without diabetes.	Metformin	13-22	C-reactive protein	Homo sapiens	141-159
22016348-0	2012	Addition of metformin to sildenafil treatment for erectile dysfunction in eugonadal nondiabetic men with insulin resistance.	Metformin	12-21	insulin	Homo sapiens	105-112
22498320-11	2012	The use of metformin first, in those without insulin, provided an HR of 0.40 (0.17-0.94).	Metformin	11-20	insulin	Homo sapiens	45-52
22525431-4	2012	The protective effects of the metformin treatment on the onset of fructose-induced non-alcoholic fatty liver disease (NAFLD) were associated with a protection against the loss of the tight junction proteins occludin and zonula occludens 1 in the duodenum of fructose-fed mice and the increased translocation of bacterial endotoxin found in mice only fed with fructose.	Metformin	30-39	occludin	Mus musculus	207-215
22525431-5	2012	In line with these findings, in metformin-treated fructose-fed animals, hepatic expression of genes of the toll-like receptor-4-dependent signalling cascade as well as the plasminogen-activator inhibitor/cMet-regulated lipid export were almost at the level of controls.	Metformin	32-41	toll-like receptor 4	Mus musculus	107-127
22575507-0	2012	Metformin induces differentiation in acute promyelocytic leukemia by activating the MEK/ERK signaling pathway.	Metformin	0-9	mitogen-activated protein kinase kinase 7	Homo sapiens	84-87
22659796-6	2012	Human insulin and analogs activated AKT/mTOR signaling and stimulated ALL cell proliferation (as measured by flow cytometric methods), but metformin and rosiglitazone blocked AKT/mTOR signaling and inhibited proliferation.	Metformin	139-148	AKT serine/threonine kinase 1	Homo sapiens	175-178
22659796-6	2012	Human insulin and analogs activated AKT/mTOR signaling and stimulated ALL cell proliferation (as measured by flow cytometric methods), but metformin and rosiglitazone blocked AKT/mTOR signaling and inhibited proliferation.	Metformin	139-148	mechanistic target of rapamycin kinase	Homo sapiens	179-183
22659796-9	2012	In addition, metformin increased etoposide-induced and L-asparaginase-induced apoptosis; rosiglitazone increased etoposide-induced and vincristine-induced apoptosis.	Metformin	13-22	asparaginase and isoaspartyl peptidase 1	Homo sapiens	55-69
22562515-9	2012	Metformin also prevented the expression of Cox-2 and phosphorylation of p65, and increased the activation of AMPK in the ciliary bodies and retinal tissues.	Metformin	0-9	synaptotagmin 1	Rattus norvegicus	72-75
22562515-10	2012	Moreover, metformin prevented the expression of Cox-2, iNOS, and activation of NF-kB in the HNPECs and decreased the levels of NO and PGE2 in cell culture media.	Metformin	10-19	nitric oxide synthase 2	Rattus norvegicus	55-59
23071876-7	2012	No cure has yet been found for the disease; however, treatment modalities include lifestyle modifications, treatment of obesity, oral hypoglycemic agents, and insulin sensitizers like metformin, a biguanide that reduces insulin resistance, is still the recommended first line medication especially for obese patients.	Metformin	184-193	insulin	Homo sapiens	159-166
23071876-7	2012	No cure has yet been found for the disease; however, treatment modalities include lifestyle modifications, treatment of obesity, oral hypoglycemic agents, and insulin sensitizers like metformin, a biguanide that reduces insulin resistance, is still the recommended first line medication especially for obese patients.	Metformin	184-193	insulin	Homo sapiens	220-227
22713099-1	2012	BACKGROUND: We are hereby investigating for the first time the effect of the association ethinylestradiol30mug-drospirenone 3mg (DRP/EE30mug) plus metformin and weight loss on endothelial status and C-reactive protein (hsCRP) levels in polycystic ovary syndrome (PCOS).	Metformin	147-156	C-reactive protein	Homo sapiens	199-217
22575507-5	2012	U0126, a specific MEK/ERK activation inhibitor, abrogated metformin-induced differentiation.	Metformin	58-67	mitogen-activated protein kinase kinase 7	Homo sapiens	18-21
22575507-5	2012	U0126, a specific MEK/ERK activation inhibitor, abrogated metformin-induced differentiation.	Metformin	58-67	mitogen-activated protein kinase 1	Homo sapiens	22-25
22575507-6	2012	Finally, we found that metformin induced the degradation of the oncoproteins PML-RARalpha and c-Myc and activated caspase-3.	Metformin	23-32	caspase 3	Homo sapiens	114-123
22575507-0	2012	Metformin induces differentiation in acute promyelocytic leukemia by activating the MEK/ERK signaling pathway.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	88-91
22575507-4	2012	Further analysis revealed that a strong synergistic effect existed between metformin and all-trans retinoic acid (ATRA) during APL cell maturation and that metformin induced the hyperphosphorylation of extracellular signal-regulated kinase (ERK) in APL cells.	Metformin	156-165	mitogen-activated protein kinase 1	Homo sapiens	202-239
22575507-4	2012	Further analysis revealed that a strong synergistic effect existed between metformin and all-trans retinoic acid (ATRA) during APL cell maturation and that metformin induced the hyperphosphorylation of extracellular signal-regulated kinase (ERK) in APL cells.	Metformin	156-165	mitogen-activated protein kinase 1	Homo sapiens	241-244
22607767-0	2012	Effect of different doses of metformin on serum testosterone and insulin in non-diabetic women with breast cancer: a randomized study.	Metformin	29-38	insulin	Homo sapiens	65-72
22611195-3	2012	We provide a unique genome-wide analysis of translational targets of canonical mTOR inhibitors (rapamycin and PP242) compared with metformin, revealing that metformin controls gene expression at the level of mRNA translation to an extent comparable to that of canonical mTOR inhibitors.	Metformin	157-166	mechanistic target of rapamycin kinase	Homo sapiens	79-83
22611195-3	2012	We provide a unique genome-wide analysis of translational targets of canonical mTOR inhibitors (rapamycin and PP242) compared with metformin, revealing that metformin controls gene expression at the level of mRNA translation to an extent comparable to that of canonical mTOR inhibitors.	Metformin	157-166	mechanistic target of rapamycin kinase	Homo sapiens	270-274
22686204-3	2012	The comparative PON1 activities at the beginning and at the end of the study were 5.528 +- 0.588 and 4.743 +- 0.619 nmol/mg protein/min (NS) for control group and 3.229 +- 0.403 and 5.135 +- 0.585 nmol/mg protein/min (p < 0.02) for the metformin group.	Metformin	239-248	paraoxonase 1	Homo sapiens	16-20
22686204-4	2012	Our data showed an enhance of PON1 activity in patients with metabolic syndrome treated with metformin, although in them, the raise of HDL concentration was less than control patients, suggesting that the increase in quality (measured here as PON1 activity) could be at least as important as an increase in its concentration.	Metformin	93-102	paraoxonase 1	Homo sapiens	30-34
22686204-4	2012	Our data showed an enhance of PON1 activity in patients with metabolic syndrome treated with metformin, although in them, the raise of HDL concentration was less than control patients, suggesting that the increase in quality (measured here as PON1 activity) could be at least as important as an increase in its concentration.	Metformin	93-102	paraoxonase 1	Homo sapiens	243-247
22399368-7	2012	The combination of diet and exercise followed by metformin in the early phase of "insulin resistance" may reduce or delay both atherosclerosis and arteriosclerosis complications associated with diabetes.	Metformin	49-58	insulin	Homo sapiens	82-89
22512264-7	2012	CONCLUSION: The addition of vildagliptin to metformin gave a better improvement of glycemic control, insulin resistance, and beta-cell function compared with metformin alone.	Metformin	44-53	insulin	Homo sapiens	101-108
22407892-0	2012	Ablation of both organic cation transporter (OCT)1 and OCT2 alters metformin pharmacokinetics but has no effect on tissue drug exposure and pharmacodynamics.	Metformin	67-76	POU domain, class 2, transcription factor 2	Mus musculus	55-59
22407892-1	2012	Organic cation transporter (OCT)1 and OCT2 mediate hepatic uptake and secretory renal clearance of metformin, respectively.	Metformin	99-108	POU domain, class 2, transcription factor 2	Mus musculus	38-42
22676459-0	2012	Relation between augmentation index and adiponectin during one-year metformin treatment for nonalcoholic steatohepatosis: effects beyond glucose lowering?	Metformin	68-77	adiponectin, C1Q and collagen domain containing	Homo sapiens	40-51
22676459-7	2012	Liver function and adiponectin levels did not change during the study.In multiple linear regression analysis, the independent predictors of arterial stiffness improvement were metformin treatment and increase in circulating adiponectin levels.Among metformin treated patients: AI decreased significantly during the study.	Metformin	249-258	adiponectin, C1Q and collagen domain containing	Homo sapiens	224-235
22607767-4	2012	Metformin reduces hyperglycemia and insulin levels in patients with diabetes.	Metformin	0-9	insulin	Homo sapiens	36-43
22607767-5	2012	In women without diabetes and with polycystic ovary syndrome, metformin lowers both insulin and testosterone levels.	Metformin	62-71	insulin	Homo sapiens	84-91
22607767-8	2012	The aim of the present study was to test the effect of different doses of metformin on serum levels of insulin and testosterone in those postmenopausal patients with breast cancer and without diabetes who have basal testosterone levels >=0.28 ng/mL (median value).	Metformin	74-83	insulin	Homo sapiens	103-110
22406476-12	2012	Aspirin and metformin (an activator of AMPK) increased inhibition of mTOR and Akt, as well as autophagy in CRC cells.	Metformin	12-21	mechanistic target of rapamycin kinase	Homo sapiens	69-73
22676459-9	2012	Serum adiponectin level tended to increase during treatment period with metformin.	Metformin	72-81	adiponectin, C1Q and collagen domain containing	Homo sapiens	6-17
22676459-11	2012	These beneficial vascular effects was associated with exposure to metformin per se as well as change in adiponectin levels suggesting that metformin may mediate its vascular effects via glycemic control-independent mechanisms.	Metformin	139-148	adiponectin, C1Q and collagen domain containing	Homo sapiens	104-115
22406476-12	2012	Aspirin and metformin (an activator of AMPK) increased inhibition of mTOR and Akt, as well as autophagy in CRC cells.	Metformin	12-21	AKT serine/threonine kinase 1	Homo sapiens	78-81
22449736-9	2012	Additionally, a small number of studies suggested that metformin, an insulin-sensitizing agent, has therapeutic potential for endometrial cancer.	Metformin	55-64	insulin	Homo sapiens	69-76
22486858-11	2012	CONCLUSIONS: A combination of metformin, peginterferon alfa-2a, and ribavirin improved insulin sensitivity and increased the SVR rate of patients with hepatitis C genotype 1 and IR, with a good safety profile.	Metformin	30-39	insulin	Homo sapiens	87-94
22493491-8	2012	Metformin inhibits PTP and improves IFNalpha response in insulin-resistant cells.	Metformin	0-9	interferon alpha 1	Homo sapiens	36-44
22493491-8	2012	Metformin inhibits PTP and improves IFNalpha response in insulin-resistant cells.	Metformin	0-9	insulin	Homo sapiens	57-64
22469973-0	2012	Luteinizing hormone facilitates angiogenesis in ovarian epithelial tumor             cells and metformin inhibits the effect through the mTOR signaling pathway.	Metformin	95-104	mechanistic target of rapamycin kinase	Homo sapiens	137-141
21301998-2	2012	Several potential mechanisms have been suggested for the ability of metformin to suppress cancer growth in vitro and vivo: (1) activation of LKB1/AMPK pathway, (2) induction of cell cycle arrest and/or apoptosis, (3) inhibition of protein synthesis, (4) reduction in circulating insulin levels, (5) inhibition of the unfolded protein response (UPR), (6) activation of the immune system, and (7) eradication of cancer stem cells.	Metformin	68-77	insulin	Homo sapiens	279-286
22469973-5	2012	Real-time PCR was used to investigate the effect of metformin on LH induction of VEGF and slit2 expression.	Metformin	52-61	vascular endothelial growth factor A	Homo sapiens	81-85
22469973-7	2012	However, metformin inhibited the mTOR signaling pathway and further blocked LH-induced VEGF and slit2 expression.	Metformin	9-18	mechanistic target of rapamycin kinase	Homo sapiens	33-37
22469973-7	2012	However, metformin inhibited the mTOR signaling pathway and further blocked LH-induced VEGF and slit2 expression.	Metformin	9-18	vascular endothelial growth factor A	Homo sapiens	87-91
22469973-9	2012	However, metformin could inhibit tumor angiogenesis by blocking the mTOR signaling pathway.	Metformin	9-18	mechanistic target of rapamycin kinase	Homo sapiens	68-72
22398127-6	2012	The body weight, body mass index, fasting insulin and insulin resistance index decreased significantly in the metformin group, but increased in the placebo group during the 12-week follow-up period.	Metformin	110-119	insulin	Homo sapiens	42-49
22389381-2	2012	Recent studies showed that the antidiabetic agent metformin decreases proliferation of cancer cells through 5"-AMP-activated protein kinase (AMPK)-dependent inhibition of mTOR.	Metformin	50-59	mechanistic target of rapamycin kinase	Homo sapiens	171-175
22389381-7	2012	Treatment with metformin was associated with inhibition of mTOR/p70S6K/pS6 signaling and downregulation of pERK in both TT and MZ-CRC-1 cells.	Metformin	15-24	mechanistic target of rapamycin kinase	Homo sapiens	59-63
22592687-0	2012	Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility.	Metformin	27-36	insulin	Homo sapiens	0-7
22592687-3	2012	Insulin-sensitising agents such as metformin may be effective in treating the features of PCOS, including anovulation.	Metformin	35-44	insulin	Homo sapiens	0-7
22643892-8	2012	Among the messenger RNAs downregulated by metformin, we found c-MYC, IRS-2 and HIF1alpha.	Metformin	42-51	hypoxia inducible factor 1 subunit alpha	Homo sapiens	79-88
22398127-6	2012	The body weight, body mass index, fasting insulin and insulin resistance index decreased significantly in the metformin group, but increased in the placebo group during the 12-week follow-up period.	Metformin	110-119	insulin	Homo sapiens	54-61
22398127-9	2012	CONCLUSION: Metformin was effective and safe in attenuating antipsychotic-induced weight gain and insulin resistance in first-episode schizophrenia patients.	Metformin	12-21	insulin	Homo sapiens	98-105
22525678-1	2012	The aim of the present study is to determine the effects and molecular mechanisms by which activation of LKB1-AMP-activated protein kinase (AMPK) by metformin regulates vascular smooth muscle contraction.	Metformin	149-158	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	105-138
22394605-1	2012	Members of the human SLC superfamily such as organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, and organic cation transporter 1 (OCT1) are drug uptake transporters that are localised on the basolateral membrane of hepatocytes mediating the uptake of drugs such as atorvastatin and metformin into hepatocytes.	Metformin	294-303	solute carrier organic anion transporter family member 1B3	Homo sapiens	99-106
22525678-1	2012	The aim of the present study is to determine the effects and molecular mechanisms by which activation of LKB1-AMP-activated protein kinase (AMPK) by metformin regulates vascular smooth muscle contraction.	Metformin	149-158	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	140-144
22394605-1	2012	Members of the human SLC superfamily such as organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, and organic cation transporter 1 (OCT1) are drug uptake transporters that are localised on the basolateral membrane of hepatocytes mediating the uptake of drugs such as atorvastatin and metformin into hepatocytes.	Metformin	294-303	solute carrier family 22 member 1	Homo sapiens	112-140
22394605-1	2012	Members of the human SLC superfamily such as organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, and organic cation transporter 1 (OCT1) are drug uptake transporters that are localised on the basolateral membrane of hepatocytes mediating the uptake of drugs such as atorvastatin and metformin into hepatocytes.	Metformin	294-303	solute carrier family 22 member 1	Homo sapiens	142-146
22525678-4	2012	In cultured rat VSMCs, AMPK activation through LKB1 by metformin-inhibited phenylephrine-mediated myosin light chain kinase (MLCK) and myosin light chain phosphorylation (p-MLC).	Metformin	55-64	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	23-27
22525678-4	2012	In cultured rat VSMCs, AMPK activation through LKB1 by metformin-inhibited phenylephrine-mediated myosin light chain kinase (MLCK) and myosin light chain phosphorylation (p-MLC).	Metformin	55-64	myosin light chain kinase	Rattus norvegicus	98-123
22525678-4	2012	In cultured rat VSMCs, AMPK activation through LKB1 by metformin-inhibited phenylephrine-mediated myosin light chain kinase (MLCK) and myosin light chain phosphorylation (p-MLC).	Metformin	55-64	myosin light chain kinase	Rattus norvegicus	125-129
22525678-6	2012	Measurement of the tension trace in rat aortic rings also showed that the effect of AMPK activation by metformin decreased phenylephrine-induced contraction.	Metformin	103-112	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	84-88
22593441-4	2012	Therefore, simultaneously targeting AMPK through metformin and the PI3K/AKT/mTOR pathway by an mTOR inhibitor could become a therapeutic approach.	Metformin	49-58	mechanistic target of rapamycin kinase	Homo sapiens	95-99
22593441-9	2012	Metformin alone inhibited cell proliferation and induced apoptosis in different breast cancer cell lines (ERalpha-positive, HER2-positive, and triple-negative).	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	124-128
22059736-9	2012	A greater reduction in the fasting proinsulin/insulin ratio and a greater increase in homeostasis model assessment of beta-cell function (HOMA-beta) were observed with sitagliptin/metformin than with pioglitazone, while greater decreases in fasting insulin and HOMA of insulin resistance (HOMA-IR), and a greater increase in quantitative insulin sensitivity check index (QUICKI) were observed with pioglitazone than with sitagliptin/metformin.	Metformin	180-189	insulin	Homo sapiens	35-45
21933330-5	2012	The benefits of the insulin sensitizer metformin and lifestyle intervention for reducing the incidence of metabolic syndrome have been shown in patients with impaired glucose tolerance.	Metformin	39-48	insulin	Homo sapiens	20-27
22462531-1	2012	OBJECTIVE: Evidence indicates that metformin and pioglitazone both improve insulin resistance and hirsutism among patient with polycystic ovarian syndrome (PCOS).	Metformin	35-44	insulin	Homo sapiens	75-82
22462531-6	2012	Pioglitazone was found to be significantly more effective than metformin at reducing fasting insulin level (P = 0.002, standardized mean differences [SMD] = -0.37, 95% confidence interval [CI] [-0.61, -0.13]).	Metformin	63-72	insulin	Homo sapiens	93-100
22059736-9	2012	A greater reduction in the fasting proinsulin/insulin ratio and a greater increase in homeostasis model assessment of beta-cell function (HOMA-beta) were observed with sitagliptin/metformin than with pioglitazone, while greater decreases in fasting insulin and HOMA of insulin resistance (HOMA-IR), and a greater increase in quantitative insulin sensitivity check index (QUICKI) were observed with pioglitazone than with sitagliptin/metformin.	Metformin	180-189	insulin	Homo sapiens	38-45
22059736-9	2012	A greater reduction in the fasting proinsulin/insulin ratio and a greater increase in homeostasis model assessment of beta-cell function (HOMA-beta) were observed with sitagliptin/metformin than with pioglitazone, while greater decreases in fasting insulin and HOMA of insulin resistance (HOMA-IR), and a greater increase in quantitative insulin sensitivity check index (QUICKI) were observed with pioglitazone than with sitagliptin/metformin.	Metformin	180-189	insulin	Homo sapiens	46-53
22059736-9	2012	A greater reduction in the fasting proinsulin/insulin ratio and a greater increase in homeostasis model assessment of beta-cell function (HOMA-beta) were observed with sitagliptin/metformin than with pioglitazone, while greater decreases in fasting insulin and HOMA of insulin resistance (HOMA-IR), and a greater increase in quantitative insulin sensitivity check index (QUICKI) were observed with pioglitazone than with sitagliptin/metformin.	Metformin	180-189	insulin	Homo sapiens	46-53
22059736-9	2012	A greater reduction in the fasting proinsulin/insulin ratio and a greater increase in homeostasis model assessment of beta-cell function (HOMA-beta) were observed with sitagliptin/metformin than with pioglitazone, while greater decreases in fasting insulin and HOMA of insulin resistance (HOMA-IR), and a greater increase in quantitative insulin sensitivity check index (QUICKI) were observed with pioglitazone than with sitagliptin/metformin.	Metformin	180-189	insulin	Homo sapiens	46-53
22068250-6	2012	In the pioglitazone + metformin group (24 hours off medication), fasting plasma glucose fell from 109 to 102 mg/dL; plasma glucose area under the curve decreased by 12.0%; insulin sensitivity and beta-cell function improved by 42% and 50%, respectively (all P<.001); 14.3% converted to normal glucose tolerance; and no patient developed diabetes.	Metformin	22-31	insulin	Homo sapiens	172-179
22349108-0	2012	Metformin ameliorates IL-6-induced hepatic insulin resistance via induction of orphan nuclear receptor small heterodimer partner (SHP) in mouse models.	Metformin	0-9	interleukin 6	Mus musculus	22-26
22349108-3	2012	Here, we demonstrate that metformin-mediated activation of AMP-activated protein kinase (AMPK) increases SHP protein production and regulates IL-6-induced hepatic insulin resistance.	Metformin	26-35	interleukin 6	Mus musculus	142-146
22349108-4	2012	METHODS: We investigated metformin-mediated SHP production improved insulin resistance through the regulation of an IL-6-dependent pathway (involving signal transducer and activator of transcription 3 [STAT3] and suppressor of cytokine signalling 3 [SOCS3]) in both Shp knockdown and Shp null mice.	Metformin	25-34	interleukin 6	Mus musculus	116-120
22349108-4	2012	METHODS: We investigated metformin-mediated SHP production improved insulin resistance through the regulation of an IL-6-dependent pathway (involving signal transducer and activator of transcription 3 [STAT3] and suppressor of cytokine signalling 3 [SOCS3]) in both Shp knockdown and Shp null mice.	Metformin	25-34	signal transducer and activator of transcription 3	Mus musculus	150-200
22349108-4	2012	METHODS: We investigated metformin-mediated SHP production improved insulin resistance through the regulation of an IL-6-dependent pathway (involving signal transducer and activator of transcription 3 [STAT3] and suppressor of cytokine signalling 3 [SOCS3]) in both Shp knockdown and Shp null mice.	Metformin	25-34	signal transducer and activator of transcription 3	Mus musculus	202-207
22349108-5	2012	RESULTS: IL-6-induced STAT3 transactivation and SOCS3 production were significantly repressed by metformin, adenoviral constitutively active AMPK (Ad-CA-AMPK), and adenoviral SHP (Ad-SHP), but not in Shp knockdown, or with the adenoviral dominant negative form of AMPK (Ad-DN-AMPK).	Metformin	97-106	interleukin 6	Mus musculus	9-13
22349108-5	2012	RESULTS: IL-6-induced STAT3 transactivation and SOCS3 production were significantly repressed by metformin, adenoviral constitutively active AMPK (Ad-CA-AMPK), and adenoviral SHP (Ad-SHP), but not in Shp knockdown, or with the adenoviral dominant negative form of AMPK (Ad-DN-AMPK).	Metformin	97-106	signal transducer and activator of transcription 3	Mus musculus	22-27
22349108-9	2012	CONCLUSIONS/INTERPRETATION: Our results demonstrate that SHP upregulation by metformin may prevent hepatic disorders by regulating the IL-6-dependent pathway, and that this pathway can help to ameliorate the pathogenesis of cytokine-mediated metabolic dysfunction.	Metformin	77-86	interleukin 6	Mus musculus	135-139
22245693-7	2012	Metformin up-regulated the expression of miR-26a, miR-192 and let-7c in a dose-dependent manner.	Metformin	0-9	microRNA 192	Homo sapiens	50-57
22245693-10	2012	Nude mice xenograft models confirmed that metformin up-regulated the level of miR-26a and surpressed the expression of HMGA1 in vivo.	Metformin	42-51	high mobility group AT-hook 1	Mus musculus	119-124
22068250-7	2012	In the pioglitazone + metformin + exenatide group (24 hours off medication), fasting plasma glucose fell from 109 to 98 mg/dL; plasma glucose area under the curve decreased by 21.2%; insulin sensitivity and beta-cell function improved by 52% and 109%, respectively (all P<.001); 59.1% of patients with IGT reverted to normal glucose tolerance; and no patient developed diabetes.	Metformin	22-31	insulin	Homo sapiens	183-190
22252099-0	2012	Metformin potentiates the effects of paclitaxel in endometrial cancer cells through inhibition of cell proliferation and modulation of the mTOR pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	139-143
22252099-6	2012	Western immunoblotting was performed to determine the effect of metformin/paclitaxel on the mTOR pathway.	Metformin	64-73	mechanistic target of rapamycin kinase	Homo sapiens	92-96
22252099-15	2012	CONCLUSIONS: Metformin potentiates the effects of paclitaxel in endometrial cancer cells through inhibition of cell proliferation and modulation of the mTOR pathway.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	152-156
22322462-0	2012	MicroRNA-21-mediated regulation of Sprouty2 protein expression enhances the cytotoxic effect of 5-fluorouracil and metformin in colon cancer cells.	Metformin	115-124	sprouty RTK signaling antagonist 2	Homo sapiens	35-43
22322462-3	2012	Expression of Spry2 inhibited             the growth of a colon cancer cell line, HCT116, and induced sensitization to fluorouracil             (5-FU) and metformin.	Metformin	155-164	sprouty RTK signaling antagonist 2	Homo sapiens	14-19
22322462-5	2012	Treatment of Spry2-HCT116             cells with metformin resulted in a more prominent effect on the inhibition of             cell migration.	Metformin	49-58	sprouty RTK signaling antagonist 2	Homo sapiens	13-18
22009336-0	2012	Metformin and placebo therapy in adjunct with lifestyle intervention both improve weight loss and insulin resistance in obese adolescents.	Metformin	0-9	insulin	Homo sapiens	98-105
22494745-0	2012	Re: addition of metformin to sildenafil treatment for erectile dysfunction in eugonadal non-diabetic men with insulin resistance.	Metformin	16-25	insulin	Homo sapiens	110-117
22517929-13	2012	In a random effects model, metformin and insulin resulted in reduced HbA(1c), weight gain, and insulin dose, compared with insulin alone; trial sequential analyses showed sufficient evidence for a HbA(1c) reduction of 0.5%, lower weight gain of 1 kg, and lower insulin dose of 5 U/day.	Metformin	27-36	insulin	Homo sapiens	95-102
22517929-13	2012	In a random effects model, metformin and insulin resulted in reduced HbA(1c), weight gain, and insulin dose, compared with insulin alone; trial sequential analyses showed sufficient evidence for a HbA(1c) reduction of 0.5%, lower weight gain of 1 kg, and lower insulin dose of 5 U/day.	Metformin	27-36	insulin	Homo sapiens	95-102
22517929-13	2012	In a random effects model, metformin and insulin resulted in reduced HbA(1c), weight gain, and insulin dose, compared with insulin alone; trial sequential analyses showed sufficient evidence for a HbA(1c) reduction of 0.5%, lower weight gain of 1 kg, and lower insulin dose of 5 U/day.	Metformin	27-36	insulin	Homo sapiens	95-102
22442275-9	2012	Adverse effects of insulin, including weight gain and hypoglycemia, can be minimized by initial use of basal insulins in combination with metformin, incretin mimetics, or dipeptidyl-peptidase-IV inhibitors.	Metformin	138-147	insulin	Homo sapiens	19-26
22559241-9	2012	Metformin is recommended to be prescribed with insulin as compared to oral hypoglycemic agents which should be discontinued while starting insulin.	Metformin	0-9	insulin	Homo sapiens	47-54
22262811-2	2012	Experimental models show that metformin inhibits the growth of certain neoplasms by cell autonomous mechanisms such as activation of AMP kinase with secondary inhibition of protein synthesis or by an indirect mechanism involving reduction in gluconeogenesis leading to a decline in insulin levels and reduced proliferation of insulin-responsive cancers.	Metformin	30-39	insulin	Homo sapiens	282-289
22415520-5	2012	When comparing various substrates such as MPP+, TEA, metformin and lamivudine, the effects of the OCT1 genetic polymorphisms on their uptake were not identical.	Metformin	53-62	solute carrier family 22 member 1	Homo sapiens	98-102
22415520-7	2012	In conclusion, the effect of genetic variations of OCT1 and OCT2 on the uptake of MPP+, TEA, metformin and lamivudine was substrate-dependent.	Metformin	93-102	solute carrier family 22 member 1	Homo sapiens	51-55
22576211-2	2012	Here, we show that melanoma cells that are driven by oncogenic BRAF are resistant to the growth-inhibitory effects of metformin because RSK sustains TORC1 activity even when AMP-activated protein kinase (AMPK) is activated.	Metformin	118-127	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	63-67
22576211-0	2012	Metformin accelerates the growth of BRAF V600E-driven melanoma by upregulating VEGF-A.	Metformin	0-9	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	36-40
22576211-0	2012	Metformin accelerates the growth of BRAF V600E-driven melanoma by upregulating VEGF-A.	Metformin	0-9	vascular endothelial growth factor A	Homo sapiens	79-85
22406377-0	2012	Metformin-mediated Bambi expression in hepatic stellate cells induces prosurvival Wnt/beta-catenin signaling.	Metformin	0-9	BMP and activin membrane bound inhibitor	Homo sapiens	19-24
22406377-7	2012	AICAR-mediated HSC cell death was paralleled by loss of expression of the TGF-beta decoy receptor Bambi, whereas metformin increased Bambi expression.	Metformin	113-122	BMP and activin membrane bound inhibitor	Homo sapiens	133-138
22406377-11	2012	The finding that metformin increases Bambi expression and activates Wnt/beta-catenin signaling provides a possible mechanistic explanation for this observation.	Metformin	17-26	BMP and activin membrane bound inhibitor	Homo sapiens	37-42
22576211-2	2012	Here, we show that melanoma cells that are driven by oncogenic BRAF are resistant to the growth-inhibitory effects of metformin because RSK sustains TORC1 activity even when AMP-activated protein kinase (AMPK) is activated.	Metformin	118-127	ribosomal protein S6 kinase A2	Homo sapiens	136-139
22576211-5	2012	Unexpectedly, however, when VEGF signaling is inhibited, instead of accelerating tumor growth, metformin inhibits tumor growth.	Metformin	95-104	vascular endothelial growth factor A	Homo sapiens	28-32
22576211-7	2012	SIGNIFICANCE: Metformin inhibits the growth of most tumor cells, but BRAF-mutant melanoma cells are resistant to metformin in vitro, and metformin accelerates their growth in vivo.	Metformin	113-122	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	69-73
22576211-8	2012	Unexpectedly, VEGF inhibitors and metformin synergize to suppress the growth of BRAF-mutant tumors, revealing a combination of drugs that may be effective in these patients.	Metformin	34-43	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	80-84
22221769-7	2012	Vegetarianism and metformin use contribute to depressed vitamin B12 levels and may independently increase the risk for cognitive impairment.	Metformin	18-27	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	64-67
22330083-5	2012	Metformin also markedly reduced hepatic TNF-alpha mRNA content and blood TNF-alpha level.	Metformin	0-9	tumor necrosis factor	Mus musculus	40-49
22330083-5	2012	Metformin also markedly reduced hepatic TNF-alpha mRNA content and blood TNF-alpha level.	Metformin	0-9	tumor necrosis factor	Mus musculus	73-82
22564101-9	2012	Insulin efficacy may be enhanced by continuing metformin and/or incretin therapies, while discontinuing other drugs as appropriate.	Metformin	47-56	insulin	Homo sapiens	0-7
22421144-8	2012	Mechanistically, metformin caused G 1 arrest, which coincided with a decrease in the protein levels of CDKs (2, 4 and 6), cyclins (D1 and E) and CDK inhibitors (p15, p16, p18 and p27), but no change in p19 and p21.	Metformin	17-26	cyclin dependent kinase inhibitor 2B	Homo sapiens	161-164
22421144-8	2012	Mechanistically, metformin caused G 1 arrest, which coincided with a decrease in the protein levels of CDKs (2, 4 and 6), cyclins (D1 and E) and CDK inhibitors (p15, p16, p18 and p27), but no change in p19 and p21.	Metformin	17-26	cyclin dependent kinase inhibitor 2A	Homo sapiens	166-169
22421144-8	2012	Mechanistically, metformin caused G 1 arrest, which coincided with a decrease in the protein levels of CDKs (2, 4 and 6), cyclins (D1 and E) and CDK inhibitors (p15, p16, p18 and p27), but no change in p19 and p21.	Metformin	17-26	H3 histone pseudogene 12	Homo sapiens	171-174
22421144-8	2012	Mechanistically, metformin caused G 1 arrest, which coincided with a decrease in the protein levels of CDKs (2, 4 and 6), cyclins (D1 and E) and CDK inhibitors (p15, p16, p18 and p27), but no change in p19 and p21.	Metformin	17-26	cyclin dependent kinase inhibitor 2A	Homo sapiens	202-205
22565037-0	2012	Metformin-induced preferential killing of breast cancer initiating CD44+CD24-/low cells is sufficient to overcome primary resistance to trastuzumab in HER2+ human breast cancer xenografts.	Metformin	0-9	CD24 molecule	Homo sapiens	72-76
25505509-3	2012	Some studies have assessed the effects of hyperinsulinemia and insulin resistance in relationship with insulin sensitizing agents such as Metformin (Met).	Metformin	138-147	insulin	Homo sapiens	47-54
25505509-3	2012	Some studies have assessed the effects of hyperinsulinemia and insulin resistance in relationship with insulin sensitizing agents such as Metformin (Met).	Metformin	138-147	insulin	Homo sapiens	63-70
21995500-0	2012	Inhibition of p42 MAPK using a nonviral vector-delivered siRNA potentiates the anti-tumor effect of metformin in prostate cancer cells.	Metformin	100-109	mitogen-activated protein kinase 1	Homo sapiens	14-22
21995500-1	2012	AIMS: The aim of this work was to study if a G1-polyamidoamine dendrimer/siRNA dendriplex can remove the p42 MAPK protein in prostate cancer cells and to potentiate the anti-tumoral effect of the antidiabetic drug metformin and taxane docetaxel.	Metformin	214-223	mitogen-activated protein kinase 1	Homo sapiens	105-113
21995500-5	2012	RESULTS: The dendriplex siRNA/G1-polyamidoamine dendrimer decreased both p42 MAPK mRNA and protein levels by more than 80%, which potentiates the anti-tumoral effects of metformin.	Metformin	170-179	mitogen-activated protein kinase 1	Homo sapiens	73-81
22565037-0	2012	Metformin-induced preferential killing of breast cancer initiating CD44+CD24-/low cells is sufficient to overcome primary resistance to trastuzumab in HER2+ human breast cancer xenografts.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	151-155
22565037-5	2012	Upon isolation for breast cancer initiating CD44+CD24-/low cells by employing magnetic activated cell sorting, we observed the kinetics of metformin-induced killing drastically varied among CSC and non-CSC subpopulations.	Metformin	139-148	CD24 molecule	Homo sapiens	49-53
22565037-6	2012	Metformin"s cell killing effect increased dramatically by more than 10-fold in CD44+CD24-/low breast CSC cells compared to non-CD44+CD24-/low immunophenotypes.	Metformin	0-9	CD24 molecule	Homo sapiens	84-88
22565037-6	2012	Metformin"s cell killing effect increased dramatically by more than 10-fold in CD44+CD24-/low breast CSC cells compared to non-CD44+CD24-/low immunophenotypes.	Metformin	0-9	CD24 molecule	Homo sapiens	132-136
22565037-9	2012	Given that metformin-induced preferential killing of breast cancer initiating CD44+CD24-/low subpopulations is sufficient to overcome in vivo primary resistance to trastuzumab, the incorporation of metformin into trastuzumab-based regimens may provide a valuable strategy for treatment of HER2+ breast cancer patients.	Metformin	11-20	CD24 molecule	Homo sapiens	83-87
22565037-9	2012	Given that metformin-induced preferential killing of breast cancer initiating CD44+CD24-/low subpopulations is sufficient to overcome in vivo primary resistance to trastuzumab, the incorporation of metformin into trastuzumab-based regimens may provide a valuable strategy for treatment of HER2+ breast cancer patients.	Metformin	11-20	erb-b2 receptor tyrosine kinase 2	Homo sapiens	289-293
22443173-12	2012	Metformin activates AMPK, which inhibits the mammalian target of rapamycin (mTOR) pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	45-74
22355097-2	2012	Metformin, effective in treating type 2 diabetes and the insulin resistance syndromes, improves insulin resistance by reducing hepatic gluconeogenesis and by enhancing glucose uptake by skeletal muscle.	Metformin	0-9	insulin	Homo sapiens	57-64
22355097-2	2012	Metformin, effective in treating type 2 diabetes and the insulin resistance syndromes, improves insulin resistance by reducing hepatic gluconeogenesis and by enhancing glucose uptake by skeletal muscle.	Metformin	0-9	insulin	Homo sapiens	96-103
22443173-12	2012	Metformin activates AMPK, which inhibits the mammalian target of rapamycin (mTOR) pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	76-80
22436702-11	2012	In addition, insulin, metformin, BLX-1002, pioglitazone, and candesartan significantly decreased the caspase-3 activity and the subsequent DNA fragmentation evoked by palmitate, suggesting a protective effect of the drugs against lipoapoptosis.	Metformin	22-31	caspase 3	Homo sapiens	101-110
22355097-5	2012	The effects of metformin on circulating insulin levels indicate a potential efficacy towards cancers associated with hyperinsulinaemia; however, metformin may also directly inhibit tumour growth.	Metformin	15-24	insulin	Homo sapiens	40-47
22182833-5	2012	Early studies in PCOS suggested that metformin indirectly reduces insulin level, dyslipidemia and systemic inflammation; however, recent placebo-controlled trials failed to demonstrate significant metabolic benefit.	Metformin	37-46	insulin	Homo sapiens	66-73
22325091-5	2012	Expression of orexigenic peptides neuropeptide Y (NPY) and agouti-related protein (AgRP) decreased in the hypothalamus of metformin-treated diabetic rats, though anorexigenic peptides pro-opiomelanocortin (POMC) did not change significantly.	Metformin	122-131	neuropeptide Y	Rattus norvegicus	34-48
22325091-5	2012	Expression of orexigenic peptides neuropeptide Y (NPY) and agouti-related protein (AgRP) decreased in the hypothalamus of metformin-treated diabetic rats, though anorexigenic peptides pro-opiomelanocortin (POMC) did not change significantly.	Metformin	122-131	neuropeptide Y	Rattus norvegicus	50-53
22325091-8	2012	The anorexic effect of metformin may be mediated by inhibition of NPY and AgRP gene expression through the STAT3 signaling pathway.	Metformin	23-32	neuropeptide Y	Rattus norvegicus	66-69
22356767-3	2012	Metformin significantly enhanced the number of MEFs entering a senescent stage in response to doxorubicin, an anthracycline that induces cell senescence by activating DNA damage signaling pathways (e.g., ATM/ATR) in a reactive oxygen species (ROS)-dependent manner.	Metformin	0-9	ATR serine/threonine kinase	Homo sapiens	208-211
22356767-7	2012	Metformin-induced SIS in BJ-1 fibroblasts was accompanied by the striking activation of several microRNAs belonging to the miR-200s family (miR-200a, miR-141 and miR429) and miR-205, thus mimicking a recently described ability of ROS to chemosensitize cancer cells by specifically upregulating anti-EMT (epithelial-to-mesenchymal transition) miR-200s.	Metformin	0-9	microRNA 141	Homo sapiens	150-157
22356767-7	2012	Metformin-induced SIS in BJ-1 fibroblasts was accompanied by the striking activation of several microRNAs belonging to the miR-200s family (miR-200a, miR-141 and miR429) and miR-205, thus mimicking a recently described ability of ROS to chemosensitize cancer cells by specifically upregulating anti-EMT (epithelial-to-mesenchymal transition) miR-200s.	Metformin	0-9	microRNA 429	Homo sapiens	162-168
22333588-3	2012	We recently envisioned that intervention strategies aimed at reversing the bioenergetic signature of cancer cells (e.g., the antidiabetic biguanide metformin) should correct oncogene (e.g., HER2)-driven MHC-I defects, thus preventing immune escape of oncogene transformants.	Metformin	148-157	erb-b2 receptor tyrosine kinase 2	Homo sapiens	190-194
21835833-6	2012	In the majority of cases, no specific treatment is recommended, but where there is a history of low birth weight, with associated insulin resistance, intervention with the insulin sensitising agent metformin may be considered on a case by case basis.	Metformin	198-207	insulin	Homo sapiens	130-137
21835833-6	2012	In the majority of cases, no specific treatment is recommended, but where there is a history of low birth weight, with associated insulin resistance, intervention with the insulin sensitising agent metformin may be considered on a case by case basis.	Metformin	198-207	insulin	Homo sapiens	172-179
22333588-4	2012	First, we explored how metformin treatment impacted mitochondrial biogenesis in cultured breast cancer cells overexpressing the membrane tyrosine kinase receptor HER2, the best-characterized downregulator of MHC-I.	Metformin	23-32	erb-b2 receptor tyrosine kinase 2	Homo sapiens	162-166
22378068-0	2012	Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy.	Metformin	12-21	mechanistic target of rapamycin kinase	Homo sapiens	85-89
22378068-5	2012	Metformin-induced AMPK activation was associated with the inhibition of the mTOR signaling without involving AKT.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	76-80
22378068-6	2012	Moreover, lymphoma cell response to the chemotherapeutic agent doxorubicin and mTOR inhibitor temsirolimus was significantly enhanced when co-treated with metformin.	Metformin	155-164	mechanistic target of rapamycin kinase	Homo sapiens	79-83
22107872-5	2012	We found that metformin activates the PERK-ATF4 but not the ATF6 or IRE1-XBP1 branch in ERSS and leads to a strong upregulation of CHOP mRNA and protein.	Metformin	14-23	DNA damage inducible transcript 3	Homo sapiens	131-135
22086681-5	2012	Metformin also decreased the expression of CSC markers,CD44, EpCAM,EZH2, Notch-1, Nanog and Oct4, and caused reexpression of miRNAs (let-7a,let-7b, miR-26a, miR-101, miR-200b, and miR-200c) that are typically lost in pancreatic cancer and especially in pancreatospheres.	Metformin	0-9	epithelial cell adhesion molecule	Homo sapiens	61-66
22086681-5	2012	Metformin also decreased the expression of CSC markers,CD44, EpCAM,EZH2, Notch-1, Nanog and Oct4, and caused reexpression of miRNAs (let-7a,let-7b, miR-26a, miR-101, miR-200b, and miR-200c) that are typically lost in pancreatic cancer and especially in pancreatospheres.	Metformin	0-9	enhancer of zeste 2 polycomb repressive complex 2 subunit	Homo sapiens	67-71
22086681-5	2012	Metformin also decreased the expression of CSC markers,CD44, EpCAM,EZH2, Notch-1, Nanog and Oct4, and caused reexpression of miRNAs (let-7a,let-7b, miR-26a, miR-101, miR-200b, and miR-200c) that are typically lost in pancreatic cancer and especially in pancreatospheres.	Metformin	0-9	notch receptor 1	Homo sapiens	73-80
22086681-5	2012	Metformin also decreased the expression of CSC markers,CD44, EpCAM,EZH2, Notch-1, Nanog and Oct4, and caused reexpression of miRNAs (let-7a,let-7b, miR-26a, miR-101, miR-200b, and miR-200c) that are typically lost in pancreatic cancer and especially in pancreatospheres.	Metformin	0-9	microRNA 200b	Homo sapiens	166-174
22107872-6	2012	Surprisingly, long-term induction of CHOP by metformin is not accompanied by apoptosis even though CHOP is regarded to be a mediator of ER-stress-induced apoptosis.	Metformin	45-54	DNA damage inducible transcript 3	Homo sapiens	37-41
22701828-10	2012	CONCLUSION: Addition of vildagliptin and FDC of vildagliptin and metformin is an effective strategy in glycemic control, reduction in dose of insulin and weight of patients suffering with T2DM.	Metformin	65-74	insulin	Homo sapiens	142-149
22170794-10	2012	Plasma fetuin A levels decreased significantly after metformin treatment compared with placebo (-40 +- 47 vs 15 +- 82 mg/l, P = 0.008).	Metformin	53-62	alpha 2-HS glycoprotein	Homo sapiens	7-15
22170794-11	2012	Metformin induced a dose-dependent decrease in fetuin A secretion in vitro.	Metformin	0-9	alpha 2-HS glycoprotein	Homo sapiens	47-55
22170794-14	2012	Metformin decreased fetuin A levels in vitro.	Metformin	0-9	alpha 2-HS glycoprotein	Homo sapiens	20-28
21567395-6	2012	Pharmacological activation of AMPK by treatment with 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), metformin, or adiponectin lowered TGF-beta-induced expression of COL1A and myofibroblast marker alpha-smooth muscle actin (alpha-SMA).	Metformin	117-126	transforming growth factor beta 1	Homo sapiens	151-159
22038047-0	2012	Caveolin-1 is essential for metformin inhibitory effect on IGF1 action in non-small-cell lung cancer cells.	Metformin	28-37	caveolin 1	Homo sapiens	0-10
22100460-5	2012	Metformin dose-dependently inhibited the formation of AGEs modification of bovine serum albumin (BSA).	Metformin	0-9	albumin	Homo sapiens	82-95
22038047-0	2012	Caveolin-1 is essential for metformin inhibitory effect on IGF1 action in non-small-cell lung cancer cells.	Metformin	28-37	insulin like growth factor 1	Homo sapiens	59-63
22038047-2	2012	Since caveolin-1 (Cav-1) plays a role in AMPK activation and energy balance, we investigated whether Cav-1 could participate in metformin"s inhibitory effect on IGF1 signaling.	Metformin	128-137	caveolin 1	Homo sapiens	101-106
22038047-2	2012	Since caveolin-1 (Cav-1) plays a role in AMPK activation and energy balance, we investigated whether Cav-1 could participate in metformin"s inhibitory effect on IGF1 signaling.	Metformin	128-137	insulin like growth factor 1	Homo sapiens	161-165
22038047-4	2012	In Calu-1, but not in Calu-6 cells, metformin reduced phosphorylation of type 1 insulin-like growth factor receptor (IGF-IR) substrates Akt and Forkhead transcription factor 3a (FOXO3a), inhibited IGF1-dependent FOXO3a nuclear exit, and decreased IGF1-dependent cell proliferation.	Metformin	36-45	AKT serine/threonine kinase 1	Homo sapiens	136-139
22038047-4	2012	In Calu-1, but not in Calu-6 cells, metformin reduced phosphorylation of type 1 insulin-like growth factor receptor (IGF-IR) substrates Akt and Forkhead transcription factor 3a (FOXO3a), inhibited IGF1-dependent FOXO3a nuclear exit, and decreased IGF1-dependent cell proliferation.	Metformin	36-45	forkhead box O3	Homo sapiens	178-184
22038047-4	2012	In Calu-1, but not in Calu-6 cells, metformin reduced phosphorylation of type 1 insulin-like growth factor receptor (IGF-IR) substrates Akt and Forkhead transcription factor 3a (FOXO3a), inhibited IGF1-dependent FOXO3a nuclear exit, and decreased IGF1-dependent cell proliferation.	Metformin	36-45	insulin like growth factor 1	Homo sapiens	197-201
22038047-4	2012	In Calu-1, but not in Calu-6 cells, metformin reduced phosphorylation of type 1 insulin-like growth factor receptor (IGF-IR) substrates Akt and Forkhead transcription factor 3a (FOXO3a), inhibited IGF1-dependent FOXO3a nuclear exit, and decreased IGF1-dependent cell proliferation.	Metformin	36-45	forkhead box O3	Homo sapiens	212-218
22038047-4	2012	In Calu-1, but not in Calu-6 cells, metformin reduced phosphorylation of type 1 insulin-like growth factor receptor (IGF-IR) substrates Akt and Forkhead transcription factor 3a (FOXO3a), inhibited IGF1-dependent FOXO3a nuclear exit, and decreased IGF1-dependent cell proliferation.	Metformin	36-45	insulin like growth factor 1	Homo sapiens	247-251
22038047-5	2012	Here, we show that sensitivity of NSCLC cells to metformin was dependent on Cav-1 expression and that metformin required Cav-1 to induce AMPK phosphorylation and AMP/ATP ratio increase.	Metformin	49-58	caveolin 1	Homo sapiens	76-81
22038047-5	2012	Here, we show that sensitivity of NSCLC cells to metformin was dependent on Cav-1 expression and that metformin required Cav-1 to induce AMPK phosphorylation and AMP/ATP ratio increase.	Metformin	102-111	caveolin 1	Homo sapiens	121-126
22038047-6	2012	Cav-1 silencing in Calu-1 and overexpression in Calu-6 reduced and improved, respectively, the inhibitory effect of metformin on IGF1-dependent Akt phosphorylation.	Metformin	116-125	caveolin 1	Homo sapiens	0-5
22214489-1	2012	INTRODUCTION: Although traditionally used as a final treatment option, early use of insulin is a therapeutic option after metformin failure in type 2 diabetes.	Metformin	122-131	insulin	Homo sapiens	84-91
22038047-6	2012	Cav-1 silencing in Calu-1 and overexpression in Calu-6 reduced and improved, respectively, the inhibitory effect of metformin on IGF1-dependent Akt phosphorylation.	Metformin	116-125	insulin like growth factor 1	Homo sapiens	129-133
22038047-6	2012	Cav-1 silencing in Calu-1 and overexpression in Calu-6 reduced and improved, respectively, the inhibitory effect of metformin on IGF1-dependent Akt phosphorylation.	Metformin	116-125	AKT serine/threonine kinase 1	Homo sapiens	144-147
22038047-7	2012	Prolonged metformin treatment in Calu-6 cells induced a dose-dependent expression increase of Cav-1 and OCT1, a metformin transporter.	Metformin	10-19	caveolin 1	Homo sapiens	94-99
22038047-7	2012	Prolonged metformin treatment in Calu-6 cells induced a dose-dependent expression increase of Cav-1 and OCT1, a metformin transporter.	Metformin	10-19	solute carrier family 22 member 1	Homo sapiens	104-108
22048751-1	2012	We tested the hypothesis that metformin produces arterial dilatation indirectly, by directly exposing the endothelial surface, of an occluded test segment of the pig iliac artery in vivo, to test blood containing metformin or excess insulin, with and without the presence of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester hydrochloride.	Metformin	30-39	nitric oxide synthase 2	Sus scrofa	279-305
22038047-8	2012	Cav-1 and OCT1 expression was associated with the antiproliferative effect of metformin in Calu-6 cells (IC(50)=18 mM).	Metformin	78-87	caveolin 1	Homo sapiens	0-5
22038047-8	2012	Cav-1 and OCT1 expression was associated with the antiproliferative effect of metformin in Calu-6 cells (IC(50)=18 mM).	Metformin	78-87	solute carrier family 22 member 1	Homo sapiens	10-14
22038047-9	2012	In summary, these data suggest that Cav-1 is required for metformin action in NSCLC cells.	Metformin	58-67	caveolin 1	Homo sapiens	36-41
22490993-5	2012	RESULTS: Metformin could block the mitogenic effects of insulin, but this effect does not entirely explain the reduction in cancer incidence.	Metformin	9-18	insulin	Homo sapiens	56-63
22490993-6	2012	Metformin also plays a direct inhibition of cancer cell growth via the inhibitory effects of AMP-activated protein kinase on the mTOR pathway, which regulates cell growth and proliferation.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	129-133
21920717-0	2012	ENPP1 mRNA levels in white blood cells and prediction of metformin efficacy in type 2 diabetic patients: a preliminary evidence.	Metformin	57-66	ectonucleotide pyrophosphatase/phosphodiesterase 1	Homo sapiens	0-5
22375259-0	2012	Comparative Effects of Glibenclamide and Metformin on C-Reactive Protein and Oxidant/Antioxidant Status in Patients with Type II Diabetes Mellitus.	Metformin	41-50	C-reactive protein	Homo sapiens	54-72
22375259-1	2012	OBJECTIVES: This study aimed to compare the effects of metformin and glibenclamide on high sensitivity serum C-reactive protein (hs-CRP) and oxidative stress, represented by serum malondialdehyde (MDA) and total antioxidant status (TAS) in newly-diagnosed patients with Type 2 diabetes mellitus (DM) at baseline and after 2 months of therapy in comparison to controls.	Metformin	55-64	C-reactive protein	Homo sapiens	109-127
22154980-1	2012	AIMS: Metformin is an insulin sensitizing agent with beneficial effects in diabetic patients on glycemic levels and in the cardiovascular system.	Metformin	6-15	insulin	Homo sapiens	22-29
22189713-10	2012	In summary, Stat3 is a critical regulator of metformin action in TN cancer cells, providing the potential for enhancing metformin"s efficacy in the clinical setting.	Metformin	120-129	signal transducer and activator of transcription 3	Homo sapiens	12-17
22189713-0	2012	Metformin targets Stat3 to inhibit cell growth and induce apoptosis in triple-negative breast cancers.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	18-23
22451180-1	2012	AIM: to compare the effectiveness of metformin and pioglitazone in ameliorating insulin resistance and cardiovascular risk factors in women with polycystic ovary syndrome (PCOS).	Metformin	37-46	insulin	Homo sapiens	80-87
22189713-3	2012	Because TN cells are particularly sensitive to the anti-diabetic agent metformin, we hypothesized that it may target JAK2/Stat3 signaling.	Metformin	71-80	signal transducer and activator of transcription 3	Homo sapiens	122-127
22189713-4	2012	The effects of metformin upon Stat3 expression and activation were examined in four human TN cell lines.	Metformin	15-24	signal transducer and activator of transcription 3	Homo sapiens	30-35
22189713-6	2012	Metformin inhibited Stat3 activation (P-Stat3) at Tyr705 and Ser727 and downstream signaling in each of the four parental cell lines.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	20-25
22189713-6	2012	Metformin inhibited Stat3 activation (P-Stat3) at Tyr705 and Ser727 and downstream signaling in each of the four parental cell lines.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	40-45
22189713-7	2012	CA-Stat3 transfection attenuated, whereas Stat3 knockdown enhanced, the effects of metformin upon growth inhibition and apoptosis induction.	Metformin	83-92	signal transducer and activator of transcription 3	Homo sapiens	3-8
22189713-7	2012	CA-Stat3 transfection attenuated, whereas Stat3 knockdown enhanced, the effects of metformin upon growth inhibition and apoptosis induction.	Metformin	83-92	signal transducer and activator of transcription 3	Homo sapiens	42-47
22189713-8	2012	A Stat3 specific inhibitor acted synergistically with metformin in reducing cell growth and inducing apoptosis.	Metformin	54-63	signal transducer and activator of transcription 3	Homo sapiens	2-7
22189713-10	2012	In summary, Stat3 is a critical regulator of metformin action in TN cancer cells, providing the potential for enhancing metformin"s efficacy in the clinical setting.	Metformin	45-54	signal transducer and activator of transcription 3	Homo sapiens	12-17
23390858-14	2012	The insulin resistance was improved in 80% of the PCOS patients after six months therapy with Metformin 2 x 850 mg/p.d.	Metformin	94-103	insulin	Homo sapiens	4-11
23244125-0	2012	Use of oral antidiabetic drugs (metformin and pioglitazone) in diabetic patients with breast cancer: how does it effect serum Hif-1 alpha and 8Ohdg levels?	Metformin	32-41	hypoxia inducible factor 1 subunit alpha	Homo sapiens	126-137
22331759-5	2012	A noncompartment pharmacokinetic method was employed to determine the pharmacokinetic parameters (Cmax, Tmax, AUC0-t, AUC0-  and t1/2) of metformin using WinNonlin-Node 4.0 software.	Metformin	138-147	CD6 molecule	Homo sapiens	118-133
22994747-3	2012	Our research indicates that metformin displays anticancer activity against HCC through inhibition of the mTOR translational pathway in an AMPK-independent manner, leading to G1 arrest in the cell-cycle and subsequent cell apoptosis through the mitochondrion-dependent pathway.	Metformin	28-37	mechanistic target of rapamycin kinase	Homo sapiens	105-109
23244125-8	2012	However, posttreatment serum HIF-1alpha ve 8-OHdG levels was found lower than pretreatment levels in patients receiving metformin, but not with pioglitazone.	Metformin	120-129	hypoxia inducible factor 1 subunit alpha	Homo sapiens	29-39
23244125-12	2012	CONCLUSIONS: HIF-1alpha levels decreased significantly in the patient group receiving metformin.	Metformin	86-95	hypoxia inducible factor 1 subunit alpha	Homo sapiens	13-23
21769504-4	2012	Since this protein has important immune-modulatory properties, we have investigated the expression of Hsp60 in human THP-1 monocyte cells exposed to metformin.	Metformin	149-158	GLI family zinc finger 2	Homo sapiens	117-122
21769504-0	2012	Metformin induced expression of Hsp60 in human THP-1 monocyte cells.	Metformin	0-9	GLI family zinc finger 2	Homo sapiens	47-52
21769504-7	2012	This suggested a possible modulation of the differentiation rates of the THP-1 cells during exposure to metformin.	Metformin	104-113	GLI family zinc finger 2	Homo sapiens	73-78
22049096-1	2012	Pioglitazone and metformin are insulin sensitisers used for the treatment of T2DM.	Metformin	17-26	insulin	Homo sapiens	31-38
22090360-6	2012	The effect of the drug metformin on overcoming mutant p53-associated radiation resistance was examined in vitro as well as in vivo, using an orthotopic xenograft model.	Metformin	23-32	tumor protein p53	Homo sapiens	54-57
22090360-10	2012	The mitochondrial agent metformin potentiated the effects of radiation in the presence of a disruptive TP53 mutation partially via senescence.	Metformin	24-33	tumor protein p53	Homo sapiens	103-107
22090360-13	2012	Metformin can serve as a radiosensitizer for HNSCC with disruptive TP53, presaging the possibility of personalizing HNSCC treatment.	Metformin	0-9	tumor protein p53	Homo sapiens	67-71
22040838-0	2012	Independent and combined effects of exercise training and metformin on insulin sensitivity in individuals with prediabetes.	Metformin	58-67	insulin	Homo sapiens	71-78
22040838-1	2012	OBJECTIVE: Physical activity or metformin enhances insulin sensitivity and opposes the progression from prediabetes to type 2 diabetes.	Metformin	32-41	insulin	Homo sapiens	51-58
22040838-9	2012	CONCLUSIONS: Insulin sensitivity was considerably higher after 12 weeks of exercise training and/or metformin in men and women with prediabetes.	Metformin	100-109	insulin	Homo sapiens	13-20
22826635-3	2012	Common and effective treatment options added to metformin therapy (basal insulin, sulfonylureas, and pioglitazone) contribute to weight gain, which makes the addition of GLP-1RAs advantageous.	Metformin	48-57	insulin	Homo sapiens	73-80
22124463-0	2012	Sirtuin 1-mediated cellular metabolic memory of high glucose via the LKB1/AMPK/ROS pathway and therapeutic effects of metformin.	Metformin	118-127	sirtuin 1	Rattus norvegicus	0-9
22124463-6	2012	Of importance, this study also demonstrated that metformin suppressed the "memory" of hyperglycemia stress in the diabetic retinas, which may be involved in the SIRT1/LKB1/AMPK pathway.	Metformin	49-58	sirtuin 1	Rattus norvegicus	161-166
22124463-6	2012	Of importance, this study also demonstrated that metformin suppressed the "memory" of hyperglycemia stress in the diabetic retinas, which may be involved in the SIRT1/LKB1/AMPK pathway.	Metformin	49-58	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	172-176
23118742-0	2012	Metformin stimulates FGF21 expression in primary hepatocytes.	Metformin	0-9	fibroblast growth factor 21	Homo sapiens	21-26
22194737-4	2012	This concept has stimulated several clinical studies where antidiabetic drugs, such as insulin sensitizers including metformin, have been evaluated in insulin-resistant, NAFLD patients.	Metformin	117-126	insulin	Homo sapiens	151-158
23118742-2	2012	Metabolic status plays an important role in the regulation of FGF21, and we therefore examined whether metformin, an indirect AMPK-activator, regulates FGF21 expression in hepatocytes.	Metformin	103-112	fibroblast growth factor 21	Homo sapiens	152-157
23118742-6	2012	This effect was blocked by addition of the AMPK-inhibitor Compound C. The study shows that metformin is a potent inducer of hepatic FGF21 expression and that the effect of metformin seems to be mediated through AMPK activation.	Metformin	91-100	fibroblast growth factor 21	Homo sapiens	132-137
23118742-7	2012	As FGF21 therapy normalizes blood glucose in animal models of type 2 diabetes, the induction of hepatic FGF21 by metformin might play an important role in metformin"s antidiabetic effect.	Metformin	113-122	fibroblast growth factor 21	Homo sapiens	3-8
23118742-7	2012	As FGF21 therapy normalizes blood glucose in animal models of type 2 diabetes, the induction of hepatic FGF21 by metformin might play an important role in metformin"s antidiabetic effect.	Metformin	113-122	fibroblast growth factor 21	Homo sapiens	104-109
23118742-7	2012	As FGF21 therapy normalizes blood glucose in animal models of type 2 diabetes, the induction of hepatic FGF21 by metformin might play an important role in metformin"s antidiabetic effect.	Metformin	155-164	fibroblast growth factor 21	Homo sapiens	3-8
23118742-7	2012	As FGF21 therapy normalizes blood glucose in animal models of type 2 diabetes, the induction of hepatic FGF21 by metformin might play an important role in metformin"s antidiabetic effect.	Metformin	155-164	fibroblast growth factor 21	Homo sapiens	104-109
22088206-1	2012	OBJECTIVE: To evaluate the ovarian function during early infancy in daughters of women with polycystic ovary syndrome (PCOS) treated with metformin throughout pregnancy (PCOSd+M), as a means to reduce androgen and insulin levels, compared with daughters of nontreated PCOS women (PCOSd-M) and daughters of women who belong to a healthy comparison group (HCd).	Metformin	138-147	insulin	Homo sapiens	214-221
22481889-1	2012	Metformin (dimethyl-biguanide) is an insulin-sensitizing agent that lowers fasting plasma-insulin concentration, wherefore it"s wide use for patients with a variety of insulin-resistant and prediabetic states, including impaired glucose tolerance.	Metformin	0-9	insulin	Homo sapiens	37-44
22481889-1	2012	Metformin (dimethyl-biguanide) is an insulin-sensitizing agent that lowers fasting plasma-insulin concentration, wherefore it"s wide use for patients with a variety of insulin-resistant and prediabetic states, including impaired glucose tolerance.	Metformin	0-9	insulin	Homo sapiens	90-97
22481889-1	2012	Metformin (dimethyl-biguanide) is an insulin-sensitizing agent that lowers fasting plasma-insulin concentration, wherefore it"s wide use for patients with a variety of insulin-resistant and prediabetic states, including impaired glucose tolerance.	Metformin	0-9	insulin	Homo sapiens	90-97
22481889-1	2012	Metformin (dimethyl-biguanide) is an insulin-sensitizing agent that lowers fasting plasma-insulin concentration, wherefore it"s wide use for patients with a variety of insulin-resistant and prediabetic states, including impaired glucose tolerance.	Metformin	11-29	insulin	Homo sapiens	37-44
22481889-1	2012	Metformin (dimethyl-biguanide) is an insulin-sensitizing agent that lowers fasting plasma-insulin concentration, wherefore it"s wide use for patients with a variety of insulin-resistant and prediabetic states, including impaired glucose tolerance.	Metformin	11-29	insulin	Homo sapiens	90-97
22481889-1	2012	Metformin (dimethyl-biguanide) is an insulin-sensitizing agent that lowers fasting plasma-insulin concentration, wherefore it"s wide use for patients with a variety of insulin-resistant and prediabetic states, including impaired glucose tolerance.	Metformin	11-29	insulin	Homo sapiens	90-97
22451839-9	2012	The results of several clinical trials that have used insulin sensitizers (metformin and PPAR-gamma agonists) have been inconclusive.	Metformin	75-84	insulin	Homo sapiens	54-61
22863784-9	2012	Preincubation of endothelial cells with AGE-BSA and metformin, an anti-diabetic drug known to have an mTOR inhibition effect, significantly reduced AGE-stimulated LOX-1 expression.	Metformin	52-61	mechanistic target of rapamycin kinase	Homo sapiens	102-106
22080879-2	2012	LY294002 (PI3K inhibitor) and metformin (5"-adenosine monophosphate [AMP]-activated protein kinase [AMPK] activator) are 2 drugs that were known to inhibit mTOR expression through the AKT-dependent and AKT-independent pathways, respectively.	Metformin	30-39	mechanistic target of rapamycin kinase	Homo sapiens	156-160
22080879-2	2012	LY294002 (PI3K inhibitor) and metformin (5"-adenosine monophosphate [AMP]-activated protein kinase [AMPK] activator) are 2 drugs that were known to inhibit mTOR expression through the AKT-dependent and AKT-independent pathways, respectively.	Metformin	30-39	AKT serine/threonine kinase 1	Homo sapiens	184-187
22080879-2	2012	LY294002 (PI3K inhibitor) and metformin (5"-adenosine monophosphate [AMP]-activated protein kinase [AMPK] activator) are 2 drugs that were known to inhibit mTOR expression through the AKT-dependent and AKT-independent pathways, respectively.	Metformin	30-39	AKT serine/threonine kinase 1	Homo sapiens	202-205
22080879-7	2012	RESULTS: Our study showed that LY294002 and metformin in combination could simultaneously enhance the repression of the PI3K/AKT/mTOR pathway and the activation of the AMPK/ACC pathway.	Metformin	44-53	AKT serine/threonine kinase 1	Homo sapiens	125-128
22080879-7	2012	RESULTS: Our study showed that LY294002 and metformin in combination could simultaneously enhance the repression of the PI3K/AKT/mTOR pathway and the activation of the AMPK/ACC pathway.	Metformin	44-53	mechanistic target of rapamycin kinase	Homo sapiens	129-133
22715547-8	2012	Only insulin sensitizing drugs like metformin and pioglitazone have been consistently shown to reduce cardiovascular risk.	Metformin	36-45	insulin	Homo sapiens	5-12
24829630-4	2012	Metformin is an oral hypoglycemic agent known to improve insulin resistance.	Metformin	0-9	insulin	Homo sapiens	57-64
23094143-0	2012	Effects of metformin on the regulation of free Fatty acids in insulin resistance: a double-blind, placebo-controlled study.	Metformin	11-20	insulin	Homo sapiens	62-69
23094143-3	2012	Our aim was to evaluate plasma FFA changes in insulin resistance in a physiological situation after improvement of insulin sensitivity by metformin.	Metformin	138-147	insulin	Homo sapiens	115-122
23094143-5	2012	A double-blind, placebo-controlled intervention with metformin was carried out in patients with insulin resistance.	Metformin	53-62	insulin	Homo sapiens	96-103
23094143-10	2012	Fasting plasma glucose, FFA, and HOMA-IR tended to decrease after metformin, suggesting improved insulin sensitivity.	Metformin	66-75	insulin	Homo sapiens	97-104
23094143-15	2012	Metformin in insulin resistance did not lead to improved FFA dynamics despite a trend of improved insulin sensitivity.	Metformin	0-9	insulin	Homo sapiens	13-20
23094143-15	2012	Metformin in insulin resistance did not lead to improved FFA dynamics despite a trend of improved insulin sensitivity.	Metformin	0-9	insulin	Homo sapiens	98-105
22570949-0	2012	The effects of metformin on inflammatory mediators in obese adolescents with insulin resistance: controlled randomized clinical trial.	Metformin	15-24	insulin	Homo sapiens	77-84
22570949-5	2012	Serum fasting insulin concentrations (pmol/L) increased in the placebo group (189.45 +/- 112.64-266.06 +/- 167.79; p=0.01) and showed a slight decrease in the metformin group (256.82 +/- 113.89-229.25 +/- 86.53; p=0.64).	Metformin	159-168	insulin	Homo sapiens	14-21
22570949-7	2012	In the metformin group, significant reductions were found in the variances of serum TNFalpha concentrations (p=0.006; Levene test).	Metformin	7-16	tumor necrosis factor	Homo sapiens	84-92
21964537-2	2012	Exercise, AICAR, and metformin, all known activators of AMPK, induce delayed cardioprotection which protects the heart against ischemia-reperfusion injury.	Metformin	21-30	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	56-60
21964537-9	2012	Seventy eight different genes were overlapping the exercise and AICAR group at 24 h. Ingenuity identified six overlapping genes between the exercise, AICAR, and metformin groups including NR4A3, TNFRSF12A, HBB, PENK, PAP, and MAP4K4.	Metformin	161-170	TNF receptor superfamily member 12A	Rattus norvegicus	195-204
23152807-9	2012	In vivo, we show that sucrose fed rats also develop fatty liver that is blocked by metformin in association with both a reduction in AMPD activity and an increase in AMPK activity.	Metformin	83-92	adenosine monophosphate deaminase 1	Rattus norvegicus	133-137
21968881-9	2012	Remarkably, metformin targeted the side population of T-ALL cell lines as well as a putative leukemia-initiating cell subpopulation (CD34(+)/CD7(-)/CD4(-)) in patient samples.	Metformin	12-21	CD4 molecule	Homo sapiens	148-151
23108012-11	2012	Metformin (the best known clinical activator of AMPK) and another AMPK activator (AICAR) suppressed the albumin-induced ER stress via inhibition of ROS through induction of endogenous antioxidant thioredoxin.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	48-52
23108012-11	2012	Metformin (the best known clinical activator of AMPK) and another AMPK activator (AICAR) suppressed the albumin-induced ER stress via inhibition of ROS through induction of endogenous antioxidant thioredoxin.	Metformin	0-9	thioredoxin 1	Rattus norvegicus	196-207
23108012-12	2012	AMPK inhibitor blocked the effect of metformin and AICAR.	Metformin	37-46	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	0-4
22343549-8	2012	Metformin treatment blocked ghrelin-induced activation of hypothalamic AMPK/ACC/Raptor and restored mTOR activity without affecting S6K phosphorylation.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	100-104
22343549-10	2012	CONCLUSION: Metformin could reduce food intake by preventing ghrelin-induced AMPK signalling and mTOR inhibition in the hypotalamus.	Metformin	12-21	mechanistic target of rapamycin kinase	Homo sapiens	97-101
23166782-8	2012	ERRalpha mRNA expression was regulated in a similar manner as SIRT3 mRNA by glucagon, cAMP and metformin.	Metformin	95-104	estrogen related receptor, alpha	Mus musculus	0-8
22363765-4	2012	Both bortezomib and metformin have been proposed as potential therapeutics in TSC.	Metformin	20-29	TSC complex subunit 1	Homo sapiens	78-81
23166782-9	2012	However, a higher metformin concentration was required for downregulation of ERRalpha than SIRT3.	Metformin	18-27	estrogen related receptor, alpha	Mus musculus	77-85
23133528-7	2012	Moreover, metformin treatment increased gene expression of PI3K, IRS1, MAP3K, AKT and PTEN more than >1.5 fold.	Metformin	10-19	AKT serine/threonine kinase 1	Homo sapiens	78-81
22363765-0	2012	Therapeutic trial of metformin and bortezomib in a mouse model of tuberous sclerosis complex (TSC).	Metformin	21-30	TSC complex subunit 1	Homo sapiens	94-97
23196582-5	2012	Metformin treatment is useful to improve insulin resistance in DM1.	Metformin	0-9	insulin	Homo sapiens	41-48
23091851-8	2012	The CHD and MS patients who carried the Pro allele showed a significant metformin-induced reduction in weight, waist circumference, body mass index, and concentrations of TC, C-peptide, and cytokines, such IL-1beta, IL-6, IL-8, and TNF-alpha.	Metformin	72-81	interleukin 1 beta	Homo sapiens	206-214
22500211-5	2012	Both metformin and ionizing radiation activated AMPK leading to inactivation of mTOR and suppression of its downstream effectors such as S6K1 and 4EBP1, a crucial signaling pathway for proliferation and survival of cancer cells, in vitro as well as in the in vivo tumors.	Metformin	5-14	mechanistic target of rapamycin kinase	Homo sapiens	80-84
22500211-6	2012	CONCLUSION: Metformin kills and radiosensitizes cancer cells and eradicates radioresistant cancer stem cells by activating AMPK and suppressing mTOR.	Metformin	12-21	mechanistic target of rapamycin kinase	Homo sapiens	144-148
21349749-0	2012	The effect of oral metformin on insulin sensitivity in insulin-resistant ponies.	Metformin	19-28	insulin	Homo sapiens	32-39
21349749-1	2012	Metformin may be an effective therapeutic option for insulin-resistant (I-R) horses/ponies because, in humans, it reportedly enhances insulin sensitivity (SI) of peripheral tissues without stimulating insulin secretion.	Metformin	0-9	insulin	Homo sapiens	53-60
21349749-1	2012	Metformin may be an effective therapeutic option for insulin-resistant (I-R) horses/ponies because, in humans, it reportedly enhances insulin sensitivity (SI) of peripheral tissues without stimulating insulin secretion.	Metformin	0-9	insulin	Homo sapiens	134-141
23091851-8	2012	The CHD and MS patients who carried the Pro allele showed a significant metformin-induced reduction in weight, waist circumference, body mass index, and concentrations of TC, C-peptide, and cytokines, such IL-1beta, IL-6, IL-8, and TNF-alpha.	Metformin	72-81	interleukin 6	Homo sapiens	216-220
23091851-8	2012	The CHD and MS patients who carried the Pro allele showed a significant metformin-induced reduction in weight, waist circumference, body mass index, and concentrations of TC, C-peptide, and cytokines, such IL-1beta, IL-6, IL-8, and TNF-alpha.	Metformin	72-81	C-X-C motif chemokine ligand 8	Homo sapiens	222-226
23091851-8	2012	The CHD and MS patients who carried the Pro allele showed a significant metformin-induced reduction in weight, waist circumference, body mass index, and concentrations of TC, C-peptide, and cytokines, such IL-1beta, IL-6, IL-8, and TNF-alpha.	Metformin	72-81	tumor necrosis factor	Homo sapiens	232-241
22196251-18	2011	CONCLUSIONS: Carbohydrate restriction in conjunction with metformin and liraglutide is an effective treatment option for patients with advanced diabetes who are candidates for instituting insulin or who are in need of intensified insulin treatment.	Metformin	58-67	insulin	Homo sapiens	188-195
21958877-0	2011	Metformin regulates hepatic lipid metabolism through activating AMP-activated protein kinase and inducing ATGL in laying hens.	Metformin	0-9	patatin like phospholipase domain containing 2	Gallus gallus	106-110
22021366-3	2011	We report that AMPK activators, such as metformin and 5-aminoimidazole-4-carboxamide ribonucleotide, suppress activation of the mTOR pathway in BCR-ABL-expressing cells.	Metformin	40-49	mechanistic target of rapamycin kinase	Homo sapiens	128-132
21424914-9	2011	In the metformin group, body mass index, PPG, HbA1c, IL-6, ICAM-1, and TNF-alpha levels were significantly decreased after 12 weeks compared with the basal levels.	Metformin	7-16	interleukin 6	Homo sapiens	53-57
21424914-9	2011	In the metformin group, body mass index, PPG, HbA1c, IL-6, ICAM-1, and TNF-alpha levels were significantly decreased after 12 weeks compared with the basal levels.	Metformin	7-16	serglycin	Homo sapiens	41-44
21424914-9	2011	In the metformin group, body mass index, PPG, HbA1c, IL-6, ICAM-1, and TNF-alpha levels were significantly decreased after 12 weeks compared with the basal levels.	Metformin	7-16	tumor necrosis factor	Homo sapiens	71-80
21801267-7	2011	Treatment with metformin significantly reduced IL-6, especially in PCOS patients with IRS-2 homozygous Asp variant.	Metformin	15-24	interleukin 6	Homo sapiens	47-51
21733059-14	2011	Metformin mediates a phenotypic shift away from lipid accretion through AMPK-NAMPT-SIRT1 mediated changes in clock components, supporting chronotherapeutic treatment approaches for obesity.	Metformin	0-9	nicotinamide phosphoribosyltransferase	Mus musculus	77-82
21920351-0	2011	Metformin suppresses pregnane X receptor (PXR)-regulated transactivation of CYP3A4 gene.	Metformin	0-9	nuclear receptor subfamily 1 group I member 2	Homo sapiens	21-40
21920351-0	2011	Metformin suppresses pregnane X receptor (PXR)-regulated transactivation of CYP3A4 gene.	Metformin	0-9	nuclear receptor subfamily 1 group I member 2	Homo sapiens	42-45
21920351-0	2011	Metformin suppresses pregnane X receptor (PXR)-regulated transactivation of CYP3A4 gene.	Metformin	0-9	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	76-82
21920351-4	2011	In this study, we hypothesize that metformin suppresses the expression of CYP3A4, a main detoxification enzyme and a target gene of PXR, due to SHP up-regulation.	Metformin	35-44	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	74-80
21920351-4	2011	In this study, we hypothesize that metformin suppresses the expression of CYP3A4, a main detoxification enzyme and a target gene of PXR, due to SHP up-regulation.	Metformin	35-44	nuclear receptor subfamily 1 group I member 2	Homo sapiens	132-135
21920351-6	2011	We show that metformin dramatically suppresses PXR-mediated expression of CYP3A4 in hepatocytes.	Metformin	13-22	nuclear receptor subfamily 1 group I member 2	Homo sapiens	47-50
21920351-6	2011	We show that metformin dramatically suppresses PXR-mediated expression of CYP3A4 in hepatocytes.	Metformin	13-22	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	74-80
21920351-10	2011	We show that metformin disrupts PXR"s interaction with steroid receptor coactivator-1 (SRC1) in a two-hybrid assay independently of the PXR ligand binding pocket.	Metformin	13-22	nuclear receptor subfamily 1 group I member 2	Homo sapiens	32-35
21920351-11	2011	Metformin also inhibited vitamin D receptor-, glucocorticoid receptor- and constitutive androstane receptor (CAR)-mediated induction of CYP3A4 mRNA in human hepatocytes.	Metformin	0-9	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	136-142
21920351-12	2011	We show, therefore, a suppressive effect of metformin on PXR and other ligand-activated nuclear receptors in transactivation of the main detoxification enzyme CYP3A4 in human hepatocytes.	Metformin	44-53	nuclear receptor subfamily 1 group I member 2	Homo sapiens	57-60
21920351-12	2011	We show, therefore, a suppressive effect of metformin on PXR and other ligand-activated nuclear receptors in transactivation of the main detoxification enzyme CYP3A4 in human hepatocytes.	Metformin	44-53	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	159-165
21733059-7	2011	3T3-L1 adipocytes were incubated with metformin, EX527 or FK866, inhibitors of SIRT1 and NAMPT, respectively.	Metformin	38-47	nicotinamide phosphoribosyltransferase	Mus musculus	89-94
21733059-11	2011	Metformin increased AMPK activity in WAT of db/db mice and in metformin-treated adipocytes, with increased NAMPT, SIRT1 and circadian component expression.	Metformin	0-9	nicotinamide phosphoribosyltransferase	Mus musculus	107-112
21733059-12	2011	Metformin-mediated induction of Clock mRNA in adipocytes was blocked by inhibition of NAMPT and SIRT1.	Metformin	0-9	nicotinamide phosphoribosyltransferase	Mus musculus	86-91
21947382-9	2011	Finally, we demonstrated that the increase in AMP:ATP ratio in hepatocytes from liver-specific Ampkalpha1/2 (also known as Prkaa1/2) knockout mice and humans is due to a similar and specific inhibition of the mitochondrial respiratory-chain complex 1 by metformin.	Metformin	254-263	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	95-107
21947382-9	2011	Finally, we demonstrated that the increase in AMP:ATP ratio in hepatocytes from liver-specific Ampkalpha1/2 (also known as Prkaa1/2) knockout mice and humans is due to a similar and specific inhibition of the mitochondrial respiratory-chain complex 1 by metformin.	Metformin	254-263	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	123-131
21947382-5	2011	RESULTS: Metformin dose- and time-dependently increased AMPK activity in rat and human hepatocytes, an effect associated with a significant rise in cellular AMP:ATP ratio.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	56-60
21950959-11	2011	Further study of lifestyle and pharmacologic interventions that reduce insulin resistance, such as metformin, are needed to demonstrate that they are effective in reducing the risk of diabetes, endometrial abnormalities and cardiovascular disease events in women with polycystic ovary syndrome.	Metformin	99-108	insulin	Homo sapiens	71-78
21866433-7	2011	Patients with eGFR >= 60 ml/min/1.73 m (2) receiving contrast medium can continue metformin normally.	Metformin	85-94	epidermal growth factor receptor	Homo sapiens	14-18
21971158-0	2011	Mechanisms underlying metformin-induced secretion of glucagon-like peptide-1 from the intestinal L cell.	Metformin	22-31	glucagon	Homo sapiens	53-76
25610182-2	2011	Our aim was to examine the effect of metformin treatment either alone or in combination with non-steroidal anti-inflammatory drugs (NSAID) on plasma levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in patients with early stage MS (MS-es) and generalized MS (MS-ge).	Metformin	37-46	nerve growth factor	Homo sapiens	159-178
25610182-2	2011	Our aim was to examine the effect of metformin treatment either alone or in combination with non-steroidal anti-inflammatory drugs (NSAID) on plasma levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in patients with early stage MS (MS-es) and generalized MS (MS-ge).	Metformin	37-46	nerve growth factor	Homo sapiens	180-183
25610182-10	2011	NGF levels were decreased in both groups after treatment with metformin.	Metformin	62-71	nerve growth factor	Homo sapiens	0-3
25610182-11	2011	NGF levels were significantly higher in MS-ge patients on combined therapy than in those on metformin only.	Metformin	92-101	nerve growth factor	Homo sapiens	0-3
25610182-12	2011	CONCLUSION: The combination of metformin and NSAID treatment is more effective than metformin alone on NGF and BDNF production as well as on metabolism-related anthropometric and laboratory features.	Metformin	31-40	nerve growth factor	Homo sapiens	103-106
25610182-12	2011	CONCLUSION: The combination of metformin and NSAID treatment is more effective than metformin alone on NGF and BDNF production as well as on metabolism-related anthropometric and laboratory features.	Metformin	84-93	nerve growth factor	Homo sapiens	103-106
22158450-6	2011	The positive effects of metformin are correlated with the reduction in insulin resistance, which is responsible for both the onset and development of heart failure in diabetic patients.	Metformin	24-33	insulin	Homo sapiens	71-78
21979311-3	2011	Metformin, a drug widely used in the treatment of type II diabetes, has recently received attention owing to new findings regarding its effect on apoptosis through mitochondrial permeability transition and cytochrome c release.	Metformin	0-9	cytochrome c, somatic	Homo sapiens	206-218
21979311-11	2011	Gentamicin increased cleaved PARP and caspase-3, but metformin inhibited the expression of caspase-3 and cleavage of PARP.	Metformin	53-62	caspase 3	Homo sapiens	91-100
21979311-11	2011	Gentamicin increased cleaved PARP and caspase-3, but metformin inhibited the expression of caspase-3 and cleavage of PARP.	Metformin	53-62	poly(ADP-ribose) polymerase 1	Homo sapiens	117-121
21631893-5	2011	Metformin achieves glycemic control by reducing hepatic glucose production and increasing the muscle intake of glucose, thus lowering levels of circulating glucose and, consequently, insulin.	Metformin	0-9	insulin	Homo sapiens	183-190
21631893-6	2011	The major molecular targets of metformin are the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) signaling and mammalian target of rapamycin (mTOR) pathways, which are central in the regulation of cellular energy homeostasis and play a crucial role in the control of cell division and cell proliferation.	Metformin	31-40	mechanistic target of rapamycin kinase	Homo sapiens	122-151
21631893-6	2011	The major molecular targets of metformin are the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) signaling and mammalian target of rapamycin (mTOR) pathways, which are central in the regulation of cellular energy homeostasis and play a crucial role in the control of cell division and cell proliferation.	Metformin	31-40	mechanistic target of rapamycin kinase	Homo sapiens	153-157
22590838-9	2011	Mean blood glucose level was not significantly different in the two groups at the beginning of the ICU admission; however, mean glucose level in insulin-metformin group, twelve hours after the initiation of the study, was significantly lower than insulin group (p < 0.05).	Metformin	153-162	insulin	Homo sapiens	145-152
22203527-2	2011	Metformin"s molecular targets in cancer cells (e.g., mTOR, HER2) are similar to those currently being used for directed cancer therapy.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	53-57
22203527-2	2011	Metformin"s molecular targets in cancer cells (e.g., mTOR, HER2) are similar to those currently being used for directed cancer therapy.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	59-63
22590838-10	2011	In addition, mean doses of potassium and insulin demand as well as mean number of episodes of hyperglycemia, hypoglycemia and glucose levels out of the accepted range were significantly lower in insulin-metformin group (p < 0.05).	Metformin	203-212	insulin	Homo sapiens	41-48
20567254-0	2011	Genotype-dependent effects of inhibitors of the organic cation transporter, OCT1: predictions of metformin interactions.	Metformin	97-106	solute carrier family 22 member 1	Homo sapiens	76-80
20567254-1	2011	Common genetic variants of the liver-specific human organic cation transporter 1 (OCT1; SLC22A1) have reduced transport capacity for substrates such as the antidiabetic drug metformin.	Metformin	174-183	solute carrier family 22 member 1	Homo sapiens	52-80
20567254-1	2011	Common genetic variants of the liver-specific human organic cation transporter 1 (OCT1; SLC22A1) have reduced transport capacity for substrates such as the antidiabetic drug metformin.	Metformin	174-183	solute carrier family 22 member 1	Homo sapiens	82-86
20567254-1	2011	Common genetic variants of the liver-specific human organic cation transporter 1 (OCT1; SLC22A1) have reduced transport capacity for substrates such as the antidiabetic drug metformin.	Metformin	174-183	solute carrier family 22 member 1	Homo sapiens	88-95
19771523-3	2011	This patient demonstrated a poor response to GH therapy and developed physical and biochemical findings of insulin resistance responsive to metformin therapy.	Metformin	140-149	insulin	Homo sapiens	107-114
20567254-4	2011	In the second part OCT1-mediated (14)C-metformin uptake was studied in the presence of drugs administered concomitantly with metformin.	Metformin	39-48	solute carrier family 22 member 1	Homo sapiens	19-23
20567254-8	2011	Concomitantly administered drugs, such as verapamil and amitriptyline, revealed potential drug-drug interactions at clinical plasma concentrations of metformin for OCT1-M420del.	Metformin	150-159	solute carrier family 22 member 1	Homo sapiens	164-168
21989078-1	2011	OBJECTIVE: The aim of this study was to evaluate the effect of genetic variations in OCT1, OCT2, MATE1, MATE 2, and PMAT on the trough steady-state plasma concentration of metformin and hemoglobin A1c (Hb1Ac).	Metformin	172-181	solute carrier family 22 member 1	Homo sapiens	85-89
21989078-4	2011	RESULTS: The mean trough steady-state metformin plasma concentration was estimated to be 576 ng/ml (range, 54-4133 ng/ml, p = 0.55) and correlated to the number of reduced function alleles in OCT1 (none, one or two: 642, 542, 397 ng/ml; P = 0.001).	Metformin	38-47	solute carrier family 22 member 1	Homo sapiens	192-196
21989078-5	2011	The absolute decrease in Hb1Ac both initially and long term was also correlated to the number of reduced function alleles in OCT1 resulting in diminished pharmacodynamic effect of metformin after 6 and 24 months.	Metformin	180-189	solute carrier family 22 member 1	Homo sapiens	125-129
21946410-0	2011	IGF1/insulin receptor kinase inhibition by BMS-536924 is better tolerated than alloxan-induced hypoinsulinemia and more effective than metformin in the treatment of experimental insulin-responsive breast cancer.	Metformin	135-144	insulin like growth factor 1	Homo sapiens	0-4
21989078-6	2011	CONCLUSION: In a large cohort of type 2 diabetics, we either confirm or show for the first time: (a) an enormous (80-fold) variability in trough steady-state metformin plasma concentration, (b) OCT1 activity affects metformin steady-state pharmacokinetics, and (c) OCT1 genotype has a bearing on HbA1c during metformin treatment.	Metformin	158-167	solute carrier family 22 member 1	Homo sapiens	265-269
21989078-6	2011	CONCLUSION: In a large cohort of type 2 diabetics, we either confirm or show for the first time: (a) an enormous (80-fold) variability in trough steady-state metformin plasma concentration, (b) OCT1 activity affects metformin steady-state pharmacokinetics, and (c) OCT1 genotype has a bearing on HbA1c during metformin treatment.	Metformin	216-225	solute carrier family 22 member 1	Homo sapiens	194-198
21989078-6	2011	CONCLUSION: In a large cohort of type 2 diabetics, we either confirm or show for the first time: (a) an enormous (80-fold) variability in trough steady-state metformin plasma concentration, (b) OCT1 activity affects metformin steady-state pharmacokinetics, and (c) OCT1 genotype has a bearing on HbA1c during metformin treatment.	Metformin	216-225	solute carrier family 22 member 1	Homo sapiens	194-198
21907790-0	2011	Metformin protects against doxorubicin-induced cardiotoxicity: involvement of the adiponectin cardiac system.	Metformin	0-9	adiponectin, C1Q and collagen domain containing	Homo sapiens	82-93
21907790-2	2011	Metformin exerts cardioprotective actions via AMP-activated protein kinase (AMPK) and increases the expression of adiponectin and its receptors (adipoR1 and adipoR2) in skeletal muscle and adipose tissue, but its effect on cardiac tissue is still unknown.	Metformin	0-9	adiponectin, C1Q and collagen domain containing	Homo sapiens	114-125
21907790-8	2011	In addition, metformin up-regulated the expression of adiponectin and its receptors, adipoR1 and adipoR2, in cardiomyocytes.	Metformin	13-22	adiponectin, C1Q and collagen domain containing	Homo sapiens	54-65
21946410-5	2011	Metformin, which lowers insulin levels only in settings of hyperinsulinemia, had minimal activity in this normoinsulinemic model.	Metformin	0-9	insulin	Homo sapiens	24-31
21986525-3	2011	The organic cation transporter 1 (OCT1) is known to play an important role in cellular uptake of metformin in the liver.	Metformin	97-106	solute carrier family 22 member 1	Homo sapiens	4-32
21986525-3	2011	The organic cation transporter 1 (OCT1) is known to play an important role in cellular uptake of metformin in the liver.	Metformin	97-106	solute carrier family 22 member 1	Homo sapiens	34-38
21986525-4	2011	We show that siRNA knockdown of OCT1 reduced sensitivity of epithelial ovarian cancer cells to metformin, but interestingly not to another biguanide, phenformin, with respect to both activation of AMP kinase and inhibition of proliferation.	Metformin	95-104	solute carrier family 22 member 1	Homo sapiens	32-36
21926282-4	2011	Insulin sensitizer medication use (metformin and/or thiazolidinediones) was assessed by prescription medication inventory.	Metformin	35-44	insulin	Homo sapiens	0-7
21802961-0	2011	Elevated circulating vaspin levels were decreased by rosiglitazone therapy in T2DM patients with poor glycemic control on metformin alone.	Metformin	122-131	serpin family A member 12	Homo sapiens	21-27
21831508-10	2011	The effects of metformin and NAC on insulin sensitivity are not associated with TNF-alpha.	Metformin	15-24	insulin	Homo sapiens	36-43
21862166-4	2011	Metformin was associated with higher levels of lipids (other than LDL-C) and homocysteine (P<0.001).	Metformin	0-9	component of oligomeric golgi complex 2	Homo sapiens	66-71
22059955-20	2011	Most studies suggested that metformin led to a significant reduction in insulin resistance.	Metformin	28-37	insulin	Homo sapiens	72-79
22673924-1	2011	OBJECTIVE: The aim of the study was to determine whether metformin or vitamin E treatment for six months is effective in reducing body weight, blood pressure, and also ameliorating insulin resistance, adiponectin, and tumor necrosis factor (TNF)-alpha in obese adolescents with non-alcoholic fatty liver disease (NAFLD).	Metformin	57-66	insulin	Homo sapiens	181-188
22673924-1	2011	OBJECTIVE: The aim of the study was to determine whether metformin or vitamin E treatment for six months is effective in reducing body weight, blood pressure, and also ameliorating insulin resistance, adiponectin, and tumor necrosis factor (TNF)-alpha in obese adolescents with non-alcoholic fatty liver disease (NAFLD).	Metformin	57-66	adiponectin, C1Q and collagen domain containing	Homo sapiens	201-212
22673924-1	2011	OBJECTIVE: The aim of the study was to determine whether metformin or vitamin E treatment for six months is effective in reducing body weight, blood pressure, and also ameliorating insulin resistance, adiponectin, and tumor necrosis factor (TNF)-alpha in obese adolescents with non-alcoholic fatty liver disease (NAFLD).	Metformin	57-66	tumor necrosis factor	Homo sapiens	218-251
22673924-5	2011	Moreover, in comparingson of changes in HOMA among the groups, the metformin- treated group showed significantly improved metabolic control and insulin sensitivity (HOMA) at the end of the study.	Metformin	67-76	insulin	Homo sapiens	144-151
22673924-7	2011	CONCLUSION: These data suggest that metformin treatment is more effective than dietary advice and vitamin E treatment in reducing insulin resistance, and also in ameliorating metabolic parameters such as fasting insulin and lipid levels, in obese adolescents having NAFLD.	Metformin	36-45	insulin	Homo sapiens	130-137
22673924-7	2011	CONCLUSION: These data suggest that metformin treatment is more effective than dietary advice and vitamin E treatment in reducing insulin resistance, and also in ameliorating metabolic parameters such as fasting insulin and lipid levels, in obese adolescents having NAFLD.	Metformin	36-45	insulin	Homo sapiens	212-219
21839072-7	2011	Metformin/rosiglitazone co-treatment prevented all the in vivo and ex vivo anti-osteogenic effects of rosiglitazone monotherapy, with a reversion back to control levels of PPARgamma, Runx2/Cbfa1 and AMP-kinase phosphorylation of BMPC.	Metformin	0-9	RUNX family transcription factor 2	Rattus norvegicus	183-188
21865358-9	2011	Both simvastatin and metformin improved menstrual cyclicity and decreased hirsutism, acne, ovarian volume, body mass index, C-reactive protein, and soluble vascular cell adhesion molecule-1.	Metformin	21-30	C-reactive protein	Homo sapiens	124-142
21865358-9	2011	Both simvastatin and metformin improved menstrual cyclicity and decreased hirsutism, acne, ovarian volume, body mass index, C-reactive protein, and soluble vascular cell adhesion molecule-1.	Metformin	21-30	vascular cell adhesion molecule 1	Homo sapiens	156-189
21839072-7	2011	Metformin/rosiglitazone co-treatment prevented all the in vivo and ex vivo anti-osteogenic effects of rosiglitazone monotherapy, with a reversion back to control levels of PPARgamma, Runx2/Cbfa1 and AMP-kinase phosphorylation of BMPC.	Metformin	0-9	RUNX family transcription factor 2	Rattus norvegicus	189-194
21806981-4	2011	The expression of tumor suppressor protein p53 was increased, while the mRNA levels of anti-apoptotic Bcl-2 were reduced by metformin, as revealed by cell-based ELISA and real-time RT-PCR, respectively.	Metformin	124-133	B cell leukemia/lymphoma 2	Mus musculus	102-107
21970867-5	2011	Orlistat can be useful as an adjunct to lifestyle changes in severely obese adolescents and metformin can be used in older children and adolescents with clinical insulin resistance.	Metformin	92-101	insulin	Homo sapiens	162-169
21806981-10	2011	These data suggest that anti-melanoma effects of metformin are mediated through p21- and AMPK-independent cell cycle arrest, apoptosis and autophagy associated with p53/Bcl-2 modulation, mitochondrial damage and oxidative stress.	Metformin	49-58	B cell leukemia/lymphoma 2	Mus musculus	169-174
21700905-11	2011	We concluded that the AMPK activators AICAR and metformin inhibited transcriptional activities of PPAR-alpha and PPAR-gamma, whereas inhibition of AMPK with compound C activated both PPARs.	Metformin	48-57	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	22-26
22067284-5	2011	Since persistent constitutive DNA replication stress, particularly when paralleled by mTOR signaling, is considered to be the major cause of aging, the present findings are consistent with the notion that metformin, by reducing both DNA replication stress and mTOR-signaling, slows down aging and/or cell senescence processes.	Metformin	205-214	mechanistic target of rapamycin kinase	Homo sapiens	86-90
22067284-5	2011	Since persistent constitutive DNA replication stress, particularly when paralleled by mTOR signaling, is considered to be the major cause of aging, the present findings are consistent with the notion that metformin, by reducing both DNA replication stress and mTOR-signaling, slows down aging and/or cell senescence processes.	Metformin	205-214	mechanistic target of rapamycin kinase	Homo sapiens	260-264
21338323-5	2011	Pre-incubation with metformin (24 h, 1 mM) inhibited forskolin-, isoproterenol-, IBMX-, LPS-, IL-1beta- and TNF-alpha-induced glycerol release and prevented p(Ser554)HSL decrease and p(Ser-552)HSL increase due to lipolytic and inflammatory agents.	Metformin	20-29	interleukin 1 beta	Homo sapiens	94-102
21338323-5	2011	Pre-incubation with metformin (24 h, 1 mM) inhibited forskolin-, isoproterenol-, IBMX-, LPS-, IL-1beta- and TNF-alpha-induced glycerol release and prevented p(Ser554)HSL decrease and p(Ser-552)HSL increase due to lipolytic and inflammatory agents.	Metformin	20-29	tumor necrosis factor	Homo sapiens	108-117
21779873-0	2011	Association of the SLC30A8 missense polymorphism R325W with proinsulin levels at baseline and after lifestyle, metformin or troglitazone intervention in the Diabetes Prevention Program.	Metformin	111-120	solute carrier family 30 member 8	Homo sapiens	19-26
21779873-2	2011	In the Diabetes Prevention Program (DPP), increased proinsulin levels predicted type 2 diabetes and proinsulin levels were significantly reduced following treatment with metformin, lifestyle modification or troglitazone compared with placebo.	Metformin	170-179	insulin	Homo sapiens	52-62
21779873-2	2011	In the Diabetes Prevention Program (DPP), increased proinsulin levels predicted type 2 diabetes and proinsulin levels were significantly reduced following treatment with metformin, lifestyle modification or troglitazone compared with placebo.	Metformin	170-179	insulin	Homo sapiens	100-110
21949222-9	2011	CONCLUSIONS: Children exposed to metformin had larger measures of subcutaneous fat, but overall body fat was the same as in children whose mothers were treated with insulin alone.	Metformin	33-42	insulin	Homo sapiens	165-172
22015290-3	2011	Metformin, a commonly used diabetes drug, lowers insulin in non-breast diabetic cancer patients, likely by reducing hepatic gluconeogenesis; it also appears to have potential insulin independent direct effects on tumor cells which are mediated by activation of AMPK with downstream inhibition of mTOR.	Metformin	0-9	insulin	Homo sapiens	49-56
22015290-3	2011	Metformin, a commonly used diabetes drug, lowers insulin in non-breast diabetic cancer patients, likely by reducing hepatic gluconeogenesis; it also appears to have potential insulin independent direct effects on tumor cells which are mediated by activation of AMPK with downstream inhibition of mTOR.	Metformin	0-9	insulin	Homo sapiens	175-182
22015290-3	2011	Metformin, a commonly used diabetes drug, lowers insulin in non-breast diabetic cancer patients, likely by reducing hepatic gluconeogenesis; it also appears to have potential insulin independent direct effects on tumor cells which are mediated by activation of AMPK with downstream inhibition of mTOR.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	296-300
21949222-10	2011	Further follow-up is required to examine whether these findings persist into later life and whether children exposed to metformin will develop less visceral fat and be more insulin sensitive.	Metformin	120-129	insulin	Homo sapiens	173-180
21664031-0	2011	Does metformin influence the insulin-, IGF I- and IGF II-receptor gene expression and Akt phosphorylation in human decidualized endometrial stromal cells?	Metformin	5-14	insulin	Homo sapiens	29-36
21664031-0	2011	Does metformin influence the insulin-, IGF I- and IGF II-receptor gene expression and Akt phosphorylation in human decidualized endometrial stromal cells?	Metformin	5-14	insulin like growth factor 1	Homo sapiens	39-44
21664031-1	2011	OBJECTIVE: To assess the effects of metformin on insulin-, IGF I-, and IGF II-receptor gene expression and Akt phosphorylation in decidualized human endometrial stromal cells (ESC) after stimulation with insulin, IGF I and II.	Metformin	36-45	insulin like growth factor 1	Homo sapiens	71-76
21664031-0	2011	Does metformin influence the insulin-, IGF I- and IGF II-receptor gene expression and Akt phosphorylation in human decidualized endometrial stromal cells?	Metformin	5-14	AKT serine/threonine kinase 1	Homo sapiens	86-89
21664031-1	2011	OBJECTIVE: To assess the effects of metformin on insulin-, IGF I-, and IGF II-receptor gene expression and Akt phosphorylation in decidualized human endometrial stromal cells (ESC) after stimulation with insulin, IGF I and II.	Metformin	36-45	insulin	Homo sapiens	49-56
21664031-1	2011	OBJECTIVE: To assess the effects of metformin on insulin-, IGF I-, and IGF II-receptor gene expression and Akt phosphorylation in decidualized human endometrial stromal cells (ESC) after stimulation with insulin, IGF I and II.	Metformin	36-45	insulin like growth factor 1	Homo sapiens	59-64
24250430-3	2011	Metformin, an oral anti-hyperglycemic agent, may introduce a new treatment protocol in critically ill patients with insulin-resistance hyperglycemia.	Metformin	0-9	insulin	Homo sapiens	116-123
21764223-5	2011	Measures which enhance adipocyte insulin sensitivity--such as pioglitazone, astaxanthin, and spirulina--may also be helpful in this regard, as may agents that boost hepatocyte capacity for fatty acid oxidation, such as metformin, carnitine, hydroxycitrate, long-chain omega-3 fats, and glycine.	Metformin	219-228	insulin	Homo sapiens	33-40
21697722-7	2011	Verapamil, carvedilol, imipramine, and cimetidine were competitive inhibitors of OCT3-mediated metformin uptake (Ki 3.6-15.8 muM).	Metformin	95-104	latexin	Homo sapiens	125-128
21862872-0	2011	Potent anti-proliferative effects of metformin on trastuzumab-resistant breast cancer cells via inhibition of erbB2/IGF-1 receptor interactions.	Metformin	37-46	erb-b2 receptor tyrosine kinase 2	Homo sapiens	110-115
21926952-7	2011	CONCLUSION: This collateral diagnosis that accompanies the diagnosis of Polycystic Ovary Syndrome seems important since this type of patients could be treated with metformin or with thiazoles to reduce insulin-resistance and steatosis as well.	Metformin	164-173	insulin	Homo sapiens	202-209
21936900-4	2011	The AMP activated protein kinase (AMPK) activators, metformin and A769662, inhibited translation regulation signaling pathways, eIF4F complex formation, nascent protein synthesis in injured nerves and sodium channel-dependent excitability of sensory neurons resulting in a resolution of neuropathic allodynia.	Metformin	52-61	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	4-32
21936900-4	2011	The AMP activated protein kinase (AMPK) activators, metformin and A769662, inhibited translation regulation signaling pathways, eIF4F complex formation, nascent protein synthesis in injured nerves and sodium channel-dependent excitability of sensory neurons resulting in a resolution of neuropathic allodynia.	Metformin	52-61	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	34-38
21862872-10	2011	Metformin disrupts erbB2/IGF-1R complexes, erbB3 and IGF-1R expression and activity, as well as Src kinase and/or PI-3K/Akt signaling.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	19-24
21862872-12	2011	Our findings provide a rationale to study the effects of metformin on patients with erbB2 positive tumors treated with trastuzumab, with or without resistance.	Metformin	57-66	erb-b2 receptor tyrosine kinase 2	Homo sapiens	84-89
21862872-1	2011	We have shown that erbB2 altered breast cancer cells are less sensitive to the anti-proliferative effects of metformin than triple negative cells, and have described the differences of molecular mechanisms of metformin action by tumor subtypes.	Metformin	109-118	erb-b2 receptor tyrosine kinase 2	Homo sapiens	19-24
21862872-1	2011	We have shown that erbB2 altered breast cancer cells are less sensitive to the anti-proliferative effects of metformin than triple negative cells, and have described the differences of molecular mechanisms of metformin action by tumor subtypes.	Metformin	209-218	erb-b2 receptor tyrosine kinase 2	Homo sapiens	19-24
21862872-2	2011	We hypothesized that metformin may be more effective against trastuzumab-resistant erbB2-overexpressing breast cancer cells because it targets the critical signaling pathways that are altered with resistance.	Metformin	21-30	erb-b2 receptor tyrosine kinase 2	Homo sapiens	83-88
21679232-6	2011	Women treated with insulin had higher rates of Caesarean delivery (45.6% insulin, 37% metformin, 34% diet, P = 0.02) than women treated with metformin or diet.	Metformin	86-95	insulin	Homo sapiens	19-26
21168492-5	2011	We attempt to investigate the interaction of metformin, PR and IGF-II expression, and identify whether metformin can enhance the antitumor effect of medroxyprogesterone acetate (MPA) using Ishikawa and HEC-1B EC cell lines.	Metformin	103-112	NDC80 kinetochore complex component	Homo sapiens	202-207
22345987-1	2011	BACKGROUND: Genetic variants of the organic cation transporter (OCT1) gene could influence interindividual variation in clinical response to metformin therapy.	Metformin	141-150	solute carrier family 22 member 1	Homo sapiens	64-68
22345987-10	2011	The data observed in this study would justify further pharmacogenetic studies to potentially evaluate the role of OCT1 gene polymorphism in the therapeutic efficacy of metformin.	Metformin	168-177	solute carrier family 22 member 1	Homo sapiens	114-118
21168492-0	2011	Metformin promotes progesterone receptor expression via inhibition of mammalian target of rapamycin (mTOR) in endometrial cancer cells.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	70-99
21168492-0	2011	Metformin promotes progesterone receptor expression via inhibition of mammalian target of rapamycin (mTOR) in endometrial cancer cells.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	101-105
21168492-8	2011	The effects of metformin on PR A/B and p70S6K are partially reversed by an AMPK inhibitor.	Metformin	15-24	S100 calcium binding protein A6	Homo sapiens	28-32
21655990-11	2011	Messenger RNA expression was significantly downregulated by metformin for PDE3B (phosphodiesterase 3B, cGMP-inhibited; a critical regulator of cAMP levels that affect activation of AMP-activated protein kinase, AMPK), confirmed by immunohistochemistry, SSR3, TP53 and CCDC14.	Metformin	60-69	tumor protein p53	Homo sapiens	259-263
21411114-0	2011	Treatment with insulin sensitizer metformin improves arterial properties, metabolic parameters, and liver function in patients with nonalcoholic fatty liver disease: a randomized, placebo-controlled trial.	Metformin	34-43	insulin	Homo sapiens	15-22
21572014-13	2011	Molecular analyses suggested that altered AMP kinase phosphorylation status and low insulin levels mediate the salutary effects of metformin.	Metformin	131-140	insulin	Homo sapiens	84-91
21655990-11	2011	Messenger RNA expression was significantly downregulated by metformin for PDE3B (phosphodiesterase 3B, cGMP-inhibited; a critical regulator of cAMP levels that affect activation of AMP-activated protein kinase, AMPK), confirmed by immunohistochemistry, SSR3, TP53 and CCDC14.	Metformin	60-69	coiled-coil domain containing 14	Homo sapiens	268-274
21655990-12	2011	By ingenuity pathway analysis, the tumour necrosis factor receptor 1 (TNFR1) signaling pathway was most affected by metformin: TGFB and MEKK were upregulated and cdc42 downregulated; mTOR and AMPK pathways were also affected.	Metformin	116-125	transforming growth factor beta 1	Homo sapiens	127-131
21655990-12	2011	By ingenuity pathway analysis, the tumour necrosis factor receptor 1 (TNFR1) signaling pathway was most affected by metformin: TGFB and MEKK were upregulated and cdc42 downregulated; mTOR and AMPK pathways were also affected.	Metformin	116-125	mechanistic target of rapamycin kinase	Homo sapiens	183-187
21655990-13	2011	Gene set analysis additionally revealed that p53, BRCA1 and cell cycle pathways also had reduced expression following metformin.	Metformin	118-127	tumor protein p53	Homo sapiens	45-48
21851178-8	2011	Several proposed interventions were pharmaceutical, myostatin inhibition, losartan, Janus kinase (JAK) pathway inhibitors, and enalapril for frailty and sarcopenia, and metformin to promote the Nrf2 antiinflammation response.	Metformin	169-178	NFE2 like bZIP transcription factor 2	Homo sapiens	194-198
21696266-7	2011	RESULTS: The mean changes in TC and A1C for the rosiglitazone and metformin/sulfonylurea groups were 9 vs -10 mg/dL for TC, -2 vs -9 mg/dL for LDL-C, and -0.8% vs. -1.2% for A1C, respectively.	Metformin	66-75	component of oligomeric golgi complex 2	Homo sapiens	143-148
21752887-1	2011	CONTEXT: Insulin resistance plays a role in hepatocarcinogenesis and is decreased by metformin treatment.	Metformin	85-94	insulin	Homo sapiens	9-16
20189584-2	2011	Recent progress shed light on various factors, including adiponectin, MIF, H11K, and metformin in the activation of AMPK.	Metformin	85-94	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	116-120
21774820-5	2011	Modulation of LPS-induced adipokine production by metformin and AMPK activation might represent an alternative way to treat both, insulin resistance and breast cancer.	Metformin	50-59	insulin	Homo sapiens	130-137
21457706-11	2011	At the transcriptional levels, metformin treatment caused significant restoration in diabetic nephropathy-induced oxidative stress mRNA levels, particularly GSTalpha, NQO1, and CAT genes, whereas inhibited TNF-alpha and IL-6 pro-inflammatory genes.	Metformin	31-40	NAD(P)H quinone dehydrogenase 1	Rattus norvegicus	167-171
21774820-9	2011	Induction of IL-6 mRNA by LPS was reduced by metformin (p < 0.01), while the LPS-induced mRNA expression of the naturally occurring anti-inflammatory cytokine interleukin 1 receptor antagonist was increased (p < 0.01).	Metformin	45-54	interleukin 6	Homo sapiens	13-17
21457706-11	2011	At the transcriptional levels, metformin treatment caused significant restoration in diabetic nephropathy-induced oxidative stress mRNA levels, particularly GSTalpha, NQO1, and CAT genes, whereas inhibited TNF-alpha and IL-6 pro-inflammatory genes.	Metformin	31-40	tumor necrosis factor	Rattus norvegicus	206-215
21457706-11	2011	At the transcriptional levels, metformin treatment caused significant restoration in diabetic nephropathy-induced oxidative stress mRNA levels, particularly GSTalpha, NQO1, and CAT genes, whereas inhibited TNF-alpha and IL-6 pro-inflammatory genes.	Metformin	31-40	interleukin 6	Rattus norvegicus	220-224
21552292-6	2011	Furthermore, metformin suppressed the phosphorylation of Akt/protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in response to pressure overload in wild type mice, but not in AMPKalpha2-/- mice.	Metformin	13-22	AKT serine/threonine kinase 1	Homo sapiens	57-60
21552292-6	2011	Furthermore, metformin suppressed the phosphorylation of Akt/protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in response to pressure overload in wild type mice, but not in AMPKalpha2-/- mice.	Metformin	13-22	AKT serine/threonine kinase 1	Homo sapiens	79-82
21552292-0	2011	Metformin attenuates pressure overload-induced cardiac hypertrophy via AMPK activation.	Metformin	0-9	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	71-75
21552292-6	2011	Furthermore, metformin suppressed the phosphorylation of Akt/protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in response to pressure overload in wild type mice, but not in AMPKalpha2-/- mice.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	88-117
21552292-5	2011	RESULTS: Metformin significantly attenuated cardiac hypertrophy induced by pressure overload in wild type mice, but the antihypertrophic actions of metformin were ablated in AMPKalpha2-/- mice.	Metformin	148-157	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	174-184
21552292-6	2011	Furthermore, metformin suppressed the phosphorylation of Akt/protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in response to pressure overload in wild type mice, but not in AMPKalpha2-/- mice.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	119-123
21552292-7	2011	CONCLUSION: Long-term administration of metformin may attenuate cardiac hypertrophy induced by pressure overload in nondiabetic mice, and this attenuation is highly dependent on AMPK activation.	Metformin	40-49	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	178-182
21146883-7	2011	Significant restoration of C reactive protein (p<0.05) was noticed after metformin therapy.	Metformin	76-85	C-reactive protein	Homo sapiens	27-45
21540236-0	2011	Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	40-44
21540236-2	2011	Many studies show that metformin inhibits cancer cell viability through the inhibition of mTOR.	Metformin	23-32	mechanistic target of rapamycin kinase	Homo sapiens	90-94
21540236-4	2011	We identified REDD1 (also known as DDIT4 and RTP801), a negative regulator of mTOR, as a new molecular target of metformin.	Metformin	113-122	mechanistic target of rapamycin kinase	Homo sapiens	78-82
21540236-5	2011	We show that metformin increases REDD1 expression in a p53-dependent manner.	Metformin	13-22	tumor protein p53	Homo sapiens	55-58
21540236-6	2011	REDD1 invalidation, using siRNA or REDD1(-/-) cells, abrogates metformin inhibition of mTOR.	Metformin	63-72	mechanistic target of rapamycin kinase	Homo sapiens	87-91
21540236-8	2011	Finally, we show the contribution of p53 in mediating metformin action in prostate cancer cells.	Metformin	54-63	tumor protein p53	Homo sapiens	37-40
21540236-9	2011	These results highlight the p53/REDD1 axis as a new molecular target in anticancer therapy in response to metformin treatment.	Metformin	106-115	tumor protein p53	Homo sapiens	28-31
21410627-6	2011	Homeostasis model assessment of beta-cell function (HOMA-beta) and fasting proinsulin/insulin ratio were significantly improved with sitagliptin/metformin FDC versus metformin monotherapy.	Metformin	145-154	insulin	Homo sapiens	75-85
21410627-6	2011	Homeostasis model assessment of beta-cell function (HOMA-beta) and fasting proinsulin/insulin ratio were significantly improved with sitagliptin/metformin FDC versus metformin monotherapy.	Metformin	145-154	insulin	Homo sapiens	78-85
21455728-8	2011	In parallel, the effect of metformin on AMPK and insulin-signalling pathways was investigated in 3T3-L1 adipocytes.	Metformin	27-36	insulin	Homo sapiens	49-56
21455728-12	2011	Adipose AMPK activity was increased following metformin compared with gliclazide therapy (0.057 +- 0.007 vs 0.030 +- 0.005 [mean +- SEM] nmol min(-1) [mg lysate](-1); p < 0.005), independent of AMPK level, glycaemia or plasma adiponectin concentrations.	Metformin	46-55	adiponectin, C1Q and collagen domain containing	Homo sapiens	229-240
21709296-0	2011	Changes over time in glycemic control, insulin sensitivity, and beta-cell function in response to low-dose metformin and thiazolidinedione combination therapy in patients with impaired glucose tolerance.	Metformin	107-116	insulin	Homo sapiens	39-46
21602511-8	2011	In contrast, FoxO1 suppression by metformin was essentially accounted for by its nuclear export by metformin-activated AMPK.	Metformin	34-43	forkhead box O1	Homo sapiens	13-18
21602511-8	2011	In contrast, FoxO1 suppression by metformin was essentially accounted for by its nuclear export by metformin-activated AMPK.	Metformin	99-108	forkhead box O1	Homo sapiens	13-18
21709296-4	2011	RESULTS: Glycemic parameters and insulin sensitivity improved in the rosiglitazone/metformin arm in year 1, but deteriorated in the years thereafter as in the placebo arm.	Metformin	83-92	insulin	Homo sapiens	33-40
21619869-9	2011	Metformin activated phosphorylation of p38 mitogen-activated protein kinase (MAPK); compound C inhibited metformin-activated phosphorylation of p38 MAPK.	Metformin	0-9	mitogen-activated protein kinase 14	Homo sapiens	39-75
21550959-3	2011	RESULTS: In both insulin treatment groups, metformin/thiazolidinedione-treated patients had significantly greater improvement in A1C levels (-2.19% to -2.36%), lower end point A1C values, and lower rates of occurrence of hypoglycemia in comparison with metformin/sulfonylurea-treated patients (all P<.05).	Metformin	43-52	insulin	Homo sapiens	17-24
21550959-5	2011	CONCLUSION: In these post hoc analyses, patients with type 2 diabetes initiating premixed or basal insulin therapy and treated concomitantly with the OHA combination of metformin/thiazolidinedione at baseline demonstrated significantly greater A1C improvement with less hypoglycemia in comparison with patients treated with metformin/sulfonylurea.	Metformin	324-333	insulin	Homo sapiens	99-106
21575951-1	2011	OBJECTIVE: To study the relationship between the responsiveness to metformin in girls with androgen excess and combinations of genetic variants-as reflected in a polymorphism score-in single nucleotide polymorphisms (OCT1, STK11, and FTO genes) and in the repeat numbers within the AR and SHBG genes.	Metformin	67-76	solute carrier family 22 member 1	Homo sapiens	217-221
21619869-9	2011	Metformin activated phosphorylation of p38 mitogen-activated protein kinase (MAPK); compound C inhibited metformin-activated phosphorylation of p38 MAPK.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	39-42
21619869-10	2011	SB203580, as an inhibitor of p38 MAPK, significantly inhibited metformin-induced MUC5B mRNA expression, while U0126, as an inhibitor of ERK1/2 MAPK, had no effect.	Metformin	63-72	mitogen-activated protein kinase 1	Homo sapiens	29-32
21619869-11	2011	In addition, knockdown of p38 MAPK by p38 MAPK siRNA significantly blocked metformin-induced MUC5B mRNA expression.	Metformin	75-84	mitogen-activated protein kinase 1	Homo sapiens	26-29
21619869-11	2011	In addition, knockdown of p38 MAPK by p38 MAPK siRNA significantly blocked metformin-induced MUC5B mRNA expression.	Metformin	75-84	mitogen-activated protein kinase 1	Homo sapiens	38-41
21600878-4	2011	In this work, we have examined the effect of metformin on the expression of UPR-related markers (GRP94 and CHOP) induced by glucosamine (GlcN), 2-deoxyglucose (2-DOG) and tunicamycin (TUNI) in renal proximal tubular epithelial cells and in murine mesangial cells.	Metformin	45-54	heat shock protein 90 beta family member 1	Canis lupus familiaris	97-102
21439975-6	2011	KEY FINDINGS: The respective analyses showed that the baicalin- and the metformin and baicalin-treated groups had statistically significant increases (p <0.05) in the activity and expression of the antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) compared with vehicle- and metformin-treated groups.	Metformin	72-81	catalase	Rattus norvegicus	244-252
21740847-10	2011	Metformin also increased phosphorylation of AMPK and eNOS, and reduced the expression of TGF-beta1, basic fibroblast growth factor (bFGF), and tumor necrosis factor (TNF)-alpha.	Metformin	0-9	nitric oxide synthase 3	Homo sapiens	53-57
21501658-5	2011	Chemical activators of AMPK (AICAR [5-aminoimidazole-4-carboxamide riboside], metformin) suppressed Wnt3a-induced TCF-dependent transcriptional activity.	Metformin	78-87	hepatocyte nuclear factor 4 alpha	Homo sapiens	114-117
21740847-10	2011	Metformin also increased phosphorylation of AMPK and eNOS, and reduced the expression of TGF-beta1, basic fibroblast growth factor (bFGF), and tumor necrosis factor (TNF)-alpha.	Metformin	0-9	transforming growth factor beta 1	Homo sapiens	89-98
21740847-10	2011	Metformin also increased phosphorylation of AMPK and eNOS, and reduced the expression of TGF-beta1, basic fibroblast growth factor (bFGF), and tumor necrosis factor (TNF)-alpha.	Metformin	0-9	fibroblast growth factor 2	Homo sapiens	100-130
21740847-10	2011	Metformin also increased phosphorylation of AMPK and eNOS, and reduced the expression of TGF-beta1, basic fibroblast growth factor (bFGF), and tumor necrosis factor (TNF)-alpha.	Metformin	0-9	fibroblast growth factor 2	Homo sapiens	132-136
21740847-10	2011	Metformin also increased phosphorylation of AMPK and eNOS, and reduced the expression of TGF-beta1, basic fibroblast growth factor (bFGF), and tumor necrosis factor (TNF)-alpha.	Metformin	0-9	tumor necrosis factor	Homo sapiens	143-176
21740847-11	2011	CONCLUSIONS: Metformin has beneficial effects on cardiomyocytes, and this effect involves activation of the AMPK-eNOS pathway.	Metformin	13-22	nitric oxide synthase 3	Homo sapiens	113-117
21680296-3	2011	Metformin activates the AMP-activated protein kinase (AMPK) pathway, a major sensor of the energy status of the cell and an inhibitor of mammalian target of rapamycin (mTOR) catalytic activity, inducing a decrease in blood glucose by decreasing hepatic gluconeogenesis and stimulating glucose uptake in the muscle.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	137-166
21083860-8	2011	Fifteen (31.9%) of the 47 women randomised to metformin needed supplemental insulin.	Metformin	46-55	insulin	Homo sapiens	76-83
21680296-3	2011	Metformin activates the AMP-activated protein kinase (AMPK) pathway, a major sensor of the energy status of the cell and an inhibitor of mammalian target of rapamycin (mTOR) catalytic activity, inducing a decrease in blood glucose by decreasing hepatic gluconeogenesis and stimulating glucose uptake in the muscle.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	168-172
21388661-2	2011	METHODS: After treatment with metformin and/or cisplatin, OVCAR-3 and OVCAR-4 cellular apoptosis was assessed by flow cytometry and caspase 3/7 activity.	Metformin	30-39	caspase 3	Homo sapiens	132-141
21388661-4	2011	Modulation of protein expression of the Bcl-2 family after treatment with metformin and/or cisplatin was determined by Western blotting.	Metformin	74-83	BCL2 apoptosis regulator	Homo sapiens	40-45
21388661-6	2011	Moreover, we established that metformin can induce apoptosis in OVCAR-3 and OVCAR-4 cells by activating caspases 3/7, down-regulating Bcl-2 and Bcl-xL expression, and up-regulating Bax and Bad expression.	Metformin	30-39	caspase 3	Homo sapiens	104-117
21388661-6	2011	Moreover, we established that metformin can induce apoptosis in OVCAR-3 and OVCAR-4 cells by activating caspases 3/7, down-regulating Bcl-2 and Bcl-xL expression, and up-regulating Bax and Bad expression.	Metformin	30-39	BCL2 apoptosis regulator	Homo sapiens	134-139
21388661-6	2011	Moreover, we established that metformin can induce apoptosis in OVCAR-3 and OVCAR-4 cells by activating caspases 3/7, down-regulating Bcl-2 and Bcl-xL expression, and up-regulating Bax and Bad expression.	Metformin	30-39	BCL2 like 1	Homo sapiens	144-150
21388661-6	2011	Moreover, we established that metformin can induce apoptosis in OVCAR-3 and OVCAR-4 cells by activating caspases 3/7, down-regulating Bcl-2 and Bcl-xL expression, and up-regulating Bax and Bad expression.	Metformin	30-39	BCL2 associated X, apoptosis regulator	Homo sapiens	181-184
21609436-4	2011	RESULTS: Single agent metformin inhibited proliferation in 12 out of 19 cell lines irrespective of the BRAF mutation status, but in one NRASQ61K mutant cell line it powerfully stimulated cell growth.	Metformin	22-31	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	103-107
21840335-25	2011	Promising candidates are those that intersect with the critical signaling pathways identified above and include biguanides such as metformin that target the insulin signaling pathway, stilbenes (e.g. resveratrol) that affect sirtuin activity and drugs such as rapamycin that interact with mTOR signaling.	Metformin	131-140	mechanistic target of rapamycin kinase	Homo sapiens	289-293
21605417-2	2011	Because of the significant prevalence of insulin resistance and glucose intolerance in PCOS patients, and their putative role in ovulatory dysfunction, the use of metformin was touted as a means to improve ovulatory function and reproductive outcomes in PCOS patients.	Metformin	163-172	insulin	Homo sapiens	41-48
20034685-8	2011	In addition, combined treatment with atorvastatin and metformin reduces the post-glucose loading levels of TNF-alpha compared to metformin monotherapy.	Metformin	54-63	tumor necrosis factor	Homo sapiens	107-116
21237153-8	2011	GLP-1 based therapy is thus a novel and now well established therapy of type 2 diabetes, with a particular value in combination with metformin in patients who are inadequately controlled by metformin alone.	Metformin	190-199	glucagon	Homo sapiens	0-5
20034685-8	2011	In addition, combined treatment with atorvastatin and metformin reduces the post-glucose loading levels of TNF-alpha compared to metformin monotherapy.	Metformin	129-138	tumor necrosis factor	Homo sapiens	107-116
21677353-8	2011	Although metformin is not metabolized, the latest research has shown that it is actively transported into hepatocytes and renal tubular epithelium, by OCT1 (organic cation transporter 1, encoded by the SLC22A1 gene) and OCT2 (organic cation transporter 2, encoded by the SLC22A2 gene), respectively.	Metformin	9-18	solute carrier family 22 member 1	Homo sapiens	151-155
21677353-8	2011	Although metformin is not metabolized, the latest research has shown that it is actively transported into hepatocytes and renal tubular epithelium, by OCT1 (organic cation transporter 1, encoded by the SLC22A1 gene) and OCT2 (organic cation transporter 2, encoded by the SLC22A2 gene), respectively.	Metformin	9-18	solute carrier family 22 member 1	Homo sapiens	157-185
21677353-8	2011	Although metformin is not metabolized, the latest research has shown that it is actively transported into hepatocytes and renal tubular epithelium, by OCT1 (organic cation transporter 1, encoded by the SLC22A1 gene) and OCT2 (organic cation transporter 2, encoded by the SLC22A2 gene), respectively.	Metformin	9-18	solute carrier family 22 member 1	Homo sapiens	202-209
21415383-4	2011	RESULTS: Measures of beta-cell function and insulin sensitivity from an OGTT showed more favorable changes over time with rosiglitazone versus metformin or glyburide.	Metformin	143-152	insulin	Homo sapiens	44-51
21478464-0	2011	Metformin inhibits nuclear receptor TR4-mediated hepatic stearoyl-CoA desaturase 1 gene expression with altered insulin sensitivity.	Metformin	0-9	nuclear receptor subfamily 2, group C, member 2	Mus musculus	36-39
21478464-5	2011	RESULTS: TR4 transactivation is inhibited via phosphorylation by metformin-induced AMP-activated protein kinase (AMPK) at the amino acid serine 351, which results in the suppression of SCD1 gene expression.	Metformin	65-74	nuclear receptor subfamily 2, group C, member 2	Mus musculus	9-12
21277073-0	2011	Effect of dose escalation of metformin on clinical features, insulin sensitivity and androgen profile in polycystic ovary syndrome.	Metformin	29-38	insulin	Homo sapiens	61-68
21194687-2	2011	The use of metformin was associated with a statistically significant reduction in insulin resistance and sex hormone-binding globulin levels, a statistically significant increase in serum androgen levels, and a consequent improvement in semen characteristics.	Metformin	11-20	insulin	Homo sapiens	82-89
21194687-2	2011	The use of metformin was associated with a statistically significant reduction in insulin resistance and sex hormone-binding globulin levels, a statistically significant increase in serum androgen levels, and a consequent improvement in semen characteristics.	Metformin	11-20	sex hormone binding globulin	Homo sapiens	105-133
21465524-0	2011	Metformin sensitizes insulin signaling through AMPK-mediated PTEN down-regulation in preadipocyte 3T3-L1 cells.	Metformin	0-9	phosphatase and tensin homolog	Mus musculus	61-65
21465524-4	2011	To gain insight into the role of PTEN, we examined the effect of metformin on PTEN expression.	Metformin	65-74	phosphatase and tensin homolog	Mus musculus	78-82
21465524-5	2011	Metformin suppressed the expression of PTEN in an AMP-activated protein kinase (AMPK)-dependent manner in preadipocyte 3T3-L1 cells.	Metformin	0-9	phosphatase and tensin homolog	Mus musculus	39-43
21465524-7	2011	Metformin also increased the phosphorylation of c-Jun N-terminal kinase (JNK)-c-Jun and mammalian target of rapamycin (mTOR)-p70S6 kinase pathways.	Metformin	0-9	mitogen-activated protein kinase 8	Homo sapiens	48-71
21465524-7	2011	Metformin also increased the phosphorylation of c-Jun N-terminal kinase (JNK)-c-Jun and mammalian target of rapamycin (mTOR)-p70S6 kinase pathways.	Metformin	0-9	mitogen-activated protein kinase 8	Homo sapiens	73-76
21465524-7	2011	Metformin also increased the phosphorylation of c-Jun N-terminal kinase (JNK)-c-Jun and mammalian target of rapamycin (mTOR)-p70S6 kinase pathways.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	88-117
21307134-0	2011	The metabolic status modulates the effect of metformin on the antimullerian hormone-androgens-insulin interplay in obese women with polycystic ovary syndrome.	Metformin	45-54	insulin	Homo sapiens	94-101
21465524-7	2011	Metformin also increased the phosphorylation of c-Jun N-terminal kinase (JNK)-c-Jun and mammalian target of rapamycin (mTOR)-p70S6 kinase pathways.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	119-123
21307134-12	2011	Data were further analyzed after dividing patients on the basis of pretreatment insulinemic response to the oral glucose tolerance test; metformin was effective in reducing insulin secretion, AMH levels, and, interestingly, ovarian volume exclusively in PCOS patients with hyperinsulinism; none of these changes occurred in the normoinsulinemic group.	Metformin	137-146	insulin	Homo sapiens	80-87
21465524-9	2011	Knock-down of AMPK recovered the metformin-induced PTEN down-regulation, suggesting the involvement of AMPK in PTEN regulation.	Metformin	33-42	phosphatase and tensin homolog	Mus musculus	51-55
21465524-9	2011	Knock-down of AMPK recovered the metformin-induced PTEN down-regulation, suggesting the involvement of AMPK in PTEN regulation.	Metformin	33-42	phosphatase and tensin homolog	Mus musculus	111-115
21465524-10	2011	PTEN promoter activity was suppressed by metformin and inhibition of mTOR and JNK by pharmacologic inhibitors blocked metformin-induced PTEN promoter activity suppression.	Metformin	41-50	phosphatase and tensin homolog	Mus musculus	0-4
21465524-10	2011	PTEN promoter activity was suppressed by metformin and inhibition of mTOR and JNK by pharmacologic inhibitors blocked metformin-induced PTEN promoter activity suppression.	Metformin	118-127	phosphatase and tensin homolog	Mus musculus	0-4
21465524-10	2011	PTEN promoter activity was suppressed by metformin and inhibition of mTOR and JNK by pharmacologic inhibitors blocked metformin-induced PTEN promoter activity suppression.	Metformin	118-127	phosphatase and tensin homolog	Mus musculus	136-140
21465524-11	2011	These findings provide evidence for a novel role of AMPK on PTEN expression and thus suggest a possible mechanism by which metformin may contribute to its beneficial effects on insulin signaling.	Metformin	123-132	phosphatase and tensin homolog	Mus musculus	60-64
21277873-5	2011	In the present study we have determined the effect of metformin on neuronal insulin resistance and AD-associated characteristics in an in vitro model of "type 3 diabetes" by differentiating neuronal cell line Neuro-2a under prolonged presence of insulin.	Metformin	54-63	insulin	Homo sapiens	76-83
21422199-0	2011	Metformin induces both caspase-dependent and poly(ADP-ribose) polymerase-dependent cell death in breast cancer cells.	Metformin	0-9	poly(ADP-ribose) polymerase 1	Homo sapiens	45-72
21422199-8	2011	Metformin-induced, PARP-dependent cell death is associated with a striking enlargement of mitochondria.	Metformin	0-9	poly(ADP-ribose) polymerase 1	Homo sapiens	19-23
21277873-8	2011	The results thus demonstrate possible therapeutic efficacy of peripheral insulin-sensitizer drug metformin in AD by its ability to sensitize neuronal insulin resistance.	Metformin	97-106	insulin	Homo sapiens	73-80
21277873-8	2011	The results thus demonstrate possible therapeutic efficacy of peripheral insulin-sensitizer drug metformin in AD by its ability to sensitize neuronal insulin resistance.	Metformin	97-106	insulin	Homo sapiens	150-157
21091653-0	2011	Metformin inhibits HMGB1 release in LPS-treated RAW 264.7 cells and increases survival rate of endotoxaemic mice.	Metformin	0-9	toll-like receptor 4	Mus musculus	36-39
21532889-6	2011	Metformin-induced activation of AMPK/mTOR pathway was accompanied by decreased microvessel density and vascular endothelial growth factor expression.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	37-41
21532889-6	2011	Metformin-induced activation of AMPK/mTOR pathway was accompanied by decreased microvessel density and vascular endothelial growth factor expression.	Metformin	0-9	vascular endothelial growth factor A	Homo sapiens	103-137
21470407-4	2011	The ability of metformin to lower circulating insulin may be particularly important for the treatment of cancers known to be associated with hyperinsulinemia, such as those of the breast and colon.	Metformin	15-24	insulin	Homo sapiens	46-53
21470407-5	2011	Moreover, metformin may exhibit direct inhibitory effects on cancer cells by inhibiting mammalian target of rapamycin (mTOR) signaling and protein synthesis.	Metformin	10-19	mechanistic target of rapamycin kinase	Homo sapiens	88-117
21470407-5	2011	Moreover, metformin may exhibit direct inhibitory effects on cancer cells by inhibiting mammalian target of rapamycin (mTOR) signaling and protein synthesis.	Metformin	10-19	mechanistic target of rapamycin kinase	Homo sapiens	119-123
21147283-9	2011	Moreover, upstream stimulatory factor-1 (USF-1) specifically mediated metformin-induced SHP gene expression.	Metformin	70-79	upstream transcription factor 1	Mus musculus	10-39
21147283-9	2011	Moreover, upstream stimulatory factor-1 (USF-1) specifically mediated metformin-induced SHP gene expression.	Metformin	70-79	upstream transcription factor 1	Mus musculus	41-46
21147283-13	2011	These results suggest that metformin may stimulate osteoblast differentiation through the transactivation of Runx2 via AMPK/USF-1/SHP regulatory cascade in mouse calvaria-derived cells.	Metformin	27-36	upstream transcription factor 1	Mus musculus	124-129
20458531-1	2011	We here demonstrate that the anti-diabetic drug metformin interacts synergistically with the anti-HER2 monoclonal antibody trastuzumab (Tzb; Herceptin ) to eliminate stem/progenitor cell populations in HER2-gene-amplified breast carcinoma cells.	Metformin	48-57	erb-b2 receptor tyrosine kinase 2	Homo sapiens	98-102
20458531-1	2011	We here demonstrate that the anti-diabetic drug metformin interacts synergistically with the anti-HER2 monoclonal antibody trastuzumab (Tzb; Herceptin ) to eliminate stem/progenitor cell populations in HER2-gene-amplified breast carcinoma cells.	Metformin	48-57	erb-b2 receptor tyrosine kinase 2	Homo sapiens	202-206
20458531-2	2011	When using the mammosphere culture technique, graded concentrations of single-agent metformin (range 50-1,000 mumol/l) were found to dose-dependently reduce the number of mammospheres formed by SKBR3 (a Tzb-naive model), SKBR3 TzbR (a model of acquired auto-resistance to Tzb) and JIMT-1 (a model of refractoriness to Tzb and other HER2-targeted therapies ab initio) HER2-overexpressing breast cancer cells.	Metformin	84-93	erb-b2 receptor tyrosine kinase 2	Homo sapiens	332-336
20458531-2	2011	When using the mammosphere culture technique, graded concentrations of single-agent metformin (range 50-1,000 mumol/l) were found to dose-dependently reduce the number of mammospheres formed by SKBR3 (a Tzb-naive model), SKBR3 TzbR (a model of acquired auto-resistance to Tzb) and JIMT-1 (a model of refractoriness to Tzb and other HER2-targeted therapies ab initio) HER2-overexpressing breast cancer cells.	Metformin	84-93	erb-b2 receptor tyrosine kinase 2	Homo sapiens	367-371
21091653-2	2011	This study investigated the effect of metformin on the expression of pro-inflammatory cytokines including high mobility group box 1 (HMGB1) in lipopolysaccharide (LPS)-treated animals and cells.	Metformin	38-47	toll-like receptor 4	Mus musculus	163-166
21091653-3	2011	EXPERIMENTAL APPROACH: We investigated whether metformin inhibits the release of HMGB1 in LPS-treated RAW 264.7 cells and increases survival rate in endotoxaemic mice (lethal endotoxaemia was induced by an i.p.	Metformin	47-56	toll-like receptor 4	Mus musculus	90-93
21091653-6	2011	KEY RESULTS: Both pre- and post-treatment with metformin significantly improved survival of animals during lethal endotoxaemia (survival rate was monitored up to 2 weeks), decreased serum levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta, HMGB1 expression and myeloperoxidase activity in lungs.	Metformin	47-56	tumor necrosis factor	Mus musculus	228-237
21091653-6	2011	KEY RESULTS: Both pre- and post-treatment with metformin significantly improved survival of animals during lethal endotoxaemia (survival rate was monitored up to 2 weeks), decreased serum levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta, HMGB1 expression and myeloperoxidase activity in lungs.	Metformin	47-56	interleukin 1 beta	Mus musculus	240-257
21091653-10	2011	Compound C (pharmacological inhibitor of AMPK) and siAMPKalpha1 reversed the anti-inflammatory effect of metformin in LPS-treated cells.	Metformin	105-114	toll-like receptor 4	Mus musculus	118-121
21091653-11	2011	CONCLUSIONS AND IMPLICATIONS: Our data indicate that metformin significantly attenuates the pro-inflammatory response induced by LPS both in vivo and in vitro.	Metformin	53-62	toll-like receptor 4	Mus musculus	129-132
21635988-16	2011	An aggressive regimen including metformin, a thiazolidinedione, and a GLP-1 receptor agonist may improve insulin sensitivity and enhance beta-cell function.	Metformin	32-41	insulin	Homo sapiens	105-112
21368581-0	2011	Micro(mi)RNA expression profile of breast cancer epithelial cells treated with the anti-diabetic drug metformin: induction of the tumor suppressor miRNA let-7a and suppression of the TGFbeta-induced oncomiR miRNA-181a.	Metformin	102-111	transforming growth factor beta 1	Homo sapiens	183-190
21368581-6	2011	We then explored the ability of metformin to impede TGFbeta-enhanced propensity of breast cancer stem cells to form mammospheres in a miRNA-181a-related manner.	Metformin	32-41	transforming growth factor beta 1	Homo sapiens	52-59
21368581-8	2011	In addition, metformin co-treatment fully prevented TGFbeta-induced down-regulation of the tumor suppressor miRNA-96 (~10-fold).	Metformin	13-22	transforming growth factor beta 1	Homo sapiens	52-59
21368581-8	2011	In addition, metformin co-treatment fully prevented TGFbeta-induced down-regulation of the tumor suppressor miRNA-96 (~10-fold).	Metformin	13-22	microRNA 96	Homo sapiens	108-116
21368581-9	2011	Metformin"s molecular functioning to prevent invasive breast cancer can be explained in terms of its previously unrecognized ability to efficiently up-regulate the tumor-suppressive miRNAs let-7a & miRNA-96 and inhibit the oncogenic miRNA-181a, thus epigenetically preserving the differentiated phenotype of mammary epithelium while preventing EMT-related cancer-initiating cell self-renewal.	Metformin	0-9	microRNA 96	Homo sapiens	202-210
21435929-8	2011	Renal complications were not monitored carefully enough (missing value for albuminuria: 42%; -4.5 points), and 46% of those with a glomerular filtration rate less than 60 mL/min/1.73 m2 were taking metformin.	Metformin	198-207	CD59 molecule (CD59 blood group)	Homo sapiens	174-179
21735693-12	2011	The metformin therapy improved insulin sensitivity as evidenced by an increase in ISI by 41.5% (p = 0.0005).	Metformin	4-13	insulin	Homo sapiens	31-38
21236717-2	2011	In healthy individuals, metformin affects glucose, vitamin B12 and the digestive uptake of bile salts.	Metformin	24-33	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	59-62
21735693-15	2011	CONCLUSIONS: Metformin administration decreases the circulating PAI-1 concentration and simultaneously improves insulin sensitivity and BMI in PCOS women with hyperinsulinemia.	Metformin	13-22	insulin	Homo sapiens	112-119
20455996-7	2011	Both drugs affected signalling in the protein kinases B (AKT)/mammalian target of rapamycin pathway; metformin activated adenosine monophosphate (AMP)-activated protein kinase whereas rosiglitazone increased chromosome ten level.	Metformin	101-110	AKT serine/threonine kinase 1	Homo sapiens	57-60
20857458-0	2011	Metformin induces Rab4 through AMPK and modulates GLUT4 translocation in skeletal muscle cells.	Metformin	0-9	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	50-55
20857458-5	2011	Metformin stimulated the phosphorylation of AS160, Akt substrate, and Rab GTPase activating protein (GAP), and also increased the phosphorylation of PKC-zeta, which is a critical molecule for glucose uptake.	Metformin	0-9	thymoma viral proto-oncogene 1	Mus musculus	51-54
20857458-11	2011	Together, these results demonstrate that metformin induces Rab4 expression via AMPK-AS160-PKC-zeta and modulates insulin-mediated GLUT4 translocation.	Metformin	41-50	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	130-135
21102522-0	2011	Diet and tumor LKB1 expression interact to determine sensitivity to anti-neoplastic effects of metformin in vivo.	Metformin	95-104	serine/threonine kinase 11	Mus musculus	15-19
21316309-0	2011	Metformin modulates IL-8, IL-1beta, ICAM and IGFBP-1 expression in human endometrial stromal cells.	Metformin	0-9	C-X-C motif chemokine ligand 8	Homo sapiens	20-24
21316309-0	2011	Metformin modulates IL-8, IL-1beta, ICAM and IGFBP-1 expression in human endometrial stromal cells.	Metformin	0-9	interleukin 1 beta	Homo sapiens	26-34
21316309-7	2011	The negative effect of insulin on IL-8 (4.8 fold) and IL-1beta (9.3 fold) gene expression was similarly found in cells incubated with metformin.	Metformin	134-143	insulin	Homo sapiens	23-30
21316309-7	2011	The negative effect of insulin on IL-8 (4.8 fold) and IL-1beta (9.3 fold) gene expression was similarly found in cells incubated with metformin.	Metformin	134-143	C-X-C motif chemokine ligand 8	Homo sapiens	34-38
21316309-7	2011	The negative effect of insulin on IL-8 (4.8 fold) and IL-1beta (9.3 fold) gene expression was similarly found in cells incubated with metformin.	Metformin	134-143	interleukin 1 beta	Homo sapiens	54-62
21102522-2	2011	We treated both tumor LKB1 expression and host diet as variables, and observed that metformin inhibited tumor growth and reduced insulin receptor activation in tumors of mice with diet-induced hyperinsulinemia, independent of tumor LKB1 expression.	Metformin	84-93	serine/threonine kinase 11	Mus musculus	22-26
21102522-3	2011	In the absence of hyperinsulinemia, metformin inhibited only the growth of tumors transfected with short hairpin RNA against LKB1, a finding attributable neither to an effect on host insulin level nor to activation of AMPK within the tumor.	Metformin	36-45	serine/threonine kinase 11	Mus musculus	125-129
21102522-4	2011	Further investigation in vitro showed that cells with reduced LKB1 expression are more sensitive to metformin-induced adenosine triphosphate depletion owing to impaired ability to activate LKB1-AMPK-dependent energy-conservation mechanisms.	Metformin	100-109	serine/threonine kinase 11	Mus musculus	62-66
21102522-5	2011	Thus, loss of function of LKB1 can accelerate proliferation in contexts where it functions as a tumor suppressor, but can also sensitize cells to metformin.	Metformin	146-155	serine/threonine kinase 11	Mus musculus	26-30
21102522-6	2011	These findings predict that any clinical utility of metformin or similar compounds in oncology will be restricted to subpopulations defined by host insulin levels and/or loss of function of LKB1.	Metformin	52-61	serine/threonine kinase 11	Mus musculus	190-194
21054339-0	2011	Metformin inhibits P-glycoprotein expression via the NF-kappaB pathway and CRE transcriptional activity through AMPK activation.	Metformin	0-9	ATP binding cassette subfamily B member 1	Homo sapiens	19-33
21054339-2	2011	We investigated whether metformin (1,1-dimethylbiguanide hydrochloride) down-regulates MDR1 expression in MCF-7/adriamycin (MCF-7/adr) cells.	Metformin	24-33	ATP binding cassette subfamily B member 1	Homo sapiens	87-91
21054339-2	2011	We investigated whether metformin (1,1-dimethylbiguanide hydrochloride) down-regulates MDR1 expression in MCF-7/adriamycin (MCF-7/adr) cells.	Metformin	35-70	ATP binding cassette subfamily B member 1	Homo sapiens	87-91
21054339-5	2011	KEY RESULTS: Metformin significantly inhibited MDR1 expression by blocking MDR1 gene transcription.	Metformin	13-22	ATP binding cassette subfamily B member 1	Homo sapiens	47-51
21054339-5	2011	KEY RESULTS: Metformin significantly inhibited MDR1 expression by blocking MDR1 gene transcription.	Metformin	13-22	ATP binding cassette subfamily B member 1	Homo sapiens	75-79
21054339-6	2011	Metformin also significantly increased the intracellular accumulation of the fluorescent P-gp substrate rhodamine-123.	Metformin	0-9	ATP binding cassette subfamily B member 1	Homo sapiens	89-93
21054339-8	2011	Moreover, transduction of MCF-7/adr cells with the p65 subunit of NF-kappaB induced MDR1 promoter activity and expression, and this effect was attenuated by metformin.	Metformin	157-166	ATP binding cassette subfamily B member 1	Homo sapiens	84-88
21054339-9	2011	The suppression of MDR1 promoter activity and protein expression was mediated through metformin-induced activation of AMP-activated protein kinase (AMPK).	Metformin	86-95	ATP binding cassette subfamily B member 1	Homo sapiens	19-23
21054339-10	2011	Small interfering RNA methods confirmed that reduction of AMPK levels attenuates the inhibition of MDR1 activation associated with metformin exposure.	Metformin	131-140	ATP binding cassette subfamily B member 1	Homo sapiens	99-103
21054339-11	2011	Furthermore, the inhibitory effects of metformin on MDR1 expression and cAMP-responsive element binding protein (CREB) phosphorylation were reversed by overexpression of a dominant-negative mutant of AMPK.	Metformin	39-48	ATP binding cassette subfamily B member 1	Homo sapiens	52-56
21054339-12	2011	CONCLUSIONS AND IMPLICATIONS: These results suggest that metformin activates AMPK and suppresses MDR1 expression in MCF-7/adr cells by inhibiting the activation of NF-kappaB and CREB.	Metformin	57-66	ATP binding cassette subfamily B member 1	Homo sapiens	97-101
21282369-3	2011	RESEARCH DESIGN AND METHODS: We explored the effects of metformin on the expression of HIF-1alpha using human renal proximal tubular epithelial cells (HRPTECs).	Metformin	56-65	hypoxia inducible factor 1 subunit alpha	Homo sapiens	87-97
21518564-14	2011	CONCLUSIONS: Metformin can improve insulin resistance and imbalance of endocrine hormones.	Metformin	13-22	insulin	Homo sapiens	35-42
21518564-17	2011	Our study might suggest that metformin is the better choice in PCOS patients with serious obese and rosiglitazone plus metformin would be more effective in patients with severe insulin resistance or those do not respond to metformin.	Metformin	119-128	insulin	Homo sapiens	177-184
21518564-17	2011	Our study might suggest that metformin is the better choice in PCOS patients with serious obese and rosiglitazone plus metformin would be more effective in patients with severe insulin resistance or those do not respond to metformin.	Metformin	119-128	insulin	Homo sapiens	177-184
21209024-0	2011	Phosphorylation and activation of AMP-activated protein kinase (AMPK) by metformin in the human ovary requires insulin.	Metformin	73-82	insulin	Homo sapiens	111-118
21209024-3	2011	In the ovary, metformin directly decreased estradiol and progesterone production by human granulosa cells, and inhibition of progesterone production by metformin in rat granulosa cells caused an increase in phosphorylated AMPK (pAMPK).	Metformin	152-161	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	222-226
21209024-8	2011	The addition of compound C, an inhibitor of AMPK, negated the effect of metformin in the presence of insulin on pAMPK.	Metformin	72-81	insulin	Homo sapiens	101-108
21209024-10	2011	In summary, the presence of insulin was required to cause a metformin-induced increase in pAMPK in these human ovarian cells.	Metformin	60-69	insulin	Homo sapiens	28-35
21209024-11	2011	Although previous data suggest that metformin may act via an insulin-independent pathway, our results therefore imply that insulin may be required to initiate an effect.	Metformin	36-45	insulin	Homo sapiens	61-68
21209024-11	2011	Although previous data suggest that metformin may act via an insulin-independent pathway, our results therefore imply that insulin may be required to initiate an effect.	Metformin	36-45	insulin	Homo sapiens	123-130
21285388-7	2011	CONCLUSIONS: In metformin-treated patients, exenatide BID was noninferior to PIA for glycemic control but superior for hypoglycemia and weight control.	Metformin	16-25	BH3 interacting domain death agonist	Homo sapiens	54-57
21209036-6	2011	The KGN granulosa-cell line was used to investigate the effect of insulin and metformin on Akt activation and glucose transporter-4 (Glut-4) expression.	Metformin	78-87	AKT serine/threonine kinase 1	Homo sapiens	91-94
21088829-1	2011	OBJECTIVE: To compare the effect of metformin and sulphonylureas on the risks of switching to insulin therapy, hospitalisation for macrovascular disease and all-cause mortality.	Metformin	36-45	insulin	Homo sapiens	94-101
21088829-4	2011	RESULTS: Compared with patients who started on metformin, those who started on sulphonylureas were at a higher risk of switching to insulin (adjusted hazard ratio and 95% CI, 1.55; 1.43, 1.68), hospitalisation (1.15; 1.08, 1.21), and death (1.37; 1.26, 1.49).	Metformin	47-56	insulin	Homo sapiens	132-139
21088829-6	2011	The risks of switching to insulin and hospitalisation were both increased among patients who switched from metformin to another oral hypoglycaemic agent or combined initial monotherapy with another agent.	Metformin	107-116	insulin	Homo sapiens	26-33
21209036-0	2011	Action of metformin on the insulin-signaling pathway and on glucose transport in human granulosa cells.	Metformin	10-19	insulin	Homo sapiens	27-34
21209036-1	2011	CONTEXT: Hyperinsulinemia in polycystic ovary syndrome is widely treated with the insulin sensitizer metformin, which, in addition to its systemic effects, directly affects the ovarian insulin-stimulated steroidogenesis pathway.	Metformin	101-110	insulin	Homo sapiens	14-21
21209036-2	2011	OBJECTIVE: Our aim was to investigate the interaction of metformin with the other insulin-stimulated ovarian pathway, namely that leading to glucose uptake.	Metformin	57-66	insulin	Homo sapiens	82-89
21209036-5	2011	MAIN OUTCOME MEASURES: The effect of metformin on insulin-receptor substrate proteins 1 and 2 (IRS-1 and -2) mRNA and protein expression was determined.	Metformin	37-46	insulin	Homo sapiens	50-57
21209036-11	2011	Metformin in the presence of insulin activated Akt and this was dependent on phosphoinositide-3 kinase, as was translocation of Glut-4 to the membrane.	Metformin	0-9	insulin	Homo sapiens	29-36
21040499-8	2011	The addition of metformin to rosiglitazone decreased insulin resistance and reduced weight gain, but had no additional effect on beta-cell mass.	Metformin	16-25	insulin	Homo sapiens	53-60
21040499-10	2011	Although the combination of rosiglitazone and metformin did not affect beta-cell mass at 26 weeks of age, it did result in reduced body weight and insulin resistance.	Metformin	46-55	insulin	Homo sapiens	147-154
21040499-11	2011	CONCLUSION: The results of the present study suggest that the addition of metformin to rosiglitazone improves the metabolic profile through an effect on insulin resistance and not beta-cell mass.	Metformin	74-83	insulin	Homo sapiens	153-160
21209036-11	2011	Metformin in the presence of insulin activated Akt and this was dependent on phosphoinositide-3 kinase, as was translocation of Glut-4 to the membrane.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	47-50
21209036-12	2011	Metformin was able to substantially enhance the insulin-stimulated translocation of Glut-4 transporters from the cytosol to the membrane.	Metformin	0-9	insulin	Homo sapiens	48-55
21419041-0	2011	[Effects of antidiabetic drug metformin on human breast carcinoma cells with different estrogen receptor expressing in vitro].	Metformin	30-39	estrogen receptor 1	Homo sapiens	87-104
21419041-1	2011	AIM: To research different effects of human breast carcinoma cells with different estrogen receptor expressing by antidiabetic drug metformin, and preliminary explore the possible underlying molecular mechanisms.	Metformin	132-141	estrogen receptor 1	Homo sapiens	82-99
21419041-12	2011	CONCLUSION: The effect of metformin for human breast carcinoma cell with estrogen receptor was better than the one without estrogen receptor.	Metformin	26-35	estrogen receptor 1	Homo sapiens	73-90
21419041-12	2011	CONCLUSION: The effect of metformin for human breast carcinoma cell with estrogen receptor was better than the one without estrogen receptor.	Metformin	26-35	estrogen receptor 1	Homo sapiens	123-140
21262823-5	2011	We find that metformin stimulates AMPK, resulting in inhibition of both CFTR and the mTOR pathways.	Metformin	13-22	CF transmembrane conductance regulator	Homo sapiens	72-76
21262823-5	2011	We find that metformin stimulates AMPK, resulting in inhibition of both CFTR and the mTOR pathways.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	85-89
21241070-17	2011	However, intersubject differences in the levels of expression of OCT1 and OCT3 in the liver are very large and may contribute more to the variations in the hepatic uptake and clinical effect of metformin.	Metformin	194-203	solute carrier family 22 member 1	Homo sapiens	65-69
21143620-0	2011	Metformin improves cardiac function in rats via activation of AMP-activated protein kinase.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	62-90
21143620-12	2011	These beneficial effects of metformin were associated with increased AMPK and eNOS phosphorylation, as well as reductions in insulin, TGF-beta1, basic fibroblast growth factor and tumour necrosis factor-alpha levels in the circulation and/or myocardium.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	69-73
21143620-12	2011	These beneficial effects of metformin were associated with increased AMPK and eNOS phosphorylation, as well as reductions in insulin, TGF-beta1, basic fibroblast growth factor and tumour necrosis factor-alpha levels in the circulation and/or myocardium.	Metformin	28-37	transforming growth factor, beta 1	Rattus norvegicus	134-143
21143620-14	2011	The results indicate that chronic low-dose metformin confers significant cardioprotective effects against chronic heart failure by activating the AMPK-eNOS pathway.	Metformin	43-52	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	146-150
20972533-0	2011	Metformin regulates the incretin receptor axis via a pathway dependent on peroxisome proliferator-activated receptor-alpha in mice.	Metformin	0-9	peroxisome proliferator activated receptor alpha	Mus musculus	74-122
20972533-4	2011	METHODS: Metformin action was assessed in Glp1r(-/-), Gipr(-/-), Glp1r:Gipr(-/-), Pparalpha (also known as Ppara)(-/-) and hyperglycaemic obese wild-type mice with or without the GLP-1 receptor (GLP1R) antagonist exendin(9-39).	Metformin	9-18	peroxisome proliferator activated receptor alpha	Mus musculus	82-91
21116606-5	2011	Moreover, they show that metformin enhances the expression of the genes encoding the receptors for both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in mouse islets and also increases the effects of GIP and GLP-1 on insulin secretion from beta cells.	Metformin	25-34	gastric inhibitory polypeptide	Mus musculus	114-158
21116606-5	2011	Moreover, they show that metformin enhances the expression of the genes encoding the receptors for both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in mouse islets and also increases the effects of GIP and GLP-1 on insulin secretion from beta cells.	Metformin	25-34	gastric inhibitory polypeptide	Mus musculus	160-163
20972533-4	2011	METHODS: Metformin action was assessed in Glp1r(-/-), Gipr(-/-), Glp1r:Gipr(-/-), Pparalpha (also known as Ppara)(-/-) and hyperglycaemic obese wild-type mice with or without the GLP-1 receptor (GLP1R) antagonist exendin(9-39).	Metformin	9-18	peroxisome proliferator activated receptor alpha	Mus musculus	82-87
20972533-9	2011	Levels of mRNA transcripts for Glp1r, Gipr and Pparalpha were significantly increased in islets from metformin-treated mice.	Metformin	101-110	peroxisome proliferator activated receptor alpha	Mus musculus	47-56
20972533-12	2011	CONCLUSIONS/INTERPRETATION: As metformin modulates multiple components of the incretin axis, and enhances expression of the Glp1r and related insulinotropic islet receptors through a mechanism requiring PPAR-alpha, metformin may be mechanistically well suited for combination with incretin-based therapies.	Metformin	31-40	peroxisome proliferator activated receptor alpha	Mus musculus	203-213
21116606-5	2011	Moreover, they show that metformin enhances the expression of the genes encoding the receptors for both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in mouse islets and also increases the effects of GIP and GLP-1 on insulin secretion from beta cells.	Metformin	25-34	gastric inhibitory polypeptide	Mus musculus	215-218
21116606-6	2011	Interestingly, these incretin-sensitising effects of metformin appear to be mediated by a peroxisome proliferator-activated receptor alpha-dependent pathway, as opposed to the more commonly ascribed pathway of metformin action involving AMP-activated protein kinase.	Metformin	53-62	peroxisome proliferator activated receptor alpha	Mus musculus	90-138
21228310-2	2011	Our objective was to determine whether metformin treatment causes weight loss and improves obesity-related comorbidities in obese children, who are insulin-resistant.	Metformin	39-48	insulin	Homo sapiens	148-155
21199262-2	2011	Efficacy with metformin therapy is usually of limited duration, which necessitates the early introduction of one or two additional oral agents or the initiation of injections, glucagon-like peptide-1 (GLP-1) agonists or insulin.	Metformin	14-23	glucagon	Homo sapiens	176-199
21199262-2	2011	Efficacy with metformin therapy is usually of limited duration, which necessitates the early introduction of one or two additional oral agents or the initiation of injections, glucagon-like peptide-1 (GLP-1) agonists or insulin.	Metformin	14-23	glucagon	Homo sapiens	201-206
21199262-2	2011	Efficacy with metformin therapy is usually of limited duration, which necessitates the early introduction of one or two additional oral agents or the initiation of injections, glucagon-like peptide-1 (GLP-1) agonists or insulin.	Metformin	14-23	insulin	Homo sapiens	220-227
21228310-7	2011	Fasting plasma glucose (P = 0.007) and homeostasis model assessment (HOMA) insulin resistance index (P = 0.006) also improved more in metformin-treated children than in placebo-treated children.	Metformin	134-143	insulin	Homo sapiens	75-82
21270604-8	2011	In addition, medroxyprogesterone acetate-induced mTOR phosphorylation was blocked by metformin.	Metformin	85-94	mechanistic target of rapamycin kinase	Homo sapiens	49-53
21031343-0	2011	Effects of rosiglitazone/metformin fixed-dose combination therapy and metformin monotherapy on serum vaspin, adiponectin and IL-6 levels in drug-naive patients with type 2 diabetes.	Metformin	70-79	serpin family A member 12	Homo sapiens	101-107
21031343-12	2011	CONCLUSIONS: Both rosiglitazone/metformin combination therapy and metformin monotherapy decreased serum vaspin levels through glucose and insulin sensitivity regulation, while they exerted differential effects on adiponectin, IL-6 and other cardiovascular risk factors in drug-naive patients with T2DM.	Metformin	32-41	serpin family A member 12	Homo sapiens	104-110
21031343-12	2011	CONCLUSIONS: Both rosiglitazone/metformin combination therapy and metformin monotherapy decreased serum vaspin levels through glucose and insulin sensitivity regulation, while they exerted differential effects on adiponectin, IL-6 and other cardiovascular risk factors in drug-naive patients with T2DM.	Metformin	32-41	insulin	Homo sapiens	138-145
21031343-12	2011	CONCLUSIONS: Both rosiglitazone/metformin combination therapy and metformin monotherapy decreased serum vaspin levels through glucose and insulin sensitivity regulation, while they exerted differential effects on adiponectin, IL-6 and other cardiovascular risk factors in drug-naive patients with T2DM.	Metformin	66-75	serpin family A member 12	Homo sapiens	104-110
21031343-12	2011	CONCLUSIONS: Both rosiglitazone/metformin combination therapy and metformin monotherapy decreased serum vaspin levels through glucose and insulin sensitivity regulation, while they exerted differential effects on adiponectin, IL-6 and other cardiovascular risk factors in drug-naive patients with T2DM.	Metformin	66-75	insulin	Homo sapiens	138-145
21031343-12	2011	CONCLUSIONS: Both rosiglitazone/metformin combination therapy and metformin monotherapy decreased serum vaspin levels through glucose and insulin sensitivity regulation, while they exerted differential effects on adiponectin, IL-6 and other cardiovascular risk factors in drug-naive patients with T2DM.	Metformin	66-75	adiponectin, C1Q and collagen domain containing	Homo sapiens	213-224
21031343-12	2011	CONCLUSIONS: Both rosiglitazone/metformin combination therapy and metformin monotherapy decreased serum vaspin levels through glucose and insulin sensitivity regulation, while they exerted differential effects on adiponectin, IL-6 and other cardiovascular risk factors in drug-naive patients with T2DM.	Metformin	66-75	interleukin 6	Homo sapiens	226-230
21270604-9	2011	Metformin abolishes mTOR phosphorylation and inhibits GloI expression, attenuating proliferation and inducing apoptosis in progestin-resistant Ishikawa cells.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	20-24
21084384-7	2011	A 24 h exposure to metformin stimulated AMP-activated protein kinase (AMPK), suppressed activation of translation factors- both the mammalian target of rapamycin (mTOR; also known as mechanistic target of rapamycin, MTOR)-dependent ones (eukaryotic initiation factor 4E-binding protein 1 and ribosomal protein S6) and the mTOR-independent eukaryotic elongation factor 2-, and inhibited protein synthesis; a 72 h exposure resulted in 50% dead cells.	Metformin	19-28	mechanistic target of rapamycin kinase	Homo sapiens	132-161
21389294-6	2011	Glucagon-like peptide-1 agonists may be used alone in patients intolerant of metformin or in combination with metformin, thiazolidinediones, and sulfonylureas (or in any combination therereof).	Metformin	77-86	glucagon	Homo sapiens	0-23
21389294-6	2011	Glucagon-like peptide-1 agonists may be used alone in patients intolerant of metformin or in combination with metformin, thiazolidinediones, and sulfonylureas (or in any combination therereof).	Metformin	110-119	glucagon	Homo sapiens	0-23
21084384-7	2011	A 24 h exposure to metformin stimulated AMP-activated protein kinase (AMPK), suppressed activation of translation factors- both the mammalian target of rapamycin (mTOR; also known as mechanistic target of rapamycin, MTOR)-dependent ones (eukaryotic initiation factor 4E-binding protein 1 and ribosomal protein S6) and the mTOR-independent eukaryotic elongation factor 2-, and inhibited protein synthesis; a 72 h exposure resulted in 50% dead cells.	Metformin	19-28	mechanistic target of rapamycin kinase	Homo sapiens	163-167
21084384-7	2011	A 24 h exposure to metformin stimulated AMP-activated protein kinase (AMPK), suppressed activation of translation factors- both the mammalian target of rapamycin (mTOR; also known as mechanistic target of rapamycin, MTOR)-dependent ones (eukaryotic initiation factor 4E-binding protein 1 and ribosomal protein S6) and the mTOR-independent eukaryotic elongation factor 2-, and inhibited protein synthesis; a 72 h exposure resulted in 50% dead cells.	Metformin	19-28	mechanistic target of rapamycin kinase	Homo sapiens	216-220
21084384-7	2011	A 24 h exposure to metformin stimulated AMP-activated protein kinase (AMPK), suppressed activation of translation factors- both the mammalian target of rapamycin (mTOR; also known as mechanistic target of rapamycin, MTOR)-dependent ones (eukaryotic initiation factor 4E-binding protein 1 and ribosomal protein S6) and the mTOR-independent eukaryotic elongation factor 2-, and inhibited protein synthesis; a 72 h exposure resulted in 50% dead cells.	Metformin	19-28	mechanistic target of rapamycin kinase	Homo sapiens	322-326
21119073-1	2011	BACKGROUND: Preliminary evidence suggests that metformin may decrease breast cancer risk by decreasing insulin levels and reducing cell proliferation.	Metformin	47-56	insulin	Homo sapiens	103-110
21128816-0	2011	Metformin treatment for small benign thyroid nodules in patients with insulin resistance.	Metformin	0-9	insulin	Homo sapiens	70-77
20680652-1	2011	Substrates for the Organic Cation Transporter 1, encoded by the SLC22A1 gene, are metformin, amantadine, pramipexole, and, possibly, levodopa.	Metformin	82-91	solute carrier family 22 member 1	Homo sapiens	19-47
20680652-1	2011	Substrates for the Organic Cation Transporter 1, encoded by the SLC22A1 gene, are metformin, amantadine, pramipexole, and, possibly, levodopa.	Metformin	82-91	solute carrier family 22 member 1	Homo sapiens	64-71
21187071-2	2011	An AMPK activator (AICAR or metformin) stimulated osteoblast differentiation with increases in ALP and OC protein production as well as the induction of AMPK phosphorylation in MC3T3E1 cells.	Metformin	28-37	alopecia, recessive	Mus musculus	95-98
21114978-0	2011	Metformin reduces cisplatin-mediated apoptotic death of cancer cells through AMPK-independent activation of Akt.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	108-111
21114978-8	2011	On the other hand, metformin induced Akt activation in cisplatin-treated cells and Akt inhibitor 10-DEBC hydrochloride or phosphoinositide 3-kinase/Akt inhibitor LY294002 abolished metformin-mediated antioxidant and antiapoptotic effects.	Metformin	19-28	AKT serine/threonine kinase 1	Homo sapiens	37-40
21114978-8	2011	On the other hand, metformin induced Akt activation in cisplatin-treated cells and Akt inhibitor 10-DEBC hydrochloride or phosphoinositide 3-kinase/Akt inhibitor LY294002 abolished metformin-mediated antioxidant and antiapoptotic effects.	Metformin	19-28	AKT serine/threonine kinase 1	Homo sapiens	83-86
21114978-8	2011	On the other hand, metformin induced Akt activation in cisplatin-treated cells and Akt inhibitor 10-DEBC hydrochloride or phosphoinositide 3-kinase/Akt inhibitor LY294002 abolished metformin-mediated antioxidant and antiapoptotic effects.	Metformin	19-28	AKT serine/threonine kinase 1	Homo sapiens	83-86
21114978-8	2011	On the other hand, metformin induced Akt activation in cisplatin-treated cells and Akt inhibitor 10-DEBC hydrochloride or phosphoinositide 3-kinase/Akt inhibitor LY294002 abolished metformin-mediated antioxidant and antiapoptotic effects.	Metformin	181-190	AKT serine/threonine kinase 1	Homo sapiens	37-40
21114978-8	2011	On the other hand, metformin induced Akt activation in cisplatin-treated cells and Akt inhibitor 10-DEBC hydrochloride or phosphoinositide 3-kinase/Akt inhibitor LY294002 abolished metformin-mediated antioxidant and antiapoptotic effects.	Metformin	181-190	AKT serine/threonine kinase 1	Homo sapiens	83-86
21114978-8	2011	On the other hand, metformin induced Akt activation in cisplatin-treated cells and Akt inhibitor 10-DEBC hydrochloride or phosphoinositide 3-kinase/Akt inhibitor LY294002 abolished metformin-mediated antioxidant and antiapoptotic effects.	Metformin	181-190	AKT serine/threonine kinase 1	Homo sapiens	83-86
21114978-9	2011	In conclusion, the antidiabetic drug metformin reduces cisplatin in vitro anticancer activity through AMPK-independent upregulation of Akt survival pathway.	Metformin	37-46	AKT serine/threonine kinase 1	Homo sapiens	135-138
21340016-5	2011	CAT, glutathione reductase (GR), TAS, and GSH remained significantly reduced in the diabetic rats treated with metformin and/or glibenclamide.	Metformin	111-120	catalase	Rattus norvegicus	0-3
21340016-6	2011	In contrast, metformin or glibenclamide combined with honey significantly increased CAT, GR, TAS, and GSH.	Metformin	13-22	catalase	Rattus norvegicus	84-87
20947819-10	2011	Metformin did not affect postprandial lipemia and could be used to treat insulin resistance in this population.	Metformin	0-9	insulin	Homo sapiens	73-80
21863614-7	2011	Insulin sensitisers include both metformin and glitazones.	Metformin	33-42	insulin	Homo sapiens	0-7
21625101-10	2011	Insulin sensitizers such as metformin and PPAR-gamma agonists are either contraindicated or sparingly used due to their potential side effects, even in CHD patients with overt diabetes mellitus.	Metformin	28-37	insulin	Homo sapiens	0-7
21083698-22	2011	In cardiomyocytes, metformin inhibited AngII-induced protein synthesis, an effect that was suppressed by the AMPK inhibitor compound C or the eNOS inhibitor L-NAME.	Metformin	19-28	angiotensinogen	Rattus norvegicus	39-44
21391472-4	2011	The aim of the study was to assess whether sex hormone binding globulin (SHBG) (a surrogate marker of insulin resistance) could predict a positive response to metformin treatment in women with PCOS.	Metformin	159-168	sex hormone binding globulin	Homo sapiens	43-71
21391472-4	2011	The aim of the study was to assess whether sex hormone binding globulin (SHBG) (a surrogate marker of insulin resistance) could predict a positive response to metformin treatment in women with PCOS.	Metformin	159-168	sex hormone binding globulin	Homo sapiens	73-77
21391472-8	2011	In this group, patients who responded to metformin treatment had significantly lower SHBG levels compared to those who did not (median SHBG 37.5 nmol/L compared to 56.0 nmol/L) (p = 0.016, Mann-Whitney U-test).	Metformin	41-50	sex hormone binding globulin	Homo sapiens	85-89
21391472-8	2011	In this group, patients who responded to metformin treatment had significantly lower SHBG levels compared to those who did not (median SHBG 37.5 nmol/L compared to 56.0 nmol/L) (p = 0.016, Mann-Whitney U-test).	Metformin	41-50	sex hormone binding globulin	Homo sapiens	135-139
21391472-10	2011	CONCLUSIONS: Patients with a positive response to metformin treatment had significantly lower pre-treatment SHBG levels.	Metformin	50-59	sex hormone binding globulin	Homo sapiens	108-112
21391472-11	2011	For every unit increase in SHBG, the odds of a patient having a positive outcome to metformin treatment fell by a factor of 0.983.	Metformin	84-93	sex hormone binding globulin	Homo sapiens	27-31
20956498-0	2011	OCT1 Expression in adipocytes could contribute to increased metformin action in obese subjects.	Metformin	60-69	solute carrier family 22 member 1	Homo sapiens	0-4
20929990-8	2011	Triple therapy (rosiglitazone, metformin, and any insulin) resulted in a greater reduction in A1C than rosiglitazone plus insulin (-0.50 +- 0.14%, P < 0.001) and metformin plus insulin (-0.45 +- 0.14%, P < 0.001).	Metformin	165-174	insulin	Homo sapiens	50-57
20956498-10	2011	Furthermore, metformin decreased IL-6 and MCP-1 gene expression in comparison with differentiated adipocytes.	Metformin	13-22	interleukin 6	Homo sapiens	33-37
20956498-14	2011	Increased OCT1 gene expression in adipose tissue of obese subjects might contribute to increased metformin action in these subjects.	Metformin	97-106	solute carrier family 22 member 1	Homo sapiens	10-14
21325745-0	2011	The effect of weight loss and treatment with metformin on serum vaspin levels in women with polycystic ovary syndrome.	Metformin	45-54	serpin family A member 12	Homo sapiens	64-70
20980415-0	2011	Metformin and cancer occurrence in insulin-treated type 2 diabetic patients.	Metformin	0-9	insulin	Homo sapiens	35-42
20980415-2	2011	The aim of this study was to assess the effect of metformin on cancer incidence in a consecutive series of insulin-treated patients.	Metformin	50-59	insulin	Homo sapiens	107-114
20980415-6	2011	After adjustment for comorbidity, glargine, and total insulin doses, exposure to metformin, but not to sulfonylureas, was associated with reduced incidence of cancer (odds ratio 0.46 [95% CI 0.25-0.85], P = 0.014 and 0.75 [0.39-1.45], P = 0.40, respectively).	Metformin	81-90	insulin	Homo sapiens	54-61
20980415-7	2011	CONCLUSIONS: The reduction of cancer risk could be a further relevant reason for maintaining use of metformin in insulin-treated patients.	Metformin	100-109	insulin	Homo sapiens	113-120
21325745-2	2011	The aim of the study was to assess serum vaspin levels in PCOS and the effects on vaspin levels of metformin or of weight loss.	Metformin	99-108	serpin family A member 12	Homo sapiens	82-88
20684955-0	2011	Effect of the insulin sensitizers metformin and pioglitazone on endothelial function in young women with polycystic ovary syndrome: a prospective randomized study.	Metformin	34-43	insulin	Homo sapiens	14-21
20684955-14	2011	CONCLUSION(S): In young women with PCOS, treatment with metformin or pioglitazone for 6 months induces a similar beneficial effect on endothelial function; this may be partially attributed to an improvement in insulin resistance.	Metformin	56-65	insulin	Homo sapiens	210-217
21325745-10	2011	In normal weight patients with PCOS, metformin reduced vaspin levels non-significantly.	Metformin	37-46	serpin family A member 12	Homo sapiens	55-61
21647332-5	2011	AMPK activation by either AICAR or metformin decreases Srebp-1c promoter activity by about 75%.	Metformin	35-44	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	0-4
24363693-9	2011	Glasgow Coma Scale (GCS) and APACHE II had significant correlation with MACR in metformin treated patients (p < 0.05; R(2) = 0.134 and p < 0.05; R(2) = 0.149) while in insulin treated patients only the values of GCS had significant correlation with MACR values (p < 0.05, R(2) = 0.124).	Metformin	80-89	insulin	Homo sapiens	174-181
21349801-7	2011	These new encouraging experimental data supporting the anti-cancer effects of metformin urgently require further clinical studies in order to establish its use as a synergistic therapy targeting the AMPK/mTOR signaling pathway.	Metformin	78-87	mechanistic target of rapamycin kinase	Homo sapiens	204-208
19874425-4	2011	We also show that metformin-mediated effect on AMPK is dependent on liver kinase B1 (LKB1) as it failed to activate AMPK-ACC pathway and cell cycle arrest in LKB1 null mouse embryo fibroblasts (mefs).	Metformin	18-27	serine/threonine kinase 11	Mus musculus	68-83
19874425-4	2011	We also show that metformin-mediated effect on AMPK is dependent on liver kinase B1 (LKB1) as it failed to activate AMPK-ACC pathway and cell cycle arrest in LKB1 null mouse embryo fibroblasts (mefs).	Metformin	18-27	serine/threonine kinase 11	Mus musculus	85-89
21672339-1	2011	Metformin and rosiglitazone combination therapy is known to improve insulin resistance and postpone diabetes mellitus development in subjects with impaired glucose tolerance.	Metformin	0-9	insulin	Homo sapiens	68-75
21672339-5	2011	Metformin plus rosiglitazone significantly decreased blood pressure, lipids, BMI, and fasting and postmeal insulin levels.	Metformin	0-9	insulin	Homo sapiens	107-114
21672339-8	2011	The metformin and rosiglitazone combination increased insulin sensitivity and beta-cell function recovered.	Metformin	4-13	insulin	Homo sapiens	54-61
21281021-7	2011	Lifestyle modification to reduce weight in obese women and treatment with insulin-sensitising drugs such as metformin in women with glucose intolerance result in the improvement of some metabolic abnormalities and hyperandrogenic disorders with the consequent restoration of normal menstrual and ovulatory function in a significant number of women with polycystic ovaries.	Metformin	108-117	insulin	Homo sapiens	74-81
22117989-0	2011	Combination therapy with metformin and fenofibrate for insulin resistance in obesity.	Metformin	25-34	insulin	Homo sapiens	55-62
22117989-1	2011	This randomized controlled study investigated metformin and fenofibrate, compared with metformin alone, for the treatment of peripheral insulin resistance in patients with simple obesity with hyperinsulinaemia but not diabetes.	Metformin	46-55	insulin	Homo sapiens	136-143
22117989-6	2011	In addition, combined metformin and fenofibrate therapy showed significantly  decreased fasting and postmeal insulin levels relative to baseline and relative to the placebo group.	Metformin	22-31	insulin	Homo sapiens	109-116
22117989-8	2011	Metformin and fenofibrate can increase insulin sensitivity and recover beta-cell function in patients with simple obesity accompanied by insulin resistance.	Metformin	0-9	insulin	Homo sapiens	39-46
22117989-8	2011	Metformin and fenofibrate can increase insulin sensitivity and recover beta-cell function in patients with simple obesity accompanied by insulin resistance.	Metformin	0-9	insulin	Homo sapiens	137-144
21954641-1	2011	The use of metformin during the first month of treatment of patients with coronary artery disease and diabetes type 2 led to the decrease of insulin resistance and reduced activity of systemic inflammation (significant decrease in the concentrations of IL-1, IL-6, IL-8 and TNF-alpha).	Metformin	11-20	insulin	Homo sapiens	141-148
20152998-0	2011	Addition of metformin to exogenous glucagon-like peptide-1 results in increased serum glucagon-like peptide-1 concentrations and greater glucose lowering in type 2 diabetes mellitus.	Metformin	12-21	glucagon	Homo sapiens	35-58
21954641-1	2011	The use of metformin during the first month of treatment of patients with coronary artery disease and diabetes type 2 led to the decrease of insulin resistance and reduced activity of systemic inflammation (significant decrease in the concentrations of IL-1, IL-6, IL-8 and TNF-alpha).	Metformin	11-20	interleukin 6	Homo sapiens	259-263
20152998-0	2011	Addition of metformin to exogenous glucagon-like peptide-1 results in increased serum glucagon-like peptide-1 concentrations and greater glucose lowering in type 2 diabetes mellitus.	Metformin	12-21	glucagon	Homo sapiens	86-109
21954641-1	2011	The use of metformin during the first month of treatment of patients with coronary artery disease and diabetes type 2 led to the decrease of insulin resistance and reduced activity of systemic inflammation (significant decrease in the concentrations of IL-1, IL-6, IL-8 and TNF-alpha).	Metformin	11-20	C-X-C motif chemokine ligand 8	Homo sapiens	265-269
20152998-8	2011	Mean area under curve (AUC) (0-180 minutes) plasma glucose responses were lowest after Metformin + GLP-1 (mean +- SEM, 1629 +- 90 mmol/[L min]) compared with GLP-1 (1885 +- 86 mmol/[L min], P < .002) and Metformin (2045 +- 115 mmol/[L min], P < .001).	Metformin	87-96	glucagon	Homo sapiens	99-104
20152998-10	2011	Mean AUC for plasma DPP-4 activity was lower after Metformin + GLP-1 (1505 +- 2 mumol/[mL min], P < .001) and Metformin (1508 +- 2 mumol/[mL min], P < .002) compared with GLP-1 (1587 +- 3 mumol/[mL min]).	Metformin	51-60	glucagon	Homo sapiens	177-182
20152998-11	2011	Mean AUC measures for plasma active GLP-1 concentrations were higher after Metformin + GLP-1 (820 x 104 +- 51 x 104 pmol/[L min]) compared with GLP-1 (484 x 104 +- 31 x 104 pmol/[L min], P < .001) and Metformin (419 x 104 +- 34 x 104 pmol/[L min], P < .001), respectively.	Metformin	75-84	glucagon	Homo sapiens	36-41
20152998-11	2011	Mean AUC measures for plasma active GLP-1 concentrations were higher after Metformin + GLP-1 (820 x 104 +- 51 x 104 pmol/[L min]) compared with GLP-1 (484 x 104 +- 31 x 104 pmol/[L min], P < .001) and Metformin (419 x 104 +- 34 x 104 pmol/[L min], P < .001), respectively.	Metformin	204-213	glucagon	Homo sapiens	36-41
21954641-1	2011	The use of metformin during the first month of treatment of patients with coronary artery disease and diabetes type 2 led to the decrease of insulin resistance and reduced activity of systemic inflammation (significant decrease in the concentrations of IL-1, IL-6, IL-8 and TNF-alpha).	Metformin	11-20	tumor necrosis factor	Homo sapiens	274-283
20153488-8	2011	Heparin-releasable LPL was increased after treatment with AICAR (P < .05) and high-dose metformin (P < .01).	Metformin	91-100	lipoprotein lipase	Rattus norvegicus	19-22
20152998-12	2011	In patients with type 2 diabetes mellitus, metformin inhibits DPP-4 activity and thus increases active GLP-1 concentrations after subcutaneous injection.	Metformin	43-52	glucagon	Homo sapiens	103-108
21961686-11	2011	In one study in adolescents metformin treatment showed a reduction of HbA1c by 0.6% (95% CI: -1.16-0.04) and a slight decrease in daily total insulin dose.	Metformin	28-37	insulin	Homo sapiens	142-149
20152998-14	2011	Metformin enhances serum concentrations of injected active GLP-1(7-36)amide, and the combination results in added glucose-lowering potency.	Metformin	0-9	glucagon	Homo sapiens	59-64
20153488-0	2011	Does long-term metformin treatment increase cardiac lipoprotein lipase?	Metformin	15-24	lipoprotein lipase	Rattus norvegicus	52-70
21895401-0	2011	Metformin induces apoptosis of lung cancer cells through activating JNK/p38 MAPK pathway and GADD153.	Metformin	0-9	mitogen-activated protein kinase 8	Homo sapiens	68-71
21895401-0	2011	Metformin induces apoptosis of lung cancer cells through activating JNK/p38 MAPK pathway and GADD153.	Metformin	0-9	mitogen-activated protein kinase 14	Homo sapiens	72-75
21625374-8	2011	The combination treatment of insulin infusion plus oral metformin is shown to be superior than the monotherapy with oral metformin only.	Metformin	121-130	insulin	Homo sapiens	29-36
21895401-0	2011	Metformin induces apoptosis of lung cancer cells through activating JNK/p38 MAPK pathway and GADD153.	Metformin	0-9	DNA damage inducible transcript 3	Homo sapiens	93-100
21895401-4	2011	We also found that metformin treatment can activate AMP-activated protein kinase, JNK/p38 MAPK signaling pathway and caspases, as well as upregulate the expression of growth arrest and DNA damage inducible gene 153 (GADD153).	Metformin	19-28	mitogen-activated protein kinase 8	Homo sapiens	82-85
21895401-4	2011	We also found that metformin treatment can activate AMP-activated protein kinase, JNK/p38 MAPK signaling pathway and caspases, as well as upregulate the expression of growth arrest and DNA damage inducible gene 153 (GADD153).	Metformin	19-28	mitogen-activated protein kinase 14	Homo sapiens	86-89
21895401-4	2011	We also found that metformin treatment can activate AMP-activated protein kinase, JNK/p38 MAPK signaling pathway and caspases, as well as upregulate the expression of growth arrest and DNA damage inducible gene 153 (GADD153).	Metformin	19-28	DNA damage inducible transcript 3	Homo sapiens	167-214
21895401-4	2011	We also found that metformin treatment can activate AMP-activated protein kinase, JNK/p38 MAPK signaling pathway and caspases, as well as upregulate the expression of growth arrest and DNA damage inducible gene 153 (GADD153).	Metformin	19-28	DNA damage inducible transcript 3	Homo sapiens	216-223
21895401-5	2011	Either blockade of JNK/p38 MAPK pathway or knockdown of GADD153 gene abrogated the apoptosis-inducing effect of metformin.	Metformin	112-121	mitogen-activated protein kinase 8	Homo sapiens	19-22
21895401-5	2011	Either blockade of JNK/p38 MAPK pathway or knockdown of GADD153 gene abrogated the apoptosis-inducing effect of metformin.	Metformin	112-121	DNA damage inducible transcript 3	Homo sapiens	56-63
21895401-6	2011	Taken together, our data suggest that metformin inhibits the growth of lung cancer cells and induces apoptosis through activating JNK/p38 MAPK pathway and GADD153.	Metformin	38-47	mitogen-activated protein kinase 8	Homo sapiens	130-133
21895401-6	2011	Taken together, our data suggest that metformin inhibits the growth of lung cancer cells and induces apoptosis through activating JNK/p38 MAPK pathway and GADD153.	Metformin	38-47	mitogen-activated protein kinase 14	Homo sapiens	134-137
21895401-6	2011	Taken together, our data suggest that metformin inhibits the growth of lung cancer cells and induces apoptosis through activating JNK/p38 MAPK pathway and GADD153.	Metformin	38-47	DNA damage inducible transcript 3	Homo sapiens	155-162
21372608-0	2011	In vitro and in vivo effects of metformin on human adipose tissue adiponectin.	Metformin	32-41	adiponectin, C1Q and collagen domain containing	Homo sapiens	66-77
21372608-1	2011	OBJECTIVE: The effects of metformin on adiponectin production are controversial and have never been investigated in human adipose tissue.	Metformin	26-35	adiponectin, C1Q and collagen domain containing	Homo sapiens	39-50
21372608-2	2011	We analysed whether metformin modulates, in vitro and in vivo, gene expression, protein content, and secretion of adiponectin.	Metformin	20-29	adiponectin, C1Q and collagen domain containing	Homo sapiens	114-125
21372608-6	2011	RESULTS: In in vitro experiments, treatment with metformin increased the expression and secretion of adiponectin in SAT, but not in VAT explants.	Metformin	49-58	adiponectin, C1Q and collagen domain containing	Homo sapiens	101-112
21372608-8	2011	CONCLUSION: These results demonstrate that metformin is able to up-regulate adiponectin gene expression, both in vivo and in vitro, and to stimulate adiponectin protein secretion from human SAT in vitro.	Metformin	43-52	adiponectin, C1Q and collagen domain containing	Homo sapiens	76-87
21372608-8	2011	CONCLUSION: These results demonstrate that metformin is able to up-regulate adiponectin gene expression, both in vivo and in vitro, and to stimulate adiponectin protein secretion from human SAT in vitro.	Metformin	43-52	adiponectin, C1Q and collagen domain containing	Homo sapiens	149-160
21372608-9	2011	It could be hypothesised that metformin-induced adiponectin increase within adipose tissue may have an unexpected role in the reduction of local inflammation.	Metformin	30-39	adiponectin, C1Q and collagen domain containing	Homo sapiens	48-59
21109968-0	2011	The anti-diabetic drug metformin suppresses the metastasis-associated protein CD24 in MDA-MB-468 triple-negative breast cancer cells.	Metformin	23-32	LY6/PLAUR domain containing 5	Homo sapiens	48-77
21109968-0	2011	The anti-diabetic drug metformin suppresses the metastasis-associated protein CD24 in MDA-MB-468 triple-negative breast cancer cells.	Metformin	23-32	CD24 molecule	Homo sapiens	78-82
21109968-4	2011	Here, we reveal that suppression of CD24 protein expression is a crucial event in the molecular mechanisms underlying the growth-inhibitory effects of the anti-diabetic drug metformin in MDA-MB-468 triple-negative (basal-like) breast cancer cells.	Metformin	174-183	CD24 molecule	Homo sapiens	36-40
21109968-7	2011	Third, high-content indirect immunofluorescence imaging assays revealed that CD24 protein levels were drastically decreased in the presence of growth-inhibitory concentrations of metformin.	Metformin	179-188	CD24 molecule	Homo sapiens	77-81
21109968-8	2011	Fourth, to preliminary assess the clinical relevance of metformin"s anti-CD24 effects we took advantage of the recently developed ROCK online interface (http://rock.icr.ac.uk/), a publicly accessible portal that allows rapid integration of breast cancer functional and molecular profiling datasets.	Metformin	56-65	CD24 molecule	Homo sapiens	73-77
21109968-10	2011	These findings, altogether, suggest that the ability of metformin to suppress the oncogene, metastasis promoter and breast cancer stem cell marker CD24 may open a novel molecular avenue in the therapeutic management of highly-metastastic subgroups of triple-negative (basal-like) breast cancers naturally enriched with CD44posCD24pos tumor-initiating cell populations.	Metformin	56-65	CD24 molecule	Homo sapiens	147-151
21776823-0	2011	Antidiabetic drug metformin induces apoptosis in human MCF breast cancer via targeting ERK signaling.	Metformin	18-27	mitogen-activated protein kinase 1	Homo sapiens	87-90
21776823-5	2011	Metformin induced apoptosis by arresting cells in G1 phase and reducing cyclin D level and increasing the expression of p21 and cyclin E. Molecular and cellular studies indicated that metformin significantly elevated p53 and Bax levels and reduced STAT3 and Bcl-2.	Metformin	0-9	tumor protein p53	Homo sapiens	217-220
21776823-5	2011	Metformin induced apoptosis by arresting cells in G1 phase and reducing cyclin D level and increasing the expression of p21 and cyclin E. Molecular and cellular studies indicated that metformin significantly elevated p53 and Bax levels and reduced STAT3 and Bcl-2.	Metformin	0-9	BCL2 associated X, apoptosis regulator	Homo sapiens	225-228
21776823-5	2011	Metformin induced apoptosis by arresting cells in G1 phase and reducing cyclin D level and increasing the expression of p21 and cyclin E. Molecular and cellular studies indicated that metformin significantly elevated p53 and Bax levels and reduced STAT3 and Bcl-2.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	248-253
21776823-5	2011	Metformin induced apoptosis by arresting cells in G1 phase and reducing cyclin D level and increasing the expression of p21 and cyclin E. Molecular and cellular studies indicated that metformin significantly elevated p53 and Bax levels and reduced STAT3 and Bcl-2.	Metformin	0-9	BCL2 apoptosis regulator	Homo sapiens	258-263
21776823-5	2011	Metformin induced apoptosis by arresting cells in G1 phase and reducing cyclin D level and increasing the expression of p21 and cyclin E. Molecular and cellular studies indicated that metformin significantly elevated p53 and Bax levels and reduced STAT3 and Bcl-2.	Metformin	184-193	BCL2 apoptosis regulator	Homo sapiens	258-263
21776823-8	2011	Furthermore, MEK inhibitor significantly suppressed metformin-induced p53 and Bax elevation while ERK inhibitor generated a slight reduction in p53 levels.	Metformin	52-61	mitogen-activated protein kinase kinase 7	Homo sapiens	13-16
21776823-5	2011	Metformin induced apoptosis by arresting cells in G1 phase and reducing cyclin D level and increasing the expression of p21 and cyclin E. Molecular and cellular studies indicated that metformin significantly elevated p53 and Bax levels and reduced STAT3 and Bcl-2.	Metformin	184-193	tumor protein p53	Homo sapiens	217-220
21776823-5	2011	Metformin induced apoptosis by arresting cells in G1 phase and reducing cyclin D level and increasing the expression of p21 and cyclin E. Molecular and cellular studies indicated that metformin significantly elevated p53 and Bax levels and reduced STAT3 and Bcl-2.	Metformin	184-193	BCL2 associated X, apoptosis regulator	Homo sapiens	225-228
21776823-8	2011	Furthermore, MEK inhibitor significantly suppressed metformin-induced p53 and Bax elevation while ERK inhibitor generated a slight reduction in p53 levels.	Metformin	52-61	tumor protein p53	Homo sapiens	70-73
21776823-5	2011	Metformin induced apoptosis by arresting cells in G1 phase and reducing cyclin D level and increasing the expression of p21 and cyclin E. Molecular and cellular studies indicated that metformin significantly elevated p53 and Bax levels and reduced STAT3 and Bcl-2.	Metformin	184-193	signal transducer and activator of transcription 3	Homo sapiens	248-253
21776823-8	2011	Furthermore, MEK inhibitor significantly suppressed metformin-induced p53 and Bax elevation while ERK inhibitor generated a slight reduction in p53 levels.	Metformin	52-61	BCL2 associated X, apoptosis regulator	Homo sapiens	78-81
21776823-10	2011	Finally, SAPK/JNK, known to be involved in apoptosis, was activated in cells treated with metformin and the activation appeared to occur downstream of ERK.	Metformin	90-99	mitogen-activated protein kinase 1	Homo sapiens	151-154
21776823-11	2011	All these results suggested that metformin activated p53, Bax, and induced tumor cell apoptosis through the ERK signaling pathway.	Metformin	33-42	tumor protein p53	Homo sapiens	53-56
21776823-11	2011	All these results suggested that metformin activated p53, Bax, and induced tumor cell apoptosis through the ERK signaling pathway.	Metformin	33-42	BCL2 associated X, apoptosis regulator	Homo sapiens	58-61
21776823-11	2011	All these results suggested that metformin activated p53, Bax, and induced tumor cell apoptosis through the ERK signaling pathway.	Metformin	33-42	mitogen-activated protein kinase 1	Homo sapiens	108-111
22068032-1	2011	BACKGROUND: The potential utility of 5"-adenosine monophosphate-activated protein kinase (AMPK)-activating agents, such as metformin, in inducing angiogenesis, could be a promising approach to promote healing of gastric ulcers complicated by diabetes mellitus.	Metformin	123-132	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	37-88
22068032-1	2011	BACKGROUND: The potential utility of 5"-adenosine monophosphate-activated protein kinase (AMPK)-activating agents, such as metformin, in inducing angiogenesis, could be a promising approach to promote healing of gastric ulcers complicated by diabetes mellitus.	Metformin	123-132	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	90-94
22068032-2	2011	The aim of the present study was to assess the effect of a drug that activates AMPK, namely metformin, in gastric ulcer healing in streptozotocin-induced diabetic rats.	Metformin	92-101	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	79-83
22068032-8	2011	RESULTS: Administration of metformin, but not pioglitazone, resulted in a significant decrease in the gastric ulcer area, a significant increase in epithelial regeneration assessed histologically, a significant increase in the number of microvessels in the ulcer margin, a significant increase in gastric vascular endothelial growth factor concentration and gastric von Willebrand factor as well as a significant increase in gastric phospho-AMPK.	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	441-445
22068032-9	2011	Compound C, an inhibitor of AMPK, blocked metformin-induced changes in assessed parameters suggesting that the effect of metformin was mediated mainly through activation of AMPK.	Metformin	42-51	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	28-32
22068032-9	2011	Compound C, an inhibitor of AMPK, blocked metformin-induced changes in assessed parameters suggesting that the effect of metformin was mediated mainly through activation of AMPK.	Metformin	42-51	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	173-177
22068032-9	2011	Compound C, an inhibitor of AMPK, blocked metformin-induced changes in assessed parameters suggesting that the effect of metformin was mediated mainly through activation of AMPK.	Metformin	121-130	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	28-32
22068032-9	2011	Compound C, an inhibitor of AMPK, blocked metformin-induced changes in assessed parameters suggesting that the effect of metformin was mediated mainly through activation of AMPK.	Metformin	121-130	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	173-177
22132214-0	2011	Metformin represses self-renewal of the human breast carcinoma stem cells via inhibition of estrogen receptor-mediated OCT4 expression.	Metformin	0-9	estrogen receptor 1	Homo sapiens	92-109
21390459-0	2011	Vitamin B12 in metformin-treated diabetic patients: a cross-sectional study in Brazil.	Metformin	15-24	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	8-11
21779389-1	2011	Metformin, an oral insulin-sensitizing drug, is actively transported into cells by organic cation transporters (OCT) 1, 2, and 3 (encoded by SLC22A1, SLC22A2, or SLC22A3), which are tissue specifically expressed at significant levels in various organs such as liver, muscle, and kidney.	Metformin	0-9	solute carrier family 22 member 1	Homo sapiens	141-148
21779389-6	2011	All tested PPIs significantly inhibited metformin uptake by OCT1, OCT2, and OCT3 in a concentration-dependent manner.	Metformin	40-49	solute carrier family 22 member 1	Homo sapiens	60-64
21390459-5	2011	Serum vitamin B12 levels were negatively associated with age (B = -3.17; beta= -0.171; p = 0.037) and duration of metformin use (B= -33.36; beta= -0.161; p = 0.048), and positively associated with the estimated intake of vitamin B12 (B= 67.96; beta= 0.249; p = 0.002).	Metformin	114-123	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	14-17
21390459-6	2011	CONCLUSION: The present findings suggest a high prevalence of vitamin B12 deficiency in metformin-treated diabetic patients.	Metformin	88-97	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	70-73
21106483-3	2010	Accordingly, the benefit of metformin for treating patients with type 1 diabetes was documented (as an add-on therapy to insulin, primarily in adult patients with the phenotype of type 2 diabetes).	Metformin	28-37	insulin	Homo sapiens	121-128
21516824-5	2011	Also, we showed that metformin prevented the accumulation of fibroblasts with large area of nuclei; high activity of senescence-associated beta-galactosidase (SA-beta-gal), and high fluorescence intensity after staining for gamma-H2AX.	Metformin	21-30	H2A.X variant histone	Mus musculus	224-234
21628978-2	2011	However, we hypothesized that retinoid X receptor (RXR) agonists, which are researched for the treatment of type 2 diabetes, will also be useful like metformin, which shows insulin-sparing effect in type 1 diabetes.	Metformin	150-159	insulin	Homo sapiens	173-180
21098287-0	2010	Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling.	Metformin	10-19	mechanistic target of rapamycin kinase	Homo sapiens	52-56
20869956-10	2010	Both doses of UA lowered splenic IL-6 levels, whereas metformin increased IFN-gamma, IL-6 and TNF-alpha levels compared to the untreated diabetic mice.	Metformin	54-63	interferon gamma	Mus musculus	74-83
20869956-10	2010	Both doses of UA lowered splenic IL-6 levels, whereas metformin increased IFN-gamma, IL-6 and TNF-alpha levels compared to the untreated diabetic mice.	Metformin	54-63	interleukin 6	Mus musculus	85-89
20869956-10	2010	Both doses of UA lowered splenic IL-6 levels, whereas metformin increased IFN-gamma, IL-6 and TNF-alpha levels compared to the untreated diabetic mice.	Metformin	54-63	tumor necrosis factor	Mus musculus	94-103
20861072-8	2010	Treatment with the AMPK activators AICAR (2 mM) or metformin (1 mM) reduced basolateral KCNQ1 currents in apically permeabilized polarized mpkCCD(c14) cells.	Metformin	51-60	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	19-23
20596715-8	2010	CONCLUSION: The results of this study show that 2,500 mg daily dose of metformin in obese patients with PCOS is effective in the reduction of BMI, waist hip/ratio, LDL, serum insulin and increases SHBG.	Metformin	71-80	insulin	Homo sapiens	175-182
20596715-8	2010	CONCLUSION: The results of this study show that 2,500 mg daily dose of metformin in obese patients with PCOS is effective in the reduction of BMI, waist hip/ratio, LDL, serum insulin and increases SHBG.	Metformin	71-80	sex hormone binding globulin	Homo sapiens	197-201
20868233-4	2010	However, higher concentrations of metformin (100-1000 mum) increased (1.3-1.5-fold; p<0.001) insulin release at basal glucose concentrations, but had no effect on glucose-stimulated insulin secretion.	Metformin	34-43	insulin	Homo sapiens	96-103
20868233-5	2010	There were no apparent acute effects of metformin on intracellular Ca2(+) concentrations, but metformin enhanced (p<0.05 to p<0.01) the acute insulinotropic actions of GIP and GLP-1.	Metformin	94-103	gastric inhibitory polypeptide	Homo sapiens	174-177
20868233-6	2010	Exposure for 48 h to 200 mum metformin improved aspects of beta-cell insulin secretory function, whereas these benefits were lost at 1 mm metformin.	Metformin	29-38	insulin	Homo sapiens	69-76
21106483-6	2010	The use of metformin in type 2 diabetic patients with insulin treatment can result in a decrease in insulin dose, an improvement in glycaemic control, a beneficial effect in weight changes and a decrease in risk of macrovascular complications.	Metformin	11-20	insulin	Homo sapiens	54-61
21106483-6	2010	The use of metformin in type 2 diabetic patients with insulin treatment can result in a decrease in insulin dose, an improvement in glycaemic control, a beneficial effect in weight changes and a decrease in risk of macrovascular complications.	Metformin	11-20	insulin	Homo sapiens	100-107
20724929-2	2010	Insulin resistance represents a major pathophysiological feature of the syndrome and, therefore, insulin-sensitizing agents (metformin and thiazolidinediones) have been applied in PCOS women.	Metformin	125-134	insulin	Homo sapiens	0-7
22166651-0	2010	Appropriate insulin initiation dosage for insulin-naive type 2 diabetes outpatients receiving insulin monotherapy or in combination with metformin and/or pioglitazone.	Metformin	137-146	insulin	Homo sapiens	12-19
20724929-2	2010	Insulin resistance represents a major pathophysiological feature of the syndrome and, therefore, insulin-sensitizing agents (metformin and thiazolidinediones) have been applied in PCOS women.	Metformin	125-134	insulin	Homo sapiens	97-104
20739883-7	2010	Given these new findings, it can be anticipated that FCHL patients could also benefit from insulin-sensitizing therapy such as pioglitazone and metformin.	Metformin	144-153	insulin	Homo sapiens	91-98
20977579-7	2010	RESULTS: At the University of Chicago Diabetes Center, 36 of 234 (15.3%) patients with an eGFR of <60 ml/min/1.73 m(2) were receiving metformin.	Metformin	137-146	CD59 molecule (CD59 blood group)	Homo sapiens	108-113
20977579-8	2010	Data from NHANES, age >18 years and eGFR <60 ml/min/1.73 m(2) showed that Blacks with advanced nephropathy were three times more likely to receive metformin.	Metformin	153-162	CD59 molecule (CD59 blood group)	Homo sapiens	54-59
20977579-9	2010	CONCLUSIONS: We conclude that metformin utilization occurs with a higher frequency than predicted by serum creatinine in people with eGFR <60 ml/min/1.73 m(2) .	Metformin	30-39	CD59 molecule (CD59 blood group)	Homo sapiens	148-153
21075654-11	2010	From a clinical and fundamental point of view, it was concluded that, at the onset of diabetes, an initial triggering of GLP-1 secretion-by metformin coupled with a DPP4 inhibitor-would help to activate the gut-peripheral axis and, hence, restore adequate regulation of glycaemia.	Metformin	140-149	glucagon	Homo sapiens	121-126
20852028-12	2010	In vitro migration and angiogenesis were significantly increased in serum from PCOS women (P < 0.01) compared with matched control subjects; these effects were significantly attenuated by metformin treatment (P < 0.01) plausibly through the regulation of omentin-1 levels via NF-kappaB and Akt pathways.	Metformin	191-200	nuclear factor kappa B subunit 1	Homo sapiens	282-291
20852028-12	2010	In vitro migration and angiogenesis were significantly increased in serum from PCOS women (P < 0.01) compared with matched control subjects; these effects were significantly attenuated by metformin treatment (P < 0.01) plausibly through the regulation of omentin-1 levels via NF-kappaB and Akt pathways.	Metformin	191-200	AKT serine/threonine kinase 1	Homo sapiens	296-299
21126943-2	2010	This study was designed to show the effect of metformin, one of the most important drugs used to reduce insulin resistance in patients with polycystic ovary syndrome (PCOS), on these adipokines.	Metformin	46-55	insulin	Homo sapiens	104-111
20691435-0	2010	Efficacy of metformin therapy in adolescent girls with androgen excess: relation to sex hormone-binding globulin and androgen receptor polymorphisms.	Metformin	12-21	androgen receptor	Homo sapiens	117-134
20691435-2	2010	Longer SHBG (TAAAA)(n) alleles (>8 repeats) were associated with more improvement of the lipid profile after 1 year on metformin, whereas longer AR (CAG)(n) alleles were related to more normalization of the androgen and lipid levels after therapy; longer alleles in both genes had an additive effect on the beneficial changes of SHBG, T, and lipids after metformin.	Metformin	122-131	sex hormone binding globulin	Homo sapiens	7-11
21246005-5	2010	A treatment paradigm shift is recommended in which combination therapy is initiated with diet/exercise, metformin (which has antiatherogenic effects and improves hepatic insulin sensitivity), a TZD (which improves insulin sensitivity and preserves beta-cell function with proven durability), and a GLP-1 analog (which improves beta, alpha-cell function and promotes weight loss) or a dipeptidyl peptidase IV inhibitor in patients with type 2 diabetes mellitus.	Metformin	104-113	insulin	Homo sapiens	170-177
21311678-4	2010	Coinfusion of metformin (150 mg/kg/24 h) with isoproterenol partially inhibited cardiac hypertrophy that was followed by reduced IL-6, TGF-beta, ANP, collagen I and III, and MMP-2.	Metformin	14-23	interleukin 6	Mus musculus	129-133
21088486-0	2010	Metformin against TGFbeta-induced epithelial-to-mesenchymal transition (EMT): from cancer stem cells to aging-associated fibrosis.	Metformin	0-9	transforming growth factor beta 1	Homo sapiens	18-25
20863201-6	2010	These results suggest that the inhibitory potential of sitagliptin on OCT1 may attenuate the first step of metformin action, that is, the phosphorylation of AMPK.	Metformin	107-116	solute carrier family 22 member 1	Homo sapiens	70-74
21088486-9	2010	Remarkably, metformin exposure not only impedes TGFb-promoted loss of the epithelial marker E-cadherin in MCF-7 breast cancer cells but it prevents further TGF-induced cell scattering and accumulation of the mesenchymal marker vimentin in Madin-Darby canine kidney (MDCK) cells.	Metformin	12-21	transforming growth factor beta 1	Homo sapiens	48-52
21088486-9	2010	Remarkably, metformin exposure not only impedes TGFb-promoted loss of the epithelial marker E-cadherin in MCF-7 breast cancer cells but it prevents further TGF-induced cell scattering and accumulation of the mesenchymal marker vimentin in Madin-Darby canine kidney (MDCK) cells.	Metformin	12-21	cadherin 1	Homo sapiens	92-102
21088486-9	2010	Remarkably, metformin exposure not only impedes TGFb-promoted loss of the epithelial marker E-cadherin in MCF-7 breast cancer cells but it prevents further TGF-induced cell scattering and accumulation of the mesenchymal marker vimentin in Madin-Darby canine kidney (MDCK) cells.	Metformin	12-21	transforming growth factor beta 1	Homo sapiens	48-51
21088486-10	2010	We now propose that metformin, by weakening the ability of TGFb signaling to fully induce mesenchymal cell states in a variety of pathological processes including fibrosis (e.g. chronic renal disease, non-alcoholic steatohepatitis, heart failure or sclerosis) and malignant progression (and likely by reducing TGFb-regulated inflammation and immune responses -inflamm-aging-), molecularly behaves as a bona fide anti-aging modality.	Metformin	20-29	transforming growth factor beta 1	Homo sapiens	59-63
21088486-10	2010	We now propose that metformin, by weakening the ability of TGFb signaling to fully induce mesenchymal cell states in a variety of pathological processes including fibrosis (e.g. chronic renal disease, non-alcoholic steatohepatitis, heart failure or sclerosis) and malignant progression (and likely by reducing TGFb-regulated inflammation and immune responses -inflamm-aging-), molecularly behaves as a bona fide anti-aging modality.	Metformin	20-29	transforming growth factor beta 1	Homo sapiens	310-314
20947488-1	2010	Metformin, an insulin-lowering agent, has been associated with decreased cancer risk in epidemiologic studies in diabetic patients.	Metformin	0-9	insulin	Homo sapiens	14-21
20079899-12	2010	CONCLUSION(S): This report has demonstrated that the combination of metformin and simvastatin could lead to a better reduction of T and LH levels and thus reversing the LH:FSH ratio, lipid profile, and insulin resistance in patients with PCOS and may be an appropriate management option for patients with PCOS.	Metformin	68-77	insulin	Homo sapiens	202-209
20652679-2	2010	METHODS: IL-6-stimulated expression of the genes for acute-phase response markers serum amyloid A (SAA1, SAA2) and haptoglobin (HP) in the human hepatocarcinoma cell line HepG2 were quantified after modulation of AMPK activity by pharmacological agonists (5-amino-4-imidazole-carboxamideriboside [AICAR], metformin) or by using small interfering (si) RNA transfection.	Metformin	305-314	interleukin 6	Homo sapiens	9-13
20652679-2	2010	METHODS: IL-6-stimulated expression of the genes for acute-phase response markers serum amyloid A (SAA1, SAA2) and haptoglobin (HP) in the human hepatocarcinoma cell line HepG2 were quantified after modulation of AMPK activity by pharmacological agonists (5-amino-4-imidazole-carboxamideriboside [AICAR], metformin) or by using small interfering (si) RNA transfection.	Metformin	305-314	serum amyloid A1	Homo sapiens	99-103
20652679-4	2010	RESULTS: AICAR and metformin markedly blunt the IL-6-stimulated expression of SAA cluster genes as well as of haptoglobin in a dose-dependent manner.	Metformin	19-28	interleukin 6	Homo sapiens	48-52
20652679-4	2010	RESULTS: AICAR and metformin markedly blunt the IL-6-stimulated expression of SAA cluster genes as well as of haptoglobin in a dose-dependent manner.	Metformin	19-28	haptoglobin	Homo sapiens	110-121
20528570-4	2010	Lifestyle intervention, oral contraceptives, and insulin sensitises such as metformin are the most commonly used treatment modalities.	Metformin	76-85	insulin	Homo sapiens	49-56
21437106-3	2010	Complementary combination therapy with sitagliptin-metformin lowers glucose via enhancement of insulin secretion, suppression of glucagon secretion, and insulin sensitization.	Metformin	51-60	insulin	Homo sapiens	95-102
20688914-8	2010	In addition, metformin or overexpression of a constitutively active form of AMPK (Ad-CA-AMPK) inhibited S171A-mediated PEPCK and G6Pase gene expression, and hepatic glucose production and knockdown of SHP partially relieved the metformin- and Ad-CA-AMPK-mediated repression of hepatic gluconeogenic enzyme gene expression in primary rat hepatocytes.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	243-253
20688914-8	2010	In addition, metformin or overexpression of a constitutively active form of AMPK (Ad-CA-AMPK) inhibited S171A-mediated PEPCK and G6Pase gene expression, and hepatic glucose production and knockdown of SHP partially relieved the metformin- and Ad-CA-AMPK-mediated repression of hepatic gluconeogenic enzyme gene expression in primary rat hepatocytes.	Metformin	228-237	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	76-80
20688914-8	2010	In addition, metformin or overexpression of a constitutively active form of AMPK (Ad-CA-AMPK) inhibited S171A-mediated PEPCK and G6Pase gene expression, and hepatic glucose production and knockdown of SHP partially relieved the metformin- and Ad-CA-AMPK-mediated repression of hepatic gluconeogenic enzyme gene expression in primary rat hepatocytes.	Metformin	228-237	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	82-92
20599791-6	2010	This was reversed by restoration of normal growth medium, while the insulin resistance was prevented by pioglitazone or metformin.	Metformin	120-129	insulin	Homo sapiens	68-75
20919907-0	2010	Pharmacokinetics of metformin after enteral administration in insulin-resistant ponies.	Metformin	20-29	insulin	Homo sapiens	62-69
20919907-1	2010	OBJECTIVE: To determine pharmacokinetics and plasma steady-state kinetics of metformin after oral or nasogastric administration in insulin-resistant (IR) ponies.	Metformin	77-86	insulin	Homo sapiens	131-138
20406215-10	2010	The hepatic uptake of metformin is mediated by organic cation transporters 1 and 3, and the liver is not important for the elimination or action of the dipeptidylpeptidase 4 inhibitors sitagliptin, vildagliptin and saxagliptin.	Metformin	22-31	solute carrier family 22 member 1	Homo sapiens	47-82
20712585-0	2010	Metformin and energy metabolism in breast cancer: from insulin physiology to tumour-initiating stem cells.	Metformin	0-9	insulin	Homo sapiens	55-62
20639355-0	2010	Metformin and placebo therapy both improve weight management and fasting insulin in obese insulin-resistant adolescents: a prospective, placebo-controlled, randomized study.	Metformin	0-9	insulin	Homo sapiens	73-80
20920046-8	2010	In conclusion, in type 2 diabetic patients starting basal insulin analogue therapy, continuing both metformin and secretagogues results in more hypoglycaemia and weight gain and lower insulin doses than only maintaining metformin.	Metformin	100-109	insulin	Homo sapiens	58-65
20920046-8	2010	In conclusion, in type 2 diabetic patients starting basal insulin analogue therapy, continuing both metformin and secretagogues results in more hypoglycaemia and weight gain and lower insulin doses than only maintaining metformin.	Metformin	100-109	insulin	Homo sapiens	184-191
20639355-6	2010	The insulin sensitivity index, however, only improved in the metformin group.	Metformin	61-70	insulin	Homo sapiens	4-11
19931080-9	2010	The area under the curve for insulin was significantly decreased by DRP/EE20 and DRP/EE20 plus metformin, but it was significantly increased by DRP/EE20 plus CPA.	Metformin	95-104	insulin	Homo sapiens	29-36
20730705-0	2010	Treatment of polycystic ovary syndrome (PCOS) with metformin ameliorates insulin resistance in parallel with the decrease of serum interleukin-6 concentrations.	Metformin	51-60	insulin	Homo sapiens	73-80
20730705-0	2010	Treatment of polycystic ovary syndrome (PCOS) with metformin ameliorates insulin resistance in parallel with the decrease of serum interleukin-6 concentrations.	Metformin	51-60	interleukin 6	Homo sapiens	131-144
20730705-2	2010	We aimed to study if the changes observed in the insulin sensitivity of PCOS patients during treatment with oral contraceptives or metformin associate changes in the serum inflammatory markers interleukin-6 (IL-6) and interleukin-18 (IL-18).	Metformin	131-140	interleukin 6	Homo sapiens	193-206
20730705-2	2010	We aimed to study if the changes observed in the insulin sensitivity of PCOS patients during treatment with oral contraceptives or metformin associate changes in the serum inflammatory markers interleukin-6 (IL-6) and interleukin-18 (IL-18).	Metformin	131-140	interleukin 6	Homo sapiens	208-212
20730705-6	2010	PCOS women treated with metformin showed a decrease in IL-6 levels throughout the study compared with women treated with Diane (35) Diario (-33% change vs. +23% change, F=3.709, p=0.048; intention-to-treat analysis: F=5.569, p=0.011).	Metformin	24-33	interleukin 6	Homo sapiens	55-59
20730705-8	2010	The decrease in IL-6 levels in women receiving metformin occurred in parallel to the increase in the insulin sensitivity index (r=-0.579, p=0.048; intention-to-treat analysis, r=-0.687, p=0.001).	Metformin	47-56	interleukin 6	Homo sapiens	16-20
20730705-8	2010	The decrease in IL-6 levels in women receiving metformin occurred in parallel to the increase in the insulin sensitivity index (r=-0.579, p=0.048; intention-to-treat analysis, r=-0.687, p=0.001).	Metformin	47-56	insulin	Homo sapiens	101-108
20730705-9	2010	In conclusion, serum IL-6 levels decreased during treatment with metformin in parallel to amelioration of insulin resistance, whereas oral contraceptives slightly increased circulating IL-6 levels without changing insulin sensitivity.	Metformin	65-74	interleukin 6	Homo sapiens	21-25
20730705-9	2010	In conclusion, serum IL-6 levels decreased during treatment with metformin in parallel to amelioration of insulin resistance, whereas oral contraceptives slightly increased circulating IL-6 levels without changing insulin sensitivity.	Metformin	65-74	insulin	Homo sapiens	106-113
21966106-3	2010	Simultaneously the role of metformin (an insulin sensitizing agent) in modulating insulin resistance and serum androgen level was also analyzed.	Metformin	27-36	insulin	Homo sapiens	82-89
19998243-10	2010	CONCLUSIONS: Long-term treatment with metformin in women with PCOS appears to reduce androgen excess due to increased SHBG and decreased TT levels resulting in improvement of hirsutism as a clinical sign of androgen excess.	Metformin	38-47	sex hormone binding globulin	Homo sapiens	118-122
20441727-0	2010	The effect of metformin on anthropometrics and insulin resistance in patients receiving atypical antipsychotic agents: a meta-analysis.	Metformin	14-23	insulin	Homo sapiens	47-54
20441727-2	2010	While metformin has been shown to attenuate weight gain and insulin resistance, not all studies have shown a benefit in the reduction of antipsychotic-induced weight gain and insulin resistance.	Metformin	6-15	insulin	Homo sapiens	60-67
20441727-3	2010	OBJECTIVE: To characterize metformin"s impact on anthropometrics and insulin resistance in patients taking AAPs.	Metformin	27-36	insulin	Homo sapiens	69-76
21966106-6	2010	Follow up of cases with metformin for 3 months revealed a significant fall in serum insulin (P < 0.05) with improvement in insulin resistance along with a nonsignificant fall in testosterone level.	Metformin	24-33	insulin	Homo sapiens	84-91
21966106-6	2010	Follow up of cases with metformin for 3 months revealed a significant fall in serum insulin (P < 0.05) with improvement in insulin resistance along with a nonsignificant fall in testosterone level.	Metformin	24-33	insulin	Homo sapiens	126-133
20639304-1	2010	Organic cation transporter 1 (OCT1; SLC22A1) seems to play a role in the efficacy and disposition of the widely used antidiabetic drug metformin.	Metformin	135-144	solute carrier family 22 member 1	Homo sapiens	0-28
20660041-0	2010	Organic cation transporter 1 polymorphisms predict the metabolic response to metformin in women with the polycystic ovary syndrome.	Metformin	77-86	solute carrier family 22 member 1	Homo sapiens	0-28
20660041-2	2010	Organic cation transporter 1 (OCT1) plays a trigger role in the hepatic uptake of metformin.	Metformin	82-91	solute carrier family 22 member 1	Homo sapiens	0-28
20660041-2	2010	Organic cation transporter 1 (OCT1) plays a trigger role in the hepatic uptake of metformin.	Metformin	82-91	solute carrier family 22 member 1	Homo sapiens	30-34
20660041-3	2010	In cellular studies, it was recently shown that seven polymorphisms of OCT1 exhibit reduced transport of metformin.	Metformin	105-114	solute carrier family 22 member 1	Homo sapiens	71-75
20660041-5	2010	OBJECTIVE: The aim was testing the hypothesis that polymorphisms in OCT1 may contribute to the variability in the response to metformin in PCOS.	Metformin	126-135	solute carrier family 22 member 1	Homo sapiens	68-72
20660041-13	2010	CONCLUSIONS: Genetic variation in OCT1 may be associated with heterogeneity in the metabolic response to metformin in women with PCOS.	Metformin	105-114	solute carrier family 22 member 1	Homo sapiens	34-38
20639304-1	2010	Organic cation transporter 1 (OCT1; SLC22A1) seems to play a role in the efficacy and disposition of the widely used antidiabetic drug metformin.	Metformin	135-144	solute carrier family 22 member 1	Homo sapiens	30-34
20639304-1	2010	Organic cation transporter 1 (OCT1; SLC22A1) seems to play a role in the efficacy and disposition of the widely used antidiabetic drug metformin.	Metformin	135-144	solute carrier family 22 member 1	Homo sapiens	36-43
20639304-4	2010	The goal of this study is to identify genetic variants of OCT1 in Chinese and Japanese populations, which may potentially modulate response to metformin.	Metformin	143-152	solute carrier family 22 member 1	Homo sapiens	58-62
20639304-8	2010	The uptake of metformin in cells expressing Q97K, P117L, and R206C was significantly reduced relative to the OCT1 reference (62 +- 4.3, 55 +- 6.8, and 22 +- 1.5% for Q97K, P117L, and R206C, respectively).	Metformin	14-23	solute carrier family 22 member 1	Homo sapiens	109-113
20639304-12	2010	This study suggests that nonsynonymous variants of OCT1 in Chinese and Japanese populations may affect the differential response to metformin.	Metformin	132-141	solute carrier family 22 member 1	Homo sapiens	51-55
20003069-9	2010	Metformin improves markers of insulin sensitivity and reduces BMI in children and adolescents with clinical insulin resistance or pre-diabetes.	Metformin	0-9	insulin	Homo sapiens	30-37
20003069-9	2010	Metformin improves markers of insulin sensitivity and reduces BMI in children and adolescents with clinical insulin resistance or pre-diabetes.	Metformin	0-9	insulin	Homo sapiens	108-115
20840272-3	2010	Metformin has been introduced as a therapeutic option in PCOS, targeting of cardiometabolic and reproductive abnormalities on the basis of its action on the reduction of glucose levels and the attenuation of insulin resistance.	Metformin	0-9	insulin	Homo sapiens	208-215
21264109-3	2010	Deficiency of Vitamin B12 (vit B(12)) is a known sequel of prolonged metformin therapy.	Metformin	69-78	vitrin	Homo sapiens	27-30
21264109-4	2010	It was recommended to have annual measurement of serum vit B(12) levels in patients on long term metformin therapy way back in 1970 itself.	Metformin	97-106	vitrin	Homo sapiens	55-58
21264109-5	2010	After more than 50 years of use of metformin, we have come to know that metformin induced vit B(12) deficiency can cause neuropathy; forcing to change the recommendation from annual screening of vit B(12) levels to annual supplementation of vit B(12).	Metformin	35-44	vitrin	Homo sapiens	90-93
21264109-5	2010	After more than 50 years of use of metformin, we have come to know that metformin induced vit B(12) deficiency can cause neuropathy; forcing to change the recommendation from annual screening of vit B(12) levels to annual supplementation of vit B(12).	Metformin	72-81	vitrin	Homo sapiens	90-93
21714292-7	2010	Thus, metformin and ramipril combination in patients with MS leads to decrease in insulin resistancy, carbohydrate and lipid metabolism normalization, to restoration of endothelium functions that is possible to consider as prophylaxis of the development of type 2 diabetes melitus and its cardiovascular complications.	Metformin	6-15	insulin	Homo sapiens	82-89
19937362-9	2010	There was also significant reductions in serum C reactive protein levels in both sibutramine (P = 0.045, P = 0.02) and sibutramine plus metformin groups (P = 0.007, P = 0.001) after 3 and 12 months, respectively.	Metformin	136-145	C-reactive protein	Homo sapiens	47-65
29699342-10	2010	Treatment with an insulin-sensitizing agent (metformin) improves the levels of glycodelin, insulin-like growth factor binding protein 1, and blood flow in spiral arteries during the peri-implantation period.	Metformin	45-54	insulin	Homo sapiens	18-25
29699342-13	2010	Metformin treatment improves the levels of insulin, the homeostasis model assessment for insulin resistance, and plasminogen activator inhibitor activity, and decreases early pregnancy loss.	Metformin	0-9	insulin	Homo sapiens	43-50
29699342-13	2010	Metformin treatment improves the levels of insulin, the homeostasis model assessment for insulin resistance, and plasminogen activator inhibitor activity, and decreases early pregnancy loss.	Metformin	0-9	insulin	Homo sapiens	89-96
20204498-2	2010	Metformin, a caloric restriction mimetic, has a long history of safe use as an insulin sensitizer in diabetics and has been shown to reduce cancer incidence and cancer-related mortality in humans.	Metformin	0-9	insulin	Homo sapiens	79-86
20204498-5	2010	Metformin therapy with the various diets indicated that metformin can be highly effective at suppressing systemic metabolic biomarkers such as IGF-1, insulin and glucose, especially in the high energy diet treated animals.	Metformin	0-9	insulin	Homo sapiens	150-157
20204498-5	2010	Metformin therapy with the various diets indicated that metformin can be highly effective at suppressing systemic metabolic biomarkers such as IGF-1, insulin and glucose, especially in the high energy diet treated animals.	Metformin	56-65	insulin	Homo sapiens	150-157
20810671-2	2010	(beginning on page 1066 in this issue of the journal) assessing the efficacy of the antidiabetes drug metformin in a mouse model of lung carcinogenesis suggests protective effects via two possible avenues: Decreased circulating insulin and insulin-like growth factor levels and energy stress leading to inhibition of mammalian target of rapamycin signaling.	Metformin	102-111	mechanistic target of rapamycin kinase	Homo sapiens	317-346
20656475-1	2010	Metformin is widely used in the treatment of diabetes mellitus type 2 where it reduces insulin resistance and diabetes-related morbidity and mortality.	Metformin	0-9	insulin	Homo sapiens	87-94
20455892-8	2010	Insulin sensitization, initially with metformin but later with trials of additional agents such as thiazolidinediones, is the mainstay of early therapy, but insulin replacement, eventually with very high doses, is required once diabetes has supervened.	Metformin	38-47	insulin	Homo sapiens	0-7
20656475-6	2010	Reversal of these processes through reduction of insulin resistance by the oral anti-diabetic drug metformin is an attractive anti-cancer strategy.	Metformin	99-108	insulin	Homo sapiens	49-56
19628413-8	2010	Metformin stimulated the expression of Runx2 and IGF-1 in three glucose groups, but it did not affect IGF-1R.	Metformin	0-9	RUNX family transcription factor 2	Rattus norvegicus	39-44
20624011-0	2010	Metformin administration restores allopregnanolone response to adrenocorticotropic hormone (ACTH) stimulation in overweight hyperinsulinemic patients with PCOS.	Metformin	0-9	proopiomelanocortin	Homo sapiens	63-90
20624011-0	2010	Metformin administration restores allopregnanolone response to adrenocorticotropic hormone (ACTH) stimulation in overweight hyperinsulinemic patients with PCOS.	Metformin	0-9	proopiomelanocortin	Homo sapiens	92-96
20624011-10	2010	RESULTS: Metformin administration reduced significantly LH, A, T, insulin and BMI, while allopregnanolone was significantly increased with no change in progesterone plasma levels.	Metformin	9-18	insulin	Homo sapiens	66-73
20626240-7	2010	In contrast, only in patients treated with metformin a statistically significant decrease in fasting insulin and cholesterol levels as well as BMI was observed.	Metformin	43-54	insulin	Homo sapiens	101-108
19628413-10	2010	Metformin not only significantly decreased intracellular ROS and apoptosis, but also had a direct osteogenic effect on osteoblasts at all glucose concentrations, which could be partially mediated via promotion of Runx2 and IGF-1 expression.	Metformin	0-9	RUNX family transcription factor 2	Rattus norvegicus	213-218
21446088-14	2010	CONCLUSION: Administration of metformin in type 2 diabetes with metabolic syndrome decreased cardiovascular risk factors by reducing glycemia, triglycerides, BMI, central obesity and insulin resistance.	Metformin	30-39	insulin	Homo sapiens	183-190
21234175-1	2010	AIMS: To evaluate if 2-h post glucose insulin level is an effective tool to monitor insulin resistance in response to metformin therapy, in infertile women with polycystic ovarian syndrome (PCOS).	Metformin	118-127	insulin	Homo sapiens	38-45
21234175-8	2010	CONCLUSION: 2-h post glucose insulin level is an effective tool to monitor insulin resistance in PCOS patients and improves significantly after metformin therapy, similar to improvements observed in clinical, hormonal and metabolic parameters.	Metformin	144-153	insulin	Homo sapiens	29-36
20938417-8	2010	CONCLUSION: In this series of males with metabolic syndrome, treatment with metformin associated with healthy dietary modifications and a mild physical activity increment resulted in significant improvement of insulin sensitivity and increase in total and free testosterone levels, regardless of the presence of hypogonadism.	Metformin	76-85	insulin	Homo sapiens	210-217
20832741-1	2010	Metformin lowers blood glucose by reducing hepatic glucose output, increasing insulin sensitivity and enhancing peripheral glucose uptake.	Metformin	0-9	insulin	Homo sapiens	78-85
21098866-0	2010	Metformin has adenosine-monophosphate activated protein kinase (AMPK)-independent effects on LPS-stimulated rat primary microglial cultures.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	64-68
21098866-3	2010	Adenosine-monophosphate-activated protein kinase (AMPK) activation is the most well-known mechanism of metformin action; however, some of the biological responses to metformin are not limited to AMPK activation but are mediated by AMPK-independent mechanisms.	Metformin	103-112	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	0-48
21098866-3	2010	Adenosine-monophosphate-activated protein kinase (AMPK) activation is the most well-known mechanism of metformin action; however, some of the biological responses to metformin are not limited to AMPK activation but are mediated by AMPK-independent mechanisms.	Metformin	103-112	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	50-54
21098866-3	2010	Adenosine-monophosphate-activated protein kinase (AMPK) activation is the most well-known mechanism of metformin action; however, some of the biological responses to metformin are not limited to AMPK activation but are mediated by AMPK-independent mechanisms.	Metformin	166-175	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	0-48
21098866-3	2010	Adenosine-monophosphate-activated protein kinase (AMPK) activation is the most well-known mechanism of metformin action; however, some of the biological responses to metformin are not limited to AMPK activation but are mediated by AMPK-independent mechanisms.	Metformin	166-175	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	50-54
21098866-3	2010	Adenosine-monophosphate-activated protein kinase (AMPK) activation is the most well-known mechanism of metformin action; however, some of the biological responses to metformin are not limited to AMPK activation but are mediated by AMPK-independent mechanisms.	Metformin	166-175	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	195-199
21098866-3	2010	Adenosine-monophosphate-activated protein kinase (AMPK) activation is the most well-known mechanism of metformin action; however, some of the biological responses to metformin are not limited to AMPK activation but are mediated by AMPK-independent mechanisms.	Metformin	166-175	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	195-199
21098866-5	2010	The presented evidence supports the conclusion that metformin-activated AMPK participates in regulating the release of TNF-alpha.	Metformin	52-61	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	72-76
21098866-5	2010	The presented evidence supports the conclusion that metformin-activated AMPK participates in regulating the release of TNF-alpha.	Metformin	52-61	tumor necrosis factor	Rattus norvegicus	119-128
20135346-6	2010	siRNA methods confirmed that reduction of AMPK levels attenuates both the IRS-1 Ser(789) phosphorylation and the inhibition of AKT activation associated with metformin exposure.	Metformin	158-167	AKT serine/threonine kinase 1	Homo sapiens	127-130
20135346-0	2010	Metformin and rapamycin have distinct effects on the AKT pathway and proliferation in breast cancer cells.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	53-56
20135346-7	2010	Although both rapamycin and metformin inhibit mTOR (the former directly and the latter through AMPK signaling), our results demonstrate previously unrecognized differences between these agents.	Metformin	28-37	mechanistic target of rapamycin kinase	Homo sapiens	46-50
20135346-2	2010	Adenosine 5"- monophosphate-activated protein kinase (AMPK) activators such as metformin have similar actions, in keeping with the TSC2/1 pathway linking activation of AMPK to inhibition of mTOR.	Metformin	79-88	mechanistic target of rapamycin kinase	Homo sapiens	190-194
20135346-4	2010	We observed that metformin exposure decreases AKT activation, an action opposite to that of rapamycin.	Metformin	17-26	AKT serine/threonine kinase 1	Homo sapiens	46-49
20399918-1	2010	Adenosine 5"-monophosphate-activated protein kinase (AMPK), a regulator of energy homeostasis, has a central role in mediating the appetite-modulating and metabolic effects of many hormones and antidiabetic drugs metformin and glitazones.	Metformin	213-222	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	0-51
20399918-5	2010	We demonstrated that treatment of ROS 17/2.8 cells with AICAR and metformin stimulates Thr-172 phosphorylation of AMPK and dose-dependently increases its activity.	Metformin	66-75	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	114-118
20399918-1	2010	Adenosine 5"-monophosphate-activated protein kinase (AMPK), a regulator of energy homeostasis, has a central role in mediating the appetite-modulating and metabolic effects of many hormones and antidiabetic drugs metformin and glitazones.	Metformin	213-222	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	53-57
20686344-7	2010	The AMPK-activator 5-aminoimidazole-4-Carboxamide-1-beta-Ribofuranoside (AICAR) unexpectedly repressed PB-induced CYP2B mRNA expression as well as AMPK-inhibitor compound C. In contrast, both the AMPK-activator metformin and the constitutive active form of AMPK enhanced PB-induced PB-responsive enhancer module-driven reporter gene expression.	Metformin	211-220	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	4-8
20206412-5	2010	The TRIC-1 study demonstrated that adding metformin to routine treatment improves the possibilities of cure in women and in patients whose insulin sensitivity returns to normal during treatment.	Metformin	42-51	insulin	Homo sapiens	139-146
22278418-5	2012	Furthermore, the influence of pretreatment with insulin or with chemotherapeutic agents on metformin-induced growth inhibition was investigated in thyroid carcinoma cells, in a doxorubicin-resistant thyroid carcinoma cell line, and in derived carcinoma stem cells.	Metformin	91-100	insulin	Homo sapiens	48-55
22278418-7	2012	In addition, metformin antagonized the growth-stimulatory effect of insulin, inhibited clonal cell growth, reduced thyroid cancer sphere formation, and potentiated the antimitogenic effect of chemotherapeutic agents such as doxorubicin and cisplatin on undifferentiated thyroid carcinoma cells.	Metformin	13-22	insulin	Homo sapiens	68-75
22278418-10	2012	CONCLUSIONS: Metformin markedly diminished growth stimulation by insulin and showed an additive antimitogenic effect to chemotherapeutics agents.	Metformin	13-22	insulin	Homo sapiens	65-72
20583965-1	2010	CONTEXT: Metformin improves hyperglycaemia via mechanisms which include activation of AMP-activated protein kinase (AMPK).	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	86-114
20799766-9	2010	The patient was advised to avoid taking recombinant human insulin for the rest of his life and to control hyperglycemia with acarbose and metformin.	Metformin	138-147	insulin	Homo sapiens	58-65
20590612-7	2010	In addition, metformin strongly repressed the PMA-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and protein kinase C(PKC)alpha, whereas the phosphorylation of p38 mitogen-activated protein kinase was not affected by metformin.	Metformin	13-22	mitogen-activated protein kinase 1	Homo sapiens	77-114
20590612-7	2010	In addition, metformin strongly repressed the PMA-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and protein kinase C(PKC)alpha, whereas the phosphorylation of p38 mitogen-activated protein kinase was not affected by metformin.	Metformin	13-22	mitogen-activated protein kinase 1	Homo sapiens	116-119
20590612-7	2010	In addition, metformin strongly repressed the PMA-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and protein kinase C(PKC)alpha, whereas the phosphorylation of p38 mitogen-activated protein kinase was not affected by metformin.	Metformin	13-22	mitogen-activated protein kinase 8	Homo sapiens	122-151
20590612-7	2010	In addition, metformin strongly repressed the PMA-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and protein kinase C(PKC)alpha, whereas the phosphorylation of p38 mitogen-activated protein kinase was not affected by metformin.	Metformin	13-22	mitogen-activated protein kinase 14	Homo sapiens	215-251
20590612-10	2010	CONCLUSIONS AND IMPLICATIONS: Metformin inhibited PMA-induced invasion and migration of human fibrosarcoma cells via Ca(2+)-dependent PKCalpha/ERK and JNK/AP-1-signalling pathways.	Metformin	30-39	protein kinase C alpha	Homo sapiens	134-142
20590612-10	2010	CONCLUSIONS AND IMPLICATIONS: Metformin inhibited PMA-induced invasion and migration of human fibrosarcoma cells via Ca(2+)-dependent PKCalpha/ERK and JNK/AP-1-signalling pathways.	Metformin	30-39	mitogen-activated protein kinase 1	Homo sapiens	143-146
20590612-10	2010	CONCLUSIONS AND IMPLICATIONS: Metformin inhibited PMA-induced invasion and migration of human fibrosarcoma cells via Ca(2+)-dependent PKCalpha/ERK and JNK/AP-1-signalling pathways.	Metformin	30-39	mitogen-activated protein kinase 8	Homo sapiens	151-154
20350924-9	2010	CONCLUSION: The addition of insulin glargine early in the diabetes treatment paradigm in patients for whom sulfonylurea or metformin monotherapy had failed resulted in significantly greater improvements in glycemic control in comparison with the addition of pioglitazone.	Metformin	123-132	insulin	Homo sapiens	28-35
20590612-0	2010	Metformin blocks migration and invasion of tumour cells by inhibition of matrix metalloproteinase-9 activation through a calcium and protein kinase Calpha-dependent pathway: phorbol-12-myristate-13-acetate-induced/extracellular signal-regulated kinase/activator protein-1.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	214-251
20583965-1	2010	CONTEXT: Metformin improves hyperglycaemia via mechanisms which include activation of AMP-activated protein kinase (AMPK).	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	116-120
20583965-2	2010	Recent findings indicate that some metabolic actions of metformin occur also by AMPK-independent mechanisms.	Metformin	56-65	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	80-84
20577046-1	2010	Metformin has become a mainstay in the modest therapeutic armamentarium for the treatment of the insulin resistance of type 2 diabetes mellitus.	Metformin	0-9	insulin	Homo sapiens	97-104
20577053-2	2010	Recently the LKB1/AMP-activated protein kinase (LKB1/AMPK) pathway was proposed to mediate the action of metformin on hepatic gluconeogenesis.	Metformin	105-114	serine/threonine kinase 11	Mus musculus	13-17
20577053-2	2010	Recently the LKB1/AMP-activated protein kinase (LKB1/AMPK) pathway was proposed to mediate the action of metformin on hepatic gluconeogenesis.	Metformin	105-114	serine/threonine kinase 11	Mus musculus	48-52
20577053-11	2010	In conclusion, we demonstrate that metformin inhibits hepatic gluconeogenesis in an LKB1- and AMPK-independent manner via a decrease in hepatic energy state.	Metformin	35-44	serine/threonine kinase 11	Mus musculus	84-88
21350615-10	2010	CONCLUSION: Among insulin sensitizers, metformin has more favorable, persistent and multifacet effects in MS with SSUF.	Metformin	39-48	insulin	Homo sapiens	18-25
20371705-0	2010	Metformin, an antidiabetic agent, suppresses the production of tumor necrosis factor and tissue factor by inhibiting early growth response factor-1 expression in human monocytes in vitro.	Metformin	0-9	tumor necrosis factor	Homo sapiens	63-84
20371705-5	2010	Metformin significantly inhibited both TNF production and TF expression in isolated human monocytes stimulated with LPS or oxLDL.	Metformin	0-9	tumor necrosis factor	Homo sapiens	39-42
20371705-6	2010	Metformin also significantly inhibited TNF and TF mRNA in human monocytes stimulated with LPS.	Metformin	0-9	tumor necrosis factor	Homo sapiens	39-42
20371705-7	2010	Although metformin did not inhibit the activation of either nuclear factor-kappaB or activator protein-1, it inhibited the expression of early growth response factor-1 (Egr-1) and phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2 in monocytes stimulated with LPS or oxLDL.	Metformin	9-18	mitogen-activated protein kinase 3	Homo sapiens	199-254
20371705-8	2010	These results suggest that metformin may attenuate the inflammatory responses, at least in part, by suppressing the production of both TNF and TF through the inhibition of the ERK1/2-Egr-1 pathway in human monocytes.	Metformin	27-36	tumor necrosis factor	Homo sapiens	135-138
20564343-2	2010	Adenosine monophosphate-activated protein kinase (AMPK) is known to be activated by metformin and to inhibit the mammalian target of rapamycin (mTOR) pathway.	Metformin	84-93	mechanistic target of rapamycin kinase	Homo sapiens	144-148
20228137-0	2010	Metformin blocks the stimulative effect of a high-energy diet on colon carcinoma growth in vivo and is associated with reduced expression of fatty acid synthase.	Metformin	0-9	fatty acid synthase	Mus musculus	141-160
20597621-4	2010	Metformin induces higher glucose uptake, thus inducing a lower synthesis/secretion of insulin.	Metformin	0-9	insulin	Homo sapiens	86-93
20573187-10	2010	Based on six trials with placebo or no treatment controls, metformin reduced fasting insulin (WMD -8.94 mU/L; CI -13.0, -4.90), triglycerides (WMD -42.87 mg/dL; CI -73.3, -12.5), body mass index (WMD -0.70 kg/m2; CI -1.09, -0.31) and waist-to-hip ratio (WMD -0.02; CI -0.03, 0.00).	Metformin	59-68	insulin	Homo sapiens	85-92
20573187-16	2010	Metformin was the only insulin-sensitizer to demonstrate beneficial effects on all three components of HALS.	Metformin	0-9	insulin	Homo sapiens	23-30
20554237-3	2010	Treatments inducing elevated plasma insulin seem to increase cancer risk but insulin-sensitizers (metformine, thiazolidinediones) seem to reduce cancer risk.	Metformin	98-108	insulin	Homo sapiens	77-84
20228137-6	2010	We observed that metformin blocked the effect of the high-energy diet on tumor growth, reduced insulin levels, and attenuated the effect of diet on phosphorylation of AKT and expression of FASN.	Metformin	17-26	thymoma viral proto-oncogene 1	Mus musculus	167-170
20228137-6	2010	We observed that metformin blocked the effect of the high-energy diet on tumor growth, reduced insulin levels, and attenuated the effect of diet on phosphorylation of AKT and expression of FASN.	Metformin	17-26	fatty acid synthase	Mus musculus	189-193
20610860-9	2010	In addition, metformin reduced the glucose-induced abundance of SGLT-1 in BBM and increased those of GLUT2, concomitantly increasing the phosphorylation of intracellular AMPKalpha2.	Metformin	13-22	solute carrier family 5 member 1	Homo sapiens	64-70
20299472-7	2010	Likewise, AMPK activation by pharmacological (5"-aminoimidazole-4-carboxymide-1-beta-d-ribofuranoside, metformin, and statin) or genetic means (adenoviral overexpression of constitutively active AMPK mutants) significantly mitigated ER stress and SERCA oxidation and improved the endothelium-dependent relaxation in isolated mouse aortae.	Metformin	103-112	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	10-14
24843413-8	2010	Furthermore, we found that metformin and pioglitazone, both of which have the ability to reduce diabetic vascular complications, could ameliorate hyperglycemia-induced mtROS production by the induction of PPARgamma coactivator-1alpha (PGC-1alpha) and MnSOD and/or activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK).	Metformin	27-36	superoxide dismutase 2, mitochondrial	Mus musculus	251-256
20015525-8	2010	There were no significant variations of ADN, R, or TNF-alpha with sitagliptin, whereas a significant increase of ADN and a significant decrease of R and TNF-alpha values were recorded with metformin.	Metformin	189-198	tumor necrosis factor	Homo sapiens	153-162
20015525-10	2010	There was a significant correlation between HOMA-IR decrease and ADN increase, and between HOMA-IR decrease and R and TNF-alpha decrease in pioglitazone plus metformin group after the treatment.	Metformin	158-167	tumor necrosis factor	Homo sapiens	118-127
20015525-11	2010	The addition of both sitagliptin or metformin to pioglitazone gave an improvement of HbA(1c), FPG, and PPG; but metformin led also to a decrease of body weight and to a faster and better improvement of insulin resistance and inflammatory state parameters, even if sitagliptin produced a better protection of beta-cell function.	Metformin	36-45	insulin	Homo sapiens	202-209
20015525-11	2010	The addition of both sitagliptin or metformin to pioglitazone gave an improvement of HbA(1c), FPG, and PPG; but metformin led also to a decrease of body weight and to a faster and better improvement of insulin resistance and inflammatory state parameters, even if sitagliptin produced a better protection of beta-cell function.	Metformin	112-121	insulin	Homo sapiens	202-209
20363874-3	2010	The AMPK activator metformin stimulated AMPK Thr172 phosphorylation and inhibited IGF-I-stimulated phosphorylation of Akt/tuberous sclerosis 2 (TSC2)/mammalian target of rapamycin (mTOR)/p70S6 kinase (p70S6K).	Metformin	19-28	insulin like growth factor 1	Homo sapiens	82-87
20363874-3	2010	The AMPK activator metformin stimulated AMPK Thr172 phosphorylation and inhibited IGF-I-stimulated phosphorylation of Akt/tuberous sclerosis 2 (TSC2)/mammalian target of rapamycin (mTOR)/p70S6 kinase (p70S6K).	Metformin	19-28	mechanistic target of rapamycin kinase	Homo sapiens	150-179
20363874-3	2010	The AMPK activator metformin stimulated AMPK Thr172 phosphorylation and inhibited IGF-I-stimulated phosphorylation of Akt/tuberous sclerosis 2 (TSC2)/mammalian target of rapamycin (mTOR)/p70S6 kinase (p70S6K).	Metformin	19-28	mechanistic target of rapamycin kinase	Homo sapiens	181-185
20363874-10	2010	These findings are relevant to whole animal physiology because administration of metformin to mice resulted in inhibition of IGF-I-stimulated phosphorylation of Akt/mTOR/p70S6K.	Metformin	81-90	thymoma viral proto-oncogene 1	Mus musculus	161-164
20547605-1	2010	Metformin is a biguanide, insulin sensitiser that reduces blood sugar levels.	Metformin	0-9	insulin	Homo sapiens	26-33
20404854-12	2010	Agents that decrease intestinal carbohydrate digestion (alpha-glucosidase inhibitors) or decrease insulin resistance (metformin) might be alternative adjunctive therapies in T1DM, though its benefits are marginally supported by clinical data.	Metformin	118-127	insulin	Homo sapiens	98-105
20815278-7	2010	The elevated PTP1B expression in liver of T2DM rats was decreased in the TFLC treated group, but unchanged in the metformin treated group.	Metformin	114-123	protein tyrosine phosphatase, non-receptor type 1	Rattus norvegicus	13-18
20398632-0	2010	Metformin reduces intracellular reactive oxygen species levels by upregulating expression of the antioxidant thioredoxin via the AMPK-FOXO3 pathway.	Metformin	0-9	forkhead box O3	Homo sapiens	134-139
20939194-7	2010	Metformin can significantly alleviate the lesions of hepatic steatosis and fibrosis, markedly reduce the expressions of alpha-SMA and TGFbeta1 in liver tissue of type 2 diabetic rats.	Metformin	0-9	transforming growth factor, beta 1	Rattus norvegicus	134-142
20398632-9	2010	CONCLUSION: These results suggest that metformin reduces ROS levels by inducing Trx expression through activation of the AMPK-FOXO3 pathway.	Metformin	39-48	forkhead box O3	Homo sapiens	126-131
20444419-3	2010	It is thought that agents that increase the cellular AMP/ATP ratio, such as the antidiabetic biguanides metformin and phenformin, inhibit mTORC1 through AMPK activation of TSC1/2-dependent or -independent mechanisms.	Metformin	104-113	TSC complex subunit 1	Homo sapiens	172-176
20038265-4	2010	Metformin significantly inhibited palmitate-induced cell death and apoptosis via caspase-3 activation.	Metformin	0-9	caspase 3	Homo sapiens	81-90
20038265-5	2010	Metformin also blocked the induction of ER stress proteins (GRP78, Chop, Cleaved ATF-6, p-eIF2 alpha and XBP-1) and regulated serine phosphorylation of IRS-1.	Metformin	0-9	heat shock protein family A (Hsp70) member 5	Homo sapiens	60-65
20038265-5	2010	Metformin also blocked the induction of ER stress proteins (GRP78, Chop, Cleaved ATF-6, p-eIF2 alpha and XBP-1) and regulated serine phosphorylation of IRS-1.	Metformin	0-9	DNA damage inducible transcript 3	Homo sapiens	67-71
20559501-6	2010	In contrast, the combination of glibenclamide, metformin and honey significantly up-regulated CAT activity and down-regulated GPx activity while TBARS levels were significantly reduced.	Metformin	47-56	catalase	Rattus norvegicus	94-97
20394912-5	2010	The use of insulin sensitizers i.e. metformin in PCOS should be restricted to women with glucose intolerance and/or insulin resistance.	Metformin	36-45	insulin	Homo sapiens	11-18
20394912-5	2010	The use of insulin sensitizers i.e. metformin in PCOS should be restricted to women with glucose intolerance and/or insulin resistance.	Metformin	36-45	insulin	Homo sapiens	116-123
20465505-4	2010	There is also a growing interest in the use of metformin, which has been shown to possess antitumor activity resulting from activation of AMP-activated protein kinase and subsequent inhibiton of mTOR, as well as from decreased circulating insulin levels.	Metformin	47-56	mechanistic target of rapamycin kinase	Homo sapiens	195-199
20388847-0	2010	Crosstalk between insulin/insulin-like growth factor-1 receptors and G protein-coupled receptor signaling systems: a novel target for the antidiabetic drug metformin in pancreatic cancer.	Metformin	156-165	insulin	Homo sapiens	18-25
20388847-0	2010	Crosstalk between insulin/insulin-like growth factor-1 receptors and G protein-coupled receptor signaling systems: a novel target for the antidiabetic drug metformin in pancreatic cancer.	Metformin	156-165	insulin	Homo sapiens	26-33
20388847-6	2010	Recent results show that metformin-induced activation of AMPK disrupts crosstalk between insulin/IGF-1 receptor and GPCR signaling in pancreatic cancer cells and inhibits the growth of these cells in xenograft models.	Metformin	25-34	insulin	Homo sapiens	89-96
20388847-6	2010	Recent results show that metformin-induced activation of AMPK disrupts crosstalk between insulin/IGF-1 receptor and GPCR signaling in pancreatic cancer cells and inhibits the growth of these cells in xenograft models.	Metformin	25-34	insulin like growth factor 1	Homo sapiens	97-102
20388847-9	2010	We posit that crosstalk between insulin/IGF-1 receptor and GPCR signaling is a mechanism for promoting the development of certain types of cancer and a target for the prevention and therapy of these diseases via metformin administration.	Metformin	212-221	insulin	Homo sapiens	32-39
20388847-9	2010	We posit that crosstalk between insulin/IGF-1 receptor and GPCR signaling is a mechanism for promoting the development of certain types of cancer and a target for the prevention and therapy of these diseases via metformin administration.	Metformin	212-221	insulin like growth factor 1	Homo sapiens	40-45
20465505-4	2010	There is also a growing interest in the use of metformin, which has been shown to possess antitumor activity resulting from activation of AMP-activated protein kinase and subsequent inhibiton of mTOR, as well as from decreased circulating insulin levels.	Metformin	47-56	insulin	Homo sapiens	239-246
20465505-5	2010	Metformin has been shown to inhibit proliferation, invasion and angiogenesis of neoplastic cells and to overcome resistance of breast cancer to chemotherapy, hormonal therapy and HER2 inhibition.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	179-183
30861688-5	2010	Metformin is an insulin sensitizer that effectively acts against insulin resistance, one of the predominant metabolic defects in T2DM.	Metformin	0-9	insulin	Homo sapiens	16-23
30861688-5	2010	Metformin is an insulin sensitizer that effectively acts against insulin resistance, one of the predominant metabolic defects in T2DM.	Metformin	0-9	insulin	Homo sapiens	65-72
20442309-3	2010	Second, metformin decreases insulin resistance and indirectly reduces insulin level, a beneficial effect because insulin promotes cancer cell growth.	Metformin	8-17	insulin	Homo sapiens	28-35
20057994-5	2010	Metformin was associated with reductions in: (1) insulin-dose requirement (5.7-10.1 U/day in six of seven studies); (2) HbA(1c) (0.6-0.9% in four of seven studies); (3) weight (1.7-6.0 kg in three of six studies); and (4) total cholesterol (0.3-0.41 mmol/l in three of seven studies).	Metformin	0-9	insulin	Homo sapiens	49-56
20057994-9	2010	CONCLUSIONS/INTERPRETATION: Metformin reduces insulin-dose requirement in type 1 diabetes but it is unclear whether this is sustained beyond 1 year and whether there are benefits for cardiovascular and other key clinical outcomes.	Metformin	28-37	insulin	Homo sapiens	46-53
20442309-3	2010	Second, metformin decreases insulin resistance and indirectly reduces insulin level, a beneficial effect because insulin promotes cancer cell growth.	Metformin	8-17	insulin	Homo sapiens	70-77
19694967-1	2010	Insulin sensitizers like metformin generally act through pathways triggered by adenosine monophosphate-activated protein kinase.	Metformin	25-34	insulin	Homo sapiens	0-7
20446599-4	2010	Combined use of metformin and TZDs has theoretical benefit as it targets two main pathophysiologic defects in type 2 diabetes, such as increased gluconeogenesis and peripheral insulin resistance.	Metformin	16-25	insulin	Homo sapiens	176-183
20415692-0	2010	Adding insulin glargine vs. NPH insulin to metformin results in a more efficient postprandial beta-cell protection in individuals with type 2 diabetes.	Metformin	43-52	insulin	Homo sapiens	7-14
20350646-6	2010	Metformin was transported by P-glycoprotein (58 +/- 20%) and breast cancer resistance protein (25 +/- 14%).	Metformin	0-9	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	61-93
20425680-5	2010	A diabetes therapy with insulin or sulfonylureas, which leads to elevated exogenous or endogenous insulin levels, appears to be related with an increased cancer risk, whereas administration of metformin or thiazolidinediones, which is associated with a decrease of insulin concentrations, results in risk reduction.	Metformin	193-202	insulin	Homo sapiens	24-31
20425680-5	2010	A diabetes therapy with insulin or sulfonylureas, which leads to elevated exogenous or endogenous insulin levels, appears to be related with an increased cancer risk, whereas administration of metformin or thiazolidinediones, which is associated with a decrease of insulin concentrations, results in risk reduction.	Metformin	193-202	insulin	Homo sapiens	98-105
20425680-5	2010	A diabetes therapy with insulin or sulfonylureas, which leads to elevated exogenous or endogenous insulin levels, appears to be related with an increased cancer risk, whereas administration of metformin or thiazolidinediones, which is associated with a decrease of insulin concentrations, results in risk reduction.	Metformin	193-202	insulin	Homo sapiens	98-105
20417856-14	2010	These findings support the use of liraglutide as an effective GLP-1 agent to add to metformin.	Metformin	84-93	glucagon	Homo sapiens	62-67
20097729-9	2010	Increased cardiac expression of phosphorylated AKT (pAKT), pGSK3beta, and atrial natriuretic peptide (ANP) was detected in the nonischemic Dpp4(-/-) heart, and HO-1, ANP, and pGSK3beta proteins were induced in nonischemic hearts from diabetic mice treated with sitagliptin or metformin.	Metformin	276-285	thymoma viral proto-oncogene 1	Mus musculus	47-50
20068133-1	2010	OBJECTIVE: The aim of this study was to investigate whether apolipoprotein B100 of LDL suffers increased damage by glycation, oxidation, and nitration in patients with type 2 diabetes, including patients receiving metformin therapy.	Metformin	214-223	apolipoprotein B	Homo sapiens	60-79
20380657-1	2010	To evaluate the effect of metformin on basal and insulin-induced glucose uptake in subcutaneous and visceral preadipocyte-derived adipocytes from obese and non-obese patients, preadipocytes were obtained from subcutaneous and visceral fat depots during abdominal surgery.	Metformin	26-35	insulin	Homo sapiens	49-56
20380657-9	2010	Combined treatment with metformin and insulin increased glucose uptake in subcutaneous preadipocyte-derived adipocytes from both non-obese and obese patients (p < 0.001 vs. insulin alone).	Metformin	24-33	insulin	Homo sapiens	176-183
20215559-2	2010	Metformin inhibits transcription of key gluconeogenesis genes in the liver, increases glucose uptake in skeletal muscle, and decreases circulating insulin levels.	Metformin	0-9	insulin	Homo sapiens	147-154
20106839-8	2010	In both of these groups, and without difference between them, serum androgens and indices of insulin resistance improved significantly (P < 0.05) after metformin treatment.	Metformin	155-164	insulin	Homo sapiens	93-100
20687400-0	2010	Low-dose metformin improves pregnancy rate in in vitro fertilization repeaters without polycystic ovary syndrome: prediction of effectiveness by multiple parameters related to insulin resistance.	Metformin	9-18	insulin	Homo sapiens	176-183
20687400-14	2010	CONCLUSIONS: Low-dose metformin improved pregnancy rate in IVF repeaters without PCOS, probably by decreasing insulin resistance.	Metformin	22-31	insulin	Homo sapiens	110-117
20156067-1	2010	BACKGROUND: Obese women with polycystic ovary syndrome (PCOS) manifest impaired insulin-stimulated release of a d-chiro-inositol-containing inositolphosphoglycan (DCI-IPG) insulin mediator during oral glucose tolerance testing (OGTT), which appears to be restored by the administration of metformin.	Metformin	289-298	insulin	Homo sapiens	80-87
20215500-0	2010	Targeting cancer cell metabolism: the combination of metformin and 2-deoxyglucose induces p53-dependent apoptosis in prostate cancer cells.	Metformin	53-62	tumor protein p53	Homo sapiens	90-93
20215500-6	2010	At the cellular level, the combination of metformin and 2DG induced p53-dependent apoptosis via the energy sensor pathway AMP kinase, and the reexpression of a functional p53 in p53-deficient prostate cancer cells restored caspase-3 activity.	Metformin	42-51	tumor protein p53	Homo sapiens	68-71
20215500-6	2010	At the cellular level, the combination of metformin and 2DG induced p53-dependent apoptosis via the energy sensor pathway AMP kinase, and the reexpression of a functional p53 in p53-deficient prostate cancer cells restored caspase-3 activity.	Metformin	42-51	tumor protein p53	Homo sapiens	171-174
20215500-6	2010	At the cellular level, the combination of metformin and 2DG induced p53-dependent apoptosis via the energy sensor pathway AMP kinase, and the reexpression of a functional p53 in p53-deficient prostate cancer cells restored caspase-3 activity.	Metformin	42-51	caspase 3	Homo sapiens	223-232
20215500-7	2010	In addition to apoptosis, the combination of metformin and 2DG arrested prostate cancer cells in G(2)-M. This G(2)-M arrest was independent of p53 and correlated with a stronger decrease in cell viability than obtained with either drug.	Metformin	45-54	tumor protein p53	Homo sapiens	143-146
20215559-3	2010	Metformin reduces levels of circulating glucose, increases insulin sensitivity, and reduces insulin resistance-associated hyperinsulinemia.	Metformin	0-9	insulin	Homo sapiens	59-66
20053525-5	2010	Metformin treatment attenuated the main components of the fibrovascular tissue, wet weight, vascularization (Hb content), macrophage recruitment (NAG activity), collagen deposition and the levels of transforming growth factor (TGF-beta1) intraimplant.	Metformin	0-9	alpha-N-acetylglucosaminidase (Sanfilippo disease IIIB)	Mus musculus	146-149
20023292-6	2010	RESULTS: (i) In newborns, SHBG levels were higher in the metformin group.	Metformin	57-66	sex hormone binding globulin	Homo sapiens	26-30
20148739-6	2010	A significant reduction in serum fasting insulin, HOMA index, waist and testosterone levels was only observed with metformin.	Metformin	115-124	insulin	Homo sapiens	41-48
20148739-9	2010	These findings suggest that metformin has an additive effect to diet and exercise to improve parameters of hyperandrogenism and insulin resistance.	Metformin	28-37	insulin	Homo sapiens	128-135
20023292-11	2010	CONCLUSIONS: Intrauterine metformin exposure seems to result in elevated SHBG levels in newborns.	Metformin	26-35	sex hormone binding globulin	Homo sapiens	73-77
19815243-0	2010	Effects of rosiglitazone and metformin treatment on apelin, visfatin, and ghrelin levels in patients with type 2 diabetes mellitus.	Metformin	29-38	apelin	Homo sapiens	52-58
20158555-8	2010	Metformin use was clearly associated with lower vitamin B12 levels.	Metformin	0-9	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	56-59
20158555-9	2010	In patients aged 65 and older, an inverse correlation was found between vitamin B12 levels and albumin, metformin, and angiotensin-converting enzyme (ACE) inhibitor use.	Metformin	104-113	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	80-83
19815243-6	2010	Both rosiglitazone and metformin led to similar, significant improvement in glycemic profile and apelin levels, whereas lipid parameters, fat mass, and visfatin remained almost unaffected (P > .05).	Metformin	23-32	apelin	Homo sapiens	97-103
19815243-12	2010	Both rosiglitazone and metformin favorably changed glycemic indexes and apelin levels.	Metformin	23-32	apelin	Homo sapiens	72-78
19887597-0	2010	AICAR and metformin, but not exercise, increase muscle glucose transport through AMPK-, ERK-, and PDK1-dependent activation of atypical PKC.	Metformin	10-19	mitogen-activated protein kinase 1	Mus musculus	88-91
20134380-0	2010	Metformin-induced vitamin B12 deficiency presenting as a peripheral neuropathy.	Metformin	0-9	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	26-29
20134380-1	2010	Chronic metformin use results in vitamin B12 deficiency in 30% of patients.	Metformin	8-17	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	41-44
20134380-6	2010	To my knowledge, this is the first report of metformin-induced vitamin B12 deficiency causing neuropathy.	Metformin	45-54	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	71-74
20102700-0	2010	Metformin reduces lipid accumulation in macrophages by inhibiting FOXO1-mediated transcription of fatty acid-binding protein 4.	Metformin	0-9	forkhead box O1	Homo sapiens	66-71
20102700-6	2010	Metformin promoted the expression of carnitine palmitoyltransferase I (CPT-1), while reduced the expression of fatty acid-binding protein 4 (FABP4) which was involved in PA-induced lipid accumulation.	Metformin	0-9	carnitine palmitoyltransferase 1A	Homo sapiens	71-76
20102700-11	2010	Metformin reduced FABP4 expression by promoting FOXO1 nuclear exclusion and subsequently inhibiting its activity.	Metformin	0-9	forkhead box O1	Homo sapiens	48-53
20102700-12	2010	CONCLUSIONS: Taken together, these results suggest that metformin reduces lipid accumulation in macrophages by repressing FOXO1-mediated FABP4 transcription.	Metformin	56-65	forkhead box O1	Homo sapiens	122-127
19887597-5	2010	Finally, in intact rodents, AICAR and metformin activated aPKC in muscle, but not in liver, despite activating AMPK in both tissues.	Metformin	38-47	protein kinase C, zeta	Mus musculus	58-62
19887597-6	2010	The findings demonstrate that in muscle AICAR and metformin activate aPKC via sequential activation of AMPK, ERK, and PDK1 and the AMPK/ERK/PDK1/aPKC pathway is required for metformin- and AICAR-stimulated increases in glucose transport.	Metformin	50-59	protein kinase C, zeta	Mus musculus	69-73
19887597-6	2010	The findings demonstrate that in muscle AICAR and metformin activate aPKC via sequential activation of AMPK, ERK, and PDK1 and the AMPK/ERK/PDK1/aPKC pathway is required for metformin- and AICAR-stimulated increases in glucose transport.	Metformin	50-59	mitogen-activated protein kinase 1	Mus musculus	109-112
19887597-0	2010	AICAR and metformin, but not exercise, increase muscle glucose transport through AMPK-, ERK-, and PDK1-dependent activation of atypical PKC.	Metformin	10-19	pyruvate dehydrogenase kinase, isoenzyme 1	Mus musculus	98-102
19887597-6	2010	The findings demonstrate that in muscle AICAR and metformin activate aPKC via sequential activation of AMPK, ERK, and PDK1 and the AMPK/ERK/PDK1/aPKC pathway is required for metformin- and AICAR-stimulated increases in glucose transport.	Metformin	50-59	pyruvate dehydrogenase kinase, isoenzyme 1	Mus musculus	118-122
19887597-6	2010	The findings demonstrate that in muscle AICAR and metformin activate aPKC via sequential activation of AMPK, ERK, and PDK1 and the AMPK/ERK/PDK1/aPKC pathway is required for metformin- and AICAR-stimulated increases in glucose transport.	Metformin	50-59	mitogen-activated protein kinase 1	Mus musculus	136-139
19887597-1	2010	Activators of 5"-AMP-activated protein kinase (AMPK) 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), metformin, and exercise activate atypical protein kinase C (aPKC) and ERK and stimulate glucose transport in muscle by uncertain mechanisms.	Metformin	117-126	protein kinase C, zeta	Mus musculus	150-175
19887597-6	2010	The findings demonstrate that in muscle AICAR and metformin activate aPKC via sequential activation of AMPK, ERK, and PDK1 and the AMPK/ERK/PDK1/aPKC pathway is required for metformin- and AICAR-stimulated increases in glucose transport.	Metformin	50-59	pyruvate dehydrogenase kinase, isoenzyme 1	Mus musculus	140-144
19887597-6	2010	The findings demonstrate that in muscle AICAR and metformin activate aPKC via sequential activation of AMPK, ERK, and PDK1 and the AMPK/ERK/PDK1/aPKC pathway is required for metformin- and AICAR-stimulated increases in glucose transport.	Metformin	50-59	protein kinase C, zeta	Mus musculus	145-149
19887597-6	2010	The findings demonstrate that in muscle AICAR and metformin activate aPKC via sequential activation of AMPK, ERK, and PDK1 and the AMPK/ERK/PDK1/aPKC pathway is required for metformin- and AICAR-stimulated increases in glucose transport.	Metformin	174-183	mitogen-activated protein kinase 1	Mus musculus	136-139
19887597-6	2010	The findings demonstrate that in muscle AICAR and metformin activate aPKC via sequential activation of AMPK, ERK, and PDK1 and the AMPK/ERK/PDK1/aPKC pathway is required for metformin- and AICAR-stimulated increases in glucose transport.	Metformin	174-183	pyruvate dehydrogenase kinase, isoenzyme 1	Mus musculus	140-144
19887597-6	2010	The findings demonstrate that in muscle AICAR and metformin activate aPKC via sequential activation of AMPK, ERK, and PDK1 and the AMPK/ERK/PDK1/aPKC pathway is required for metformin- and AICAR-stimulated increases in glucose transport.	Metformin	174-183	protein kinase C, zeta	Mus musculus	145-149
19887597-1	2010	Activators of 5"-AMP-activated protein kinase (AMPK) 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), metformin, and exercise activate atypical protein kinase C (aPKC) and ERK and stimulate glucose transport in muscle by uncertain mechanisms.	Metformin	117-126	protein kinase C, zeta	Mus musculus	177-181
19887597-1	2010	Activators of 5"-AMP-activated protein kinase (AMPK) 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), metformin, and exercise activate atypical protein kinase C (aPKC) and ERK and stimulate glucose transport in muscle by uncertain mechanisms.	Metformin	117-126	mitogen-activated protein kinase 1	Mus musculus	187-190
19892338-0	2010	Metformin versus laparoscopic ovarian drilling in clomiphene- and insulin-resistant women with polycystic ovary syndrome.	Metformin	0-9	insulin	Homo sapiens	66-73
19892338-8	2010	CONCLUSION: Although metformin results in a better attenuation of insulin resistance, laparoscopic ovarian drilling is associated with higher rates of ovulation and pregnancy.	Metformin	21-30	insulin	Homo sapiens	66-73
19996308-8	2010	Metformin also reduced weight (P < 0.001), waist circumference (P < 0.001), and triglycerides (P = 0.004) and increased adiponectin (P = 0.001) but did not affect testosterone or other metabolic measures.	Metformin	0-9	adiponectin, C1Q and collagen domain containing	Homo sapiens	126-137
20229055-4	2010	Two known AMPK activators (metformin and AICAR) were used to verify the hypothesis that a transitory activation of AMPK at reperfusion may exert cardioprotection, as reflected in a reduction in myocardial infarct size.	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	115-119
20229055-11	2010	In addition, alpha-AMPK phosphorylation was significantly increased in the metformin treated group during the initial 30 min of reperfusion.	Metformin	75-84	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	19-23
19496972-1	2010	The aim of this randomized, placebo-controlled study was to explore the effect of metformin in children with a neurogenic or myogenic motor deficit, who are therefore prone to develop overweight, adiposity, and insulin resistance.	Metformin	82-91	insulin	Homo sapiens	211-218
19594306-7	2010	We found that metformin administration both in vivo and in vitro caused an increase in alkaline phosphatase activity, type I collagen synthesis, osteocalcin expression, and extracellular calcium deposition of BMPCs.	Metformin	14-23	bone gamma-carboxyglutamate protein	Rattus norvegicus	145-156
19594306-9	2010	In vivo, metformin administration enhanced the expression of osteoblast-specific transcription factor Runx2/Cbfa1 and activation of AMPK in a time-dependent manner.	Metformin	9-18	RUNX family transcription factor 2	Rattus norvegicus	102-107
19594306-9	2010	In vivo, metformin administration enhanced the expression of osteoblast-specific transcription factor Runx2/Cbfa1 and activation of AMPK in a time-dependent manner.	Metformin	9-18	RUNX family transcription factor 2	Rattus norvegicus	108-113
19594306-12	2010	In conclusion, our results indicate that metformin causes an osteogenic effect both in vivo and in vitro, possibly mediated by Runx2/Cbfa1 and AMPK activation, suggesting a possible action of metformin in a shift toward the osteoblastic differentiation of BMPCs.	Metformin	41-50	RUNX family transcription factor 2	Rattus norvegicus	127-132
19594306-12	2010	In conclusion, our results indicate that metformin causes an osteogenic effect both in vivo and in vitro, possibly mediated by Runx2/Cbfa1 and AMPK activation, suggesting a possible action of metformin in a shift toward the osteoblastic differentiation of BMPCs.	Metformin	41-50	RUNX family transcription factor 2	Rattus norvegicus	133-138
19594306-12	2010	In conclusion, our results indicate that metformin causes an osteogenic effect both in vivo and in vitro, possibly mediated by Runx2/Cbfa1 and AMPK activation, suggesting a possible action of metformin in a shift toward the osteoblastic differentiation of BMPCs.	Metformin	192-201	RUNX family transcription factor 2	Rattus norvegicus	133-138
20012266-0	2010	Metformin increases phagocytosis and acidifies lysosomal/endosomal compartments in AMPK-dependent manner in rat primary microglia.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	83-87
20012266-6	2010	To elucidate the mechanism of metformin action, we used 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside as an activator of adenosine monophosphate-activated protein kinase (AMPK) and compound C as a confirmed pharmacological inhibitor of AMPK.	Metformin	30-39	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	130-178
20012266-6	2010	To elucidate the mechanism of metformin action, we used 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside as an activator of adenosine monophosphate-activated protein kinase (AMPK) and compound C as a confirmed pharmacological inhibitor of AMPK.	Metformin	30-39	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	180-184
20012266-6	2010	To elucidate the mechanism of metformin action, we used 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside as an activator of adenosine monophosphate-activated protein kinase (AMPK) and compound C as a confirmed pharmacological inhibitor of AMPK.	Metformin	30-39	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	245-249
20012266-7	2010	We have shown that metformin increased AMPK activity in microglial cells and that all observed effects are AMPK-dependent because the pretreatment of microglia with compound C reversed the effects of the drug.	Metformin	19-28	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	39-43
20640230-7	2010	In conjunction with weight reduction and exercise, a pharmacologic reduction in insulin levels by either metformin or thiazolidinediones ameliorates both hyperinsulinemia and hyperandrogenism.	Metformin	105-114	insulin	Homo sapiens	80-87
19496972-5	2010	As compared to placebo, metformin intake for 6 months exerted an insulin sensitizing effect and lowered weight (mean difference of 2 kg within 6 months, p = 0.007) and BMI (p = 0.016).	Metformin	24-33	insulin	Homo sapiens	65-72
19496972-8	2010	In conclusion, metformin treatment for 6 months was associated with a rise in insulin sensitivity and with a reduction of visceral adiposity in children and adolescents with a primary muscle disorder or with a neural tube defect.	Metformin	15-24	insulin	Homo sapiens	78-85
19906888-5	2010	Treatment with metformin (10 mM) for 24 h reduced cell proliferation and the levels of cyclin D2 and E, and increased the associations cyclin D2/p21 and cyclin D2/p27 without affecting cell viability in response to IGF1 (10(-8) M).	Metformin	15-24	cyclin dependent kinase inhibitor 1A	Bos taurus	145-148
19906888-8	2010	Adenovirus-mediated expression of dominant-negative AMPK totally abolished the effects of metformin on cell proliferation and phosphorylation of P70S6K in response to IGF1.	Metformin	90-99	ribosomal protein S6 kinase B1	Bos taurus	145-151
20948845-3	2010	Co-administered metformin seems to mitigate the risk associated with insulin.	Metformin	16-25	insulin	Homo sapiens	69-76
20126541-8	2010	Administration of the glycolytic inhibitor 2-deoxy-D-glucose (2DG) or the mitochondrial toxin and anti-Type II Diabetes drug, metformin, or AMP mimetic AICAR results in activation of AMPK, repression of the mTOR pathway and prevents maintenance of Late-Phase LTP (L-LTP).	Metformin	126-135	mechanistic target of rapamycin kinase	Homo sapiens	207-211
20091537-0	2010	Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility.	Metformin	27-36	insulin	Homo sapiens	0-7
20091537-3	2010	If insulin sensitising agents such as metformin are effective in treating features of PCOS, then they could have wider health benefits than just treating the symptoms of the syndrome.	Metformin	38-47	insulin	Homo sapiens	3-10
19884247-0	2010	Incorporating the antidiabetic drug metformin in HER2-positive breast cancer treated with neo-adjuvant chemotherapy and trastuzumab: an ongoing clinical-translational research experience at the Catalan Institute of Oncology.	Metformin	36-45	erb-b2 receptor tyrosine kinase 2	Homo sapiens	49-53
19330342-6	2010	EE/CA-metformin group showed higher proportional reduction fasting insulin concentrations, HOMA-IR and free testosterone levels than metformin alone and EE/CA-spironolactone groups.	Metformin	6-15	insulin	Homo sapiens	67-74
20216906-7	2010	Management approaches included treatment switching and metformin, both of which have shown benefit for insulin-resistant individuals with isolated fat accumulation.	Metformin	55-64	insulin	Homo sapiens	103-110
20823565-10	2010	The Rosiglitazone/Metformin combination further increased these gene expressions, especially PPARalpha.	Metformin	18-27	peroxisome proliferator activated receptor alpha	Mus musculus	93-102
20130740-8	2010	Therefore, these results suggest that HPS3 may partly ameliorate hyperglycemia and hyperlipidemia associated with type 2 diabetes through increased insulin secretion, inhibition of lipid peroxidation, promotion of sensitivity to insulin, suppression of gluconeogenesis and reduction in the biosynthesis fatty acid, cholesterol and cell cytokines related to insulin resistance, and it could be a useful adjunct therapy to a proven first-line therapy for type 2 diabetes using metformin.	Metformin	475-484	HPS3, biogenesis of lysosomal organelles complex 2 subunit 1	Mus musculus	38-42
19761871-3	2010	OBJECTIVES: TONIC is conducted to test whether treatment with metformin, an insulin sensitizer, or vitamin E, a naturally available antioxidant, will lead to improvements in biochemical and histological features of nondiabetic children with biopsy-proven NAFLD.	Metformin	62-71	insulin	Homo sapiens	76-83
20332619-0	2010	Metformin treatment of diabetes mellitus increases the risk for pancreatitis in patients bearing the CFTR-mutation S573C.	Metformin	0-9	CF transmembrane conductance regulator	Homo sapiens	101-105
20332619-7	2010	Yet here, we find that S573C-CFTR manifests a metformin-inhibitable whole cell chloride-conductance after cAMP elevation.	Metformin	46-55	CF transmembrane conductance regulator	Homo sapiens	29-33
20332619-10	2010	We conclude that defective S573C-CFTR remains both poorly conducting and inhibited by metformin and intracellular acidosis.	Metformin	86-95	CF transmembrane conductance regulator	Homo sapiens	33-37
19822355-13	2010	In parallel, treatment with metformin decreased phosphorylation of S6 protein, a key target of the mTOR pathway.	Metformin	28-37	mechanistic target of rapamycin kinase	Homo sapiens	99-103
19808911-3	2010	RESEARCH DESIGN AND METHODS: In A Diabetes Outcome Progression Trial (ADOPT), we examined the long-term effects of rosiglitazone, glyburide, and metformin on CRP and the relationship among CRP, weight, and glycemic variables in 904 subjects over 4 years.	Metformin	145-154	C-reactive protein	Homo sapiens	158-161
19808911-5	2010	CRP reduction was greater in the rosiglitazone group by -47.6% relative to glyburide and by -30.5% relative to metformin at 48 months.	Metformin	111-120	C-reactive protein	Homo sapiens	0-3
19808911-7	2010	The change in CRP from baseline to 12 months was correlated positively with change in BMI in glyburide (r = 0.18) and metformin (r = 0.20) groups but not in the rosiglitazone (r = -0.05, NS) group.	Metformin	118-127	C-reactive protein	Homo sapiens	14-17
19808911-10	2010	CRP in the glyburide and metformin groups was positively associated with changes in weight, but this was not the case with rosiglitazone.	Metformin	25-34	C-reactive protein	Homo sapiens	0-3
19019358-10	2010	CONCLUSION(S): In polycystic ovary syndrome, metformin improves insulin resistance, inflammatory markers, and endothelial function.	Metformin	45-54	insulin	Homo sapiens	64-71
19564648-1	2010	Metformin is a biguanide, insulin sensitiser that reduces blood sugar levels.	Metformin	0-9	insulin	Homo sapiens	26-33
19772969-5	2010	RESULTS: The benefits of metformin were mostly maintained during the posttreatment year so that, after 5 years, metformin therapy was associated with more lean mass; with less total, visceral, and hepatic fat; with lower circulating levels of androgens and leptin; and with elevated levels of high-molecular-weight adiponectin and undercarboxylated osteocalcin.	Metformin	25-34	bone gamma-carboxyglutamate protein	Homo sapiens	349-360
20798858-2	2010	To assess the long-term effects of metformin in combination with lifestyle intervention and its association between insulin levels and the degree of steatosis at ultrasonography (US) in obese adolescents.	Metformin	35-44	insulin	Homo sapiens	116-123
20798858-10	2010	Long-term therapy plus metformin significantly reduced body weight, body mass index, insulin, HOMA-IR, and visceral fat.	Metformin	23-32	insulin	Homo sapiens	85-92
20798864-0	2010	Metformin Improves Insulin Signaling in Obese Rats via Reduced IKKbeta Action in a Fiber-Type Specific Manner.	Metformin	0-9	inhibitor of nuclear factor kappa B kinase subunit beta	Rattus norvegicus	63-70
20798864-2	2010	Metformin has been shown to activate AMPK in skeletal muscle; however, its effects on the inhibitor of kappaB kinasebeta (IKKbeta) in this same tissue are unknown.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	37-41
20798864-2	2010	Metformin has been shown to activate AMPK in skeletal muscle; however, its effects on the inhibitor of kappaB kinasebeta (IKKbeta) in this same tissue are unknown.	Metformin	0-9	inhibitor of nuclear factor kappa B kinase subunit beta	Rattus norvegicus	122-129
20798864-3	2010	The aim of this study was to (1) determine the ability of metformin to attenuate IKKbeta action, (2) determine whether changes in AMPK activity are associated with changes in IKKbeta action in skeletal muscle, and (3) examine whether changes in AMPK and IKKbeta function are consistent with improved insulin signaling.	Metformin	58-67	inhibitor of nuclear factor kappa B kinase subunit beta	Rattus norvegicus	81-88
20798864-7	2010	Further, metformin increased IkappaBalpha levels in both WG (150%) and RG (67%) of obese rats, indicative of reduced IKKbeta activity (P < .05), and was associated with reduced IRS1-pSer(307) (30%) in the WG of obese rats (P < .02).	Metformin	9-18	inhibitor of nuclear factor kappa B kinase subunit beta	Rattus norvegicus	117-124
20798864-7	2010	Further, metformin increased IkappaBalpha levels in both WG (150%) and RG (67%) of obese rats, indicative of reduced IKKbeta activity (P < .05), and was associated with reduced IRS1-pSer(307) (30%) in the WG of obese rats (P < .02).	Metformin	9-18	insulin receptor substrate 1	Rattus norvegicus	180-184
20798864-8	2010	From these data we conclude that metformin treatment appears to exert an inhibitory influence on skeletal muscle IKKbeta activity, as evidenced by elevated IkappaBalpha levels and reduced IRS1-Ser(307) phosphorylation in a fiber-type specific manner.	Metformin	33-42	inhibitor of nuclear factor kappa B kinase subunit beta	Rattus norvegicus	113-120
20798864-8	2010	From these data we conclude that metformin treatment appears to exert an inhibitory influence on skeletal muscle IKKbeta activity, as evidenced by elevated IkappaBalpha levels and reduced IRS1-Ser(307) phosphorylation in a fiber-type specific manner.	Metformin	33-42	insulin receptor substrate 1	Rattus norvegicus	188-192
19772969-5	2010	RESULTS: The benefits of metformin were mostly maintained during the posttreatment year so that, after 5 years, metformin therapy was associated with more lean mass; with less total, visceral, and hepatic fat; with lower circulating levels of androgens and leptin; and with elevated levels of high-molecular-weight adiponectin and undercarboxylated osteocalcin.	Metformin	112-121	bone gamma-carboxyglutamate protein	Homo sapiens	349-360
20831045-6	2010	The use of combination of metformin with glyclazide MB provides advantages in lowering of insulin resistance, contol glycemia, and lessening of hypertrophy of left ventricular myocardium.	Metformin	26-35	insulin	Homo sapiens	90-97
19898263-0	2010	Interaction between polymorphisms in the OCT1 and MATE1 transporter and metformin response.	Metformin	72-81	solute carrier family 22 member 1	Homo sapiens	41-45
21812223-8	2010	The aim of the pharmacological therapy is to decrease insulin resistance, namely by metformin.	Metformin	84-93	insulin	Homo sapiens	54-61
19898263-1	2010	OBJECTIVE: Metformin is transported into the hepatocyte by organic cation transporter 1 (OCT1) and out of the hepatocyte by multidrug and toxin extrusion 1 (MATE1).	Metformin	11-20	solute carrier family 22 member 1	Homo sapiens	59-87
19898263-1	2010	OBJECTIVE: Metformin is transported into the hepatocyte by organic cation transporter 1 (OCT1) and out of the hepatocyte by multidrug and toxin extrusion 1 (MATE1).	Metformin	11-20	solute carrier family 22 member 1	Homo sapiens	89-93
19898263-2	2010	Recently, we discovered that polymorphisms rs622342 A>C in the SLC22A1 gene, coding for OCT1, and rs2289669 G>A in the SLC47A1 gene, coding for MATE1, are associated with the degree of glucose lowering by metformin.	Metformin	211-220	solute carrier family 22 member 1	Homo sapiens	66-73
19898263-2	2010	Recently, we discovered that polymorphisms rs622342 A>C in the SLC22A1 gene, coding for OCT1, and rs2289669 G>A in the SLC47A1 gene, coding for MATE1, are associated with the degree of glucose lowering by metformin.	Metformin	211-220	solute carrier family 22 member 1	Homo sapiens	91-95
19898263-9	2010	CONCLUSION: The effect of the MATE1 rs2289669 polymorphism on the glucose lowering effect of metformin is larger in incident users with the OCT1 rs622342 CC genotype than in incident users with the AA genotype.	Metformin	93-102	solute carrier family 22 member 1	Homo sapiens	140-144
20873243-4	2010	RESULTS: As compared with the patients receiving insulin monotherapy, the patients taking metformin alone or in combination showed a more effective recovery of carbohydrate and lipid metabolic disturbances, diminished insulin resistance (IR), lowered blood pressure and albuminuria, reduced diastolic dysfunction, and a smaller cardiovascular risk.	Metformin	90-99	insulin	Homo sapiens	49-56
20107300-5	2010	Medications that decrease insulin needs like metformin, thiazolidinediones, or pramlintide may help, but some patients also need high doses of insulin.	Metformin	45-54	insulin	Homo sapiens	26-33
20873243-4	2010	RESULTS: As compared with the patients receiving insulin monotherapy, the patients taking metformin alone or in combination showed a more effective recovery of carbohydrate and lipid metabolic disturbances, diminished insulin resistance (IR), lowered blood pressure and albuminuria, reduced diastolic dysfunction, and a smaller cardiovascular risk.	Metformin	90-99	insulin	Homo sapiens	218-225
20873243-5	2010	When metformin was used in combination with gliclaside (Group 2) for 12 months, there was the maximum IR reduction, an increase in insulin sensitivity, and better results in reaching the goal values of carbohydrate metabolism; there was left ventricular myocardial reverse remodeling.	Metformin	5-14	insulin	Homo sapiens	131-138
20356474-11	2010	(2) Fasting insulin as well as 30 min and 120 min insulin levels after oral glucose tolerance test and insulin area under the curve in the metformin group were significantly reduced after 4 and 8 weeks of treatment as compared with those of baseline (P < 0.05 and P < 0.01).	Metformin	139-148	insulin	Homo sapiens	12-19
20356474-11	2010	(2) Fasting insulin as well as 30 min and 120 min insulin levels after oral glucose tolerance test and insulin area under the curve in the metformin group were significantly reduced after 4 and 8 weeks of treatment as compared with those of baseline (P < 0.05 and P < 0.01).	Metformin	139-148	insulin	Homo sapiens	50-57
20356474-11	2010	(2) Fasting insulin as well as 30 min and 120 min insulin levels after oral glucose tolerance test and insulin area under the curve in the metformin group were significantly reduced after 4 and 8 weeks of treatment as compared with those of baseline (P < 0.05 and P < 0.01).	Metformin	139-148	insulin	Homo sapiens	50-57
20356474-13	2010	The insulin action index in the metformin group was higher than that in the fosinopril group after 4 weeks of treatment (P < 0.05), but there was no significant difference between the two groups after 8 weeks of treatment (P > 0.05).	Metformin	32-41	insulin	Homo sapiens	4-11
19765050-3	2009	Metformin and thiazolidinediones are both antihyperglycaemic drugs, both lower blood glucose concentrations in type 2 diabetes without causing overt hypoglycaemia and both require the presence of insulin to generate their therapeutic effects, but act without stimulating insulin secretion.	Metformin	0-9	insulin	Homo sapiens	196-203
19858366-0	2009	LKB1 and mammalian target of rapamycin as predictive factors for the anticancer efficacy of metformin.	Metformin	92-101	mechanistic target of rapamycin kinase	Homo sapiens	9-38
20002081-16	2009	RESULTS: Treatment with metformin increased the mean AUC (07.30-16.30 h) of plasma ghrelin by 24% (P= 0.003), while decreasing those of glucose by 19% (P < 0.001) and insulin by 19% (P= 0.001).	Metformin	24-33	insulin	Homo sapiens	170-177
19845037-0	2009	Treatment of insulin resistance with metformin in naive genotype 1 chronic hepatitis C patients receiving peginterferon alfa-2a plus ribavirin.	Metformin	37-46	insulin	Homo sapiens	13-20
19845037-1	2009	UNLABELLED: Insulin resistance affects sustained virological response (SVR) in chronic hepatitis C. To know whether adding metformin to standard antiviral treatment improves SVR, we conducted a prospective, multicentered, randomized, double-blinded, placebo-controlled trial in 19 Spanish hospitals, including 123 consecutive patients with genotype 1 chronic hepatitis C and insulin resistance.	Metformin	123-132	insulin	Homo sapiens	12-19
19845037-10	2009	CONCLUSION: Adding metformin to peginterferon and ribavirin was safe and improved insulin sensitivity.	Metformin	19-28	insulin	Homo sapiens	82-89
19925384-4	2009	The greater (slower) intravenous AUCs (CL(NR)s) of metformin in 24-h and 96-h ECLPS rats were due to the slower hepatic intrinsic clearance (CL(int)) because of a decrease in the protein expression of hepatic cytochrome P450 (CYP) 2C11 and/or CYP3A subfamily than controls.	Metformin	51-60	cytochrome P450, family 3, subfamily a, polypeptide 62	Rattus norvegicus	243-248
20388946-7	2009	Metformin and thiazolidinediones may improve insulin sensitivity, serum aminotransferase level and liver histology.	Metformin	0-9	insulin	Homo sapiens	45-52
19858375-0	2009	If mammalian target of metformin indirectly is mammalian target of rapamycin, then the insulin-like growth factor-1 receptor axis will audit the efficacy of metformin in cancer clinical trials.	Metformin	23-32	mechanistic target of rapamycin kinase	Homo sapiens	47-76
19661063-6	2009	In addition to adiponectin, metformin also induces APPL1-APPL2 dissociation.	Metformin	28-37	adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2	Homo sapiens	57-62
19858375-0	2009	If mammalian target of metformin indirectly is mammalian target of rapamycin, then the insulin-like growth factor-1 receptor axis will audit the efficacy of metformin in cancer clinical trials.	Metformin	157-166	mechanistic target of rapamycin kinase	Homo sapiens	47-76
19768675-1	2009	Metformin, a biguanide that has been used to treat type 2 diabetes mellitus, is reportedly transported into human hepatocytes by human organic cation transporter 1 (hOCT1).	Metformin	0-9	solute carrier family 22 member 1	Homo sapiens	135-163
19768675-1	2009	Metformin, a biguanide that has been used to treat type 2 diabetes mellitus, is reportedly transported into human hepatocytes by human organic cation transporter 1 (hOCT1).	Metformin	0-9	solute carrier family 22 member 1	Homo sapiens	165-170
19768675-0	2009	A comparison of uptake of metformin and phenformin mediated by hOCT1 in human hepatocytes.	Metformin	26-35	solute carrier family 22 member 1	Homo sapiens	63-68
19836986-3	2009	However, with insulin and analgesic treatment, the patient"s symptoms improved markedly within a few months; the patient gained 50 kg, while insulin was tapered and then withdrawn, to be replaced by metformin, which maintained perfect diabetes control.	Metformin	199-208	insulin	Homo sapiens	14-21
20144400-1	2009	BACKGROUND: The aim of our study was to examine the efficacy of short-term intravenous insulin intervention followed by oral pioglitazone/metformin therapy to prevent patients from continuous insulin application.	Metformin	138-147	insulin	Homo sapiens	192-199
19817775-6	2009	Select starting insulin analogue treatment strategies for patients who are not at treatment goals with metformin + lifestyle intervention.	Metformin	103-112	insulin	Homo sapiens	16-23
19672815-4	2009	Metformin and the potential therapeutic drug for type 2 diabetes, 5-amino-4-imidazolecarboxamide riboside (AICAR), are both known activators of AMPK.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	144-148
20144400-0	2009	Combined pioglitazone and metformin treatment maintains the beneficial effect of short-term insulin infusion in patients with type 2 diabetes: results from a pilot study.	Metformin	26-35	insulin	Homo sapiens	92-99
20144400-13	2009	CONCLUSIONS: Our pilot study demonstrated that a beneficial effect of a short-term intravenous insulin application on glycemic control was effectively maintained by pioglitazone/metformin treatment for at least 4 months.	Metformin	178-187	insulin	Homo sapiens	95-102
19664596-0	2009	Metformin suppresses glucose-6-phosphatase expression by a complex I inhibition and AMPK activation-independent mechanism.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	84-88
19665995-7	2009	Furthermore, curcuminoids increased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target acetyl-CoA carboxylase (ACC) in H4IIE and Hep3B cells with 400 times (curcumin) to 100,000 times (THC) the potency of metformin.	Metformin	239-248	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	59-87
19665995-7	2009	Furthermore, curcuminoids increased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target acetyl-CoA carboxylase (ACC) in H4IIE and Hep3B cells with 400 times (curcumin) to 100,000 times (THC) the potency of metformin.	Metformin	239-248	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	89-93
19664596-2	2009	Both metformin and rotenone, an inhibitor of respiratory chain complex I, suppressed glucose-6-phosphatase (G6pc), a rate limiting enzyme of liver glucose production, mRNA expression in a rat hepatoma cell line accompanied by a reduction of intracellular ATP concentration and an activation of AMP-activated protein kinase (AMPK).	Metformin	5-14	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	294-322
19664596-2	2009	Both metformin and rotenone, an inhibitor of respiratory chain complex I, suppressed glucose-6-phosphatase (G6pc), a rate limiting enzyme of liver glucose production, mRNA expression in a rat hepatoma cell line accompanied by a reduction of intracellular ATP concentration and an activation of AMP-activated protein kinase (AMPK).	Metformin	5-14	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	324-328
19664596-5	2009	Since NDI1 can functionally complement the complex I under the presence of metformin or rotenone, our results indicate that metformin induces down-regulation of G6pc expression through an inhibition of complex I and an activation of AMPK-independent mechanism.	Metformin	124-133	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	233-237
19821299-0	2009	Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility.	Metformin	27-36	insulin	Homo sapiens	0-7
19821299-3	2009	If insulin sensitising agents such as metformin are effective in treating features of PCOS, then they could have wider health benefits than just treating the symptoms of the syndrome.	Metformin	38-47	insulin	Homo sapiens	3-10
19531054-3	2009	Two primary hypotheses were tested in a hierarchical manner: (i) treatment with the repaglinide/metformin FDC BID is non-inferior to that of the rosiglitazone/metformin FDC BID as measured by changes in haemoglobin A1c (HbA1c) (results presented in companion paper) and (ii) repaglinide/metformin BID is non-inferior to repaglinide/metformin TID (as measured by changes in HbA1c).	Metformin	96-105	BH3 interacting domain death agonist	Homo sapiens	110-113
19574398-7	2009	Metformin significantly inhibited basal and insulin-stimulated aromatase mRNA expression, with parallel results from the aromatase activity assay and protein assessment.	Metformin	0-9	insulin	Homo sapiens	44-51
19574398-9	2009	Involvement of the ERK signaling pathway was demonstrated by the significant increase in phosphorylated ERK-1,2 with the combined metformin and insulin treatment.	Metformin	130-139	mitogen-activated protein kinase 1	Homo sapiens	19-22
19574398-1	2009	Metformin treatment, now widely prescribed in polycystic ovary syndrome, is aimed at correcting the associated insulin resistance, but it has also been shown to directly inhibit ovarian steroidogenesis.	Metformin	0-9	insulin	Homo sapiens	111-118
19574398-9	2009	Involvement of the ERK signaling pathway was demonstrated by the significant increase in phosphorylated ERK-1,2 with the combined metformin and insulin treatment.	Metformin	130-139	mitogen-activated protein kinase 3	Homo sapiens	104-111
19574398-10	2009	We have shown for the first time in human granulosa cells that metformin signficantly attenuated basal and insulin-stimulated P450 aromatase mRNA expression and activity, via silencing of key promoters.	Metformin	63-72	insulin	Homo sapiens	107-114
20069140-7	2009	Metformin is currently the preferred insulin-sensitizing drug for chronic treatment of PCOS and has been shown to improve the metabolic profile, menstrual cyclicity and fertility in women with PCOS, and is associated with weight loss.	Metformin	0-9	insulin	Homo sapiens	37-44
19552904-4	2009	RESULTS: After 1 cycle, BMI, total T level, and percentage of participants with insulin resistance were significantly decreased in the metformin group, without any significant decrease in LH, FSH, and DHEAS levels; and in the second cycle, CC treatment resulted in a higher ovulation rate and a thicker endometrium in the metformin group.	Metformin	135-144	insulin	Homo sapiens	80-87
19709092-8	2009	Metformin treatment, and diets low in milk protein content and glycaemic index reduce increased IGF-1 signalling.	Metformin	0-9	insulin like growth factor 1	Homo sapiens	96-101
19552904-6	2009	CONCLUSION: The short-course pretreatment with metformin decreased hyperandrogenism and insulin resistance and improved cervical sores, ovulation rate, and pregnancy rate among women with CC-resistant PCOS.	Metformin	47-56	insulin	Homo sapiens	88-95
20058777-6	2009	However, there are interesting data concerning drugs that lower plasma insulin levels, particularly metformin, but also, to a certain degree, pioglitazone.	Metformin	100-109	insulin	Homo sapiens	71-78
19591196-6	2009	Transport of metformin by recombinant human OCT1 and OCT3 was compared using transfected cells.	Metformin	13-22	solute carrier family 22 member 1	Homo sapiens	44-48
21105563-3	2009	Administration of various insulin sensitizing drugs, such as metformin and troglitazone have been shown to decrease serum androgen concentrations and to increase ovulation rates, increase conception and decrease miscarriage in affected women.	Metformin	61-70	insulin	Homo sapiens	26-33
19560877-0	2009	Is it the time for metformin to take place in adjuvant treatment of Her-2 positive breast cancer?	Metformin	19-28	erb-b2 receptor tyrosine kinase 2	Homo sapiens	68-73
19560877-9	2009	Metformin causes Her-2 suppression via the inhibition of mTOR in breast cancer cells.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	17-22
19560877-9	2009	Metformin causes Her-2 suppression via the inhibition of mTOR in breast cancer cells.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	57-61
19560877-10	2009	Thus, we believe that the time has arrived both to target insulin reduction and to alter Her-2 oncogene based molecular pathogenetic steps in breast cancer by using metformin as an adjuvant therapy in breast cancer patients.	Metformin	165-174	erb-b2 receptor tyrosine kinase 2	Homo sapiens	89-94
19909598-9	2009	Promising treatments for PCOS seem to be insulin sensitizers such as metformin and glitazones.	Metformin	69-78	insulin	Homo sapiens	41-48
19496776-7	2009	The total daily insulin dose (IU) was significantly reduced in the metformin group compared to placebo after 24 weeks (-5.9 +/- 2.2 vs. 2.9 +/- 1.7, P = 0.004.	Metformin	67-76	insulin	Homo sapiens	16-23
19496776-12	2009	Metformin, as adjunct to intensive insulin therapy, was associated with a reduction in the total daily insulin dose and a significant weight loss in patients with type 1 diabetes mellitus.	Metformin	0-9	insulin	Homo sapiens	103-110
19721204-3	2009	Recent epidemiologic studies have shown that the fracture rate was decreased in patients treated with metformin, one of the anti-hyperglycemic agents by improving insulin resistance.	Metformin	102-111	insulin	Homo sapiens	163-170
19502540-7	2009	CONCLUSIONS: Metformin appears to be moderately efficacious in reducing BMI and insulin resistance in hyperinsulinemic obese children and adolescents in the short term.	Metformin	13-22	insulin	Homo sapiens	80-87
19536068-0	2009	The effects of genetic polymorphisms in the organic cation transporters OCT1, OCT2, and OCT3 on the renal clearance of metformin.	Metformin	119-128	solute carrier family 22 member 1	Homo sapiens	72-76
19536068-2	2009	We explored metformin pharmacokinetics in relation to genetic variations in OCT1, OCT2, OCT3, OCTN1, and MATE1 in 103 healthy male Caucasians.	Metformin	12-21	solute carrier family 22 member 1	Homo sapiens	76-80
19536068-7	2009	Renal OCT1 expression may be important not only in relation to metformin but with respect to other drugs as well.	Metformin	63-72	solute carrier family 22 member 1	Homo sapiens	6-10
19476470-6	2009	Reductions in HbA1c values became apparent at earlier times for repaglinide/metformin FDC BID treatment than rosiglitazone/metformin FDC BID, and final changes in HbA1c were not significantly different between treatment arms (p = 0.8186); thus, the predefined statistical criterion for non-inferiority was met.	Metformin	76-85	BH3 interacting domain death agonist	Homo sapiens	90-93
19476470-8	2009	CONCLUSIONS: The repaglinide/metformin FDC BID regimen showed efficacy that was non-inferior to that of the rosiglitazone/metformin FDC BID regimen currently in clinical use and a more rapid reduction of HbA1c values.	Metformin	29-38	BH3 interacting domain death agonist	Homo sapiens	43-46
19476470-9	2009	Thus, repaglinide/metformin FDC BID is a clinically feasible alternative to rosiglitazone/metformin FDC BID.	Metformin	18-27	BH3 interacting domain death agonist	Homo sapiens	32-35
19502455-8	2009	Metformin alone was able to modulate serum P and E(2) levels, lipoperoxidation, SOD and CAT, and the 5,5-dimethyl-1-pyrroline N-oxide/(*)OH signal.	Metformin	0-9	catalase	Mus musculus	88-91
19783765-5	2009	Although current practice guidelines do not include specific recommendations about when and how to incorporate incretin-based agents, a consensus statement published by the American Diabetes Association/European Association for the Study of Diabetes suggests the addition of a glucagon-like peptide-1 (GLP-1) agonist for patients not at goal A1C with metformin and lifestyle changes.	Metformin	351-360	glucagon	Homo sapiens	277-300
19528204-10	2009	CONCLUSIONS: In pT2DM patients, plasma FGF-21 levels are increased, but significantly decreased after the treatment with rosiglitazone on top of ongoing metformin therapy.	Metformin	153-162	fibroblast growth factor 21	Homo sapiens	39-45
19690559-1	2009	A question often asked by health-care providers is whether metformin has added benefits if continued after patients with type 2 diabetes mellitus switch to insulin.	Metformin	59-68	insulin	Homo sapiens	156-163
19820276-5	2009	Most conventional antidiabetes agents, including sulfonylureas, thiazolidinediones, and insulin, improve glycemic control but are associated with weight gain or, as with metformin, are weight-neutral or weight-sparing.	Metformin	170-179	insulin	Homo sapiens	88-95
19688265-4	2009	Orlistat and sibutramine are FDA-approved for treatment of pediatric obesity; metformin may be considered in the presence of clinically significant insulin resistance.	Metformin	78-87	insulin	Homo sapiens	148-155
19414528-0	2009	Metformin decreases angiogenesis via NF-kappaB and Erk1/2/Erk5 pathways by increasing the antiangiogenic thrombospondin-1.	Metformin	0-9	mitogen-activated protein kinase 3	Homo sapiens	51-57
19679549-3	2009	Metformin, the most widely used drug in the treatment of type 2 diabetes, activates AMP kinase (AMPK), which negatively regulates mTOR.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	130-134
19679549-6	2009	Metformin pretreatment completely abrogated insulin-induced potentiation of Ca(2+) signaling but did not interfere with the effect of GPCR agonists alone.	Metformin	0-9	insulin	Homo sapiens	44-51
19679549-8	2009	Low doses of metformin (0.1-0.5 mmol/L) blocked the stimulation of DNA synthesis, and the anchorage-dependent and anchorage-independent growth induced by insulin and GPCR agonists.	Metformin	13-22	insulin	Homo sapiens	154-161
19414528-0	2009	Metformin decreases angiogenesis via NF-kappaB and Erk1/2/Erk5 pathways by increasing the antiangiogenic thrombospondin-1.	Metformin	0-9	thrombospondin 1	Homo sapiens	105-121
19414528-7	2009	After 6 months of metformin treatment, there was a significant increase in serum TSP-1 (P < 0.05) and a corresponding decrease in PAI-1 and PAI-1 activity (P < 0.01).	Metformin	18-27	thrombospondin 1	Homo sapiens	81-86
19414528-8	2009	In vitro migration and angiogenesis were significantly increased in serum from PCOS women (P < 0.01); these effects were significantly attenuated by metformin treatment (P < 0.01) through the regulation of TSP-1 levels via nuclear factor-kappaB (NF-kappaB), extracellular regulated-signal kinase 1/2 (Erk1/2) and Erk5 pathways.	Metformin	152-161	thrombospondin 1	Homo sapiens	212-217
19414528-8	2009	In vitro migration and angiogenesis were significantly increased in serum from PCOS women (P < 0.01); these effects were significantly attenuated by metformin treatment (P < 0.01) through the regulation of TSP-1 levels via nuclear factor-kappaB (NF-kappaB), extracellular regulated-signal kinase 1/2 (Erk1/2) and Erk5 pathways.	Metformin	152-161	mitogen-activated protein kinase 3	Homo sapiens	307-313
19414528-12	2009	Metformin treatment increases serum TSP-1 in these women.	Metformin	0-9	thrombospondin 1	Homo sapiens	36-41
19808125-1	2009	BACKGROUND: Insulin is recommended as a second-line treatment after diet and metformin fail to reach and/or maintain glycemic targets considered to minimize the risk for long-term diabetic complications.	Metformin	77-86	insulin	Homo sapiens	12-19
19490068-3	2009	Adiponectin, 5-aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR) and metformin activate the AMP-kinase that exerts anti-inflammatory effects, and the influence of adiponectin and these drugs on monocytic CD163 was analysed, and cellular and sCD163 were determined in obesity and type 2 diabetes.	Metformin	75-84	adiponectin, C1Q and collagen domain containing	Homo sapiens	169-180
19381165-0	2009	Genetic variation in the organic cation transporter 1 is associated with metformin response in patients with diabetes mellitus.	Metformin	73-82	solute carrier family 22 member 1	Homo sapiens	25-53
19387874-1	2009	This study assessed the efficacy of adding metformin to a structured lifestyle intervention in reducing BMI in obese adolescents with insulin resistance.	Metformin	43-52	insulin	Homo sapiens	134-141
19394976-8	2009	Fasting plasma insulin and postprandial plasma insulin values were higher in the group treated with glimepiride + metformin compared with the other groups.	Metformin	114-123	insulin	Homo sapiens	15-22
19394976-8	2009	Fasting plasma insulin and postprandial plasma insulin values were higher in the group treated with glimepiride + metformin compared with the other groups.	Metformin	114-123	insulin	Homo sapiens	47-54
19394976-10	2009	Pioglitazone-metformin-based therapeutic control is associated with the most quantitatively relevant improvement in insulin resistance-related parameters, whereas the sulfonylurea-metformin-including protocol has less relevant effects.	Metformin	13-22	insulin	Homo sapiens	116-123
19381165-1	2009	The organic cation transporter 1, encoded by the SLC22A1 gene, is responsible for the uptake of the anti-hyperglycaemic drug, metformin, in the hepatocyte.	Metformin	126-135	solute carrier family 22 member 1	Homo sapiens	4-32
19381165-1	2009	The organic cation transporter 1, encoded by the SLC22A1 gene, is responsible for the uptake of the anti-hyperglycaemic drug, metformin, in the hepatocyte.	Metformin	126-135	solute carrier family 22 member 1	Homo sapiens	49-56
19381165-2	2009	We assessed whether a genetic variation in the SLC22A1 gene is associated with the glucose-lowering effect of metformin.	Metformin	110-119	solute carrier family 22 member 1	Homo sapiens	47-54
19381165-9	2009	To conclude, genetic variation at rs622342 in the SLC22A1 gene was associated with the glucose-lowering effect of metformin in patients with diabetes mellitus.	Metformin	114-123	solute carrier family 22 member 1	Homo sapiens	50-57
19634921-3	2009	Thus, the use of insulin-sensitizing drugs, such as metformin and thiazolidinediones, has been proposed for PCOS treatment.	Metformin	52-61	insulin	Homo sapiens	17-24
19588338-3	2009	If insulin sensitising agents such as metformin are effective in treating features of PCOS, then they could have wider health benefits than just treating the symptoms of the syndrome.	Metformin	38-47	insulin	Homo sapiens	3-10
19588338-10	2009	Nevertheless, these benefits were not translated into live birth rates.Metformin has a significant effect in reducing fasting insulin levels (WMD -4.20 mIU/L, CI -7.68 to -0.73); however, the reduction was only significant in the non-obese group (BMI < 30 kg/m2).	Metformin	71-80	insulin	Homo sapiens	126-133
19571378-4	2009	The mRNA and protein expression of GAPD, detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively, decreased upon treatment of the cells with 10 mM metformin for 24 h. Under the conditions, metformin induced phosphorylation of AMP-activated protein kinase (AMPK).	Metformin	205-214	glyceraldehyde-3-phosphate dehydrogenase	Homo sapiens	35-39
19470778-0	2009	Regulation of visceral adipose tissue-derived serine protease inhibitor by nutritional status, metformin, gender and pituitary factors in rat white adipose tissue.	Metformin	95-104	serpin family A member 12	Rattus norvegicus	14-71
19470778-5	2009	Chronic treatment with metformin increased vaspin gene expression.	Metformin	23-32	serpin family A member 12	Rattus norvegicus	43-49
19571378-4	2009	The mRNA and protein expression of GAPD, detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively, decreased upon treatment of the cells with 10 mM metformin for 24 h. Under the conditions, metformin induced phosphorylation of AMP-activated protein kinase (AMPK).	Metformin	247-256	glyceraldehyde-3-phosphate dehydrogenase	Homo sapiens	35-39
19571378-0	2009	Regulation of glyceraldehyde 3-phosphate dehydrogenase expression by metformin in HepG2 cells.	Metformin	69-78	glyceraldehyde-3-phosphate dehydrogenase	Homo sapiens	14-54
19571378-3	2009	In this study, we examined the signaling pathway and regulatory factors for the expression of the GAPD gene triggered by metformin in HepG2 cells.	Metformin	121-130	glyceraldehyde-3-phosphate dehydrogenase	Homo sapiens	98-102
19571378-9	2009	A mutant reporter plasmid with an altered cAMP-response element (CRE) counteracted the metformin-mediated repression of GAPD transcription.	Metformin	87-96	glyceraldehyde-3-phosphate dehydrogenase	Homo sapiens	120-124
19571378-10	2009	These results suggest that signal transducers, adenylate cyclase (AC), protein kinase A (PKA), and AMPK, are involved in the signaling pathway triggered by metformin and CRE-binding protein is one of the transcription factors for the GAPD gene down-regulated by metformin.	Metformin	156-165	glyceraldehyde-3-phosphate dehydrogenase	Homo sapiens	234-238
19571378-10	2009	These results suggest that signal transducers, adenylate cyclase (AC), protein kinase A (PKA), and AMPK, are involved in the signaling pathway triggered by metformin and CRE-binding protein is one of the transcription factors for the GAPD gene down-regulated by metformin.	Metformin	262-271	glyceraldehyde-3-phosphate dehydrogenase	Homo sapiens	234-238
19440038-7	2009	At the molecular level, metformin increases P-AMPK, reduces P-EGFR, EGFR, P-MAPK, P-Src, cyclin D1 and cyclin E (but not cyclin A or B, p27 or p21), and induces PARP cleavage in a dose- and time-dependent manner.	Metformin	24-33	epidermal growth factor receptor	Homo sapiens	62-66
19440038-7	2009	At the molecular level, metformin increases P-AMPK, reduces P-EGFR, EGFR, P-MAPK, P-Src, cyclin D1 and cyclin E (but not cyclin A or B, p27 or p21), and induces PARP cleavage in a dose- and time-dependent manner.	Metformin	24-33	epidermal growth factor receptor	Homo sapiens	68-72
19440038-7	2009	At the molecular level, metformin increases P-AMPK, reduces P-EGFR, EGFR, P-MAPK, P-Src, cyclin D1 and cyclin E (but not cyclin A or B, p27 or p21), and induces PARP cleavage in a dose- and time-dependent manner.	Metformin	24-33	cyclin dependent kinase inhibitor 1A	Homo sapiens	143-146
19574203-0	2009	mTOR inhibitors and the anti-diabetic biguanide metformin: new insights into the molecular management of breast cancer resistance to the HER2 tyrosine kinase inhibitor lapatinib (Tykerb).	Metformin	48-57	erb-b2 receptor tyrosine kinase 2	Homo sapiens	137-141
19574203-6	2009	The unexpected ability of the anti-type II diabetes drug metformin to inactivate mTOR and decrease p70S6K1 activity further reveals that this biguanide, generally considered non-toxic and remarkably inexpensive, might be considered for new combinatorial lapatinib-based protocols in HER2-overexpressing breast cancer patients.	Metformin	57-66	mechanistic target of rapamycin kinase	Homo sapiens	81-85
19574203-6	2009	The unexpected ability of the anti-type II diabetes drug metformin to inactivate mTOR and decrease p70S6K1 activity further reveals that this biguanide, generally considered non-toxic and remarkably inexpensive, might be considered for new combinatorial lapatinib-based protocols in HER2-overexpressing breast cancer patients.	Metformin	57-66	erb-b2 receptor tyrosine kinase 2	Homo sapiens	283-287
21437123-3	2009	Repaglinide, a rapid-acting insulin secretagogue, targets PPG, and metformin, an insulin sensitizer, targets FBG.	Metformin	67-76	insulin	Homo sapiens	81-88
19369429-2	2009	In overweight T2D patients, metformin has been demonstrated to reduce CVD risk, and this beneficial effect may be conserved with the combination of metformin and insulin treatment.	Metformin	28-37	insulin	Homo sapiens	162-169
19533481-0	2009	Metformin administration was associated with a modification of LH, prolactin and insulin secretion dynamics in women with polycystic ovarian syndrome.	Metformin	0-9	prolactin	Homo sapiens	67-76
19533481-0	2009	Metformin administration was associated with a modification of LH, prolactin and insulin secretion dynamics in women with polycystic ovarian syndrome.	Metformin	0-9	insulin	Homo sapiens	81-88
19483665-9	2009	We observed that the renal clearance (CL(R)) and the net secretion (SrCL(R)) of metformin were significantly different between the volunteers heterozygous for the variant allele (808G/T), and the volunteers homozygous for the reference allele (808G/G) (P<0.005).	Metformin	80-89	collectin subfamily member 12	Homo sapiens	68-72
19483665-10	2009	Multivariate analysis revealed that OCT2 genotype was a significant predictor of CL(R) and SrCL(R) of metformin (P<0.01).	Metformin	102-111	collectin subfamily member 12	Homo sapiens	91-95
19483665-11	2009	CONCLUSION: We conclude that genetic variation in OCT2 plays an important role in the CL(R) and SrCL(R) of metformin in healthy volunteers.	Metformin	107-116	collectin subfamily member 12	Homo sapiens	96-100
19568428-2	2009	The oral agent pioglitazone is licensed for use with insulin when metformin is contraindicated or not tolerated.	Metformin	66-75	insulin	Homo sapiens	53-60
19494326-3	2009	We provide evidence that metformin attenuates the induction of EAE by restricting the infiltration of mononuclear cells into the CNS, down-regulating the expression of proinflammatory cytokines (IFN-gamma, TNF-alpha, IL-6, IL-17, and inducible NO synthase (iNOS)), cell adhesion molecules, matrix metalloproteinase 9, and chemokine (RANTES).	Metformin	25-34	interferon gamma	Homo sapiens	195-204
19494326-3	2009	We provide evidence that metformin attenuates the induction of EAE by restricting the infiltration of mononuclear cells into the CNS, down-regulating the expression of proinflammatory cytokines (IFN-gamma, TNF-alpha, IL-6, IL-17, and inducible NO synthase (iNOS)), cell adhesion molecules, matrix metalloproteinase 9, and chemokine (RANTES).	Metformin	25-34	tumor necrosis factor	Homo sapiens	206-215
19494326-3	2009	We provide evidence that metformin attenuates the induction of EAE by restricting the infiltration of mononuclear cells into the CNS, down-regulating the expression of proinflammatory cytokines (IFN-gamma, TNF-alpha, IL-6, IL-17, and inducible NO synthase (iNOS)), cell adhesion molecules, matrix metalloproteinase 9, and chemokine (RANTES).	Metformin	25-34	interleukin 6	Homo sapiens	217-221
19494326-3	2009	We provide evidence that metformin attenuates the induction of EAE by restricting the infiltration of mononuclear cells into the CNS, down-regulating the expression of proinflammatory cytokines (IFN-gamma, TNF-alpha, IL-6, IL-17, and inducible NO synthase (iNOS)), cell adhesion molecules, matrix metalloproteinase 9, and chemokine (RANTES).	Metformin	25-34	nitric oxide synthase 2	Homo sapiens	234-255
19494326-3	2009	We provide evidence that metformin attenuates the induction of EAE by restricting the infiltration of mononuclear cells into the CNS, down-regulating the expression of proinflammatory cytokines (IFN-gamma, TNF-alpha, IL-6, IL-17, and inducible NO synthase (iNOS)), cell adhesion molecules, matrix metalloproteinase 9, and chemokine (RANTES).	Metformin	25-34	nitric oxide synthase 2	Homo sapiens	257-261
19494326-5	2009	Metformin activated AMPK in macrophages and thereby inhibited biosynthesis of phospholipids as well as neutral lipids and also down-regulated the expression of endotoxin (LPS)-induced proinflammatory cytokines and their mediators (iNOS and cyclooxygenase 2).	Metformin	0-9	nitric oxide synthase 2	Homo sapiens	231-235
19494326-5	2009	Metformin activated AMPK in macrophages and thereby inhibited biosynthesis of phospholipids as well as neutral lipids and also down-regulated the expression of endotoxin (LPS)-induced proinflammatory cytokines and their mediators (iNOS and cyclooxygenase 2).	Metformin	0-9	prostaglandin-endoperoxide synthase 2	Homo sapiens	240-256
19336679-0	2009	Reduced-function SLC22A1 polymorphisms encoding organic cation transporter 1 and glycemic response to metformin: a GoDARTS study.	Metformin	102-111	solute carrier family 22 member 1	Homo sapiens	17-24
19490902-2	2009	(2009) shows how metformin circumvents a block between insulin and atypical protein kinase C in obese and diabetic mice to inhibit gluconeogenesis by stimulating the phosphorylation of CBP and the disassembly of the CREB transcriptional complex.	Metformin	17-26	cAMP responsive element binding protein 1	Mus musculus	216-220
18440534-8	2009	Insulin sensitivity indexes were statistically significantly worse in patients who ovulated under metformin and statistically significantly better in patients who ovulated under CC.	Metformin	98-107	insulin	Homo sapiens	0-7
18440534-12	2009	CONCLUSION(S): Insulin-resistant PCOS patients with low BMI are more likely to respond to metformin whereas CC treatment is more effective in less hyperandrogenic and insulin-resistant PCOS patients with low BMI.	Metformin	90-99	insulin	Homo sapiens	15-22
19336679-1	2009	OBJECTIVE: Metformin is actively transported into the liver by the organic cation transporter (OCT)1 (encoded by SLC22A1).	Metformin	11-20	solute carrier family 22 member 1	Homo sapiens	95-100
19336679-1	2009	OBJECTIVE: Metformin is actively transported into the liver by the organic cation transporter (OCT)1 (encoded by SLC22A1).	Metformin	11-20	solute carrier family 22 member 1	Homo sapiens	113-120
19336679-2	2009	In 12 normoglycemic individuals, reduced-function variants in SLC22A1 were shown to decrease the ability of metformin to reduce glucose excursion in response to oral glucose.	Metformin	108-117	solute carrier family 22 member 1	Homo sapiens	62-69
19336679-3	2009	We assessed the effect of two common loss-of-function polymorphisms in SLC22A1 on metformin response in a large cohort of patients with type 2 diabetes.	Metformin	82-91	solute carrier family 22 member 1	Homo sapiens	71-78
19336679-5	2009	R61C and 420del variants of SLC22A1 were genotyped in 3,450 patients with type 2 diabetes who were incident users of metformin.	Metformin	117-126	solute carrier family 22 member 1	Homo sapiens	28-35
19364111-4	2009	The rats treated with baicalin and metformin + baicalin had significantly elevated (p < 0.05) hepatic activities of superoxide dismutase, catalase, and glutathione peroxidase compared with the vehicle- and metformin-treated groups.	Metformin	35-44	catalase	Rattus norvegicus	141-149
19480717-7	2009	RESULTS: After six months of metformin, in both PCOS treated groups, a similar improvement in testosterone (T) and insulin resistance indexes was observed.	Metformin	29-38	insulin	Homo sapiens	115-122
19469001-8	2009	Moreover, we report an OR for HCC of 2.99 (CI 1.34-6.65, P = 0.007) in diabetic patients treated with insulin or sulphanylureas, and an OR of 0.33 (CI 0.1-0.7, P = 0.006) in diabetic patients treated with metformin.	Metformin	205-214	insulin	Homo sapiens	102-109
19178532-0	2009	The effects of metformin on endogenous androgens and SHBG in women: a systematic review and meta-analysis.	Metformin	15-24	sex hormone binding globulin	Homo sapiens	53-57
18597869-0	2009	Metformin inhibits TNF-alpha-induced IkappaB kinase phosphorylation, IkappaB-alpha degradation and IL-6 production in endothelial cells through PI3K-dependent AMPK phosphorylation.	Metformin	0-9	tumor necrosis factor	Homo sapiens	19-28
18597869-0	2009	Metformin inhibits TNF-alpha-induced IkappaB kinase phosphorylation, IkappaB-alpha degradation and IL-6 production in endothelial cells through PI3K-dependent AMPK phosphorylation.	Metformin	0-9	NFKB inhibitor alpha	Homo sapiens	69-82
18597869-0	2009	Metformin inhibits TNF-alpha-induced IkappaB kinase phosphorylation, IkappaB-alpha degradation and IL-6 production in endothelial cells through PI3K-dependent AMPK phosphorylation.	Metformin	0-9	interleukin 6	Homo sapiens	99-103
18597869-4	2009	The effects of metformin on TNF-alpha-induced IL-6 production were investigated.	Metformin	15-24	tumor necrosis factor	Homo sapiens	28-37
18597869-7	2009	Pre-treatment with metformin (100-1000 micromol/L) also inhibited TNF-alpha-induced IL-6 production, phosphorylation of IkappaB kinase (IKK) alpha/beta and IkappaB-alpha degradation.	Metformin	19-28	tumor necrosis factor	Homo sapiens	66-75
18597869-7	2009	Pre-treatment with metformin (100-1000 micromol/L) also inhibited TNF-alpha-induced IL-6 production, phosphorylation of IkappaB kinase (IKK) alpha/beta and IkappaB-alpha degradation.	Metformin	19-28	interleukin 6	Homo sapiens	84-88
18597869-7	2009	Pre-treatment with metformin (100-1000 micromol/L) also inhibited TNF-alpha-induced IL-6 production, phosphorylation of IkappaB kinase (IKK) alpha/beta and IkappaB-alpha degradation.	Metformin	19-28	NFKB inhibitor alpha	Homo sapiens	156-169
18597869-8	2009	Metformin increased phosphorylation of AMP-activated kinase (AMPK) but wortmannin, a PI3K inhibitor, negated its effects on AMPK phosphorylation and TNF-alpha-induced IkappaB-alpha degradation.	Metformin	0-9	tumor necrosis factor	Homo sapiens	149-158
18597869-8	2009	Metformin increased phosphorylation of AMP-activated kinase (AMPK) but wortmannin, a PI3K inhibitor, negated its effects on AMPK phosphorylation and TNF-alpha-induced IkappaB-alpha degradation.	Metformin	0-9	NFKB inhibitor alpha	Homo sapiens	167-180
18597869-10	2009	Transfection of siRNA against alpha1-AMPK eradicated the inhibitory effects of metformin on TNF-alpha-induced IL-6, implying the essential role of AMPK.	Metformin	79-88	tumor necrosis factor	Homo sapiens	92-101
18597869-10	2009	Transfection of siRNA against alpha1-AMPK eradicated the inhibitory effects of metformin on TNF-alpha-induced IL-6, implying the essential role of AMPK.	Metformin	79-88	interleukin 6	Homo sapiens	110-114
18597869-11	2009	CONCLUSIONS: Metformin had anti-inflammatory effects on endothelial cells and inhibited TNF-alpha-induced IKKalpha/beta phosphorylation, IkappaB-alpha degradation and IL-6 production in HUVEC.	Metformin	13-22	tumor necrosis factor	Homo sapiens	88-97
18597869-11	2009	CONCLUSIONS: Metformin had anti-inflammatory effects on endothelial cells and inhibited TNF-alpha-induced IKKalpha/beta phosphorylation, IkappaB-alpha degradation and IL-6 production in HUVEC.	Metformin	13-22	NFKB inhibitor alpha	Homo sapiens	137-150
18597869-11	2009	CONCLUSIONS: Metformin had anti-inflammatory effects on endothelial cells and inhibited TNF-alpha-induced IKKalpha/beta phosphorylation, IkappaB-alpha degradation and IL-6 production in HUVEC.	Metformin	13-22	interleukin 6	Homo sapiens	167-171
19178532-15	2009	CONCLUSIONS: Our systematic review and meta-analysis provides evidence of metformin-induced changes in circulating androgens and SHBG levels in women but the quality of evidence is not high.	Metformin	74-83	sex hormone binding globulin	Homo sapiens	129-133
19488607-1	2009	OBJECTIVE: To study if metformin, when administered to first-degree relatives of type 2 diabetes mellitus subjects who have metabolic syndrome and normal glucose tolerance, could improve the cardiovascular risk profile and reduce the levels of both C-reactive protein and fibrinogen.	Metformin	23-32	C-reactive protein	Homo sapiens	249-267
19175375-8	2009	Continuing metformin and/or sulphonylurea after start of therapy with basal long-acting insulin results in better glycaemic control with less insulin requirements, less weight gain and less hypoglycaemic events.	Metformin	11-20	insulin	Homo sapiens	88-95
19175375-8	2009	Continuing metformin and/or sulphonylurea after start of therapy with basal long-acting insulin results in better glycaemic control with less insulin requirements, less weight gain and less hypoglycaemic events.	Metformin	11-20	insulin	Homo sapiens	142-149
19454394-1	2009	OBJECTIVE: To determine whether metformin-treated patients with type 2 diabetes given an analogue mixture of basal and rapid-acting insulins (insulin lispro protamine suspension plus insulin lispro) would have less glycemic variability than patients given basal insulin glargine.	Metformin	32-41	insulin	Homo sapiens	132-139
19454394-1	2009	OBJECTIVE: To determine whether metformin-treated patients with type 2 diabetes given an analogue mixture of basal and rapid-acting insulins (insulin lispro protamine suspension plus insulin lispro) would have less glycemic variability than patients given basal insulin glargine.	Metformin	32-41	insulin	Homo sapiens	142-149
19454394-1	2009	OBJECTIVE: To determine whether metformin-treated patients with type 2 diabetes given an analogue mixture of basal and rapid-acting insulins (insulin lispro protamine suspension plus insulin lispro) would have less glycemic variability than patients given basal insulin glargine.	Metformin	32-41	insulin	Homo sapiens	142-149
19454394-4	2009	RESULTS: Patients on the twice-daily insulin lispro mix 75/25 (75% insulin lispro protamine suspension/25% insulin lispro) plus metformin regimen had significantly lower standard deviation, M-value, and J-index than patients on the insulin glargine plus metformin regimen, but not lower coefficient of variation or mean amplitude of glycemic excursion.	Metformin	254-263	insulin	Homo sapiens	37-44
19454394-6	2009	CONCLUSION: Use of basal plus prandial insulin lispro mixtures at 2 or 3 meals was associated with lower glycemic variability in metformin-treated patients with type 2 diabetes.	Metformin	129-138	insulin	Homo sapiens	39-46
19488607-1	2009	OBJECTIVE: To study if metformin, when administered to first-degree relatives of type 2 diabetes mellitus subjects who have metabolic syndrome and normal glucose tolerance, could improve the cardiovascular risk profile and reduce the levels of both C-reactive protein and fibrinogen.	Metformin	23-32	fibrinogen beta chain	Homo sapiens	272-282
21180541-0	2009	The Effect of Metformin and Standard Therapy versus Standard Therapy alone in Nondiabetic Patients with Insulin Resistance and Nonalcoholic Steatohepatitis (NASH): A Pilot Trial.	Metformin	14-23	insulin	Homo sapiens	104-111
19375579-0	2009	Incretin hormone secretion in women with polycystic ovary syndrome: roles of obesity, insulin sensitivity, and treatment with metformin.	Metformin	126-135	gastric inhibitory polypeptide	Homo sapiens	0-16
19375579-4	2009	Metformin may exert some of its effect on glucose metabolism by increasing GLP-1 biosynthesis and secretion and thereby increasing the incretin effect.	Metformin	0-9	glucagon	Homo sapiens	75-80
19375579-10	2009	Metformin increased GIP (AUC) and GLP-1 (AUC) in lean women with PCOS (P < .05), and a similar trend was seen in the obese women (P = .07).	Metformin	0-9	gastric inhibitory polypeptide	Homo sapiens	20-23
19375579-10	2009	Metformin increased GIP (AUC) and GLP-1 (AUC) in lean women with PCOS (P < .05), and a similar trend was seen in the obese women (P = .07).	Metformin	0-9	glucagon	Homo sapiens	34-39
19375579-11	2009	The GIP secretion is attenuated in obese women with PCOS, whereas treatment with metformin increases the levels of both GIP and GLP-1 in women with PCOS.	Metformin	81-90	gastric inhibitory polypeptide	Homo sapiens	120-123
19375579-11	2009	The GIP secretion is attenuated in obese women with PCOS, whereas treatment with metformin increases the levels of both GIP and GLP-1 in women with PCOS.	Metformin	81-90	glucagon	Homo sapiens	128-133
21180541-3	2009	This was a 12-month prospective, randomized, placebo-controlled trial comparing diet and exercise alone to diet, exercise and metformin in nondiabetic patients with insulin resistance and NASH.	Metformin	126-135	insulin	Homo sapiens	165-172
19370625-1	2009	BACKGROUND: The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation (IVF) cycles has been widely studied.	Metformin	59-68	insulin	Homo sapiens	23-30
19426682-7	2009	Metformin, which was also an anti-diabetic agent, and creatinine more potently inhibited the uptake of [(14)C]aminoguanidine by hOCT2 than that by hOCT1.	Metformin	0-9	solute carrier family 22 member 1	Homo sapiens	147-152
19370625-2	2009	Suppression of insulin levels with metformin might reduce the hyperinsulinaemia and hyperandrogenism suppression of the ovarian response.	Metformin	35-44	insulin	Homo sapiens	15-22
19388972-9	2009	CONCLUSIONS: Addition of a short-acting insulin secretagogue at main meals improves postprandial hyperglycaemia during combination therapy with basal insulin and metformin, but increases the frequency of hypolycaemia.	Metformin	162-171	insulin	Homo sapiens	40-47
19374538-1	2009	EVALUATION OF: Goodwin PJ, Pritchard KI, Ennis M, Clemons M, Graham M, Fantus IG: Insulin-lowering effects of metformin in women with early breast cancer.	Metformin	110-119	insulin	Homo sapiens	82-89
19374538-6	2009	The evaluation presented below briefly addresses the history of the issue and possible targets of metformin effects beside its insulin-related action.	Metformin	98-107	insulin	Homo sapiens	127-134
19298459-11	2009	Insulin sensitivity of FFA rose when pioglitazone was added to sulfonylurea (P<0.05), but decreased for gliclazide + metformin (P<0.05).	Metformin	120-129	insulin	Homo sapiens	0-7
19307526-11	2009	CONCLUSIONS: Metformin, added to insulin in patients with DM2, improved body weight, glycemic control, and insulin requirements but did not improve the primary end point.	Metformin	13-22	insulin	Homo sapiens	107-114
19449763-1	2009	Currently, insulin sensitizing drugs in the form of metformin as the basic drug are part of the treatment of practically any type II diabetic patient.	Metformin	52-61	insulin	Homo sapiens	11-18
19237574-0	2009	Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer"s amyloid peptides via up-regulating BACE1 transcription.	Metformin	18-27	beta-secretase 1	Homo sapiens	113-118
19221498-3	2009	Metformin showed biological activity against all estrogen receptor (ER) positive and negative, erbB2 normal and abnormal breast cancer cell lines tested.	Metformin	0-9	estrogen receptor 1	Homo sapiens	49-66
19221498-3	2009	Metformin showed biological activity against all estrogen receptor (ER) positive and negative, erbB2 normal and abnormal breast cancer cell lines tested.	Metformin	0-9	estrogen receptor 1	Homo sapiens	68-70
19221498-3	2009	Metformin showed biological activity against all estrogen receptor (ER) positive and negative, erbB2 normal and abnormal breast cancer cell lines tested.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	95-100
19221498-8	2009	In erbB2-overexpressing breast cancer cell lines, metformin reduced erbB2 expression at higher concentrations, and at lower concentrations within the therapeutic range, it inhibited erbB2 tyrosine kinase activity evidenced by a reduction of phosphorylated erbB2 (P-erbB2) at both auto- and Src- phosphorylation sites.	Metformin	50-59	erb-b2 receptor tyrosine kinase 2	Homo sapiens	3-8
19221498-8	2009	In erbB2-overexpressing breast cancer cell lines, metformin reduced erbB2 expression at higher concentrations, and at lower concentrations within the therapeutic range, it inhibited erbB2 tyrosine kinase activity evidenced by a reduction of phosphorylated erbB2 (P-erbB2) at both auto- and Src- phosphorylation sites.	Metformin	50-59	erb-b2 receptor tyrosine kinase 2	Homo sapiens	68-73
19221498-8	2009	In erbB2-overexpressing breast cancer cell lines, metformin reduced erbB2 expression at higher concentrations, and at lower concentrations within the therapeutic range, it inhibited erbB2 tyrosine kinase activity evidenced by a reduction of phosphorylated erbB2 (P-erbB2) at both auto- and Src- phosphorylation sites.	Metformin	50-59	erb-b2 receptor tyrosine kinase 2	Homo sapiens	68-73
19221498-8	2009	In erbB2-overexpressing breast cancer cell lines, metformin reduced erbB2 expression at higher concentrations, and at lower concentrations within the therapeutic range, it inhibited erbB2 tyrosine kinase activity evidenced by a reduction of phosphorylated erbB2 (P-erbB2) at both auto- and Src- phosphorylation sites.	Metformin	50-59	erb-b2 receptor tyrosine kinase 2	Homo sapiens	68-73
19221498-8	2009	In erbB2-overexpressing breast cancer cell lines, metformin reduced erbB2 expression at higher concentrations, and at lower concentrations within the therapeutic range, it inhibited erbB2 tyrosine kinase activity evidenced by a reduction of phosphorylated erbB2 (P-erbB2) at both auto- and Src- phosphorylation sites.	Metformin	50-59	erb-b2 receptor tyrosine kinase 2	Homo sapiens	68-73
19221498-9	2009	These data suggest that metformin may have potential therapeutic utility against ER positive and negative, erbB2-overexpressing and erbB2-normal expressing breast cancer cells.	Metformin	24-33	estrogen receptor 1	Homo sapiens	81-83
19221498-9	2009	These data suggest that metformin may have potential therapeutic utility against ER positive and negative, erbB2-overexpressing and erbB2-normal expressing breast cancer cells.	Metformin	24-33	erb-b2 receptor tyrosine kinase 2	Homo sapiens	107-112
19221498-9	2009	These data suggest that metformin may have potential therapeutic utility against ER positive and negative, erbB2-overexpressing and erbB2-normal expressing breast cancer cells.	Metformin	24-33	erb-b2 receptor tyrosine kinase 2	Homo sapiens	132-137
19237574-8	2009	Finally, inhibition of AMP-activated protein kinase (AMPK) by the pharmacological inhibitor Compound C largely suppresses metformin"s effect on Abeta generation and BACE1 transcription, suggesting an AMPK-dependent mechanism.	Metformin	122-131	amyloid beta precursor protein	Homo sapiens	144-149
19237574-8	2009	Finally, inhibition of AMP-activated protein kinase (AMPK) by the pharmacological inhibitor Compound C largely suppresses metformin"s effect on Abeta generation and BACE1 transcription, suggesting an AMPK-dependent mechanism.	Metformin	122-131	beta-secretase 1	Homo sapiens	165-170
19237574-9	2009	Although insulin and metformin display opposing effects on Abeta generation, in combined use, metformin enhances insulin"s effect in reducing Abeta levels.	Metformin	21-30	amyloid beta precursor protein	Homo sapiens	59-64
19237574-9	2009	Although insulin and metformin display opposing effects on Abeta generation, in combined use, metformin enhances insulin"s effect in reducing Abeta levels.	Metformin	94-103	insulin	Homo sapiens	113-120
19237574-3	2009	The present study investigates whether the widely prescribed insulin-sensitizing drug, metformin (Glucophage(R)), affects APP metabolism and Abeta generation in various cell models.	Metformin	87-96	insulin	Homo sapiens	61-68
19237574-9	2009	Although insulin and metformin display opposing effects on Abeta generation, in combined use, metformin enhances insulin"s effect in reducing Abeta levels.	Metformin	94-103	amyloid beta precursor protein	Homo sapiens	142-147
19237574-3	2009	The present study investigates whether the widely prescribed insulin-sensitizing drug, metformin (Glucophage(R)), affects APP metabolism and Abeta generation in various cell models.	Metformin	87-96	amyloid beta precursor protein	Homo sapiens	141-146
19237574-4	2009	We demonstrate that metformin, at doses that lead to activation of the AMP-activated protein kinase (AMPK), significantly increases the generation of both intracellular and extracellular Abeta species.	Metformin	20-29	amyloid beta precursor protein	Homo sapiens	187-192
19237574-5	2009	Furthermore, the effect of metformin on Abeta generation is mediated by transcriptional up-regulation of beta-secretase (BACE1), which results in an elevated protein level and increased enzymatic activity.	Metformin	27-36	amyloid beta precursor protein	Homo sapiens	40-45
19237574-5	2009	Furthermore, the effect of metformin on Abeta generation is mediated by transcriptional up-regulation of beta-secretase (BACE1), which results in an elevated protein level and increased enzymatic activity.	Metformin	27-36	beta-secretase 1	Homo sapiens	121-126
19153119-0	2009	The antidiabetic drug metformin: a pharmaceutical AMPK activator to overcome breast cancer resistance to HER2 inhibitors while decreasing risk of cardiomyopathy.	Metformin	22-31	erb-b2 receptor tyrosine kinase 2	Homo sapiens	105-109
19002567-12	2009	CONCLUSION: The antidiabetic effect of metformin may be diminished in diabetic patients with EE cholestasis, due to impaired hepatic uptake of the drug via OCT1.	Metformin	39-48	solute carrier family 22 member 1	Homo sapiens	156-160
18820825-6	2009	Treatment with pioglitazone, associated with metformin, showed a reduction of IL-6 monocyte production after their in vitro activation with LPS.	Metformin	45-54	interleukin 6	Homo sapiens	78-82
18421577-0	2009	Therapeutic metformin/AMPK activation promotes the angiogenic phenotype in the ERalpha negative MDA-MB-435 breast cancer model.	Metformin	12-21	estrogen receptor 1	Homo sapiens	79-86
19418728-0	2009	[Effect of the Gly972Arg, SNP43 and Prol2Ala polymorphisms of the genes IRS1, CAPN10 and PPARG2 on secondary failure to sulphonylurea and metformin in patients with type 2 diabetes in Yucatan, Mexico].	Metformin	138-147	peroxisome proliferator activated receptor gamma	Homo sapiens	89-95
19418728-3	2009	The association of the polymorphisms Gly972Arg, SNP43, and Pro12Ala, of the genes IRS1, CAPN10, PPARG2, with the risk of failure to sulphonylurea and metformin therapies was determinated in patients with DT2 in Yucatan, Mexico.	Metformin	150-159	calpain 10	Homo sapiens	88-94
19418728-3	2009	The association of the polymorphisms Gly972Arg, SNP43, and Pro12Ala, of the genes IRS1, CAPN10, PPARG2, with the risk of failure to sulphonylurea and metformin therapies was determinated in patients with DT2 in Yucatan, Mexico.	Metformin	150-159	peroxisome proliferator activated receptor gamma	Homo sapiens	96-102
19125418-6	2009	We found that AMPK is robustly activated in rat hepatoma McA-RH7777 cells treated with two widely used AMPK activators, AICAR and metformin, and AMPK activation sharply suppresses SREBP-1c mRNA and nuclear SREBP-1c protein, but not SREBP-1a mRNA derived from the same gene.	Metformin	130-139	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	14-18
19125418-6	2009	We found that AMPK is robustly activated in rat hepatoma McA-RH7777 cells treated with two widely used AMPK activators, AICAR and metformin, and AMPK activation sharply suppresses SREBP-1c mRNA and nuclear SREBP-1c protein, but not SREBP-1a mRNA derived from the same gene.	Metformin	130-139	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	103-107
19125418-6	2009	We found that AMPK is robustly activated in rat hepatoma McA-RH7777 cells treated with two widely used AMPK activators, AICAR and metformin, and AMPK activation sharply suppresses SREBP-1c mRNA and nuclear SREBP-1c protein, but not SREBP-1a mRNA derived from the same gene.	Metformin	130-139	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	103-107
19125418-7	2009	These inhibitory effects are reversed by the AMPK inhibitor Compound C or 8-BrAMP, demonstrating the requirement of AMPK in the suppression of SREBP-1c mRNA and nuclear SREBP-1c protein by AICAR and metformin.	Metformin	199-208	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	45-49
19125418-7	2009	These inhibitory effects are reversed by the AMPK inhibitor Compound C or 8-BrAMP, demonstrating the requirement of AMPK in the suppression of SREBP-1c mRNA and nuclear SREBP-1c protein by AICAR and metformin.	Metformin	199-208	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	116-120
19288260-4	2009	The combination tablet also contains metformin, which addresses insulin resistance.	Metformin	37-46	insulin	Homo sapiens	64-71
19135440-9	2009	Among drug treatments, metformin reduced body weight gain and fat mass, metalloproteinase activity, and TNF-alpha tissue content, while it restored PPAR-alpha expression and downregulated PPAR-gamma expression.	Metformin	23-32	tumor necrosis factor	Rattus norvegicus	104-113
18547343-0	2009	Effect of metformin, orlistat and pioglitazone treatment on mean insulin resistance and its biological variability in polycystic ovary syndrome.	Metformin	10-19	insulin	Homo sapiens	65-72
19275673-6	2009	In addition, a 0.5-0.7% reduction in glycated hemoglobin (HbA1c) levels was observed in metformin- or sulfonylurea-treated patients with type 2 diabetes and in drug-naive or insulin-treated diabetic patients.	Metformin	88-97	insulin	Homo sapiens	174-181
18547343-3	2009	OBJECTIVE: To compare the change in IR and its variability before and after treatment with insulin sensitization through metformin and pioglitazone, compared to that induced by weight loss with orlistat.	Metformin	121-130	insulin	Homo sapiens	91-98
19001513-13	2009	A level of metformin (125 microm) insufficient for the stimulation of lactate output when used alone potentiated the effects of suboptimal doses of insulin on lactate production.	Metformin	11-20	insulin	Homo sapiens	148-155
19001513-16	2009	Metformin also enhances the action of suboptimal insulin concentrations to stimulate lactate production.	Metformin	0-9	insulin	Homo sapiens	49-56
19084501-2	2009	We previously demonstrated that hyperglycemia-induced production of reactive oxygen species from mitochondria (mtROS) contributed to the development of diabetic complications, and metformin normalized mt ROS production by induction of MnSOD and promotion of mitochondrial biogenesis by activating the PGC-1alpha pathway.	Metformin	180-189	PPARG coactivator 1 alpha	Homo sapiens	301-311
18721166-9	2009	Fatty liver prevalence (p < 0.04), severity (p < 0.04), and fasting insulin (p < 0.025) improved significantly with metformin compared to placebo.	Metformin	125-134	insulin	Homo sapiens	74-81
19160294-2	2009	In type 1 diabetes, addition of metformin to insulin therapy, to improve insulin sensitivity, has been assessed in a few trials involving few patients or in uncontrolled studies of short duration.	Metformin	32-41	insulin	Homo sapiens	73-80
19133915-4	2009	Both fasting and non-fasting triglycerides have emerged as important indicators of cardiometabolic risk, while metformin, thiazolidinediones and GLP-1 modulators may prove promising tools for managing insulin resistance.	Metformin	111-120	insulin	Homo sapiens	201-208
19145963-3	2009	Metformin, which decreases hepatic glucose output and sensitizes peripheral tissues to insulin, has been shown to decrease mortality rates in patients with type 2 diabetes and is considered a first-line agent.	Metformin	0-9	insulin	Homo sapiens	87-94
18945255-1	2009	BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a form of progressive fatty liver disease that is strongly associated with insulin resistance, which suggests that insulin sensitizing agents such as metformin may be beneficial for NASH.	Metformin	202-211	insulin	Homo sapiens	127-134
18945255-1	2009	BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a form of progressive fatty liver disease that is strongly associated with insulin resistance, which suggests that insulin sensitizing agents such as metformin may be beneficial for NASH.	Metformin	202-211	insulin	Homo sapiens	167-174
18256928-0	2009	Therapeutic metformin/AMPK activation promotes the angiogenic phenotype in the ERalpha negative MDA-MB-435 breast cancer model.	Metformin	12-21	estrogen receptor 1	Homo sapiens	79-86
18256928-4	2009	Stimulation of AMPK by metformin resulted in a significant repression of cell proliferation and active MAPK1/2 in both estrogen receptor alpha (ERalpha) negative (MDA-MB-231, MDA-MB-435) and positive (MCF-7, T47D) human breast cancer cell lines.	Metformin	23-32	estrogen receptor 1	Homo sapiens	119-142
18256928-4	2009	Stimulation of AMPK by metformin resulted in a significant repression of cell proliferation and active MAPK1/2 in both estrogen receptor alpha (ERalpha) negative (MDA-MB-231, MDA-MB-435) and positive (MCF-7, T47D) human breast cancer cell lines.	Metformin	23-32	estrogen receptor 1	Homo sapiens	144-151
18256928-5	2009	However, when ERalpha negative MDA-MB-435 cells were treated with metformin, they demonstrated increased expression of vascular endothelial growth factor (VEGF) in an AMPK dependent manner; while the ERalpha positive MCF-7 cells did not.	Metformin	66-75	estrogen receptor 1	Homo sapiens	14-21
18256928-5	2009	However, when ERalpha negative MDA-MB-435 cells were treated with metformin, they demonstrated increased expression of vascular endothelial growth factor (VEGF) in an AMPK dependent manner; while the ERalpha positive MCF-7 cells did not.	Metformin	66-75	vascular endothelial growth factor A	Homo sapiens	119-153
18256928-5	2009	However, when ERalpha negative MDA-MB-435 cells were treated with metformin, they demonstrated increased expression of vascular endothelial growth factor (VEGF) in an AMPK dependent manner; while the ERalpha positive MCF-7 cells did not.	Metformin	66-75	vascular endothelial growth factor A	Homo sapiens	155-159
18256928-5	2009	However, when ERalpha negative MDA-MB-435 cells were treated with metformin, they demonstrated increased expression of vascular endothelial growth factor (VEGF) in an AMPK dependent manner; while the ERalpha positive MCF-7 cells did not.	Metformin	66-75	estrogen receptor 1	Homo sapiens	200-207
18256928-8	2009	The metformin-treated group showed increased VEGF expression, intratumoral microvascular density and reduced necrosis.	Metformin	4-13	vascular endothelial growth factor A	Homo sapiens	45-49
18256928-9	2009	Metformin treatment was sufficient, however, to reduce systemic IGF-1 and the proliferation rate of tumor cells in vascularized regions.	Metformin	0-9	insulin like growth factor 1	Homo sapiens	64-69
19106626-10	2009	Of note, co-incubation with agents that block reactive oxygen species (ROS) production (e.g., N-acetylcysteine) dramatically enhanced the ability of metformin to decrease HER2 expression.	Metformin	149-158	erb-b2 receptor tyrosine kinase 2	Homo sapiens	171-175
19106626-0	2009	The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells.	Metformin	22-31	erb-b2 receptor tyrosine kinase 2	Homo sapiens	43-47
19106626-11	2009	From the perspective of chemoprevention, these findings altogether suggest that metformin might exert a protective mostly confined to the HER2-positive breast cancer subtype.	Metformin	80-89	erb-b2 receptor tyrosine kinase 2	Homo sapiens	138-142
19106626-0	2009	The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells.	Metformin	22-31	erb-b2 receptor tyrosine kinase 2	Homo sapiens	49-55
19106626-0	2009	The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells.	Metformin	22-31	mechanistic target of rapamycin kinase	Homo sapiens	106-110
19106626-12	2009	From the perspective of intervention, the presence/absence of molecular hallmarks such as HER2 overexpression and/or p70S6K1 hyperactivation might dictate alternative responses in metformin-based treatment of early breast cancer.	Metformin	180-189	erb-b2 receptor tyrosine kinase 2	Homo sapiens	90-94
19106626-3	2009	We herein demonstrate that HER2 oncoprotein itself may represent a key cellular target involved in the anti-breast cancer actions of metformin.	Metformin	133-142	erb-b2 receptor tyrosine kinase 2	Homo sapiens	27-31
19106626-13	2009	The importance of mTOR/p70S6K1-sensed ROS status at mediating the anti-oncogenic effects of metformin might represent a previously unrecognized linkage molecularly connecting its anti-aging and anti-cancer actions.	Metformin	92-101	mechanistic target of rapamycin kinase	Homo sapiens	18-22
19106626-4	2009	First, ectopical overexpression of HER2 oncogene significantly enhances metformin-induced breast cancer cell growth inhibition.	Metformin	72-81	erb-b2 receptor tyrosine kinase 2	Homo sapiens	35-39
19106626-5	2009	Second, metformin treatment drastically downregulates HER2 protein levels (up to 85% reduction) in a dose- and time-dependent manner.	Metformin	8-17	erb-b2 receptor tyrosine kinase 2	Homo sapiens	54-58
19128368-3	2009	This study was undertaken to determine if subsequent metformin treatment after rimonabant would maintain the improvement in weight, insulin resistance and hyperandrogenaemia in PCOS.	Metformin	53-62	insulin	Homo sapiens	132-139
19106626-6	2009	Metformin-induced inhibition of HER2 take places regardless the molecular mechanism contributing to HER2 overexpression (i.e., human HER2 cDNA exogenously driven by a viral promoter and naturally occurring endogenous HER2 gene amplification).	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	32-36
19106626-6	2009	Metformin-induced inhibition of HER2 take places regardless the molecular mechanism contributing to HER2 overexpression (i.e., human HER2 cDNA exogenously driven by a viral promoter and naturally occurring endogenous HER2 gene amplification).	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	100-104
19106626-6	2009	Metformin-induced inhibition of HER2 take places regardless the molecular mechanism contributing to HER2 overexpression (i.e., human HER2 cDNA exogenously driven by a viral promoter and naturally occurring endogenous HER2 gene amplification).	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	100-104
19106626-6	2009	Metformin-induced inhibition of HER2 take places regardless the molecular mechanism contributing to HER2 overexpression (i.e., human HER2 cDNA exogenously driven by a viral promoter and naturally occurring endogenous HER2 gene amplification).	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	100-104
19106626-7	2009	Mechanistically, metformin-induced suppression of HER2 overexpression appears to occur via direct (AMPK-independent) inhibition of p70S6K1 activity.	Metformin	17-26	erb-b2 receptor tyrosine kinase 2	Homo sapiens	50-54
19106626-9	2009	HER2-positive breast cancer cells transfected with p70S6K1 siRNA become completely refractory to metformin-induced HER2 suppression.	Metformin	97-106	erb-b2 receptor tyrosine kinase 2	Homo sapiens	0-4
19106626-9	2009	HER2-positive breast cancer cells transfected with p70S6K1 siRNA become completely refractory to metformin-induced HER2 suppression.	Metformin	97-106	erb-b2 receptor tyrosine kinase 2	Homo sapiens	115-119
19754381-2	2009	As Polycystic Ovary Syndrome (PCOS) and diabetes share some altered parameters-such as abnormal glucose: insulin ratio, altered lipidic metabolism and insulin-resistance syndrome- the use of metformin has become increasingly accepted and widespread in the treatment of PCOS.	Metformin	191-200	insulin	Homo sapiens	105-112
19754381-2	2009	As Polycystic Ovary Syndrome (PCOS) and diabetes share some altered parameters-such as abnormal glucose: insulin ratio, altered lipidic metabolism and insulin-resistance syndrome- the use of metformin has become increasingly accepted and widespread in the treatment of PCOS.	Metformin	191-200	insulin	Homo sapiens	151-158
18972094-3	2009	However, effects of combined thiazolidinedione-metformin treatment on aPKC or PKB activation by sub-maximal and maximal insulin are unknown.	Metformin	47-56	AKT serine/threonine kinase 1	Homo sapiens	78-81
19092235-0	2009	Increased insulin sensitivity by metformin enhances intense-pulsed-light-assisted hair removal in patients with polycystic ovary syndrome.	Metformin	33-42	insulin	Homo sapiens	10-17
19092235-9	2009	CONCLUSION: Adding metformin to IPL in women with PCOS results in a significant improvement in insulin sensitivity and hirsutism.	Metformin	19-28	insulin	Homo sapiens	95-102
18972094-3	2009	However, effects of combined thiazolidinedione-metformin treatment on aPKC or PKB activation by sub-maximal and maximal insulin are unknown.	Metformin	47-56	insulin	Homo sapiens	120-127
18972094-5	2009	RESULTS: Following combined thiazolidinedione-metformin therapy, increases in glucose disposal and increases in sub-maximal and maximal insulin-induced activities of all four muscle signalling factors, IR, IRS-1-dependent PI3K (IRS-1/PI3K), aPKC and PKBbeta, were observed.	Metformin	46-55	insulin	Homo sapiens	136-143
18972094-8	2009	CONCLUSIONS/INTERPRETATION: Combined thiazolidinedione-metformin treatment markedly improves sub-maximal and maximal insulin signalling to IR, IRS-1/PI3K, aPKC and PKBbeta in type 2 diabetic muscle.	Metformin	55-64	insulin	Homo sapiens	117-124
18952766-10	2009	Diabetic patients receiving metformin therapy had lower vaspin levels than patients not receiving metformin.	Metformin	28-37	serpin family A member 12	Homo sapiens	56-62
19212122-10	2009	Total renin, aldosterone, androgen levels and insulin sensitivity indices were significantly improved after 6 months on metformin treatment.	Metformin	120-129	renin	Homo sapiens	6-11
19188739-4	2009	After 6 weeks of metformin therapy (n = 37) there was a significant reduction in BMI (p < 0.001), waist (p < 0.001) and CRP (p < 0.01), while at 6 months there was not only a significant reduction in BMI and waist but also in HOMA-R (p = 0.01) and IL-6 levels (p < 0.01) with no further reduction of CRP.	Metformin	17-26	C-reactive protein	Homo sapiens	126-129
19188739-4	2009	After 6 weeks of metformin therapy (n = 37) there was a significant reduction in BMI (p < 0.001), waist (p < 0.001) and CRP (p < 0.01), while at 6 months there was not only a significant reduction in BMI and waist but also in HOMA-R (p = 0.01) and IL-6 levels (p < 0.01) with no further reduction of CRP.	Metformin	17-26	interleukin 6	Homo sapiens	257-261
19188739-4	2009	After 6 weeks of metformin therapy (n = 37) there was a significant reduction in BMI (p < 0.001), waist (p < 0.001) and CRP (p < 0.01), while at 6 months there was not only a significant reduction in BMI and waist but also in HOMA-R (p = 0.01) and IL-6 levels (p < 0.01) with no further reduction of CRP.	Metformin	17-26	C-reactive protein	Homo sapiens	312-315
19188739-6	2009	While short-term metformin therapy facilitates weight loss with a concomitant reduction in CRP, long-term therapy results in a reduction of IL-6 and insulin resistance.	Metformin	17-26	C-reactive protein	Homo sapiens	91-94
19188739-7	2009	Metformin-associated reduction of CRP levels prior to any significant changes in insulin resistance or IL-6 perhaps involves different mechanisms of action.	Metformin	0-9	C-reactive protein	Homo sapiens	34-37
19188739-7	2009	Metformin-associated reduction of CRP levels prior to any significant changes in insulin resistance or IL-6 perhaps involves different mechanisms of action.	Metformin	0-9	interleukin 6	Homo sapiens	103-107
19212122-10	2009	Total renin, aldosterone, androgen levels and insulin sensitivity indices were significantly improved after 6 months on metformin treatment.	Metformin	120-129	insulin	Homo sapiens	46-53
19212122-12	2009	Metformin treatment was shown to significantly reduce total renin levels.	Metformin	0-9	renin	Homo sapiens	60-65
19522426-2	2009	A high incidence of ovulation failure is observed in PCO women and perhaps linked to insulin resistance related to metabolic features In the last few years some studies assessed hyperinsulinimea and insulin resistance attenuation effects, by insulin sensitizing agents such as metformin, in PCOS women suggesting potential scope for these drugs in CC ovulation induction quality improvement.	Metformin	277-286	insulin	Homo sapiens	85-92
18997670-2	2009	We here compared the response of serum adiponectin and leptin levels to the amelioration of androgen excess by means of treatment with an antiandrogenic oral contraceptive pill, as compared with the response to insulin sensitization with metformin.	Metformin	238-247	insulin	Homo sapiens	211-218
19811343-1	2009	OBJECTIVE: The antidiabetic agent metformin is regularly discussed as a promising treatment for non-alcoholic fatty liver disease (NAFLD), which is characterized by insulin resistance.	Metformin	34-43	insulin	Homo sapiens	165-172
19084933-7	2008	In Western blot studies, metformin induced poly-ADP-ribose polymerase (PARP) cleavage (an indicator of caspase activation) in all pancreatic cancer cell lines.	Metformin	25-34	poly(ADP-ribose) polymerase 1	Homo sapiens	43-69
19084933-7	2008	In Western blot studies, metformin induced poly-ADP-ribose polymerase (PARP) cleavage (an indicator of caspase activation) in all pancreatic cancer cell lines.	Metformin	25-34	poly(ADP-ribose) polymerase 1	Homo sapiens	71-75
19084933-8	2008	The general caspase inhibitor (VAD-fmk) completely abolished metformin-induced PARP cleavage and apoptosis in ASPC-1 BxPc-3 and PANC-1, the caspase-8 specific inhibitor (IETD-fmk) and the caspase-9 specific inhibitor (LEHD-fmk) only partially abrogated metformin-induced apoptosis and PARP cleavage in BxPc-3 and PANC-1 cells.	Metformin	61-70	poly(ADP-ribose) polymerase 1	Homo sapiens	79-83
19084933-8	2008	The general caspase inhibitor (VAD-fmk) completely abolished metformin-induced PARP cleavage and apoptosis in ASPC-1 BxPc-3 and PANC-1, the caspase-8 specific inhibitor (IETD-fmk) and the caspase-9 specific inhibitor (LEHD-fmk) only partially abrogated metformin-induced apoptosis and PARP cleavage in BxPc-3 and PANC-1 cells.	Metformin	61-70	poly(ADP-ribose) polymerase 1	Homo sapiens	285-289
19084933-9	2008	We also observed that metformin treatment dramatically reduced epidermal growth factor receptor (EGFR) and phosphorylated mitogen activated protein kinase (P-MAPK) in both a time- and dose-dependent manner in all cell lines tested.	Metformin	22-31	epidermal growth factor receptor	Homo sapiens	63-95
19084933-9	2008	We also observed that metformin treatment dramatically reduced epidermal growth factor receptor (EGFR) and phosphorylated mitogen activated protein kinase (P-MAPK) in both a time- and dose-dependent manner in all cell lines tested.	Metformin	22-31	epidermal growth factor receptor	Homo sapiens	97-101
19084933-11	2008	And the metformin-induced apoptosis is associated with PARP cleavage, activation of caspase-3, -8, and -9 in a time- and dose-dependent manner.	Metformin	8-17	poly(ADP-ribose) polymerase 1	Homo sapiens	55-59
19084933-11	2008	And the metformin-induced apoptosis is associated with PARP cleavage, activation of caspase-3, -8, and -9 in a time- and dose-dependent manner.	Metformin	8-17	caspase 3	Homo sapiens	84-105
19522426-2	2009	A high incidence of ovulation failure is observed in PCO women and perhaps linked to insulin resistance related to metabolic features In the last few years some studies assessed hyperinsulinimea and insulin resistance attenuation effects, by insulin sensitizing agents such as metformin, in PCOS women suggesting potential scope for these drugs in CC ovulation induction quality improvement.	Metformin	277-286	insulin	Homo sapiens	183-190
19522426-2	2009	A high incidence of ovulation failure is observed in PCO women and perhaps linked to insulin resistance related to metabolic features In the last few years some studies assessed hyperinsulinimea and insulin resistance attenuation effects, by insulin sensitizing agents such as metformin, in PCOS women suggesting potential scope for these drugs in CC ovulation induction quality improvement.	Metformin	277-286	insulin	Homo sapiens	183-190
19522426-13	2009	CONCLUSION: The ovulatory response to clomifene can be increased in polycystic ovary syndrome women by decreasing insulin secretion with metformin.	Metformin	137-146	insulin	Homo sapiens	114-121
19073504-0	2008	Insulin-lowering effects of metformin in women with early breast cancer.	Metformin	28-37	insulin	Homo sapiens	0-7
19084097-3	2008	Hyperinsulinemia, as demonstrated by elevated insulin levels on a 2-hour 75-g load glucose tolerance test, is an important parameter in deciding whether or not to initiate metformin therapy to women with PCOS with the hope of preventing or delaying the onset of type 2 diabetes mellitus (DM).	Metformin	172-181	insulin	Homo sapiens	5-12
19073504-3	2008	Metformin, a biguanide derivative used in the treatment of diabetes, reduces insulin levels in subjects with type 2 diabetes and other insulin-resistant states.	Metformin	0-9	insulin	Homo sapiens	77-84
19073504-3	2008	Metformin, a biguanide derivative used in the treatment of diabetes, reduces insulin levels in subjects with type 2 diabetes and other insulin-resistant states.	Metformin	0-9	insulin	Homo sapiens	135-142
19073504-4	2008	If metformin lowers insulin levels in women with breast cancer, it may also improve breast cancer outcomes.	Metformin	3-12	insulin	Homo sapiens	20-27
19073504-5	2008	PATIENTS AND METHODS: We administered metformin (1500 mg per day) to 32 women with early breast cancer whose baseline insulin levels were at least 45 pmol/L to determine its effect on insulin levels.	Metformin	38-47	insulin	Homo sapiens	184-191
18410553-1	2008	CONTEXT: Weight loss and metformin therapy are reported to be beneficial in improving the biochemical hyperandrogenaemia and insulin resistance of polycystic ovary syndrome (PCOS).	Metformin	25-34	insulin	Homo sapiens	125-132
19073504-9	2008	Metformin significantly lowered fasting insulin levels by 15.8 pmol/L (22.4%; P=.024) and improved insulin sensitivity by 25.6% (P=.018), total cholesterol by 5.3%, and low-density lipoprotein (LDL) cholesterol by 9.1%.	Metformin	0-9	insulin	Homo sapiens	40-47
19073504-9	2008	Metformin significantly lowered fasting insulin levels by 15.8 pmol/L (22.4%; P=.024) and improved insulin sensitivity by 25.6% (P=.018), total cholesterol by 5.3%, and low-density lipoprotein (LDL) cholesterol by 9.1%.	Metformin	0-9	insulin	Homo sapiens	99-106
19073504-11	2008	CONCLUSION: Metformin significantly lowers insulin levels, and it improves insulin resistance in nondiabetic women with breast cancer.	Metformin	12-21	insulin	Homo sapiens	43-50
19073504-11	2008	CONCLUSION: Metformin significantly lowers insulin levels, and it improves insulin resistance in nondiabetic women with breast cancer.	Metformin	12-21	insulin	Homo sapiens	75-82
18435831-0	2008	Metformin increases fasting plasma peptide tyrosine tyrosine (PYY) in women with polycystic ovarian syndrome (PCOS).	Metformin	0-9	peptide YY	Homo sapiens	62-65
18435831-4	2008	DESIGN AND PATIENTS: We examined the acute effects of orally administrated metformin on fasting PYY levels in eight healthy normal-weight female subjects.	Metformin	75-84	peptide YY	Homo sapiens	96-99
18835932-8	2008	Exposure of HUVECs to either AICAR or metformin caused AMPK-dependent upregulation of both UCP-2 mRNA and UCP-2 protein.	Metformin	38-47	uncoupling protein 2 (mitochondrial, proton carrier)	Mus musculus	91-96
18435831-5	2008	Subsequently, we evaluated the effects of 6 months metformin treatment on fasting PYY levels and anthropometric measurements in 20 women with PCOS.	Metformin	51-60	peptide YY	Homo sapiens	82-85
18435831-6	2008	RESULTS: In normal-weight females 10 days" metformin treatment increased fasting PYY levels (P < 0.01).	Metformin	43-52	peptide YY	Homo sapiens	81-84
18835932-8	2008	Exposure of HUVECs to either AICAR or metformin caused AMPK-dependent upregulation of both UCP-2 mRNA and UCP-2 protein.	Metformin	38-47	uncoupling protein 2 (mitochondrial, proton carrier)	Mus musculus	106-111
18839134-11	2008	CONCLUSIONS/INTERPRETATION: Within the DPP study population, common variants in FTO and INSIG2 are nominally associated with quantitative measures of obesity, directly and possibly by interacting with metformin or lifestyle intervention.	Metformin	201-210	insulin induced gene 2	Homo sapiens	88-94
19000376-5	2008	In addition, alkaline phosphate activity and Western blot analysis for core binding factor a1 (Cbfa1) and peroxisome proliferator-activated receptor gamma 2 (PPARgamma2) proteins also confirmed that metformin inhibited adipocyte differentiation and promoted osteoblast differentiation.	Metformin	199-208	RUNX family transcription factor 2	Rattus norvegicus	71-93
18435831-7	2008	Similarly, in PCOS subjects metformin treatment increased fasting PYY concentrations (P < 0.05).	Metformin	28-37	peptide YY	Homo sapiens	66-69
18435831-8	2008	In both groups a marked variation in PYY increase in response to metformin was observed.	Metformin	65-74	peptide YY	Homo sapiens	37-40
18435831-11	2008	CONCLUSIONS: Acute and chronic oral metformin administration increase fasting PYY levels and may contribute to metformin"s weight loss effect.	Metformin	36-45	peptide YY	Homo sapiens	78-81
18435831-12	2008	Further studies are now required to clarify whether changes in circulating PYY levels in response to metformin treatment can be used to predict which patients will subsequently lose weight long-term and gain cycle restoration.	Metformin	101-110	peptide YY	Homo sapiens	75-78
19000376-5	2008	In addition, alkaline phosphate activity and Western blot analysis for core binding factor a1 (Cbfa1) and peroxisome proliferator-activated receptor gamma 2 (PPARgamma2) proteins also confirmed that metformin inhibited adipocyte differentiation and promoted osteoblast differentiation.	Metformin	199-208	RUNX family transcription factor 2	Rattus norvegicus	95-100
18815214-7	2008	However, myocytes were not protected from sunitinib treatment by pretreating them with the AMPK-activating antidiabetic drug metformin.	Metformin	125-134	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	91-95
18813215-6	2008	Of note, 46% of metformin-treated women required supplemental insulin.	Metformin	16-25	insulin	Homo sapiens	62-69
19046439-0	2008	Cell cycle arrest in Metformin treated breast cancer cells involves activation of AMPK, downregulation of cyclin D1, and requires p27Kip1 or p21Cip1.	Metformin	21-30	cyclin dependent kinase inhibitor 1A	Homo sapiens	141-148
19046439-11	2008	The metformin-resistant cell line MDA-MB-231 expresses significantly lower levels of p27Kip1 and p21Cip1 than the metformin-sensitive cell line, MCF7.	Metformin	4-13	cyclin dependent kinase inhibitor 1A	Homo sapiens	97-104
19046439-12	2008	When p27Kip1 or p21Cip1 were overexpressed in MDA-MB-231, the cells became sensitive to cell cycle arrest in response to metformin.	Metformin	121-130	cyclin dependent kinase inhibitor 1A	Homo sapiens	16-23
18803638-9	2008	In contrast, metformin activated AMPK in the intestinal polyps, resulting in the inhibition of the activation of mammalian target of rapamycin, which play important roles in the protein synthesis machinery.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	113-142
18761646-1	2008	OBJECTIVE: Although metformin (MET) is an insulin sensitizer currently used as an adjunct to the treatment of some of the complications of childhood obesity besides type 2 diabetes mellitus, few studies have comprehensively examined its metabolic and clinical effects in obese children with normal glucose tolerance (NGT).	Metformin	20-29	insulin	Homo sapiens	42-49
18728234-8	2008	CONCLUSIONS: The lack of skeletal muscle AMPK alpha2 activity exacerbates the development of glucose intolerance and insulin resistance caused by high-fat feeding and supports the thesis that AMPK alpha2 is an important target for the prevention/amelioration of skeletal muscle insulin resistance through lifestyle (exercise) and pharmacologic (e.g., metformin) treatments.	Metformin	351-360	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	41-52
18728234-8	2008	CONCLUSIONS: The lack of skeletal muscle AMPK alpha2 activity exacerbates the development of glucose intolerance and insulin resistance caused by high-fat feeding and supports the thesis that AMPK alpha2 is an important target for the prevention/amelioration of skeletal muscle insulin resistance through lifestyle (exercise) and pharmacologic (e.g., metformin) treatments.	Metformin	351-360	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	192-203
18788725-1	2008	The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic drugs including the antidiabetic drug metformin and the anticancer agents oxaliplatin and imatinib.	Metformin	134-143	solute carrier family 22 member 1	Homo sapiens	53-57
18769904-0	2008	Effects of pioglitazone and metformin on NEFA-induced insulin resistance in type 2 diabetes.	Metformin	28-37	insulin	Homo sapiens	54-61
18769904-1	2008	AIMS/HYPOTHESIS: We sought to determine whether pioglitazone and metformin alter NEFA-induced insulin resistance in type 2 diabetes and, if so, the mechanism whereby this is effected.	Metformin	65-74	insulin	Homo sapiens	94-101
18769904-6	2008	Metformin increased (p < 0.001) glucose disappearance during IL/H to rates present during glycerol treatment, indicating protection against NEFA-induced insulin resistance in extrahepatic tissues.	Metformin	0-9	insulin	Homo sapiens	156-163
18721796-0	2008	Metformin enhances the differentiation and mineralization of osteoblastic MC3T3-E1 cells via AMP kinase activation as well as eNOS and BMP-2 expression.	Metformin	0-9	bone morphogenetic protein 2	Mus musculus	135-140
18721796-4	2008	Moreover, metformin significantly activated AMPK in dose- and time-dependent manners, and induced endothelial nitric oxide synthase (eNOS) and bone morphogenetic protein-2 (BMP-2) expressions.	Metformin	10-19	bone morphogenetic protein 2	Mus musculus	143-171
18721796-4	2008	Moreover, metformin significantly activated AMPK in dose- and time-dependent manners, and induced endothelial nitric oxide synthase (eNOS) and bone morphogenetic protein-2 (BMP-2) expressions.	Metformin	10-19	bone morphogenetic protein 2	Mus musculus	173-178
18721796-5	2008	Supplementation of Ara-A (0.1mM), a specific AMPK inhibitor, significantly reversed the metformin-induced eNOS and BMP-2 expressions.	Metformin	88-97	bone morphogenetic protein 2	Mus musculus	115-120
19024576-4	2008	The most frequent causes are gastric disorders, pancreatic insufficiency, or chronic drug treatment (proton pump inhibitors or metformin) that interfere with the digestion of vitamin B12 digestion, or disorders of the ileum mucosa reducing the absorption of vitamin B12.	Metformin	127-136	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	183-186
19024576-4	2008	The most frequent causes are gastric disorders, pancreatic insufficiency, or chronic drug treatment (proton pump inhibitors or metformin) that interfere with the digestion of vitamin B12 digestion, or disorders of the ileum mucosa reducing the absorption of vitamin B12.	Metformin	127-136	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	266-269
18788725-1	2008	The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic drugs including the antidiabetic drug metformin and the anticancer agents oxaliplatin and imatinib.	Metformin	134-143	solute carrier family 22 member 1	Homo sapiens	59-66
18800870-0	2008	Metformin increases HDL3-cholesterol and decreases subcutaneous truncal fat in nondiabetic patients with HIV-associated lipodystrophy.	Metformin	0-9	HDL3	Homo sapiens	20-24
18841263-6	2008	The primary end point of the study is the change in adiponectin level (from baseline to 12 weeks) in the rosiglitazone versus metformin or sulfonylurea arms.	Metformin	126-135	adiponectin, C1Q and collagen domain containing	Homo sapiens	52-63
18800870-10	2008	Thus, metformin use in LDHIV increases HDL3-cholesterol (probably due to improved maturation of HDL) and decreases blood pressure, weight, waist, and subcutaneous truncal fat, making this an attractive option for preventing cardiovascular disease in this population.	Metformin	6-15	HDL3	Homo sapiens	39-43
18248643-13	2008	Metformin treatment induced a significant decrease in insulin levels (P < 0.01) and the concomitant recovery of NPY secretory capacity in response to ghrelin (AUC-NPY: P < 0.05 vs. baseline) in PCOS women.	Metformin	0-9	insulin	Homo sapiens	54-61
18222436-5	2008	INTERVENTION(S): Insulin sensitization with metformin.	Metformin	44-53	insulin	Homo sapiens	17-24
18222436-7	2008	RESULT(S): Metformin, without weight loss or increased physical activity, resulted in restoration of menstrual cycle, reduction in serum T, and improvement in insulin resistance (IR).	Metformin	11-20	insulin	Homo sapiens	159-166
18687824-7	2008	The aim of this work was to analyse the involvement of UCP2 on the effects of metformin in white adipocytes.	Metformin	78-87	uncoupling protein 2 (mitochondrial, proton carrier)	Mus musculus	55-59
18834342-4	2008	In the past few years, metformin, an insulin sensitizer, has been extensively evaluated for induction of ovulation.	Metformin	23-32	insulin	Homo sapiens	37-44
18834342-24	2008	CONCLUSION: In women with PCOS, continuous use of metformin during pregnancy significantly reduced the rate of miscarriage, gestational diabetes requiring insulin treatment and fetal growth restriction.	Metformin	50-59	insulin	Homo sapiens	155-162
18678646-6	2008	Treatment of both primary cells and cancer cell lines with rapamycin, metformin, and pyrvinium resulted in an increase in p73 levels, as did RNA interference-mediated knockdown of mTOR.	Metformin	70-79	mechanistic target of rapamycin kinase	Homo sapiens	180-184
18687824-10	2008	Metformin also increases lipolysis in these cells although only when the levels of ROS and UCP2 have decreased.	Metformin	0-9	uncoupling protein 2 (mitochondrial, proton carrier)	Mus musculus	91-95
18687824-12	2008	Furthermore, treatment of C57BL/6 mice with metformin also augmented the levels of UCP2 in epididymal white adipose tissue.	Metformin	44-53	uncoupling protein 2 (mitochondrial, proton carrier)	Mus musculus	83-87
18687824-13	2008	We conclude that metformin treatment leads to the overexpression of UCP2 in adipocytes to minimize the oxidative stress that is probably due to the inhibition of respiration caused by the drug.	Metformin	17-26	uncoupling protein 2 (mitochondrial, proton carrier)	Mus musculus	68-72
18794619-12	2008	In subgroup analysis of patients exposed to insulin, all-cause mortality remained decreased in metformin users (adjusted HR 0.62, P < 0.04).	Metformin	95-104	insulin	Homo sapiens	44-51
17825080-6	2008	The pharmacological tools available to improve insulin sensitivity include the biguanides (metformin) and thiazolidinediones (rosiglitazone and pioglitazone).	Metformin	91-100	insulin	Homo sapiens	47-54
18979454-3	2008	Metformin is beneficial in improving glucose tolerance and insulin sensitivity, in lowering insulinemia, and in reducing elevated androgen levels.	Metformin	0-9	insulin	Homo sapiens	59-66
18034844-7	2008	Metformin improves sensitivity to insulin and most likely affects positively ED.	Metformin	0-9	insulin	Homo sapiens	34-41
18606228-7	2008	Embryo resorption correlates with the lack of PIBF expression, diminished IL-6 levels and increased IL-2 concentration while metformin was able to reverse the effect of DHEA on both PIBF and COX2 expression and IL-6 levels.	Metformin	125-134	interleukin 6	Mus musculus	74-78
18606228-7	2008	Embryo resorption correlates with the lack of PIBF expression, diminished IL-6 levels and increased IL-2 concentration while metformin was able to reverse the effect of DHEA on both PIBF and COX2 expression and IL-6 levels.	Metformin	125-134	interleukin 6	Mus musculus	211-215
18721657-5	2008	In the past 10 years, insulin sensitization with weight loss or metformin has been shown to be a safe and effective treatment for PCOS infertility that eliminates the risk of multiple pregnancy and may reduce the risk of early pregnancy loss as compared with ovulation-inductor drugs.	Metformin	64-73	insulin	Homo sapiens	22-29
18702951-6	2008	To address this, we investigated the effects of representative insulin-sensitizing therapies such as pioglitazone, metformin, and aerobic exercise on fetuin-A levels.	Metformin	115-124	alpha 2-HS glycoprotein	Homo sapiens	150-158
18606183-5	2008	It mediates the effects of several important adipokines such as leptin and adiponectin and is thought to be responsible for the antidiabetic effects of metformin and thiazolidinediones.	Metformin	152-161	adiponectin, C1Q and collagen domain containing	Homo sapiens	75-86
18346173-17	2008	In addition, in patients given metformin, CRP levels decreased.	Metformin	31-40	C-reactive protein	Homo sapiens	42-45
24692813-3	2008	Biguanides, such as metformin, and thiazolidinediones (TZDs), such as pioglitazone, improve insulin resistance.	Metformin	20-29	insulin	Homo sapiens	92-99
18636232-0	2008	How does blood glucose control with metformin influence intensive insulin protocols?	Metformin	36-45	insulin	Homo sapiens	66-73
18690305-3	2008	Then metformin (500 mg bid) or placebo was administrated with risperidone (6 mg) for the patients.	Metformin	5-14	BH3 interacting domain death agonist	Homo sapiens	23-26
18436790-6	2008	MEASUREMENTS AND MAIN RESULTS: Inhibition of complex I with either rotenone or the antihyperglycemic agent metformin was associated with increased intracellular levels of both superoxide and hydrogen peroxide, as well as inhibition of LPS-induced I kappaB-alpha degradation, NF-kappaB nuclear accumulation, and proinflammatory cytokine production.	Metformin	107-116	nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha	Mus musculus	247-261
18484962-8	2008	Isoform specific AMPK activity was measured 2 hr after administration of metformin or saline.	Metformin	73-82	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	17-21
18484962-2	2008	The energy sensing enzyme AMP-activated protein kinase (AMPK) has been indicated to play an important protective role in the ischaemic heart and is activated by metformin.	Metformin	161-170	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	26-54
18484962-2	2008	The energy sensing enzyme AMP-activated protein kinase (AMPK) has been indicated to play an important protective role in the ischaemic heart and is activated by metformin.	Metformin	161-170	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	56-60
18484962-3	2008	The aim of this study was to determine whether a single dose of metformin protects the myocardium against experimentally induced ischaemia 24 hr after the administration, and furthermore to determine whether a single dose of metformin results in an acute increase in myocardial AMPK activity.	Metformin	64-73	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	278-282
18636232-8	2008	RESULTS: The addition of metformin to the IIT protocol decreased insulin requirement and concentration of insulin and C-peptide.	Metformin	25-34	insulin	Homo sapiens	65-72
18636232-8	2008	RESULTS: The addition of metformin to the IIT protocol decreased insulin requirement and concentration of insulin and C-peptide.	Metformin	25-34	insulin	Homo sapiens	106-113
18636232-14	2008	CONCLUSION: Metformin plus insulin appears to lower the incidence of insulin resistance, lower insulin requirement while maintaining blood glucose level control, and consequently lower the incidence of adverse effects related to high-dose insulin therapy, particularly hypoglycaemia, and also declined nursing workload.	Metformin	12-21	insulin	Homo sapiens	69-76
18636232-14	2008	CONCLUSION: Metformin plus insulin appears to lower the incidence of insulin resistance, lower insulin requirement while maintaining blood glucose level control, and consequently lower the incidence of adverse effects related to high-dose insulin therapy, particularly hypoglycaemia, and also declined nursing workload.	Metformin	12-21	insulin	Homo sapiens	69-76
18636232-14	2008	CONCLUSION: Metformin plus insulin appears to lower the incidence of insulin resistance, lower insulin requirement while maintaining blood glucose level control, and consequently lower the incidence of adverse effects related to high-dose insulin therapy, particularly hypoglycaemia, and also declined nursing workload.	Metformin	12-21	insulin	Homo sapiens	69-76
18484962-11	2008	In conclusion, a single dose of metformin results in an acute increase in myocardial AMPK activity measured 2 hr after administration and induces a significant reduction in myocardial infarct size 24 hr after metformin administration.	Metformin	32-41	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	85-89
18484962-10	2008	A single oral dose of metformin resulted in an approximately ~2-fold increase in AMPK-alpha2 activity 2 hr after administration (P < 0.015, n = 10).	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	81-85
18484962-12	2008	Increased AMPK activity may be an important signal mediator involved in the mechanisms behind the cardioprotective effects afforded by metformin.	Metformin	135-144	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	10-14
18358555-7	2008	Our results indicated that, metformin addition had beneficial effect on VEGF and PAI-1 levels in obese type 2 diabetic patients under MNT+REP, independent from its" favourable effects on BMI and glycemic control.	Metformin	28-37	vascular endothelial growth factor A	Homo sapiens	72-76
18390799-8	2008	Metformin improved insulin resistance by 35%, whereas the OCP worsened insulin resistance by 33%.	Metformin	0-9	insulin	Homo sapiens	19-26
18358555-0	2008	The effect of metformin treatment on VEGF and PAI-1 levels in obese type 2 diabetic patients.	Metformin	14-23	vascular endothelial growth factor A	Homo sapiens	37-41
18358555-6	2008	After metformin addition, there was a significant decrement in BMI, waist circumference, fat percentage, fasting and postprandial plasma glucose, hemoglobin A1C, plasminogen activator inhibitor-1 (PAI-1), vascular endothelial growth factor (VEGF) and increment in beta cell reserve values of the patients.	Metformin	6-15	vascular endothelial growth factor A	Homo sapiens	205-239
18358555-6	2008	After metformin addition, there was a significant decrement in BMI, waist circumference, fat percentage, fasting and postprandial plasma glucose, hemoglobin A1C, plasminogen activator inhibitor-1 (PAI-1), vascular endothelial growth factor (VEGF) and increment in beta cell reserve values of the patients.	Metformin	6-15	vascular endothelial growth factor A	Homo sapiens	241-245
18603639-1	2008	For many patients with type 2 diabetes mellitus, metformin plus appropriate treatment for cardiovascular risk factors form the cornerstone of drug therapy.1 However, the progressive impairment of both the secretion and action of insulin in the condition mean that high blood glucose concentrations usually worsen over time, so necessitating escalation of hypoglycaemic therapy.	Metformin	49-58	insulin	Homo sapiens	229-236
18608522-3	2008	Metformin, an insulin-sensitizing drug, has been shown to improve such metabolic abnormality.	Metformin	0-9	insulin	Homo sapiens	14-21
18608522-15	2008	Metformin significantly decreased fasting insulin concentrations (p < 0.05 and p < 0.01) and increased the insulin sensitivity (p < 0.05) in both obese and non-obese PCOS patients, while no significant changes were observed in the Diane35 group.	Metformin	0-9	insulin	Homo sapiens	42-49
18608522-15	2008	Metformin significantly decreased fasting insulin concentrations (p < 0.05 and p < 0.01) and increased the insulin sensitivity (p < 0.05) in both obese and non-obese PCOS patients, while no significant changes were observed in the Diane35 group.	Metformin	0-9	insulin	Homo sapiens	113-120
18608522-16	2008	In addition, insulin levels also decreased (p < 0.05) in the Diane35/metformin group.	Metformin	72-81	insulin	Homo sapiens	13-20
18608522-17	2008	CONCLUSIONS: Our data show that a combination of metformin and contraceptive pill may be more effective in suppressing the hyperandrogenemia of obese and non-obese PCOS patients than metformin alone and may reduce insulin levels more than contraceptive pill alone.	Metformin	49-58	insulin	Homo sapiens	214-221
18645710-1	2008	OBJECTIVES: Most research confirms that metformin therapy has a positive influence on cardiovascular risk factors (CVRF) such as dyslipidemia, insulin resistance and hyperandrogenism in polycystic ovary syndrome (PCOS).	Metformin	40-49	insulin	Homo sapiens	143-150
18645710-8	2008	Plasma adiponectin increased significantly after metformin treatment, but levels of inflammatory factors did not change.	Metformin	49-58	adiponectin, C1Q and collagen domain containing	Homo sapiens	7-18
18387000-5	2008	In contrast, activating the AMPK pathway by administration of metformin, phenformin or A-769662 to PTEN(+/-) mice significantly delayed tumour onset.	Metformin	62-71	phosphatase and tensin homolog	Mus musculus	99-103
18555836-12	2008	Metformin increased AdipoR1 and R2 expression in muscle (P < .01) and AdipoR1 (P < .01) in WAT.	Metformin	0-9	adiponectin receptor 1	Rattus norvegicus	20-27
18555837-0	2008	An observational study of reduction of insulin resistance and prevention of development of type 2 diabetes mellitus in women with polycystic ovary syndrome treated with metformin and diet.	Metformin	169-178	insulin	Homo sapiens	39-46
18795211-7	2008	Eighteen percent of mothers treated with metformin needed supplementary insulin therapy.	Metformin	41-50	insulin	Homo sapiens	72-79
18408882-8	2008	When the therapeutic target is not achieved, insulin with metformin could be suggested, but is this approach the ideal one for all patients?	Metformin	58-67	insulin	Homo sapiens	45-52
18375721-0	2008	Metabolic actions of metformin in the heart can occur by AMPK-independent mechanisms.	Metformin	21-30	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	57-61
18375721-1	2008	The metabolic actions of the antidiabetic agent metformin reportedly occur via the activation of the AMP-activated protein kinase (AMPK) in the heart and other tissues in the presence or absence of changes in cellular energy status.	Metformin	48-57	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	101-129
18375721-1	2008	The metabolic actions of the antidiabetic agent metformin reportedly occur via the activation of the AMP-activated protein kinase (AMPK) in the heart and other tissues in the presence or absence of changes in cellular energy status.	Metformin	48-57	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	131-135
18375721-2	2008	In this study, we tested the hypothesis that metformin has AMPK-independent effects on metabolism in heart muscle.	Metformin	45-54	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	59-63
18375721-6	2008	Furthermore, the inhibition of AMPK by 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine (Compound C), a well-recognized pharmacological inhibitor of AMPK, or the overexpression of a dominant-negative form of AMPK failed to prevent the metabolic actions of metformin in H9c2 cells.	Metformin	289-298	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	31-35
18477733-14	2008	Metformin may also have a positive effect on metabolic parameters such as waist circumference, fasting insulin and glucose levels, and triglycerides.	Metformin	0-9	insulin	Homo sapiens	103-110
18501722-0	2008	Metformin reduces cellular lysophosphatidylcholine and thereby may lower apolipoprotein B secretion in primary human hepatocytes.	Metformin	0-9	apolipoprotein B	Homo sapiens	73-89
18501722-2	2008	Further, a moderate improvement of dyslipidemia by metformin was reported, and therefore, the effect of metformin on the release of apolipoprotein B (ApoB) and ApoE in primary human hepatocytes was determined.	Metformin	104-113	apolipoprotein B	Homo sapiens	132-148
18501722-2	2008	Further, a moderate improvement of dyslipidemia by metformin was reported, and therefore, the effect of metformin on the release of apolipoprotein B (ApoB) and ApoE in primary human hepatocytes was determined.	Metformin	104-113	apolipoprotein B	Homo sapiens	150-154
18501722-2	2008	Further, a moderate improvement of dyslipidemia by metformin was reported, and therefore, the effect of metformin on the release of apolipoprotein B (ApoB) and ApoE in primary human hepatocytes was determined.	Metformin	104-113	apolipoprotein E	Homo sapiens	160-164
18501722-3	2008	Metformin at 0.5 and 1 mM reduced hepatic ApoB secretion but ApoE was not altered.	Metformin	0-9	apolipoprotein B	Homo sapiens	42-46
18501722-4	2008	Metformin is well known to stimulate the AMP kinase that subsequently reduces hepatic nuclear factor 4-alpha (HNF4-alpha) and HNF4-alpha regulated genes like ApoB.	Metformin	0-9	hepatocyte nuclear factor 4 alpha	Homo sapiens	78-108
18501722-4	2008	Metformin is well known to stimulate the AMP kinase that subsequently reduces hepatic nuclear factor 4-alpha (HNF4-alpha) and HNF4-alpha regulated genes like ApoB.	Metformin	0-9	hepatocyte nuclear factor 4 alpha	Homo sapiens	110-120
18501722-4	2008	Metformin is well known to stimulate the AMP kinase that subsequently reduces hepatic nuclear factor 4-alpha (HNF4-alpha) and HNF4-alpha regulated genes like ApoB.	Metformin	0-9	hepatocyte nuclear factor 4 alpha	Homo sapiens	126-136
18501722-4	2008	Metformin is well known to stimulate the AMP kinase that subsequently reduces hepatic nuclear factor 4-alpha (HNF4-alpha) and HNF4-alpha regulated genes like ApoB.	Metformin	0-9	apolipoprotein B	Homo sapiens	158-162
18501722-5	2008	However, HNF4-alpha was only diminished by 1 mM metformin and ApoB mRNA was not suppressed indicating that this pathway may not explain reduced ApoB release.	Metformin	48-57	hepatocyte nuclear factor 4 alpha	Homo sapiens	9-19
18501722-10	2008	Supplementation with lysoPC led to a selective elevation of endogenous lysoPC and rescued ApoB secretion in metformin-treated cells.	Metformin	108-117	apolipoprotein B	Homo sapiens	90-94
18501722-11	2008	Therefore, it is concluded that metformin reduces lysoPC in human hepatocytes and this may secondarily lead to a therapeutically beneficial lower release of ApoB.	Metformin	32-41	apolipoprotein B	Homo sapiens	157-161
18314419-6	2008	However, OATP-mediated BSP and pravastatin uptake and OCT1-mediated MPP(+) and metformin uptake were significantly inhibited by repaglinide (half-maximal inhibitory concentration [IC(50)] 1.6-5.6 micromol/l) and rosiglitazone (IC(50) 5.2-30.4 micromol/l).	Metformin	79-88	solute carrier family 22 member 1	Homo sapiens	54-58
18288595-5	2008	The anti-atherogenic effects of metformin include reductions in insulin resistance, hyperinsulinaemia and obesity.	Metformin	32-41	insulin	Homo sapiens	64-71
18375437-0	2008	Metformin decreases the adipokine vaspin in overweight women with polycystic ovary syndrome concomitant with improvement in insulin sensitivity and a decrease in insulin resistance.	Metformin	0-9	serpin family A member 12	Homo sapiens	34-40
18375437-0	2008	Metformin decreases the adipokine vaspin in overweight women with polycystic ovary syndrome concomitant with improvement in insulin sensitivity and a decrease in insulin resistance.	Metformin	0-9	insulin	Homo sapiens	124-131
18375437-0	2008	Metformin decreases the adipokine vaspin in overweight women with polycystic ovary syndrome concomitant with improvement in insulin sensitivity and a decrease in insulin resistance.	Metformin	0-9	insulin	Homo sapiens	162-169
18375437-5	2008	Ex vivo regulation of adipose tissue vaspin and the effects of metformin treatment on circulating vaspin levels in PCOS subjects were also studied.	Metformin	63-72	serpin family A member 12	Homo sapiens	98-104
18375437-11	2008	Also, after 6 months of metformin treatment, there was a significant decrease in serum vaspin levels in PCOS women (P < 0.001).	Metformin	24-33	serpin family A member 12	Homo sapiens	87-93
18375437-12	2008	Furthermore, multivariate regression analysis revealed that following metformin therapy, changes in circulating glucose levels were predictive of changes in serum vaspin levels (P = 0.014).	Metformin	70-79	serpin family A member 12	Homo sapiens	163-169
18375437-14	2008	More importantly, metformin treatment decreases serum vaspin levels, a novel observation.	Metformin	18-27	serpin family A member 12	Homo sapiens	54-60
18437350-3	2008	This study investigates whether the glycation inhibitors aminoguanidine and pyridoxamine, the insulin sensitiser metformin and the cross-link breaker alagebrium can inhibit and/or reverse the methylglyoxal-mediated glycation of ApoA-I and whether these changes can preserve or restore the ability of ApoA-I to activate LCAT.	Metformin	113-122	insulin	Homo sapiens	94-101
18437350-4	2008	METHODS: Inhibition of ApoA-I glycation was assessed by incubating aminoguanidine, pyridoxamine, metformin and alagebrium with mixtures of methylglyoxal and discoidal reconstituted HDL (rHDL) containing phosphatidylcholine and ApoA-I, ([A-I]rHDL).	Metformin	97-106	apolipoprotein A1	Homo sapiens	23-29
18437350-7	2008	RESULTS: Aminoguanidine, pyridoxamine, metformin and alagebrium all decreased the methylglyoxal-mediated glycation of the ApoA-I in discoidal rHDL and conserved the ability of the particles to act as substrates for LCAT.	Metformin	39-48	apolipoprotein A1	Homo sapiens	122-128
18273753-7	2008	AGEs-treatment of osteoblast-like cells enhanced RAGE protein expression, and this up-regulation was prevented in the presence of metformin.	Metformin	130-139	advanced glycosylation end product-specific receptor	Mus musculus	49-53
18518780-9	2008	Since metformin reduces hepatic glucose production and increases GLP-1 release, combined therapy with sitagliptin becomes complementary and has been shown to have important additive effects.	Metformin	6-15	glucagon	Homo sapiens	65-70
18322300-12	2008	CONCLUSIONS: A 6-month therapy with insulin sensitizers resulted in marked improvement in adipose tissue GLUT4 mRNA expression in PCOS patients, rosiglitazone being more effective when compared with metformin.	Metformin	199-208	insulin	Homo sapiens	36-43
18597582-10	2008	Metformin is recommended for initial drug therapy; TZDs, sulfonylureas, and insulin are useful options as add-on therapy for patients whose A1C levels remain >or= 7% despite treatment with metformin and lifestyle interventions.	Metformin	192-201	insulin	Homo sapiens	76-83
18082302-6	2008	After an 8-week treatment with metformin, the body weight, fasting levels of glucose, triglyceride, and insulin, insulin secretion, and insulin resistance significantly decreased.	Metformin	31-40	insulin	Homo sapiens	104-111
18492523-0	2008	Addition of metformin to a lifestyle modification program in adolescents with insulin resistance.	Metformin	12-21	insulin	Homo sapiens	78-85
18080084-0	2008	Metformin protects the ischemic heart by the Akt-mediated inhibition of mitochondrial permeability transition pore opening.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	45-48
18080084-2	2008	We hypothesized that metformin cardioprotects the ischemic heart through the Akt-mediated inhibition of mitochondrial permeability transition pore (mPTP) opening.	Metformin	21-30	AKT serine/threonine kinase 1	Homo sapiens	77-80
18080084-9	2008	LY294002 abolished the metformin-induced Akt phosphorylation and the infarct-limiting effect of metformin in Wistar (61 +/- 6.7% metformin + LY294002 vs. 35 +/- 2.7% metformin: P < 0.05) and GK rats (56 +/- 5.7% metformin + LY294002 vs. 43 +/- 4.7% metformin: P < 0.05).	Metformin	23-32	AKT serine/threonine kinase 1	Rattus norvegicus	41-44
18080084-11	2008	CONCLUSIONS: We report that metformin given at the time of reperfusion reduces myocardial infarct size in both the non-diabetic and diabetic heart and this protective effect is mediated through PI3K and is associated with Akt phosphorylation.	Metformin	28-37	AKT serine/threonine kinase 1	Homo sapiens	222-225
18558611-0	2008	Improvement of autoimmune hypoglycemia by decreasing circulating free insulin concentrations with metformin.	Metformin	98-107	insulin	Homo sapiens	70-77
19902051-7	2008	RESULTS: Comparative analysis amongst various insulin regimens shows that combination of metformin, and glimeperide with SC administration of basal insulin Lantus required the least daily dose of insulin with least consequential hypoglycemia as well as weight gain.	Metformin	89-98	insulin	Homo sapiens	46-53
17350746-0	2008	Effect of metformin on IGF-1 and IGFBP-1 levels in obese patients with polycystic ovary syndrome.	Metformin	10-19	insulin like growth factor 1	Homo sapiens	23-28
18319306-7	2008	RESULTS: Metformin-treated girls gained on average 5.5 kg (or approximately 50%) less fat, after 4 yr were less insulin resistant and less hyperandrogenic, had lower IGF-I levels and a less atherogenic lipid profile, and were less likely to be post-menarcheal than untreated girls, whereas their gain in height, lean mass, and bone mineral density were similar.	Metformin	9-18	insulin	Homo sapiens	112-119
18319306-7	2008	RESULTS: Metformin-treated girls gained on average 5.5 kg (or approximately 50%) less fat, after 4 yr were less insulin resistant and less hyperandrogenic, had lower IGF-I levels and a less atherogenic lipid profile, and were less likely to be post-menarcheal than untreated girls, whereas their gain in height, lean mass, and bone mineral density were similar.	Metformin	9-18	insulin like growth factor 1	Homo sapiens	166-171
18192541-3	2008	RESULTS: Baseline adiponectin was a strong independent predictor of incident diabetes in all treatment groups (hazard ratio per approximately 3 microg/ml higher level; 0.61 in the lifestyle, 0.76 in the metformin, and the 0.79 in placebo groups; all P < 0.001, P = 0.13 comparing groups).	Metformin	203-212	adiponectin, C1Q and collagen domain containing	Homo sapiens	18-29
18568311-4	2008	Retrospective analyses indicate a rather positive effect of the insulin sensitizers metformin and glitazones and a neutral or rather negative effect of insulin and sulfonylureas in diabetic patients with heart failure.	Metformin	84-93	insulin	Homo sapiens	64-71
18556965-1	2008	AIM: To determine whether metformin treatment for 6 months is effective in reducing body weight and hyperinsulinemia and also ameliorating insulin sensitivity indices in obese adolescents with hyperinsulinemia.	Metformin	26-35	insulin	Homo sapiens	105-112
18252787-1	2008	CONTEXT: Insulin sensitizers, including metformin and thiazolidinediones (TZDs), improve hyperinsulinemia and reproductive dysfunctions in some women with hyperandrogenism.	Metformin	40-49	insulin	Homo sapiens	9-16
18556965-7	2008	After metformin, there was a significant decline in body mass index (from 28.5 +/- 3.4 to 26.7 +/- 4 kg/m2, p < 0.001), fasting insulin (from 19.2 +/- 10.4 to 11.1 +/- 6.1 microU/ml, p < 0.001) and 120 min insulin levels (from 103.7 +/- 73.8 to 49.8 +/- 30.9 microU/ml, p < 0.001).	Metformin	6-15	insulin	Homo sapiens	131-138
18556965-7	2008	After metformin, there was a significant decline in body mass index (from 28.5 +/- 3.4 to 26.7 +/- 4 kg/m2, p < 0.001), fasting insulin (from 19.2 +/- 10.4 to 11.1 +/- 6.1 microU/ml, p < 0.001) and 120 min insulin levels (from 103.7 +/- 73.8 to 49.8 +/- 30.9 microU/ml, p < 0.001).	Metformin	6-15	insulin	Homo sapiens	212-219
18556965-10	2008	Moreover, in comparison of changes in insulin sensitivity indices between the metformin treated and control groups, the metformin treated group showed significantly improved metabolic control at the end of the study.	Metformin	78-87	insulin	Homo sapiens	38-45
18556965-10	2008	Moreover, in comparison of changes in insulin sensitivity indices between the metformin treated and control groups, the metformin treated group showed significantly improved metabolic control at the end of the study.	Metformin	120-129	insulin	Homo sapiens	38-45
18556965-11	2008	CONCLUSION: These data suggest that metformin treatment is effective in reducing insulin resistance and also ameliorating metabolic complications of insulin resistance syndrome in obese adolescents with hyperinsulinemia.	Metformin	36-45	insulin	Homo sapiens	81-88
18384255-6	2008	Metformin is not metabolized but is transported by at least two organic cation transporters (OCT), OCT1 and OCT2.	Metformin	0-9	solute carrier family 22 member 1	Homo sapiens	99-103
18077446-5	2008	However, another AMPK activator, Metformin, did not alter either the C17.2-NSC or E14-NSC undifferentiated state although both Metformin and AICAR can activate the AMPK pathway in NSC.	Metformin	33-42	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	17-21
18077446-5	2008	However, another AMPK activator, Metformin, did not alter either the C17.2-NSC or E14-NSC undifferentiated state although both Metformin and AICAR can activate the AMPK pathway in NSC.	Metformin	127-136	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	164-168
18160120-9	2008	In contrast, gliclazide in combination with metformin therapy caused increases in both post-load serum glucose and insulin excursions after 2 years, whereas metformin add-on to sulfonylurea did not have a significant effect on post-load serum glucose concentrations and resulted in an increase in insulin levels.	Metformin	44-53	insulin	Homo sapiens	115-122
18245179-12	2008	CONCLUSIONS: Metformin was effective and safe in attenuating olanzapine-induced weight gain and insulin resistance in drug-naive first-episode schizophrenia patients.	Metformin	13-22	insulin	Homo sapiens	96-103
17548076-11	2008	After hCG injection, CRP increased in both the metformin and the placebo groups with no significant difference between the groups.	Metformin	47-56	C-reactive protein	Homo sapiens	21-24
18280440-6	2008	Metformin improved glycemic control and reduced insulin resistance in obese type 2 diabetes mellitus patients.	Metformin	0-9	insulin	Homo sapiens	48-55
21221185-3	2008	Metformin and the thiazolidinediones, pioglitazone and rosiglitazone, are insulin-sensitizing agents available for treatment of type 2 diabetes.	Metformin	0-9	insulin	Homo sapiens	74-81
17609683-0	2008	Effect of genetic variation in the organic cation transporter 1, OCT1, on metformin pharmacokinetics.	Metformin	74-83	solute carrier family 22 member 1	Homo sapiens	35-63
21221185-5	2008	The fixed-dose combination of metformin and pioglitazone appears to be a good option for treating diabetes in insulin-resistant patients.	Metformin	30-39	insulin	Homo sapiens	110-117
18250273-3	2008	METHODS AND RESULTS: Exposure of human umbilical vein endothelial cells or bovine aortic endothelial cells to metformin significantly increased AMPK activity and the phosphorylation of both AMPK at Thr172 and LKB1 at Ser428, an AMPK kinase, which was paralleled by increased activation of protein kinase C (PKC)-zeta, as evidenced by increased activity, phosphorylation (Thr410/403), and nuclear translocation of PKC-zeta.	Metformin	110-119	protein kinase C zeta	Bos taurus	289-316
17609683-0	2008	Effect of genetic variation in the organic cation transporter 1, OCT1, on metformin pharmacokinetics.	Metformin	74-83	solute carrier family 22 member 1	Homo sapiens	65-69
17609683-1	2008	The goal of this study was to determine the effects of genetic variation in the organic cation transporter 1, OCT1, on the pharmacokinetics of the antidiabetic drug, metformin.	Metformin	166-175	solute carrier family 22 member 1	Homo sapiens	80-108
17609683-1	2008	The goal of this study was to determine the effects of genetic variation in the organic cation transporter 1, OCT1, on the pharmacokinetics of the antidiabetic drug, metformin.	Metformin	166-175	solute carrier family 22 member 1	Homo sapiens	110-114
17609683-4	2008	OCT1 genotypes had a significant (P<0.05) effect on metformin pharmacokinetics, with a higher area under the plasma concentration-time curve (AUC), higher maximal plasma concentration (Cmax), and lower oral volume of distribution (V/F) in the individuals carrying a reduced function OCT1 allele (R61C, G401S, 420del, or G465R).	Metformin	55-64	solute carrier family 22 member 1	Homo sapiens	0-4
17609683-6	2008	Our studies suggest that OCT1 genotype is a determinant of metformin pharmacokinetics.	Metformin	59-68	solute carrier family 22 member 1	Homo sapiens	25-29
17909097-6	2008	Metformin-induced SHP gene expression was abolished by adenovirus containing the dominant negative form of AMPK (Ad-DN-AMPK), as well as by compound C. Metformin inhibited hepatocyte nuclear factor-4alpha-or FoxA2-mediated promoter activity of PEPCK and G6Pase, and the inhibition was blocked with siRNA SHP.	Metformin	0-9	forkhead box A2	Mus musculus	208-213
18261504-6	2008	CONCLUSION: Metformin treatment in persons at risk for diabetes improves weight, lipid profiles, and insulin resistance, and reduces new-onset diabetes by 40%.	Metformin	12-21	insulin	Homo sapiens	101-108
18024851-8	2008	CONCLUSIONS: Insulin-sensitizing treatment with metformin is not associated with a higher incidence of bone fractures, suggesting that the negative effect of thiazolidinediones is due to a specific action on bone metabolism rather a reduction of insulinemia.	Metformin	48-57	insulin	Homo sapiens	13-20
18057090-2	2008	RESEARCH DESIGN AND METHODS: TSP1 gene expression was quantified in subcutaneous adipose tissue (SAT) of 86 nondiabetic subjects covering a wide range of BMI and insulin sensitivity, from visceral adipose (VAT) and SAT from 14 surgical patients and from 38 subjects with impaired glucose tolerance randomized to receive either pioglitazone or metformin for 10 weeks.	Metformin	343-352	thrombospondin 1	Homo sapiens	29-33
18210332-0	2008	The investigation and management of severe hyperandrogenism pre- and postmenopause: non-tumor disease is strongly associated with metabolic syndrome and typically responds to insulin-sensitization with metformin.	Metformin	202-211	insulin	Homo sapiens	175-182
18210332-11	2008	A fall in serum T level in response to insulin-sensitizing therapy with metformin and lifestyle change may be a reassuring indicator that such women are highly unlikely to harbor an androgen-secreting tumor.	Metformin	72-81	insulin	Homo sapiens	39-46
17909097-6	2008	Metformin-induced SHP gene expression was abolished by adenovirus containing the dominant negative form of AMPK (Ad-DN-AMPK), as well as by compound C. Metformin inhibited hepatocyte nuclear factor-4alpha-or FoxA2-mediated promoter activity of PEPCK and G6Pase, and the inhibition was blocked with siRNA SHP.	Metformin	152-161	forkhead box A2	Mus musculus	208-213
18182600-8	2008	The lifestyle-plus-metformin group had mean decreases in body mass index (BMI) of 1.8 (95% confidence interval [CI], 1.3-2.3), insulin resistance index of 3.6 (95% CI, 2.7-4.5), and waist circumference of 2.0 cm (95% CI, 1.5-2.4 cm).	Metformin	19-28	insulin	Homo sapiens	127-134
18220291-10	2008	AMPK activation by AICAR or metformin inhibits HSC proliferation via suppression of ROS production and subsequent inhibition of AKT pathway.	Metformin	28-37	AKT serine/threonine kinase 1	Homo sapiens	128-131
18171434-5	2008	Thus we suggest that DPP-4 inhibitors or long-acting GLP-1 mimetics will be used as either first-line therapy or as an early addition to metformin.	Metformin	137-146	glucagon	Homo sapiens	53-58
18182600-9	2008	The metformin-alone group had mean decreases in BMI of 1.2 (95% CI, 0.9-1.5), insulin resistance index of 3.5 (95% CI, 2.7-4.4), and waist circumference of 1.3 cm (95% CI, 1.1-1.5 cm).	Metformin	4-13	insulin	Homo sapiens	78-85
18182600-15	2008	Metformin alone was more effective in weight loss and improving insulin sensitivity than lifestyle intervention alone.	Metformin	0-9	insulin	Homo sapiens	64-71
17914032-7	2008	Insulin-induced suppression of free fatty acids was greater (P < 0.05) after treatment with pioglitazone (0.14 +/- 0.03 vs. 0.06 +/- 0.01 mmol/l) but unchanged with metformin (0.12 +/- 0.03 vs. 0.15 +/- 0.07 mmol/l).	Metformin	168-177	insulin	Homo sapiens	0-7
17968971-6	2008	Metformin also limits weight gain associated with insulin therapy.	Metformin	0-9	insulin	Homo sapiens	50-57
17653063-7	2008	Metformin does appear to mitigate the adverse effects of insulin on body weight.	Metformin	0-9	insulin	Homo sapiens	57-64
18156614-6	2008	The risk for non-fatal myocardial infarction and stroke increased significantly in patients on insulin (HR 1.73, 95% CI 1.26-2.37; P = 0.0007), whereas this risk was lower among those on metformin (HR 0.63, CI 0.42-0.95; P = 0.03) and unchanged with sulphonylureas (HR 0.81, 95% CI 0.57-1.14; P = 0.23).	Metformin	187-196	insulin	Homo sapiens	95-102
18166815-2	2008	However, in non-obese T2DM patients, metformin, targeting insulin resistance, is non-inferior to the prandial insulin secretagogue, repaglinide, controlling overall glycaemia (HbA1c).	Metformin	37-46	insulin	Homo sapiens	58-65
18166815-9	2008	In contrast, fasting levels and AUC of total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (non-HDL) cholesterol and serum insulin were lower during metformin than repaglinide (mean (95% confidence intervals), LDL cholesterol difference metformin versus repaglinide: AUC: -0.17 mmol/l (-0.26; -0.08)).	Metformin	188-197	insulin	Homo sapiens	162-169
18166815-9	2008	In contrast, fasting levels and AUC of total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (non-HDL) cholesterol and serum insulin were lower during metformin than repaglinide (mean (95% confidence intervals), LDL cholesterol difference metformin versus repaglinide: AUC: -0.17 mmol/l (-0.26; -0.08)).	Metformin	276-285	insulin	Homo sapiens	162-169
19065992-9	2008	Use of sitagliptin in conjunction with the insulin-sensitizing medication metformin has been shown to decrease HbAlc levels more significantly than does either drug alone.	Metformin	74-83	insulin	Homo sapiens	43-50
18819351-7	2008	Combined treatment of insulin with meformin or glyclaside with metformin is indicated to patients having compensated type 2 DM and a small ulcerative defect (Wagner"s stages I-II) in the absence of infection, obesity, and IR.	Metformin	63-72	insulin	Homo sapiens	22-29
17876861-3	2007	Uptake of metformin was facilitated by over-expression of hOCT1 and hOCT2 and showed saturable processes, indicating that metformin is a substrate of hOCT1 and hOCT2.	Metformin	10-19	solute carrier family 22 member 1	Homo sapiens	58-63
18561513-7	2008	Both fasting and prandial glucose are reduced by DPP-4 inhibition in combination with metformin in association with improvement of insulin secretion and insulin resistance and increase in concentrations of active GLP-1.	Metformin	86-95	glucagon	Homo sapiens	213-218
17876861-3	2007	Uptake of metformin was facilitated by over-expression of hOCT1 and hOCT2 and showed saturable processes, indicating that metformin is a substrate of hOCT1 and hOCT2.	Metformin	10-19	solute carrier family 22 member 1	Homo sapiens	150-155
17876861-3	2007	Uptake of metformin was facilitated by over-expression of hOCT1 and hOCT2 and showed saturable processes, indicating that metformin is a substrate of hOCT1 and hOCT2.	Metformin	122-131	solute carrier family 22 member 1	Homo sapiens	58-63
17876861-3	2007	Uptake of metformin was facilitated by over-expression of hOCT1 and hOCT2 and showed saturable processes, indicating that metformin is a substrate of hOCT1 and hOCT2.	Metformin	122-131	solute carrier family 22 member 1	Homo sapiens	150-155
17876861-4	2007	The IC(50) values of TAAs for hOCT2 were lower than hOCT1 and decreased with increasing alkyl chain length, indicating that the inhibitory potential of TAAs on metformin uptake was greater in hOCT2 than in hOCT1 and increased with increasing alkyl chain length.	Metformin	160-169	solute carrier family 22 member 1	Homo sapiens	206-211
17666089-9	2007	RESULTS: After 6 months of metformin therapy, women with PCOS had decreased LH, total testosterone, free androgen index and slightly increased SHBG levels.	Metformin	27-36	sex hormone binding globulin	Homo sapiens	143-147
18075846-6	2007	After 3 months of metformin treatment, BMI, WHR, ASP, C3, fasting glucose, fasting insulin, HOMA-IR, total cholesterol, TG, VLDL-C and free testosterone decreased significantly, whereas apolipoprotein A-I and high-density lipoprotein cholesterol increased significantly.	Metformin	18-27	apolipoprotein A1	Homo sapiens	186-204
18082089-7	2007	Pharmacological treatment with either rosuvastatin or metformin lead to reductions in IL-6, TNFalpha, GSH and GPx levels and an increase in the SOD level, and there were significant interactions between the two treatment groups for these variables.	Metformin	54-63	interleukin 6	Homo sapiens	86-90
18074413-0	2007	Effect of rosiglitazone and metformin on insulin resistance in patients infected with human immunodeficiency virus receiving highly active antiretroviral therapy containing protease inhibitor: randomized prospective controlled clinical trial.	Metformin	28-37	insulin	Homo sapiens	41-48
18074413-1	2007	AIM: To evaluate and compare effects of 48-week treatment with rosiglitazone and metformin on insulin resistance in patients infected with Human Immunodeficiency Virus (HIV) receiving highly active antiretroviral therapy (HAART), containing a protease inhibitor.	Metformin	81-90	insulin	Homo sapiens	94-101
18074413-6	2007	RESULTS: After 48 weeks of treatment, the fasting insulin concentration (+/-standard deviation) in rosiglitazone group significantly declined from 39.0+/-3.35 to 19.7+/-3.99 mIU/L (P<0.001; 49% decrease) and in metformin group from 40.3+/-2.29 to 29.2+/-2.82 mIU/L (P<0.001; 27% decrease).	Metformin	214-223	insulin	Homo sapiens	50-57
18082089-7	2007	Pharmacological treatment with either rosuvastatin or metformin lead to reductions in IL-6, TNFalpha, GSH and GPx levels and an increase in the SOD level, and there were significant interactions between the two treatment groups for these variables.	Metformin	54-63	tumor necrosis factor	Homo sapiens	92-100
18082089-7	2007	Pharmacological treatment with either rosuvastatin or metformin lead to reductions in IL-6, TNFalpha, GSH and GPx levels and an increase in the SOD level, and there were significant interactions between the two treatment groups for these variables.	Metformin	54-63	superoxide dismutase 1	Homo sapiens	144-147
18006825-0	2007	Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	19-48
18006825-8	2007	The decrease in translation caused by metformin was associated with mammalian target of rapamycin (mTOR) inhibition, and a decrease in the phosphorylation of S6 kinase, ribosomal protein S6, and eIF4E-binding protein 1.	Metformin	38-47	mechanistic target of rapamycin kinase	Homo sapiens	68-97
18006825-8	2007	The decrease in translation caused by metformin was associated with mammalian target of rapamycin (mTOR) inhibition, and a decrease in the phosphorylation of S6 kinase, ribosomal protein S6, and eIF4E-binding protein 1.	Metformin	38-47	mechanistic target of rapamycin kinase	Homo sapiens	99-103
18006825-11	2007	These results show that metformin-mediated AMPK activation leads to inhibition of mTOR and a reduction in translation initiation, thus providing a possible mechanism of action of metformin in the inhibition of cancer cell growth.	Metformin	24-33	mechanistic target of rapamycin kinase	Homo sapiens	82-86
18006825-11	2007	These results show that metformin-mediated AMPK activation leads to inhibition of mTOR and a reduction in translation initiation, thus providing a possible mechanism of action of metformin in the inhibition of cancer cell growth.	Metformin	179-188	mechanistic target of rapamycin kinase	Homo sapiens	82-86
17717055-5	2007	Furthermore, the daily oral and intracerebroventricular treatment with biguanide antidiabetic drug metformin also induced AMPK phosphorylation in the central nervous system and increased food intake and life span in anorexic TB rats.	Metformin	99-108	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	122-126
17984247-1	2007	OBJECTIVE: Addition of androgen receptor (AR) blockade (flutamide) to insulin-sensitising therapy (metformin) may confer synergistic benefits in girls with hyperinsulinaemic androgen excess.	Metformin	99-108	insulin	Homo sapiens	70-77
17698034-8	2007	Metformin treatment of the hepatocytes resulted in activation of the AMP-activated kinase, attenuation of the mTOR/S6K1 pathway, reduction of IRS-1 phosphorylation, and a leftward shift in the insulin dose-response curve for PKB activation.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	110-114
18158076-4	2007	OBJECTIVE: The aim of this study was to test the hypothesis that treatment with a premixed insulin analogue containing 50/50 basal + prandial insulins administered before each meal would achieve lower overall and mealtime glycemic control than once-daily basal insulin analogue, both plus metformin (Met), in patients with type 2 diabetes mellitus.	Metformin	289-298	insulin	Homo sapiens	91-98
18158076-4	2007	OBJECTIVE: The aim of this study was to test the hypothesis that treatment with a premixed insulin analogue containing 50/50 basal + prandial insulins administered before each meal would achieve lower overall and mealtime glycemic control than once-daily basal insulin analogue, both plus metformin (Met), in patients with type 2 diabetes mellitus.	Metformin	289-298	insulin	Homo sapiens	142-149
17890232-7	2007	CONCLUSIONS: A single analogue-insulin formulation added to metformin and sulfonylurea resulted in a glycated hemoglobin level of 6.5% or less in a minority of patients at 1 year.	Metformin	60-69	insulin	Homo sapiens	31-38
17698034-8	2007	Metformin treatment of the hepatocytes resulted in activation of the AMP-activated kinase, attenuation of the mTOR/S6K1 pathway, reduction of IRS-1 phosphorylation, and a leftward shift in the insulin dose-response curve for PKB activation.	Metformin	0-9	insulin	Homo sapiens	193-200
18059616-10	2007	Prevention of T2DM with lifestyle intervention is at least as effective in non-obese as in obese prediabetic subjects, and recent data suggest that metformin treatment targeting insulin resistance and non-glycemic cardiovascular disease risk factors is as beneficial in non-obese as in obese patients with T2DM.	Metformin	148-157	insulin	Homo sapiens	178-185
17987221-8	2007	Metformin improves insulin resistance and is the first-line antidiabetic drug in use today.	Metformin	0-9	insulin	Homo sapiens	19-26
17600084-3	2007	Metformin has been shown to be transported by the human organic cation transporters 1 and 2 (hOCT1-2).	Metformin	0-9	solute carrier family 22 member 1	Homo sapiens	56-91
17600084-3	2007	Metformin has been shown to be transported by the human organic cation transporters 1 and 2 (hOCT1-2).	Metformin	0-9	solute carrier family 22 member 1	Homo sapiens	93-100
17567959-9	2007	Moreover, after 1 h of IVM, metformin decreased RPS6 phosphorylation and increased EEF2 phosphorylation, suggesting that protein synthesis rates were lower in oocytes from metformin-treated COCs.	Metformin	28-37	40S ribosomal protein S6	Bos taurus	48-52
17374431-5	2007	Oral metformin 850mg bid was administered to PCOS patients.	Metformin	5-14	BH3 interacting domain death agonist	Homo sapiens	21-24
17718786-1	2007	AIM: In a previous study we showed that metformin reduced BMI z-scores and fasting glucose and insulin concentrations, and increased whole body insulin sensitivity in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes.	Metformin	40-49	insulin	Homo sapiens	95-102
17718786-1	2007	AIM: In a previous study we showed that metformin reduced BMI z-scores and fasting glucose and insulin concentrations, and increased whole body insulin sensitivity in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes.	Metformin	40-49	insulin	Homo sapiens	144-151
17718786-2	2007	We analyzed the data from this study to determine (a) if metformin reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations during the 6-month trial, and (b) if the response to pharmacotherapy varied along gender or ethnic lines.	Metformin	57-66	solute carrier family 17 member 5	Homo sapiens	116-142
17718786-2	2007	We analyzed the data from this study to determine (a) if metformin reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations during the 6-month trial, and (b) if the response to pharmacotherapy varied along gender or ethnic lines.	Metformin	57-66	solute carrier family 17 member 5	Homo sapiens	144-147
17718786-6	2007	Metformin had no effect on ALT levels or the ALT to AST ratio in the five African American adolescents enrolled in the study but reduced their fasting insulin concentrations from 26.1 to 19.5 muU/mL (p < 0.05).	Metformin	0-9	insulin	Homo sapiens	151-158
18062354-7	2007	Metformin, Thiazolidinediones and Acarbose are anti-hyperglycemic drugs of choice: they reduce the incidence of DM2 and IR (or improve insulin sensitivity) and they decrease or stabilize the visceral adipose tissue mass (Thiazolidinediones increases subcutaneous fat only).	Metformin	0-9	insulin	Homo sapiens	135-142
17608755-1	2007	BACKGROUND: Discontinuation of metformin therapy, if started beyond menarche in adolescents or young women with hyperinsulinaemia following low birthweight, is rapidly followed by rebound deteriorations in body fat, insulin resistance and blood lipid profile.	Metformin	31-40	insulin	Homo sapiens	117-124
17575082-3	2007	This study tests the hypothesis that AMP kinase (AMPK) activation with metformin directly improves insulin signaling within the blastocyst, leading to improved pregnancy outcomes.	Metformin	71-80	insulin	Homo sapiens	99-106
17908667-0	2007	Hyperhomocysteinemia, deep vein thrombosis and vitamin B12 deficiency in a metformin-treated diabetic patient.	Metformin	75-84	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	55-58
17908667-1	2007	Vitamin B12 deficiency may be induced by long-term use of metformin, which may in turn lead to hyperhomocysteinemia.	Metformin	58-67	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	8-11
17908667-8	2007	Our findings highly suggested the role of metformin in causing vitamin B12 deficiency, which may serve as an additional risk factor for venous thrombosis in diabetic patients.	Metformin	42-51	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	71-74
17908667-9	2007	Our report also highlights the need to check vitamin B12 levels during metformin treatment.	Metformin	71-80	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	53-56
18092442-5	2007	Furthermore, drugs able to reduce insulin resistance, such as metformin and thiazolidinediones, already in the therapeutic armamentarium of type 2 diabetes, could be used in subjects with the metabolic syndrome as a preventive measure.	Metformin	62-71	insulin	Homo sapiens	34-41
18038714-14	2007	However, metformin at a higher dose and in combination with rosiglitazone resulted in improvement of pancreatic beta-cell function, shown by markedly improved first-phase insulin response to glucose measured by AIR.	Metformin	9-18	insulin	Homo sapiens	171-178
18038714-17	2007	CONCLUSION: We suggest that early initiation of combined therapy comprising a high dose of metformin plus rosiglitazone may be valuable in managing insulin resistance and DM2 in children with AS.	Metformin	91-100	insulin	Homo sapiens	148-155
17846932-7	2007	Insulin only (IO), bedtime insulin with sulphonylurea (glipizide) (IS), or bedtime insulin with metformin (IM).	Metformin	96-105	insulin	Homo sapiens	83-90
18088046-10	2007	Metformin and thiazolidinendiones are used to treat insulin resistance, but have different mechanisms of action.	Metformin	0-9	insulin	Homo sapiens	52-59
18088046-11	2007	Metformin reduces free fatty amino acids effluvium from fat cells, thereby suppressing hepatic glucose production and indirectly improving peripheral insulin sensitivity and the endothelial function.	Metformin	0-9	insulin	Homo sapiens	150-157
18019665-8	2007	Through its effect on RBP4 expression in adipocytes, metformin may improve total insulin sensitivity in obese individuals including those with MS and delay the onset of manifest DM.	Metformin	53-62	insulin	Homo sapiens	81-88
17691915-7	2007	Insulin sensitizers such as thiazolidinediones and metformin show promise, and several studies have explored the role of lipid lowering agents, antioxidants, and cytoprotective agents.	Metformin	51-60	insulin	Homo sapiens	0-7
17767338-8	2007	In several prospective and retrospective studies on women with PCOS, metformin was shown to prevent early pregnancy loss, decrease insulin resistance, reduce insulin and testosterone levels, and decrease the incidence of gestational diabetes when these women got pregnant while on metformin and continued to take it throughout their pregnancy.	Metformin	69-78	insulin	Homo sapiens	131-138
17767338-8	2007	In several prospective and retrospective studies on women with PCOS, metformin was shown to prevent early pregnancy loss, decrease insulin resistance, reduce insulin and testosterone levels, and decrease the incidence of gestational diabetes when these women got pregnant while on metformin and continued to take it throughout their pregnancy.	Metformin	69-78	insulin	Homo sapiens	158-165
17504902-0	2007	Metformin suppresses interleukin (IL)-1beta-induced IL-8 production, aromatase activation, and proliferation of endometriotic stromal cells.	Metformin	0-9	C-X-C motif chemokine ligand 8	Homo sapiens	52-56
17335818-8	2007	RESULT(S): In the metformin group, there was a significant decrease in the fasting glucose, fasting insulin, and total T. In the N-acetyl cysteine group, there was no significant difference in the fasting glucose or fasting insulin and there was a significant decrease in total T. There was no significant difference in the fasting glucose-fasting insulin ratio in both groups.	Metformin	18-27	insulin	Homo sapiens	100-107
17519312-2	2007	OBJECTIVE: The objective of the study was to evaluate the effects of metformin suspension on insulin sensitivity in PCOS patients.	Metformin	69-78	insulin	Homo sapiens	93-100
17519312-9	2007	During treatment, the clamp insulin sensitivity index was significantly improved (P < 0.05) in the metformin group in comparison with baseline and placebo group, without significant differences between the 6- and 12-month assessments.	Metformin	102-111	insulin	Homo sapiens	28-35
17519312-10	2007	At 6 and 12 months after treatment suspension, in the metformin group, insulin sensitivity index significantly (P < 0.05) worsened in comparison with that observed at baseline and during treatment and with that observed in the placebo and control groups.	Metformin	54-63	insulin	Homo sapiens	71-78
17519312-11	2007	CONCLUSION: In normal-weight anovulatory PCOS patients, long-term metformin administration exerts beneficial effects on peripheral insulin sensitivity.	Metformin	66-75	insulin	Homo sapiens	131-138
17504902-5	2007	RESULTS: Metformin dose-dependently suppressed IL-1beta-induced IL-8 production, cAMP-induced mRNA expression and aromatase activity, and 5-bromo-2"-deoxyuridine incorporation in ESCs.	Metformin	9-18	interleukin 1 beta	Homo sapiens	47-55
17504902-5	2007	RESULTS: Metformin dose-dependently suppressed IL-1beta-induced IL-8 production, cAMP-induced mRNA expression and aromatase activity, and 5-bromo-2"-deoxyuridine incorporation in ESCs.	Metformin	9-18	C-X-C motif chemokine ligand 8	Homo sapiens	64-68
17654257-9	2007	Compound C, an AMPK inhibitor, reversed apoptosis and changes in the apoptotic markers, suggesting a role of AMPK activation by metformin in the apoptotic process.	Metformin	128-137	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	109-113
17638885-10	2007	Metformin-treated cells compensated for this suppression of oxidative phosphorylation by increasing their rate of glycolysis in a p53-dependent manner.	Metformin	0-9	tumor protein p53	Homo sapiens	130-133
17654257-1	2007	The antidiabetic effect of metformin is mediated by activation of AMP-activated kinase (AMPK).	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	66-86
17654257-1	2007	The antidiabetic effect of metformin is mediated by activation of AMP-activated kinase (AMPK).	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	88-92
17525164-0	2007	Activation of 5"-AMP-activated kinase with diabetes drug metformin induces casein kinase Iepsilon (CKIepsilon)-dependent degradation of clock protein mPer2.	Metformin	57-66	period circadian clock 2	Mus musculus	150-155
17525164-5	2007	We discovered that the circadian period of Rat-1 fibroblasts treated with metformin was shortened by 1 h. One of the regulators of the period length is casein kinase Iepsilon (CKIepsilon), which by phosphorylating and inducing the degradation of the circadian clock component, mPer2, shortens the period length.	Metformin	74-83	period circadian clock 2	Mus musculus	277-282
17525164-7	2007	In peripheral tissues, injection of metformin leads to mPer2 degradation and a phase advance in the circadian expression pattern of clock genes in wild-type mice but not in AMPK alpha2 knock-out mice.	Metformin	36-45	period circadian clock 2	Mus musculus	55-60
17638885-0	2007	Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth.	Metformin	46-55	tumor protein p53	Homo sapiens	76-79
17638885-2	2007	Treatment with metformin selectively suppressed the tumor growth of HCT116 p53(-/-) xenografts.	Metformin	15-24	tumor protein p53	Homo sapiens	75-78
17638885-3	2007	Following treatment with metformin, we detected increased apoptosis in p53(-/-) tumor sections and an enhanced susceptibility of p53(-/-) cells to undergo apoptosis in vitro when subject to nutrient deprivation.	Metformin	25-34	tumor protein p53	Homo sapiens	71-74
17638885-11	2007	Together, these data suggest that metformin treatment forces a metabolic conversion that p53(-/-) cells are unable to execute.	Metformin	34-43	tumor protein p53	Homo sapiens	89-92
17638885-3	2007	Following treatment with metformin, we detected increased apoptosis in p53(-/-) tumor sections and an enhanced susceptibility of p53(-/-) cells to undergo apoptosis in vitro when subject to nutrient deprivation.	Metformin	25-34	tumor protein p53	Homo sapiens	129-132
17638885-8	2007	Treatment with either metformin or AICAR also led to enhanced fatty acid beta-oxidation in p53(+/+) MEFs, but not in p53(-/-) MEFs.	Metformin	22-31	tumor protein p53	Homo sapiens	91-94
17638885-12	2007	Thus, metformin is selectively toxic to p53-deficient cells and provides a potential mechanism for the reduced incidence of tumors observed in patients being treated with metformin.	Metformin	6-15	tumor protein p53	Homo sapiens	40-43
17638885-12	2007	Thus, metformin is selectively toxic to p53-deficient cells and provides a potential mechanism for the reduced incidence of tumors observed in patients being treated with metformin.	Metformin	171-180	tumor protein p53	Homo sapiens	40-43
17559747-2	2007	However, when metformin fails, the recommended add-on treatment options (sulphonylureas, glitazones and basal insulin) can lead to significant weight gain.	Metformin	14-23	insulin	Homo sapiens	110-117
17426085-11	2007	On the contrary, the insulin sensitivity index increased with metformin but did not change with Diane(35) Diario.	Metformin	62-71	insulin	Homo sapiens	21-28
17587394-1	2007	AIM: The aim of this randomized placebo-controlled study was to evaluate the safety and efficacy of pioglitazone administered alone or in combination with metformin in reducing insulin dosage requirements for improved glycaemic control in patients with type 2 diabetes previously poorly controlled with combination therapy.	Metformin	155-164	insulin	Homo sapiens	177-184
17929538-1	2007	INTRODUCTION: The main causes of reduced glucose levels during metformin therapy appear to be an increase in insulin action in peripheral tissues and reduced hepatic glucose output due to inhibition gluconeogenesis.	Metformin	63-72	insulin	Homo sapiens	109-116
17929538-14	2007	CONCLUSION: It can be concluded that, as compared to place- bo, metformin is more efficient in reducing insulin resistance in obese patients with DM type 2.	Metformin	64-73	insulin	Homo sapiens	104-111
17391168-8	2007	However, body weight, waist circumference, fasting serum levels of insulin and C-peptide were lower and less number of patients experienced hypoglycaemia during treatment with metformin vs. repaglinide.	Metformin	176-185	insulin	Homo sapiens	67-74
17403121-3	2007	RESULTS: Insulin dose at week 24 was significantly lower with rosiglitazone + metformin (33.5 +/- 1.5 U/day, mean +/- se) compared with placebo [59.0 +/- 3.0 U/day; model-adjusted difference -26.6 (95% CI -37.7, -15,5) U/day, P < 0.001].	Metformin	78-87	insulin	Homo sapiens	9-16
17403121-8	2007	CONCLUSIONS: Addition of insulin to rosiglitazone + metformin enabled more people to reach glycaemic targets with less insulin, and was generally well tolerated.	Metformin	52-61	insulin	Homo sapiens	119-126
17587750-11	2007	The combination of thiazolinediones and metformin is associated with a slight but significant improvement in the long-term blood pressure control of these patients, and with an improvement in the anti-inflammatory state, both of which are related to a similar reduction in insulin-resistance.	Metformin	40-49	insulin	Homo sapiens	273-280
17489673-5	2007	Nevertheless, appropriate treatment of MS components often requires pharmacologic intervention with insulin-sensitizing agents, such as metformin and thiazolidinediones, while statins and fibrates, or angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are the first-line lipid-modifying or antihypertensive drugs.	Metformin	136-145	insulin	Homo sapiens	100-107
17299064-1	2007	CONTEXT AND OBJECTIVE: One of the treatments for hyperinsulinemic hyperandrogenism in nonobese women is combined androgen receptor blockade (with flutamide; Flu), insulin sensitization (with metformin; Met) plus an estroprogestagen contraceptive.	Metformin	191-200	insulin	Homo sapiens	54-61
17476355-6	2007	make significant progress by integrating diverse data supporting the hypothesis that genetic variation in organic cation transporter 1 (OCT1) affects the response to the widely used biguanide metformin (see the related article beginning on page 1422).	Metformin	192-201	solute carrier family 22 member 1	Homo sapiens	106-134
17476355-6	2007	make significant progress by integrating diverse data supporting the hypothesis that genetic variation in organic cation transporter 1 (OCT1) affects the response to the widely used biguanide metformin (see the related article beginning on page 1422).	Metformin	192-201	solute carrier family 22 member 1	Homo sapiens	136-140
17493545-6	2007	METHODS: Newly diagnosed treatment-naive patients with type 2 diabetes had their hepatic triglyceride (TG) content measured by magnetic resonance spectroscopy at baseline and after 3 months of treatment with BiAsp 30 insulin, in combination with metformin.	Metformin	246-255	insulin	Homo sapiens	217-224
17940431-1	2007	PURPOSE OF REVIEW: The aim of this article is to describe the role of insulin resistance in the etiology of polycystic ovary syndrome and to review the results of treatment with the insulin sensitizing drug metformin.	Metformin	207-216	insulin	Homo sapiens	70-77
17940431-1	2007	PURPOSE OF REVIEW: The aim of this article is to describe the role of insulin resistance in the etiology of polycystic ovary syndrome and to review the results of treatment with the insulin sensitizing drug metformin.	Metformin	207-216	insulin	Homo sapiens	182-189
17505944-0	2007	Effects of metformin treatment in women with polycystic ovary syndrome depends on insulin resistance.	Metformin	11-20	insulin	Homo sapiens	82-89
17395752-6	2007	Adjustment for weight, fasting insulin, proinsulin, and other metabolic factors combined explained 81% of the beneficial metformin effect, but it remained nominally significant (P = 0.034).	Metformin	121-130	insulin	Homo sapiens	31-38
17395752-6	2007	Adjustment for weight, fasting insulin, proinsulin, and other metabolic factors combined explained 81% of the beneficial metformin effect, but it remained nominally significant (P = 0.034).	Metformin	121-130	insulin	Homo sapiens	40-50
17395752-8	2007	Treatment of high-risk subjects with metformin results in modest weight loss and favorable changes in insulin sensitivity and proinsulin, which contribute to a reduction in the risk of diabetes apart from the associated reductions in fasting glucose.	Metformin	37-46	insulin	Homo sapiens	102-109
17395752-8	2007	Treatment of high-risk subjects with metformin results in modest weight loss and favorable changes in insulin sensitivity and proinsulin, which contribute to a reduction in the risk of diabetes apart from the associated reductions in fasting glucose.	Metformin	37-46	insulin	Homo sapiens	126-136
17505944-5	2007	This implies that, by improving insulin and carbohydrate metabolism, metformin administration in PCOS patients could indirectly contribute to increase SHBG concentration.	Metformin	69-78	insulin	Homo sapiens	32-39
17505944-5	2007	This implies that, by improving insulin and carbohydrate metabolism, metformin administration in PCOS patients could indirectly contribute to increase SHBG concentration.	Metformin	69-78	sex hormone binding globulin	Homo sapiens	151-155
17505944-6	2007	The aim of the present study was to assess the effects of metformin treatment in PCOS patients both with and without insulin resistance.	Metformin	58-67	insulin	Homo sapiens	117-124
17505944-12	2007	Considering the favorable effects of metformin treatment in PCOS patients both with insulin resistance and without it, it is purposeful to use this drug in both groups of women.	Metformin	37-46	insulin	Homo sapiens	84-91
17525501-0	2007	Effect of metformin therapy on plasma adiponectin and leptin levels in obese and insulin resistant postmenopausal females with type 2 diabetes.	Metformin	10-19	adiponectin, C1Q and collagen domain containing	Homo sapiens	38-49
17525501-9	2007	In summary, our data suggest that hypoadiponectinemia in PM may be explained by only IR because the amelioration of whole-body insulin action by 6-month Metformin therapy leads to increase of plasma adiponectin levels; leptin levels did not significantly change after 6-month Metformin therapy.	Metformin	153-162	adiponectin, C1Q and collagen domain containing	Homo sapiens	38-49
17525501-9	2007	In summary, our data suggest that hypoadiponectinemia in PM may be explained by only IR because the amelioration of whole-body insulin action by 6-month Metformin therapy leads to increase of plasma adiponectin levels; leptin levels did not significantly change after 6-month Metformin therapy.	Metformin	276-285	adiponectin, C1Q and collagen domain containing	Homo sapiens	38-49
17849796-8	2007	CONCLUSION: A 3 month course of metformin therapy in women with polycystic ovary syndrome did not improve menstrual cyclicity, albeit significant decrease in insulin, insulin resistance and hirsutism was obtained.	Metformin	32-41	insulin	Homo sapiens	158-165
17849796-8	2007	CONCLUSION: A 3 month course of metformin therapy in women with polycystic ovary syndrome did not improve menstrual cyclicity, albeit significant decrease in insulin, insulin resistance and hirsutism was obtained.	Metformin	32-41	insulin	Homo sapiens	167-174
17458042-7	2007	(4) In a randomised unblinded trial the addition of metformin to ongoing insulin therapy in 106 children reduced both mean HbA1c levels and weight gain after one year of treatment.	Metformin	52-61	insulin	Homo sapiens	73-80
17224152-0	2007	Acute effects of metformin therapy include improvement of insulin resistance and ovarian morphology.	Metformin	17-26	insulin	Homo sapiens	58-65
17224152-1	2007	OBJECTIVE: To evaluate the acute effects of metformin therapy on biochemical markers and polycystic ovarian morphology among insulin-resistant (IR) and noninsulin-resistant (NIR) patients with polycystic ovary syndrome (PCOS).	Metformin	44-53	insulin	Homo sapiens	125-132
17458042-8	2007	About one-third of children treated with metformin were able to stop using insulin and maintain satisfactory glycaemic control.	Metformin	41-50	insulin	Homo sapiens	75-82
17458042-12	2007	Metformin addition to ongoing insulin therapy allows some patients to stop using insulin altogether.	Metformin	0-9	insulin	Homo sapiens	81-88
17307426-7	2007	High-sensitivity C-reactive protein levels decreased by an average of 68% in the rosiglitazone group (5.99 +/- 0.88 to 1.91 +/- 0.28 mg/L, P < .001), compared with a nonsignificant 4% reduction in hsCRP with metformin (5.69 +/- 0.83 to 5.46 +/- 0.92 mg/L; P = nonsignificant).	Metformin	211-220	C-reactive protein	Homo sapiens	17-35
17123942-10	2007	Metformin decreased phosphorylation levels of MAPK3/MAPK1 and MAPK14 in a dose- and time-dependent manner.	Metformin	0-9	mitogen-activated protein kinase 1	Bos taurus	52-57
17414590-0	2007	Metformin plus low-dose glimeperide significantly improves Homeostasis Model Assessment for insulin resistance (HOMA(IR)) and beta-cell function (HOMA(beta-cell)) without hyperinsulinemia in patients with type 2 diabetes mellitus.	Metformin	0-9	insulin	Homo sapiens	92-99
17123942-12	2007	Thus, in bovine granulosa cells, metformin decreases steroidogenesis and MAPK3/MAPK1 phosphorylation through AMPK activation.	Metformin	33-42	mitogen-activated protein kinase 1	Bos taurus	79-84
17454168-2	2007	The use of insulin-sensitizer compounds, such as metformin, permits great improvement of such metabolic abnormality, restoring ovarian function and gonadal steroid synthesis and reducing insulin resistance.	Metformin	49-58	insulin	Homo sapiens	11-18
17184171-6	2007	PGC-1alpha expressed in human aortic smooth (HASMCs) and endothelial cells (HAECs) is upregulated by AMP-activated protein kinase activators, including metformin, rosiglitazone and alpha-lipoic acid.	Metformin	152-161	PPARG coactivator 1 alpha	Homo sapiens	0-10
17454168-2	2007	The use of insulin-sensitizer compounds, such as metformin, permits great improvement of such metabolic abnormality, restoring ovarian function and gonadal steroid synthesis and reducing insulin resistance.	Metformin	49-58	insulin	Homo sapiens	187-194
17454168-6	2007	RESULTS: Plasma LH, estradiol, insulin and C-peptide were decreased significantly by metformin treatment in the entire group of PCOS patients.	Metformin	85-94	insulin	Homo sapiens	31-38
17454168-6	2007	RESULTS: Plasma LH, estradiol, insulin and C-peptide were decreased significantly by metformin treatment in the entire group of PCOS patients.	Metformin	85-94	insulin	Homo sapiens	43-52
19888409-0	2007	Impact of treatment with rosiglitazone or metformin on biomarkers for insulin resistance and metabolic syndrome in patients with polycystic ovary syndrome.	Metformin	42-51	insulin	Homo sapiens	70-77
17327307-7	2007	Insulin resistance was improved by metformin and worsened by the high-dose OCP.	Metformin	35-44	insulin	Homo sapiens	0-7
17327307-9	2007	CONCLUSIONS: In overweight women with PCOS, metformin and low- and high-dose OCP preparations have similar efficacy but differential effects on insulin resistance and arterial function.	Metformin	44-53	insulin	Homo sapiens	144-151
17293706-5	2007	We have reported elsewhere that metformin did not prevent olanzapine-induced weight gain, and the insulin resistance index significantly decreased after metformin and placebo; Baptista T, et al.	Metformin	153-162	insulin	Homo sapiens	98-105
17331860-9	2007	Metformin and rosiglitazone significantly decreased levels of triglyceride (TG), low-density lipoprotein (LDL), total cholesterol (total-C), HbA1c, insulin, and homeostasis model assessment (HOMA).	Metformin	0-9	insulin	Homo sapiens	148-155
19888409-7	2007	Adiponectin levels increased in both treatment arms (metformin: 8.6+/-3.3 to 16.7+/-7.2 mg/liter, p < 0.001; rosiglitazone: 8.2+/-3.5 to 26.2+/-9.5 mg/liter, p < 0.001), but the increase was more pronounced with rosiglitazone (p < 0.001).	Metformin	53-62	adiponectin, C1Q and collagen domain containing	Homo sapiens	0-11
17018841-6	2007	Metformin and 5-aminoimidazole-4-carboxamide-1beta-riboside (AICAR) increased AMPK phosphorylation, inhibited high-glucose stimulation of protein synthesis, and prevented high-glucose-induced changes in phosphorylation of 4E binding protein 1 and eukaryotic elongation factor 2.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	78-82
17362692-2	2007	The aim of this study was to evaluate the feasibility, acceptability, and efficacy of insulin with metformin for newly diagnosed, treatment-naive patients with T2DM.	Metformin	99-108	insulin	Homo sapiens	86-93
17018841-9	2007	In diabetic rats, metformin and AICAR increased renal AMPK phosphorylation, reversed mTOR activation, and inhibited renal hypertrophy, without affecting hyperglycemia.	Metformin	18-27	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	54-58
17489777-13	2007	Metformin therapy in PCOS women reduces CRP level, hyperinsulinaemia and cardiovascular risk.	Metformin	0-9	C-reactive protein	Homo sapiens	40-43
17489777-8	2007	Mean serum C-RP levels significantly decreased after metformin treatment ((6,37+/-1,72 vs. 1,67+/-0,73 mg/l; p<0,05).	Metformin	53-62	C-reactive protein	Homo sapiens	11-15
17259403-10	2007	We further hypothesize that the diabetes-preventive effect of metformin may interact with the impact of these variants on insulin regulation.	Metformin	62-71	insulin	Homo sapiens	122-129
17489777-9	2007	Level of insulin reduced for 37% after metformin treatment (234+/-68 vs. 148+/-39 pmol/l).	Metformin	39-48	insulin	Homo sapiens	9-16
17273659-0	2007	Are the beneficial cardiovascular effects of simvastatin and metformin also associated with a hormone-dependent mechanism improving insulin sensitivity?	Metformin	61-70	insulin	Homo sapiens	132-139
17273659-6	2007	Insulin resistance determined by the homeostasis model assessment decreased only with metformin.	Metformin	86-95	insulin	Homo sapiens	0-7
17454455-9	2007	Short-term treatment with metformin may be useful in women with insulin resistance.	Metformin	26-35	insulin	Homo sapiens	64-71
17258675-5	2007	Metformin (an insulin sensitizer) reduces hepatic glucose production.	Metformin	0-9	insulin	Homo sapiens	14-21
17229249-1	2007	BACKGROUND: Metformin is considered the gold standard for type 2 diabetes treatment as monotherapy and in combination with sulphonylureas and insulin, whereas the combination of metformin with thiazolidinediones is relatively less studied.	Metformin	12-21	insulin	Homo sapiens	142-149
17986832-7	2007	In the absence of a specific diagnosis and therapy, metformin is a useful insulin sensitizer and should be used in conjunction with aggressive diet and exercise interventions.	Metformin	52-61	insulin	Homo sapiens	74-81
17253562-14	2007	Metformin was more effective than the OCP in reducing fasting insulin (WMD -3.46, 95% CI -5.39 to -1.52) and not increasing triglyceride (WMD -0.48, 95% -0.86 to -0.09) levels, but there was insufficient evidence regarding comparative effects on reducing fasting glucose or cholesterol levels.	Metformin	0-9	insulin	Homo sapiens	62-69
17253562-15	2007	AUTHORS" CONCLUSIONS: Up to 12-months treatment with the OCP is associated with an improvement in menstrual pattern and serum androgen levels compared with metformin; but metformin treatment results in a reduction in fasting insulin and lower triglyceride levels than with the OCP.	Metformin	171-180	insulin	Homo sapiens	225-232
17610348-0	2007	Effects of simvastatin and metformin on inflammation and insulin resistance in individuals with mild metabolic syndrome.	Metformin	27-36	insulin	Homo sapiens	57-64
17610348-2	2007	OBJECTIVE: To study the effect of simvastatin and metformin on insulin sensitivity and inflammatory markers.	Metformin	50-59	insulin	Homo sapiens	63-70
17610348-5	2007	RESULTS: As expected, when compared with simvastatin, metformin therapy resulted in significant reductions in mean BMI, fasting plasma glucose, and homeostasis model assessment-insulin resistance (HOMA-IR), whereas simvastatin treatment resulted in significantly reduced total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and apolipoprotein B levels.	Metformin	54-63	insulin	Homo sapiens	177-184
17610348-5	2007	RESULTS: As expected, when compared with simvastatin, metformin therapy resulted in significant reductions in mean BMI, fasting plasma glucose, and homeostasis model assessment-insulin resistance (HOMA-IR), whereas simvastatin treatment resulted in significantly reduced total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and apolipoprotein B levels.	Metformin	54-63	apolipoprotein B	Homo sapiens	339-355
16968813-8	2007	Insulin secretion in response to arginine at maximally potentiating glucose levels (AIR(max)) tended to increase after metformin and to decrease after pioglitazone; however, when adjusted for S(I), the changes were not significant.	Metformin	119-128	insulin	Homo sapiens	0-7
17652778-4	2007	Demonstration that metformin, a common drug for Type 2 diabetes, requires LKB1 for full therapeutic benefit has increased interest in AMPK signaling.	Metformin	19-28	serine/threonine kinase 11	Mus musculus	74-78
16953257-13	2007	(3) After metformin and lifestyle intervention, clinical symptoms were ameliorated, serum adiponectin levels were actually increased and HOMA-IR was dropped in 20/30 MS children who had finished a 3-months follow-up (all P<0.01).	Metformin	10-19	adiponectin, C1Q and collagen domain containing	Homo sapiens	90-101
17199734-0	2007	The addition of metformin in type 1 diabetes improves insulin sensitivity, diabetic control, body composition and patient well-being.	Metformin	16-25	insulin	Homo sapiens	54-61
17199734-1	2007	AIM: As many overweight people with T1DM are insulin resistant, adjuvant therapy with insulin sensitising agents, such as metformin, may be beneficial.	Metformin	122-131	insulin	Homo sapiens	86-93
17199734-15	2007	CONCLUSION: Adjuvant metformin can improve QOL, insulin sensitivity and glycaemic control in overweight adults with T1DM.	Metformin	21-30	insulin	Homo sapiens	48-55
17426408-11	2007	Insulin sensitizers such as metformin are a new class of drugs utilized in treatment of PCOS.	Metformin	28-37	insulin	Homo sapiens	0-7
17426408-13	2007	Metformin also helps to increase SHBG, decrease androgen levels and induce ovulation.	Metformin	0-9	sex hormone binding globulin	Homo sapiens	33-37
17460368-0	2007	Comparison of the effects of pioglitazone and metformin on insulin resistance and hormonal markers in patients with impaired glucose tolerance and early diabetes.	Metformin	46-55	insulin	Homo sapiens	59-66
18613325-3	2007	Metformin lowers, rather than increases, fasting plasma insulin concentrations and acts by enhancing insulin sensitivity, inducing greater peripheral uptake of glucose, and decreasing hepatic glucose output.	Metformin	0-9	insulin	Homo sapiens	56-63
17111267-0	2007	Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and therapeutic effects of metformin.	Metformin	95-104	solute carrier family 22 member 1	Homo sapiens	34-38
17111267-2	2007	In this study we analyzed variants of OCT1 and OCT2 genes in 33 patients (24 responders and nine non-responders) based on the hypothesis that polymorphisms in both genes contribute to large inter-patient variability in the clinical efficacy of metformin.	Metformin	244-253	solute carrier family 22 member 1	Homo sapiens	38-42
17111267-5	2007	Age, body mass index (BMI) and treatment with lipid-lowering agents were demonstrated as positive predictors, and two mutations in the OCT1 gene, -43T > G in intron 1 and 408Met > Val (1222A > G) in exon 7, were negative and positive predictors, respectively, for the efficacy of metformin; the predictive accuracy was 55.5% (P < 0.05).	Metformin	289-298	solute carrier family 22 member 1	Homo sapiens	135-139
18613325-3	2007	Metformin lowers, rather than increases, fasting plasma insulin concentrations and acts by enhancing insulin sensitivity, inducing greater peripheral uptake of glucose, and decreasing hepatic glucose output.	Metformin	0-9	insulin	Homo sapiens	101-108
18200800-6	2007	The combination of nateglinide with insulin-sensitising agents, such as metformin and thiazolidinediones, targets both insulin deficiency and insulin resistance and results in reductions in HbA1c that could not be achieved by monotherapy with other antidiabetic agents.	Metformin	72-81	insulin	Homo sapiens	36-43
17208384-6	2007	We have previously shown that troglitazone and metformin exert opposing actions on adiponectin production, indicating that combined use of troglitazone and metformin is a more efficient strategy as compared to metformin treatment.	Metformin	47-56	adiponectin, C1Q and collagen domain containing	Homo sapiens	83-94
17208384-6	2007	We have previously shown that troglitazone and metformin exert opposing actions on adiponectin production, indicating that combined use of troglitazone and metformin is a more efficient strategy as compared to metformin treatment.	Metformin	156-165	adiponectin, C1Q and collagen domain containing	Homo sapiens	83-94
17208384-6	2007	We have previously shown that troglitazone and metformin exert opposing actions on adiponectin production, indicating that combined use of troglitazone and metformin is a more efficient strategy as compared to metformin treatment.	Metformin	156-165	adiponectin, C1Q and collagen domain containing	Homo sapiens	83-94
17208384-7	2007	Here, we will provide additional arguments which stress the need for a fixed dose of troglitazone and metformin in order to preserve endogenous adiponectin production.	Metformin	102-111	adiponectin, C1Q and collagen domain containing	Homo sapiens	144-155
18200815-3	2007	Of all the hypoglycemic agents in the pharmacological arsenal against diabetes, thiazolidinediones, in particular pioglitazone, as well as metformin appear to have additional effects in ameliorating oxidative stress and inflammation; rendering them attractive tools for prevention of insulin resistance and diabetes.	Metformin	139-148	insulin	Homo sapiens	284-291
17203528-10	2006	In the placebo-controlled trials, metformin improved insulin resistance markers and liver function tests, but not histological scores.	Metformin	34-43	insulin	Homo sapiens	53-60
17203528-11	2006	In the single-arm trials, metformin and thiazolidinediones improved insulin resistance markers and liver function tests, and beneficial histological changes were reported.	Metformin	26-35	insulin	Homo sapiens	68-75
17151157-12	2006	CONCLUSIONS: Metformin therapy is safe and effective in abrogating weight gain, decreased insulin sensitivity, and abnormal glucose metabolism resulting from treatment of children and adolescents with atypicals.	Metformin	13-22	insulin	Homo sapiens	90-97
16902066-2	2006	The purposes of the present study were 1) to confirm whether acute metformin administration induced AMPK phosphorylation and 2) to determine whether chronic metformin treatment increased the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) protein expression, glycolytic and oxidative enzyme activities, and cytochrome c and glucose transporter-4 (GLUT4) protein expressions in the rat soleus and red and white gastrocnemius muscles.	Metformin	157-166	PPARG coactivator 1 alpha	Rattus norvegicus	191-258
17121522-0	2006	Effects of pioglitazone and metformin on plasma adiponectin in newly detected type 2 diabetes mellitus.	Metformin	28-37	adiponectin, C1Q and collagen domain containing	Homo sapiens	48-59
17121522-1	2006	OBJECTIVE: This prospective study evaluates the effect of insulin sensitizers, pioglitazone (PGZ) and metformin (MET) on plasma adiponectin and leptin levels in subjects newly diagnosed with type 2 diabetes mellitus (T2DM).	Metformin	102-111	adiponectin, C1Q and collagen domain containing	Homo sapiens	128-139
17139582-8	2006	The best results of insulin treatment with regard to weight control are obtained with basal insulin combined with metformin rather than insulin alone, prandial insulin substitution or intensified insulin treatment.	Metformin	114-123	insulin	Homo sapiens	20-27
16902066-0	2006	Metformin increases the PGC-1alpha protein and oxidative enzyme activities possibly via AMPK phosphorylation in skeletal muscle in vivo.	Metformin	0-9	PPARG coactivator 1 alpha	Rattus norvegicus	24-34
16902066-0	2006	Metformin increases the PGC-1alpha protein and oxidative enzyme activities possibly via AMPK phosphorylation in skeletal muscle in vivo.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	88-92
16902066-1	2006	AMP-activated protein kinase (AMPK), which was activated by an antihyperglycemic drug metformin, has been hypothesized to mediate metabolic adaptations.	Metformin	86-95	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	0-28
16902066-1	2006	AMP-activated protein kinase (AMPK), which was activated by an antihyperglycemic drug metformin, has been hypothesized to mediate metabolic adaptations.	Metformin	86-95	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	30-34
16902066-2	2006	The purposes of the present study were 1) to confirm whether acute metformin administration induced AMPK phosphorylation and 2) to determine whether chronic metformin treatment increased the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) protein expression, glycolytic and oxidative enzyme activities, and cytochrome c and glucose transporter-4 (GLUT4) protein expressions in the rat soleus and red and white gastrocnemius muscles.	Metformin	157-166	PPARG coactivator 1 alpha	Rattus norvegicus	260-270
16902066-2	2006	The purposes of the present study were 1) to confirm whether acute metformin administration induced AMPK phosphorylation and 2) to determine whether chronic metformin treatment increased the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) protein expression, glycolytic and oxidative enzyme activities, and cytochrome c and glucose transporter-4 (GLUT4) protein expressions in the rat soleus and red and white gastrocnemius muscles.	Metformin	67-76	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	100-104
16902066-3	2006	The single oral administration of metformin (300 mg/kg body wt) enhanced the AMPK phosphorylation at 5 and/or 6 h after treatment.	Metformin	34-43	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	77-81
16902066-6	2006	Metformin increased the PGC-1alpha content in all three muscles.	Metformin	0-9	PPARG coactivator 1 alpha	Rattus norvegicus	24-34
16902066-10	2006	These results suggest that metformin enhances the PGC-1alpha expression and mitochondrial biogenesis possibly at least in part via AMPK phosphorylation in the skeletal muscle.	Metformin	27-36	PPARG coactivator 1 alpha	Rattus norvegicus	50-60
16902066-10	2006	These results suggest that metformin enhances the PGC-1alpha expression and mitochondrial biogenesis possibly at least in part via AMPK phosphorylation in the skeletal muscle.	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	131-135
17140168-0	2006	Metformin and antihypertensive therapy with drugs blocking the renin angiotensin system, a cause of concern?	Metformin	0-9	renin	Homo sapiens	63-68
17140168-12	2006	CONCLUSION: We believe that the incidence of metformin-associated lactic acidosis in Norway may become more frequent due to increased use of metformin and drugs blocking the renin angiotensin system.	Metformin	45-54	renin	Homo sapiens	174-179
17145645-5	2006	The insulin-sensitizing agents available commercially include metformin, rosiglitazone and pioglitazone.	Metformin	62-71	insulin	Homo sapiens	4-11
17026491-10	2006	Under additional metformin therapy, the increment of insulin requirement of all patients (n = 40) was significantly lower (11 vs. 26%, p < 0.01), and there was no significant difference between the groups with different BMIs.	Metformin	17-26	insulin	Homo sapiens	53-60
17026491-13	2006	Additional metformin therapy reduces insulin requirement in patients with and without overweight.	Metformin	11-20	insulin	Homo sapiens	37-44
17087306-4	2006	The agents that improve insulin resistance, such as metformin and pioglitazone, have multiple effects to improve glucose and lipid metabolism by increasing sensitivity for insulin without increasing insulin secretion and exert anti-atherogenic properties resulting in preventing development of atherosclerosis.	Metformin	52-61	insulin	Homo sapiens	24-31
17062894-10	2006	Metformin treatment significantly improved hyperandrogenism, menstrual cyclicity, body weight, and insulin resistance independent of GNAS1 genotype.	Metformin	0-9	insulin	Homo sapiens	99-106
17087306-4	2006	The agents that improve insulin resistance, such as metformin and pioglitazone, have multiple effects to improve glucose and lipid metabolism by increasing sensitivity for insulin without increasing insulin secretion and exert anti-atherogenic properties resulting in preventing development of atherosclerosis.	Metformin	52-61	insulin	Homo sapiens	172-179
19610566-1	2006	50 years old female patient, with history of diabetes mellitus and hypertension, receiving metformin (500 mg BID) and atenolol (50 mg BID), presented to the Emergency Room with asthenia and dizziness.	Metformin	91-100	BH3 interacting domain death agonist	Homo sapiens	109-112
16940989-1	2006	BACKGROUND AND PURPOSE: The types of hepatic microsomal cytochrome P450 (CYP) isozymes responsible for the metabolism of metformin in humans and rats have not been published to date.	Metformin	121-130	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	56-71
16940989-1	2006	BACKGROUND AND PURPOSE: The types of hepatic microsomal cytochrome P450 (CYP) isozymes responsible for the metabolism of metformin in humans and rats have not been published to date.	Metformin	121-130	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	73-76
16978371-8	2006	Compared with baseline (60 +/- 14 units), total daily insulin dose was significantly lower following the addition of metformin (50 +/- 13 units; P < 0.05) and this final total daily insulin dose in the metformin group was lower compared with placebo (58 +/- 12 units, P < 0.05).	Metformin	117-126	insulin	Homo sapiens	54-61
16978371-8	2006	Compared with baseline (60 +/- 14 units), total daily insulin dose was significantly lower following the addition of metformin (50 +/- 13 units; P < 0.05) and this final total daily insulin dose in the metformin group was lower compared with placebo (58 +/- 12 units, P < 0.05).	Metformin	205-214	insulin	Homo sapiens	54-61
16978371-8	2006	Compared with baseline (60 +/- 14 units), total daily insulin dose was significantly lower following the addition of metformin (50 +/- 13 units; P < 0.05) and this final total daily insulin dose in the metformin group was lower compared with placebo (58 +/- 12 units, P < 0.05).	Metformin	205-214	insulin	Homo sapiens	185-192
16978371-10	2006	CONCLUSION: Metformin can effectively improve glycaemic control and reduce the total daily insulin dose in overweight people with Type 1 diabetes.	Metformin	12-21	insulin	Homo sapiens	91-98
16957566-6	2006	Addition of rosiglitazone to metformin also reduced levels of plasminogen activator inhibitor-1 antigen and activity, C-reactive protein, von Willebrand factor and fibrinogen compared with addition of glyburide.	Metformin	29-38	C-reactive protein	Homo sapiens	118-159
17039655-3	2006	Metformin and rosiglitazone are 2 pharmacologic agents useful in conditions characterized by insulin resistance.	Metformin	0-9	insulin	Homo sapiens	93-100
17077202-10	2006	The limited effectiveness of metformin in older persons may reflect age-related differences in insulin action and secretion.	Metformin	29-38	insulin	Homo sapiens	95-102
17172088-0	2006	Some effect of metformin on insulin resistance in an infant with leprechaunism.	Metformin	15-24	insulin	Homo sapiens	28-35
16760380-6	2006	Metformin treatment (10 mM, 24 h) also reduced cell proliferation and the levels of CCND2 and CCNE proteins without affecting cell viability, both in the basal state and in response to FSH.	Metformin	0-9	cyclin E1	Rattus norvegicus	94-98
16949486-5	2006	RESULTS: In comparison with placebo (n = 17), metformin recipients (n = 16) showed significant reductions in weight and in homeostatic model assessment for insulin resistance (p < 0.05, intention to treat).	Metformin	46-55	insulin	Homo sapiens	156-163
17214387-3	2006	Metformin, an insulin-sensitizing agent, has been proven to be of clinical usefulness both in the short-term aiding of infertility treatments and, potentially, in the prevention of the long-term sequelae for patients with PCOS.	Metformin	0-9	insulin	Homo sapiens	14-21
16918591-0	2006	Insulin sensitivity during oral glucose tolerance test and its relations to parameters of glucose metabolism and endothelial function in type 2 diabetic subjects under metformin and thiazolidinedione.	Metformin	168-177	insulin	Homo sapiens	0-7
16868748-0	2006	Metformin influences cardiomyocyte cell death by pathways that are dependent and independent of caspase-3.	Metformin	0-9	caspase 3	Homo sapiens	96-105
16868748-2	2006	We hypothesised that metformin could prevent both caspase-3 activation and apoptosis when induced by palmitic acid.	Metformin	21-30	caspase 3	Homo sapiens	50-59
16868748-8	2006	This beneficial effect of metformin was associated with increased AMPK phosphorylation, palmitic acid oxidation and suppression of high-fat-induced increases in (1) long chain base biosynthesis protein 1 levels, (2) ceramide levels, and (3) caspase-3 activity.	Metformin	26-35	caspase 3	Homo sapiens	241-250
16918591-1	2006	AIM: This study was designed to assess the usefulness of a model-based index of insulin sensitivity during an oral glucose tolerance test (OGTT) in the identification of possible changes in this metabolic parameter produced by pharmacological agents known to be potent insulin sensitizers, that is metformin (M) and thiazolidinedione (T).	Metformin	298-307	insulin	Homo sapiens	80-87
16941277-10	2006	In conclusion, it was found that in these participants metformin acts in insulin resistance; it increases glucose muscle uptake and blood flow.	Metformin	55-64	insulin	Homo sapiens	73-80
17185789-8	2006	Insulin-sensitizing drugs such as metformin may also have a place in treatment of PCOS.	Metformin	34-43	insulin	Homo sapiens	0-7
16901933-1	2006	In patients with type 2 non-insulin-dependent diabetes mellitus (NIDDM), the biguanide, metformin, exerts its antihyperglycemic effect by improving insulin sensitivity, which is associated with decreased level of circulating free fatty acids (FFA).	Metformin	88-97	insulin	Homo sapiens	28-35
16901933-0	2006	Metformin reduces lipolysis in primary rat adipocytes stimulated by tumor necrosis factor-alpha or isoproterenol.	Metformin	0-9	tumor necrosis factor	Rattus norvegicus	68-95
16901933-6	2006	Treatment with metformin attenuated TNF-alpha-mediated lipolysis by suppressing phosphorylation of extracellular signal-related kinase 1/2 and reversing the downregulation of perilipin protein in TNF-alpha-stimulated adipocytes.	Metformin	15-24	tumor necrosis factor	Rattus norvegicus	36-45
16901933-6	2006	Treatment with metformin attenuated TNF-alpha-mediated lipolysis by suppressing phosphorylation of extracellular signal-related kinase 1/2 and reversing the downregulation of perilipin protein in TNF-alpha-stimulated adipocytes.	Metformin	15-24	tumor necrosis factor	Rattus norvegicus	196-205
16901933-9	2006	Metformin not only inhibits the basal lipolysis simulated by high glucose, but also suppresses the high glucose-enhanced lipolysis response to TNF-alpha or isoproterenol.	Metformin	0-9	tumor necrosis factor	Rattus norvegicus	143-152
16901933-10	2006	The antilipolytic action in adipocytes could be the mechanism by which cellular action by metformin reduces systemic FFA concentration and thus improves insulin sensitivity in obese patients and the hyperglycemic conditions of NIDDM.	Metformin	90-99	insulin	Homo sapiens	153-160
16850272-7	2006	MATE1 transported not only organic cations such as cimetidine and metformin but also the zwitterionic compound cephalexin.	Metformin	66-75	solute carrier family 47 member 1	Rattus norvegicus	0-5
16827766-9	2006	The metformin group had significantly lower total cholesterol (P= 0.02), low-density lipoprotein cholesterol (P= 0.02) and cholesterol:high-density lipoprotein cholesterol ratio (P= 0.05), but there was no statistically significant treatment effect on androgens, insulin, insulin resistance, triglycerides, ovulation or pregnancy.	Metformin	4-13	insulin	Homo sapiens	263-270
16839832-2	2006	This study was designed to investigate the effect of adiponectin on carotid arterial stiffness in type 2 diabetic patients treated with pioglitazone and metformin.	Metformin	153-162	adiponectin, C1Q and collagen domain containing	Homo sapiens	53-64
16839832-6	2006	The changes in stiffness parameter beta were significantly and inversely correlated with change in plasma adiponectin level after treatment with pioglitazone or metformin in the group of all subjects (r = -0.472, P = .036).	Metformin	161-170	adiponectin, C1Q and collagen domain containing	Homo sapiens	106-117
16839832-7	2006	In conclusion, the present study is the first to demonstrate that increase in adiponectin level after treatment with the insulin sensitizers pioglitazone and metformin may improve arterial stiffness in patients with type 2 diabetes mellitus.	Metformin	158-167	adiponectin, C1Q and collagen domain containing	Homo sapiens	78-89
16478780-0	2006	Metformin counters the insulin-induced suppression of fatty acid oxidation and stimulation of triacylglycerol storage in rodent skeletal muscle.	Metformin	0-9	insulin	Homo sapiens	23-30
16478780-3	2006	Metformin did not alter basal FA metabolism but countered the effects of insulin on FA oxidation and incorporation into triacylglyerol (TAG).	Metformin	0-9	insulin	Homo sapiens	73-80
16478780-4	2006	Specifically, metformin prevented the insulin-induced suppression of FA oxidation in SOL but did not alter FA incorporation into lipid pools.	Metformin	14-23	insulin	Homo sapiens	38-45
16478780-6	2006	In SOL, metformin resulted in a 50% increase in AMP-activated protein kinase alpha2 activity and prevented the insulin-induced increase in malonyl-CoA content.	Metformin	8-17	insulin	Homo sapiens	111-118
16478780-9	2006	Because increased muscle lipid storage and impaired FA oxidation have been associated with insulin resistance in this tissue, the ability of metformin to reverse these abnormalities in muscle FA metabolism may be a part of the mechanism by which metformin improves glucose clearance and insulin sensitivity.	Metformin	141-150	insulin	Homo sapiens	91-98
16478780-9	2006	Because increased muscle lipid storage and impaired FA oxidation have been associated with insulin resistance in this tissue, the ability of metformin to reverse these abnormalities in muscle FA metabolism may be a part of the mechanism by which metformin improves glucose clearance and insulin sensitivity.	Metformin	141-150	insulin	Homo sapiens	287-294
16478780-9	2006	Because increased muscle lipid storage and impaired FA oxidation have been associated with insulin resistance in this tissue, the ability of metformin to reverse these abnormalities in muscle FA metabolism may be a part of the mechanism by which metformin improves glucose clearance and insulin sensitivity.	Metformin	246-255	insulin	Homo sapiens	287-294
16827766-9	2006	The metformin group had significantly lower total cholesterol (P= 0.02), low-density lipoprotein cholesterol (P= 0.02) and cholesterol:high-density lipoprotein cholesterol ratio (P= 0.05), but there was no statistically significant treatment effect on androgens, insulin, insulin resistance, triglycerides, ovulation or pregnancy.	Metformin	4-13	insulin	Homo sapiens	272-279
16776753-6	2006	On the contrary, in the per protocol (PP) population, moxonidine statistically significantly (p = 0.025) decreased the AUC for insulin from baseline in the PP population; for metformin, the treatment effect on insulin was a small, net increase resulting in a statistically significant between-group difference of 16.2% (95% CI = 0.1-35.0).	Metformin	175-184	insulin	Homo sapiens	210-217
16817823-0	2006	Metformin therapy improves coronary microvascular function in patients with polycystic ovary syndrome and insulin resistance.	Metformin	0-9	insulin	Homo sapiens	106-113
16817823-2	2006	Metformin therapy reduces whole-body insulin resistance (IR) in patients with type-2 diabetes mellitus (DM).	Metformin	0-9	insulin	Homo sapiens	37-44
16817823-3	2006	OBJECTIVE: As insulin resistance accompanying PCOS may be reversed by metformin therapy, we hypothesized that metformin therapy might improve coronary microvascular functions in women with PCOS and IR.	Metformin	110-119	insulin	Homo sapiens	14-21
16822926-2	2006	BACKGROUND: Adult patients with type 2 diabetes controlled with insulin frequently require the addition of insulin sensitising drugs such as metformin and sometimes glitazones to achieve optimum glycaemic control.	Metformin	141-150	insulin	Homo sapiens	64-71
16950750-2	2006	This theoretical background is now supported by substantial evidence for treating women with PCOS with insulin sensitising agents such as metformin or the thiazolidinediones.	Metformin	138-147	insulin	Homo sapiens	103-110
16916482-1	2006	OBJECTIVE: To determine whether women with polycystic ovary syndrome (PCOS) and abnormal insulin levels treated with metformin had different rates of ovulation and pregnancy from women with PCOS and normal insulin levels.	Metformin	117-126	insulin	Homo sapiens	89-96
16916482-6	2006	After treatment with metformin, cumulative rates of ovulation were similar in women with elevated fasting serum insulin levels (48.8%) and those with normal levels (44.7%).	Metformin	21-30	insulin	Homo sapiens	112-119
16822926-2	2006	BACKGROUND: Adult patients with type 2 diabetes controlled with insulin frequently require the addition of insulin sensitising drugs such as metformin and sometimes glitazones to achieve optimum glycaemic control.	Metformin	141-150	insulin	Homo sapiens	107-114
16406190-7	2006	The daily insulin dose (units), total and per kg/BW was significantly lower [p < 0.001] with metformin (51 +/- 5, 0.51 +/- 0.10), glimepiride (40 +/- 4, 0.42 +/- 0.09) as well as with both drugs (23 +/- 7, 0.21 +/- 0.07) in comparison to placebo (82 +/- 10, 0.82 +/- 0.12).	Metformin	96-105	insulin	Homo sapiens	10-17
16766204-2	2006	It mediates some of the effects of peripheral hormones such as leptin, ghrelin and adiponectin, and it is involved in the insulin-sensitizing role of the antidiabetic drug metformin.	Metformin	172-181	adiponectin, C1Q and collagen domain containing	Homo sapiens	83-94
16513829-5	2006	Metformin-induced stimulation of transport was not inhibited by treatment with wortmannin and was additive with that of insulin.	Metformin	0-9	insulin	Homo sapiens	120-127
16513829-6	2006	These data suggest that the metformin effect is mediated by a signaling route independent of phosphatidylinositol 3-kinase and Akt.	Metformin	28-37	AKT serine/threonine kinase 1	Homo sapiens	127-130
16513829-7	2006	Surprisingly, however, levels of both phospho-AMP-activated protein kinase and phospho-Akt were increased 4- and 3-fold, respectively, after metformin treatment.	Metformin	141-150	AKT serine/threonine kinase 1	Homo sapiens	87-90
16513829-9	2006	Cotreatment with metformin bypassed this insulin resistance by maintaining high transport levels.	Metformin	17-26	insulin	Homo sapiens	41-48
16513829-14	2006	This accounts for metformin"s ability to enhance hexose transport activity above insulin-stimulated and Akt-dependent levels.	Metformin	18-27	insulin	Homo sapiens	81-88
16513829-14	2006	This accounts for metformin"s ability to enhance hexose transport activity above insulin-stimulated and Akt-dependent levels.	Metformin	18-27	AKT serine/threonine kinase 1	Homo sapiens	104-107
16406190-10	2006	CONCLUSION: Glimepiride and metformin are effective individually in achieving a glycemic goal with a less daily insulin dose, weight gain, and hypoglycemic episodes in comparison to insulin monotherapy in subjects with type 2 diabetes mellitus with further marked reduction in these parameters when used concurrently.	Metformin	28-37	insulin	Homo sapiens	112-119
16492692-9	2006	Metformin was also associated with lower insulin resistance and leptin and IGF-I levels and higher SHBG and IGF-binding protein-1 levels and with a more favorable lipid profile.	Metformin	0-9	insulin	Homo sapiens	41-48
16636195-5	2006	Metformin also dose-dependently inhibited tumor necrosis factor (TNF)-alpha-induced NF-kappaB activation and TNF-alpha-induced IkappaB kinase activity.	Metformin	0-9	tumor necrosis factor	Homo sapiens	42-75
16636195-5	2006	Metformin also dose-dependently inhibited tumor necrosis factor (TNF)-alpha-induced NF-kappaB activation and TNF-alpha-induced IkappaB kinase activity.	Metformin	0-9	tumor necrosis factor	Homo sapiens	109-118
16636195-6	2006	Furthermore, metformin attenuated the TNF-alpha-induced gene expression of various proinflammatory and cell adhesion molecules, such as vascular cell adhesion molecule-1, E-selectin, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1, in HUVECs.	Metformin	13-22	tumor necrosis factor	Homo sapiens	38-47
16636195-6	2006	Furthermore, metformin attenuated the TNF-alpha-induced gene expression of various proinflammatory and cell adhesion molecules, such as vascular cell adhesion molecule-1, E-selectin, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1, in HUVECs.	Metformin	13-22	vascular cell adhesion molecule 1	Homo sapiens	136-169
16636195-9	2006	The small interfering RNA for AMPKalpha1 attenuated metformin or AICAR-induced inhibition of NF-kappaB activation by TNF-alpha, suggesting a possible role of AMPK in the regulation of cell inflammation.	Metformin	52-61	tumor necrosis factor	Homo sapiens	117-126
16595599-0	2006	Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: improvement in body composition and fasting insulin.	Metformin	32-41	insulin	Homo sapiens	150-157
16492692-9	2006	Metformin was also associated with lower insulin resistance and leptin and IGF-I levels and higher SHBG and IGF-binding protein-1 levels and with a more favorable lipid profile.	Metformin	0-9	insulin like growth factor 1	Homo sapiens	75-80
16492692-9	2006	Metformin was also associated with lower insulin resistance and leptin and IGF-I levels and higher SHBG and IGF-binding protein-1 levels and with a more favorable lipid profile.	Metformin	0-9	sex hormone binding globulin	Homo sapiens	99-103
16764619-10	2006	RESULTS: Serum androgens and insulin response to OGTT decreased significantly after metformin therapy.	Metformin	84-93	insulin	Homo sapiens	29-36
16764619-13	2006	CONCLUSIONS: Metformin improves insulin resistance, reduces androgen levels and significantly increases the ovulation and pregnancy rates in infertile women, following LOD.	Metformin	13-22	insulin	Homo sapiens	32-39
16792841-9	2006	In conclusion, administration of metformin allowed the identification of two subsets of PCOS women in whom neuroendocrine abnormalities may improve independently of the presence of insulin resistance or hyperinsulinaemia.	Metformin	33-42	insulin	Homo sapiens	181-188
16595599-9	2006	Metformin had a greater treatment effect over placebo for weight (-4.35 kg, P = 0.02), body mass index (-1.26 kg/m(2), P = 0.002), waist circumference (-2.8 cm, P = 0.003), sc abdominal adipose tissue (-52.5 cm(2), P = 0.002), and fasting insulin (-2.2 mU/liter, P = 0.011).	Metformin	0-9	insulin	Homo sapiens	239-246
16595599-11	2006	CONCLUSIONS: Metformin therapy for obese insulin-resistant pediatric patients results in significant improvement in body composition and fasting insulin.	Metformin	13-22	insulin	Homo sapiens	41-48
16886591-5	2006	CONCLUSIONS: In adolescents with PCOS, metformin-diet reduces weight, insulin, IR, cholesterol, and triglycerides, and facilitates resumption of regular menses.	Metformin	39-48	insulin	Homo sapiens	70-77
16768125-0	2006	[Insulin sensitizer--anti-diabetic drugs, metformin and pioglitazone that can improve insulin resistance].	Metformin	42-51	insulin	Homo sapiens	1-8
16768125-0	2006	[Insulin sensitizer--anti-diabetic drugs, metformin and pioglitazone that can improve insulin resistance].	Metformin	42-51	insulin	Homo sapiens	86-93
16768125-5	2006	The insulin-sensitizing drugs, which were biguanides (metformin) and thiazolidinediones (pioglitazone) have been shown to correct not only insulin resistance but also steatosis and inflammation in the liver.	Metformin	54-63	insulin	Homo sapiens	4-11
16768125-5	2006	The insulin-sensitizing drugs, which were biguanides (metformin) and thiazolidinediones (pioglitazone) have been shown to correct not only insulin resistance but also steatosis and inflammation in the liver.	Metformin	54-63	insulin	Homo sapiens	139-146
16792841-2	2006	The present study applied frequent blood sampling to assess the response of LH to metformin treatment in insulin-resistant women with PCOS.	Metformin	82-91	insulin	Homo sapiens	105-112
16796890-17	2006	(3) The serum TNF-alpha levels of the rosiglitazone and metformin treatment groups were 124.6 pg/mL +/- 21.0 pg/mL, 154.9 pg/mL +/- 32.5 pg/mL respectively, both significantly lower than that of the NAFLD group (324.2 pg/mL +/- 34.2 pg/mL, P < 0.001 and P < 0.05).	Metformin	56-65	tumor necrosis factor	Rattus norvegicus	14-23
16796890-18	2006	The liver TNF-alpha levels of the rosiglitazone and metformin treatment groups were 0.24 +/- 0.14 and 0.30 +/- 0.12 respectively, both significantly lower than that of the NAFLD group (0.85 +/- 0.12, both P < 0.001).	Metformin	52-61	tumor necrosis factor	Rattus norvegicus	10-19
16647382-9	2006	CONCLUSION(S): Metformin has shown to be effective in an insulin-resistant PCOS woman with RM.	Metformin	15-24	insulin	Homo sapiens	57-64
16879115-7	2006	Three months later, the group treated with insulin and metformin showed improvement in the monitored parameters, namely significant reduction in HbA1c (p = 0.003), MFBG (p = 0.0009), PPG (p = 0.028).	Metformin	55-64	serglycin	Homo sapiens	183-186
16407452-3	2006	Recent studies indicate that a low-dose combination of flutamide (Flu; a generic androgen-receptor blocker) and metformin (Met; a generic insulin-sensitizer) normalizes the adolescent PCOS spectrum more than an oral contraceptive (OC); in young women, the PCOS spectrum was found to be more normalized by OC plus Flu-Met than by OC alone.	Metformin	112-121	insulin	Homo sapiens	138-145
16564524-6	2006	Metformin induced activation and redistribution of phosphorylated extracellular signal-regulated kinase (P-ERK) in a transient manner, and dose-dependently stimulated the expression of endothelial and inducible nitric oxide synthases (e/iNOS).	Metformin	0-9	nitric oxide synthase 2	Homo sapiens	237-241
16700860-6	2006	Metformin (NNT = 14), acarbose (NNT = 11) and troglitazone (NNT = 6) have been shown to prevent/delay T2DM and angiotensin-converting enzyme (ACE) inhibitors and statins appear to have an adjunctive role (NNT = 42 and 112, respectively).	Metformin	0-9	angiotensin I converting enzyme	Homo sapiens	111-140
16700860-6	2006	Metformin (NNT = 14), acarbose (NNT = 11) and troglitazone (NNT = 6) have been shown to prevent/delay T2DM and angiotensin-converting enzyme (ACE) inhibitors and statins appear to have an adjunctive role (NNT = 42 and 112, respectively).	Metformin	0-9	angiotensin I converting enzyme	Homo sapiens	142-145
16516166-7	2006	Moreover, AICAR and metformin inhibited the ability of insulin and IGF-1 to induce HIF-1alpha expression.	Metformin	20-29	insulin	Homo sapiens	55-62
16516166-7	2006	Moreover, AICAR and metformin inhibited the ability of insulin and IGF-1 to induce HIF-1alpha expression.	Metformin	20-29	insulin like growth factor 1	Homo sapiens	67-72
16516166-7	2006	Moreover, AICAR and metformin inhibited the ability of insulin and IGF-1 to induce HIF-1alpha expression.	Metformin	20-29	hypoxia inducible factor 1 subunit alpha	Homo sapiens	83-93
16564524-7	2006	These results show for the first time a direct osteogenic effect of metformin on osteoblasts in culture, which could be mediated by activation/redistribution of ERK-1/2 and induction of e/iNOS.	Metformin	68-77	mitogen-activated protein kinase 3	Homo sapiens	161-168
16564524-7	2006	These results show for the first time a direct osteogenic effect of metformin on osteoblasts in culture, which could be mediated by activation/redistribution of ERK-1/2 and induction of e/iNOS.	Metformin	68-77	nitric oxide synthase 2	Homo sapiens	188-192
16567505-0	2006	5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside and metformin inhibit hepatic glucose phosphorylation by an AMP-activated protein kinase-independent effect on glucokinase translocation.	Metformin	59-68	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	115-143
16767294-6	2006	Recently, oral contraceptives are being substituted for insulin sensitizing agents (metformin and glitazones) in the PCOS treatment, due to their effects on insulin resistance and cardiovascular risk.	Metformin	84-93	insulin	Homo sapiens	56-63
16767294-6	2006	Recently, oral contraceptives are being substituted for insulin sensitizing agents (metformin and glitazones) in the PCOS treatment, due to their effects on insulin resistance and cardiovascular risk.	Metformin	84-93	insulin	Homo sapiens	157-164
16567505-3	2006	We report here that 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), metformin, and oligomycin activated AMPK and inhibited glucose phosphorylation and glycolysis in rat hepatocytes.	Metformin	84-93	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	120-124
16488580-8	2006	On the other hand, as in the case of metformin taken up by organic cation transporter 1, drug distribution to the tissue(s) may enhance its toxicity.	Metformin	37-46	solute carrier family 22 member 1	Homo sapiens	59-87
16385087-4	2006	METHODS AND RESULTS: Metformin dose-dependently inhibited IL-1beta-induced release of the pro-inflammatory cytokines IL-6 and IL-8 in ECs, SMCs, and Mphis.	Metformin	21-30	interleukin 1 beta	Homo sapiens	58-66
16385087-4	2006	METHODS AND RESULTS: Metformin dose-dependently inhibited IL-1beta-induced release of the pro-inflammatory cytokines IL-6 and IL-8 in ECs, SMCs, and Mphis.	Metformin	21-30	interleukin 6	Homo sapiens	117-121
16520442-9	2006	Measures of insulin sensitivity, including insulin area under the curve and HOMA (homeostasis model assessment), demonstrated improvement only with metformin, but these did not reach statistical significance.	Metformin	148-157	insulin	Homo sapiens	12-19
16385087-4	2006	METHODS AND RESULTS: Metformin dose-dependently inhibited IL-1beta-induced release of the pro-inflammatory cytokines IL-6 and IL-8 in ECs, SMCs, and Mphis.	Metformin	21-30	C-X-C motif chemokine ligand 8	Homo sapiens	126-130
16520442-9	2006	Measures of insulin sensitivity, including insulin area under the curve and HOMA (homeostasis model assessment), demonstrated improvement only with metformin, but these did not reach statistical significance.	Metformin	148-157	insulin	Homo sapiens	43-50
16385087-5	2006	Investigation of potential signaling pathways demonstrated that metformin diminished IL-1beta-induced activation and nuclear translocation of nuclear factor-kappa B (NF-kappaB) in SMCs.	Metformin	64-73	interleukin 1 beta	Homo sapiens	85-93
16385087-5	2006	Investigation of potential signaling pathways demonstrated that metformin diminished IL-1beta-induced activation and nuclear translocation of nuclear factor-kappa B (NF-kappaB) in SMCs.	Metformin	64-73	nuclear factor kappa B subunit 1	Homo sapiens	142-164
16385087-5	2006	Investigation of potential signaling pathways demonstrated that metformin diminished IL-1beta-induced activation and nuclear translocation of nuclear factor-kappa B (NF-kappaB) in SMCs.	Metformin	64-73	nuclear factor kappa B subunit 1	Homo sapiens	166-175
16385087-6	2006	Furthermore, metformin suppressed IL-1beta-induced activation of the pro-inflammatory phosphokinases Akt, p38, and Erk, but did not affect PI3 kinase (PI3K) activity.	Metformin	13-22	interleukin 1 beta	Homo sapiens	34-42
16385087-6	2006	Furthermore, metformin suppressed IL-1beta-induced activation of the pro-inflammatory phosphokinases Akt, p38, and Erk, but did not affect PI3 kinase (PI3K) activity.	Metformin	13-22	AKT serine/threonine kinase 1	Homo sapiens	101-104
16385087-6	2006	Furthermore, metformin suppressed IL-1beta-induced activation of the pro-inflammatory phosphokinases Akt, p38, and Erk, but did not affect PI3 kinase (PI3K) activity.	Metformin	13-22	mitogen-activated protein kinase 14	Homo sapiens	106-109
16385087-6	2006	Furthermore, metformin suppressed IL-1beta-induced activation of the pro-inflammatory phosphokinases Akt, p38, and Erk, but did not affect PI3 kinase (PI3K) activity.	Metformin	13-22	mitogen-activated protein kinase 1	Homo sapiens	115-118
16385087-8	2006	Pretreatment with metformin also decreased phosphorylation of Akt and protein kinase C (PKC) in ECs under these conditions.	Metformin	18-27	AKT serine/threonine kinase 1	Homo sapiens	62-65
16385087-9	2006	CONCLUSIONS: These data suggest that metformin can exert a direct vascular anti-inflammatory effect by inhibiting NF-kappaB through blockade of the PI3K-Akt pathway.	Metformin	37-46	nuclear factor kappa B subunit 1	Homo sapiens	114-123
16385087-9	2006	CONCLUSIONS: These data suggest that metformin can exert a direct vascular anti-inflammatory effect by inhibiting NF-kappaB through blockade of the PI3K-Akt pathway.	Metformin	37-46	AKT serine/threonine kinase 1	Homo sapiens	153-156
16492202-4	2006	Although evidence is accumulating that metformin is useful and has a role in polycystic ovary syndrome, a condition of insulin resistance, it is not yet accepted as treatment for Type 2 diabetes in pregnancy and gestational diabetes.	Metformin	39-48	insulin	Homo sapiens	119-126
16477438-7	2006	RESULTS: Both TZDs and metformin enhance insulin suppression of endogenous glucose production and fasting plasma glucose clearance.	Metformin	23-32	insulin	Homo sapiens	41-48
16492202-6	2006	Metformin may become an important treatment for women with either gestational or Type 2 diabetes in pregnancy and indeed may have additional important benefits for women, including reducing insulin resistance, body weight and long-term risk of diabetes.	Metformin	0-9	insulin	Homo sapiens	190-197
16322356-8	2006	Increases in biomarkers of inflammation (e.g., interleukin 6, interferon gamma, and neutrophil number) were also blunted by metformin treatment.	Metformin	124-133	interleukin 6	Rattus norvegicus	47-60
16352680-2	2006	No data of the exact point and the impact of insulin resistance (IR) on metformin"s efficacy exist.	Metformin	72-81	insulin	Homo sapiens	45-52
16352680-12	2006	Insulin sensitivity improved within 4 wk after beginning of metformin as shown by an increased area under the curve glucose to insulin ratio, compared with baseline (P < 0.005).	Metformin	60-69	insulin	Homo sapiens	0-7
16352680-12	2006	Insulin sensitivity improved within 4 wk after beginning of metformin as shown by an increased area under the curve glucose to insulin ratio, compared with baseline (P < 0.005).	Metformin	60-69	insulin	Homo sapiens	127-134
16514202-9	2006	Finally, when DHEA was administered alone it increased the serum tumor necrosis factor-alpha (TNF-alpha ) levels when compared with controls; however, when metformin was administered together with DHEA, serum TNF-alpha levels were similar to controls.	Metformin	156-165	tumor necrosis factor	Mus musculus	209-218
16395615-0	2006	Metformin improves atypical protein kinase C activation by insulin and phosphatidylinositol-3,4,5-(PO4)3 in muscle of diabetic subjects.	Metformin	0-9	insulin	Homo sapiens	59-66
16246375-7	2006	Troglitazone had a better antihyperglycemic potency than metformin when insulin was added.	Metformin	57-66	insulin	Homo sapiens	72-79
16522281-3	2006	Weight loss, metformin, and thiazolidinediones ameliorate insulin resistance and decrease concentrations of PAI-1.	Metformin	13-22	insulin	Homo sapiens	58-65
16395615-8	2006	Metformin therapy for 8 to 12 months improved insulin-stimulated, as well as basal aPKC activity in muscle.	Metformin	0-9	insulin	Homo sapiens	46-53
16395615-4	2006	Nevertheless, the effects of metformin on insulin-sensitive signalling factors in human muscle have only been partly characterised to date.	Metformin	29-38	insulin	Homo sapiens	42-49
16443786-0	2006	Activation of the AMP-activated kinase by antidiabetes drug metformin stimulates nitric oxide synthesis in vivo by promoting the association of heat shock protein 90 and endothelial nitric oxide synthase.	Metformin	60-69	nitric oxide synthase 3	Homo sapiens	170-203
16443786-3	2006	Exposure of cultured bovine aortic endothelial cells (BAECs) to clinically relevant concentrations of metformin (50-500 micromol/l) dose-dependently increased serine-1179 (Ser1179) phosphorylation (equal to human Ser1179) of endothelial nitric oxide (NO) synthase (eNOS) as well as its association with heat shock protein (hsp)-90, resulting in increased activation of eNOS and NO bioactivity (cyclic GMP).	Metformin	102-111	nitric oxide synthase 3	Homo sapiens	265-269
16443786-5	2006	Furthermore, administration of metformin as well as 5-aminoimidazole-4-carboxamide ribonucleoside, an AMPK agonist, significantly increased eNOS Ser1179 phosphorylation, NO bioactivity, and coimmunoprecipitation of eNOS with hsp90 in wild-type C57BL6 mice but not in AMPK-alpha1 knockout mice, suggesting that AMPK is required for metformin-enhanced eNOS activation in vivo.	Metformin	31-40	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	267-271
16443786-5	2006	Furthermore, administration of metformin as well as 5-aminoimidazole-4-carboxamide ribonucleoside, an AMPK agonist, significantly increased eNOS Ser1179 phosphorylation, NO bioactivity, and coimmunoprecipitation of eNOS with hsp90 in wild-type C57BL6 mice but not in AMPK-alpha1 knockout mice, suggesting that AMPK is required for metformin-enhanced eNOS activation in vivo.	Metformin	331-340	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	102-106
16443786-6	2006	Finally, incubation of BAECs with clinically relevant concentrations of metformin dramatically attenuated high-glucose (30 mmol/l)-induced reduction in the association of hsp90 with eNOS, which resulted in increased NO bioactivity with a reduction in overexpression of adhesion molecules and endothelial apoptosis caused by high-glucose exposure.	Metformin	72-81	nitric oxide synthase 3	Homo sapiens	182-186
16443786-7	2006	Taken together, our results indicate that metformin might improve vascular endothelial functions in diabetes by increasing AMPK-dependent, hsp90-mediated eNOS activation.	Metformin	42-51	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	123-127
16443786-7	2006	Taken together, our results indicate that metformin might improve vascular endothelial functions in diabetes by increasing AMPK-dependent, hsp90-mediated eNOS activation.	Metformin	42-51	nitric oxide synthase 3	Homo sapiens	154-158
16443869-12	2006	CONCLUSIONS: Patients with type 2 diabetes exposed to sulfonylureas and exogenous insulin had a significantly increased risk of cancer-related mortality compared with patients exposed to metformin.	Metformin	187-196	insulin	Homo sapiens	82-89
16443786-3	2006	Exposure of cultured bovine aortic endothelial cells (BAECs) to clinically relevant concentrations of metformin (50-500 micromol/l) dose-dependently increased serine-1179 (Ser1179) phosphorylation (equal to human Ser1179) of endothelial nitric oxide (NO) synthase (eNOS) as well as its association with heat shock protein (hsp)-90, resulting in increased activation of eNOS and NO bioactivity (cyclic GMP).	Metformin	102-111	nitric oxide synthase 3	Homo sapiens	369-373
16443786-4	2006	These effects of metformin were mimicked or completely abrogated by adenoviral overexpression of a constitutively active 5"-AMP-activated kinase (AMPK) mutant or a kinase-inactive AMPK-alpha, respectively.	Metformin	17-26	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	146-150
16443786-5	2006	Furthermore, administration of metformin as well as 5-aminoimidazole-4-carboxamide ribonucleoside, an AMPK agonist, significantly increased eNOS Ser1179 phosphorylation, NO bioactivity, and coimmunoprecipitation of eNOS with hsp90 in wild-type C57BL6 mice but not in AMPK-alpha1 knockout mice, suggesting that AMPK is required for metformin-enhanced eNOS activation in vivo.	Metformin	31-40	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	102-106
16443786-5	2006	Furthermore, administration of metformin as well as 5-aminoimidazole-4-carboxamide ribonucleoside, an AMPK agonist, significantly increased eNOS Ser1179 phosphorylation, NO bioactivity, and coimmunoprecipitation of eNOS with hsp90 in wild-type C57BL6 mice but not in AMPK-alpha1 knockout mice, suggesting that AMPK is required for metformin-enhanced eNOS activation in vivo.	Metformin	31-40	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	267-278
16523411-0	2006	Metformin increases insulin sensitivity and plasma beta-endorphin in human subjects.	Metformin	0-9	proopiomelanocortin	Homo sapiens	51-65
16472047-6	2006	Metformin is known to reduce the risk of developing diabetes, and more recent evidence suggests it also lowers C-reactive protein, in part because of its modest weight-reducing effect.	Metformin	0-9	C-reactive protein	Homo sapiens	111-129
16523411-11	2006	In conclusion, metformin causes a significant parallel increase in insulin sensitivity and plasma beta-endorphin level in human subjects.	Metformin	15-24	proopiomelanocortin	Homo sapiens	98-112
16624028-0	2006	[Metformin hydrochloride ameliorates adiponectin levels and insulin sensitivity in adolescents with metabolic syndrome].	Metformin	1-24	adiponectin, C1Q and collagen domain containing	Homo sapiens	37-48
16501671-8	2006	Patients on sulphonylurea and on sulphonylurea plus metformin groups showed significantly elevated TC (p<0.001, p<0.0001), TG (p<0.001, p<0.01), LDL-C (p<0.01, p<0.001) and LDL-C/HDL-C (p<0.0001, p<0.0001) compared with controls.	Metformin	52-61	component of oligomeric golgi complex 2	Homo sapiens	157-162
16501671-8	2006	Patients on sulphonylurea and on sulphonylurea plus metformin groups showed significantly elevated TC (p<0.001, p<0.0001), TG (p<0.001, p<0.01), LDL-C (p<0.01, p<0.001) and LDL-C/HDL-C (p<0.0001, p<0.0001) compared with controls.	Metformin	52-61	component of oligomeric golgi complex 2	Homo sapiens	191-196
16501671-9	2006	Insulin therapy group showed significantly decreased TC, TG, LDL-C, LDL-C/HDL-C levels compared with sulphonylurea and sulphonylurea plus metformin treated groups, however, no significant difference was noted in the levels of above mentioned parameters and controls.	Metformin	138-147	insulin	Homo sapiens	0-7
16624028-0	2006	[Metformin hydrochloride ameliorates adiponectin levels and insulin sensitivity in adolescents with metabolic syndrome].	Metformin	1-24	insulin	Homo sapiens	60-67
16624028-3	2006	The aim of this study was to measure the changes of serum adiponectin levels, insulin sensitivity and other biochemical markers after metformin therapy in adolescents with MS, which might provide some information for set up a unified therapeutic measure for MS in adolescents.	Metformin	134-143	adiponectin, C1Q and collagen domain containing	Homo sapiens	58-69
16624028-11	2006	(2) HOMA-IR after metformin therapy decreased [5.7 (1.9-12.4) vs. 2.9 (0.9-7.4), t = 5.05, P < 0.01]; while the serum adiponectin levels increased with significant differences [(3.0 +/- 0.9) mg/L vs. (6.1 +/- 1.9) mg/L, t = 6.19, P < 0.01].	Metformin	18-27	adiponectin, C1Q and collagen domain containing	Homo sapiens	121-132
16624028-14	2006	Metformin can improve or ameliorate adiponectin levels, insulin sensitivity and some clinical markers.	Metformin	0-9	adiponectin, C1Q and collagen domain containing	Homo sapiens	36-47
16624028-14	2006	Metformin can improve or ameliorate adiponectin levels, insulin sensitivity and some clinical markers.	Metformin	0-9	insulin	Homo sapiens	56-63
16817087-2	2006	The biguanide metformin has encouraging effects on several metabolic aspects of the syndrome, including insulin sensitivity, plasma glucose concentration and lipid profile.	Metformin	14-23	insulin	Homo sapiens	104-111
17489164-9	2006	Combined treatment with Diane35 and metformin led to reduction of weight, fat mass and abdominal fat distribution; possessed significant antiandrogenic effect; did not decrease blood glucose levels; supressed glucose-stimulated insulin levels; had beneficial effect on HDL-cholesterol and neutral effect on other lipid parameters and atherogenic indices; decreased diastolic blood pressure.	Metformin	36-45	insulin	Homo sapiens	228-235
16914073-0	2006	Metformin and pioglitazone: Effectively treating insulin resistance.	Metformin	0-9	insulin	Homo sapiens	49-56
16585812-6	2006	RESULTS: The adjusted rate ratio of an injurious crash was 1.4 (95% CI: 1.0-2.0) for current users of insulin monotherapy relative to non-users and 1.3 (95% CI: 1.0-1.7) for sulfonylurea and metformin combined.	Metformin	191-200	insulin	Homo sapiens	102-109
16585812-10	2006	CONCLUSIONS: L Elderly drivers treated with insulin monotherapy or a combination of sulfonylurea and metformin, especially at high doses, have a small increased risk of injurious crashes.	Metformin	101-110	insulin	Homo sapiens	44-51
16914073-3	2006	Two key classes of insulin-sensitizing agents--the biguanides (principally metformin) and thiazolidinediones (pioglitazone and rosiglitazone)--have distinct molecular mechanisms of action and differing effects on metabolic dysfunction.	Metformin	75-84	insulin	Homo sapiens	19-26
16914073-6	2006	FINDINGS: The different insulin-sensitizing mechanisms of metformin and the thiazolidinediones are manifest in partially distinct effects on hepatic and peripheral glucose homeostasis, and clinical studies show improved glucose control with combination therapy.	Metformin	58-67	insulin	Homo sapiens	24-31
16914073-11	2006	CONCLUSION: The distinct, but complementary, mechanisms of action of the thiazolidinediones and metformin provide the opportunity for effective combination therapy with two insulin-sensitizing agents.	Metformin	96-105	insulin	Homo sapiens	173-180
16380484-4	2006	Treatment with metformin and AICAR inhibited hyperglycemia-induced intracellular and mtROS production, stimulated AMP-activated protein kinase (AMPK) activity, and increased the expression of peroxisome proliferator-activated response-gamma coactivator-1alpha (PGC-1alpha) and manganese superoxide dismutase (MnSOD) mRNAs.	Metformin	15-24	PPARG coactivator 1 alpha	Homo sapiens	261-271
16380496-13	2006	In parallel to improved insulin sensitivity, plasma BPI significantly increased in the metformin group but not in the placebo group.	Metformin	87-96	insulin	Homo sapiens	24-31
16380484-6	2006	In addition, metformin and AICAR increased the mRNA expression of nuclear respiratory factor-1 and mitochondrial DNA transcription factor A (mtTFA) and stimulated the mitochondrial proliferation.	Metformin	13-22	transcription factor A, mitochondrial	Homo sapiens	99-139
16380484-6	2006	In addition, metformin and AICAR increased the mRNA expression of nuclear respiratory factor-1 and mitochondrial DNA transcription factor A (mtTFA) and stimulated the mitochondrial proliferation.	Metformin	13-22	transcription factor A, mitochondrial	Homo sapiens	141-146
16380484-8	2006	These results suggest that metformin normalizes hyperglycemia-induced mtROS production by induction of MnSOD and promotion of mitochondrial biogenesis through the activation of AMPK-PGC-1alpha pathway.	Metformin	27-36	PPARG coactivator 1 alpha	Homo sapiens	182-192
17037948-15	2006	Metformin, by decreasing insulin resistance, alleviates many of the hormonal disturbances and restores menses in a considerable proportion of patients.	Metformin	0-9	insulin	Homo sapiens	25-32
16627381-5	2006	In contradistinction, metformin, an effective insulin sensitizer, causes less weight gain.	Metformin	22-31	insulin	Homo sapiens	46-53
16522532-2	2006	The use of insulin-sensitizer compounds, such as metformin, permits great improvement of such metabolic abnormality and the restoration of normal ovarian function.	Metformin	49-58	insulin	Homo sapiens	11-18
16522532-3	2006	Metformin administration reduces insulin resistance and androgen production both from the ovary and adrenal gland.	Metformin	0-9	insulin	Homo sapiens	33-40
16423593-1	2006	OBJECTIVE: To assess the use of oral glucose tolerance testing (OGTT) to predict efficacy of insulin sensitization (metformin) or suppression (octreotide) because insulin resistance and insulin hypersecretion may impact pharmacotherapeutic efficacy in obese children.	Metformin	116-125	insulin	Homo sapiens	93-100
16423593-12	2006	CONCLUSIONS: Efficacy of metformin was predicted by pretreatment insulin resistance.	Metformin	25-34	insulin	Homo sapiens	65-72
16354680-7	2006	Knockdown of Raptor as well as activators of the LKB1/AMPK pathway, such as the widely used antidiabetic compound metformin, suppress IRS-1 Ser636/639 phosphorylation and reverse mTOR-mediated inhibition on PI3-kinase/Akt signaling.	Metformin	114-123	mechanistic target of rapamycin kinase	Homo sapiens	179-183
16354680-7	2006	Knockdown of Raptor as well as activators of the LKB1/AMPK pathway, such as the widely used antidiabetic compound metformin, suppress IRS-1 Ser636/639 phosphorylation and reverse mTOR-mediated inhibition on PI3-kinase/Akt signaling.	Metformin	114-123	AKT serine/threonine kinase 1	Homo sapiens	218-221
17347533-2	2006	The treatment of PCOS patients with insulin sensitizers, such as metformin or thiazolidinediones, increases the ovulation rate and the number of successful pregnancies.	Metformin	65-74	insulin	Homo sapiens	36-43
16800161-7	2006	RESULTS: The combination therapy of rosiglitazone with metformin or sulfonylurea produces better glycaemic control than conventional care of metformin with sulfonylurea and insulin in most patients, extends the viability of oral therapy before requiring insulin, and typically leads to lifetime cost increases across all treatment types.	Metformin	55-64	insulin	Homo sapiens	254-261
16229818-7	2005	To confirm that the increase in IL-6 production is ascribed to AMPK activation, we used another known AMPK activator, metformin.	Metformin	118-127	interleukin 6	Mus musculus	32-36
16308421-0	2005	The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin.	Metformin	81-90	serine/threonine kinase 11	Mus musculus	11-15
16308421-6	2005	Finally, we show that metformin, one of the most widely prescribed type 2 diabetes therapeutics, requires LKB1 in the liver to lower blood glucose levels.	Metformin	22-31	serine/threonine kinase 11	Mus musculus	106-110
16503324-7	2005	RESULTS: Immediate hospitalization and discontinuation of metformin treatment led to improvements in liver function (decreased AST, ALT, ALP, and total bilirubin concentrations) and resolution of the presented symptoms within 3 weeks.	Metformin	58-67	solute carrier family 17 member 5	Homo sapiens	127-130
16503324-7	2005	RESULTS: Immediate hospitalization and discontinuation of metformin treatment led to improvements in liver function (decreased AST, ALT, ALP, and total bilirubin concentrations) and resolution of the presented symptoms within 3 weeks.	Metformin	58-67	alkaline phosphatase, placental	Homo sapiens	137-140
16454597-13	2005	The group treated with metformin showed levels of triglycerides (TG) significantly higher than those of the diet controlled group (p = 0.009) and insulin group (p < 0.001).	Metformin	23-32	insulin	Homo sapiens	146-153
16107611-2	2005	Insulin (33 to 34% vs. 21%) or insulin plus metformin (27 to 39% vs. 21%) significantly (P < 0.01) increased the rates of blastocyst formation, whereas metformin alone had no effect when added during the first half (0-22 h), the latter half (22-44 h), or the entire (0-44 h) maturation period.	Metformin	155-164	insulin	Homo sapiens	31-38
16107611-4	2005	When supplemented during IVC, insulin (34% vs. 23%) or insulin plus metformin (35% vs. 23%) significantly (P < 0.05) increased the rates of blastocyst formation, whereas metformin alone had no effect.	Metformin	173-182	insulin	Homo sapiens	55-62
16107611-7	2005	In addition, the effect of insulin was enhanced when supplemented with metformin compared to insulin alone (52% vs. 40%).	Metformin	71-80	insulin	Homo sapiens	27-34
16107611-9	2005	Insulin significantly (P < 0.01) increased oocyte GSH content (6.2 pmol vs. 4.3 pmol) and metformin significantly (P < 0.01) enhanced the action of insulin on GSH content (7.3 pmol vs. 6.2 pmol) and tyrosine kinase activity (1.9 arbitrary units [AU] vs. 1.5 AU) when compared to insulin alone.	Metformin	93-102	insulin	Homo sapiens	154-161
16107611-9	2005	Insulin significantly (P < 0.01) increased oocyte GSH content (6.2 pmol vs. 4.3 pmol) and metformin significantly (P < 0.01) enhanced the action of insulin on GSH content (7.3 pmol vs. 6.2 pmol) and tyrosine kinase activity (1.9 arbitrary units [AU] vs. 1.5 AU) when compared to insulin alone.	Metformin	93-102	insulin	Homo sapiens	285-292
16107611-10	2005	In conclusion, insulin increased the developmental potential of porcine oocytes and embryos, and metformin enhanced the action of insulin when supplemented during the entire IVM and IVC.	Metformin	97-106	insulin	Homo sapiens	130-137
16316811-9	2005	CONCLUSIONS: Clinical outcomes of metformin therapy may be categorized on the basis of basal BMI and insulin levels in PCOS patients.	Metformin	34-43	insulin	Homo sapiens	101-108
16289780-7	2005	The aim of the pharmacological therapy is to decrease insulin resistance, namely by metformin.	Metformin	84-93	insulin	Homo sapiens	54-61
16381638-11	2005	Furthermore, metformin treatment lowered serum TG, liver lipid accumulation and the production of FFA and TNF alpha.	Metformin	13-22	tumor necrosis factor	Rattus norvegicus	106-115
16483179-1	2005	AIM: The aim of this study was to assess the effects of metformin and rosiglitazone on insulin resistance and serum androgen levels in both obese and lean patients with polycystic ovary syndrome (PCOS).	Metformin	56-65	insulin	Homo sapiens	87-94
16483179-14	2005	CONCLUSIONS: Our data showed that both metformin and rosiglitazone increased insulin sensitivity in obese patients with PCOS as expected, and in lean patients as well.	Metformin	39-48	insulin	Homo sapiens	77-84
16259573-7	2005	Lifestyle therapy is indicated as the first intervention; however, metformin as an insulin sensitising agent has a role in first-line medical therapy in women with PCOS.	Metformin	67-76	insulin	Homo sapiens	83-90
16219007-1	2005	The biguanide, metformin, sensitizes the liver to the effect of insulin, suppressing hepatic glucose output.	Metformin	15-24	insulin	Homo sapiens	64-71
16219007-4	2005	Metformin in combination with insulin has been shown to significantly improve blood glucose levels while lowering total daily insulin dose and body weight.	Metformin	0-9	insulin	Homo sapiens	126-133
16219009-6	2005	RESULTS: Metformin acts by increasing tissue sensitivity to insulin, principally in the liver.	Metformin	9-18	insulin	Homo sapiens	60-67
16219009-7	2005	Beneficial properties of metformin include weight reduction, favourable effects on the lipid profile and the fibrinolytic pathway, and improvement of ovarian function in some insulin-resistant women.	Metformin	25-34	insulin	Homo sapiens	175-182
16219011-0	2005	Treating insulin resistance in type 2 diabetes with metformin and thiazolidinediones.	Metformin	52-61	insulin	Homo sapiens	9-16
16219011-2	2005	Metformin and thiazolidinediones (pioglitazone and rosiglitazone) counter insulin resistance by different cellular mechanisms and with complementary effects, making them suited for use in combination.	Metformin	0-9	insulin	Homo sapiens	74-81
16275246-0	2005	Effect of metformin on the growth hormone response to growth hormone-releasing hormone in obese women with polycystic ovary syndrome.	Metformin	10-19	growth hormone 1	Homo sapiens	27-41
16275246-0	2005	Effect of metformin on the growth hormone response to growth hormone-releasing hormone in obese women with polycystic ovary syndrome.	Metformin	10-19	growth hormone releasing hormone	Homo sapiens	54-86
16275246-12	2005	CONCLUSION(S): These data suggest that metformin is able to affect GH secretion in obese women with PCOS, even with minimal metabolic modifications.	Metformin	39-48	growth hormone 1	Homo sapiens	67-69
16250043-9	2005	Finally, the ability of insulin-sensitizing, pharmacological agents to treat NAFLD by reducing IR in the liver (metformin) and in the periphery (thiazolidinediones) are discussed.	Metformin	112-121	insulin	Homo sapiens	24-31
16278525-8	2005	Glucose-lowering agents may be indicated, and drugs such as metformin and thiazolidinediones, which reduce insulin resistance, should form the basis of therapy.	Metformin	60-69	insulin	Homo sapiens	107-114
16515237-4	2005	Metformin is a hepato-selective insulin sensitizer.	Metformin	0-9	insulin	Homo sapiens	32-39
16210009-0	2005	Metformin alters insulin signaling and viability of human granulosa cells.	Metformin	0-9	insulin	Homo sapiens	17-24
16210009-1	2005	OBJECTIVE: To study whether insulin signaling pathways in the ovary are altered by metformin.	Metformin	83-92	insulin	Homo sapiens	28-35
16210009-8	2005	CONCLUSION(S): Besides systemic effects, the ovulation inducing action of metformin may at least partially be due to direct effects on insulin signaling intermediates and follicular growth patterns in the ovary.	Metformin	74-83	insulin	Homo sapiens	135-142
15958399-8	2005	CONCLUSION: In insulin-resistant women with PCOS, metformin pre-treatment and co-administration with hpFSH increases the mono-ovulatory cycles.	Metformin	50-59	insulin	Homo sapiens	15-22
16179727-5	2005	Interestingly, insulin-sensitizing agents (e.g., thiazolidinediones, metformin) improve aPKC activation by insulin in vivo and PIP3 in vitro, most likely by activating 5"-adenosine monophosphate-activated protein kinase, which favorably alters intracellular lipid metabolism.	Metformin	69-78	insulin	Homo sapiens	15-22
16179727-5	2005	Interestingly, insulin-sensitizing agents (e.g., thiazolidinediones, metformin) improve aPKC activation by insulin in vivo and PIP3 in vitro, most likely by activating 5"-adenosine monophosphate-activated protein kinase, which favorably alters intracellular lipid metabolism.	Metformin	69-78	insulin	Homo sapiens	107-114
16599037-12	2005	On Metformin, the median fasting serum insulin decreased from 23.6 micro U/ml to 20.2 micro U/ml (P<0.05).	Metformin	3-12	insulin	Homo sapiens	39-46
16178991-5	2005	The combination of nateglinide with insulin-sensitising agents, for example, metformin and thiazolidinediones, addresses the dual defects of loss of insulin secretion and insulin resistance to provide optimal management of type 2 diabetes, and more patients achieve HbA 1c goal with nateglinide combination therapy rather than with monotherapy with other oral agents.	Metformin	77-86	insulin	Homo sapiens	36-43
16108864-0	2005	Metformin reduces C-reactive protein but not complement factor C3 in overweight patients with Type 2 diabetes mellitus.	Metformin	0-9	C-reactive protein	Homo sapiens	18-36
16200335-2	2005	Treatment with insulin sensitizers (metformin, rosiglitazone) can ameliorate insulin resistance.	Metformin	36-45	insulin	Homo sapiens	15-22
16200335-2	2005	Treatment with insulin sensitizers (metformin, rosiglitazone) can ameliorate insulin resistance.	Metformin	36-45	insulin	Homo sapiens	77-84
16200335-12	2005	This improvement in insulin secretion could be clearly demonstrated when the sums of insulin concentrations after oral glucose tolerance test were compared: 548-/+13 to 345-/+11.8 mIU/l in the rosiglitazone group (37% decrease, p<0.01) and from 552-/+15 to 420-/+12 mIU/l in the metformin group (24% decrease, p<0.01).	Metformin	282-291	insulin	Homo sapiens	20-27
16231594-7	2005	Two classes of drugs have been shown to correct insulin resistance: biguanides (e.g., metformin) and thiazolidinediones (e.g., rosiglitazone and pioglitazone).	Metformin	86-95	insulin	Homo sapiens	48-55
16108864-1	2005	AIMS: To determine the influence of metformin treatment on plasma C-reactive protein (CRP) and complement factor C3.	Metformin	36-45	C-reactive protein	Homo sapiens	66-84
16108864-1	2005	AIMS: To determine the influence of metformin treatment on plasma C-reactive protein (CRP) and complement factor C3.	Metformin	36-45	C-reactive protein	Homo sapiens	86-89
16108864-8	2005	The difference in ratios of CRP levels at each visit to baseline between placebo- (n = 16) and metformin-treated (n = 26) subjects was significantly different at the 12-week (P = 0.002) and 24-week (P = 0.03) visits.	Metformin	95-104	C-reactive protein	Homo sapiens	28-31
16108864-13	2005	CONCLUSION: Metformin may have a specific interaction with mechanisms involved in CRP synthesis or secretion, not directly related to improved insulin sensitivity and dampening of chronic inflammation.	Metformin	12-21	C-reactive protein	Homo sapiens	82-85
16039647-0	2005	Metformin reduces adiponectin protein expression and release in 3T3-L1 adipocytes involving activation of AMP activated protein kinase.	Metformin	0-9	adiponectin, C1Q and collagen domain containing	Homo sapiens	18-29
16115299-6	2005	Metformin improved insulin resistance compared with placebo group (HOMA-IR from 3.39 to 2.5 vs. 3.42 to 3.37; 26% reduction in HOMA-IR, P = 0.01).	Metformin	0-9	insulin	Homo sapiens	19-26
16115299-8	2005	CONCLUSION: Metformin improves both endothelial function and insulin resistance in patients with MS.	Metformin	12-21	insulin	Homo sapiens	61-68
16039647-1	2005	The drugs troglitazone and metformin are used to reduce the degree of insulin resistance in type 2 diabetes.	Metformin	27-36	insulin	Homo sapiens	70-77
16039647-3	2005	This study compared the effects of troglitazone and metformin on adiponectin production by 3T3-L1 adipocytes during 48 h culture.	Metformin	52-61	adiponectin, C1Q and collagen domain containing	Homo sapiens	65-76
16039647-7	2005	These data indicate that metformin and troglitazone exert opposing effects on adiponectin expression and release by differentiated 3T3-L1 adipocytes.	Metformin	25-34	adiponectin, C1Q and collagen domain containing	Homo sapiens	78-89
15990591-7	2005	Treatments aimed at weight loss remain a primary option; among pharmacological interventions, insulin sensitizers (glitazones and metformin) have confirmed beneficial effects on both biochemical and histological data, but new treatments are on the horizon.	Metformin	130-139	insulin	Homo sapiens	94-101
16026380-0	2005	Long-term effects of pioglitazone and metformin on insulin sensitivity in patients with Type 2 diabetes mellitus.	Metformin	38-47	insulin	Homo sapiens	51-58
16026380-1	2005	AIM: Despite their comparable glycaemic effects in patients with Type 2 diabetes mellitus (T2DM), pioglitazone and metformin may have different effects on insulin sensitivity because they have different mechanisms of action.	Metformin	115-124	insulin	Homo sapiens	155-162
16026380-2	2005	We studied the changes in insulin sensitivity, as assessed by the Quantitative Insulin Sensitivity Check Index (QUICKI), in patients with T2DM who used metformin or pioglitazone as monotherapy or in combination therapy with sulphonylurea.	Metformin	152-161	insulin	Homo sapiens	26-33
16026380-12	2005	CONCLUSION: Pioglitazone differed from metformin in its effects on insulin sensitivity despite both drugs having comparable glycaemic effects.	Metformin	39-48	insulin	Homo sapiens	67-74
16043735-0	2005	Improved meal-related beta-cell function and insulin sensitivity by the dipeptidyl peptidase-IV inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1 year.	Metformin	122-131	insulin	Homo sapiens	45-52
16157982-0	2005	Markedly improved glycemic control and enhanced insulin sensitivity in a patient with type 2 diabetes complicated by a suprasellar tumor treated with pioglitazone and metformin.	Metformin	167-176	insulin	Homo sapiens	48-55
16294070-9	2005	Metformin did significantly increase the fractional synthetic rate of muscle protein which increased even further with insulin administration.	Metformin	0-9	insulin	Homo sapiens	119-126
16091082-8	2005	CONCLUSION: Metformin is safe and may represent a useful adjunct to the management of type 1 diabetes mellitus in adolescents and young adults who have poor glycemic control despite a large amount of insulin.	Metformin	12-21	insulin	Homo sapiens	200-207
15975107-0	2005	Does metformin decrease blood pressure in patients with Type 2 diabetes intensively treated with insulin?	Metformin	5-14	insulin	Homo sapiens	97-104
15955124-3	2005	We examined whether the insulin-sensitizing agents, metformin and rosiglitazone, improve intestinal lipoprotein metabolism in obese insulin-resistant individuals.	Metformin	52-61	insulin	Homo sapiens	24-31
15955124-6	2005	RESULTS: Metformin and rosiglitazone both significantly improved insulin sensitivity, but this was not paralleled by improvement in dyslipidaemia.	Metformin	9-18	insulin	Homo sapiens	65-72
15955124-8	2005	CONCLUSION: In obese insulin-resistant subjects metformin and rosiglitazone both improve insulin sensitivity, as measured by HOMA, without improvement in lipid metabolism.	Metformin	48-57	insulin	Homo sapiens	21-28
15983226-9	2005	Treatment of HASMCs with metformin decreased leptin-induced ROS production and activation of PKC, ERK1/2, and NF-kappaB.	Metformin	25-34	mitogen-activated protein kinase 3	Homo sapiens	98-104
15983226-9	2005	Treatment of HASMCs with metformin decreased leptin-induced ROS production and activation of PKC, ERK1/2, and NF-kappaB.	Metformin	25-34	nuclear factor kappa B subunit 1	Homo sapiens	110-119
15983227-3	2005	Rosiglitazone and metformin act by different mechanisms to improve insulin sensitivity and thereby reduce beta-cell secretory demand, resulting in decreased release of insulin and islet amyloid polypeptide (IAPP), the unique constituent of islet amyloid deposits.	Metformin	18-27	islet amyloid polypeptide	Mus musculus	168-205
15975107-1	2005	AIMS: We investigated in a double-blind study whether metformin reduces blood pressure (BP) in patients with Type 2 diabetes intensively treated with insulin.	Metformin	54-63	insulin	Homo sapiens	150-157
15983227-3	2005	Rosiglitazone and metformin act by different mechanisms to improve insulin sensitivity and thereby reduce beta-cell secretory demand, resulting in decreased release of insulin and islet amyloid polypeptide (IAPP), the unique constituent of islet amyloid deposits.	Metformin	18-27	islet amyloid polypeptide	Mus musculus	207-211
15983320-1	2005	OBJECTIVE: Thiazolidinediones (TZDs) and metformin are insulin-sensitizing antihyperglycemic agents with reported benefits on atherosclerosis.	Metformin	41-50	insulin	Homo sapiens	55-62
15911461-2	2005	Clomiphene citrate has been standard therapy for ovulation induction in patients seeking pregnancy, but recent evidence suggests that insulin sensitizing agents such as metformin may also be effective.	Metformin	169-178	insulin	Homo sapiens	134-141
15864539-0	2005	Enhanced insulin-stimulated glycogen synthesis in response to insulin, metformin or rosiglitazone is associated with increased mRNA expression of GLUT4 and peroxisomal proliferator activator receptor gamma co-activator 1.	Metformin	71-80	insulin	Homo sapiens	9-16
15864539-0	2005	Enhanced insulin-stimulated glycogen synthesis in response to insulin, metformin or rosiglitazone is associated with increased mRNA expression of GLUT4 and peroxisomal proliferator activator receptor gamma co-activator 1.	Metformin	71-80	insulin	Homo sapiens	62-69
15864539-0	2005	Enhanced insulin-stimulated glycogen synthesis in response to insulin, metformin or rosiglitazone is associated with increased mRNA expression of GLUT4 and peroxisomal proliferator activator receptor gamma co-activator 1.	Metformin	71-80	peroxisome proliferator activated receptor gamma	Homo sapiens	156-205
15864539-5	2005	RESULTS: Insulin-stimulated glycogen synthesis was significantly increased in cultured human myotubes treated with insulin, rosiglitazone or metformin for 8 days, compared with non-treated cells.	Metformin	141-150	insulin	Homo sapiens	9-16
15864539-8	2005	Exposure to insulin, rosiglitazone or metformin increased mRNA expression of PGC1 and GLUT4, while AICAR or 25 mmol/l glucose treatment increased GLUT1 mRNA expression.	Metformin	38-47	PPARG coactivator 1 alpha	Homo sapiens	77-81
15864539-11	2005	These data show that chronic treatment of human myotubes with insulin, metformin or rosiglitazone has a direct positive effect on insulin action and mRNA expression.	Metformin	71-80	insulin	Homo sapiens	130-137
15955371-6	2005	Although in recent years the emphasis on initial therapy has been shifting from insulin secretagogues to insulin sensitizers such as metformin and thiazolidinediones, questions remain as to genetic and/or phenotypic factors may dictate a different choice of the first antidiabetic drug to be used.	Metformin	133-142	insulin	Homo sapiens	105-112
15927899-9	2005	Metformin monotherapy was associated with a delay in the onset of secondary failure (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.82-0.98), in the progression to combination therapy (HR 0.79, 95% CI 0.71-0.87), and in the start of insulin therapy (HR 0.65, 95% CI 0.51-0.82).	Metformin	0-9	insulin	Homo sapiens	241-248
15632102-2	2005	This study was designed to determine whether the insulin sensitizer drugs pioglitazone and metformin would improve glucose intolerance and insulin sensitivity by decreasing IMCL.	Metformin	91-100	insulin	Homo sapiens	49-56
23577416-5	2005	However, in polycystic ovary syndrome, with its excessive follicle pool, short-term reduction of insulin promoted LH action by metformin treatment has failed to influence follicle responses to exogenous FSH.	Metformin	127-136	insulin	Homo sapiens	97-104
15991679-1	2005	Based on the favourable international experience with metformin in the most common female endocrine disease, the polycystic ovary syndrome, which has insulin resistance in the background, the author"s treatment advice has been this in such cases since early 2002: for sexually active women who do not want to become pregnant for the time being, anti-androgenic contraceptive pill; for those who do not want to take contraceptives, contraceptives are contraindicated, or who do want to conceive, metformin.	Metformin	54-63	insulin	Homo sapiens	150-157
15855334-0	2005	Effects of metformin and rosiglitazone treatment on insulin signaling and glucose uptake in patients with newly diagnosed type 2 diabetes: a randomized controlled study.	Metformin	11-20	insulin	Homo sapiens	52-59
15853834-1	2005	OBJECTIVE: Treatment with metformin, an insulin-lowering agent, increases serum glycodelin, a progesterone-regulated lipocalin protein of the reproductive axis that may play a role in foeto-maternal defence mechanisms.	Metformin	26-35	insulin	Homo sapiens	40-47
15855334-1	2005	The effect of metformin or rosiglitazone monotherapy versus placebo on insulin signaling and gene expression in skeletal muscle of patients with newly diagnosed type 2 diabetes was determined.	Metformin	14-23	insulin	Homo sapiens	71-78
15855334-3	2005	Insulin-mediated whole-body and leg muscle glucose uptake was enhanced 36 and 32%, respectively, after rosiglitazone (P < 0.01) but not after metformin or placebo treatment.	Metformin	145-154	insulin	Homo sapiens	0-7
15855347-5	2005	Metformin reduced CRP in women compared with the placebo group.	Metformin	0-9	C-reactive protein	Homo sapiens	18-21
15855347-7	2005	In women, the changes in CRP from baseline to follow-up were -29% in the lifestyle group, -14% in the metformin group, and 0% in the placebo group.	Metformin	102-111	C-reactive protein	Homo sapiens	25-28
16350724-5	2005	There is known the first description of atypical endometrial hyperplasia resistant to progestogen therapy, which was subsequently treated with an insulin-sensitizng agent, metformin.	Metformin	172-181	insulin	Homo sapiens	146-153
16350724-8	2005	In contrast, metformin lowers the rate of gluconeogenesis in the presence of insulin.	Metformin	13-22	insulin	Homo sapiens	77-84
16350724-31	2005	Theoretically, metformin, a treatment which is now widely used to treat infertile women with PCOS, may have a role in preventing endometrial hyperstimulation by lowering insulin concentrations and restoring ovulation.	Metformin	15-24	insulin	Homo sapiens	170-177
15665022-1	2005	BACKGROUND: Recent evidence suggests that one of the modes of action of metformin may be through phosphorylation of the insulin receptor and insulin receptor substrates.	Metformin	72-81	insulin	Homo sapiens	120-127
15842521-0	2005	Continuing metformin when starting insulin in patients with Type 2 diabetes: a double-blind randomized placebo-controlled trial.	Metformin	11-20	insulin	Homo sapiens	35-42
15842521-1	2005	AIMS: To test the effect of continuing metformin on weight gain and glycaemic control in patients with poorly controlled Type 2 diabetes who need to start insulin.	Metformin	39-48	insulin	Homo sapiens	155-162
15842521-7	2005	CONCLUSIONS: Metformin decreases weight gain, lowers insulin requirement, and improves glycaemic control, and should be continued in patients with Type 2 diabetes who transfer to insulin.	Metformin	13-22	insulin	Homo sapiens	53-60
15842521-7	2005	CONCLUSIONS: Metformin decreases weight gain, lowers insulin requirement, and improves glycaemic control, and should be continued in patients with Type 2 diabetes who transfer to insulin.	Metformin	13-22	insulin	Homo sapiens	179-186
15665022-9	2005	CONCLUSION: There was a differential effect of metformin therapy in PCOS women on the basis of IRS genotype.	Metformin	47-56	isoleucyl-tRNA synthetase 1	Homo sapiens	95-98
15665022-1	2005	BACKGROUND: Recent evidence suggests that one of the modes of action of metformin may be through phosphorylation of the insulin receptor and insulin receptor substrates.	Metformin	72-81	insulin	Homo sapiens	141-148
15665022-7	2005	RESULTS: Metformin had differential effects on fasting insulin levels, insulin resistance as demonstrated by homeostasis model assessment (HOMA), LH, total testosterone, dehydroepiandrosterone sulphate and free testosterone index on the basis of IRS genotype.	Metformin	9-18	insulin	Homo sapiens	55-62
15665022-7	2005	RESULTS: Metformin had differential effects on fasting insulin levels, insulin resistance as demonstrated by homeostasis model assessment (HOMA), LH, total testosterone, dehydroepiandrosterone sulphate and free testosterone index on the basis of IRS genotype.	Metformin	9-18	insulin	Homo sapiens	71-78
15665022-7	2005	RESULTS: Metformin had differential effects on fasting insulin levels, insulin resistance as demonstrated by homeostasis model assessment (HOMA), LH, total testosterone, dehydroepiandrosterone sulphate and free testosterone index on the basis of IRS genotype.	Metformin	9-18	isoleucyl-tRNA synthetase 1	Homo sapiens	246-249
15938589-8	2005	Rosiglitazone plus metformin significantly improved long-term control of insulin resistance-related parameters compared with glimepiride plus metformin, although glimepiride treatment was associated with a slight improvement in cholesterolaemia, not observed in the rosiglitazone-treated patients, and with significant improvements in non-traditional risk factors for cardiovascular disease, such as basal homocysteinaemia and plasma Lp(a) levels.	Metformin	19-28	insulin	Homo sapiens	73-80
15899724-12	2005	CONCLUSIONS: The rosiglitazone-metformin combination significantly improved the long-term control of all insulin resistance-related parameters compared with the glimepiride-metformin combination.	Metformin	31-40	insulin	Homo sapiens	105-112
16124352-1	2005	BACKGROUND: The extended-release formulation of metformin (MXR) prolongs drug absorption in the upper gastrointestinal tract and permits once-daily dosing in patients with type 2 diabetes mellitus (T2DM).	Metformin	48-57	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	59-62
16035301-7	2005	Insulin secretagogues can be used as monotherapy, in association with metformin or a glitazone, or even in combination with a basal insulin regimen.	Metformin	70-79	insulin	Homo sapiens	0-7
15817918-9	2005	CONCLUSIONS: Metformin co-treatment in a group of insulin-resistant, normogonadotrophic, anovulatory patients resulted in normalization of the endocrine profile and facilitated monofollicular development during the FSH induction of ovulation.	Metformin	13-22	insulin	Homo sapiens	50-57
15844237-6	2005	For prevention and/or treatment, exercise and optimal diet are useful, and metformin and rosiglitazone have been shown to improve insulin resistance.	Metformin	75-84	insulin	Homo sapiens	130-137
15715892-1	2005	OBJECTIVES: To measure the effect of metformin on the body composition, insulin resistance and sensitivity in subjects with risk factors for type 2 diabetes mellitus (type 2 DM).	Metformin	37-46	insulin	Homo sapiens	72-79
15868769-8	2005	CONCLUSIONS: Race, age, residential setting, preexisting comorbidities and diabetes complications, other oral diabetes drug use, and insulin use are statistically significant predictors of initial prescribing of TZD or metformin in a Medicaid MCO population.	Metformin	219-228	insulin	Homo sapiens	133-140
15717887-14	2005	Metformin improved hyperglycemia through increased insulin-independent glucose uptake in peripheral muscle.	Metformin	0-9	insulin	Homo sapiens	51-58
15715892-12	2005	CONCLUSIONS: The administration of metformin for 2 months improves the parameters of body composition and insulin dynamics in subjects with risk factors for type 2 DM.	Metformin	35-44	insulin	Homo sapiens	106-113
15688205-5	2005	More body fat was deposited centrally in patients receiving insulin alone than those receiving insulin with an oral hypoglycaemic agent (metformin).	Metformin	137-146	insulin	Homo sapiens	95-102
15598674-0	2005	Responses of serum androgen and insulin resistance to metformin and pioglitazone in obese, insulin-resistant women with polycystic ovary syndrome.	Metformin	54-63	insulin	Homo sapiens	32-39
15598674-0	2005	Responses of serum androgen and insulin resistance to metformin and pioglitazone in obese, insulin-resistant women with polycystic ovary syndrome.	Metformin	54-63	insulin	Homo sapiens	91-98
15598674-5	2005	Fasting serum insulin concentration (P < 0.001 for both drugs) and the area under the insulin curve during a 2-h oral glucose tolerance test decreased after pioglitazone (P < 0.002) or metformin (P < 0.05) treatment.	Metformin	191-200	insulin	Homo sapiens	14-21
15677775-7	2005	CONCLUSIONS: Initiating insulin treatment by adding basal insulin glargine once daily to glimepiride plus metformin treatment was safer and more effective than beginning twice-daily injections of 70/30 and discontinuing OADs in type 2 diabetic patients inadequately controlled with OADs.	Metformin	106-115	insulin	Homo sapiens	24-31
15688205-8	2005	The possible role of metformin in reducing central fat accumulation following insulin treatment warrants further investigation into its mechanism and potential long-term benefits.	Metformin	21-30	insulin	Homo sapiens	78-85
15653205-7	2005	RESULTS: Much better and faster decrease in the level of testosterone and free androgen index in group with combined use of metformin and Diane35 was established, without deterioration of the anthropometric and biochemical indices and insulin sensitivity.	Metformin	124-133	insulin	Homo sapiens	235-242
15690319-0	2005	Differential regulation of insulin action and tumor necrosis factor alpha system activity by metformin.	Metformin	93-102	insulin	Homo sapiens	27-34
15745936-2	2005	Insulin sensitizers, especially metformin, have been shown to improve these metabolic disturbances, but there are only a few studies on their effects on serum lipids in polycystic ovary syndrome.	Metformin	32-41	insulin	Homo sapiens	0-7
15690319-0	2005	Differential regulation of insulin action and tumor necrosis factor alpha system activity by metformin.	Metformin	93-102	tumor necrosis factor	Homo sapiens	46-73
15690319-10	2005	CONCLUSIONS: Metformin is able to reverse insulin resistance and hyperglycemia in high-risk subjects for type 2 diabetes mellitus independently of the effects on tumor necrosis factor alpha system activity.	Metformin	13-22	insulin	Homo sapiens	42-49
15901207-7	2005	Metformin improves dyslipidemia and altered hemostasis and decreases plasma C-reactive protein levels with little or no effect on blood pressure.	Metformin	0-9	C-reactive protein	Homo sapiens	76-94
15607747-1	2005	Polyunsaturated fatty acids (PUFA) and a number of drugs (metformin, thiazolidinediones) and hormones (leptin, adiponectin) that activate AMP-activated protein kinase (AMPK) have been reported to improve insulin sensitivity.	Metformin	58-67	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	138-166
15607747-1	2005	Polyunsaturated fatty acids (PUFA) and a number of drugs (metformin, thiazolidinediones) and hormones (leptin, adiponectin) that activate AMP-activated protein kinase (AMPK) have been reported to improve insulin sensitivity.	Metformin	58-67	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	168-172
16372821-15	2005	The biguanide metformin is not significantly metabolised but polymorphisms in the organic cation transporter (OCT) 1 and OCT2 may determine its pharmacokinetic variability.	Metformin	14-23	solute carrier family 22 member 1	Homo sapiens	82-116
15386819-9	2005	When insulin was added to an initial therapy, CHF incidence was increased 2.33 times (p < 0.0001) and 2.66 times (p < 0.0001) compared to the addition of sulphonylurea or metformin respectively.	Metformin	177-186	insulin	Homo sapiens	5-12
24790303-4	2005	Metformin is considered to be the most effective oral agent as monotherapy for Japanese young persons with type 2 diabetes, because most of them are obese with insulin resistance.	Metformin	0-9	insulin	Homo sapiens	160-167
15513975-1	2005	BACKGROUND: The aim of this study was to evaluate the effects of metformin and acarbose on insulin resistance, hormone profiles and ovulation rates in patients with clomiphene citrate-resistant polycystic ovary syndrome (PCOS).	Metformin	65-74	insulin	Homo sapiens	91-98
15642799-1	2005	To investigate whether the long-term administration of metformin or pioglitazone to women with polycystic ovary syndrome (PCOS) could induce changes in their hypothalamic dopaminergic (DA) tone and to analyze whether these changes correlated with modifications in insulin resistance, we originally studied 57 obese hyperinsulinemic, non-diabetic, insulin resistant women with PCOS, but only 34 completed the study.	Metformin	55-64	insulin	Homo sapiens	264-271
15722622-8	2005	The use of metformin, an insulin sensitizer, for affected adolescents is the topic of a presently heated debate.	Metformin	11-20	insulin	Homo sapiens	25-32
15702440-0	2005	Effects of a combination of rhGH and metformin on adiponectin levels in patients with metabolic syndrome.	Metformin	37-46	adiponectin, C1Q and collagen domain containing	Homo sapiens	50-61
15642799-1	2005	To investigate whether the long-term administration of metformin or pioglitazone to women with polycystic ovary syndrome (PCOS) could induce changes in their hypothalamic dopaminergic (DA) tone and to analyze whether these changes correlated with modifications in insulin resistance, we originally studied 57 obese hyperinsulinemic, non-diabetic, insulin resistant women with PCOS, but only 34 completed the study.	Metformin	55-64	insulin	Homo sapiens	320-327
15642799-9	2005	The present results suggests that either pioglitazone or metformin administration was associated with a clear improvement in the endogenous hypothalamic DA tone, simultaneously with an amelioration of the insulin resistance status in these obese women with PCOS.	Metformin	57-66	insulin	Homo sapiens	205-212
16514819-0	2005	[Use of metformin (siofor) in patients with gout and insulin resistance (pilot 6-month results)].	Metformin	8-17	insulin	Homo sapiens	53-60
16116971-4	2005	After treatment for 6 months in the CPA+ metformin group, BMI and WHR were significantly decreased, while insulin sensitivity was significantly decreased as Compared with those before treatment.	Metformin	41-50	insulin	Homo sapiens	106-113
16116971-6	2005	Combined use of CPA and metformin could result in the reduction of serum androstenedione and increases of serum SHBG levels as compared with the CPA treatment alone.	Metformin	24-33	sex hormone binding globulin	Homo sapiens	112-116
16116971-7	2005	It was concluded that combined use of CPA and metformin could improve the insulin sensitivity, and further suppress the hyperandrogenism in non-obese women with PCOS.	Metformin	46-55	insulin	Homo sapiens	74-81
15606381-16	2005	CONCLUSIONS: In patients with type 2 diabetes treated with insulin, metformin treatment was associated with improvement of endothelial function, which was largely unrelated to changes in glycaemic control, but not with improvement of chronic, low-grade inflammation.	Metformin	68-77	insulin	Homo sapiens	59-66
15562389-0	2005	Metformin-diet benefits in women with polycystic ovary syndrome in the bottom and top quintiles for insulin resistance.	Metformin	0-9	insulin	Homo sapiens	100-107
15562389-4	2005	After 12 months on metformin-diet, weight fell by 7% in both insulin-resistant groups (P < .0001), insulin, IR, and insulin secretion fell in the top insulin-resistant group by 60%, 64%, and 39% (all P < .0001), with smaller reductions in the bottom insulin-resistant group of 18%, 13% (P > .05 for both), and 22% (P < .01), respectively.	Metformin	19-28	insulin	Homo sapiens	61-68
15562389-10	2005	Metformin-diet should benefit most women with PCOS, even those with normal serum insulin, without IR.	Metformin	0-9	insulin	Homo sapiens	81-88
16514819-0	2005	[Use of metformin (siofor) in patients with gout and insulin resistance (pilot 6-month results)].	Metformin	19-25	insulin	Homo sapiens	53-60
16514819-1	2005	AIM: To evaluate metformin efficacy and safety in patients with gout and insulin resistance (IR).	Metformin	17-26	insulin	Homo sapiens	73-80
16514819-6	2005	RESULTS: A 6-month metformin therapy significantly changed the levels of glucose, insulin, HDLP and LDLP cholesterol, uric acid, HOMA index.	Metformin	19-28	insulin	Homo sapiens	82-89
15887627-0	2004	Effects of metformin on glucagon-like peptide-1 levels in obese patients with and without Type 2 diabetes.	Metformin	11-20	glucagon	Homo sapiens	24-47
15561641-4	2004	The concept that insulin-resistance, coupled with oxidative stress, may be the underlying mechanism responsible for fat accumulation and disease progression points to insulin-sensitizing agents (metformin, thiazolidinediones) as the most promising drugs.	Metformin	195-204	insulin	Homo sapiens	17-24
15561641-4	2004	The concept that insulin-resistance, coupled with oxidative stress, may be the underlying mechanism responsible for fat accumulation and disease progression points to insulin-sensitizing agents (metformin, thiazolidinediones) as the most promising drugs.	Metformin	195-204	insulin	Homo sapiens	167-174
15579189-11	2004	Metformin treatment for 6 months in insulin-resistant PCOS women (n = 9) had no effect on plasma adiponectin (P = 0.59) despite significant loss of weight and fat mass and improvement in hyperandrogenaemia.	Metformin	0-9	insulin	Homo sapiens	36-43
15887627-1	2004	Metformin has been shown to increase glucagon-like peptide-1 (GLP-1) levels after an oral glucose load in obese non-diabetic subjects.	Metformin	0-9	glucagon	Homo sapiens	37-60
15887627-1	2004	Metformin has been shown to increase glucagon-like peptide-1 (GLP-1) levels after an oral glucose load in obese non-diabetic subjects.	Metformin	0-9	glucagon	Homo sapiens	62-67
15887627-3	2004	GLP-1 was measured before and after a 100 g glucose load at baseline, after a single oral dose of 850 mg of metformin, and after 4 weeks of treatment with metformin 850 mg three times daily.	Metformin	108-117	glucagon	Homo sapiens	0-5
15887627-7	2004	In conclusion, GLP-1 levels after an oral glucose load in obese type 2 diabetic patients were increased by 4 weeks of metformin treatment in a similar fashion as in obese subjects with normal glucose tolerance.	Metformin	118-127	glucagon	Homo sapiens	15-20
15578517-6	2004	Moreover, activation of AMPK by metformin or AICAR largely blocked the ability of ethanol to increase levels of mature SREBP-1 protein.	Metformin	32-41	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	24-28
15388683-1	2004	Women with polycystic ovary syndrome (PCOS) are increasingly being treated with metformin as an insulin sensitizing agent to reduce symptoms of hyperandrogenism and promote fertility.	Metformin	80-89	insulin	Homo sapiens	96-103
15598336-18	2004	Several pharmacological agents have been used including ursodeoxycholic acid, vitamin E, betaine, n-acetyl cysteine, and insulin sensitizing agents like metformin, rosiglitazone, and pioglitazone.	Metformin	153-162	insulin	Homo sapiens	121-128
15569129-10	2004	RESULTS: Rosiglitazone increased insulin-stimulated myocardial glucose uptake by 38% (from 38.7 +/- 3.4 to 53.3 +/- 3.6 micromol 100 g(-1) min(-1), P = 0.004) and whole body glucose uptake by 36% (P = 0.01), while metformin treatment had no significant effect on myocardial (40.5 +/- 3.5 vs. 36.6 +/- 5.2, NS) or whole body glucose uptake.	Metformin	214-223	insulin	Homo sapiens	33-40
15519498-1	2004	Metformin improves insulin sensitivity, which is correlated to phospholipid fatty acid composition in obese type 2 diabetics.	Metformin	0-9	insulin	Homo sapiens	19-26
15531508-5	2004	Twenty-four-hour incubation of T2D islets with metformin was associated with increased insulin content, increased number and density of mature insulin granules, improved glucose-induced insulin release, and increased insulin mRNA expression.	Metformin	47-56	insulin	Homo sapiens	87-94
15371448-0	2004	AMP-activated protein kinase is required for the lipid-lowering effect of metformin in insulin-resistant human HepG2 cells.	Metformin	74-83	insulin	Homo sapiens	87-94
15371448-13	2004	Metformin lowers hepatic lipid content by activating AMPK, thereby mediating beneficial effects in hyperglycemia and insulin resistance.	Metformin	0-9	insulin	Homo sapiens	117-124
15517078-10	2004	The luteal progesterone level may be enhanced in PCOS by decreasing insulin secretion with metformin.	Metformin	91-100	insulin	Homo sapiens	68-75
15531508-5	2004	Twenty-four-hour incubation of T2D islets with metformin was associated with increased insulin content, increased number and density of mature insulin granules, improved glucose-induced insulin release, and increased insulin mRNA expression.	Metformin	47-56	insulin	Homo sapiens	143-150
15531508-5	2004	Twenty-four-hour incubation of T2D islets with metformin was associated with increased insulin content, increased number and density of mature insulin granules, improved glucose-induced insulin release, and increased insulin mRNA expression.	Metformin	47-56	insulin	Homo sapiens	143-150
15531508-5	2004	Twenty-four-hour incubation of T2D islets with metformin was associated with increased insulin content, increased number and density of mature insulin granules, improved glucose-induced insulin release, and increased insulin mRNA expression.	Metformin	47-56	insulin	Homo sapiens	143-150
15265871-9	2004	In addition, metformin significantly increased the co-immunoprecipitation of AMPK and its upstream kinase, LKB1, in C57BL6 mice administered to metformin in vivo.	Metformin	13-22	serine/threonine kinase 11	Mus musculus	107-111
15495054-18	2004	Combination therapy with bedtime NPH insulin resulted in statistically significantly less weight gain compared to insulin monotherapy, provided metformin was used +/-sulphonylurea.	Metformin	144-153	insulin	Homo sapiens	37-44
15495054-20	2004	REVIEWERS" CONCLUSIONS: Bedtime NPH insulin combined with oral hypoglycaemic agents provides comparable glycaemic control to insulin monotherapy and is associated with less weight gain if metformin is used.	Metformin	188-197	insulin	Homo sapiens	36-43
15265871-9	2004	In addition, metformin significantly increased the co-immunoprecipitation of AMPK and its upstream kinase, LKB1, in C57BL6 mice administered to metformin in vivo.	Metformin	144-153	serine/threonine kinase 11	Mus musculus	107-111
15482765-8	2004	RESULT(S): Frequencies of ovulation were higher after treatment with an insulin-sensitizing drug (ovulations per subject in 6 months: metformin, 3.3; rosiglitazone, 2.4; and combination, 3.4) than with placebo (0.4).	Metformin	134-143	insulin	Homo sapiens	72-79
15175014-7	2004	Finally, metformin impaired the t-butyl hydroperoxide-induced cell death, as judged by Trypan Blue exclusion, propidium iodide staining and cytochrome c release.	Metformin	9-18	cytochrome c, somatic	Homo sapiens	140-152
15469778-4	2004	Combining an insulin secretagogue (ie, sulfonylurea or meglitinide) and an insulin sensitizer (ie, metformin or a glitazone) capitalizes on unique mechanisms of action and results in significant A1C lowering (SOR: C).	Metformin	99-108	insulin	Homo sapiens	75-82
15697072-9	2004	Body weight, free testosterone, insulin and insulin resistance levels decreased significantly after metformin therapy.	Metformin	100-109	insulin	Homo sapiens	32-39
15372361-5	2004	Metformin treatment significantly reduced their body weights (p < 0.01), body mass index (BMI) (p < 0.01), the levels of HbA1c (p < 0.001), fasting blood glucose (FBG) (p < 0.05), serum insulin (p < 0.05), C-peptide (p < 0.01), triglyceride (p < 0.01), and total cholesterol (p < 0.05).	Metformin	0-9	insulin	Homo sapiens	198-205
15697072-3	2004	This study was designed to evaluate the effects of metformin and flutamide on metabolic parameters and insulin resistance in non-obese women with PCOS.	Metformin	51-60	insulin	Homo sapiens	103-110
15697072-9	2004	Body weight, free testosterone, insulin and insulin resistance levels decreased significantly after metformin therapy.	Metformin	100-109	insulin	Homo sapiens	44-51
15697073-5	2004	The mean IGF-I levels decreased significantly on metformin therapy.	Metformin	49-58	insulin like growth factor 1	Homo sapiens	9-14
15697073-7	2004	Only the change in serum levels of progesterone and IGF-I on metformin were statistically significant between responders and non-responders; metformin-induced decremental change in IGF-I levels were greater in responders.	Metformin	61-70	insulin like growth factor 1	Homo sapiens	52-57
15697073-7	2004	Only the change in serum levels of progesterone and IGF-I on metformin were statistically significant between responders and non-responders; metformin-induced decremental change in IGF-I levels were greater in responders.	Metformin	141-150	insulin like growth factor 1	Homo sapiens	181-186
15697073-9	2004	By decreasing insulin and IGF-I levels, metformin therapy offers additional beneficial effects in resumption of regular menses.	Metformin	40-49	insulin	Homo sapiens	14-21
15697073-9	2004	By decreasing insulin and IGF-I levels, metformin therapy offers additional beneficial effects in resumption of regular menses.	Metformin	40-49	insulin like growth factor 1	Homo sapiens	26-31
15697073-10	2004	Thus, in PCOS patients with elevated levels of IGF-I, metformin may be considered as an appropriate agent to be used for the regulation of menstrual cycles.	Metformin	54-63	insulin like growth factor 1	Homo sapiens	47-52
15356029-2	2004	Recently, we disclosed the efficacy of insulin sensitization with metformin to disrupt progression from PP to PCOS in formerly LBW girls who were postmenarche.	Metformin	66-75	insulin	Homo sapiens	39-46
15356029-7	2004	In the prepubertal study (group A), comparisons of untreated vs. treated girls disclosed normalizing effects of metformin on SHBG, androstenedione, dehydroepiandrosterone sulfate, low and high density lipoprotein cholesterol, triglycerides, IL-6, adiponectin, total and abdominal fat mass, and lean body mass.	Metformin	112-121	sex hormone binding globulin	Homo sapiens	125-129
15529521-0	2004	Avandamet: combined metformin-rosiglitazone treatment for insulin resistance in type 2 diabetes.	Metformin	20-29	insulin	Homo sapiens	58-65
15647716-5	2004	Therefore, agents that improve beta-cell function (such as sulfonylureas and meglitinides) and insulin sensitizers (such as metformin and thiazolidinediones) both are useful alone or in combination for treating type 2 diabetes.	Metformin	124-133	insulin	Homo sapiens	95-102
15529521-2	2004	Metformin (a biguanide) and rosiglitazone (a thiazolidinedione) counter insulin resistance, acting by different cellular mechanisms.	Metformin	0-9	insulin	Homo sapiens	72-79
15647714-3	2004	Metformin has been joined by thiazolidinediones to reduce insulin resistance.	Metformin	0-9	insulin	Homo sapiens	58-65
15262344-6	2004	Metformin, as insulin-sensitizing drug, is being evaluated for its potential long-term disease-modifying effect, such as prevention of diabetes.	Metformin	0-9	insulin	Homo sapiens	14-21
15159410-8	2004	Metformin and 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside were used to activate AMPK in neonatal rat cardiac myocytes.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	91-95
15242807-0	2004	Metformin-induced stimulation of AMP-activated protein kinase in beta-cells impairs their glucose responsiveness and can lead to apoptosis.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	33-61
15242807-3	2004	The present study demonstrates that metformin (0.5-2mM) also dose-dependently activates AMPK in insulin-producing MIN6 cells and in primary rat beta-cells, leading to increased phosphorylation of acetyl coA carboxylase (ACC).	Metformin	36-45	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	88-92
15242807-5	2004	After 24h exposure to metformin (0.5-1mM), rat beta-cells exhibited a reduced secretory and synthetic responsiveness to 10mM glucose, which was also the case following 24h culture with the AMPK-activator 5-amino-imidazole-4-carboxamide riboside (AICAR; 1mM).	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	189-193
15242807-6	2004	Longer metformin exposure (>24h) resulted in a progressive increase in apoptotic beta-cells as was also reported for AICAR; metformin-induced apoptosis was reduced by compound C, an AMPK-inhibitor.	Metformin	7-16	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	185-189
15242807-6	2004	Longer metformin exposure (>24h) resulted in a progressive increase in apoptotic beta-cells as was also reported for AICAR; metformin-induced apoptosis was reduced by compound C, an AMPK-inhibitor.	Metformin	127-136	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	185-189
15242807-8	2004	It is concluded that metformin-induced AMPK-activation in beta-cells reduces their glucose responsiveness and may, following sustained exposure, result in apoptosis.	Metformin	21-30	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	39-43
15211369-2	2004	We aimed to compare the effect of orlistat and orlistat plus metformin combination therapy on weight loss and insulin resistance in obese women.	Metformin	61-70	insulin	Homo sapiens	110-117
15475228-4	2004	Despite its use for a number of years, metformin"s role as an insulin sensitizer has only recently been appreciated.	Metformin	39-48	insulin	Homo sapiens	62-69
15625771-3	2004	Therefore this review aims to discuss the current evidence on the use of metformin, a commonly used insulin-sensitizing agent, in treating both the short-term and the long-term problems of women with PCOS.	Metformin	73-82	insulin	Homo sapiens	100-107
15165912-2	2004	Metformin, an insulin sensitizer, may decrease the occurrence of these outcomes.	Metformin	0-9	insulin	Homo sapiens	14-21
15239026-1	2004	The effects of a combination of repaglinide and metformin on the insulin secretion pattern and insulin sensitivity were studied in a fixed-dose, open-label, placebo-controlled cross-over study.	Metformin	48-57	insulin	Homo sapiens	65-72
15239026-7	2004	The insulin sensitivity index (ISI) was increased by 35 % after 1 week of combination therapy with repaglinide plus metformin (1.11 +/- 0.03 x 10 (2) vs. 0.83 +/- 0.21 x 10 (2) mg x kg (-1) body weight x min (-1) x pmol (-1) x l, respectively; p = 0.033).	Metformin	116-125	insulin	Homo sapiens	4-11
14871885-0	2004	Metformin, but not leptin, regulates AMP-activated protein kinase in pancreatic islets: impact on glucose-stimulated insulin secretion.	Metformin	0-9	insulin	Homo sapiens	117-124
14871885-6	2004	Incubation with metformin (0.2-1 mM) activated AMPK in both human islets and MIN6 beta-cells in parallel with an inhibition of insulin secretion, whereas leptin (10-100 nM) was without effect in MIN6 cells.	Metformin	16-25	insulin	Homo sapiens	127-134
14871885-8	2004	The inhibitory effects of metformin on insulin secretion may therefore need to be considered with respect to the use of this drug for the treatment of type 2 diabetes.	Metformin	26-35	insulin	Homo sapiens	39-46
15247056-8	2004	Drugs that inhibit glycolysis (2-deoxyglucose) or enhance insulin action (metformin) are being assessed as CR mimetics.	Metformin	74-83	insulin	Homo sapiens	58-65
15163284-6	2004	Improvement of insulin sensitivity can be obtained with metformin and thiazolidinediones.	Metformin	56-65	insulin	Homo sapiens	15-22
15129054-1	2004	PURPOSE OF REVIEW: The use of insulin sensitizing drugs such as metformin in polycystic ovary syndrome has been increasingly popular and validated by systematic reviews.	Metformin	64-73	insulin	Homo sapiens	30-37
15645955-12	2004	Insulin resistance decreased significantly with metformin and pioglitazone, beta cell fuhction also showed improvement CONCLUSIONS: Glycaemic control was seen in all study groups, the improvement was better in drug treated groups than in the control group.	Metformin	48-57	insulin	Homo sapiens	0-7
15334791-10	2004	Metformin significantly lowered fasting plasma insulin and postprandial plasma insulin.	Metformin	0-9	insulin	Homo sapiens	47-54
15334791-10	2004	Metformin significantly lowered fasting plasma insulin and postprandial plasma insulin.	Metformin	0-9	insulin	Homo sapiens	79-86
15645955-14	2004	Metformin and pioglitazone had beneficial effects on lipid levels, improved insulin sensitivity and improved insulin secretion also.	Metformin	0-9	insulin	Homo sapiens	76-83
15645955-14	2004	Metformin and pioglitazone had beneficial effects on lipid levels, improved insulin sensitivity and improved insulin secretion also.	Metformin	0-9	insulin	Homo sapiens	109-116
15136950-15	2004	CONCLUSION: Metformin improves significantly hyperandrogenism and insulin resistance in PCOS patients and appears to be an efficacious mode of therapy.	Metformin	12-21	insulin	Homo sapiens	66-73
15115425-5	2004	In some circumstances (eg, severe insulin resistance), metformin therapy during pregnancy may be warranted.	Metformin	55-64	insulin	Homo sapiens	34-41
15140339-0	2004	Pioglitazone as monotherapy or in combination with sulfonylurea or metformin enhances insulin sensitivity (HOMA-S or QUICKI) in patients with type 2 diabetes.	Metformin	67-76	insulin	Homo sapiens	86-93
15140339-5	2004	STUDY AIM: To evaluate the effect of PIO monotherapy and in combination therapy with sulfonylurea (SU) or metformin (MET) on insulin sensitivity as assessed by HOMA-S and QUICKI in a large group of patients (approximately 1000).	Metformin	106-115	insulin	Homo sapiens	125-132
15063962-10	2004	CONCLUSIONS: The present study shows that metformin therapy not only restores normal levels of insulin and testosterone, but also decreases the pool of free-bioactive IGF-I by increasing the levels of circulating IGFBP-1.	Metformin	42-51	insulin	Homo sapiens	95-102
15125825-13	2004	CONCLUSIONS: Bedtime NPH insulin added to maximal therapy with sulfonylurea and metformin is an effective, simple, well-tolerated approach for patients with uncontrolled type 2 diabetes.	Metformin	80-89	insulin	Homo sapiens	25-32
15063962-10	2004	CONCLUSIONS: The present study shows that metformin therapy not only restores normal levels of insulin and testosterone, but also decreases the pool of free-bioactive IGF-I by increasing the levels of circulating IGFBP-1.	Metformin	42-51	insulin like growth factor 1	Homo sapiens	167-172
15063962-0	2004	Metformin therapy increases insulin-like growth factor binding protein-1 in hyperinsulinemic women with polycystic ovary syndrome.	Metformin	0-9	insulin	Homo sapiens	28-35
15063962-2	2004	This study was designed to evaluate effects of metformin therapy on serum levels of IGFBP-1 and IGF-I.	Metformin	47-56	insulin like growth factor 1	Homo sapiens	96-101
15063963-12	2004	RESULTS: Serum androgens and insulin response to OGTT decreased significantly after metformin therapy.	Metformin	84-93	insulin	Homo sapiens	29-36
15063962-8	2004	Metformin treatment also significantly decreased testosterone (by 37%, P = 0.0001) and increased SHBG concentration (by 16%, P = 0.04).	Metformin	0-9	sex hormone binding globulin	Homo sapiens	97-101
15063963-16	2004	CONCLUSION(S): Metformin improves insulin resistance and reduces androgen levels.	Metformin	15-24	insulin	Homo sapiens	34-41
15235215-5	2004	Treatment with insulin sensitizers, metformin and thiazolidinediones, improve both metabolic and hormonal patterns and also improve ovulation in PCOS.	Metformin	36-45	insulin	Homo sapiens	15-22
15080783-10	2004	Metformin treatment of 9 obese, insulin-resistant PCOS patients over a period of 6 months caused a significant decrease in body weight, body fat mass and total testosterone, but showed no significant decline in IL-6 or CRP concentrations.	Metformin	0-9	insulin	Homo sapiens	32-39
15149568-6	2004	Of the available insulin-sensitizing agents, metformin has been the agent most frequently studied in PCOS, and has the least undesirable pregnancy safety profile.	Metformin	45-54	insulin	Homo sapiens	17-24
15149568-7	2004	Ameliorating the metabolic syndrome associated with insulin resistance in PCOS with metformin may also prevent long-term cardiovascular and diabetes complications, pending further evidence.	Metformin	84-93	insulin	Homo sapiens	52-59
15019860-2	2004	However, the emphasis on initial therapy has been shifting from secretagogues and alpha-glucosidase inhibitors to insulin sensitizers such as metformin and the thiazolidinediones (TZDs).	Metformin	142-151	insulin	Homo sapiens	114-121
14987322-2	2004	AIM: To investigate the therapeutic effect of metformin, a well-known insulin-sensitizing agent, in the treatment of non-alcoholic steatohepatitis.	Metformin	46-55	insulin	Homo sapiens	70-77
14987322-7	2004	RESULTS: The mean serum alanine/aspartate aminotransferase, insulin and C-peptide levels decreased and the index of insulin resistance improved significantly from baseline in the group given metformin.	Metformin	191-200	insulin	Homo sapiens	60-67
14987322-7	2004	RESULTS: The mean serum alanine/aspartate aminotransferase, insulin and C-peptide levels decreased and the index of insulin resistance improved significantly from baseline in the group given metformin.	Metformin	191-200	insulin	Homo sapiens	116-123
14987322-10	2004	CONCLUSION: The data suggest that improvement of the insulin sensitivity with metformin may improve the liver disease in patients with non-alcoholic steatohepatitis.	Metformin	78-87	insulin	Homo sapiens	53-60
15001195-2	2004	Metformin improves insulin action and lower plasma FFA concentrations.	Metformin	0-9	insulin	Homo sapiens	19-26
15001195-7	2004	RESULTS: Metformin treatment, but not placebo treatment, was associated with a decrease in fasting plasma glucose (P <.05), insulin (P <.05), triglyceride (P <.05), and FFA (P <.03) concentrations and HOMA index (P <.03).	Metformin	9-18	insulin	Homo sapiens	127-134
15032652-0	2004	Insulin resistance as a therapeutic target for improved endothelial function: metformin.	Metformin	78-87	insulin	Homo sapiens	0-7
15032652-6	2004	Metformin has beneficial effects on endothelial function which appear to be mediated through its effects to improve insulin resistance.	Metformin	0-9	insulin	Homo sapiens	116-123
15641325-8	2004	Insulin secretagogues increase insulin levels, whereas insulin sensitizers, such as metformin and thiazolidinediones, decrease insulin resistance.	Metformin	84-93	insulin	Homo sapiens	55-62
15641325-8	2004	Insulin secretagogues increase insulin levels, whereas insulin sensitizers, such as metformin and thiazolidinediones, decrease insulin resistance.	Metformin	84-93	insulin	Homo sapiens	55-62
15046183-6	2004	Insulin resistance provides a target for specific treatment of non-alcoholic fatty liver, and insulin-sensitising agents (metformin or thiazolidinediones) as well as lifestyle changes to reduce visceral adiposity are the most promising therapeutic options.	Metformin	122-131	insulin	Homo sapiens	0-7
14998944-0	2004	Metformin during pregnancy reduces insulin, insulin resistance, insulin secretion, weight, testosterone and development of gestational diabetes: prospective longitudinal assessment of women with polycystic ovary syndrome from preconception throughout pregnancy.	Metformin	0-9	insulin	Homo sapiens	35-42
15032627-8	2004	This goal can be obtained with preventive measures, as physical activity, diet and drugs that can reduce insulin resistance (metformin and thiazolidinediones).	Metformin	125-134	insulin	Homo sapiens	105-112
14998944-0	2004	Metformin during pregnancy reduces insulin, insulin resistance, insulin secretion, weight, testosterone and development of gestational diabetes: prospective longitudinal assessment of women with polycystic ovary syndrome from preconception throughout pregnancy.	Metformin	0-9	insulin	Homo sapiens	44-51
14761669-4	2004	Results demonstrated that (1) Additive effect on insulin sensitization can be achieved by a combination of TZDs and metformin at lower concentration; (2) combination of TZDs and metformin act on insulin signaling molecules in insulin resistance; (3) in vitro system has the potentiality to determine possible target molecule(s) and mechanism of action of drugs.	Metformin	116-125	insulin	Homo sapiens	195-202
14761669-0	2004	Combination of metformin and thiazolidindiones restore insulin signalling in insulin-resistant cultured myotubes.	Metformin	15-24	insulin	Homo sapiens	55-62
14761669-0	2004	Combination of metformin and thiazolidindiones restore insulin signalling in insulin-resistant cultured myotubes.	Metformin	15-24	insulin	Homo sapiens	77-84
14761669-4	2004	Results demonstrated that (1) Additive effect on insulin sensitization can be achieved by a combination of TZDs and metformin at lower concentration; (2) combination of TZDs and metformin act on insulin signaling molecules in insulin resistance; (3) in vitro system has the potentiality to determine possible target molecule(s) and mechanism of action of drugs.	Metformin	116-125	insulin	Homo sapiens	195-202
14761669-1	2004	We examined the effect of combination of thiazolidinediones (TZDs) and metformin on insulin-resistant skeletal muscle cells.	Metformin	71-80	insulin	Homo sapiens	84-91
14761669-4	2004	Results demonstrated that (1) Additive effect on insulin sensitization can be achieved by a combination of TZDs and metformin at lower concentration; (2) combination of TZDs and metformin act on insulin signaling molecules in insulin resistance; (3) in vitro system has the potentiality to determine possible target molecule(s) and mechanism of action of drugs.	Metformin	178-187	insulin	Homo sapiens	49-56
14761669-2	2004	The combined use of TZDs and metformin resulted in maximum tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) at 12.5 microM of TZDs and 100 microM of metformin as compared to the maximum tyrosine phosphorylation of IR and IRS-1 achieved at 50 microM of TZDs or 400 microM of metformin.	Metformin	29-38	insulin	Homo sapiens	87-94
14761669-2	2004	The combined use of TZDs and metformin resulted in maximum tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) at 12.5 microM of TZDs and 100 microM of metformin as compared to the maximum tyrosine phosphorylation of IR and IRS-1 achieved at 50 microM of TZDs or 400 microM of metformin.	Metformin	29-38	insulin	Homo sapiens	113-120
14761669-4	2004	Results demonstrated that (1) Additive effect on insulin sensitization can be achieved by a combination of TZDs and metformin at lower concentration; (2) combination of TZDs and metformin act on insulin signaling molecules in insulin resistance; (3) in vitro system has the potentiality to determine possible target molecule(s) and mechanism of action of drugs.	Metformin	178-187	insulin	Homo sapiens	195-202
14761669-2	2004	The combined use of TZDs and metformin resulted in maximum tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) at 12.5 microM of TZDs and 100 microM of metformin as compared to the maximum tyrosine phosphorylation of IR and IRS-1 achieved at 50 microM of TZDs or 400 microM of metformin.	Metformin	191-200	insulin	Homo sapiens	87-94
14761669-4	2004	Results demonstrated that (1) Additive effect on insulin sensitization can be achieved by a combination of TZDs and metformin at lower concentration; (2) combination of TZDs and metformin act on insulin signaling molecules in insulin resistance; (3) in vitro system has the potentiality to determine possible target molecule(s) and mechanism of action of drugs.	Metformin	178-187	insulin	Homo sapiens	195-202
14761669-2	2004	The combined use of TZDs and metformin resulted in maximum tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) at 12.5 microM of TZDs and 100 microM of metformin as compared to the maximum tyrosine phosphorylation of IR and IRS-1 achieved at 50 microM of TZDs or 400 microM of metformin.	Metformin	191-200	insulin	Homo sapiens	87-94
14761669-4	2004	Results demonstrated that (1) Additive effect on insulin sensitization can be achieved by a combination of TZDs and metformin at lower concentration; (2) combination of TZDs and metformin act on insulin signaling molecules in insulin resistance; (3) in vitro system has the potentiality to determine possible target molecule(s) and mechanism of action of drugs.	Metformin	116-125	insulin	Homo sapiens	49-56
15090799-7	2004	Fasting insulin and insulin area under the curve decreased significantly more in the exercise and metformin group (P < 0.05).	Metformin	98-107	insulin	Homo sapiens	8-15
15090799-7	2004	Fasting insulin and insulin area under the curve decreased significantly more in the exercise and metformin group (P < 0.05).	Metformin	98-107	insulin	Homo sapiens	20-27
14725687-2	2004	Weight loss is beneficial, but the additional administration of insulin-lowering drugs, such as metformin, and antiandrogens may produce further benefits, due to their different spectrum of action.	Metformin	96-105	insulin	Homo sapiens	64-71
14748678-5	2004	Lifestyle changes as recommended in diabetes are fundamental for treatment; addition of insulin-sensitising agents (eg, metformin) may be valuable in circumstances such as anovulatory infertility.	Metformin	120-129	insulin	Homo sapiens	88-95
14984444-13	2004	It is possible that improving insulin sensitivity with diet, exercise and drugs such as metformin may reduce the risk of diabetes in individuals at high risk, such as women with polycystic ovary syndrome, impaired glucose tolerance, and a history of GDM.	Metformin	88-97	insulin	Homo sapiens	30-37
14764283-5	2004	Metformin is the most extensively studied insulin-sensitizing agent for the treatment of women with PCOS.	Metformin	0-9	insulin	Homo sapiens	42-49
14764283-6	2004	Use of metformin leads to a decrease in serum insulin and androgen levels, as well as an improvement in ovulatory function.	Metformin	7-16	insulin	Homo sapiens	46-53
14967373-9	2004	RESULT(S): In the metformin group of nonobese patients, the mean fasting serum insulin concentration decreased from a pretreatment value of 12.1 +/- 2.4 to 6.3 +/- 0.6 microU/mL after treatment, and the area under the curve of insulin decreased from 5,189.1 +/- 517.4 to 3,035.6 +/- 208.9 microU/mL per minute.	Metformin	18-27	insulin	Homo sapiens	79-86
14967373-9	2004	RESULT(S): In the metformin group of nonobese patients, the mean fasting serum insulin concentration decreased from a pretreatment value of 12.1 +/- 2.4 to 6.3 +/- 0.6 microU/mL after treatment, and the area under the curve of insulin decreased from 5,189.1 +/- 517.4 to 3,035.6 +/- 208.9 microU/mL per minute.	Metformin	18-27	insulin	Homo sapiens	227-234
15209435-21	2004	Metformin, a biguanide oral antidiabetic agent, was shown to affect insulin resistance by decreasing enzymatic activity of overexpressed PC-1 molecules in obese type 2 diabetics.	Metformin	0-9	insulin	Homo sapiens	68-75
14752300-1	2004	Metformin is a common treatment for women who have insulin resistance manifesting as type 2 diabetes or polycystic ovarian syndrome (PCOS).	Metformin	0-9	insulin	Homo sapiens	51-58
15209435-21	2004	Metformin, a biguanide oral antidiabetic agent, was shown to affect insulin resistance by decreasing enzymatic activity of overexpressed PC-1 molecules in obese type 2 diabetics.	Metformin	0-9	ectonucleotide pyrophosphatase/phosphodiesterase 1	Homo sapiens	137-141
14686957-0	2004	Effects of short-term metformin treatment on insulin sensitivity of blood glucose and free fatty acids.	Metformin	22-31	insulin	Homo sapiens	45-52
14693980-6	2004	Fasting insulin levels were also reduced (pioglitazone arm -1.3 micro IU/ml; metformin arm -0.8 micro IU/ml).	Metformin	77-86	insulin	Homo sapiens	8-15
14686957-1	2004	AIM: Based on the known effect of metformin (MET) in improving insulin sensitivity in type 2 diabetes, with the scope to focus the effects on glycaemic and free fatty acids (FFA) levels, we studied the effects of a short-term treatment with this drug in obese subjects and obese patients with diabetes or family history of diabetes (FHD).	Metformin	34-43	insulin	Homo sapiens	63-70
14979733-8	2004	Studies aimed at reversing insulin resistance have identified weight loss, exercise and pharmacological treatment with metformin, thiazolidinediones, HMG-CoA reductase inhibitors (statins) and ACE inhibitors as potential therapies to prevent the development of type 2 diabetes.	Metformin	119-128	insulin	Homo sapiens	27-34
14715857-0	2004	Metformin therapy increases insulin-stimulated release of D-chiro-inositol-containing inositolphosphoglycan mediator in women with polycystic ovary syndrome.	Metformin	0-9	insulin	Homo sapiens	28-35
15200348-12	2004	Metformin and thiazolidinediones affect insulin sensitivity by independent mechanisms.	Metformin	0-9	insulin	Homo sapiens	40-47
15200348-16	2004	Sulphonylureas are particularly beneficial when combined with agents such as metformin that decrease insulin resistance.	Metformin	77-86	insulin	Homo sapiens	101-108
15106708-2	2004	Insulin-sensitizing drugs like metformin may have a role in the treatment of this disease.	Metformin	31-40	insulin	Homo sapiens	0-7
14715857-4	2004	After treatment, the mean (+/-SE) area under the curve (AUC) during the oral glucose tolerance test of insulin (AUC(insulin)) decreased significantly more in the metformin group, compared with the placebo group [-3574 +/- 962 vs. +1367 +/- 1021 micro IU/min.ml (-26 +/- 7 vs. +10 +/- 7 nmol/min.liter), P = 0.003], but the AUC of DCI-IPG (AUC(DCI-IPG)) decreased similarly in both groups (-1452 +/- 968 vs. -2207 +/- 1021%/min, P = 0.60).	Metformin	162-171	insulin	Homo sapiens	103-110
14715857-4	2004	After treatment, the mean (+/-SE) area under the curve (AUC) during the oral glucose tolerance test of insulin (AUC(insulin)) decreased significantly more in the metformin group, compared with the placebo group [-3574 +/- 962 vs. +1367 +/- 1021 micro IU/min.ml (-26 +/- 7 vs. +10 +/- 7 nmol/min.liter), P = 0.003], but the AUC of DCI-IPG (AUC(DCI-IPG)) decreased similarly in both groups (-1452 +/- 968 vs. -2207 +/- 1021%/min, P = 0.60).	Metformin	162-171	insulin	Homo sapiens	116-123
14715857-2	2004	Furthermore, similar effects of DCI and metformin, an insulin-sensitizing drug, have been demonstrated in PCOS women.	Metformin	40-49	insulin	Homo sapiens	54-61
14715857-5	2004	However, the ratio of AUC(DCI-IPG)/AUC(insulin) increased by 160% after metformin and decreased by 29% after placebo (P = 0.002 between groups).	Metformin	72-81	insulin	Homo sapiens	39-46
14715857-6	2004	Moreover, metformin seemed to improve the positive correlation between AUC(DCI-IPG) and AUC(insulin) but not placebo (r = 0.32, P = 0.68 at baseline; r = 0.52, P = 0.12 after metformin; and r = -0.39, P = 0.30 after placebo).	Metformin	10-19	insulin	Homo sapiens	92-99
14715857-6	2004	Moreover, metformin seemed to improve the positive correlation between AUC(DCI-IPG) and AUC(insulin) but not placebo (r = 0.32, P = 0.68 at baseline; r = 0.52, P = 0.12 after metformin; and r = -0.39, P = 0.30 after placebo).	Metformin	175-184	insulin	Homo sapiens	92-99
14715857-3	2004	To determine whether metformin improves insulin actions by increasing biologically active DCI-IPG in women with PCOS, we analyzed DCI-IPG during an oral glucose tolerance test in 19 obese women with PCOS before and after 4-8 wk of metformin or placebo.	Metformin	21-30	insulin	Homo sapiens	40-47
14715857-7	2004	We conclude that in obese women with PCOS, metformin may improve the action of insulin in part by improving insulin-mediated release of DCI-IPG mediators, as evidenced by increased bioactive DCI-IPG released per unit of insulin.	Metformin	43-52	insulin	Homo sapiens	79-86
14715857-7	2004	We conclude that in obese women with PCOS, metformin may improve the action of insulin in part by improving insulin-mediated release of DCI-IPG mediators, as evidenced by increased bioactive DCI-IPG released per unit of insulin.	Metformin	43-52	insulin	Homo sapiens	108-115
14715857-7	2004	We conclude that in obese women with PCOS, metformin may improve the action of insulin in part by improving insulin-mediated release of DCI-IPG mediators, as evidenced by increased bioactive DCI-IPG released per unit of insulin.	Metformin	43-52	insulin	Homo sapiens	108-115
15236798-3	2004	Strategies for decreasing elevated CRP include administration of statins, thiazolidinediones, and metformin; moderate alcohol consumption and appropriate weight loss are also helpful in this regard.	Metformin	98-107	C-reactive protein	Homo sapiens	35-38
15236798-6	2004	Thus, it is proposed that metformin--or AMPK---inhibits hepatic CRP production by boosting hepatic nitric oxide synthesis, which in turn impedes Stat3 activation and CRP transcription.	Metformin	26-35	C-reactive protein	Homo sapiens	64-67
15236798-6	2004	Thus, it is proposed that metformin--or AMPK---inhibits hepatic CRP production by boosting hepatic nitric oxide synthesis, which in turn impedes Stat3 activation and CRP transcription.	Metformin	26-35	signal transducer and activator of transcription 3	Homo sapiens	145-150
15236798-6	2004	Thus, it is proposed that metformin--or AMPK---inhibits hepatic CRP production by boosting hepatic nitric oxide synthesis, which in turn impedes Stat3 activation and CRP transcription.	Metformin	26-35	C-reactive protein	Homo sapiens	166-169
15330682-3	2004	A decrease in fasting plasma insulin, a marker of insulin resistance, was seen with metformin XT but not with immediate-release (IR) metformin in one well designed trial, but changes were similar in another.	Metformin	84-93	insulin	Homo sapiens	29-36
15330682-3	2004	A decrease in fasting plasma insulin, a marker of insulin resistance, was seen with metformin XT but not with immediate-release (IR) metformin in one well designed trial, but changes were similar in another.	Metformin	84-93	insulin	Homo sapiens	50-57
14633764-4	2003	However, what is less well appreciated is the role that the COX 2 inhibitors may play in the development of renal failure which, when it occurs in a patient on metformin, can lead to a potentially disastrous outcome.	Metformin	160-169	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	60-65
15696851-11	2004	Weight loss, metformin or thiazolidinediones can improve NAFLD by increasing insulin sensitivity.	Metformin	13-22	insulin	Homo sapiens	77-84
15260389-0	2003	Beneficial effects of triple drug combination of pioglitazone with glibenclamide and metformin in type 2 diabetes mellitus patients on insulin therapy.	Metformin	85-94	insulin	Homo sapiens	135-142
14749143-11	2003	Because patients with type 2 diabetes often have excess hepatic glucose output, use of metformin is effective in lowering glycosylated hemoglobin (HbA1c) by 1 to 2 percentage points when used as monotherapy or in combination with other blood glucose-lowering agents or insulin.	Metformin	87-96	insulin	Homo sapiens	269-276
14644809-10	2003	Although initial studies suggest that Metformin may be particularly useful for treating the PCOS adolescent with insulin resistance and obesity, additional studies are needed to determine the efficacy and long-term outcome.	Metformin	38-47	insulin	Homo sapiens	113-120
14644838-6	2003	The experiences with insulin-sensitizing drugs, especially metformin, are reviewed; while their beneficial role as an adjuvant to treatment of ovulatory infertility has been well established, the effects of a long-term treatment, especially in very young patients, are still under debate.	Metformin	59-68	insulin	Homo sapiens	21-28
15260389-12	2003	CONCLUSIONS: With proper patient selection, pioglitazone with glibenclamide and metformin can be safely used in patients receiving insulin with good results.	Metformin	80-89	insulin	Homo sapiens	131-138
14535967-0	2003	Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial.	Metformin	37-46	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	107-110
14535967-3	2003	We investigated whether 16 weeks of treatment with metformin affects serum concentrations of homocysteine, folate and vitamin B12 in subjects with type 2 diabetes treated with insulin.	Metformin	51-60	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	126-129
14535967-2	2003	However, metformin may decrease vitamin B12 levels and increase levels of homocysteine, a cardiovascular risk factor.	Metformin	9-18	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	40-43
14535967-9	2003	INTERVENTION: Addition of metformin or placebo to insulin therapy.	Metformin	26-35	insulin	Homo sapiens	50-57
14576245-9	2003	Metformin has an effect in reducing fasting insulin concentrations, blood pressure, and low density lipoprotein cholesterol.	Metformin	0-9	insulin	Homo sapiens	44-51
14535967-11	2003	RESULTS: Amongst those who completed 16 weeks of treatment, metformin use, as compared with placebo, was associated with an increase in homocysteine of 4% (0.2 to 8; P=0.039) and with decreases in folate [-7% (-1.4 to -13); P=0.024] and vitamin B12 [-14% (-4.2 to -24); P<0.0001].	Metformin	60-69	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	245-248
14535967-13	2003	CONCLUSION: In patients with type 2 diabetes, 16 weeks of treatment with metformin reduces levels of folate and vitamin B12, which results in a modest increase in homocysteine.	Metformin	73-82	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	120-123
15000437-0	2003	The combination metformin/glyburide exerts its hypoglycemic effect mainly by increasing insulin secretion: a controlled, randomized, double-blind, crossover study.	Metformin	16-25	insulin	Homo sapiens	88-95
12890675-8	2003	However, Akt-dependent depression of alpha-AMPK phosphorylation could be overcome in the presence of the AMPK activator, metformin, suggesting that an override mechanism exists that can restore AMPK activity.	Metformin	121-130	thymoma viral proto-oncogene 1	Mus musculus	9-12
15000437-11	2003	Increased insulin secretion was the explanation for the additive effects of the combination (percentual change in acute insulin response during the minimal model = 5.8 vs 51.5 vs 88.2% for metformin, glyburide and the combination, p < 0.05).	Metformin	189-198	insulin	Homo sapiens	10-17
15000437-13	2003	In conclusion, the additive hypoglycemic effects of the combination glyburide/metformin was caused by increased insulin secretion.	Metformin	78-87	insulin	Homo sapiens	112-119
14514347-2	2003	The aim of the present study was to investigate whether addition of metformin for 3 Months improves metabolic control and insulin sensitivity.	Metformin	68-77	insulin	Homo sapiens	122-129
14510863-7	2003	Compared with treatment on Metformin, there was an increase in insulin sensitivity (HOMA S% 17.2-31.6) but no change in glycaemic control.	Metformin	27-36	insulin	Homo sapiens	63-70
14514347-9	2003	Peripheral glucose uptake divided by mean plasma insulin concentration was increased in the metformin group (P<0.05) but not in the placebo group.	Metformin	92-101	insulin	Homo sapiens	49-56
14499793-8	2003	The potential mechanisms of the action of metformin were the inhibition of hepatic tumor necrosis factor (TNF)alpha and several TNF-inducible responses, which are likely to promote hepatic steatosis and necrosis.	Metformin	42-51	tumor necrosis factor	Mus musculus	83-104
14557435-0	2003	Metformin reduces serum C-reactive protein levels in women with polycystic ovary syndrome.	Metformin	0-9	C-reactive protein	Homo sapiens	24-42
14557435-2	2003	Because the insulin sensitizer metformin has been shown to improve metabolic disturbances in PCOS, it was of particular interest to examine serum CRP levels during metformin therapy.	Metformin	31-40	insulin	Homo sapiens	12-19
14557435-2	2003	Because the insulin sensitizer metformin has been shown to improve metabolic disturbances in PCOS, it was of particular interest to examine serum CRP levels during metformin therapy.	Metformin	164-173	C-reactive protein	Homo sapiens	146-149
14557435-5	2003	During metformin treatment, serum CRP levels decreased significantly from 3.08 +/- 0.7 mg/liter to 1.52 +/- 0.26 mg/liter at 6 months in the whole study population (P = 0.006) and especially in obese subjects.	Metformin	7-16	C-reactive protein	Homo sapiens	34-37
14557435-8	2003	The decrease of serum CRP levels during metformin therapy is in accordance with the known beneficial metabolic effects of this drug and suggests that CRP or other inflammation parameters could be used as markers of treatment efficiency in women with PCOS.	Metformin	40-49	C-reactive protein	Homo sapiens	22-25
14557435-8	2003	The decrease of serum CRP levels during metformin therapy is in accordance with the known beneficial metabolic effects of this drug and suggests that CRP or other inflammation parameters could be used as markers of treatment efficiency in women with PCOS.	Metformin	40-49	C-reactive protein	Homo sapiens	150-153
14499793-8	2003	The potential mechanisms of the action of metformin were the inhibition of hepatic tumor necrosis factor (TNF)alpha and several TNF-inducible responses, which are likely to promote hepatic steatosis and necrosis.	Metformin	42-51	tumor necrosis factor	Mus musculus	106-115
14499793-8	2003	The potential mechanisms of the action of metformin were the inhibition of hepatic tumor necrosis factor (TNF)alpha and several TNF-inducible responses, which are likely to promote hepatic steatosis and necrosis.	Metformin	42-51	tumor necrosis factor	Mus musculus	106-109
14502098-0	2003	Reducing insulin resistance with metformin: the evidence today.	Metformin	33-42	insulin	Homo sapiens	9-16
14502098-2	2003	Metformin, the most widely-prescribed insulin-sensitizing agent in current clinical use, improves blood glucose control mainly by improving insulin-mediated suppression of hepatic glucose production, and by enhancing insulin-stimulated glucose disposal in skeletal muscle.	Metformin	0-9	insulin	Homo sapiens	38-45
14502098-3	2003	Experimental studies show that metformin-mediated improvements in insulin sensitivity may be associated with several mechanisms, including increased insulin receptor tyrosine kinase activity, enhanced glycogen synthesis, and an increase in the recruitment and activity of GLUT4 glucose transporters.	Metformin	31-40	insulin	Homo sapiens	149-156
14502098-4	2003	In adipose tissue, metformin promotes the re-esterification of free fatty acids and inhibits lipolysis, which may indirectly improve insulin sensitivity through reduced lipotoxicity.	Metformin	19-28	insulin	Homo sapiens	133-140
14502099-3	2003	The landmark UK Prospective Diabetes Study (UKPDS) showed that intensive glycaemic management with metformin significantly reduced the risk of a range of debilitating and/or life-threatening macrovascular complications, compared with other oral agents, diet and insulin who achieved similar overall glycaemic control.	Metformin	99-108	insulin	Homo sapiens	262-269
14502100-4	2003	Metformin is a biguanide compound which is antihyperglycaemic, reduces insulin resistance and has cardioprotective effects on lipids, thrombosis and blood flow.	Metformin	0-9	insulin	Homo sapiens	71-78
14502100-5	2003	Metformin has a weight neutral/weight lowering effect and reduces hypertriglyceridaemia, elevated levels of PAI-1, factor VII and C-reactive protein.	Metformin	0-9	C-reactive protein	Homo sapiens	130-148
14502102-2	2003	Metformin improves insulin sensitivity in liver and muscle as its primary antihyperglycaemic mechanism of action, and intensive glycaemic management with metformin significantly reduced the risk of macrovascular diabetic complications in the UK Prospective Diabetes Study.	Metformin	0-9	insulin	Homo sapiens	19-26
14502102-3	2003	The clinical outcome benefits in the metformin group included a significant reduction in the risk of stroke (- 41% vs + 14% with sulphonylurea or insulin treatment, p=0.032), which is well known to be highly sensitive to changes in blood pressure.	Metformin	37-46	insulin	Homo sapiens	146-153
14502105-6	2003	Metformin is a mild inhibitor of respiratory chain complex 1; it activates AMPK in several models, apparently independently of changes in the AMP-to-ATP ratio; it activates G6PDH in a model of high-fat related insulin resistance; and it has antioxidant properties by a mechanism (s), which is (are) not completely elucidated as yet.	Metformin	0-9	insulin	Homo sapiens	210-217
14502098-2	2003	Metformin, the most widely-prescribed insulin-sensitizing agent in current clinical use, improves blood glucose control mainly by improving insulin-mediated suppression of hepatic glucose production, and by enhancing insulin-stimulated glucose disposal in skeletal muscle.	Metformin	0-9	insulin	Homo sapiens	140-147
14502098-2	2003	Metformin, the most widely-prescribed insulin-sensitizing agent in current clinical use, improves blood glucose control mainly by improving insulin-mediated suppression of hepatic glucose production, and by enhancing insulin-stimulated glucose disposal in skeletal muscle.	Metformin	0-9	insulin	Homo sapiens	140-147
14502098-3	2003	Experimental studies show that metformin-mediated improvements in insulin sensitivity may be associated with several mechanisms, including increased insulin receptor tyrosine kinase activity, enhanced glycogen synthesis, and an increase in the recruitment and activity of GLUT4 glucose transporters.	Metformin	31-40	insulin	Homo sapiens	66-73
12970273-9	2003	However, metformin did reduce markers of insulin resistance.	Metformin	9-18	insulin	Homo sapiens	41-48
15255372-6	2003	The value of the insulin sensitizer metformin therapy awaits further evaluation and it should be integrated in the spectrum of therapeutical options that include the discussed surgical methods and GnRH analogues as well.	Metformin	36-45	insulin	Homo sapiens	17-24
12877648-2	2003	A new single-tablet of glyburide/metformin combination therapy (Glucovance), Bristol-Myers Squibb, Inc.) has recently been developed, which addresses the primary defects of Type 2 diabetes: beta-cell dysfunction and insulin resistance.	Metformin	33-42	insulin	Homo sapiens	216-223
12871871-5	2003	RESULTS: In 13 non-responders, on metformin diet, median serum insulin fell (21 to 16 microIU/ml, P<0.05) and insulin secretion fell from 251 to 200 (P<0.01); weight, dehydroepiandrosterone sulphate (DHEAS), testosterone and IR were unchanged (P> or =0.07).	Metformin	34-43	insulin	Homo sapiens	63-70
12877089-0	2003	[Insulin-sensitizing agents: metformin and thiazolidinedione derivatives].	Metformin	29-38	insulin	Homo sapiens	1-8
12916337-11	2003	During insulin therapy, treatment of the insulin resistance with an oral antidiabetic, mostly metformin, and the lifestyle changes must be continued.	Metformin	94-103	insulin	Homo sapiens	41-48
12877089-1	2003	Both metformin and thiazolidinedione derivatives(TZDs) improve insulin resistance, a major pathogenesis of type 2 diabetes, and decrease blood glucose levels without stimulating insulin secretion.	Metformin	5-14	insulin	Homo sapiens	63-70
12836724-6	2003	Recent studies have investigated the role of the insulin-sensitizing agent, metformin, in the treatment of PCOS.	Metformin	76-85	insulin	Homo sapiens	49-56
12757988-9	2003	During the treatment period, fasting plasma insulin (FPI) decreased significantly in both groups, more so with metformin (P<0.05).	Metformin	111-120	insulin	Homo sapiens	44-51
12757988-10	2003	Two-hour postprandial plasma insulin (PPI) levels decreased only in the metformin group (P<0.05).	Metformin	72-81	insulin	Homo sapiens	29-36
12788862-0	2003	Low-dose flutamide-metformin therapy reverses insulin resistance and reduces fat mass in nonobese adolescents with ovarian hyperandrogenism.	Metformin	19-28	insulin	Homo sapiens	46-53
12788862-3	2003	Combined antiandrogen (flutamide 250 mg/d) and insulin-sensitizing (metformin) therapy has beneficial effects, in particular on dyslipidemia and androgen excess in young women.	Metformin	68-77	insulin	Homo sapiens	47-54
12788862-10	2003	Flutamide-metformin treatment (n = 30) was followed within 3 months by marked decreases in hirsutism score and serum androgens, by a more than 50% increase in insulin sensitivity and by a less atherogenic lipid profile (all P < 0.0001).	Metformin	10-19	insulin	Homo sapiens	159-166
12788862-12	2003	Baseline GH hypersecretion and elevated serum IGF-1 normalized after 6 months on flutamide-metformin.	Metformin	91-100	insulin like growth factor 1	Homo sapiens	46-51
12788862-14	2003	In conclusion, in teenage girls with ovarian hyperandrogenism, low-dose combined flutamide-metformin therapy attenuated a spectrum of abnormalities, including insulin resistance and hyperlipidemia.	Metformin	91-100	insulin	Homo sapiens	159-166
12642010-7	2003	Treatment of HIV-related LD with metformin may ameliorate insulin resistance, but its impact on fat redistribution requires additional studies.	Metformin	33-42	insulin	Homo sapiens	58-65
12681023-0	2003	Addition of rosiglitazone to metformin is most effective in obese, insulin-resistant patients with type 2 diabetes.	Metformin	29-38	insulin	Homo sapiens	67-74
12738395-13	2003	CRP was positively associated with body mass index (BMI), serum triglycerides, and sulfonylurea therapy and negatively associated with metformin therapy.	Metformin	135-144	C-reactive protein	Homo sapiens	0-3
12749437-7	2003	Metformin dose-dependently inhibited gonadotrophin and insulin-stimulated P and E2 production (range 25%-50%).	Metformin	0-9	insulin	Homo sapiens	55-62
12746632-0	2003	Effect of metformin on insulin sensitivity and insulin secretion in female obese patients with normal glucose tolerance.	Metformin	10-19	insulin	Homo sapiens	23-30
12746632-1	2003	OBJECTIVES: Metformin is recognized as the treatment of chronic obese, insulin-resistant type 2 diabetic patients.	Metformin	12-21	insulin	Homo sapiens	71-78
12749437-8	2003	In theca, metformin inhibited A production (0%-40%) with no effect on P. In the presence of insulin, A was inhibited dose-dependently and P increased by a similar magnitude.	Metformin	10-19	insulin	Homo sapiens	92-99
12679450-7	2003	Therefore, pioglitazone and metformin are equally efficacious in regard to glycemic control, but they exert significantly different effects on insulin sensitivity due to differing mechanisms of action.	Metformin	28-37	insulin	Homo sapiens	143-150
12721499-0	2003	Effect of metformin and sulfonylurea on C-reactive protein level in well-controlled type 2 diabetics with metabolic syndrome.	Metformin	10-19	C-reactive protein	Homo sapiens	40-58
12721499-1	2003	The objective of this study was to examine the effect of the antihyperglycemic agents metformin (insulin sensitizer) and glibenclamide (insulin secretory agent) on the serum level of C-reactive protein (CRP) in well-controlled type 2 diabetics with metabolic syndrome.	Metformin	86-95	C-reactive protein	Homo sapiens	183-201
12721499-1	2003	The objective of this study was to examine the effect of the antihyperglycemic agents metformin (insulin sensitizer) and glibenclamide (insulin secretory agent) on the serum level of C-reactive protein (CRP) in well-controlled type 2 diabetics with metabolic syndrome.	Metformin	86-95	C-reactive protein	Homo sapiens	203-206
12683699-4	2003	With the introduction of metformin in the United States in the mid-1990s and the subsequent advent of thiazolidinediones, an opportunity exists to address and directly reverse, at least in part, the defects in insulin action seen in individuals with type 2 diabetes.	Metformin	25-34	insulin	Homo sapiens	210-217
12721499-8	2003	CRP level was significantly lower in patients using metformin for blood glucose control compared with those using glibenclamide, 5.56 and 8.3 mg/L, respectively (p = 0.01).	Metformin	52-61	C-reactive protein	Homo sapiens	0-3
12721499-11	2003	The data showed that metformin decreases the level of circulating CRP, a marker of inflammation, more than glibenclamide.	Metformin	21-30	C-reactive protein	Homo sapiens	66-69
12852706-2	2003	The synergistic effects of combining glipizide with metformin on glucose control may be realized by treating the primary effects of type 2 DM, impaired insulin secretion, and insulin resistance.	Metformin	52-61	insulin	Homo sapiens	152-159
12868322-4	2003	It is the case for metformin, acarbose, orlistat or various inhibitors of the renin-angiotensin system.	Metformin	19-28	renin	Homo sapiens	78-83
12634538-10	2003	Patients receiving metformin also had a significantly higher plasma concentration of insulin.	Metformin	19-28	insulin	Homo sapiens	85-92
12606507-9	2003	The adiponectin protein content of subcutaneous abdominal adipocytes was increased following troglitazone treatment and unchanged after metformin.	Metformin	136-145	adiponectin, C1Q and collagen domain containing	Homo sapiens	4-15
12605557-6	2003	Metformin, although no more effective as a glucose-lowering agent than sulfonylureas or insulin, does significantly reduce cardiovascular disease, probably as a result of its weak insulin-sensitising action.	Metformin	0-9	insulin	Homo sapiens	180-187
12634538-12	2003	This effect may be mediated by either a metformin-induced augmentation of insulin sensitivity or by increasing insulin availability.	Metformin	40-49	insulin	Homo sapiens	74-81
12589230-3	2003	Patients on monotherapy might benefit from a combination agent such as glyburide/metformin, which increases insulin secretion and reduces insulin resistance.	Metformin	81-90	insulin	Homo sapiens	108-115
12546685-6	2003	(iv) The reported beneficial effects of exercise and metformin on cardiovascular disease and insulin resistance in humans could be related to the fact that they activate AMPK.	Metformin	53-62	insulin	Homo sapiens	93-100
12686020-9	2003	Attention is currently focused on the insulin sensitizers (metformin and thiazolidinediones), as they appear to impact processes related to the insulin resistance syndrome and the vascular pathophysiologic changes of atherosclerosis.	Metformin	59-68	insulin	Homo sapiens	38-45
12942379-4	2003	The optimal treatment for insulin resistance and impaired glucose intolerance in HIV-infected patients is not known, but preliminary studies have suggested that metformin, an insulin sensitizing agent, improves insulin sensitivity, blood pressure, and waist circumference.	Metformin	161-170	insulin	Homo sapiens	26-33
12749511-1	2003	BACKGROUND: The extended-release formulation of metformin (MXR) prolongs drug absorption in the upper gastrointestinal tract and permits once-daily dosing in patients with type 2 diabetes mellitus.	Metformin	48-57	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	59-62
12511230-0	2003	Metformin modulates insulin post-receptor signaling transduction in chronically insulin-treated Hep G2 cells.	Metformin	0-9	insulin	Homo sapiens	20-27
12511230-0	2003	Metformin modulates insulin post-receptor signaling transduction in chronically insulin-treated Hep G2 cells.	Metformin	0-9	insulin	Homo sapiens	80-87
12511230-4	2003	Therapeutic concentrations (0.01-0.1 mmol/L) of metformin prevented the changes induced by chronic insulin treatment in these post-receptor components of insulin signaling pathway.	Metformin	48-57	insulin	Homo sapiens	99-106
12511230-4	2003	Therapeutic concentrations (0.01-0.1 mmol/L) of metformin prevented the changes induced by chronic insulin treatment in these post-receptor components of insulin signaling pathway.	Metformin	48-57	insulin	Homo sapiens	154-161
12511230-7	2003	In contrast, metformin in pharmacological concentration (1-10 mmol/L) further inhibited tyrosine phosphorylation of IR?, IRS1, IRS2 and the interaction of PI3K with IRS.	Metformin	13-22	isoleucyl-tRNA synthetase 1	Homo sapiens	121-124
12511230-10	2003	The effect of metformin on insulin signaling transduction represent a primary mechanism of metformin action in insulin resistant state.	Metformin	14-23	insulin	Homo sapiens	27-34
12511230-10	2003	The effect of metformin on insulin signaling transduction represent a primary mechanism of metformin action in insulin resistant state.	Metformin	14-23	insulin	Homo sapiens	111-118
12511230-10	2003	The effect of metformin on insulin signaling transduction represent a primary mechanism of metformin action in insulin resistant state.	Metformin	91-100	insulin	Homo sapiens	27-34
12511230-10	2003	The effect of metformin on insulin signaling transduction represent a primary mechanism of metformin action in insulin resistant state.	Metformin	91-100	insulin	Homo sapiens	111-118
12917943-0	2003	Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome.	Metformin	27-36	insulin	Homo sapiens	0-7
12917943-3	2003	If insulin sensitising agents such as metformin are effective in treating features of PCOS, then they could have wider health benefits than just treating the symptoms of the syndrome.	Metformin	38-47	insulin	Homo sapiens	3-10
12917943-11	2003	Metformin has a significant effect in reducing fasting insulin levels (WMD -5.37, CI -8.11 to -2.63), blood pressure and low-density lipoprotein cholesterol (LDL).	Metformin	0-9	insulin	Homo sapiens	55-62
14553866-6	2003	In particular, information on insulin-sensitizing agents-metformin and the currently available thiazolidinediones (TZDs), pioglitazone and rosiglitazone-is presented.	Metformin	57-66	insulin	Homo sapiens	30-37
14553866-7	2003	Although metformin has been shown to indirectly reduce insulin resistance, TZDs are the only available agents that have been shown to directly lower insulin resistance.	Metformin	9-18	insulin	Homo sapiens	55-62
12942379-4	2003	The optimal treatment for insulin resistance and impaired glucose intolerance in HIV-infected patients is not known, but preliminary studies have suggested that metformin, an insulin sensitizing agent, improves insulin sensitivity, blood pressure, and waist circumference.	Metformin	161-170	insulin	Homo sapiens	175-182
12942379-4	2003	The optimal treatment for insulin resistance and impaired glucose intolerance in HIV-infected patients is not known, but preliminary studies have suggested that metformin, an insulin sensitizing agent, improves insulin sensitivity, blood pressure, and waist circumference.	Metformin	161-170	insulin	Homo sapiens	175-182
12502670-1	2003	OBJECTIVE: To evaluate whether, in adolescents with type 1 diabetes, the addition of metformin to insulin and standard diabetes management results in 1) higher insulin sensitivity and 2) lower HbA1c, fasting glucose, insulin dosage (units per kilogram per day) and BMI.	Metformin	85-94	insulin	Homo sapiens	160-167
12502670-1	2003	OBJECTIVE: To evaluate whether, in adolescents with type 1 diabetes, the addition of metformin to insulin and standard diabetes management results in 1) higher insulin sensitivity and 2) lower HbA1c, fasting glucose, insulin dosage (units per kilogram per day) and BMI.	Metformin	85-94	insulin	Homo sapiens	160-167
12502670-9	2003	This was achieved at lower daily insulin dosages (metformin group -0.14 +/- 0.1 vs. placebo group 0.02 +/- 0.2 units.	Metformin	50-59	insulin	Homo sapiens	33-40
12930161-5	2003	Nonetheless, because insulin levels decline with metformin use, it has been termed an "insulin sensitiser".	Metformin	49-58	insulin	Homo sapiens	21-28
12803736-8	2003	Metformin (an insulin sensitiser) and glibenclamide (an insulin secretagogue) are well supported by decades of clinical evidence, and the pharmacokinetics of these agents support twice-daily co-administration.	Metformin	0-9	insulin	Homo sapiens	14-21
12930161-5	2003	Nonetheless, because insulin levels decline with metformin use, it has been termed an "insulin sensitiser".	Metformin	49-58	insulin	Homo sapiens	87-94
12790691-5	2003	Whenever insulin is required by the obese diabetic patient after failure to respond to oral drugs, it should be preferably prescribed in combination with an oral agent, more particularly metformin or acarbose, or possibly a thiazolidinedione.	Metformin	187-196	insulin	Homo sapiens	9-16
12669266-5	2003	Metformin (0.1 - 10 mM) dose-dependently decreased PAI-1 production (and PAI-1 mRNA) under both basal (43 % inhibition at 10 mM, p < 0.05) and interleukin-1beta (IL-1beta)-stimulated conditions where the levels were inhibited by 47.8 % at 1 mM metformin (p < 0.05) and by 100 % at 10 mM (p < 0.01).	Metformin	0-9	interleukin 1 beta	Homo sapiens	146-163
12669266-5	2003	Metformin (0.1 - 10 mM) dose-dependently decreased PAI-1 production (and PAI-1 mRNA) under both basal (43 % inhibition at 10 mM, p < 0.05) and interleukin-1beta (IL-1beta)-stimulated conditions where the levels were inhibited by 47.8 % at 1 mM metformin (p < 0.05) and by 100 % at 10 mM (p < 0.01).	Metformin	0-9	interleukin 1 beta	Homo sapiens	165-173
15526505-2	2003	Metformin is a first-line drug in the treatment of overweight and obese type 2 diabetic patients, offering a selective pathophysiological approach by its effect on insulin resistance.	Metformin	0-9	insulin	Homo sapiens	164-171
12519844-1	2003	Metformin, an insulin-sensitizing drug, has been shown to improve ovarian function and glucose metabolism in obese women with polycystic ovary syndrome (PCOS), but its effects and possible benefits in nonobese PCOS subjects are not well known.	Metformin	0-9	insulin	Homo sapiens	14-21
12519844-8	2003	Metformin improved hyperandrogenism, hyperinsulinemia, and menstrual cyclicity, most likely through its positive effect on insulin clearance and abdominal adiposity.	Metformin	0-9	insulin	Homo sapiens	42-49
15526505-6	2003	Thus metformin appears to have a broad set of pharmacological properties, making the drug potentially applicable even in nondiabetic situations such as obesity, extreme insulin resistance with acanthosis nigricans, polycystic ovary syndrome, etc.	Metformin	5-14	insulin	Homo sapiens	169-176
15526510-5	2003	Insulin resistance decreased by 14.5% (p=0.02) after metformin.	Metformin	53-62	insulin	Homo sapiens	0-7
15526510-7	2003	In conclusion, the results from the present study demonstrate that metformin contributes to a reduction in body weight, body fat mass and waist circumference, improves insulin sensitivity and decreases basal, total and stimulated insulin secretion in obese subjects.	Metformin	67-76	insulin	Homo sapiens	168-175
12466058-7	2002	In streptozotocin-induced diabetic rats, oral administration of metformin at 320 mg/kg once daily made an increase of the response to exogenous short-acting human insulin 15 d later.	Metformin	64-73	insulin	Homo sapiens	163-170
12716216-8	2003	In at least two randomized controlled studies, metformin proved to be clinically effective in increasing insulin sensitivity in hyperinsulinemic, nondiabetic adolescents.	Metformin	47-56	insulin	Homo sapiens	105-112
15981942-19	2003	More recently, metformin has shown promise in promoting weight loss and improving insulin sensitivity among adolescents.	Metformin	15-24	insulin	Homo sapiens	82-89
12466058-8	2002	This is consistent with the view that metformin can increase insulin sensitivity.	Metformin	38-47	insulin	Homo sapiens	61-68
12489380-6	2002	Metformin and the thiazolidinediones are used to treat insulin resistance, but their actions differ.	Metformin	0-9	insulin	Homo sapiens	55-62
12489380-7	2002	Metformin reduces free-fatty-acid efflux from fat cells, thereby suppressing hepatic glucose production, and indirectly improves peripheral insulin sensitivity and endothelial function.	Metformin	0-9	insulin	Homo sapiens	140-147
12489380-14	2002	Metformin and thiazolidinediones are insulin-sensitizing agents with different mechanisms of action and effects in patients with type 2 diabetes mellitus.	Metformin	0-9	insulin	Homo sapiens	37-44
12453950-1	2002	OBJECTIVE: To investigate the metabolic effects of metformin, as compared with placebo, in type 2 diabetic patients intensively treated with insulin.	Metformin	51-60	insulin	Homo sapiens	141-148
12453953-0	2002	The benefits of metformin therapy during continuous subcutaneous insulin infusion treatment of type 1 diabetic patients.	Metformin	16-25	insulin	Homo sapiens	65-72
12453950-11	2002	CONCLUSIONS-In type 2 diabetic patients who are intensively treated with insulin, the combination of insulin and metformin results in superior glycemic control compared with insulin therapy alone, while insulin requirements and weight gain are less.	Metformin	113-122	insulin	Homo sapiens	73-80
12453953-1	2002	OBJECTIVE: This study was designed to assess the insulin-sparing effect of oral administration of metformin along with a continuous subcutaneous insulin infusion (CSII) for the treatment of type 1 diabetic patients.	Metformin	98-107	insulin	Homo sapiens	49-56
12453953-4	2002	RESULTS: Treatment with metformin was associated with a reduction in daily insulin requirements between V0 and V6 of -4.3 +/- 9.9 units (-7.8 +/- 18%) compared with an increase with placebo treatment of 1.7 +/- 8.3 units (2.8 +/- 12.7%) (P = 0.0043).	Metformin	24-33	insulin	Homo sapiens	75-82
12477517-11	2002	RESULT(S): Metformin treatment was associated with significant reduction in basal free testosterone plasma levels, insulin plasma levels, and insulin response to oral glucose tolerance testing.	Metformin	11-20	insulin	Homo sapiens	115-122
12453953-5	2002	A decrease in basal requirement of insulin was also observed in patients treated with metformin of -2.6 +/- 3.2 units (-7.9 +/- 23.8%) compared with an increase with placebo treatment of 1.9 +/- 5.7 units (8.8 +/- 27.1%) (P = 0.023).	Metformin	86-95	insulin	Homo sapiens	35-42
12453953-11	2002	CONCLUSIONS: Metformin was found to be a safe insulin-sparing agent, when used in combination with CSII for the treatment of type 1 diabetes.	Metformin	13-22	insulin	Homo sapiens	46-53
12466374-4	2002	Metformin treatment was accompanied by a drop in fasting insulin and serum androgens and by a less atherogenic lipid profile (all P <or= 0.01).	Metformin	0-9	insulin	Homo sapiens	57-64
12477517-11	2002	RESULT(S): Metformin treatment was associated with significant reduction in basal free testosterone plasma levels, insulin plasma levels, and insulin response to oral glucose tolerance testing.	Metformin	11-20	insulin	Homo sapiens	142-149
12237252-8	2002	Metformin treatment restored PI 3-kinase activity in insulin-resistant myotubes.	Metformin	0-9	insulin	Homo sapiens	53-60
12419322-1	2002	Metformin was reported to increase plasma active glucagon-like peptide-1 (GLP-1) in humans.	Metformin	0-9	glucagon	Homo sapiens	49-72
12419322-1	2002	Metformin was reported to increase plasma active glucagon-like peptide-1 (GLP-1) in humans.	Metformin	0-9	glucagon	Homo sapiens	74-79
12404195-8	2002	TZD had a better antihyperglycemic potency than metformin when insulin was added (P <.001).	Metformin	48-57	insulin	Homo sapiens	63-70
12237252-0	2002	Metformin enhances insulin signalling in insulin-dependent and-independent pathways in insulin resistant muscle cells.	Metformin	0-9	insulin	Homo sapiens	19-26
12237252-0	2002	Metformin enhances insulin signalling in insulin-dependent and-independent pathways in insulin resistant muscle cells.	Metformin	0-9	insulin	Homo sapiens	41-48
12237252-13	2002	Treatment with metformin enhanced the basal activation levels of p38 in both sensitive and resistant myotubes, but insulin did not further stimulate p38 activation in metformin treated cells.	Metformin	15-24	mitogen-activated protein kinase 14	Homo sapiens	65-68
12237252-0	2002	Metformin enhances insulin signalling in insulin-dependent and-independent pathways in insulin resistant muscle cells.	Metformin	0-9	insulin	Homo sapiens	41-48
12237252-2	2002	To evaluate the insulin sensitizing action of metformin on skeletal muscle cells, we have used C2C12 skeletal muscle cells differentiated in chronic presence or absence of <protein-id="16334">insulin.	Metformin	46-55	insulin	Homo sapiens	16-23
12237252-14	2002	7 Treatment of cells with p38 inhibitor, SB203580, blocked insulin- and metformin-stimulated glucose uptake as well as p38 activation.	Metformin	72-81	mitogen-activated protein kinase 14	Homo sapiens	26-29
12237252-15	2002	8 Since the effect of metformin on glucose uptake corresponded to p38 MAPK activation, this suggests the potential role p38 in glucose uptake.	Metformin	22-31	mitogen-activated protein kinase 14	Homo sapiens	66-69
12237252-15	2002	8 Since the effect of metformin on glucose uptake corresponded to p38 MAPK activation, this suggests the potential role p38 in glucose uptake.	Metformin	22-31	mitogen-activated protein kinase 14	Homo sapiens	120-123
12237252-16	2002	9 These data demonstrate the direct insulin sensitizing action of metformin on skeletal muscle cells.	Metformin	66-75	insulin	Homo sapiens	36-43
12401970-7	2002	In some obese adolescents, metformin therapy resulted in declines in body mass index, insulin, and glucose.	Metformin	27-36	insulin	Homo sapiens	86-93
12364442-8	2002	Treatment of 10 insulin-resistant PCOS women with metformin significantly increased circulating fasting ghrelin concentrations (P &lt; 0.02).	Metformin	50-59	insulin	Homo sapiens	16-23
12425366-7	2002	Our results demonstrate that metformin reduces hyperinsulinaemia, body weight and fat mass and improves insulin sensitivity in patients with insulin resistance and acanthosis nigricans.	Metformin	29-38	insulin	Homo sapiens	52-59
12425366-7	2002	Our results demonstrate that metformin reduces hyperinsulinaemia, body weight and fat mass and improves insulin sensitivity in patients with insulin resistance and acanthosis nigricans.	Metformin	29-38	insulin	Homo sapiens	104-111
12364443-0	2002	Sustained benefits of metformin therapy on markers of cardiovascular risk in human immunodeficiency virus-infected patients with fat redistribution and insulin resistance.	Metformin	22-31	insulin	Homo sapiens	152-159
12202407-2	2002	The most extensively studied insulin-lowering agent in the treatment of PCOS is metformin: an oral antihyperglycaemic agent used initially in the treatment of type 2 diabetes mellitus.	Metformin	80-89	insulin	Homo sapiens	29-36
12387512-0	2002	Metformin adjunctive therapy with insulin improves glycemic control in patients with type 1 diabetes mellitus: a pilot study.	Metformin	0-9	insulin	Homo sapiens	34-41
12481381-7	2002	The combination of insulin capsules and glucophage tablets produced about 38% reduction in plasma glucose levels and significantly (P &lt; 0.001) higher AUC and RH compared to either glucophage, doanil tablets or enteric coated insulin capsules alone.	Metformin	40-50	insulin	Homo sapiens	228-235
12387512-1	2002	Metformin lowers blood glucose by reducing hepatic glucose output and improving insulin sensitivity without requiring an increase in circulating insulin concentration.	Metformin	0-9	insulin	Homo sapiens	80-87
12153743-2	2002	Insulin sensitising agents, such as metformin, improve both the biochemical and reproductive parameters; however, no study has been designed to specifically assess the effect of metformin on hair growth.	Metformin	36-45	insulin	Homo sapiens	0-7
12419034-5	2002	In patients treated with metformin, follicular fluid concentrations of testosterone and insulin were significantly lower (60.5 +/- 5 versus 79.1 +/- 6 ng/dl; P &lt; 0.05 and 18 +/- 2.5 versus 22 +/- 2.4 micro IU/ml; P &lt; 0.05 respectively), and the mean number of oocytes retrieved (22.3 +/- 2.4 versus 19.7 +/- 1.6) did not differ.	Metformin	25-34	insulin	Homo sapiens	88-95
12153743-10	2002	There was a non-significant improvement in both sex hormone binding globulin (SHBG) and free androgen index (FAI), although there was a significant difference between baseline and metformin treatment for SHBG (P=0.023) and FAI (P=0.036).	Metformin	180-189	sex hormone binding globulin	Homo sapiens	204-208
12150695-5	2002	Improved pregnancy outcomes in women with PCOS receiving metformin may be attributed to its ability to reduce insulin resistance, hyperinsulinaemia and hypofibrinolytic plasminogen activator inhibitor activity by the enhancement of folliculogenesis and improvement of oocyte quality.	Metformin	57-66	insulin	Homo sapiens	110-117
12062853-7	2002	After stabilisation with combination therapy, those subjects on metformin used less insulin to maintain glycaemic control (13.7+/-6.8 vs. 23.0+/-9.4 U/day, P=0.001) and had lower HbA(1c) values (8.13+/-0.89 vs. 9.05+/-1.30%, P=0.003) compared with those not given metformin.	Metformin	64-73	insulin	Homo sapiens	84-91
12151419-5	2002	Hence, PCOS should be regarded as a general health issue and the use of insulin-sensitizing drugs such as metformin should be considered for the prevention of type 2 diabetes.	Metformin	106-115	insulin	Homo sapiens	72-79
12086935-8	2002	These findings suggest that the metabolic effects of metformin in subjects with type 2 diabetes may be mediated by the activation of AMPK alpha2.	Metformin	53-62	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	133-137
12235466-11	2002	CONCLUSION: Metformin administration was associated with a reduction in total testosterone, free testosterone, and 17-hydroxyprogesterone and an increase in sex hormone binding globulin and dehydroepiandrosterone sulphate in normal males.	Metformin	12-21	sex hormone binding globulin	Homo sapiens	157-185
12093242-1	2002	Metformin is an insulin-sensitizing agent with potent antihyperglycemic properties.	Metformin	0-9	insulin	Homo sapiens	16-23
12093242-4	2002	The antihyperglycemic properties of metformin are mainly attributed to suppressed hepatic glucose production, especially hepatic gluconeogenesis, and increased peripheral tissue insulin sensitivity.	Metformin	36-45	insulin	Homo sapiens	178-185
12093242-5	2002	Although the precise mechanism of hypoglycemic action of metformin remains unclear, it probably interrupts mitochondrial oxidative processes in the liver and corrects abnormalities of intracellular calcium metabolism in insulin-sensitive tissues (liver, skeletal muscle, and adipocytes) and cardiovascular tissue.	Metformin	57-66	insulin	Homo sapiens	220-227
12086935-0	2002	Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	20-48
12086935-3	2002	We recently reported that AMPK is activated by metformin in cultured rat hepatocytes, mediating the inhibitory effects of the drug on hepatic glucose production.	Metformin	47-56	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	26-30
12086935-4	2002	In the present study, we evaluated whether therapeutic doses of metformin increase AMPK activity in vivo in subjects with type 2 diabetes.	Metformin	64-73	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	83-87
12086935-5	2002	Metformin treatment for 10 weeks significantly increased AMPK alpha2 activity in the skeletal muscle, and this was associated with increased phosphorylation of AMPK on Thr172 and decreased acetyl-CoA carboxylase-2 activity.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	57-61
12086935-5	2002	Metformin treatment for 10 weeks significantly increased AMPK alpha2 activity in the skeletal muscle, and this was associated with increased phosphorylation of AMPK on Thr172 and decreased acetyl-CoA carboxylase-2 activity.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	160-164
12086935-6	2002	The increase in AMPK alpha2 activity was likely due to a change in muscle energy status because ATP and phosphocreatine concentrations were lower after metformin treatment.	Metformin	152-161	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	16-20
12086935-7	2002	Metformin-induced increases in AMPK activity were associated with higher rates of glucose disposal and muscle glycogen concentrations.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	31-35
12093831-7	2002	After treatment, women in the OC + metformin group had significant decreases in BMI and WHR, and a significant increase in insulin sensitivity, in contrast to those in the OC group, who had insignificant changes in these parameters.	Metformin	35-44	insulin	Homo sapiens	123-130
12093831-8	2002	Adding metformin also caused significant improvements in serum androstenedione and SHBG levels compared with the OC treatment alone.	Metformin	7-16	sex hormone binding globulin	Homo sapiens	83-87
12093831-9	2002	CONCLUSIONS: Adding metformin to the OC treatment may improve the insulin sensitivity, and may further suppress the hyperandrogenaemia in non-obese women with PCOS.	Metformin	20-29	insulin	Homo sapiens	66-73
12365468-0	2002	Discontinuation of metformin in type 2 diabetes patients treated with insulin.	Metformin	19-28	insulin	Homo sapiens	70-77
12365468-1	2002	BACKGROUND: Metformin added to insulin therapy in type 2 diabetic patients improves glycaemic control and decreases the required daily dose of insulin (DDI).	Metformin	12-21	insulin	Homo sapiens	143-150
12365468-10	2002	CONCLUSIONS: In type 2 diabetic patients treated with insulin plus metformin, glycaemic control can be maintained after discontinuation of metformin by increasing the DDI substantially (20 to 36%) during application of an intensified treatment protocol.	Metformin	139-148	insulin	Homo sapiens	54-61
12032379-7	2002	Metformin, an insulin-sensitizing agent, is particularly effective in women with polycystic ovary syndrome who have significant insulin resistance.	Metformin	0-9	insulin	Homo sapiens	14-21
12032379-7	2002	Metformin, an insulin-sensitizing agent, is particularly effective in women with polycystic ovary syndrome who have significant insulin resistance.	Metformin	0-9	insulin	Homo sapiens	128-135
12032379-8	2002	Metformin use leads to a decrease in serum insulin and androgen levels as well as an improvement in ovulatory function.	Metformin	0-9	insulin	Homo sapiens	43-50
12192894-1	2002	Most patients with polycystic ovary syndrome (PCOS) have hyperinsulinemia; thus it has been postulated that insulin-lowering drugs, such as metformin, might be a useful long-term choice.	Metformin	140-149	insulin	Homo sapiens	62-69
12192894-11	2002	These results suggest that metformin is effective in decreasing hyperandrogenism, mainly by reducing insulin levels.	Metformin	27-36	insulin	Homo sapiens	101-108
12050266-3	2002	We tested this hypothesis by comparing the efficacy of anti-androgen (flutamide) or insulin-sensitizing (metformin) monotherapy to that of combined therapy in normalizing the endocrine-metabolic and anovulatory status of nonobese, young women with hyperinsulinemic hyperandrogenism.	Metformin	105-114	insulin	Homo sapiens	84-91
12050266-6	2002	Compared with monotherapy, combined flutamide-metformin therapy resulted in greater improvements in insulin sensitivity, in testosterone, androstenedione, dehydroepiandrosterone sulfate, and triglyceride levels, and in low-density lipoprotein/high-density lipoprotein-cholesterol ratio (all P &lt; 0.005).	Metformin	46-55	insulin	Homo sapiens	100-107
12223963-13	2002	We should also mention the GnRH-agonists, and finally, dietetics and metformine (in cases of insulin-resistance).	Metformin	69-79	insulin	Homo sapiens	93-100
12149814-6	2002	The appropriate treatment of altered metabolism of carbohydrate requires: 1) a customized dietary approach depending on individual BMI and lipid alterations; 2) a physical exercise programme; 3) the use of insulin sensitization drugs: metformin and thiazolidinediones and, where the therapeutic goals are not achieved or there is a contraindication for oral hypoglycaemic drugs; 4) insulin therapy with regimens similar to other diabetic patients.	Metformin	235-244	insulin	Homo sapiens	206-213
12092688-12	2002	In most surveys, practitioners prescribe insulin or an oral agent, most often metformin.	Metformin	78-87	insulin	Homo sapiens	41-48
12017222-19	2002	Four of 20 African-American children presenting with mean glucose 650 mg/dl maintained normal HbA1c levels on small doses of metformin after initial treatment with multiple insulin injections with or without metformin.	Metformin	125-134	insulin	Homo sapiens	173-180
12709286-11	2002	PCOS patients may become insulin resistant, a condition improved by the administration of metformin.	Metformin	90-99	insulin	Homo sapiens	25-32
11976561-9	2002	After one month of metformin treatment, retention of labelled insulin significantly increased (p&lt;0.001) but was still significantly lower than in the controls (p&lt;0.001).	Metformin	19-28	insulin	Homo sapiens	62-69
12017229-13	2002	Metformin did permit reduction of insulin dose in the combination group.	Metformin	0-9	insulin	Homo sapiens	34-41
11855850-15	2002	The latter may, in part, be explained by the failure of metformin to prevent GH-induced elevation of TNF in visceral fat.	Metformin	56-65	tumor necrosis factor	Rattus norvegicus	101-104
11932281-4	2002	In the present study we tested the hypothesis that metformin therapy in obese adolescents with PCOS will attenuate the adrenal steroidogenic response to ACTH, with reduction of insulin resistance/insulinemia.	Metformin	51-60	insulin	Homo sapiens	177-184
11932281-13	2002	In summary, metformin treatment of obese adolescents with PCOS and impaired glucose tolerance is beneficial in improving glucose tolerance and insulin sensitivity, in lowering insulinemia, and in reducing elevated androgen levels.	Metformin	12-21	insulin	Homo sapiens	143-150
11912566-8	2002	Also, metformin reduced the concentration of plasma glucose (P =.011), serum insulin (P=.044), and serum insulin-like growth factor -1 (IGF-1) (P=.013), while it increased serum glucagon concentration (P &lt;.001).	Metformin	6-15	insulin	Homo sapiens	77-84
11912566-8	2002	Also, metformin reduced the concentration of plasma glucose (P =.011), serum insulin (P=.044), and serum insulin-like growth factor -1 (IGF-1) (P=.013), while it increased serum glucagon concentration (P &lt;.001).	Metformin	6-15	insulin like growth factor 1	Homo sapiens	105-134
11912566-8	2002	Also, metformin reduced the concentration of plasma glucose (P =.011), serum insulin (P=.044), and serum insulin-like growth factor -1 (IGF-1) (P=.013), while it increased serum glucagon concentration (P &lt;.001).	Metformin	6-15	insulin like growth factor 1	Homo sapiens	136-141
11883961-0	2002	Metformin effects on dipeptidylpeptidase IV degradation of glucagon-like peptide-1.	Metformin	0-9	glucagon	Homo sapiens	59-82
11883961-2	2002	Data indicating that metformin increases the circulating amount of active glucagon-like peptide-1 (GLP-1) in obese nondiabetic subjects have recently been presented, and it was proposed that metformin might act as a DP IV inhibitor.	Metformin	21-30	glucagon	Homo sapiens	74-97
11883961-2	2002	Data indicating that metformin increases the circulating amount of active glucagon-like peptide-1 (GLP-1) in obese nondiabetic subjects have recently been presented, and it was proposed that metformin might act as a DP IV inhibitor.	Metformin	21-30	glucagon	Homo sapiens	99-104
11883961-2	2002	Data indicating that metformin increases the circulating amount of active glucagon-like peptide-1 (GLP-1) in obese nondiabetic subjects have recently been presented, and it was proposed that metformin might act as a DP IV inhibitor.	Metformin	191-200	glucagon	Homo sapiens	74-97
11883961-6	2002	Effects of metformin on GLP-1([7-36NH2]) degradation were assessed by mass spectrometry.	Metformin	11-20	glucagon	Homo sapiens	24-29
11883961-9	2002	Surface plasmon resonance recordings indicated that both GLP-1([7-36NH2]) and GLP-1([9-36NH2]) show micromolar affinity (K(D)) for DP IV, but neither interaction was influenced by metformin.	Metformin	180-189	glucagon	Homo sapiens	57-62
11883961-9	2002	Surface plasmon resonance recordings indicated that both GLP-1([7-36NH2]) and GLP-1([9-36NH2]) show micromolar affinity (K(D)) for DP IV, but neither interaction was influenced by metformin.	Metformin	180-189	glucagon	Homo sapiens	78-83
11883961-10	2002	The results conclusively indicate that metformin does not act directly on DP IV, therefore alternative explanations for the purported effect of metformin on circulating active GLP-1 concentrations must be considered.	Metformin	144-153	glucagon	Homo sapiens	176-181
11968579-15	2002	During metformin treatment the insulin level declined and subsequently the menstrual cycle became normal in 11 of 16 patients with hyperinsulinaeia (68.7%), incl.	Metformin	7-16	insulin	Homo sapiens	31-38
11874944-9	2002	The reduction in insulin resistance determined by hyperinsulinemic-euglycemic clamp was nearly twofold greater with troglitazone than metformin.	Metformin	134-143	insulin	Homo sapiens	17-24
11968579-17	2002	The results indicate a possible new indication of metformin in the treatment of ovarian hyperandrogenism in insulin resistant patients.	Metformin	50-59	insulin	Homo sapiens	108-115
12017763-13	2002	In cases of severe insulin resistance the use of glitazones in conjunction with metformin or sulphonylureas may be indicated.	Metformin	80-89	insulin	Homo sapiens	19-26
11925670-5	2002	Positive correlations between DHEA/S and of the results insulin tolerance were found as at the baseline (+0.4452, resp. +0.4455) as well as in the control period after the metformin administration (+0.7549, resp. +0.6073).	Metformin	172-181	insulin	Homo sapiens	56-63
11937980-6	2002	Although metformin restores cyclic pituitary- gonadal function and improves fertility, it can decrease levels of androgen and LH and increase levels of SHBG in women with PCOS.	Metformin	9-18	sex hormone binding globulin	Homo sapiens	152-156
11812753-8	2002	However, insulin stimulation of PI 3-kinase activity was augmented nearly threefold after troglitazone treatment (from 67 +/- 22% stimulation over basal pre-treatment to 211 +/- 62% post-treatment, P &lt; 0.05), whereas metformin had no effect.	Metformin	220-229	insulin	Homo sapiens	9-16
11902096-2	2002	Combining metformin with the amino acid derivative, nateglinide, tackles both beta cell dysfunction and insulin resistance, and produces a greater decrease in haemoglobin A1c levels than treatment with either drug alone.	Metformin	10-19	insulin	Homo sapiens	104-111
11815472-10	2002	Addition of metformin to high-FFA media prevented impairment in glucose-mediated insulin release, decline of first-phase insulin secretion, and reduction of glucose utilization and oxidation without significantly affecting islet triglyceride accumulation.	Metformin	12-21	insulin	Homo sapiens	81-88
11756340-12	2002	These results suggest that DMB interferes with FXIII activation and fibrin polymerization, but not only by binding to thrombin on a different location than the active site.	Metformin	27-30	coagulation factor II, thrombin	Homo sapiens	118-126
11874440-2	2002	Metformin, an antidiabetic drug, enhances insulin sensitivity in type 2 diabetic patients.	Metformin	0-9	insulin	Homo sapiens	42-49
11874440-3	2002	Previous studies have shown that metformin improves insulin sensitivity in fructose-fed rats.	Metformin	33-42	insulin	Homo sapiens	52-59
11874440-4	2002	The aim of this study was to determine the effect of metformin treatment on overall lipid metabolism and lipid peroxidation in rats that were fed a fructose-enriched diet, which leads to insulin resistance.	Metformin	53-62	insulin	Homo sapiens	187-194
11874440-11	2002	Administration of metformin (50 mg/kg/day) was associated with significant normalization of plasma insulin level and lipid alterations.	Metformin	18-27	insulin	Homo sapiens	99-106
11874440-17	2002	Improved insulin action in metformin-treated rats could be responsible for the amelioration of these abnormalities induced by fructose feeding.	Metformin	27-36	insulin	Homo sapiens	9-16
11893229-8	2002	Some drugs frequently used in patients at risk of cardiovascular disease, such as the fibric acid derivatives used in certain dyslipidaemias and metformin in type 2 (non-insulin-dependent) diabetes mellitus, also raise plasma homocysteine levels.	Metformin	145-154	insulin	Homo sapiens	170-177
11779598-8	2002	RESULT(S): Metformin therapy resulted in a significant decrease in total T, LH level, LH/FSH ratio, insulin resistance, and mean BMI.	Metformin	11-20	insulin	Homo sapiens	100-107
11756319-0	2002	Regulation of glucose transport and insulin signaling by troglitazone or metformin in adipose tissue of type 2 diabetic subjects.	Metformin	73-82	insulin	Homo sapiens	36-43
11756319-4	2002	Metformin treatment increased insulin-stimulated whole-body glucose disposal rates by 20% (P &lt; 0.05); the response to troglitazone was greater (44% increase, P &lt; 0.01 vs. baseline, P &lt; 0.05 vs. metformin).	Metformin	0-9	insulin	Homo sapiens	30-37
11756319-11	2002	Insulin-stimulated serine phosphorylation of Akt was augmented after troglitazone (170 +/- 34% of pre-Rx response, P &lt; 0.05) treatment and unchanged by metformin.	Metformin	155-164	insulin	Homo sapiens	0-7
11779598-12	2002	CONCLUSION(S): Metformin therapy not only decreases hyperandrogenism and insulin resistance but also improves ovulation rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with PCOS.	Metformin	15-24	insulin	Homo sapiens	73-80
11961383-5	2002	The best prediction of the improvement in menstrual cyclicity after metformin was achieved with a combination of basal values of 17-hydroxyprogesterone, testosterone, sex hormone binding globulin, and androstenedione.	Metformin	68-77	sex hormone binding globulin	Homo sapiens	167-195
11808829-0	2002	Insulin-metformin combination therapy in obese patients with type 2 diabetes.	Metformin	8-17	insulin	Homo sapiens	0-7
11822582-16	2002	Among the patients with DM, a higher glucagon-stimulated serum C-peptide response was associated with diet/metformin treatment, a shorter duration of DM and predicted improved glycemic control up to one year later.	Metformin	107-116	insulin	Homo sapiens	63-72
12494026-7	2002	Treatment with metformin allows to decrease insulin resistance and thus severity of derangements of metabolism.	Metformin	15-24	insulin	Homo sapiens	44-51
11808829-1	2002	The aim of the study was to evaluate the effects of insulin-metformin combination therapy compared to insulin monotherapyin obese, insulin-requiring patients with type 2 diabetes mellitus.	Metformin	60-69	insulin	Homo sapiens	52-59
11808829-5	2002	Insulin-metformin combination therapy resulted in a significant decrease in glycated hemoglobin values with a final mean reduction of 1.5% +/- 1.2% (p = 0.001).	Metformin	8-17	insulin	Homo sapiens	0-7
11808829-6	2002	FPG decreased significantly (p &lt; 0.005) by week 4 of insulin-metformin therapy, but the change was not statistically significant by week 12, and daily insulin requirements were significantly reduced during combination therapy (p &lt; 0.05).	Metformin	64-73	insulin	Homo sapiens	56-63
11808829-7	2002	These results suggest that in obese patients with type 2 diabetes mellitus receiving &gt; or = 70 U of daily insulin, the addition of metformin leads to improved glycemic control with lower daily doses of insulin and without adverse effects.	Metformin	134-143	insulin	Homo sapiens	205-212
11701439-4	2001	In the presence of metformin, identical infusion rates of insulin yielded higher insulin concentrations, namely 283 +/- 19 vs. 202 +/- 31 pmol/l for VI and II, respectively (P &lt; 0.05).	Metformin	19-28	insulin	Homo sapiens	58-65
15765617-9	2002	Thiazolidinediones are commonly used as add-on therapy for those requiring large daily doses of insulin therapy, or in addition to sulfonylurea agents and metformin for those reluctant to start insulin therapy.	Metformin	155-164	insulin	Homo sapiens	194-201
15765620-7	2002	In most studies conducted to date, metformin and the thiazolidinedione agent troglitazone have resulted in improved insulin sensitivity, resumption of regular menses and decreased serum androgen levels.	Metformin	35-44	insulin	Homo sapiens	116-123
15765627-4	2002	GLP-1 exerts additional glucose-lowering actions in patients with diabetes mellitus already treated with metformin or sulfonylurea therapy.	Metformin	105-114	glucagon	Homo sapiens	0-5
11701439-4	2001	In the presence of metformin, identical infusion rates of insulin yielded higher insulin concentrations, namely 283 +/- 19 vs. 202 +/- 31 pmol/l for VI and II, respectively (P &lt; 0.05).	Metformin	19-28	insulin	Homo sapiens	81-88
11701439-8	2001	The synergistic effects of metformin and insulin could thus be explained by a metformin-mediated decrease in the extraction of insulin by the hindquarter (4.8 +/- 0.4% vs. 8.6 +/- 0.9%, P &lt; 0.05).	Metformin	27-36	insulin	Homo sapiens	127-134
11701439-8	2001	The synergistic effects of metformin and insulin could thus be explained by a metformin-mediated decrease in the extraction of insulin by the hindquarter (4.8 +/- 0.4% vs. 8.6 +/- 0.9%, P &lt; 0.05).	Metformin	78-87	insulin	Homo sapiens	41-48
11701439-8	2001	The synergistic effects of metformin and insulin could thus be explained by a metformin-mediated decrease in the extraction of insulin by the hindquarter (4.8 +/- 0.4% vs. 8.6 +/- 0.9%, P &lt; 0.05).	Metformin	78-87	insulin	Homo sapiens	127-134
11789058-0	2001	[Effect of long-term treatment with metformin on steroid levels and parameters of insulin resistance in women with polycystic ovary syndrome].	Metformin	36-45	insulin	Homo sapiens	82-89
11727406-13	2001	The use of metformin or glitazones in combination with insulin has been demonstrated to have insulin-sparing properties.	Metformin	11-20	insulin	Homo sapiens	93-100
11735093-2	2001	It has been demonstrated that metformin, an antihyperglycemic agent, decreases hyperinsulinemia and insulin resistance leading to decreased adiposity in obese and non-insulin-dependent diabetes mellitus (NIDDM) adults.	Metformin	30-39	insulin	Homo sapiens	84-91
11735093-6	2001	Compared to the placebo group, the metformin group had greater weight loss (6.5% +/- 0.8% v 3.8 +/- 0.4%, P &lt;.01), greater decrease in body fat (P &lt;.001), greater increase in fat-free mass to body fat ratio (P &lt;.005), and greater attenuation of area under the curve (AUC) insulin response to an oral glucose tolerance test (P &lt;.001).	Metformin	35-44	insulin	Homo sapiens	281-288
11735093-7	2001	This was associated with enhanced insulin sensitivity, as determined by the fasting plasma glucose:insulin, 2-hour glucose:insulin, and AUC glucose:AUC insulin ratios, in the metformin group compared to controls (P &lt;.01).	Metformin	175-184	insulin	Homo sapiens	34-41
11724081-8	2001	Sulfonylurea and metformin with insulin was rarely used.	Metformin	17-26	insulin	Homo sapiens	32-39
11789058-14	2001	The best prediction of the improvement in menstrual cyclicity after metformin was achieved with the combination of basal 17OH progesterone, androstendione, testosterone and SHBG.	Metformin	68-77	sex hormone binding globulin	Homo sapiens	173-177
11783602-17	2001	Group B (a) was conversely treated with intensive insulin therapy to achieve a HbA1c value below 7.5% (3 daily injections of regular and 1 or 2 daily injections of intermediate acting insulin associated with metformin 500 mg twice daily in 64% of the patients).	Metformin	208-217	insulin	Homo sapiens	184-191
11703421-1	2001	BACKGROUND: Since metformin improves insulin sensitivity, it has been indicated for patients with diabetes and hypertension, which are insulin-resistant conditions.	Metformin	18-27	insulin	Homo sapiens	37-44
11703421-1	2001	BACKGROUND: Since metformin improves insulin sensitivity, it has been indicated for patients with diabetes and hypertension, which are insulin-resistant conditions.	Metformin	18-27	insulin	Homo sapiens	135-142
11703421-9	2001	Metformin induced a reduction in both insulinaemia (71.0+/-62.4 to 38.0+/-23.0 pmol/l, p &lt; 0.05) and the insulin resistance index (3.5+/-2.7 to 1.8+/-1.0, p &lt; 0.05).	Metformin	0-9	insulin	Homo sapiens	38-45
11727360-3	2001	Recent studies report that insulin-sensitizing agents, such as metformin, reduce hyperinsulinemia, reverse the endocrinopathy of PCOS and normalize endocrine, metabolic and reproductive functions, leading to the resumption of menstrual cyclicity and ovulation.	Metformin	63-72	insulin	Homo sapiens	27-34
11600523-4	2001	In this study we investigated endothelin-1 levels in women with polycystic ovary syndrome, and we evaluated the effect of an insulin sensitizer, metformin, on endothelin-1 levels.	Metformin	145-154	insulin	Homo sapiens	125-132
11600523-4	2001	In this study we investigated endothelin-1 levels in women with polycystic ovary syndrome, and we evaluated the effect of an insulin sensitizer, metformin, on endothelin-1 levels.	Metformin	145-154	endothelin 1	Homo sapiens	159-171
11600523-10	2001	Finally, after metformin therapy, endothelin-1 levels were significantly reduced in obese (endothelin-1 before, 3.25 +/- 2.2; endothelin-1 after, 1.1 +/- 0.9 pmol/liter; P &lt; 0.003) and nonobese (endothelin-1 before, 2.7 +/- 2; endothelin-1 after, 0.7 +/- 0.4 pmol/liter; P &lt; 0.01) women with polycystic ovary syndrome, with no change in body mass index.	Metformin	15-24	endothelin 1	Homo sapiens	34-46
11600523-10	2001	Finally, after metformin therapy, endothelin-1 levels were significantly reduced in obese (endothelin-1 before, 3.25 +/- 2.2; endothelin-1 after, 1.1 +/- 0.9 pmol/liter; P &lt; 0.003) and nonobese (endothelin-1 before, 2.7 +/- 2; endothelin-1 after, 0.7 +/- 0.4 pmol/liter; P &lt; 0.01) women with polycystic ovary syndrome, with no change in body mass index.	Metformin	15-24	endothelin 1	Homo sapiens	91-103
11600523-10	2001	Finally, after metformin therapy, endothelin-1 levels were significantly reduced in obese (endothelin-1 before, 3.25 +/- 2.2; endothelin-1 after, 1.1 +/- 0.9 pmol/liter; P &lt; 0.003) and nonobese (endothelin-1 before, 2.7 +/- 2; endothelin-1 after, 0.7 +/- 0.4 pmol/liter; P &lt; 0.01) women with polycystic ovary syndrome, with no change in body mass index.	Metformin	15-24	endothelin 1	Homo sapiens	91-103
11600523-10	2001	Finally, after metformin therapy, endothelin-1 levels were significantly reduced in obese (endothelin-1 before, 3.25 +/- 2.2; endothelin-1 after, 1.1 +/- 0.9 pmol/liter; P &lt; 0.003) and nonobese (endothelin-1 before, 2.7 +/- 2; endothelin-1 after, 0.7 +/- 0.4 pmol/liter; P &lt; 0.01) women with polycystic ovary syndrome, with no change in body mass index.	Metformin	15-24	endothelin 1	Homo sapiens	91-103
11600523-10	2001	Finally, after metformin therapy, endothelin-1 levels were significantly reduced in obese (endothelin-1 before, 3.25 +/- 2.2; endothelin-1 after, 1.1 +/- 0.9 pmol/liter; P &lt; 0.003) and nonobese (endothelin-1 before, 2.7 +/- 2; endothelin-1 after, 0.7 +/- 0.4 pmol/liter; P &lt; 0.01) women with polycystic ovary syndrome, with no change in body mass index.	Metformin	15-24	endothelin 1	Homo sapiens	91-103
11600523-11	2001	Moreover, after metformin therapy, hyperandrogenemia and hyperinsulinemia were normalized, and glucose utilization improved [obese before: total T, 0.9 +/- 0.15 ng/ml; fasting insulin, 22.2 +/- 12.1 U/liter; glucose utilization, 2.15 +/- 0.5 mg/kg.min; obese after: total T, 0.5 +/- 0.2 ng/ml; fasting insulin, 11.6 +/- 6 U/liter; glucose utilization, 4.7 +/- 1.4 mg/kg.min 9P &lt; 0.003, P &lt; 0.006, and P &lt; 0.002, respectively); nonobese before: total T, 1 +/- 0.5 ng/ml; fasting insulin, 15.5 +/- 7.6 U/liter; glucose utilization, 3.4 +/- 0.7 mg/kg.min; nonobese after: total T, 0.8 +/- 0.5 ng/ml; fasting insulin, 9 +/- 3.8 U/liter; glucose utilization, 6 +/- 1.7 mg/kg.min (P &lt; 0.04, P &lt; 0.02, and P &lt; 0.0008, respectively)].	Metformin	16-25	insulin	Homo sapiens	62-69
11600523-11	2001	Moreover, after metformin therapy, hyperandrogenemia and hyperinsulinemia were normalized, and glucose utilization improved [obese before: total T, 0.9 +/- 0.15 ng/ml; fasting insulin, 22.2 +/- 12.1 U/liter; glucose utilization, 2.15 +/- 0.5 mg/kg.min; obese after: total T, 0.5 +/- 0.2 ng/ml; fasting insulin, 11.6 +/- 6 U/liter; glucose utilization, 4.7 +/- 1.4 mg/kg.min 9P &lt; 0.003, P &lt; 0.006, and P &lt; 0.002, respectively); nonobese before: total T, 1 +/- 0.5 ng/ml; fasting insulin, 15.5 +/- 7.6 U/liter; glucose utilization, 3.4 +/- 0.7 mg/kg.min; nonobese after: total T, 0.8 +/- 0.5 ng/ml; fasting insulin, 9 +/- 3.8 U/liter; glucose utilization, 6 +/- 1.7 mg/kg.min (P &lt; 0.04, P &lt; 0.02, and P &lt; 0.0008, respectively)].	Metformin	16-25	insulin	Homo sapiens	176-183
11600523-11	2001	Moreover, after metformin therapy, hyperandrogenemia and hyperinsulinemia were normalized, and glucose utilization improved [obese before: total T, 0.9 +/- 0.15 ng/ml; fasting insulin, 22.2 +/- 12.1 U/liter; glucose utilization, 2.15 +/- 0.5 mg/kg.min; obese after: total T, 0.5 +/- 0.2 ng/ml; fasting insulin, 11.6 +/- 6 U/liter; glucose utilization, 4.7 +/- 1.4 mg/kg.min 9P &lt; 0.003, P &lt; 0.006, and P &lt; 0.002, respectively); nonobese before: total T, 1 +/- 0.5 ng/ml; fasting insulin, 15.5 +/- 7.6 U/liter; glucose utilization, 3.4 +/- 0.7 mg/kg.min; nonobese after: total T, 0.8 +/- 0.5 ng/ml; fasting insulin, 9 +/- 3.8 U/liter; glucose utilization, 6 +/- 1.7 mg/kg.min (P &lt; 0.04, P &lt; 0.02, and P &lt; 0.0008, respectively)].	Metformin	16-25	insulin	Homo sapiens	176-183
11600523-11	2001	Moreover, after metformin therapy, hyperandrogenemia and hyperinsulinemia were normalized, and glucose utilization improved [obese before: total T, 0.9 +/- 0.15 ng/ml; fasting insulin, 22.2 +/- 12.1 U/liter; glucose utilization, 2.15 +/- 0.5 mg/kg.min; obese after: total T, 0.5 +/- 0.2 ng/ml; fasting insulin, 11.6 +/- 6 U/liter; glucose utilization, 4.7 +/- 1.4 mg/kg.min 9P &lt; 0.003, P &lt; 0.006, and P &lt; 0.002, respectively); nonobese before: total T, 1 +/- 0.5 ng/ml; fasting insulin, 15.5 +/- 7.6 U/liter; glucose utilization, 3.4 +/- 0.7 mg/kg.min; nonobese after: total T, 0.8 +/- 0.5 ng/ml; fasting insulin, 9 +/- 3.8 U/liter; glucose utilization, 6 +/- 1.7 mg/kg.min (P &lt; 0.04, P &lt; 0.02, and P &lt; 0.0008, respectively)].	Metformin	16-25	insulin	Homo sapiens	176-183
11600523-13	2001	In addition, 6 months of metformin therapy reduces endothelin-1 levels and improves their hormonal and metabolic profile.	Metformin	25-34	endothelin 1	Homo sapiens	51-63
11703421-12	2001	CONCLUSIONS: Reductions in both the insulin levels and the resistance index reinforced metformin capacity to improve peripheral sensitivity.	Metformin	87-96	insulin	Homo sapiens	36-43
11566961-5	2001	Metformin therapy also improves insulin sensitivity and has been associated with decreases in cardiovascular events in obese diabetic patients.	Metformin	0-9	insulin	Homo sapiens	32-39
11523631-3	2001	In past experiments, we used both labeled glucose uptake, lipogenesis, and stimulation of calmodulin gene expression to quantify the ability of the antidiabetic drugs (pioglitazone and metformin) to reverse tumor necrosis factor-alpha (TNF-alpha)-induced IR in these insulin-treated cells.	Metformin	185-194	calmodulin 1	Homo sapiens	90-100
11547215-3	2001	Thiazolidinediones (TZD) are a new class of insulin sensitizers recently approved in Europe, in combination therapy with sulfonylureas or/and metformin, for the treatment of type 2 diabetes.	Metformin	142-151	insulin	Homo sapiens	44-51
11549648-9	2001	The latter finding may be due to an IGF-I-reducing effect of metformin, as after 14 d of metformin treatment baseline levels of IGF-I were significantly lower than in the placebo condition (236.9 +/- 13.9 vs. 263.2 +/- 14.4 microg/liter; P = 0.015).	Metformin	61-70	insulin like growth factor 1	Homo sapiens	36-41
11549648-9	2001	The latter finding may be due to an IGF-I-reducing effect of metformin, as after 14 d of metformin treatment baseline levels of IGF-I were significantly lower than in the placebo condition (236.9 +/- 13.9 vs. 263.2 +/- 14.4 microg/liter; P = 0.015).	Metformin	61-70	insulin like growth factor 1	Homo sapiens	128-133
11549648-9	2001	The latter finding may be due to an IGF-I-reducing effect of metformin, as after 14 d of metformin treatment baseline levels of IGF-I were significantly lower than in the placebo condition (236.9 +/- 13.9 vs. 263.2 +/- 14.4 microg/liter; P = 0.015).	Metformin	89-98	insulin like growth factor 1	Homo sapiens	128-133
11515833-9	2001	While current management usually involves oral contraceptives, future treatment may include insulin-lowering medications, such as metformin, to improve symptoms.	Metformin	130-139	insulin	Homo sapiens	92-99
11523631-3	2001	In past experiments, we used both labeled glucose uptake, lipogenesis, and stimulation of calmodulin gene expression to quantify the ability of the antidiabetic drugs (pioglitazone and metformin) to reverse tumor necrosis factor-alpha (TNF-alpha)-induced IR in these insulin-treated cells.	Metformin	185-194	tumor necrosis factor	Homo sapiens	207-234
11523631-3	2001	In past experiments, we used both labeled glucose uptake, lipogenesis, and stimulation of calmodulin gene expression to quantify the ability of the antidiabetic drugs (pioglitazone and metformin) to reverse tumor necrosis factor-alpha (TNF-alpha)-induced IR in these insulin-treated cells.	Metformin	185-194	tumor necrosis factor	Homo sapiens	236-245
11523631-3	2001	In past experiments, we used both labeled glucose uptake, lipogenesis, and stimulation of calmodulin gene expression to quantify the ability of the antidiabetic drugs (pioglitazone and metformin) to reverse tumor necrosis factor-alpha (TNF-alpha)-induced IR in these insulin-treated cells.	Metformin	185-194	insulin	Homo sapiens	267-274
11485138-10	2001	Metformin was added and six months following discharge the patient"s blood glucose was well controlled with 36 units of insulin per day.	Metformin	0-9	insulin	Homo sapiens	120-127
11473953-1	2001	BACKGROUND: Metformin, an insulin-sensitizing agent, has been used successfully as the first-line drug to induce ovulation in women with polycystic ovary syndrome.	Metformin	12-21	insulin	Homo sapiens	26-33
11431640-0	2001	[Effects of metformin on insulin resistance and on ovarian steroidogenesis in women with polycystic ovary syndrome].	Metformin	12-21	insulin	Homo sapiens	25-32
11431640-3	2001	Objective of this study was to verify if the reduction of the circulating insulin levels, obtained through therapy with metformin, caused the reduction of LH levels, LH:FSH ratio, of testosterone and androstenedione levels, but also of cholesterolemia, triglyceridemia, BMI, and naturally of insulinemia, glycemia, as well as an increase in HDLC (high density lipoprotein cholesterol).	Metformin	120-129	insulin	Homo sapiens	74-81
11431640-4	2001	METHODS: The presence of insulin-resistance and hyperinsulinemia, in 15 women aged between 20 and 30 with BMI &gt;26 kg/m2, has been verified with test loaded with glucose; 500 mg of metformin have been given to these women three times a day before meals for 12 weeks.	Metformin	183-192	insulin	Homo sapiens	25-32
11485138-14	2001	Metformin increases the sensitivity of peripheral tissues to insulin and appeared to be useful in this patient.	Metformin	0-9	insulin	Homo sapiens	61-68
11436194-22	2001	Metformin safely and effectively reduces CHD risk factors (weight, fasting insulin, leptin, LDL cholesterol, centripetal obesity) in morbidly obese, nondiabetic subjects with BMI &gt; 30, probably by virtue of its insulin-sensitizing action.	Metformin	0-9	insulin	Homo sapiens	75-82
11436194-0	2001	Metformin reduces weight, centripetal obesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30.	Metformin	0-9	insulin	Homo sapiens	47-54
11436194-14	2001	On metformin, there were linear trends in decrements in weight, girth, waist circumference, waist/hip ratio, insulin, and leptin throughout the study period (P &lt;.007).	Metformin	3-12	insulin	Homo sapiens	109-116
11436194-20	2001	The greater the reduction in insulin on metformin, the greater the reduction in leptin (partial R(2) = 8%, P =.03).	Metformin	40-49	insulin	Homo sapiens	29-36
11436194-22	2001	Metformin safely and effectively reduces CHD risk factors (weight, fasting insulin, leptin, LDL cholesterol, centripetal obesity) in morbidly obese, nondiabetic subjects with BMI &gt; 30, probably by virtue of its insulin-sensitizing action.	Metformin	0-9	insulin	Homo sapiens	214-221
11453331-7	2001	Metformin, an oral hypoglycaemic agent that increases insulin sensitivity, has been shown to reduce serum concentrations of insulin and androgens, to reduce hirsutism, and to improve ovulation rates.	Metformin	0-9	insulin	Homo sapiens	54-61
11453331-10	2001	The effects of metformin on lipid abnormalities, hypertension or premature vascular disease are unknown, but the relative safety, moderate cost, and efficacy in reducing insulin resistance suggest that metformin may prove to be of benefit in combating these components of the "metabolic" syndrome in PCOS.	Metformin	202-211	insulin	Homo sapiens	170-177
11331217-1	2001	OBJECTIVE: To determine the clinical, hormonal and biochemical effect of 4-5 months of insulin-sensitizing therapy (hypocaloric diet+metformin) in obese patients with polycystic ovary syndrome (PCOS).	Metformin	133-142	insulin	Homo sapiens	87-94
11411059-3	2001	The aim of our open, prospective, placebo controlled study was to assess the effect of metformin in poorly controlled diabetic patients type 1 with high insulin requirements.	Metformin	87-96	insulin	Homo sapiens	153-160
11411059-4	2001	METHODS AND RESULTS: In the group comprised of 19 type 1 diabetic patients the insulin resistance was assessed by hyperinsulinemic euglycemic clamp and indirect calorimetry at the beginning of the study (B), 3 months later when metformin in the dose of 2 x 850 mg was added to existing insulin therapy (M) and after 3 months of placebo therapy (P).	Metformin	228-237	insulin	Homo sapiens	79-86
11411059-10	2001	CONCLUSIONS: The combination of metformin and the intensive insulin therapy in type 1 diabetic patients led, in contrast to placebo, to the significant reduction in weight (p &lt; 0.001), to the reduction in insulin requirements (p &lt; 0.05), to the improved control of glycaemia (p &lt; 0.01) and to the decrease of FFA during clamp (p &lt; 0.01).	Metformin	32-41	insulin	Homo sapiens	208-215
11300445-4	2001	The effects of metformin, an antidiabetic agent that improves insulin sensitivity, on endothelial function have not been reported.	Metformin	15-24	insulin	Homo sapiens	62-69
11300445-9	2001	There was a significant improvement in insulin resistance with metformin (32.5% reduction in HOMA-IR, p = 0.01), and by stepwise multivariate analysis insulin resistance was the sole predictor of endothelium-dependent blood flow following treatment (r = -0.659, p = 0.0012).	Metformin	63-72	insulin	Homo sapiens	39-46
11300445-10	2001	CONCLUSIONS: Metformin treatment improved both insulin resistance and endothelial function, with a strong statistical link between these variables.	Metformin	13-22	insulin	Homo sapiens	47-54
11335776-17	2001	Metformin caused a progressive decline in fasting blood glucose (from a mean of 84.9 to 75.1 mg%) and a reduction in fasting insulin levels (from 31.3 to 19.3 microU/mL).	Metformin	0-9	insulin	Homo sapiens	125-132
11335776-19	2001	Insulin sensitivity, as assessed by the ratio of fasting insulin to glucose concentrations and the quantitative insulin sensitivity check index (1/[log fasting insulin + log fasting glucose]) and homeostasis model assessment insulin resistance index (fasting insulin x fasting glucose/22.5) indices, increased slightly in the metformin-treated participants.	Metformin	326-335	insulin	Homo sapiens	0-7
11460576-0	2001	Metformin, the rebirth of a biguanide: mechanism of action and place in the prevention and treatment of insulin resistance.	Metformin	0-9	insulin	Homo sapiens	104-111
11289473-1	2001	OBJECTIVE: To evaluate the effects of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels.	Metformin	38-47	glucagon	Homo sapiens	51-74
11289473-1	2001	OBJECTIVE: To evaluate the effects of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels.	Metformin	38-47	glucagon	Homo sapiens	76-81
11289473-6	2001	Metformin induced a significant (P &lt; 0.05) increase of GLP-1(7-36)amide/(7-37) at 30 and 60 min after the oral glucose load (63.8 +/- 29.0 vs. 50.3 +/- 15.6 pmol/l and 75.8 +/- 35.4 vs. 46.9 +/- 20.0 pmol/l, respectively), without affecting baseline GLP-1 levels.	Metformin	0-9	glucagon	Homo sapiens	58-63
11289473-6	2001	Metformin induced a significant (P &lt; 0.05) increase of GLP-1(7-36)amide/(7-37) at 30 and 60 min after the oral glucose load (63.8 +/- 29.0 vs. 50.3 +/- 15.6 pmol/l and 75.8 +/- 35.4 vs. 46.9 +/- 20.0 pmol/l, respectively), without affecting baseline GLP-1 levels.	Metformin	0-9	glucagon	Homo sapiens	253-258
11289473-8	2001	In pooled human plasma, metformin (0.1-0.5 microg/ml) significantly inhibited degradation of GLP-1(7-36)amide after a 30-min incubation at 37 degrees C; similar results were obtained in a buffer solution containing DPP-IV.	Metformin	24-33	glucagon	Homo sapiens	93-98
11289473-9	2001	CONCLUSIONS: Metformin significantly increases GLP-1 levels after an oral glucose load in obese nondiabetic subjects; this effect could be due to an inhibition of GLP-1 degradation.	Metformin	13-22	glucagon	Homo sapiens	47-52
11289473-9	2001	CONCLUSIONS: Metformin significantly increases GLP-1 levels after an oral glucose load in obese nondiabetic subjects; this effect could be due to an inhibition of GLP-1 degradation.	Metformin	13-22	glucagon	Homo sapiens	163-168
11239532-11	2001	Metformin led to modulation of preovulatory of follicular fluid IGF levels with increases of IGF-I (140 +/- 8 vs. 109 +/- 7ng/mL) and decreased of IGFBP-1 (133 +/- 8 vs.153 +/- 9ng/mL).	Metformin	0-9	insulin like growth factor 1	Homo sapiens	93-98
11238496-0	2001	Insulin reduction with metformin increases luteal phase serum glycodelin and insulin-like growth factor-binding protein 1 concentrations and enhances uterine vascularity and blood flow in the polycystic ovary syndrome.	Metformin	23-32	insulin	Homo sapiens	0-7
11238496-6	2001	In the metformin group, the mean (+/-SE) area under the serum insulin curve after glucose administration decreased from 62 +/- 6 to 19 +/- 2 nmol/L.min (P &lt; 0.001).	Metformin	7-16	insulin	Homo sapiens	62-69
11158071-0	2001	Increased PAI-1 and tPA antigen levels are reduced with metformin therapy in HIV-infected patients with fat redistribution and insulin resistance.	Metformin	56-65	plasminogen activator, tissue type	Homo sapiens	20-23
11158071-0	2001	Increased PAI-1 and tPA antigen levels are reduced with metformin therapy in HIV-infected patients with fat redistribution and insulin resistance.	Metformin	56-65	insulin	Homo sapiens	127-134
11158071-8	2001	Twelve weeks of metformin treatment resulted in decreased tPA antigen levels (-1.9 +/- 1.4 vs +1.4 +/- 1.0 microg/L in the placebo-treated group P = 0.02).	Metformin	16-25	plasminogen activator, tissue type	Homo sapiens	58-61
11158071-12	2001	Metformin reduces PAI-1 and tPA antigen concentrations in these patients and may ultimately improve associated CVD risk.	Metformin	0-9	plasminogen activator, tissue type	Homo sapiens	28-31
11460577-5	2001	The category of insulin sensitizers includes metformin and thiazolidinediones.	Metformin	45-54	insulin	Homo sapiens	16-23
12622887-6	2001	The association biguanides and S, in particular glibenclamide plus metformin, is now widely used by diabetologists in SF since glibenclamide improves insulin secretion while metformin exerts its antidiabetic.	Metformin	67-76	insulin	Homo sapiens	150-157
11118008-6	2000	Metformin reduced that rate by 24% (to 0.53 +/- 0.03 mmol x m(-2) x min(-1), P = 0.0009) and fasting plasma glucose concentration by 30% (to 10.8 +/- 0.9 mmol/l, P = 0.0002).	Metformin	0-9	CD59 molecule (CD59 blood group)	Homo sapiens	68-74
15635851-1	2001	UNLABELLED: The objective of the investigation was to evaluate the effect of metformin added to the usual insulin treatment on insulin resistance, on the dose of substituted insulin and on the compensation of type 1 diabetes.	Metformin	77-86	insulin	Homo sapiens	127-134
15635851-1	2001	UNLABELLED: The objective of the investigation was to evaluate the effect of metformin added to the usual insulin treatment on insulin resistance, on the dose of substituted insulin and on the compensation of type 1 diabetes.	Metformin	77-86	insulin	Homo sapiens	127-134
15635851-8	2001	Insulin resistance was assessed by means of a hyperinsular euglycaemic clamp (insulinaemia 100 mlU/l) at the onset of the study (B), after three months of metformin treatment which was added to the insulin regimen in a dose of 2 x 850 mg (M).	Metformin	155-164	insulin	Homo sapiens	0-7
15635851-17	2001	CONCLUSION: After adding metformin to the insulin regimen of type 2 diabetics after three months a statistically significant drop of body weight and the daily insulin dose occurred.	Metformin	25-34	insulin	Homo sapiens	42-49
15635851-17	2001	CONCLUSION: After adding metformin to the insulin regimen of type 2 diabetics after three months a statistically significant drop of body weight and the daily insulin dose occurred.	Metformin	25-34	insulin	Homo sapiens	159-166
11257323-11	2000	Insulin resistance measured by the homeostasis model decreased more in the metformin group than in the glibenclamide group.	Metformin	75-84	insulin	Homo sapiens	0-7
11257323-13	2000	CONCLUSIONS: Metformin significantly decreased the urine albumin excretion rate with none of the expected changes in renal hemodynamics, probably due to its favorable effects on blood pressure, lipid profile, metabolic control, and insulin resistance.	Metformin	13-22	insulin	Homo sapiens	232-239
11246821-7	2000	Metformin 0.1-10 mM inhibited interleukin-8 release by 20-50% (p &lt; 0.05) and mRNA expression by 20-90% (p &lt; 0.05).	Metformin	0-9	C-X-C motif chemokine ligand 8	Homo sapiens	30-43
11129120-5	2000	Metformin and the recently introduced thiazolidinediones have beneficial effects on reducing insulin resistance as well as providing glycaemic control.	Metformin	0-9	insulin	Homo sapiens	93-100
11087006-10	2000	The combination of insulin with metformin or a thiazolidinedione is more logical as insulin resistance is targeted directly.	Metformin	32-41	insulin	Homo sapiens	84-91
11965830-7	2000	Metformin, which reduces insulin resistance and hyperinsulinaemia, is being assessed in this same trial.	Metformin	0-9	insulin	Homo sapiens	25-32
11061495-3	2000	We tested the hypothesis by assessing the effects of an insulin-sensitizing agent, metformin, given at a daily dose of 1275 mg for 6 months to 10 nonobese adolescent girls (mean age, 16.8 yr; body mass index, 21.9 kg/m2; birth weight, 2.7 kg) with hirsutism, ovarian hyperandrogenism (diagnosis by GnRH agonist test), oligomenorrhea, dyslipidemia, and hyperinsulinemia after precocious pubarche.	Metformin	83-92	insulin	Homo sapiens	56-63
11061495-5	2000	Metformin treatment was well tolerated and was accompanied by a marked drop in hirsutism score, insulin response to oral glucose tolerance test, free androgen index, and baseline testosterone, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate levels (all P &lt; 0.01).	Metformin	0-9	insulin	Homo sapiens	96-103
11225659-17	2000	Although metformin monotherapy ameliorated the imbalance between free radical-induced increase in lipid peroxidation (by reducing the MDA level in both erythrocytes and plasma) and decreased plasma and cellular antioxidant defences (by increasing the erythrocyte activities of Cu, Zn, SOD, catalase and GSH level) and decreased erythrocyte susceptibility to oxidative stress, it had negligible effect to scavenge Fe ion-induced free radical generation in a phospholipid-liposome system.	Metformin	9-18	superoxide dismutase 1	Homo sapiens	285-288
10946879-0	2000	Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome.	Metformin	35-44	insulin	Homo sapiens	127-134
10946879-2	2000	Dietary-induced weight loss and the administration of insulin-lowering drugs, such as metformin, are usually followed by improved hyperandrogenism and related clinical abnormalities.	Metformin	86-95	insulin	Homo sapiens	54-61
10946879-18	2000	Fasting insulin significantly decreased in both PCOS women and controls, regardless of treatment, whereas glucose-stimulated insulin significantly decreased only in PCOS women and controls treated with metformin.	Metformin	202-211	insulin	Homo sapiens	125-132
11225659-17	2000	Although metformin monotherapy ameliorated the imbalance between free radical-induced increase in lipid peroxidation (by reducing the MDA level in both erythrocytes and plasma) and decreased plasma and cellular antioxidant defences (by increasing the erythrocyte activities of Cu, Zn, SOD, catalase and GSH level) and decreased erythrocyte susceptibility to oxidative stress, it had negligible effect to scavenge Fe ion-induced free radical generation in a phospholipid-liposome system.	Metformin	9-18	catalase	Homo sapiens	290-298
11789189-4	2000	RESULTS: After treatment for three months with metformin or TGF, fasting and the integrated insulin response to the glucose load decreased.	Metformin	47-56	insulin	Homo sapiens	92-99
10904511-13	2000	CONCLUSIONS: This study suggests that a relatively low dosage of metformin reduces insulin resistance and related cardiovascular risk parameters in HIV-infected patients with lipodystrophy.	Metformin	65-74	insulin	Homo sapiens	83-90
10856473-7	2000	RESULT(S): Metformin therapy resulted in a significant decrease in fasting insulin and total T and an increase in SHBG, leading to a decrease in the free T index.	Metformin	11-20	insulin	Homo sapiens	75-82
12132467-1	2000	Metformin for insulin and heart problems?	Metformin	0-9	insulin	Homo sapiens	14-21
11242605-0	2000	How long can insulin therapy be avoided in the patient with type 2 diabetes mellitus by use of a combination of metformin and a sulfonylurea?	Metformin	112-121	insulin	Homo sapiens	13-20
11242605-7	2000	CONCLUSION: When oral monotherapy fails (that is, glycosylated hemoglobin values exceed 8.0%) in patients with type 2 diabetes, combination therapy with a sulfonylurea and metformin is potentially effective in maintaining glycemic control and avoiding the addition of insulin or a thiazolidinedione for a mean duration of 7.9 years.	Metformin	172-181	insulin	Homo sapiens	268-275
10929918-3	2000	Metformin is a biguanide antihyperglycemic agent that increases peripheral insulin sensitivity, reduces hepatic gluconeogenesis, and decreases intestinal glucose absorption.	Metformin	0-9	insulin	Homo sapiens	75-82
10929918-13	2000	CONCLUSIONS: Combination therapy with metformin and insulin improves glycemic control and reduces insulin requirements.	Metformin	38-47	insulin	Homo sapiens	98-105
10856473-7	2000	RESULT(S): Metformin therapy resulted in a significant decrease in fasting insulin and total T and an increase in SHBG, leading to a decrease in the free T index.	Metformin	11-20	sex hormone binding globulin	Homo sapiens	114-118
10900588-4	2000	Metformin, a medication that improves insulin sensitivity and decreases serum insulin levels, restores menstrual cyclicity and ovulatory function and may improve fertility rates in women with PCOS.	Metformin	0-9	insulin	Homo sapiens	38-45
10900588-4	2000	Metformin, a medication that improves insulin sensitivity and decreases serum insulin levels, restores menstrual cyclicity and ovulatory function and may improve fertility rates in women with PCOS.	Metformin	0-9	insulin	Homo sapiens	78-85
10900588-9	2000	CONCLUSION: These three patients reflect the heterogeneous nature of PCOS, and treating their underlying insulin resistance with metformin resulted in pregnancy.	Metformin	129-138	insulin	Homo sapiens	105-112
10872292-7	2000	The group of insulin sensitizers includes the biguanide, metformin and the thiazolidinediones or glitazones (rosiglitazone, pioglitazone).	Metformin	57-66	insulin	Homo sapiens	13-20
10831236-12	2000	The extract, as well as metformin, significantly increased the activity of SOD and CAT, but had no significant effect on GSH-Px activity in diabetic rats.	Metformin	24-33	catalase	Rattus norvegicus	83-86
11467307-6	2000	Among antidiabetic agents, sulfonylureas and insulin are associated with risk for severe hypoglycemia, metformin with risk for lactic acidosis, and troglitazone with risk for idiosyncratic hepatocellular injury.	Metformin	103-112	insulin	Homo sapiens	45-52
10770203-0	2000	Effect of metformin on insulin-like growth factor (IGF) I and IGF-binding protein I in polycystic ovary syndrome.	Metformin	10-19	insulin	Homo sapiens	23-30
10770203-1	2000	The objective of the present study was to investigate whether metformin affected plasma concentrations of insulin-like growth factor (IGF) I and IGF-binding protein I (IGFBP-I) in polycystic ovary syndrome (PCOS) patients.	Metformin	62-71	insulin like growth factor 1	Homo sapiens	106-140
10770203-7	2000	A nonsignificant increase in plasma IGF-I levels was observed after metformin (276 +/-48 vs. 291 +/- 71 mcg/L), with a significant increase in plasma IGFBP-I levels (0.56 +/- 0.2 vs. 0.98 +/- 0.38 mcg/L; P &lt; 0.05).	Metformin	68-77	insulin like growth factor 1	Homo sapiens	36-41
10770203-9	2000	In conclusion, it seems to be appropriate to intervene with an insulin-sensitizing agent such as metformin in an attempt to break the pathogenetic link between hyperinsulinemia and hormonal perturbations in PCOS.	Metformin	97-106	insulin	Homo sapiens	63-70
10928231-1	2000	Unlike other pharmacological therapies used in obese type 2 diabetic patients, metformin has been shown to improve glycemic control with lower insulin levels and not to involve weight gain.	Metformin	79-88	insulin	Homo sapiens	143-150
10928231-6	2000	Total exogenous insulin requirements decreased from 53 +/- 10 to 35 +/- 7 units during metformin treatment (p = 0.02 vs. placebo).	Metformin	87-96	insulin	Homo sapiens	16-23
10928231-9	2000	During the oral glucose tolerance test no differences were observed in the areas under the curve for glucose and insulin while that for C-peptide showed a tendency to increase during metformin administration.	Metformin	183-192	insulin	Homo sapiens	136-145
10928231-11	2000	With adjunct metformin, approximately 30% less exogenous insulin is required.	Metformin	13-22	insulin	Homo sapiens	57-64
10928231-12	2000	With respect to glycemia and lipids, adjunct metformin can be a reasonable treatment alternative in selected obese patients with type 2 diabetes already on intensive insulin therapy.	Metformin	45-54	insulin	Homo sapiens	166-173
10789389-2	2000	A new class of insulin-sensitizing agents, the thiazolidinediones, reduce insulin resistance and improve glycaemia both as monotherapy and in combination with sulphonylureas or metformin.	Metformin	177-186	insulin	Homo sapiens	15-22
11225759-11	2000	When glucose targets are not met using repaglinide monotherapy, the combination of repaglinide with metformin can further improve glycaemic control by enhancing insulin secretion and improving insulin sensitivity.	Metformin	100-109	insulin	Homo sapiens	161-168
10707032-3	2000	METHODS: A randomised double-blind trial comparing metformin treatment (850 mg bid) with placebo.	Metformin	51-60	BH3 interacting domain death agonist	Homo sapiens	79-82
10707032-5	2000	In comparison with the placebo group, fasting plasma insulin (p&lt;0.04), total cholesterol (p&lt;0.05) and Apo B (p&lt;0.008) concentrations decreased more in the metformin group in the BIGPRO 1.	Metformin	164-173	apolipoprotein B	Homo sapiens	108-113
11419922-8	2000	The dose of insulin was reduced from a baseline of 62 to 41 U per patient in the insulin-only treatment group, from 36 to 12 U per patient in the group treated with insulin and sulfonylurea, and from 28 to 11 U per patient in the group treated with insulin and metformin.	Metformin	261-270	insulin	Homo sapiens	12-19
11419922-9	2000	In the group treated with insulin, sulfonylurea, and metformin, the dose of insulin was decreased from 36 to 13 U.	Metformin	53-62	insulin	Homo sapiens	76-83
11844361-7	2000	Strategies to lower serum insulin concentrations include diet, exercise and possibly, oral insulin sensitizing agents such as metformin.	Metformin	126-135	insulin	Homo sapiens	26-33
10776038-0	2000	[Effectiveness of treatment with metformin in patients with type 2 diabetes mellitus poorly controlled with insulin treatment].	Metformin	33-42	insulin	Homo sapiens	108-115
10776038-1	2000	Combined treatment with insulin plus metformin could be a good alternative to improve the glycemic control in patients with type 2 diabetes mellitus poorly controlled with insulin therapy.	Metformin	37-46	insulin	Homo sapiens	172-179
10776038-5	2000	Our results suggest that the addition of metformin to insulin treatment is a safe and effective strategy for the improvement of glycemic control among obese type 2 diabetic patients.	Metformin	41-50	insulin	Homo sapiens	54-61
10634377-0	2000	Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation.	Metformin	0-9	insulin	Homo sapiens	78-85
10634377-7	2000	Women given metformin showed reduced plasma insulin (at fasting: P = 0.057; during the clamp studies: P&lt;0.01) and increased insulin sensitivity (P&lt;0.05).	Metformin	12-21	insulin	Homo sapiens	44-51
10634377-7	2000	Women given metformin showed reduced plasma insulin (at fasting: P = 0.057; during the clamp studies: P&lt;0.01) and increased insulin sensitivity (P&lt;0.05).	Metformin	12-21	insulin	Homo sapiens	127-134
10634377-16	2000	Higher plasma insulin, lower serum androstenedione, and less severe menstrual abnormalities are baseline predictors of clinical response to metformin.	Metformin	140-149	insulin	Homo sapiens	14-21
10643226-3	1999	The rationale for adding metformin in these cases is that it can reduce insulin resistance.	Metformin	25-34	insulin	Homo sapiens	72-79
10643226-7	1999	A combination of insulin and metformin is recommended especially for obese type II diabetes patients on high insulin doses.	Metformin	29-38	insulin	Homo sapiens	109-116
10605995-3	1999	Acarbose, metformin, miglitol, pioglitazone, rosiglitazone and troglitazone help the patient"s own insulin control glucose levels and allow early treatment with little risk of hypoglycemia.	Metformin	10-19	insulin	Homo sapiens	99-106
11844364-6	2000	The recognition of an association between hyperinsulinaemia and PCOS has resulted in the use of insulin sensitizing agents, such as metformin, which appear to ameliorate the biochemical profile and improve reproductive function.	Metformin	132-141	insulin	Homo sapiens	47-54
10611182-0	2000	Metformin treatment reduces ovarian cytochrome P-450c17alpha response to human chorionic gonadotrophin in women with insulin resistance-related polycystic ovary syndrome.	Metformin	0-9	insulin	Homo sapiens	117-124
10611182-7	2000	The administration of metformin was associated with a decrease in area under the curve for insulin during a 2h, 75g oral glucose tolerance test, in plasma free testosterone concentrations and an increase in plasma sex hormone binding globulin concentration.	Metformin	22-31	insulin	Homo sapiens	91-98
10593368-1	1999	OBJECTIVE: To determine whether the administration of metformin, an insulin-sensitizing agent, is followed by changes in adrenal steroidogenesis in women with polycystic ovary syndrome (PCOS).	Metformin	54-63	insulin	Homo sapiens	68-75
10580431-0	1999	A comparison of troglitazone and metformin on insulin requirements in euglycemic intensively insulin-treated type 2 diabetic patients.	Metformin	33-42	insulin	Homo sapiens	46-53
10580431-4	1999	Insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp 1) at baseline, 2) after 4 weeks of CSII, and 3) after CSII plus either troglitazone or metformin.	Metformin	160-169	insulin	Homo sapiens	0-7
10580431-10	1999	Insulin sensitivity did not change significantly with CSII alone or with CSII plus metformin, but improved 29% with CSII plus troglitazone (P &lt; 0.005 vs. CSII alone) and was then 45% higher than in the CSII plus metformin patients (P &lt; 0.005).	Metformin	215-224	insulin	Homo sapiens	0-7
10593368-10	1999	The administration of metformin was associated with a significant reduction in the response of 17alpha-hydroxyprogesterone, testosterone, free testosterone, and androstenedione to ACTH.	Metformin	22-31	proopiomelanocortin	Homo sapiens	180-184
10593368-12	1999	CONCLUSION(S): The administration of metformin to unselected women with PCOS led to a reduction in the adrenal steroidogenesis response to ACTH.	Metformin	37-46	proopiomelanocortin	Homo sapiens	139-143
10535741-6	1999	At present, metformin and thiazolidinediones are the only therapies for T2DM that directly address aspects of insulin resistance.	Metformin	12-21	insulin	Homo sapiens	110-117
10630028-1	1999	OBJECTIVES: Principal: to show that the addition of metformin to insulin treatment in type-2 DM obese patients with poor metabolic control (HbA1c &gt; 7.5%) causes a 50% increase after one year in the number of patients with acceptable (HbA1c &lt; or = 7.5%) or good (HbA1c &lt; 6.5%) control, and to determine how many patients reduced their HbA1c by a point.	Metformin	52-61	insulin	Homo sapiens	65-72
10630028-12	1999	CONCLUSIONS: Adding metformin to the treatment of obese type-2 DM patients with poor metabolic control and on insulin treatment improved their control.	Metformin	20-29	insulin	Homo sapiens	110-117
10634965-0	1999	Reversal of increased lymphocyte PC-1 activity in patients with type 2 diabetes treated with metformin.	Metformin	93-102	ectonucleotide pyrophosphatase/phosphodiesterase 1	Homo sapiens	33-37
10634965-2	1999	Metformin increases peripheral insulin sensitivity and, therefore, we have studied the effect of metformin treatment on lymphocyte PC-1 (ecto-alkaline phosphodiesterase I, APD) in patients with Type 2 diabetes.	Metformin	97-106	ectonucleotide pyrophosphatase/phosphodiesterase 1	Homo sapiens	131-135
10634965-4	1999	RESULTS: Lymphocyte PC-1 in patients with Type 2 diabetes was increased significantly (p&lt;0.001) over control; however, metformin treatment brought its activity in unstimulated and Con A-stimulated lymphocytes to the control level.	Metformin	122-131	ectonucleotide pyrophosphatase/phosphodiesterase 1	Homo sapiens	20-24
10634965-5	1999	PMA-stimulated PC-1 in patients with Type 2 diabetes was 17-times higher than in controls, and was reduced to near the control level by 3-month metformin treatment.	Metformin	144-153	ectonucleotide pyrophosphatase/phosphodiesterase 1	Homo sapiens	15-19
10634965-8	1999	CONCLUSION: This study has shown an increased activity of lymphocyte PC-1 in Type 2 diabetes and its reversal by 3-month metformin treatment, corresponding to the improvement of insulin sensitivity.	Metformin	121-130	ectonucleotide pyrophosphatase/phosphodiesterase 1	Homo sapiens	69-73
10634965-9	1999	Data obtained are consistent with a role of PC-1 in insulin resistance and suggest a new mechanism of action for metformin via PC-1 inhibition.	Metformin	113-122	ectonucleotide pyrophosphatase/phosphodiesterase 1	Homo sapiens	127-131
15251651-7	1999	This reassessment followed a 12-week period of therapy to determine whether treatment of insulin resistance with the combination of metformin and troglitazone could normalize the impaired glucose tolerance in type 2 diabetes.	Metformin	132-141	insulin	Homo sapiens	89-96
15251651-11	1999	Combination treatment with metformin and troglitazone for 12 weeks resulted in a significant reduction in the C-peptide response and glucose variables after the glucose load.	Metformin	27-36	insulin	Homo sapiens	110-119
10601079-2	1999	The aim of this study was to examine the effects of the insulin sensitizing drug, metformin, on ovarian function, follicular growth, and ovulation rate in obese women with oligomenorrhoea.	Metformin	82-91	insulin	Homo sapiens	56-63
10428734-4	1999	OBJECTIVE: To evaluate the efficacy of metformin in combination with insulin in patients with type 2 diabetes poorly controlled with insulin therapy alone.	Metformin	39-48	insulin	Homo sapiens	133-140
10428734-11	1999	For patients who received placebo, the insulin dose increased 22.8 units (CI, 11 to 44 units) or 29% more than did the dose for patients who received metformin (P = 0.002); for these patients, the insulin dose decreased slightly.	Metformin	150-159	insulin	Homo sapiens	39-46
10468995-0	1999	The effects of metformin on insulin resistance and ovarian steroidogenesis in women with polycystic ovary syndrome.	Metformin	15-24	insulin	Homo sapiens	28-35
20625965-8	2010	Treatment with metformin to improve insulin resistance and address the diabetes proved successful.	Metformin	15-24	insulin	Homo sapiens	36-43
10477209-8	1999	CONCLUSIONS: These results indicate that metformin administration to patients with IGT is associated with enhanced glucose disposal at baseline insulin concentrations and a fall in blood pressure.	Metformin	41-50	insulin	Homo sapiens	144-151
10468995-4	1999	The aim of the present study was to determine whether reduction of insulin levels by metformin would attenuate FSH, LH, 17-Hydroxyprogesterone (17-OHP) and androstenedione hyperresponsiveness to buserelin testing in PCOS women.	Metformin	85-94	insulin	Homo sapiens	67-74
10468995-10	1999	Metformin therapy improved menstrual disturbances in 25% of the women with PCOS and also resulted in some improvement in insulin sensitivity and reduced basal and post glucose load insulin levels.	Metformin	0-9	insulin	Homo sapiens	121-128
10468995-10	1999	Metformin therapy improved menstrual disturbances in 25% of the women with PCOS and also resulted in some improvement in insulin sensitivity and reduced basal and post glucose load insulin levels.	Metformin	0-9	insulin	Homo sapiens	181-188
10468995-13	1999	These abnormalities explain the increased prevalence of glucose intolerance in women with PCOS and metformin has beneficial effects on insulin sensitivity in women with PCOS.	Metformin	99-108	insulin	Homo sapiens	135-142
10477209-1	1999	AIMS: This study was initiated to test the hypothesis that metformin treatment leads to enhanced glucose disposal at ambient insulin concentrations.	Metformin	59-68	insulin	Homo sapiens	125-132
10477209-4	1999	RESULTS: The average benefit of metformin was 0.6 mmol/l for glucose (95% confidence interval (CI) 0.2-0.9 P = 0.002), 2.8 pmol/l for insulin (95% CI 0.2-5.4, P = 0.019).	Metformin	32-41	insulin	Homo sapiens	134-141
10448935-3	1999	These cells possessed the specialized protein and, when treated with insulin (2 microM) plus metformin (20 microM), showed a markedly enhanced hexose transport activity (2.4-fold increase over basal) as compared to that of cells incubated in the presence of insulin alone (1.8-fold increase over basal).	Metformin	93-102	insulin	Homo sapiens	258-265
10480188-4	1999	The treatment of insulin resistance was for a long time limited to dietary and exercise programmes, a biguanide, metformine, and benfluorex, a phenylethylamine derivative; the mechanisms of action of both drugs are now better understood and their indications more precisely targeted.	Metformin	113-123	insulin	Homo sapiens	17-24
10352923-5	1999	The results of recent clinical studies of insulin-sensitizing agents such as metformin and the thiazoladinedione troglitazone in PCOS have provided encouragement that improvement of insulin sensitivity and consequent lowering of circulating insulin levels by these agents may be of therapeutic value in the management of both anovulation and hirsutism.	Metformin	77-86	insulin	Homo sapiens	42-49
10352923-5	1999	The results of recent clinical studies of insulin-sensitizing agents such as metformin and the thiazoladinedione troglitazone in PCOS have provided encouragement that improvement of insulin sensitivity and consequent lowering of circulating insulin levels by these agents may be of therapeutic value in the management of both anovulation and hirsutism.	Metformin	77-86	insulin	Homo sapiens	182-189
10352923-5	1999	The results of recent clinical studies of insulin-sensitizing agents such as metformin and the thiazoladinedione troglitazone in PCOS have provided encouragement that improvement of insulin sensitivity and consequent lowering of circulating insulin levels by these agents may be of therapeutic value in the management of both anovulation and hirsutism.	Metformin	77-86	insulin	Homo sapiens	182-189
10443322-0	1999	Membrane physiology as a basis for the cellular effects of metformin in insulin resistance and diabetes.	Metformin	59-68	insulin	Homo sapiens	72-79
10443322-3	1999	Metformin interferes with several processes linked to HGP (gluconeogenesis, glycogenolysis and their regulatory mechanisms), lowering glucose production and resensitizing the liver to insulin.	Metformin	0-9	insulin	Homo sapiens	184-191
10443322-9	1999	Exciting findings show that, conversely, priming cells with very low insulin concentrations also leads to full expression of metformin"s antidiabetic activity.	Metformin	125-134	insulin	Homo sapiens	69-76
10408737-7	1999	In addition to a variety of sulfonylureas, there is metformin, troglitazone, and/or alpha-glucosidase inhibitors, that are viable options to be used before turning to insulin.	Metformin	52-61	insulin	Homo sapiens	167-174
10337452-7	1999	With the respect to the trophic effect of amyloid deposits in the pancreatic islets and to a hypothetic effect of amylin increasing insulin resistance, the present results emphasize the particular usefulness of metformin in the pharmacological treatment of NIDDM.	Metformin	211-220	insulin	Homo sapiens	132-139
10230643-5	1999	The metformin group required 47 % less insulin than the group not using metformin (p &lt; 0.001).	Metformin	4-13	insulin	Homo sapiens	39-46
10206447-10	1999	On Metformin, the median fasting serum insulin decreased from 26 microU/mL to 22 (P=.019), testosterone decreased from 61 ng/dL to 47 (P=.003), and estradiol increased from 41 pg/mL to 71 (P=.0001).	Metformin	3-12	insulin	Homo sapiens	39-46
9932725-6	1999	In the presence of metformin, the islets fully maintained the ability to significantly increase their insulin release in response to glucose, even when previously exposed to 22.2 mmol/l glucose.	Metformin	19-28	insulin	Homo sapiens	102-109
10333912-7	1999	Subjects receiving repaglinide either alone or in combination with metformin, had an increase in fasting levels of insulin between baseline and the end of the trial of 4.04 +/- 1.56 and 4.23 +/- 1.50 mU/l, respectively (P &lt; 0.02).	Metformin	67-76	insulin	Homo sapiens	115-122
10576521-0	1999	Clinical efficacy of metformin against insulin resistance parameters: sinking the iceberg.	Metformin	21-30	insulin	Homo sapiens	39-46
10576521-6	1999	Thus, the well established effect of metformin in reducing insulin resistance makes this drug an excellent candidate for the prevention of progression of impaired glucose tolerance to type 2 diabetes, and for the reduction of mortality associated with cardiovascular disease.	Metformin	37-46	insulin	Homo sapiens	59-66
10576523-1	1999	Metformin is regarded as an antihyperglycaemic agent because it lowers blood glucose concentrations in type 2 (non-insulin-dependent) diabetes without causing overt hypoglycaemia.	Metformin	0-9	insulin	Homo sapiens	115-122
10576523-4	1999	Metformin acts on the liver to suppress gluconeogenesis mainly by potentiating the effect of insulin, reducing hepatic extraction of certain substrates (e.g. lactate) and opposing the effects of glucagon.	Metformin	0-9	insulin	Homo sapiens	93-100
10576523-6	1999	Insulin-stimulated glucose uptake into skeletal muscle is enhanced by metformin.	Metformin	70-79	insulin	Homo sapiens	0-7
10576523-8	1999	Metformin also appears to increase the functional properties of insulin- and glucose-sensitive transporters.	Metformin	0-9	insulin	Homo sapiens	64-71
10576523-10	1999	Other effects involved in the blood glucose-lowering effect of metformin include an insulin-independent suppression of fatty acid oxidation and a reduction in hypertriglyceridaemia.	Metformin	63-72	insulin	Homo sapiens	84-91
10576523-13	1999	Metformin improves insulin sensitivity by increasing insulin-mediated insulin receptor tyrosine kinase activity, which activates post-receptor insulin signalling pathways.	Metformin	0-9	insulin	Homo sapiens	19-26
10576523-13	1999	Metformin improves insulin sensitivity by increasing insulin-mediated insulin receptor tyrosine kinase activity, which activates post-receptor insulin signalling pathways.	Metformin	0-9	insulin	Homo sapiens	53-60
10576523-13	1999	Metformin improves insulin sensitivity by increasing insulin-mediated insulin receptor tyrosine kinase activity, which activates post-receptor insulin signalling pathways.	Metformin	0-9	insulin	Homo sapiens	53-60
10576523-13	1999	Metformin improves insulin sensitivity by increasing insulin-mediated insulin receptor tyrosine kinase activity, which activates post-receptor insulin signalling pathways.	Metformin	0-9	insulin	Homo sapiens	53-60
10576523-15	1999	Metformin therefore improves hepatic and peripheral sensitivity to insulin, with both direct and indirect effects on liver and muscle.	Metformin	0-9	insulin	Homo sapiens	67-74
10576524-6	1999	Controlled studies have shown that metformin administration, by promoting bodyweight loss, can decrease fasting and stimulated plasma insulin levels.	Metformin	35-44	insulin	Homo sapiens	134-141
10576524-9	1999	They also suggest that long term administration of metformin might be helpful in treating insulin resistance, thus reducing risks of type 2 (non-insulin-dependent) diabetes and cardiovascular disease in these patients.	Metformin	51-60	insulin	Homo sapiens	90-97
10576524-9	1999	They also suggest that long term administration of metformin might be helpful in treating insulin resistance, thus reducing risks of type 2 (non-insulin-dependent) diabetes and cardiovascular disease in these patients.	Metformin	51-60	insulin	Homo sapiens	145-152
10576526-0	1999	Metformin prevents weight gain by reducing dietary intake during insulin therapy in patients with type 2 diabetes mellitus.	Metformin	0-9	insulin	Homo sapiens	65-72
10037253-12	1999	Metformin therapy resulted in some improvement in insulin sensitivity and reduced the basal and post-glucose load insulin levels.	Metformin	0-9	insulin	Homo sapiens	50-57
10037253-12	1999	Metformin therapy resulted in some improvement in insulin sensitivity and reduced the basal and post-glucose load insulin levels.	Metformin	0-9	insulin	Homo sapiens	114-121
10554568-2	1999	Metformin plays a particularly important role in the treatment of diabetes mellitus type 2 by decreasing insulin resistance.	Metformin	0-9	insulin	Homo sapiens	105-112
9932820-6	1999	Metformin and troglitazone, approved for use in the treatment of type 2 diabetes mellitus (DM), improve insulin sensitivity and lower plasma glucose concentrations.	Metformin	0-9	insulin	Homo sapiens	104-111
9868971-6	1998	These data suggest that adding metformin to insulin in poorly controlled Type 2 DM patients offers an advantage in terms of glycaemic control and lipid plasma profile.	Metformin	31-40	insulin	Homo sapiens	44-51
10806662-4	1998	RESULTS: After oral administration of metformin for 8-12 weeks, fasting insulin concentration in obese group and area under curve (AUC) after OGTT in lean group decreased significantly.	Metformin	38-47	insulin	Homo sapiens	72-79
9802752-3	1998	Metformin has been shown to improve insulin sensitivity and fibrinolysis.	Metformin	0-9	insulin	Homo sapiens	36-43
9802752-10	1998	In contrast to the results for PAI-1, there was a significantly greater decrease in tissue-type plasminogen activator (tPA) antigen in the metformin than in the placebo group (mean+/-SD: -1.1+/-3.1 vs. 0.2+/-3.2 ng/ml, P &lt; 0.02).	Metformin	139-148	plasminogen activator, tissue type	Homo sapiens	84-117
9802752-10	1998	In contrast to the results for PAI-1, there was a significantly greater decrease in tissue-type plasminogen activator (tPA) antigen in the metformin than in the placebo group (mean+/-SD: -1.1+/-3.1 vs. 0.2+/-3.2 ng/ml, P &lt; 0.02).	Metformin	139-148	plasminogen activator, tissue type	Homo sapiens	119-122
9802752-11	1998	The von Willebrand factor (vWF) also decreased significantly more in the metformin group (-0.17+/-0.42 vs. -0.05+/-0.38 U/I, P &lt; 0.02).	Metformin	73-82	von Willebrand factor	Homo sapiens	4-25
9802752-11	1998	The von Willebrand factor (vWF) also decreased significantly more in the metformin group (-0.17+/-0.42 vs. -0.05+/-0.38 U/I, P &lt; 0.02).	Metformin	73-82	von Willebrand factor	Homo sapiens	27-30
9802752-13	1998	Metformin had a significant effect on two factors, tPA antigen and vWF, mainly secreted by the endothelial cells, which suggests an effect of the drug on the production or the metabolism of these two hemostatic proteins.	Metformin	0-9	plasminogen activator, tissue type	Homo sapiens	51-54
9802752-13	1998	Metformin had a significant effect on two factors, tPA antigen and vWF, mainly secreted by the endothelial cells, which suggests an effect of the drug on the production or the metabolism of these two hemostatic proteins.	Metformin	0-9	von Willebrand factor	Homo sapiens	67-70
15251708-11	1998	CONCLUSION: From this retrospective study of patients with type 2 diabetes, we conclude that conversion from insulin to combination oral therapy with sulfonylureas and metformin results in a significant weight loss for up to 21 months.	Metformin	168-177	insulin	Homo sapiens	109-116
15251717-6	1998	Metformin ameliorates insulin resistance, reduces hyperinsulinemia, and counteracts weight gain.	Metformin	0-9	insulin	Homo sapiens	22-29
9824974-4	1998	The biguanide metformin is especially useful in obese, insulin-resistant patients.	Metformin	14-23	insulin	Homo sapiens	55-62
9727896-7	1998	Total glucose disposal at euglycemic-hyperinsulinemic clamp increased significantly in the metformin group by 25% at high insulin level (259 +/- 31 vs. 207 +/- 21 mg x m(-2) x min(-1), P &lt; 0.05).	Metformin	91-100	insulin	Homo sapiens	42-49
9727896-13	1998	The added effect of metformin to that of a hypocaloric diet in improving insulin-stimulated glucose utilization is marginal when blood glucose reduction is obtained by weight loss.	Metformin	20-29	insulin	Homo sapiens	73-80
15251721-1	1998	OBJECTIVE: To assess whether, in the treatment of non-insulin-dependent diabetes mellitus (NIDDM), (1) metformin in conjunction with insulin can safely cause a decrease in glycosylated hemoglobin (HbA1c) to 7% or less and (2) this combination therapy may result in weight loss and lower insulin dose in comparison with insulin treatment alone.	Metformin	103-112	insulin	Homo sapiens	54-61
9949668-0	1998	Effects of metformin on fibrinogen levels in obese patients with type 2 diabetes.	Metformin	11-20	fibrinogen beta chain	Homo sapiens	24-34
9949668-13	1998	CONCLUSIONS: In addition to improving metabolic control, metformin showed to be a good therapeutic alternative in modifying fibrinogen levels in type 2 diabetic patients.	Metformin	57-66	fibrinogen beta chain	Homo sapiens	124-134
9702437-9	1998	Finally, the ability of insulin to inhibit isoproterenol-stimulated increases in plasma FFA concentration was enhanced in metformin-treated patients (P &lt; 0.05).	Metformin	122-131	insulin	Homo sapiens	24-31
9702437-11	1998	Although overnight HGP was unchanged after treatment with metformin, the overnight glucose MCR was significantly increased, and the antilipolytic activity of insulin was also enhanced.	Metformin	58-67	insulin	Homo sapiens	158-165
9737829-3	1998	The purpose of this retrospective chart review was to determine the effects of adding metformin in an uncontrolled fashion to existing therapy in obese patients with type 2 diabetes who had suboptimal glycemic control and insulin resistance.	Metformin	86-95	insulin	Homo sapiens	222-229
9737829-5	1998	Metformin was added to patients" existing therapy in conjunction with downward titration of the sulfonylurea and insulin doses.	Metformin	0-9	insulin	Homo sapiens	113-120
9737829-11	1998	The addition of metformin to treatment with insulin or sulfonylureas, either alone or in combination, significantly improved glycemic control and cholesterol levels and promoted weight loss in obese type 2 diabetic patients with insulin resistance.	Metformin	16-25	insulin	Homo sapiens	44-51
9737829-11	1998	The addition of metformin to treatment with insulin or sulfonylureas, either alone or in combination, significantly improved glycemic control and cholesterol levels and promoted weight loss in obese type 2 diabetic patients with insulin resistance.	Metformin	16-25	insulin	Homo sapiens	229-236
9661644-6	1998	These results indicate that insulin sensitizing therapy with metformin decreases the leptin concentrations in obese PCOS women.	Metformin	61-70	insulin	Homo sapiens	28-35
9637806-2	1998	We hypothesized that reducing insulin secretion by administering metformin would increase the ovulatory response to clomiphene.	Metformin	65-74	insulin	Homo sapiens	30-37
9637806-7	1998	Among the 21 women given metformin plus clomiphene, the mean (+/-SE) area under the serum insulin curve after oral glucose administration decreased from 6745+/-2021 to 3479+/-455 microU per milliliter per minute (40.5+/-12.1 to 20.9+/-2.7 nmol per liter per minute, P=0.03), but it did not change significantly in the 25 women given placebo plus clomiphene.	Metformin	25-34	insulin	Homo sapiens	90-97
9637806-11	1998	CONCLUSIONS: The ovulatory response to clomiphene can be increased in obese women with the polycystic ovary syndrome by decreasing insulin secretion with metformin.	Metformin	154-163	insulin	Homo sapiens	131-138
11228758-6	1999	RESULTS: Lower proinsulin levels were found when therapy was initiated with metformin (M vs. G, p = 0.013 and M/G vs. G/M, p = 0.033).	Metformin	76-85	insulin	Homo sapiens	15-25
10392666-3	1999	Metformin counters insulin resistance and offers benefits against many features of the insulin resistance syndrome (Syndrome X) by preventing bodyweight gain, reducing hyperinsulinaemia and improving the lipid profile.	Metformin	0-9	insulin	Homo sapiens	19-26
10371188-0	1999	Effects of metformin on insulin resistance and central adiposity in patients receiving effective protease inhibitor therapy.	Metformin	11-20	insulin	Homo sapiens	24-31
10069357-6	1999	Improved insulin sensitivity through lifestyle modifications or pharmacologic therapy (troglitazone and metformin) will lower both insulin and glucose levels as well as diminish dyslipidemia and hypertension.	Metformin	104-113	insulin	Homo sapiens	9-16
10069357-6	1999	Improved insulin sensitivity through lifestyle modifications or pharmacologic therapy (troglitazone and metformin) will lower both insulin and glucose levels as well as diminish dyslipidemia and hypertension.	Metformin	104-113	insulin	Homo sapiens	131-138
10448935-5	1999	When metformin was added together with insulin, we mainly recorded a significant decrease in apparent Km for the sugar transported, Vmax being only marginally modified.	Metformin	5-14	insulin	Homo sapiens	39-46
10448935-6	1999	Parathyroid hormone (PTH), which is known to impair the intrinsic activity of GLUT4, prevented the stimulatory effect of metformin in both kinds of oocytes whereas cytochalasin D, which interferes with the translocation of carriers, was without effect.	Metformin	121-130	parathyroid hormone	Homo sapiens	0-19
10448935-6	1999	Parathyroid hormone (PTH), which is known to impair the intrinsic activity of GLUT4, prevented the stimulatory effect of metformin in both kinds of oocytes whereas cytochalasin D, which interferes with the translocation of carriers, was without effect.	Metformin	121-130	parathyroid hormone	Homo sapiens	21-24
9519921-6	1998	For persons whose glycemia can be adequately controlled with oral agents, the use of agents such as metformin and troglitazone--which do not raise, and may even lower, insulin concentrations--may offer an advantage.	Metformin	100-109	insulin	Homo sapiens	168-175
9589227-1	1998	OBJECTIVE: To test the hypothesis that metformin therapy, given as an adjunct to insulin therapy, improves metabolic control in insulin-treated NIDDM patients with suboptimal glycemic control.	Metformin	39-48	insulin	Homo sapiens	128-135
9589227-15	1998	CONCLUSIONS: Metformin, when given as adjunctive therapy, was well tolerated and improved glycemic control and lipid concentrations in patients with insulin-treated NIDDM whose diabetes was poorly controlled.	Metformin	13-22	insulin	Homo sapiens	149-156
9589814-4	1998	Treatment of insulin resistance includes metformin and the thiazolidinedione troglitazone.	Metformin	41-50	insulin	Homo sapiens	13-20
15251750-13	1998	CONCLUSION: Improvement in glycosylated hemoglobin level in insulin-using patients with NIDDM can be obtained with combination oral therapy alone, combination oral therapy with once-daily evening insulin, or twice-daily mixed insulin with metformin in comparison with twice-daily insulin alone.	Metformin	239-248	insulin	Homo sapiens	60-67
9559489-7	1998	When used alone or in combination with sulfonylureas, metformin tends to stabilize or decrease weight, maintains or reduces insulin levels, has beneficial effects on plasma lipid profiles, and may also have beneficial effects on blood pressure and the fibrinolytic system.	Metformin	54-63	insulin	Homo sapiens	124-131
9539300-0	1998	Therapeutic effects of metformin on insulin resistance and hyperandrogenism in polycystic ovary syndrome.	Metformin	23-32	insulin	Homo sapiens	36-43
9514089-2	1998	We now report that therapeutic concentrations (approximately 1 microg/mL) of metformin stimulated the tyrosine kinase activity of the intracellular portion of the beta-subunit of the human insulin receptor (IPbetaIRK), the intracellular portion of the epidermal growth factor receptor and pp60-src, but not cAMP-dependent protein kinase.	Metformin	77-86	epidermal growth factor receptor	Homo sapiens	252-284
9505147-1	1998	Metformin reduces insulin resistance and hyperinsulinaemia, as well as lipid levels and body weight.	Metformin	0-9	insulin	Homo sapiens	18-25
9505147-4	1998	The present investigation was undertaken to clarify whether metformin affects TNF-alpha and soluble TNF receptor levels.	Metformin	60-69	tumor necrosis factor	Homo sapiens	78-87
9505147-7	1998	Twelve weeks of metformin treatment increased TNF-alpha by 33% (P &lt; 0.05).	Metformin	16-25	tumor necrosis factor	Homo sapiens	46-55
9505147-10	1998	Since metformin reduces insulin resistance both in obese and non-obese subjects but increases TNF-alpha levels only in the latter, it is concluded that the drug does not exert its effect on insulin resistance through regulation of circulating TNF-alpha levels.	Metformin	6-15	insulin	Homo sapiens	24-31
9597374-1	1998	Metformin effects on insulin resistance and insulin/glucose relationships during an oral glucose tolerance test (OGTT) were investigated in 60 non-diabetic male patients previously treated with coronary artery bypass surgery or angioplasty in an open, 12 week prospective study.	Metformin	0-9	insulin	Homo sapiens	21-51
9597374-9	1998	Hence, metformin effects on insulin resistance and body weight appear to be mediated, at least partly, by different mechanisms, while metformin effects on insulin resistance and lipid metabolism are associated in non-diabetic subjects.	Metformin	7-16	insulin	Homo sapiens	28-35
9597374-9	1998	Hence, metformin effects on insulin resistance and body weight appear to be mediated, at least partly, by different mechanisms, while metformin effects on insulin resistance and lipid metabolism are associated in non-diabetic subjects.	Metformin	134-143	insulin	Homo sapiens	155-162
10212839-4	1998	In this brief review we discuss how the known and potential insulin sensitizers: metformin, appetite suppressants, thiazolidinediones, and the new class of centrally acting antihypertensive drugs, I1-receptor agonists, may work.	Metformin	81-90	insulin	Homo sapiens	60-67
9539300-2	1998	Sixteen obese women with PCOS on a weight-maintaining diet were studied before and after 6 months of therapy with the insulin-sensitizing antidiabetic agent metformin at a dose of 1700 mg per day.	Metformin	157-166	insulin	Homo sapiens	118-125
9539300-8	1998	These results confirm that metformin treatment can lead to improvements in insulin resistance and ovarian hyperandrogenism.	Metformin	27-36	insulin	Homo sapiens	75-82
9428831-10	1997	Relative postprandial insulin increase was 1.90 with placebo, 1.09 with acarbose, and 1.03 with metformin.	Metformin	96-105	insulin	Homo sapiens	22-29
9609021-0	1997	[Effects of metformin on insulin resistance in obese and hyperandrogenic women].	Metformin	12-21	insulin	Homo sapiens	25-32
9609021-1	1997	BACKGROUND: Metformin is a biguanide often used in obese diabetics that improves tissue sensitivity to insulin.	Metformin	12-21	insulin	Homo sapiens	103-110
9609021-2	1997	AIM: To assess the effects of metformin on tissue insulin sensitivity in obese and hyperandrogenic women.	Metformin	30-39	insulin	Homo sapiens	50-57
9609021-6	1997	RESULTS: After metformin treatment, the insulin sensitivity index improved from 0.38 (0.05-0.5) to 0.43 (0.25-0.59) in obese women and from 0.2 (0-0.36) to 0.3 (0.06-0.4) in obese and hyperandrogenic women.	Metformin	15-24	insulin	Homo sapiens	40-47
9405908-11	1997	Finally, plasma FFA concentrations in response to a low-dosage insulin infusion (5 mU.m-2.min-1) were significantly lower after metformin as compared with the placebo-treated group (P &lt; 0.001).	Metformin	128-137	insulin	Homo sapiens	63-70
9398716-4	1997	In the 19 women given metformin, the mean (+/- SE) area under the serum insulin curve after oral glucose administration decreased from 44 +/- 5 to 24 +/- 3 nmol/L.min (P = 0.003).	Metformin	22-31	insulin	Homo sapiens	72-79
9398716-7	1997	In the metformin group, serum free testosterone decreased by 70% from 18.2 +/- 3.1 to 5.5 +/- 0.7 pmol/L (P &lt; 0.001), and serum sex hormone-binding globulin increased from 84 +/- 6 to 134 +/- 15 nmol/L (P = 0.002).	Metformin	7-16	sex hormone binding globulin	Homo sapiens	131-159
9398716-10	1997	They also indicate that decreasing serum insulin with metformin reduces ovarian cytochrome P450c17 alpha activity and ameliorates the hyperandrogenism of these women.	Metformin	54-63	insulin	Homo sapiens	41-48
9609021-9	1997	CONCLUSIONS: Metformin has a favorable effect on tissue sensitivity to insulin, SHBG and serum lipids in obese and hyperandrogenic women.	Metformin	13-22	insulin	Homo sapiens	71-78
9609021-9	1997	CONCLUSIONS: Metformin has a favorable effect on tissue sensitivity to insulin, SHBG and serum lipids in obese and hyperandrogenic women.	Metformin	13-22	sex hormone binding globulin	Homo sapiens	80-84
9389387-8	1997	Since insulin appears to be required for the antihyperglycemic effect of metformin, the effect of insulin on membrane fluidity was also evaluated.	Metformin	73-82	insulin	Homo sapiens	6-13
9403324-5	1997	The central role of improved insulin concentrations and insulin-resistant state is emphasized by the fact that similar effects can be achieved by both short- and long-term administration of metformin, an insulin-lowering drug which ameliorates peripheral insulin action in non-diabetic insulin resistant states.	Metformin	190-199	insulin	Homo sapiens	29-36
9322807-7	1997	Preincubation with metformin also induced an attenuating (vasodilating-like) action of insulin on arterial tissue rings contracted by potassium.	Metformin	19-28	insulin	Homo sapiens	87-94
9322807-10	1997	Thus, metformin and thiazolidinediones may decrease arterial pressure partly by direct vasorelaxant mechanisms, with metformin having an additional effect of inducing vasorelaxation by insulin.	Metformin	117-126	insulin	Homo sapiens	185-192
9403324-5	1997	The central role of improved insulin concentrations and insulin-resistant state is emphasized by the fact that similar effects can be achieved by both short- and long-term administration of metformin, an insulin-lowering drug which ameliorates peripheral insulin action in non-diabetic insulin resistant states.	Metformin	190-199	insulin	Homo sapiens	56-63
9403324-5	1997	The central role of improved insulin concentrations and insulin-resistant state is emphasized by the fact that similar effects can be achieved by both short- and long-term administration of metformin, an insulin-lowering drug which ameliorates peripheral insulin action in non-diabetic insulin resistant states.	Metformin	190-199	insulin	Homo sapiens	56-63
9403324-5	1997	The central role of improved insulin concentrations and insulin-resistant state is emphasized by the fact that similar effects can be achieved by both short- and long-term administration of metformin, an insulin-lowering drug which ameliorates peripheral insulin action in non-diabetic insulin resistant states.	Metformin	190-199	insulin	Homo sapiens	56-63
9315389-14	1997	Metformin has been the only available drug that has been used clinically to significantly improve insulin sensitivity, but the new "glitazones" (thiazolidinediones) have a more specific effect via altered lipid metabolism.	Metformin	0-9	insulin	Homo sapiens	98-105
9314013-3	1997	Metformin resurfaced in the 1980s and was shown to increase insulin sensitivity; this has led to its introduction to clinical practice in the United States for the first time.	Metformin	0-9	insulin	Homo sapiens	60-67
9277650-10	1997	Fasting (P &lt; .001) and the integrated insulin response to the glucose load decreased (P &lt; .001) after 8 weeks of metformin treatment.	Metformin	119-128	insulin	Homo sapiens	41-48
9340472-5	1997	FINDINGS: Metformin lowers fasting blood glucose levels by an average of 25% (17 to 37%), postprandial blood glucose by up to 44.5% and HbA1c bei 1.5% (0.8 to 3.1%) Metformin reduces raised plasma insulin levels in cases of metabolic syndrome by as much as 30% and reduces the "insulin requirement" of type 2 insulin-treated diabetics by 15 to 32%.	Metformin	10-19	insulin	Homo sapiens	197-204
9340472-5	1997	FINDINGS: Metformin lowers fasting blood glucose levels by an average of 25% (17 to 37%), postprandial blood glucose by up to 44.5% and HbA1c bei 1.5% (0.8 to 3.1%) Metformin reduces raised plasma insulin levels in cases of metabolic syndrome by as much as 30% and reduces the "insulin requirement" of type 2 insulin-treated diabetics by 15 to 32%.	Metformin	10-19	insulin	Homo sapiens	278-285
9288574-0	1997	Pioglitazone and metformin reverse insulin resistance induced by tumor necrosis factor-alpha in liver cells.	Metformin	17-26	insulin	Homo sapiens	35-42
9288574-0	1997	Pioglitazone and metformin reverse insulin resistance induced by tumor necrosis factor-alpha in liver cells.	Metformin	17-26	tumor necrosis factor	Homo sapiens	65-92
9288574-3	1997	With TNF-alpha concentration at 1 ng/ml and 10(4) muU/ml INS, metformin 10 microM and pioglitazone 1.5 microM, reversed the IR induced by TNF-alpha restoring biologic response to 100% of INS effect alone.	Metformin	62-71	tumor necrosis factor	Homo sapiens	5-14
9288574-3	1997	With TNF-alpha concentration at 1 ng/ml and 10(4) muU/ml INS, metformin 10 microM and pioglitazone 1.5 microM, reversed the IR induced by TNF-alpha restoring biologic response to 100% of INS effect alone.	Metformin	62-71	tumor necrosis factor	Homo sapiens	138-147
9284429-6	1997	Recent studies demonstrated that hypoglycemic agents improving insulin resistance such as metformin and troglitazone reduce blood pressure.	Metformin	90-99	insulin	Homo sapiens	63-70
9278926-4	1997	Metformin"s clinical efficacy is primarily reflective of reduced hepatic glucose output; this action should complement the benefits of peripheral insulin sensitizers.	Metformin	0-9	insulin	Homo sapiens	146-153
9143853-11	1997	The combination of a sulphonylurea and metformin can be effective in patients in whom insulin would otherwise be required.	Metformin	39-48	insulin	Homo sapiens	86-93
9109854-0	1997	Metformin therapy is associated with a decrease in plasma plasminogen activator inhibitor-1, lipoprotein(a), and immunoreactive insulin levels in patients with the polycystic ovary syndrome.	Metformin	0-9	insulin	Homo sapiens	128-135
9134058-0	1997	Effects of glibenclamide and metformin (alone or in combination) on insulin release from isolated human pancreatic islets.	Metformin	29-38	insulin	Homo sapiens	68-75
9134058-2	1997	At 3.3 mmol/l glucose level, the addition of 5.0 mumol/l glibenclamide or 5.0 mumol/l glibenclamide plus 200 mumol/l metformin caused a significant increase of insulin release, compared with glucose alone.	Metformin	117-126	insulin	Homo sapiens	160-167
15251479-0	1997	Outcome of metformin-facilitated reinitiation of oral diabetic therapy in insulin-treated patients with non-insulin-dependent diabetes mellitus.	Metformin	11-20	insulin	Homo sapiens	74-81
9159660-1	1997	BACKGROUND: Metformin alleviates hyperglycemia of non-insulin-dependent diabetes mellitus (NIDDM) by inhibiting hepatic glucose production and improving peripheral insulin sensitivity.	Metformin	12-21	insulin	Homo sapiens	54-61
9159660-6	1997	Metformin and sulfonylureas, however, had diverse effects on body weight and fasting plasma insulin levels; both weight and insulin levels remained unchanged or decreased with metformin and increased with sulfonylureas.	Metformin	0-9	insulin	Homo sapiens	92-99
9159660-6	1997	Metformin and sulfonylureas, however, had diverse effects on body weight and fasting plasma insulin levels; both weight and insulin levels remained unchanged or decreased with metformin and increased with sulfonylureas.	Metformin	0-9	insulin	Homo sapiens	124-131
9159660-6	1997	Metformin and sulfonylureas, however, had diverse effects on body weight and fasting plasma insulin levels; both weight and insulin levels remained unchanged or decreased with metformin and increased with sulfonylureas.	Metformin	176-185	insulin	Homo sapiens	124-131
9101010-3	1997	STUDY SELECTION: All human studies using metformin with insulin were included in the analysis.	Metformin	41-50	insulin	Homo sapiens	56-63
9101010-8	1997	Experience with combination metformin and insulin therapy has consistently demonstrated a reduction in insulin requirements.	Metformin	28-37	insulin	Homo sapiens	103-110
9101010-10	1997	CONCLUSIONS: When metformin is added to insulin therapy, insulin requirements are likely to decrease.	Metformin	18-27	insulin	Homo sapiens	40-47
9101010-10	1997	CONCLUSIONS: When metformin is added to insulin therapy, insulin requirements are likely to decrease.	Metformin	18-27	insulin	Homo sapiens	57-64
9101010-12	1997	Further studies of larger size and longer duration are needed before the use of metformin with insulin can be routinely recommended in patients with type 1 diabetes.	Metformin	80-89	insulin	Homo sapiens	95-102
9137903-0	1997	Effect of metformin on insulin-stimulated tyrosine kinase activity of erythrocytes from obese women with normal glucose tolerance.	Metformin	10-19	insulin	Homo sapiens	23-30
9137903-4	1997	In addition, both the number of insulin receptors and the tyrosine kinase activity per receptor of solubilised erythrocytes were significantly greater following metformin administration.	Metformin	161-170	insulin	Homo sapiens	32-39
9137903-6	1997	In summary, oral administration of metformin led to an increase in tyrosine kinase activity or erythrocyte insulin receptors, suggesting that such action occurs in the absence of any significant change in plasma glucose concentration.	Metformin	35-44	insulin	Homo sapiens	107-114
9059766-13	1997	This study shows that CSII with moderate amounts of insulin associated with a low-calorie diet and metformin provided rapid glycaemic control, led to weight loss, maintained regulation of insulin secretion and seemed to improve insulin secretion and sensitivity.	Metformin	99-108	insulin	Homo sapiens	52-59
9059770-1	1997	Insulin-requiring diabetes (IRD) is a condition of permanent blood glucose imbalance which occurs despite a regulated diet and treatment with maximum doses of oral anti-diabetic drugs (glibenclamide 15 mg/d + metformin 1,700 mg/d).	Metformin	209-218	insulin	Homo sapiens	0-7
9209206-3	1997	Metformin, an oral biguanide, ameliorates hyperglycemia by improving peripheral sensitivity to insulin, and reducing gastrointestinal glucose absorption and hepatic glucose production.	Metformin	0-9	insulin	Homo sapiens	95-102
9024248-2	1997	We sought to determine whether metformin would reduce insulin levels in obese, nondiabetic women with PCOS during a period of weight maintenance and thus attenuate the ovarian steroidogenic response to the GnRH agonist leuprolide.	Metformin	31-40	insulin	Homo sapiens	54-61
9209206-9	1997	Limited data suggest that metformin-insulin therapy may improve glycemic control, possibly reducing insulin requirements, in type 2 diabetic patients uncontrolled by insulin alone following secondary sulfonylurea failure.	Metformin	26-35	insulin	Homo sapiens	36-43
9209206-9	1997	Limited data suggest that metformin-insulin therapy may improve glycemic control, possibly reducing insulin requirements, in type 2 diabetic patients uncontrolled by insulin alone following secondary sulfonylurea failure.	Metformin	26-35	insulin	Homo sapiens	100-107
9251926-2	1997	Oral metformin was used for 6 months with assessment of insulin status during an intravenous glucose tolerance test and hyperinsulinaemic-euglycaemic clamping before and after treatment.	Metformin	5-14	insulin	Homo sapiens	56-63
9209206-9	1997	Limited data suggest that metformin-insulin therapy may improve glycemic control, possibly reducing insulin requirements, in type 2 diabetic patients uncontrolled by insulin alone following secondary sulfonylurea failure.	Metformin	26-35	insulin	Homo sapiens	100-107
8973990-2	1996	The pharmacodynamic effects (on plasma glucose and insulin) of metformin in patients with NIDDM and in healthy subjects also were assessed.	Metformin	63-72	insulin	Homo sapiens	51-58
8914439-5	1996	Metformin, an antihyperglycemic drug of the biguanide class, may be effective in subjects with IGT by reducing hepatic glucose output, enhancing insulin sensitivity, or through other mechanisms such as weight loss.	Metformin	0-9	insulin	Homo sapiens	145-152
8973990-11	1996	In healthy subjects, single and multiple doses of metformin showed no effect on plasma glucose, but significantly attenuated the rise in immediate postprandial insulin levels.	Metformin	50-59	insulin	Homo sapiens	160-167
8894498-12	1996	Metformin is the only globally available drug for improving insulin action.	Metformin	0-9	insulin	Homo sapiens	60-67
9072666-4	1996	Glibenclamide stimulates insulin release by pancreatic beta cells (pancreatic attachment point), while metformin acts at a peripheral level by increasing glucose absorption in muscular, fatty and hepatic tissues, thus considerably reducing insulin resistance (extra-pancreatic attachment point).	Metformin	103-112	insulin	Homo sapiens	240-247
8875083-7	1996	RESULTS: Compared with placebo, metformin induced a significant weight loss, a better maintenance of fasting blood glucose, total and LDL cholesterol levels, and a greater decrease of fasting plasma insulin concentration.	Metformin	32-41	insulin	Homo sapiens	199-206
8862952-1	1996	We have investigated the effects of metformin treatment on concentrations of proinsulin-like molecules in subjects with Type 2 (non-insulin-dependent) diabetes mellitus.	Metformin	36-45	insulin	Homo sapiens	77-87
8862952-1	1996	We have investigated the effects of metformin treatment on concentrations of proinsulin-like molecules in subjects with Type 2 (non-insulin-dependent) diabetes mellitus.	Metformin	36-45	insulin	Homo sapiens	80-87
8862952-8	1996	Changes in concentrations of intact and des 31,32 proinsulin on metformin were not related to changes in body mass index or fasting glucose concentration or changes in concentrations of total triglyceride, cholesterol, and plasminogen activator inhibitor-1.	Metformin	64-73	insulin	Homo sapiens	50-60
8862952-9	1996	Therefore, metformin treatment in subjects with Type 2 diabetes mellitus significantly reduced concentrations of proinsulin-like molecules over a 12-week period.	Metformin	11-20	insulin	Homo sapiens	113-123
8862952-11	1996	We conclude that short-term effects of metformin treatment on proinsulin-like molecules are similar to those previously observed with dietary treatment in subjects with Type 2 diabetes but opposite to those of sulphonylurea treatment.	Metformin	39-48	insulin	Homo sapiens	62-72
8862952-12	1996	The effect of long-term treatment with metformin on proinsulin-like molecules needs to be assessed.	Metformin	39-48	insulin	Homo sapiens	52-62
8884164-7	1996	Although antihyperglycaemic agents such as metformin and alpha-glucosidase inhibitors do not cause hypoglycaemia alone, they may enhance the hypoglycaemic effects of potent hypoglycaemic agents such as insulin and sulphonylureas.	Metformin	43-52	insulin	Homo sapiens	202-209
8687515-6	1996	RESULTS: In the 11 women given metformin, the mean (+/- SE) area under the serum insulin curve after oral glucose administration decreased from 9303 +/- 1603 to 4982 +/- 911 microU per milliliter per minute (56 +/- 10 to 30 +/- 6 nmol per liter per minute) (P = 0.004).	Metformin	31-40	insulin	Homo sapiens	81-88
8687515-11	1996	CONCLUSIONS: In obese women with the polycystic ovary syndrome, decreasing serum insulin concentrations with metformin reduces ovarian cytochrome P450c17 alpha activity and ameliorates hyperandrogenism.	Metformin	109-118	insulin	Homo sapiens	81-88
8799647-0	1996	Metformin potentiates glucose-stimulated insulin secretion.	Metformin	0-9	insulin	Homo sapiens	41-48
8879962-12	1996	The previously reported improvement of insulin mediated liver metabolism induced by metformin is likely to be a consequence of the direct effect of the drug at hepatocyte level which is independent of HBF modifications.	Metformin	84-93	insulin	Homo sapiens	39-46
8908377-11	1996	CONCLUSIONS: Metformin is an effective, safe, and well-tolerated treatment that improves metabolic control and favorably modifies secondary clinical alterations due to insulin resistance, such as arterial hypertension, overweight, and hyperlipidemia, in obese patients with NIDDM suffering from secondary failure to sulfonylureas.	Metformin	13-22	insulin	Homo sapiens	168-175
15251529-4	1996	The biguanide metformin has been shown to suppress hepatic glucose production, augment glucose uptake, and enhance insulin action in peripheral tissues.	Metformin	14-23	insulin	Homo sapiens	115-122
8783782-9	1996	Treatment of SHR aortic smooth muscle (SM) cells with metformin (2 micrograms/mL) for 24 h significantly decreased (P &lt; .05) arginine vasopressin- and thrombin- stimulated increase in [Ca2+]i.	Metformin	54-63	arginine vasopressin	Rattus norvegicus	137-148
8783782-9	1996	Treatment of SHR aortic smooth muscle (SM) cells with metformin (2 micrograms/mL) for 24 h significantly decreased (P &lt; .05) arginine vasopressin- and thrombin- stimulated increase in [Ca2+]i.	Metformin	54-63	coagulation factor II	Rattus norvegicus	154-162
8877276-0	1996	Different effect of acute and chronic oral metformin administration on glucose and insulin response to bread and to pasta in non-insulin dependent diabetic patients.	Metformin	43-52	insulin	Homo sapiens	83-90
8829014-2	1996	Metformin is an important addition to the drug therapy options available for those patients because it reduces blood glucose levels predominantly by decreasing hepatic glucose production and release and also by increasing peripheral tissue sensitivity to insulin; it does not stimulate insulin secretion from the beta cells in the pancreas.	Metformin	0-9	insulin	Homo sapiens	255-262
8612854-0	1996	Can metformin reduce insulin resistance in polycystic ovary syndrome?	Metformin	4-13	insulin	Homo sapiens	21-28
8612854-1	1996	OBJECTIVE: To examine whether metformin is able to reduce insulin resistance in polycystic ovary syndrome (PCOS).	Metformin	30-39	insulin	Homo sapiens	58-65
8651938-0	1996	Effect of metformin on SGLT1, GLUT2, and GLUT5 hexose transporter gene expression in small intestine from rats.	Metformin	10-19	solute carrier family 2 member 5	Rattus norvegicus	41-46
8651938-1	1996	The effect of the antihyperglycaemic agent metformin was studied on gene expression of the energy-dependent sodium-hexose cotransporter (SGLT1) and the facilitative hexose transporters GLUT2 and GLUT5 in rat intestine.	Metformin	43-52	solute carrier family 2 member 5	Rattus norvegicus	195-200
8651938-4	1996	GLUT5 gene expression was increased by metformin treatment only in the jejunum.	Metformin	39-48	solute carrier family 2 member 5	Rattus norvegicus	0-5
8636369-0	1996	Improvement of insulin sensitivity by metformin treatment does not lower blood pressure of nonobese insulin-resistant hypertensive patients with normal glucose tolerance.	Metformin	38-47	insulin	Homo sapiens	15-22
8636369-6	1996	Nevertheless, after metformin treatment, the plasma high density lipoprotein cholesterol concentration increased (1.42 +/- 0.18 vs. 1.34 0.16 mmol/L), and the plasma insulin level dropped (62 +/- 10 vs. 88+/- 12 pmol/L; both P &lt; 0.05).	Metformin	20-29	insulin	Homo sapiens	166-173
8636369-7	1996	Insulin-mediated glucose disposal was higher after metformin treatment (26.1 +/- 2.4 vs. 19.3 +/- 2.3 micromol/min x kg; P &lt; 0.01), whereas hepatic glucose production was completely suppressed.	Metformin	51-60	insulin	Homo sapiens	0-7
8636369-12	1996	In conclusion, 1 month of metformin administration to patients with essential hypertension and normal glucose tolerance 1) reduces the basal plasma insulin concentration, 2) improves whole body insulin-mediated glucose utilization, and 3) improves plasma high density lipoprotein cholesterol levels.	Metformin	26-35	insulin	Homo sapiens	148-155
8636369-12	1996	In conclusion, 1 month of metformin administration to patients with essential hypertension and normal glucose tolerance 1) reduces the basal plasma insulin concentration, 2) improves whole body insulin-mediated glucose utilization, and 3) improves plasma high density lipoprotein cholesterol levels.	Metformin	26-35	insulin	Homo sapiens	194-201
8882631-15	1996	These data indicate that in addition to its known effects on hexose metabolism in insulin responsive tissues, metformin also affects the hexose transport system in vascular cells.	Metformin	110-119	insulin	Homo sapiens	82-89
8628644-3	1996	Glucose toxicity (i.e., glucose-induced insulin resistance) explains why apparently unrelated therapeutic measures to improve glycaemic control (e.g., weight reduction, and sulphonylurea, metformin or insulin administration) all also increase insulin sensitivity.	Metformin	188-197	insulin	Homo sapiens	40-47
8877276-0	1996	Different effect of acute and chronic oral metformin administration on glucose and insulin response to bread and to pasta in non-insulin dependent diabetic patients.	Metformin	43-52	solute carrier family 45 member 1	Homo sapiens	116-121
8877276-1	1996	The aim of the study was to evaluate whether acute and chronic metformin administration may influence differently the glycaemic and insulin response to foods with high and low glycaemic index (bread and pasta) in twelve non-insulin dependent diabetic (NIDDM) patients.	Metformin	63-72	insulin	Homo sapiens	132-139
8877276-1	1996	The aim of the study was to evaluate whether acute and chronic metformin administration may influence differently the glycaemic and insulin response to foods with high and low glycaemic index (bread and pasta) in twelve non-insulin dependent diabetic (NIDDM) patients.	Metformin	63-72	solute carrier family 45 member 1	Homo sapiens	203-208
8877276-4	1996	Chronic metformin treatment significantly lowered glycaemic and insulin response to both bread and pasta.	Metformin	8-17	insulin	Homo sapiens	64-71
8877276-4	1996	Chronic metformin treatment significantly lowered glycaemic and insulin response to both bread and pasta.	Metformin	8-17	solute carrier family 45 member 1	Homo sapiens	99-104
7589820-9	1995	The study consists of a randomized controlled trial with two main comparisons: 1) 3,867 patients with 1,138 allocated to conventional therapy, primarily with diet, and 2,729 allocated to intensive therapy with additional sulfonylurea or insulin, which increase insulin supply, aiming for FPG &lt; 6 mmol/l; and 2) 753 obese patients with 411 allocated to conventional therapy and 342 allocated to intensive therapy with metformin, which enhances insulin sensitivity.	Metformin	420-429	insulin	Homo sapiens	237-244
8656173-1	1996	Metformin is a biguanide that can used alone or in combination with sulfonylureas or insulin in the treatment of non-insulin-dependent diabetes mellitus (NIDDM).	Metformin	0-9	insulin	Homo sapiens	85-92
8536601-8	1996	Metformin exposure for 24 h 1) increased basal TK activity (metformin, 3.49 +/- 0.39; control, 1.77 +/- 0.39 pmol 32P incorporated/mg protein; P &lt; 0.01) without changes in insulin-or IGF-I stimulated TK activity, 2) increased 2-deoxyglucose transport in a dose-dependent manner, 3) decreased thrombin-induced elevation in [Ca]i (metformin, 10.3%; control, 35.3% over basal; P &lt; 0.05), These insulin/IGF-I-like effects of metformin may help explain some of its vascular actions.	Metformin	0-9	coagulation factor II	Rattus norvegicus	295-303
8582131-0	1995	Short administration of metformin improves insulin sensitivity in android obese subjects with impaired glucose tolerance.	Metformin	24-33	insulin	Homo sapiens	43-50
8582131-7	1995	Fasting plasma insulin levels were reduced after metformin (89.3 +/- 15.9 vs 112.4 +/- 24.3 pmol l-1; p = 0.04).	Metformin	49-58	insulin	Homo sapiens	15-22
8582131-10	1995	The demonstration that metformin rapidly improves insulin sensitivity should encourage further research to evaluate the long-term effects of metformin in android obese subjects with impaired oral glucose tolerance.	Metformin	23-32	insulin	Homo sapiens	50-57
8529763-0	1995	Changes in insulin receptor tyrosine kinase activity associated with metformin treatment of type 2 diabetes.	Metformin	69-78	insulin	Homo sapiens	11-18
8529763-5	1995	Fasting plasma glucose concentrations decreased from 8.9 to 6.4 mmol/L after 10 weeks of metformin treatment (p &lt; 0.001), in association with significantly lower (p &lt; 0.001) plasma glucose and insulin concentrations in response to an oral glucose load.	Metformin	89-98	insulin	Homo sapiens	199-206
8529763-7	1995	There was no change in erythrocyte insulin receptor binding associated with metformin treatment, but both basal and insulin-stimulated insulin receptor tyrosine kinase activities of solubilized erythrocyte insulin receptors were significantly higher after 10 weeks of metformin treatment.	Metformin	268-277	insulin	Homo sapiens	116-123
8529763-7	1995	There was no change in erythrocyte insulin receptor binding associated with metformin treatment, but both basal and insulin-stimulated insulin receptor tyrosine kinase activities of solubilized erythrocyte insulin receptors were significantly higher after 10 weeks of metformin treatment.	Metformin	268-277	insulin	Homo sapiens	116-123
8529763-8	1995	It is concluded that the increase in insulin-stimulated tyrosine kinase activity contributed to the improvement in glucose insulin and lipoprotein metabolism associated with metformin treatment of Type 2 diabetes.	Metformin	174-183	insulin	Homo sapiens	37-44
8529482-0	1995	Metformin-insulin interactions: from organ to cell.	Metformin	0-9	insulin	Homo sapiens	10-17
7581261-3	1995	We have tested the hypothesis that metformin produces vascular changes by direct interaction with VSM cells by investigating its effect on platelet-derived growth factor (PDGF)- and angiotensin II (ANG II)-stimulated intracellular calcium concentration ([Ca2+]i) and VSM cell proliferation in response to PDGF in cultured cells.	Metformin	35-44	angiotensinogen	Rattus norvegicus	182-196
7581261-3	1995	We have tested the hypothesis that metformin produces vascular changes by direct interaction with VSM cells by investigating its effect on platelet-derived growth factor (PDGF)- and angiotensin II (ANG II)-stimulated intracellular calcium concentration ([Ca2+]i) and VSM cell proliferation in response to PDGF in cultured cells.	Metformin	35-44	angiotensinogen	Rattus norvegicus	198-204
7581261-5	1995	Treatment of VSM cells with 1 or 2 microgram/ml metformin significantly decreased (p &lt; 0.05) PDGF- or ANG II-stimulated [Ca2+]i.	Metformin	48-57	angiotensinogen	Rattus norvegicus	105-111
8549022-3	1995	Pharmacological means of improving insulin action include metformin, antiobesity serotoninergic agents and, possibly, benfluorex.	Metformin	58-67	insulin	Homo sapiens	35-42
8529509-9	1995	Metformin may improve insulin sensitivity but has no effect on the beta-cell.	Metformin	0-9	insulin	Homo sapiens	22-29
7652727-8	1995	Insulin treatment should be considered only when combined treatment with metformin and sulfonylurea is contraindicated or leads to insufficient blood glucose control.	Metformin	73-82	insulin	Homo sapiens	0-7
7608255-0	1995	Effects of diet and metformin administration on sex hormone-binding globulin, androgens, and insulin in hirsute and obese women.	Metformin	20-29	sex hormone binding globulin	Homo sapiens	48-76
7608255-0	1995	Effects of diet and metformin administration on sex hormone-binding globulin, androgens, and insulin in hirsute and obese women.	Metformin	20-29	insulin	Homo sapiens	93-100
7608255-2	1995	The present study was conducted to assess the effect of administration of the biguanide metformin, a drug commonly used in the treatment of diabetes mellitus, on androgen and insulin levels in 24 hirsute patients.	Metformin	88-97	insulin	Homo sapiens	175-182
8529487-0	1995	The insulin-sparing effect of metformin in insulin-treated diabetic patients.	Metformin	30-39	insulin	Homo sapiens	4-11
8529491-0	1995	Effect of metformin on various aspects of glucose, insulin and lipid metabolism in patients with non-insulin-dependent diabetes mellitus with varying degrees of hyperglycemia.	Metformin	10-19	insulin	Homo sapiens	51-58
7988785-0	1994	Effect of metformin on insulin-stimulated glucose transport in isolated skeletal muscle obtained from patients with NIDDM.	Metformin	10-19	insulin	Homo sapiens	23-30
7737322-3	1995	The concentration of neuropeptide Y in the hypothalamic paraventricular nucleus was significantly higher in the metformin-treated and pair-fed rats when compared to the control animals.	Metformin	112-121	neuropeptide Y	Rattus norvegicus	21-35
7737322-7	1995	It is concluded that the treatment with metformin and pair-feeding, which results in comparable reductions in food intake, body weight gain and hyperinsulinaemia, similarly increase neuropeptide Y concentrations in the paraventricular nucleus while not affecting preproneuropeptide Y mRNA expression in the arcuate nucleus.	Metformin	40-49	neuropeptide Y	Rattus norvegicus	182-196
7737322-8	1995	The increase in hypothalamic neuropeptide Y content may be secondary to the reduction in hyperinsulinaemia during metformin treatment and pair-feeding.	Metformin	114-123	neuropeptide Y	Rattus norvegicus	29-43
7821127-7	1994	In addition, postprandial concentrations of glucose, insulin, free fatty acids, and TG were lower (P &lt; 0.001) following metformin treatment.	Metformin	123-132	insulin	Homo sapiens	53-60
7821127-9	1994	CONCLUSIONS: Addition of metformin to sulfonylurea-treated patients with NIDDM with less than optimal glycemic control was associated with improved glycemic control, lower postprandial insulin and TG concentrations, and a decrease in postprandial concentration of TG-rich lipoproteins of intestinal origin.	Metformin	25-34	insulin	Homo sapiens	185-192
7862618-3	1994	Interest in metformin has been revived by the recent observation of a specific activity of this agent on some of the major traits of the so called "polymetabolic syndrome" (or "syndrome X"), characterized by: insulin resistance, hypertriglyceridemia, hypertension and reduced fibrinolytic activity.	Metformin	12-21	insulin	Homo sapiens	209-216
7862618-4	1994	Metformin, in studies examining one or more of these, has been shown, possibly through its peripheral insulin sensitizing mechanism, to correct most of the major symptoms characterizing this insulin resistance syndrome.	Metformin	0-9	insulin	Homo sapiens	102-109
7862618-4	1994	Metformin, in studies examining one or more of these, has been shown, possibly through its peripheral insulin sensitizing mechanism, to correct most of the major symptoms characterizing this insulin resistance syndrome.	Metformin	0-9	insulin	Homo sapiens	191-198
8557288-11	1995	In patients with insulin resistance, therapy with metformin or troglitazone may be helpful.	Metformin	50-59	insulin	Homo sapiens	17-24
7833731-10	1995	In obese subjects metformin was as effective as the other drugs with no change in mean body weight and significant reduction in mean fasting plasma insulin concentration (-2.5 mU/l; P &lt; 0.001).	Metformin	18-27	insulin	Homo sapiens	148-155
7988785-3	1994	We investigated the effect of metformin on insulin-stimulated 3-0-methylglucose transport in isolated skeletal muscle obtained from seven patients with non-insulin-dependent diabetes mellitus (NIDDM) and from eight healthy subjects.	Metformin	30-39	insulin	Homo sapiens	43-50
7988785-6	1994	However, the two control subjects and three patients with NIDDM which displayed a low rate of insulin-mediated glucose utilization (&lt; 20 mumol.kg-1.min-1), as well as in vitro insulin resistance, demonstrated increased insulin-stimulated glucose transport in the presence of metformin at 0.1 mmol/l (p &lt; 0.05).	Metformin	278-287	insulin	Homo sapiens	94-101
7988785-7	1994	In conclusion, the concentration of metformin resulting in a potentiating effect on insulin-stimulated glucose transport in insulin-resistant human skeletal muscle is 10-fold higher than the therapeutic concentrations administered to patients with NIDDM.	Metformin	36-45	insulin	Homo sapiens	84-91
7988785-7	1994	In conclusion, the concentration of metformin resulting in a potentiating effect on insulin-stimulated glucose transport in insulin-resistant human skeletal muscle is 10-fold higher than the therapeutic concentrations administered to patients with NIDDM.	Metformin	36-45	insulin	Homo sapiens	124-131
7974348-8	1994	When the effect of treatment was compared, postabsorptive levels of C-peptide, FFA and t-PA antigen were lower after metformin than after the placebo period (p &lt; 0.05).	Metformin	117-126	plasminogen activator, tissue type	Homo sapiens	87-91
7974348-9	1994	t-PA antigen also remained lower during the clamp after metformin treatment.	Metformin	56-65	plasminogen activator, tissue type	Homo sapiens	0-4
7846898-0	1994	[The value of metformin in therapy of type 2 diabetes: effect on insulin resistance, diabetic control and cardiovascular risk factors].	Metformin	14-23	insulin	Homo sapiens	65-72
8126125-0	1994	Effects of a reduction in circulating insulin by metformin on serum dehydroepiandrosterone sulfate in nondiabetic men.	Metformin	49-58	insulin	Homo sapiens	38-45
8126125-2	1994	This study was conducted to assess the influence of physiological concentrations of insulin on serum adrenal steroid levels by lowering circulating insulin in nondiabetic men through the administration of the biguanide metformin.	Metformin	219-228	insulin	Homo sapiens	84-91
8126125-2	1994	This study was conducted to assess the influence of physiological concentrations of insulin on serum adrenal steroid levels by lowering circulating insulin in nondiabetic men through the administration of the biguanide metformin.	Metformin	219-228	insulin	Homo sapiens	148-155
8126125-6	1994	Metformin administration resulted in significant reductions in serum insulin levels and concurrent increases in serum DHEA sulfate levels in both groups of men.	Metformin	0-9	insulin	Homo sapiens	69-76
8056129-7	1994	Insulin binding to circulating monocytes was higher after metformin (4.8 +/- 0.9 vs 3.2 +/- 0.6%, P = 0.020), while the lipaemic profile showed a reduction in triglycerides (1.2 +/- 0.1 vs 1.7 +/- 0.3 mmol.l-1, P = 0.039) and an increase in HDL-cholesterol (1.3 +/- 0.1 vs 1.0 +/- 0.1 mmol.l-1, P = 0.004) without variations in total cholesterol.	Metformin	58-67	insulin	Homo sapiens	0-7
8177055-0	1994	Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy.	Metformin	0-9	insulin	Homo sapiens	60-67
8177055-4	1994	After covariance adjusting for changes in the QI and WHR, on Metformin the area under the insulin curve (IA) during oral glucose tolerance testing decreased 35% (P = .04), and the insulin area to glucose area ratio decreased 31% (P = .03).	Metformin	61-70	insulin	Homo sapiens	90-97
7846898-2	1994	Several studies demonstrate that body weight decreases and insulin resistance improves--as evaluated by peripheral glucose utilisation--under metformin treatment.	Metformin	142-151	insulin	Homo sapiens	59-66
8158383-0	1993	Short-term effects of metformin on insulin sensitivity and sodium homeostasis in essential hypertensives.	Metformin	22-31	insulin	Homo sapiens	35-42
8112499-4	1993	Metformin appears to facilitate steps in the postreceptor pathways of insulin action, and may exert effects that are independent of insulin.	Metformin	0-9	insulin	Homo sapiens	70-77
8222336-12	1993	Our data demonstrate that a defect in glucose uptake exists in erythrocytes from NIDD patients, affecting both free and stored glucose, and that this defect is reversed by Metformin treatment, indicating that this drug can increase glycogen levels even in insulin-insensitive cells.	Metformin	172-181	insulin	Homo sapiens	256-263
8269798-4	1993	RESULTS: Fasting glucose, HbA1c, fasting and glucose-stimulated insulin, blood pressure and left ventricular mass, cholesterol, triglycerides, and fibrinogen decreased significantly after metformin treatment, whereas high-density lipoprotein cholesterol increased.	Metformin	188-197	fibrinogen beta chain	Homo sapiens	147-157
7926420-10	1993	Biguanides like metformin have also been found to reduce insulin resistance.	Metformin	16-25	insulin	Homo sapiens	57-64
8412779-5	1993	Fasting hepatic glucose production (HGP) was also significantly decreased following metformin therapy (1.98 +/- 0.13 v 2.41 +/- 0.20 mg.kg-1 x min-1, P &lt; .02), whereas fasting insulin and C-peptide concentrations remained unaltered.	Metformin	84-93	CD59 molecule (CD59 blood group)	Homo sapiens	143-148
8151265-1	1994	OBJECTIVE: To study the effect of metformin and metoprolol CR on insulin sensitivity, blood lipids, fibrinolytic activity and blood pressure.	Metformin	34-43	insulin	Homo sapiens	65-72
8387542-1	1993	Metformin inhibits the stimulating effect of insulin.	Metformin	0-9	insulin	Homo sapiens	45-52
8387542-6	1993	The effect of metformin, a dimethyl-substituted biguanide, known to lower plasma insulin and PAI-1 levels in vivo was concomitantly evaluated.	Metformin	14-23	insulin	Homo sapiens	81-88
8412779-5	1993	Fasting hepatic glucose production (HGP) was also significantly decreased following metformin therapy (1.98 +/- 0.13 v 2.41 +/- 0.20 mg.kg-1 x min-1, P &lt; .02), whereas fasting insulin and C-peptide concentrations remained unaltered.	Metformin	84-93	insulin	Homo sapiens	179-186
8412779-7	1993	Insulin-stimulated glucose uptake was assessed using the hyperinsulinemic euglycemic clamp technique and was increased post-metformin (3.8 +/- 0.6 v 3.1 +/- 0.7 mg.kg-1 x min-1, P &lt; .05).	Metformin	124-133	insulin	Homo sapiens	0-7
8453955-1	1993	The efficacy and safety of metformin in the treatment of obese, non-insulin-dependent, diabetic subjects poorly controlled by insulin after secondary failure to respond to sulphonylureas has been investigated.	Metformin	27-36	insulin	Homo sapiens	68-75
8462390-12	1993	CONCLUSIONS: These findings indicate that metformin treatment improves glycemic control, and lowers insulin resistance and risk factors for cardiovascular disease, including PAI-1, and may therefore be useful in the long-term management of NIDDM subjects who have a high risk of cardiovascular disease.	Metformin	42-51	insulin	Homo sapiens	100-107
8339856-0	1993	Metformin effects on peripheral sensitivity to insulin in non diabetic obese subjects.	Metformin	0-9	insulin	Homo sapiens	47-54
8475636-5	1993	The biguanide metformin is suitable to diminish peripheral insulin resistance, gluconeogenesis, and intestinal glucose absorption on cellular mechanisms others than betacytotropic effects.	Metformin	14-23	insulin	Homo sapiens	59-66
8453955-1	1993	The efficacy and safety of metformin in the treatment of obese, non-insulin-dependent, diabetic subjects poorly controlled by insulin after secondary failure to respond to sulphonylureas has been investigated.	Metformin	27-36	insulin	Homo sapiens	126-133
8453955-4	1993	At six months, there was a relevant and significant improvement in glycaemic control in diabetics receiving the combined insulin-metformin treatment (decrease in glucose -4.1 mmol.l-1; glycosylated haemoglobin A1 decrease -1.84%).	Metformin	129-138	insulin	Homo sapiens	121-128
8453955-8	1993	The fasting insulin level was significantly lower after six months of combined insulin-metformin treatment as shown by a 25% reduction in the daily dose of insulin (-21.6 U/day).	Metformin	87-96	insulin	Homo sapiens	12-19
8453955-8	1993	The fasting insulin level was significantly lower after six months of combined insulin-metformin treatment as shown by a 25% reduction in the daily dose of insulin (-21.6 U/day).	Metformin	87-96	insulin	Homo sapiens	79-86
8453955-8	1993	The fasting insulin level was significantly lower after six months of combined insulin-metformin treatment as shown by a 25% reduction in the daily dose of insulin (-21.6 U/day).	Metformin	87-96	insulin	Homo sapiens	79-86
1600835-7	1992	In peripheral tissues metformin increases insulin-mediated glucose uptake and oxidative metabolism.	Metformin	22-31	insulin	Homo sapiens	42-49
1505458-5	1992	Exposure of muscle cells to insulin in the presence of metformin resulted in further activation of 2-deoxyglucose transport.	Metformin	55-64	insulin	Homo sapiens	28-35
1583082-3	1992	In an attempt to treat the possible insulin resistance in hypertension, an antidiabetic agent, metformin, which enhances glucose uptake, was given to non-obese, non-diabetic, untreated hypertensives in a pilot study.	Metformin	95-104	insulin	Homo sapiens	36-43
1583082-4	1992	Metformin improved insulin sensitivity, decreased plasma insulin, serum cholesterol and triglycerides, increased fibrinolytic activity and markedly decreased blood pressure.	Metformin	0-9	insulin	Homo sapiens	19-26
1583082-4	1992	Metformin improved insulin sensitivity, decreased plasma insulin, serum cholesterol and triglycerides, increased fibrinolytic activity and markedly decreased blood pressure.	Metformin	0-9	insulin	Homo sapiens	57-64
1551495-0	1992	Metformin normalizes nonoxidative glucose metabolism in insulin-resistant normoglycemic first-degree relatives of patients with NIDDM.	Metformin	0-9	insulin	Homo sapiens	56-63
1551495-2	1992	Because metformin improves peripheral insulin sensitivity, we examined the acute effect of metformin and placebo on glucose and lipid metabolism in nine insulin-resistant first-degree relatives of NIDDM patients with the euglycemic insulin-clamp technique combined with indirect calorimetry and infusion of [3-3H]glucose.	Metformin	8-17	insulin	Homo sapiens	38-45
1551495-6	1992	Insulin-stimulated glucose disposal was significantly increased by 25% after metformin compared with placebo (26.67 +/- 2.87 vs. 21.31 +/- 1.73 mumol.kg-1.min-1, P less than 0.05).	Metformin	77-86	insulin	Homo sapiens	0-7
1551495-9	1992	We conclude that acutely administered metformin improves peripheral insulin sensitivity in insulin-resistant normoglycemic individuals primarily by stimulating the nonoxidative pathway of glucose metabolism.	Metformin	38-47	insulin	Homo sapiens	68-75
1551495-9	1992	We conclude that acutely administered metformin improves peripheral insulin sensitivity in insulin-resistant normoglycemic individuals primarily by stimulating the nonoxidative pathway of glucose metabolism.	Metformin	38-47	insulin	Homo sapiens	91-98
1543016-0	1992	Metformin ameliorates extreme insulin resistance in a patient with anti-insulin receptor antibodies: description of insulin receptor and postreceptor effects in vivo and in vitro.	Metformin	0-9	insulin	Homo sapiens	30-37
1543016-1	1992	The effect of metformin on insulin binding and insulin action in the presence of anti-insulin receptor antibodies was investigated in a case of type B extreme insulin resistance.	Metformin	14-23	insulin	Homo sapiens	27-34
1543016-2	1992	Oral administration of metformin (1500 mg/d) for 10 days significantly decreased plasma blood glucose and insulin levels and enhanced the hypoglycemic response to exogenous insulin.	Metformin	23-32	insulin	Homo sapiens	106-113
1543016-2	1992	Oral administration of metformin (1500 mg/d) for 10 days significantly decreased plasma blood glucose and insulin levels and enhanced the hypoglycemic response to exogenous insulin.	Metformin	23-32	insulin	Homo sapiens	173-180
1543016-9	1992	It is suggested that metformin increases, possibly through a change in the spatial conformation of insulin receptor within the plasma membrane, the availability of pre-existing receptors to insulin binding and/or decreases the availability of specific epitopes to antibody anchoring.	Metformin	21-30	insulin	Homo sapiens	99-106
1543016-10	1992	Further, in the model of insulin resistance described here, metformin enhanced the basal rate of glucose transport through a direct insulin-mimicking activity and/or a potentiation of the sensitivity of glucose transport to the antibody.	Metformin	60-69	insulin	Homo sapiens	25-32
1543016-10	1992	Further, in the model of insulin resistance described here, metformin enhanced the basal rate of glucose transport through a direct insulin-mimicking activity and/or a potentiation of the sensitivity of glucose transport to the antibody.	Metformin	60-69	insulin	Homo sapiens	132-139
1569149-5	1992	Mean hourly concentrations of plasma insulin (411 +/- 73 vs. 364 +/- 73 pmol/L) and FFA concentrations (440 +/- 31 vs. 390 +/- 40 mumol/L) were also lower after 3 months of metformin treatment.	Metformin	173-182	insulin	Homo sapiens	37-44
1600835-13	1992	Metformin offers a useful treatment for insulin-resistant overweight NIDDM patients.	Metformin	0-9	insulin	Homo sapiens	40-47
1523352-19	1992	The very low insulin dose used in this study could be explained by complementary effects of metformin and bedtime insulin on hepatic glucose output and a putative decrease in peripheral resistance attributable both to sulfonylurea and metformin.	Metformin	92-101	insulin	Homo sapiens	13-20
1523352-19	1992	The very low insulin dose used in this study could be explained by complementary effects of metformin and bedtime insulin on hepatic glucose output and a putative decrease in peripheral resistance attributable both to sulfonylurea and metformin.	Metformin	235-244	insulin	Homo sapiens	13-20
1759920-0	1991	Metformin increases insulin sensitivity and basal glucose clearance in type 2 (non-insulin dependent) diabetes mellitus.	Metformin	0-9	insulin	Homo sapiens	20-27
1788832-7	1991	Networks developed in the presence of Metformin were found to lyse more quickly, followed by insulin and Gliclazide.	Metformin	38-47	insulin	Homo sapiens	93-100
1759920-0	1991	Metformin increases insulin sensitivity and basal glucose clearance in type 2 (non-insulin dependent) diabetes mellitus.	Metformin	0-9	insulin	Homo sapiens	83-90
1916049-4	1991	Attempts to decrease insulin resistance such as fasting, diet, or administration of an oral anti-diabetic drug such as Metformin induced a parallel decrease in plasma insulin and plasminogen activator inhibitor 1 levels.	Metformin	119-128	insulin	Homo sapiens	21-28
1752350-7	1991	Thus, metformin administration to individuals with NIDDM, who did not have significant fasting hyperglycaemia, led to a decrease in plasma glucose, insulin, FFA, and TG concentration, and an increase in plasma HDL-cholesterol concentration.	Metformin	6-15	insulin	Homo sapiens	148-155
1916049-4	1991	Attempts to decrease insulin resistance such as fasting, diet, or administration of an oral anti-diabetic drug such as Metformin induced a parallel decrease in plasma insulin and plasminogen activator inhibitor 1 levels.	Metformin	119-128	insulin	Homo sapiens	167-174
1936473-10	1991	In conclusion, metformin treatment induces an improvement in glucose metabolism both in the basal and insulin-stimulated state.	Metformin	15-24	insulin	Homo sapiens	102-109
1834486-0	1991	The insulin sparing effect of metformin in insulin-treated diabetic patients.	Metformin	30-39	insulin	Homo sapiens	4-11
1834486-3	1991	What has been established, however, since the beginning of its clinical use, is that metformin can act in the presence of insulin in "facilitating" its effects.	Metformin	85-94	insulin	Homo sapiens	122-129
1834486-9	1991	However, such a clarification of decrease insulin requirements can help in the understanding of the clinical significance of metformin"s actions in diabetes (impact on insulin resistance, receptor and post-receptor effects).	Metformin	125-134	insulin	Homo sapiens	42-49
1936485-1	1991	A randomized trial of metformin versus placebo in the correction of the metabolic abnormalities associated with insulin resistance.	Metformin	22-31	insulin	Homo sapiens	112-119
1936485-10	1991	If metformin proves to be effective in reducing the metabolic abnormalities associated with insulin resistance, it may be a possible candidate for a long term trial for primary prevention of cardiovascular accidents and diabetes.	Metformin	3-12	insulin	Homo sapiens	92-99
1900072-0	1991	Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors.	Metformin	49-58	insulin	Homo sapiens	9-16
1900072-4	1991	Metformin decreased total and LDL-cholesterol (P less than 0.01), triglyceride (P less than 0.01), fasting plasma insulin (P less than 0.01) and C-peptide levels (P less than 0.02).	Metformin	0-9	insulin	Homo sapiens	114-121
1900072-9	1991	In conclusion, metformin treatment increased insulin action, lowered blood pressure, improved the metabolic risk factor profile and tended to increase the fibrinolytic activity in these mildly hypertensive subjects.	Metformin	15-24	insulin	Homo sapiens	45-52
1955512-9	1991	In conclusion, metformin lowers the fasting plasma glucose and insulin concentrations, improves oral glucose tolerance, and decreases plasma lipid levels independent of changes in body weight.	Metformin	15-24	insulin	Homo sapiens	63-70
1773025-4	1991	The main effect of metformin was limited to daily insulin requirement and insulin units/kg bw.	Metformin	19-28	insulin	Homo sapiens	50-57
1773025-5	1991	Bearing in mind the negative effects of high insulin levels, metformin could be useful in the prevention of atherogenesis in insulin-dependent diabetic patients.	Metformin	61-70	insulin	Homo sapiens	45-52
2086278-3	1990	In addition, the effect of circulating metformin on insulin binding to isolated monocytes has been evaluated.	Metformin	39-48	insulin	Homo sapiens	52-59
2086278-11	1990	The binding of insulin to isolated human monocytes was similar in metformin-treated diabetic patients (4.48 +/- 0.45) as in healthy volunteers (4.62 +/- 0.34); insulin binding was correlated (p less than 0.05) with plasma metformin levels.	Metformin	66-75	insulin	Homo sapiens	15-22
2086278-11	1990	The binding of insulin to isolated human monocytes was similar in metformin-treated diabetic patients (4.48 +/- 0.45) as in healthy volunteers (4.62 +/- 0.34); insulin binding was correlated (p less than 0.05) with plasma metformin levels.	Metformin	222-231	insulin	Homo sapiens	15-22
1936475-7	1991	Metformin may have a potential advantage in the management of NIDDM with hyperinsulinaemia in that it does not increase insulin levels.	Metformin	0-9	insulin	Homo sapiens	78-85
1936475-8	1991	Where insulin levels have been compared in the same type II patients, metformin can achieve similar glycaemic control as a sulphonylurea (gliclazide) but with significantly lower plasma insulin levels.	Metformin	70-79	insulin	Homo sapiens	6-13
1936475-8	1991	Where insulin levels have been compared in the same type II patients, metformin can achieve similar glycaemic control as a sulphonylurea (gliclazide) but with significantly lower plasma insulin levels.	Metformin	70-79	insulin	Homo sapiens	186-193
1936478-0	1991	Comparative three-month study of the efficacies of metformin and gliclazide in the treatment of NIDD.	Metformin	51-60	zinc finger DHHC-type palmitoyltransferase 23	Homo sapiens	96-100
1936478-5	1991	The fasting serum insulin level decreased significantly in the group receiving metformin (26.2 +/- 3.2 mlU/L at entry versus 19.8 +/- 2.3 mlU/L after three months: less than 0.01), and increased in a non-significant way in the group receiving gliclazide (21.6 +/- 3 mlU/L versus 26.5 +/- 5 mlU/L after three months: NS).	Metformin	79-88	insulin	Homo sapiens	18-25
1936478-10	1991	On the other hand, fasting serum insulin levels decreased significantly in patients receiving metformin compared to gliclazide.	Metformin	94-103	insulin	Homo sapiens	33-40
1936478-11	1991	The effect of metformin on serum insulin levels is probably due to its action on insulin resistance and its lack of effect on insulin secretion, in contrast to sulphonylurea hypoglycaemic agents like gliclazide.	Metformin	14-23	insulin	Homo sapiens	33-40
1936478-11	1991	The effect of metformin on serum insulin levels is probably due to its action on insulin resistance and its lack of effect on insulin secretion, in contrast to sulphonylurea hypoglycaemic agents like gliclazide.	Metformin	14-23	insulin	Homo sapiens	81-88
1936478-11	1991	The effect of metformin on serum insulin levels is probably due to its action on insulin resistance and its lack of effect on insulin secretion, in contrast to sulphonylurea hypoglycaemic agents like gliclazide.	Metformin	14-23	insulin	Homo sapiens	81-88
1936479-10	1991	The stimulated C-peptide was significantly reduced by metformin in comparison to diet only, which supports former findings of an insulin-lowering effect of the drug.	Metformin	54-63	insulin	Homo sapiens	15-24
2272714-4	1990	They received metformin as the sole therapy when possible (sulfonylureas were discontinued in 9 cases) at a dosage of either 850 mg or 1,700 mg/day dependent on creatinine clearance values of 30-60 ml.min-1 (n = 11) and greater than 60 ml.min-1 (n = 13), respectively.	Metformin	14-23	CD59 molecule (CD59 blood group)	Homo sapiens	201-206
2258095-0	1990	[Bedtime administration of metformin may reduce insulin requirements].	Metformin	27-36	insulin	Homo sapiens	48-55
2191888-0	1990	Improvement with metformin in insulin internalization and processing in monocytes from NIDDM patients.	Metformin	17-26	insulin	Homo sapiens	30-37
33767427-3	2021	Inhibition of OXPHOS by the US Food and Drug Administration-approved drug metformin, which targets mitochondrial respiratory chain complex-I, suppresses HIV-1 replication in human CD4+ T cells and humanized mice.	Metformin	74-83	CD4 molecule	Homo sapiens	180-183
33972511-4	2021	Understanding these pathways might identify mechanisms underlying treatments for insulin resistance, such as metformin and bariatric surgery, or aid in developing new therapies and vaccination approaches.	Metformin	109-118	insulin	Homo sapiens	81-88
33820884-3	2021	Metformin, a conventional insulin sensitizer agent, has been widely prescribed in patients with diabetes.	Metformin	0-9	insulin	Homo sapiens	26-33
33798839-6	2021	Meta-analysis of 2 studies including 323 pregnant women showed significantly reduced CRP levels following treatment with metformin compared to placebo [mean difference = -1.72, 95% CI (-2.97; -0.48); p = 0.007].	Metformin	121-130	C-reactive protein	Homo sapiens	85-88
33798839-7	2021	Metformin exposure was also associated with decreased levels of the inflammatory cytokines TNFalpha, IL-1a, IL-1b and IL-6 in serum, placenta and omental tissue taken from pregnant women.	Metformin	0-9	tumor necrosis factor	Homo sapiens	91-99
33762564-0	2021	Retracted: Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway.	Metformin	34-43	AKT serine/threonine kinase 1	Homo sapiens	144-147
33798839-7	2021	Metformin exposure was also associated with decreased levels of the inflammatory cytokines TNFalpha, IL-1a, IL-1b and IL-6 in serum, placenta and omental tissue taken from pregnant women.	Metformin	0-9	interleukin 1 beta	Homo sapiens	108-113
33798839-7	2021	Metformin exposure was also associated with decreased levels of the inflammatory cytokines TNFalpha, IL-1a, IL-1b and IL-6 in serum, placenta and omental tissue taken from pregnant women.	Metformin	0-9	interleukin 6	Homo sapiens	118-122
33774848-0	2021	Insulin Resistance in Type 1 Diabetes Managed with Metformin (INTIMET): study protocol of a double-blind placebo-controlled, randomised trial.	Metformin	51-60	insulin	Homo sapiens	0-7
33774848-2	2021	Whether metformin improves hepatic, muscle or adipose tissue insulin sensitivity has not been studied in adults with Type 1 diabetes.	Metformin	8-17	insulin	Homo sapiens	61-68
33774848-3	2021	We initiated the INTIMET study (INsulin resistance in Type 1 diabetes managed with METformin), a double-blind randomised, placebo-controlled trial to measure the effect of metformin on tissue-specific insulin resistance in adults with Type 1 diabetes.	Metformin	83-92	insulin	Homo sapiens	32-39
33774848-3	2021	We initiated the INTIMET study (INsulin resistance in Type 1 diabetes managed with METformin), a double-blind randomised, placebo-controlled trial to measure the effect of metformin on tissue-specific insulin resistance in adults with Type 1 diabetes.	Metformin	172-181	insulin	Homo sapiens	201-208
33774848-8	2021	CONCLUSION: The INTIMET study is the first clinical trial to quantify the impact of metformin on liver, muscle and adipose insulin resistance in adults with Type 1 diabetes.	Metformin	84-93	insulin	Homo sapiens	123-130
33807522-9	2021	Metformin suppresses the mechanistic target of rapamycin (mTOR) by activating AMPK in pre-neoplastic cells, which leads to suppression of cell growth and an increase in apoptosis in pre-neoplastic cells.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	25-56
33807522-9	2021	Metformin suppresses the mechanistic target of rapamycin (mTOR) by activating AMPK in pre-neoplastic cells, which leads to suppression of cell growth and an increase in apoptosis in pre-neoplastic cells.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	58-62
33236135-0	2021	Metformin induces apoptosis and inhibits migration by activating the AMPK/p53 axis and suppressing PI3K/AKT signaling in human cervical cancer cells.	Metformin	0-9	tumor protein p53	Homo sapiens	74-77
33236135-0	2021	Metformin induces apoptosis and inhibits migration by activating the AMPK/p53 axis and suppressing PI3K/AKT signaling in human cervical cancer cells.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	104-107
33236135-5	2021	Following metformin treatment, the protein expression levels of p-AMP-activated protein kinase (p-AMPK), which promotes cell death, and the tumor suppressor protein p-p53 were remarkably upregulated in CaSki and C33A cells compared with the control group.	Metformin	10-19	tumor protein p53	Homo sapiens	167-170
33236135-6	2021	Furthermore, compared with the control group, metformin significantly suppressed the PI3K/AKT signaling pathway in CaSki, C33A and HeLa cells.	Metformin	46-55	AKT serine/threonine kinase 1	Homo sapiens	90-93
33768205-2	2020	Therapeutic activation of AMPK by metformin could inhibit cyst enlargement by inhibition of both the mammalian target of rapamycin pathway and fluid secretion via the CFTR chloride channel.	Metformin	34-43	mechanistic target of rapamycin kinase	Homo sapiens	101-130
33232283-0	2020	Metformin protects against myocardial ischemia-reperfusion injury and cell pyroptosis via AMPK/NLRP3 inflammasome pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	90-94
33232283-0	2020	Metformin protects against myocardial ischemia-reperfusion injury and cell pyroptosis via AMPK/NLRP3 inflammasome pathway.	Metformin	0-9	NLR family, pyrin domain containing 3	Rattus norvegicus	95-100
33232283-3	2020	In this study, we further examined the involvement of AMPK mediated activation of NLRP3 inflammasome in this cardioprotective effect of metformin.	Metformin	136-145	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	54-58
33232283-3	2020	In this study, we further examined the involvement of AMPK mediated activation of NLRP3 inflammasome in this cardioprotective effect of metformin.	Metformin	136-145	NLR family, pyrin domain containing 3	Rattus norvegicus	82-87
33232283-8	2020	Furthermore, metformin activated phosphorylated AMPK, decreased pro-inflammatory cytokines, TNF-alpha, IL-6 and IL-1beta, and decreased NLRP3 inflammasome activation.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	48-52
33232283-8	2020	Furthermore, metformin activated phosphorylated AMPK, decreased pro-inflammatory cytokines, TNF-alpha, IL-6 and IL-1beta, and decreased NLRP3 inflammasome activation.	Metformin	13-22	tumor necrosis factor	Rattus norvegicus	92-101
33232283-8	2020	Furthermore, metformin activated phosphorylated AMPK, decreased pro-inflammatory cytokines, TNF-alpha, IL-6 and IL-1beta, and decreased NLRP3 inflammasome activation.	Metformin	13-22	interleukin 6	Rattus norvegicus	103-107
33232283-8	2020	Furthermore, metformin activated phosphorylated AMPK, decreased pro-inflammatory cytokines, TNF-alpha, IL-6 and IL-1beta, and decreased NLRP3 inflammasome activation.	Metformin	13-22	interleukin 1 alpha	Rattus norvegicus	112-120
33232283-8	2020	Furthermore, metformin activated phosphorylated AMPK, decreased pro-inflammatory cytokines, TNF-alpha, IL-6 and IL-1beta, and decreased NLRP3 inflammasome activation.	Metformin	13-22	NLR family, pyrin domain containing 3	Rattus norvegicus	136-141
33232283-11	2020	Finally, in vitro studies revealed that the NLRP3 activator nigericin abolished the anti-inflammatory effects of metformin in NRVMs, but it had little effect on AMPK phosphorylation.	Metformin	113-122	NLR family, pyrin domain containing 3	Rattus norvegicus	44-49
33232283-12	2020	Collectively, our study confirmed that metformin exerts cardioprotective effects by regulating myocardial I/R injury-induced inflammatory response, which was largely dependent on the enhancement of the AMPK pathway, thereby suppressing NLRP3 inflammasome activation.	Metformin	39-48	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	202-206
33232283-12	2020	Collectively, our study confirmed that metformin exerts cardioprotective effects by regulating myocardial I/R injury-induced inflammatory response, which was largely dependent on the enhancement of the AMPK pathway, thereby suppressing NLRP3 inflammasome activation.	Metformin	39-48	NLR family, pyrin domain containing 3	Rattus norvegicus	236-241
33233350-6	2020	In this review, we present several therapeutics that target PGC-1alpha in skeletal muscle such as leucine, beta-hydroxy-beta-methylbuyrate (HMB), arginine, resveratrol, metformin and combination therapies that may have future application to conditions of disuse and recovery in humans.	Metformin	169-178	PPARG coactivator 1 alpha	Homo sapiens	60-70
32800340-6	2020	Metformin treatment significantly enhanced stemness properties and mineralized nodule formation, and increased the expression of osteogenic markers, including runt related transcription factor 2 (Runx2), osteocalcin (OCN), and alkaline phosphatase (ALP).	Metformin	0-9	RUNX family transcription factor 2	Homo sapiens	159-194
32800340-6	2020	Metformin treatment significantly enhanced stemness properties and mineralized nodule formation, and increased the expression of osteogenic markers, including runt related transcription factor 2 (Runx2), osteocalcin (OCN), and alkaline phosphatase (ALP).	Metformin	0-9	RUNX family transcription factor 2	Homo sapiens	196-201
32800340-6	2020	Metformin treatment significantly enhanced stemness properties and mineralized nodule formation, and increased the expression of osteogenic markers, including runt related transcription factor 2 (Runx2), osteocalcin (OCN), and alkaline phosphatase (ALP).	Metformin	0-9	bone gamma-carboxyglutamate protein	Homo sapiens	204-215
32800340-6	2020	Metformin treatment significantly enhanced stemness properties and mineralized nodule formation, and increased the expression of osteogenic markers, including runt related transcription factor 2 (Runx2), osteocalcin (OCN), and alkaline phosphatase (ALP).	Metformin	0-9	bone gamma-carboxyglutamate protein	Homo sapiens	217-220
32800340-6	2020	Metformin treatment significantly enhanced stemness properties and mineralized nodule formation, and increased the expression of osteogenic markers, including runt related transcription factor 2 (Runx2), osteocalcin (OCN), and alkaline phosphatase (ALP).	Metformin	0-9	alkaline phosphatase, placental	Homo sapiens	227-247
32800340-6	2020	Metformin treatment significantly enhanced stemness properties and mineralized nodule formation, and increased the expression of osteogenic markers, including runt related transcription factor 2 (Runx2), osteocalcin (OCN), and alkaline phosphatase (ALP).	Metformin	0-9	alkaline phosphatase, placental	Homo sapiens	249-252
24047401-6	2013	AMP-activated protein kinase (AMPK) activators such as resveratrol, AICAR and metformin protected endothelial cells against complement-mediated cytotoxicity through the increase in CD55, CD59, haem oxygenase-1 (HO-1) and ferritin heavy chain (ferritin H) genes, all of which were attenuated by AMPKalpha knock-down.	Metformin	78-87	CD59 molecule (CD59 blood group)	Homo sapiens	187-191
20668229-2	2010	We show in our current study that the LKB1/AMPK/TSC tumor suppressor axis is functional in AML and can be activated by the biguanide molecule metformin, resulting in a specific inhibition of mammalian target of rapamycin (mTOR) catalytic activity.	Metformin	142-151	TSC complex subunit 1	Homo sapiens	48-51
20668229-2	2010	We show in our current study that the LKB1/AMPK/TSC tumor suppressor axis is functional in AML and can be activated by the biguanide molecule metformin, resulting in a specific inhibition of mammalian target of rapamycin (mTOR) catalytic activity.	Metformin	142-151	mechanistic target of rapamycin kinase	Homo sapiens	191-220
20668229-2	2010	We show in our current study that the LKB1/AMPK/TSC tumor suppressor axis is functional in AML and can be activated by the biguanide molecule metformin, resulting in a specific inhibition of mammalian target of rapamycin (mTOR) catalytic activity.	Metformin	142-151	mechanistic target of rapamycin kinase	Homo sapiens	222-226
34942358-13	2022	VD was more effective than metformin in decreasing serum LPS and TNF-alpha levels; whereas metformin resulted in better glycemic control.	Metformin	27-36	tumor necrosis factor	Rattus norvegicus	65-74
2198745-8	1990	These data suggest that the antidiabetic action of metformin is neither related to its lactate-increasing activity nor does it depend upon its inducing an increase in insulin binding values.	Metformin	51-60	insulin	Homo sapiens	167-174
2198745-10	1990	Moreover, our data are also consistent with the hypothesis that metformin might affect insulin action at a post-receptor level.	Metformin	64-73	insulin	Homo sapiens	87-94
30740845-12	2019	CONCLUSIONS & INFERENCES: Metformin may block mast cell activation to reduce PAR-2 expression and subsequently inhibit ERK activation and clau-4 phosphorylation at serine sites to normalize the interaction of clau-4 and ZO-1 and clau-4 distribution.	Metformin	26-35	Eph receptor B1	Rattus norvegicus	119-122
26600057-7	2015	Testosterone-metformin combination therapy decreased also total and LDL cholesterol, uric acid, hsCRP, homocysteine and fibrinogen, as well as increased plasma testosterone.	Metformin	13-22	fibrinogen beta chain	Homo sapiens	120-130
25218668-2	2015	Metformin has been proposed to protect against obesity-associated cancers by decreasing serum insulin.	Metformin	0-9	insulin	Homo sapiens	94-101
25218668-9	2015	Metformin was associated with an almost significant reduction in serum levels of insulin (median -4.7% among subjects given metformin vs 23.6% increase among those given placebo, P = .08) as well as in homeostatic model assessments of insulin resistance (median -7.2% among subjects given metformin vs 38% increase among those given placebo, P = .06).	Metformin	0-9	insulin	Homo sapiens	81-88
25218668-9	2015	Metformin was associated with an almost significant reduction in serum levels of insulin (median -4.7% among subjects given metformin vs 23.6% increase among those given placebo, P = .08) as well as in homeostatic model assessments of insulin resistance (median -7.2% among subjects given metformin vs 38% increase among those given placebo, P = .06).	Metformin	0-9	insulin	Homo sapiens	235-242
25218668-12	2015	Although metformin reduced serum levels of insulin and insulin resistance, it did not discernibly alter epithelial proliferation or apoptosis in esophageal tissues.	Metformin	9-18	insulin	Homo sapiens	43-50
25218668-12	2015	Although metformin reduced serum levels of insulin and insulin resistance, it did not discernibly alter epithelial proliferation or apoptosis in esophageal tissues.	Metformin	9-18	insulin	Homo sapiens	55-62
25333776-1	2015	AIM: This study was undertaken to determine whether metformin would ameliorate insulin resistance, reduce weight and waist circumference and improve lipids in obese, but not morbidly obese, euglycemic women.	Metformin	52-61	insulin	Homo sapiens	79-86
25333776-9	2015	CONCLUSION: Treatment of euglycemic, obese, middle-aged women with metformin 1700 mg per day reduced insulin resistance and weight compared with placebo.	Metformin	67-76	insulin	Homo sapiens	101-108
25333776-10	2015	Further studies are needed to determine whether the use of metformin will prevent the progression of insulin resistance to type 2 diabetes mellitus in obese women.	Metformin	59-68	insulin	Homo sapiens	101-108
22770240-0	2012	Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation.	Metformin	0-9	CREB binding protein	Homo sapiens	36-39
22770240-5	2012	Thus, metformin, by activating an aPKC-CBP pathway, recruits neural stem cells and enhances neural function, thereby providing a candidate pharmacological approach for nervous system therapy.	Metformin	6-15	CREB binding protein	Homo sapiens	39-42
34920124-8	2022	When treated with metformin/LKB1, both SLCO1B3 expression and intracellular PTX concentration have increased.	Metformin	18-27	solute carrier organic anion transporter family member 1B3	Homo sapiens	39-46
34920124-10	2022	Moreover, in vitro and in vivo experiments have showed that metformin not only obviously inhibited A549-PTX tumor xenograft and A549-PTX proliferation alone, but also enhanced PTX efficacy to A549-PTX and this may be relevant to SLCO1B3.	Metformin	60-69	solute carrier organic anion transporter family member 1B3	Homo sapiens	229-236
34875507-4	2022	We demonstrate that both Metformin and Nano-PSO reduced aging hallmarks activities such as activated AMPK, the main energy sensor of cells as well as Nrf2 and COX IV1, regulators of oxidation, and mitochondrial activity.	Metformin	25-34	nuclear factor, erythroid derived 2, like 2	Mus musculus	150-154
34897595-6	2022	RESULTS: Twelve-month metformin treatment reduced fat content, waist circumference, glycated hemoglobin, glucose and triglycerides, as well as improved insulin sensitivity.	Metformin	22-31	insulin	Homo sapiens	152-159
33762564-0	2021	Retracted: Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway.	Metformin	34-43	mechanistic target of rapamycin kinase	Homo sapiens	148-177
33762564-0	2021	Retracted: Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway.	Metformin	34-43	mechanistic target of rapamycin kinase	Homo sapiens	179-183
33762564-2	2021	Reference: Fengli Zhang, Huixiao Chen, Jing Du, Bin Wang, Lixiao Yang: Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway.	Metformin	94-103	AKT serine/threonine kinase 1	Homo sapiens	204-207
33762564-2	2021	Reference: Fengli Zhang, Huixiao Chen, Jing Du, Bin Wang, Lixiao Yang: Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway.	Metformin	94-103	mechanistic target of rapamycin kinase	Homo sapiens	208-237
33762564-2	2021	Reference: Fengli Zhang, Huixiao Chen, Jing Du, Bin Wang, Lixiao Yang: Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway.	Metformin	94-103	mechanistic target of rapamycin kinase	Homo sapiens	239-243
34236726-0	2022	Effects of metformin on autoimmune immunoglobins and interferon-gamma in patients with early diagnosed pemphigus vulgaris: A prospective clinical trial.	Metformin	11-20	interferon gamma	Homo sapiens	53-69
34506671-5	2022	In presence of metformin in the resistant induction process to DTIC, (MET-DTIC) cells had increased antioxidant thiols, MDA, nuclear p53, 8-OH-DG, Nrf2 and reducing NF-kB, weakening the DTIC-resistant phenotype.	Metformin	15-24	nuclear factor, erythroid derived 2, like 2	Mus musculus	147-151
34309806-7	2022	RESULTS: A single passive transport coefficient, k = 0.044 +- 0.014 (h-1), can be applied, describing the uptake and release transport rate versus the linear equation v = k x (Mpl - MRBC), where Mpl is the metformin concentration in plasma and MRBC is the metformin concentration in RBCs.	Metformin	206-215	MPL proto-oncogene, thrombopoietin receptor	Homo sapiens	176-179
34890997-12	2022	Moreover, metformin reduced the phospho-NF-kB, IL-1beta in the prefrontal cortex and iNOS levels in the hippocampus.	Metformin	10-19	nitric oxide synthase 2, inducible	Mus musculus	85-89
34309806-7	2022	RESULTS: A single passive transport coefficient, k = 0.044 +- 0.014 (h-1), can be applied, describing the uptake and release transport rate versus the linear equation v = k x (Mpl - MRBC), where Mpl is the metformin concentration in plasma and MRBC is the metformin concentration in RBCs.	Metformin	206-215	MPL proto-oncogene, thrombopoietin receptor	Homo sapiens	195-198
34787028-8	2022	Indeed, metformin has been involved in repair mitochondrial dysfunction, decrease of oxidative stress, reduction of androgens levels and the enhancing of insulin sensitivity.	Metformin	8-17	insulin	Homo sapiens	154-161
34844106-8	2022	On the one hand these effects are likely attributed to the ability of metformin to inactivate NF-kappaB in an AMPK-dependent mechanism and on the other hand to the ability of the empagliflozin to inhibit the MAPKs, p38 and ERK1/2.	Metformin	70-79	nuclear factor kappa B subunit 1	Homo sapiens	94-103
34637881-5	2022	We then addressed metformin"s effects on the AMPK-AKT-mTOR-HIFA pathway on two human primary cultures: one from a VHL-mutant PCC and other from a sporadic PCC.	Metformin	18-27	AKT serine/threonine kinase 1	Homo sapiens	50-53
34637881-5	2022	We then addressed metformin"s effects on the AMPK-AKT-mTOR-HIFA pathway on two human primary cultures: one from a VHL-mutant PCC and other from a sporadic PCC.	Metformin	18-27	mechanistic target of rapamycin kinase	Homo sapiens	54-58
34957859-0	2022	Metformin Improves Skeletal Muscle Microvascular Insulin Resistance in Metabolic Syndrome.	Metformin	0-9	insulin	Homo sapiens	49-56
34637881-7	2022	Further, metformin induced AMPK phosphorylation and impaired AMPK-PI3k-AKT-mTOR pathway activation.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	27-31
34637881-7	2022	Further, metformin induced AMPK phosphorylation and impaired AMPK-PI3k-AKT-mTOR pathway activation.	Metformin	9-18	AKT serine/threonine kinase 1	Rattus norvegicus	71-74
34637881-9	2022	Metformin-induced decrease of HIF1A levels was likely mediated by proteasomal degradation.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	30-35
34957859-2	2022	Metformin improves metabolic insulin resistance in humans.	Metformin	0-9	insulin	Homo sapiens	29-36
34957859-7	2022	Metformin (not placebo) improved metabolic insulin sensitivity, (clamp glucose infusion rate, P<0.01).	Metformin	0-9	insulin	Homo sapiens	43-50
34957859-11	2022	CONCLUSIONS: Short-term metformin treatment improves both metabolic and muscle microvascular response to insulin.	Metformin	24-33	insulin	Homo sapiens	105-112
34957859-12	2022	Metformin"s effect on microvascular insulin responsiveness may contribute to its beneficial metabolic effects.	Metformin	0-9	insulin	Homo sapiens	36-43
34948457-0	2021	Metformin Treatment Attenuates Brain Inflammation and Rescues PACAP/VIP Neuropeptide Alterations in Mice Fed a High-Fat Diet.	Metformin	0-9	adenylate cyclase activating polypeptide 1	Mus musculus	62-67
34953068-11	2022	CONCLUSION: The use of insulin-metformin combinations and other noninsulin antidiabetic drugs during pregnancy has increased.	Metformin	31-40	insulin	Homo sapiens	23-30
34718940-5	2022	METHODS AND RESULTS: In this context, we created a full-thickness excisional wound model in Wistar albino rats and, investigated NF-kappaB p65 DNA-binding activity and expression levels of RELA (p65), MMP2 and MMP9 in wound samples taken on days 0, 3, 7, and 14 from diabetic/non-diabetic rats treated with metformin and saline.	Metformin	307-316	synaptotagmin 1	Rattus norvegicus	195-198
34987398-0	2021	Artesunate Combined With Metformin Ameliorate on Diabetes-Induced Xerostomia by Mitigating Superior Salivatory Nucleus and Salivary Glands Injury in Type 2 Diabetic Rats via the PI3K/AKT Pathway.	Metformin	25-34	AKT serine/threonine kinase 1	Rattus norvegicus	183-186
34948457-0	2021	Metformin Treatment Attenuates Brain Inflammation and Rescues PACAP/VIP Neuropeptide Alterations in Mice Fed a High-Fat Diet.	Metformin	0-9	vasoactive intestinal polypeptide	Mus musculus	68-71
34948457-12	2021	Treatment with metformin attenuated these neuroinflammatory signatures and reversed PI3K/AKT and PACAP/VIP alterations caused by HFD.	Metformin	15-24	thymoma viral proto-oncogene 1	Mus musculus	89-92
34948457-12	2021	Treatment with metformin attenuated these neuroinflammatory signatures and reversed PI3K/AKT and PACAP/VIP alterations caused by HFD.	Metformin	15-24	adenylate cyclase activating polypeptide 1	Mus musculus	97-102
34911941-6	2021	Time-lapse microscopy and medium transfer experiments disclosed the non-cell autonomous, paracrine nature of these mechanisms, and pharmacological interference with senescence-associated cytokine production by the NF-kappaB inhibitor metformin significantly improved radiotherapeutic performance in vitro and in vivo.	Metformin	234-243	nuclear factor kappa B subunit 1	Homo sapiens	214-223
34975743-12	2021	Conclusions: These data demonstrate that peripheral administration of the brain permeable "metformin-like" AMPK activator R481 increases blood glucose by activation of the autonomic nervous system and amplifies the glucagon response to hypoglycemia in rats.	Metformin	91-100	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	107-111
34914744-0	2021	Metformin attenuates osteoclast-mediated abnormal subchondral bone remodeling and alleviates osteoarthritis via AMPK/NF-kappaB/ERK signaling pathway.	Metformin	0-9	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	117-126
34914744-0	2021	Metformin attenuates osteoclast-mediated abnormal subchondral bone remodeling and alleviates osteoarthritis via AMPK/NF-kappaB/ERK signaling pathway.	Metformin	0-9	mitogen-activated protein kinase 1	Mus musculus	127-130
34907435-0	2022	Effect of acupuncture and metformin on insulin sensitivity in women with polycystic ovary syndrome and insulin resistance: a three-armed randomized controlled trial.	Metformin	26-35	insulin	Homo sapiens	39-46
34907435-19	2022	Further studies are needed to evaluate the effect of acupuncture combined with metformin on insulin sensitivity in these women.	Metformin	79-88	insulin	Homo sapiens	92-99
34948457-12	2021	Treatment with metformin attenuated these neuroinflammatory signatures and reversed PI3K/AKT and PACAP/VIP alterations caused by HFD.	Metformin	15-24	vasoactive intestinal polypeptide	Mus musculus	103-106
34948457-13	2021	Altogether, our findings demonstrate that metformin treatment rescues HFD-induced neuroinflammation in vulnerable brain regions, most likely by a mechanism involving the reinstatement of PACAP/VIP system homeostasis.	Metformin	42-51	adenylate cyclase activating polypeptide 1	Mus musculus	187-192
34948457-13	2021	Altogether, our findings demonstrate that metformin treatment rescues HFD-induced neuroinflammation in vulnerable brain regions, most likely by a mechanism involving the reinstatement of PACAP/VIP system homeostasis.	Metformin	42-51	vasoactive intestinal polypeptide	Mus musculus	193-196
34948457-14	2021	Data also suggests that the PI3K/AKT pathway, at least in part, mediates some of metformin"s beneficial effects.	Metformin	81-90	thymoma viral proto-oncogene 1	Mus musculus	33-36
34895333-0	2021	Loss of hexokinase 1 sensitizes ovarian cancer to high-dose metformin.	Metformin	60-69	hexokinase 1	Homo sapiens	8-20
34950736-11	2021	Our study did now significant changes in ACTH and cortisol levels in both females and males after metformin treatment.	Metformin	98-107	proopiomelanocortin	Homo sapiens	41-45
34950736-12	2021	Metformin use resulted in significant increase in luteinizing hormone (LH) and progesterone levels in males, while it was associated with significant increase in prolactin, follicular stimulating hormone (FSH), and dehydroepiandrostenedione-sulphate (DHEA-S) levels and significant decrease in total testosterone level in females.	Metformin	0-9	prolactin	Homo sapiens	162-171
34895333-11	2021	Furthermore, HK1 revertants but not HK2 revertants caused a strong increase of NADPH/NADP ratios independently on the presence of glucose or metformin.	Metformin	141-150	hexokinase 1	Homo sapiens	13-16
34895333-7	2021	RESULTS: We found that the HK1 depletion (but not the HK2 depletion) sensitized ovarian cancer cells to high-dose metformin during glucose starvation.	Metformin	114-123	hexokinase 1	Homo sapiens	27-30
34895136-0	2021	Metformin alleviates the calcification of aortic valve interstitial cells through activating the PI3K/AKT pathway in an AMPK dependent way.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	102-105
34895136-3	2021	Many studies showed that metformin exerted beneficial effects on multiple cardiovascular diseases by mediating multiple proteins such as AMPK, NF-kappaB, and AKT.	Metformin	25-34	nuclear factor kappa B subunit 1	Homo sapiens	143-152
34912022-1	2021	Metformin reduces insulin resistance, which constitutes a pathophysiological connection of diabetes with Alzheimer"s disease (AD), but the evidence of metformin on AD development was still insufficient and conflicting.	Metformin	0-9	insulin	Homo sapiens	18-25
34895136-3	2021	Many studies showed that metformin exerted beneficial effects on multiple cardiovascular diseases by mediating multiple proteins such as AMPK, NF-kappaB, and AKT.	Metformin	25-34	AKT serine/threonine kinase 1	Homo sapiens	158-161
34895136-4	2021	This study aims to verify whether metformin can inhibit aortic calcification through the PI3K/AKT signaling pathway.	Metformin	34-43	AKT serine/threonine kinase 1	Homo sapiens	94-97
34955900-9	2021	Several other agents, including metformin and statins, have been found to induce antidiuresis and AQP2 upregulation through various V2R-independent pathways in animal experiments but are not associated with hyponatremia despite being frequently used clinically.	Metformin	32-41	arginine vasopressin receptor 2	Homo sapiens	132-135
34570873-8	2021	Furthermore, metformin significantly inhibited Ang II-upregulated ET receptors and upregulated Ang II-decreased sirtuin 1 (Sirt1).	Metformin	13-22	angiotensinogen	Rattus norvegicus	47-53
34570873-8	2021	Furthermore, metformin significantly inhibited Ang II-upregulated ET receptors and upregulated Ang II-decreased sirtuin 1 (Sirt1).	Metformin	13-22	angiotensinogen	Rattus norvegicus	95-101
34570873-8	2021	Furthermore, metformin significantly inhibited Ang II-upregulated ET receptors and upregulated Ang II-decreased sirtuin 1 (Sirt1).	Metformin	13-22	sirtuin 1	Rattus norvegicus	112-121
34570873-8	2021	Furthermore, metformin significantly inhibited Ang II-upregulated ET receptors and upregulated Ang II-decreased sirtuin 1 (Sirt1).	Metformin	13-22	sirtuin 1	Rattus norvegicus	123-128
34570873-10	2021	Moreover, the in-vivo results showed that metformin not only inhibited Ang II-induced upregulation of ET receptors but also recovered Ang II-decreased p-AMPKalpha and Sirt1.	Metformin	42-51	angiotensinogen	Rattus norvegicus	71-77
34570873-10	2021	Moreover, the in-vivo results showed that metformin not only inhibited Ang II-induced upregulation of ET receptors but also recovered Ang II-decreased p-AMPKalpha and Sirt1.	Metformin	42-51	angiotensinogen	Rattus norvegicus	134-140
34570873-10	2021	Moreover, the in-vivo results showed that metformin not only inhibited Ang II-induced upregulation of ET receptors but also recovered Ang II-decreased p-AMPKalpha and Sirt1.	Metformin	42-51	sirtuin 1	Rattus norvegicus	167-172
34570873-11	2021	In addition, metformin significantly inhibited Ang II-elevated BP.	Metformin	13-22	angiotensinogen	Rattus norvegicus	47-53
34880648-12	2021	Conclusion: MGO intake potentiates the LPS-induced ALI, increases RAGE expression and ROS generation, which is normalized by metformin.	Metformin	125-134	advanced glycosylation end product-specific receptor	Mus musculus	66-70
34865016-3	2021	Our previous data in older adults without diabetes suggest a dichotomous change in insulin sensitivity and skeletal muscle mitochondrial adaptations after metformin treatment when co-prescribed with exercise.	Metformin	155-164	insulin	Homo sapiens	83-90
34628168-6	2021	Interestingly, metformin, an extensively used antidiabetic drug, inhibits mTOR by affecting the activity of AMPK.	Metformin	15-24	mechanistic target of rapamycin kinase	Homo sapiens	74-78
34851228-7	2021	Metformin could restore the isoflurane- and STZ-induced hippocampal tissue damage, cognitive and memory impairment in exposed space via improving the oxidative stress, upregulating the contents of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in the hippocampus tissues of diabetic mice.	Metformin	0-9	gastric inhibitory polypeptide	Mus musculus	233-277
34851228-7	2021	Metformin could restore the isoflurane- and STZ-induced hippocampal tissue damage, cognitive and memory impairment in exposed space via improving the oxidative stress, upregulating the contents of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in the hippocampus tissues of diabetic mice.	Metformin	0-9	gastric inhibitory polypeptide	Mus musculus	279-282
34851228-8	2021	Furthermore, chronic treatment of metformin significantly down-regulated the expression of AGEs, RAGE, pNF-kappaB, iNOS, and COX-2.	Metformin	34-43	advanced glycosylation end product-specific receptor	Mus musculus	97-101
34851228-8	2021	Furthermore, chronic treatment of metformin significantly down-regulated the expression of AGEs, RAGE, pNF-kappaB, iNOS, and COX-2.	Metformin	34-43	nitric oxide synthase 2, inducible	Mus musculus	115-119
34851228-9	2021	In conclusion, metformin can improve the isoflurane- and STZ-induced cognitive impairment in diabetic mice via improving oxidative stress and inhibiting the AGEs/RAGE/NF-kappaB signaling pathway.	Metformin	15-24	advanced glycosylation end product-specific receptor	Mus musculus	162-166
34628167-18	2021	These results demonstrate that metformin can improve memory impairments, increase BDNF, DCX and Nrf2 protein expressions and antioxidant capacities, and decrease MDA levels in MTX-treated rats.	Metformin	31-40	NFE2 like bZIP transcription factor 2	Rattus norvegicus	96-100
34480296-9	2021	RESULTS: The PI3K/AKT pathway was significantly related to one PCOS subnetwork and most drugs (metformin, letrozole, pioglitazone, and spironolactone); moreover, VEGF, EGF, TGFB1, AGT, AMBP, and RBP4 were identified as the shared proteins between the PCOS subnetwork and the drugs.	Metformin	95-104	AKT serine/threonine kinase 1	Homo sapiens	18-21
34969688-12	2021	Metformin prevented calpain 2 release in exosomes and restored insulin signaling impaired by estrogen.	Metformin	0-9	calpain 2	Homo sapiens	20-29
34969688-12	2021	Metformin prevented calpain 2 release in exosomes and restored insulin signaling impaired by estrogen.	Metformin	0-9	insulin	Homo sapiens	63-70
34895136-12	2021	Metformin treatment ameliorated AVICs calcification and apoptosis by activating the PI3K/AKT signaling pathway.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	89-92
34895136-13	2021	AMPK activation and NF-kappaB inhibition could inhibit AVICs calcification induced by PM treatment; however, AMPK and AKT inhibition reversed the protective effect of metformin.	Metformin	167-176	nuclear factor kappa B subunit 1	Homo sapiens	20-29
34895136-13	2021	AMPK activation and NF-kappaB inhibition could inhibit AVICs calcification induced by PM treatment; however, AMPK and AKT inhibition reversed the protective effect of metformin.	Metformin	167-176	AKT serine/threonine kinase 1	Homo sapiens	118-121
34895136-14	2021	CONCLUSIONS: This study, for the first time, demonstrates that metformin can inhibit AVICs in vitro calcification by activating the PI3K/AKT signaling pathway; this suggests that metformin may provide a potential target for the treatment of CAVD.	Metformin	63-72	AKT serine/threonine kinase 1	Homo sapiens	137-140
34943889-7	2021	Moreover, metformin, a deactivator of PXR, dramatically suppressed PB-mediated induction of hepatic SLC13A5 as well as its activation of the SLC13A5 luciferase reporter activity via PXR.	Metformin	10-19	nuclear receptor subfamily 1 group I member 2	Homo sapiens	38-41
34943889-7	2021	Moreover, metformin, a deactivator of PXR, dramatically suppressed PB-mediated induction of hepatic SLC13A5 as well as its activation of the SLC13A5 luciferase reporter activity via PXR.	Metformin	10-19	nuclear receptor subfamily 1 group I member 2	Homo sapiens	182-185
34665880-4	2021	The fact that reduced function variants of the key transporter that takes metformin into the liver (OCT1) do not alter glycaemic response to metformin suggests that metformin does not need to get into the liver to work.	Metformin	74-83	solute carrier family 22 member 1	Homo sapiens	100-104
34615619-5	2021	Management of hyperinsulinemia by pharmacological approaches, including metformin, SGLT2 inhibitor or beta3-adrenergic receptor agonist, decreased GRP78 gene expression in adipose tissue.	Metformin	72-81	heat shock protein 5	Mus musculus	147-152
34866061-4	2021	This case illustrates the in vivo effect of an SGLT2 inhibitor in a 30-year-old woman with MODY3 with poor glycaemic control despite the treatment with supramaximal doses of sulfonylurea and metformin.	Metformin	191-200	HNF1 homeobox A	Homo sapiens	91-96
34432352-0	2021	Pretreatment with metformin prevents microcystin-LR-induced tau hyperphosphorylation via mTOR-dependent PP2A and GSK-3beta activation.	Metformin	18-27	mechanistic target of rapamycin kinase	Homo sapiens	89-93
34432352-5	2021	The effect of metformin on PP2A activity was dependent on the inhibition of mTOR in MC-LR-treated SH-SY5Y cells.	Metformin	14-23	mechanistic target of rapamycin kinase	Homo sapiens	76-80
34555415-0	2021	Metformin attenuates diabetic neuropathic pain via AMPK/NF-kappaB signaling pathway in dorsal root ganglion of diabetic rats.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	51-55
34982428-16	2021	Metformin/donepezil ameliorates STZ-induced brain injury by activating the PI3K/AKT pathway and alleviating apoptosis.	Metformin	0-9	thymoma viral proto-oncogene 1	Mus musculus	80-83
34551339-8	2021	Metformin treated hUC-MSCs up-regulated the expression of osteogenic marker ALP, OCN and RUNX2, but down-regulated the expression of adipogenic markers PPARgamma and LPL.	Metformin	0-9	bone gamma-carboxyglutamate protein	Homo sapiens	81-84
34551339-8	2021	Metformin treated hUC-MSCs up-regulated the expression of osteogenic marker ALP, OCN and RUNX2, but down-regulated the expression of adipogenic markers PPARgamma and LPL.	Metformin	0-9	RUNX family transcription factor 2	Homo sapiens	89-94
34551339-8	2021	Metformin treated hUC-MSCs up-regulated the expression of osteogenic marker ALP, OCN and RUNX2, but down-regulated the expression of adipogenic markers PPARgamma and LPL.	Metformin	0-9	peroxisome proliferator activated receptor gamma	Homo sapiens	152-161
34490645-12	2021	Moreover, discontinuation of testosterone therapy in metformin-naive men increased glycated haemoglobin, as well as worsened insulin sensitivity.	Metformin	53-62	insulin	Homo sapiens	125-132
34717078-1	2021	BACKGROUND: Conflicting results have been reported regarding the effect of metformin on adiponectin levels in women with polycystic ovary syndrome (PCOS).	Metformin	75-84	adiponectin, C1Q and collagen domain containing	Homo sapiens	88-99
34717078-2	2021	This meta-analysis reviewed all studies comparing adiponectin levels before and after metformin treatment in PCOS women.	Metformin	86-95	adiponectin, C1Q and collagen domain containing	Homo sapiens	50-61
34717078-7	2021	RESULTS: Metformin treatment was associated with significantly increased serum adiponectin concentrations (10 studies, random-effects SMD (95% CI) -0.58 (-1.03, -0.13); I2 = 86%; P = 0.01).	Metformin	9-18	adiponectin, C1Q and collagen domain containing	Homo sapiens	79-90
34717078-8	2021	Additionally, the meta-analysis revealed that circulating tumor necrosis factor-alpha(TNF-alpha) and C-reactive protein (CRP) concentrations were significantly decreased after metformin treatment, with corresponding SMDs of 1.01 (95% CI: 0.74-1.28, P<0.00001) and 0.48(95% CI: 0.35-0.60, P<0.00001).	Metformin	176-185	tumor necrosis factor	Homo sapiens	58-85
34717078-8	2021	Additionally, the meta-analysis revealed that circulating tumor necrosis factor-alpha(TNF-alpha) and C-reactive protein (CRP) concentrations were significantly decreased after metformin treatment, with corresponding SMDs of 1.01 (95% CI: 0.74-1.28, P<0.00001) and 0.48(95% CI: 0.35-0.60, P<0.00001).	Metformin	176-185	tumor necrosis factor	Homo sapiens	86-95
34717078-8	2021	Additionally, the meta-analysis revealed that circulating tumor necrosis factor-alpha(TNF-alpha) and C-reactive protein (CRP) concentrations were significantly decreased after metformin treatment, with corresponding SMDs of 1.01 (95% CI: 0.74-1.28, P<0.00001) and 0.48(95% CI: 0.35-0.60, P<0.00001).	Metformin	176-185	C-reactive protein	Homo sapiens	101-119
34717078-8	2021	Additionally, the meta-analysis revealed that circulating tumor necrosis factor-alpha(TNF-alpha) and C-reactive protein (CRP) concentrations were significantly decreased after metformin treatment, with corresponding SMDs of 1.01 (95% CI: 0.74-1.28, P<0.00001) and 0.48(95% CI: 0.35-0.60, P<0.00001).	Metformin	176-185	C-reactive protein	Homo sapiens	121-124
34717078-9	2021	CONCLUSION: Following metformin administration, serum adiponectin concentrations of PCOS women were found to be significantly increased, accompanied by a significant improvement in other indicators.	Metformin	22-31	adiponectin, C1Q and collagen domain containing	Homo sapiens	54-65
34490645-14	2021	In metformin-naive subjects, the increase in gonadotropin levels correlated with the changes in testosterone levels and insulin sensitivity.	Metformin	3-12	insulin	Homo sapiens	120-127
34664036-7	2021	Maintaining proper blood glucose levels using oral antidiabetic drugs like Metformin reduced the detrimental effects of COVID-19 by different possible mechanisms such as Metformin-mediated anti-inflammatory and immunomodulatory activities; effect on viral entry and ACE2 stability; inhibition of virus infection; alters virus survival and endosomal pH; mTOR inhibition; and influence on gut microbiota.	Metformin	75-84	mechanistic target of rapamycin kinase	Homo sapiens	353-357
34887262-10	2021	Low-dose SN-38 or metformin abrogated PD-L1 protein expression, promoted FOXO3 protein level, and significantly increased the animal survival rate in syngeneic mouse tumor models.	Metformin	18-27	CD274 antigen	Mus musculus	38-43
34887262-11	2021	SN-38 or metformin sensitized unresponsive tumors responding to anti-PD-1 therapy by engaging NK or CD8+ T cells to infiltrate the tumor microenvironment (TME) and secret interferon-gamma and granzyme B to kill tumors.	Metformin	9-18	programmed cell death 1	Mus musculus	69-73
34887262-11	2021	SN-38 or metformin sensitized unresponsive tumors responding to anti-PD-1 therapy by engaging NK or CD8+ T cells to infiltrate the tumor microenvironment (TME) and secret interferon-gamma and granzyme B to kill tumors.	Metformin	9-18	interferon gamma	Homo sapiens	171-187
34887262-15	2021	CONCLUSION: We show that SN-38 or metformin can boost antitumor immunity in the TME by inhibiting c-Myc and STAT3 through FOXO3 activation.	Metformin	34-43	signal transducer and activator of transcription 3	Homo sapiens	108-113
34887262-15	2021	CONCLUSION: We show that SN-38 or metformin can boost antitumor immunity in the TME by inhibiting c-Myc and STAT3 through FOXO3 activation.	Metformin	34-43	forkhead box O3	Homo sapiens	122-127
34688695-8	2021	On the other hand, metformin exerted a more robust stimulatory action on the AMPKalpha that was accompanied by a notable decrease in the NF-kappaB nuclear binding activity and a decline in the p-mTOR levels.	Metformin	19-28	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	137-146
34853313-5	2021	Notably, metformin inactivates the GAP activity of GP73 and alleviates GP73-induced non-obese NAFLD.	Metformin	9-18	golgi membrane protein 1	Mus musculus	51-55
34530523-7	2021	The I/R group had significantly higher JNK, p38 MAPK, Bax, caspase-3, and NF-kappaB levels, and lower ERK and Bcl-2 levels in the bladder than the sham-operated group; these changes were significantly ameliorated by metformin and/or sildenafil treatment.	Metformin	216-225	Eph receptor B1	Rattus norvegicus	102-105
34530523-7	2021	The I/R group had significantly higher JNK, p38 MAPK, Bax, caspase-3, and NF-kappaB levels, and lower ERK and Bcl-2 levels in the bladder than the sham-operated group; these changes were significantly ameliorated by metformin and/or sildenafil treatment.	Metformin	216-225	BCL2, apoptosis regulator	Rattus norvegicus	110-115
34658106-8	2021	In the metformin group, the Dnmt1, Dnmt3a, and Hdac2 genes have significantly upregulated compared to the DHEA group.	Metformin	7-16	DNA methyltransferase (cytosine-5) 1	Mus musculus	28-33
34658106-8	2021	In the metformin group, the Dnmt1, Dnmt3a, and Hdac2 genes have significantly upregulated compared to the DHEA group.	Metformin	7-16	DNA methyltransferase 3A	Mus musculus	35-41
34658106-8	2021	In the metformin group, the Dnmt1, Dnmt3a, and Hdac2 genes have significantly upregulated compared to the DHEA group.	Metformin	7-16	histone deacetylase 2	Mus musculus	47-52
34853313-5	2021	Notably, metformin inactivates the GAP activity of GP73 and alleviates GP73-induced non-obese NAFLD.	Metformin	9-18	golgi membrane protein 1	Mus musculus	71-75
34570348-0	2021	Metformin Therapy Attenuates Pro-inflammatory Microglia by Inhibiting NF-kappaB in Cuprizone Demyelinating Mouse Model of Multiple Sclerosis.	Metformin	0-9	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	70-79
34570348-3	2021	Metformin, a glucose-lowering drug, attenuates inflammatory responses by activating adenosine monophosphate protein kinase (AMPK) which suppresses nuclear factor kappa B (NF-kappaB).	Metformin	0-9	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	147-169
34570348-3	2021	Metformin, a glucose-lowering drug, attenuates inflammatory responses by activating adenosine monophosphate protein kinase (AMPK) which suppresses nuclear factor kappa B (NF-kappaB).	Metformin	0-9	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	171-180
34570348-7	2021	Moreover, metformin treatment significantly downregulated the expression of pro-inflammatory associated genes (iNOS, H2-Aa, and TNF-alpha) in the corpus callosum, whereas expression of anti-inflammatory markers (Arg1, Mrc1, and IL10) was not promoted, compared to CPZ mice.	Metformin	10-19	histocompatibility 2, class II antigen A, alpha	Mus musculus	117-122
34570348-7	2021	Moreover, metformin treatment significantly downregulated the expression of pro-inflammatory associated genes (iNOS, H2-Aa, and TNF-alpha) in the corpus callosum, whereas expression of anti-inflammatory markers (Arg1, Mrc1, and IL10) was not promoted, compared to CPZ mice.	Metformin	10-19	tumor necrosis factor	Mus musculus	128-137
34570348-7	2021	Moreover, metformin treatment significantly downregulated the expression of pro-inflammatory associated genes (iNOS, H2-Aa, and TNF-alpha) in the corpus callosum, whereas expression of anti-inflammatory markers (Arg1, Mrc1, and IL10) was not promoted, compared to CPZ mice.	Metformin	10-19	interleukin 10	Mus musculus	228-232
34570348-10	2021	Finally, metformin administration significantly reduced the activation level of NF-kappaB in CPZ mice.	Metformin	9-18	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	80-89
34570348-11	2021	In summary, our data revealed that metformin attenuated pro-inflammatory microglia markers through suppressing NF-kappaB activity.	Metformin	35-44	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	111-120
34733370-8	2021	Specifically, metformin induced cell cycle arrest in the G0/G1 phases, accompanied by increased expression of p21 and p27, and decreased expression of cyclin D1 and cyclin-dependent kinase 4.	Metformin	14-23	cyclin D1	Canis lupus familiaris	151-160
34733370-8	2021	Specifically, metformin induced cell cycle arrest in the G0/G1 phases, accompanied by increased expression of p21 and p27, and decreased expression of cyclin D1 and cyclin-dependent kinase 4.	Metformin	14-23	cyclin dependent kinase 4	Canis lupus familiaris	165-190
34850313-0	2022	Metformin effect in models of inflammation is associated with activation of ATP-dependent potassium channels and inhibition of tumor necrosis factor-alpha production.	Metformin	0-9	tumor necrosis factor	Homo sapiens	127-154
34763093-8	2021	Moreover, metformin suppressed LL37- and TNF-alpha-induced the ROS production and MAPK-NF-kappaB signal activation in keratinocytes cells.	Metformin	10-19	tumor necrosis factor	Homo sapiens	41-50
34856689-3	2021	Compared with those before, treatment with either orlistat or metformin significantly reduced body weight, body mass index (BMI), hip circumferences, and serum insulin levels of the PCOS patients both at the end of 3 months and 6 months (P<0.05).	Metformin	62-71	insulin	Homo sapiens	160-167
34850372-3	2022	Metformin activates AMP-activated kinase (AMPK), which inhibits mechanistic target of rapamycin complex 1 (mTORC1) signaling.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	20-40
34850372-3	2022	Metformin activates AMP-activated kinase (AMPK), which inhibits mechanistic target of rapamycin complex 1 (mTORC1) signaling.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	42-46
34563556-6	2021	Moreover, some older antihyperglycemic drugs (metformin, thiazolidinediones), but also novel therapeutic concepts (new peroxisome proliferator-activated receptor agonists, incretin mimetics, sodium glucose cotransporter inhibitors, modulators of energy metabolism) can directly or indirectly reduce insulin resistance.	Metformin	46-55	insulin	Homo sapiens	299-306
34884312-9	2021	Since NF-kappaB signaling regulates Nfkbiz expression and the anti-diabetic agent metformin reportedly modulates NF-kappaB signaling, we examined the effect of metformin treatment on IL-36gamma-induced IL-23 production.	Metformin	82-91	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	113-122
34884312-10	2021	Metformin treatment impaired the phosphorylation of NF-kappaB induced by IL-36gamma stimulation with the subsequent downregulation of Nfkbiz, resulting in the inhibition of IL-23 production in BMDCs.	Metformin	0-9	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	52-61
34944598-0	2021	Metformin Improves Stemness of Human Adipose-Derived Stem Cells by Downmodulation of Mechanistic Target of Rapamycin (mTOR) and Extracellular Signal-Regulated Kinase (ERK) Signaling.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	85-116
34944598-0	2021	Metformin Improves Stemness of Human Adipose-Derived Stem Cells by Downmodulation of Mechanistic Target of Rapamycin (mTOR) and Extracellular Signal-Regulated Kinase (ERK) Signaling.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	118-122
34944598-0	2021	Metformin Improves Stemness of Human Adipose-Derived Stem Cells by Downmodulation of Mechanistic Target of Rapamycin (mTOR) and Extracellular Signal-Regulated Kinase (ERK) Signaling.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	128-165
34944598-0	2021	Metformin Improves Stemness of Human Adipose-Derived Stem Cells by Downmodulation of Mechanistic Target of Rapamycin (mTOR) and Extracellular Signal-Regulated Kinase (ERK) Signaling.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	167-170
34944598-8	2021	Investigating the possible underlying mechanism, we observed a decrease in the mTOR and ERK activity in metformin-treated ASCs.	Metformin	104-113	mechanistic target of rapamycin kinase	Homo sapiens	79-83
34944598-8	2021	Investigating the possible underlying mechanism, we observed a decrease in the mTOR and ERK activity in metformin-treated ASCs.	Metformin	104-113	mitogen-activated protein kinase 1	Homo sapiens	88-91
34944598-10	2021	We conclude that metformin treatment improves ASCs stemness by reducing mTOR and ERK signaling and enhancing autophagy.	Metformin	17-26	mechanistic target of rapamycin kinase	Homo sapiens	72-76
34944598-10	2021	We conclude that metformin treatment improves ASCs stemness by reducing mTOR and ERK signaling and enhancing autophagy.	Metformin	17-26	mitogen-activated protein kinase 1	Homo sapiens	81-84
34850313-9	2022	Metformin (1000 mg/kg) reduced the production of tumor necrosis factor-alpha induced by i.pl.	Metformin	0-9	tumor necrosis factor	Homo sapiens	49-76
34881181-0	2021	Metformin Downregulates PD-L1 Expression in Esophageal Squamous Cell Catrcinoma by Inhibiting IL-6 Signaling Pathway.	Metformin	0-9	interleukin 6	Homo sapiens	94-98
34850372-10	2022	Notably, ketamine, scopolamine, and metformin all exerted significant antidepressant-like actions, as evidenced by increased AMPK phosphorylation and BDNF expression.	Metformin	36-45	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	125-129
34753372-3	2022	One of the medications widely used in the treatment of T2DM is biguanide derivative, metformin, which exerts promising anticancer properties principally through activation of adenosine monophosphate kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) pathways.	Metformin	85-94	mechanistic target of rapamycin kinase	Homo sapiens	231-260
34881181-7	2021	PD-L1 expression in ESCC cell lines was significantly inhibited by metformin via the IL-6/JAK2/STAT3 signaling pathway but was not correlated with the canonical AMPK pathway.	Metformin	67-76	interleukin 6	Homo sapiens	85-89
34881181-7	2021	PD-L1 expression in ESCC cell lines was significantly inhibited by metformin via the IL-6/JAK2/STAT3 signaling pathway but was not correlated with the canonical AMPK pathway.	Metformin	67-76	signal transducer and activator of transcription 3	Homo sapiens	95-100
34881181-10	2021	Conclusions: Metformin downregulated PD-L1 expression by blocking the IL-6/JAK2/STAT3 signaling pathway in ESCC, which enhanced the antitumor immune response.	Metformin	13-22	interleukin 6	Homo sapiens	70-74
34881181-10	2021	Conclusions: Metformin downregulated PD-L1 expression by blocking the IL-6/JAK2/STAT3 signaling pathway in ESCC, which enhanced the antitumor immune response.	Metformin	13-22	signal transducer and activator of transcription 3	Homo sapiens	80-85
34957500-8	2022	Functional enrichment analysis for cDNA microarrays from kidney samples revealed significant enrichment of several pro-proliferative pathways including beta-catenin, hypoxia-inducible factor-1alpha, protein kinase Calpha and Notch signaling pathways in the metformin-treated mutant mice.	Metformin	257-266	protein kinase C, alpha	Mus musculus	199-220
34815475-8	2021	In CNDT2.5 and GOT1 cells, metformin suppressed EZH2 expression, and inhibited cell proliferation.	Metformin	27-36	enhancer of zeste 2 polycomb repressive complex 2 subunit	Homo sapiens	48-52
34753372-3	2022	One of the medications widely used in the treatment of T2DM is biguanide derivative, metformin, which exerts promising anticancer properties principally through activation of adenosine monophosphate kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) pathways.	Metformin	85-94	mechanistic target of rapamycin kinase	Homo sapiens	262-266
34825068-9	2021	Gene expression analysis demonestrated that metformin treatment was associated with an enhanced expression of antioxidant genes such as Nrf-2, HO-1, SOD and catalase in liver of HFD fed rats.	Metformin	44-53	NFE2 like bZIP transcription factor 2	Rattus norvegicus	136-141
34825068-9	2021	Gene expression analysis demonestrated that metformin treatment was associated with an enhanced expression of antioxidant genes such as Nrf-2, HO-1, SOD and catalase in liver of HFD fed rats.	Metformin	44-53	catalase	Rattus norvegicus	149-165
34825068-10	2021	Metformin treatment also found to modulate the expression of fat metabolizing and anti-inflammatory genes including PPAR--gamma, C/EBP-alpha, SREBP1c, FAS, AMPK and GLUT-4.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	156-160
34738701-7	2022	The offspring in the metformin group had higher high-density lipoprotein cholesterol (HDL-C) concentrations (1.72 vs. 1.54 mmol/L, p = 0.039) but lower low-density lipoprotein cholesterol (2.39 vs. 2.58 mmol/L, p = 0.046) and apolipoprotein B concentrations (0.63 vs. 0.67g/L, p = 0.043) than the offspring in the insulin group.	Metformin	21-30	apolipoprotein B	Homo sapiens	226-242
34956455-8	2021	Metformin significantly suppressed the deposition of collagen and elastic fibers in the fibrotic pleura and decreased the expression of extracellular matrix (ECM)-related genes, including Col1a1, Col3a1, Fn1, and Eln, in pleural CD90-positive myofibroblasts.	Metformin	0-9	fibronectin 1	Homo sapiens	204-207
34956455-9	2021	In human pleural mesothelial cells, metformin decreased TGFbeta1-induced upregulation of ECM-related genes and SNAI1.	Metformin	36-45	transforming growth factor beta 1	Homo sapiens	56-64
34956455-9	2021	In human pleural mesothelial cells, metformin decreased TGFbeta1-induced upregulation of ECM-related genes and SNAI1.	Metformin	36-45	snail family transcriptional repressor 1	Homo sapiens	111-116
34779103-1	2022	OBJECTIVE: To assess the efficacy and safety of sitagliptin in youth with type 2 diabetes (T2D) inadequately controlled with metformin +- insulin.	Metformin	125-134	insulin	Homo sapiens	138-145
34779127-0	2022	Metformin induces insulin secretion by preserving pancreatic aquaporin 7 expression in type 2 diabetes mellitus.	Metformin	0-9	insulin	Homo sapiens	18-25
34750365-0	2021	Metformin attenuates hypothalamic inflammation via downregulation of RIPK1-independent microglial necroptosis in diet-induced obese mice.	Metformin	0-9	receptor (TNFRSF)-interacting serine-threonine kinase 1	Mus musculus	69-74
34772914-8	2021	Activation of AMPK using metformin reversed the EMT program and impaired the metastatic capacity of FATP5-depleted HCC cells.	Metformin	25-34	solute carrier family 27 member 5	Homo sapiens	100-105
34730825-9	2021	Metformin inhibited CpG- and IFN-alpha-induced glutamine uptake, mitochondrial functions and suppressed plasmablast differentiation.	Metformin	0-9	interferon alpha 1	Homo sapiens	29-38
34761355-1	2022	PURPOSE: Metformin induces GLUT-4 mRNA expression in insulin target tissues in PCOS.	Metformin	9-18	insulin	Homo sapiens	53-60
34725961-0	2022	Metformin induces muscle atrophy by transcriptional regulation of myostatin via HDAC6 and FoxO3a.	Metformin	0-9	histone deacetylase 6	Mus musculus	80-85
34725961-9	2022	AMPK alpha2 knockdown in the background of metformin treatment reduced the myostatin expression of C2C12 myotubes (-49.86 +- 12.03%, P < 0.01) and resulted in increased myotube diameter compared with metformin (+46.62 +- 0.88%, P < 0.001).	Metformin	43-52	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	0-11
34725961-12	2022	The interaction between HDAC6 and FoxO3a induced after metformin treatment.	Metformin	55-64	histone deacetylase 6	Mus musculus	24-29
34725961-18	2022	CONCLUSIONS: Our results demonstrate that metformin treatment impairs muscle function through the regulation of myostatin in skeletal muscle cells via AMPK-FoxO3a-HDAC6 axis.	Metformin	42-51	histone deacetylase 6	Mus musculus	163-168
34607979-6	2021	Accordingly, the p27 and p21 promoter activities were enhanced while Bcl-2 and IL-6 activities were significantly reduced by metformin treatment.	Metformin	125-134	dynactin subunit 6	Homo sapiens	17-20
34764661-9	2021	Conclusion: As adjunctive therapy, the combination of lifestyle changes and metformin was found to be a safe strategy for improving related metabolic markers and increasing adiponectin.	Metformin	76-85	adiponectin, C1Q and collagen domain containing	Homo sapiens	173-184
34607979-6	2021	Accordingly, the p27 and p21 promoter activities were enhanced while Bcl-2 and IL-6 activities were significantly reduced by metformin treatment.	Metformin	125-134	BCL2 apoptosis regulator	Homo sapiens	69-74
34607979-6	2021	Accordingly, the p27 and p21 promoter activities were enhanced while Bcl-2 and IL-6 activities were significantly reduced by metformin treatment.	Metformin	125-134	interleukin 6	Homo sapiens	79-83
34607979-7	2021	Metformin diminished the phosphorylation of mTOR, p70S6K and 4E-BP1 by accelerating adenosine monophosphateactivated kinase (AMPK) in HeLa cancer cells, but it did not affect other cell lines.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	44-48
34607979-7	2021	Metformin diminished the phosphorylation of mTOR, p70S6K and 4E-BP1 by accelerating adenosine monophosphateactivated kinase (AMPK) in HeLa cancer cells, but it did not affect other cell lines.	Metformin	0-9	BP1	Homo sapiens	64-67
34331316-6	2021	The plasma concentration of glucose, insulin, and C-peptide was higher in the portal vein compared with arterialized blood (p<0.05, all) and was lowered at both sampling sites following metformin ingestion (p<0.01, all).	Metformin	186-195	insulin	Homo sapiens	37-44
34132620-3	2021	Recently, the EMA approved the SGLT inhibitors dapagliflozin and sotagliflozin as adjuvant treatments to insulin for type 1 diabetes in adults.Areas covered: This article is a survey of adjuvant treatments used against type 1 diabetes, focusing on SGLT inhibitors.Expert opinion: While GLP-1R agonists and metformin may reduce weight gain associated with insulin therapy and possibly also confer non-glycemic benefits, only the SGLT inhibitors dapagliflozin and sotagliflozin have been approved in Europe as adjunctive to insulin for type 1 diabetes.	Metformin	306-315	insulin	Homo sapiens	355-362
34705249-0	2021	Glucagon-like Peptide-1 Receptor Agonists and Cardioprotective Benefit in Patients with Type 2 Diabetes Without Baseline Metformin: A Systematic Review and Update Meta-analysis.	Metformin	121-130	glucagon	Homo sapiens	0-23
34539827-0	2021	Metformin attenuates angiotensin II-induced cardiomyocyte hypertrophy by upregulating the MuRF1 and MAFbx pathway.	Metformin	0-9	angiotensinogen	Rattus norvegicus	21-35
34539827-0	2021	Metformin attenuates angiotensin II-induced cardiomyocyte hypertrophy by upregulating the MuRF1 and MAFbx pathway.	Metformin	0-9	tripartite motif containing 63	Rattus norvegicus	90-95
34539827-0	2021	Metformin attenuates angiotensin II-induced cardiomyocyte hypertrophy by upregulating the MuRF1 and MAFbx pathway.	Metformin	0-9	F-box protein 32	Rattus norvegicus	100-105
34539827-4	2021	However, the potential role of metformin in the modulation of MuRF1 and MAFbx in cardiomyocyte hypertrophy remains poorly understood.	Metformin	31-40	tripartite motif containing 63	Rattus norvegicus	62-67
34539827-4	2021	However, the potential role of metformin in the modulation of MuRF1 and MAFbx in cardiomyocyte hypertrophy remains poorly understood.	Metformin	31-40	F-box protein 32	Rattus norvegicus	72-77
34539827-12	2021	In addition, expression of ANP and BNP was significantly reduced in metformin-treated H9C2 cells.	Metformin	68-77	natriuretic peptide B	Rattus norvegicus	35-38
34539827-13	2021	The results indicated that metformin increased the activity of MuRF1 and MAFbx and upregulated their expression, the knockdown of which resulted in deteriorative Ang II-induced cell hypertrophy, even following treatment with metformin.	Metformin	27-36	tripartite motif containing 63	Rattus norvegicus	63-68
34539827-13	2021	The results indicated that metformin increased the activity of MuRF1 and MAFbx and upregulated their expression, the knockdown of which resulted in deteriorative Ang II-induced cell hypertrophy, even following treatment with metformin.	Metformin	27-36	F-box protein 32	Rattus norvegicus	73-78
34539827-13	2021	The results indicated that metformin increased the activity of MuRF1 and MAFbx and upregulated their expression, the knockdown of which resulted in deteriorative Ang II-induced cell hypertrophy, even following treatment with metformin.	Metformin	27-36	angiotensinogen	Rattus norvegicus	162-168
34539827-13	2021	The results indicated that metformin increased the activity of MuRF1 and MAFbx and upregulated their expression, the knockdown of which resulted in deteriorative Ang II-induced cell hypertrophy, even following treatment with metformin.	Metformin	225-234	tripartite motif containing 63	Rattus norvegicus	63-68
34539827-13	2021	The results indicated that metformin increased the activity of MuRF1 and MAFbx and upregulated their expression, the knockdown of which resulted in deteriorative Ang II-induced cell hypertrophy, even following treatment with metformin.	Metformin	225-234	F-box protein 32	Rattus norvegicus	73-78
34539827-13	2021	The results indicated that metformin increased the activity of MuRF1 and MAFbx and upregulated their expression, the knockdown of which resulted in deteriorative Ang II-induced cell hypertrophy, even following treatment with metformin.	Metformin	225-234	angiotensinogen	Rattus norvegicus	162-168
34539827-14	2021	Taken together, data from the present study suggest that metformin can prevent cardiac hypertrophy through the MuRF1 and MAFbx pathways.	Metformin	57-66	tripartite motif containing 63	Rattus norvegicus	111-116
34539827-14	2021	Taken together, data from the present study suggest that metformin can prevent cardiac hypertrophy through the MuRF1 and MAFbx pathways.	Metformin	57-66	F-box protein 32	Rattus norvegicus	121-126
34815353-0	2021	Metformin reduces PD-L1 on tumor cells and enhances the anti-tumor immune response generated by vaccine immunotherapy.	Metformin	0-9	CD274 antigen	Mus musculus	18-23
34815353-3	2021	Metformin has emerged as a potential new drug for the treatment of cancer due to its effects on PD-L1 expression, T cell responses, and the immunosuppressive environment within tumors.	Metformin	0-9	CD274 antigen	Mus musculus	96-101
34815353-6	2021	The effect of metformin on IFN-gamma induced PD-L1 expression in tumor cells was assessed by flow cytometry, western blot, and RT-qPCR.	Metformin	14-23	interferon gamma	Mus musculus	27-36
34815353-6	2021	The effect of metformin on IFN-gamma induced PD-L1 expression in tumor cells was assessed by flow cytometry, western blot, and RT-qPCR.	Metformin	14-23	CD274 antigen	Mus musculus	45-50
34815353-7	2021	RESULTS: We observed that tumors that respond to metformin and vaccine immunotherapy combination show a reduction in surface PD-L1 expression compared with tumor models that do not respond to metformin.	Metformin	49-58	CD274 antigen	Mus musculus	125-130
34815353-8	2021	In vitro assays showed that the effect of metformin on tumor cell PD-L1 expression was mediated in part by AMP-activated protein kinase signaling.	Metformin	42-51	CD274 antigen	Mus musculus	66-71
34815353-10	2021	However, we observed an increased number of CD8 T cells expressing PD-1, Ki-67, Tim-3, and CD62L as well as increased effector cytokine production after treatment with metformin and tumor membrane vesicle vaccine.	Metformin	168-177	programmed cell death 1	Mus musculus	67-71
34815353-10	2021	However, we observed an increased number of CD8 T cells expressing PD-1, Ki-67, Tim-3, and CD62L as well as increased effector cytokine production after treatment with metformin and tumor membrane vesicle vaccine.	Metformin	168-177	selectin, lymphocyte	Mus musculus	91-96
34102283-10	2021	Independent of its anti-hyperglycemic effects, metformin successfully preserved mitochondrial integrity and upregulated myocardial PGC-1alpha, calcineurin, and SQSTM1 gene expression.	Metformin	47-56	PPARG coactivator 1 alpha	Rattus norvegicus	131-141
34102283-10	2021	Independent of its anti-hyperglycemic effects, metformin successfully preserved mitochondrial integrity and upregulated myocardial PGC-1alpha, calcineurin, and SQSTM1 gene expression.	Metformin	47-56	sequestosome 1	Rattus norvegicus	160-166
34102283-11	2021	omega-3 PUFAs possess synergistic cardioprotection when added to metformin, suggested by improvements in myocardial ultrastructure, autophagic activity, and SQSTM1 gene expression.	Metformin	65-74	sequestosome 1	Rattus norvegicus	157-163
34716862-8	2021	Downregulation of ERK signaling, upregulation of AMPK pathway and precision in epithelial-mesenchymal transition (EMT) pathway which were assessed by RT-PCR and Western blot provide the evidence that the combination of drugs involved in the precision of altered molecular signaling Further our results suggest that Metformin act as a demethylating agent in anaplastic thyroid cancer cells by inducing the expression of NIS and TSHR.	Metformin	315-324	mitogen-activated protein kinase 1	Homo sapiens	18-21
34452975-0	2021	Metformin prevents hyperglycaemia-associated, oxidative stress-induced vascular endothelial dysfunction: essential role for the orphan nuclear receptor, Nr4a1 (Nur77).	Metformin	0-9	nuclear receptor subfamily 4 group A member 1	Homo sapiens	153-158
34452975-0	2021	Metformin prevents hyperglycaemia-associated, oxidative stress-induced vascular endothelial dysfunction: essential role for the orphan nuclear receptor, Nr4a1 (Nur77).	Metformin	0-9	nuclear receptor subfamily 4 group A member 1	Homo sapiens	160-165
34452975-5	2021	Using in silico modelling of metformin-NR4A1 interactions, Nr4a1-mutagenesis and a transfected HEK 293T cell functional assay for metformin-activated Nr4a1, we identified two Nr4a1 prolines, P505/P549 (mouse sequences corresponding to human P501/P546), as key residues for enabling metformin to affect mitochondrial function.	Metformin	29-38	nuclear receptor subfamily 4 group A member 1	Homo sapiens	39-44
34452975-5	2021	Using in silico modelling of metformin-NR4A1 interactions, Nr4a1-mutagenesis and a transfected HEK 293T cell functional assay for metformin-activated Nr4a1, we identified two Nr4a1 prolines, P505/P549 (mouse sequences corresponding to human P501/P546), as key residues for enabling metformin to affect mitochondrial function.	Metformin	130-139	nuclear receptor subfamily 4 group A member 1	Homo sapiens	150-155
34452975-5	2021	Using in silico modelling of metformin-NR4A1 interactions, Nr4a1-mutagenesis and a transfected HEK 293T cell functional assay for metformin-activated Nr4a1, we identified two Nr4a1 prolines, P505/P549 (mouse sequences corresponding to human P501/P546), as key residues for enabling metformin to affect mitochondrial function.	Metformin	130-139	nuclear receptor subfamily 4 group A member 1	Homo sapiens	175-180
34452975-5	2021	Using in silico modelling of metformin-NR4A1 interactions, Nr4a1-mutagenesis and a transfected HEK 293T cell functional assay for metformin-activated Nr4a1, we identified two Nr4a1 prolines, P505/P549 (mouse sequences corresponding to human P501/P546), as key residues for enabling metformin to affect mitochondrial function.	Metformin	282-291	nuclear receptor subfamily 4 group A member 1	Homo sapiens	39-44
34452975-5	2021	Using in silico modelling of metformin-NR4A1 interactions, Nr4a1-mutagenesis and a transfected HEK 293T cell functional assay for metformin-activated Nr4a1, we identified two Nr4a1 prolines, P505/P549 (mouse sequences corresponding to human P501/P546), as key residues for enabling metformin to affect mitochondrial function.	Metformin	282-291	nuclear receptor subfamily 4 group A member 1	Homo sapiens	59-64
34452975-5	2021	Using in silico modelling of metformin-NR4A1 interactions, Nr4a1-mutagenesis and a transfected HEK 293T cell functional assay for metformin-activated Nr4a1, we identified two Nr4a1 prolines, P505/P549 (mouse sequences corresponding to human P501/P546), as key residues for enabling metformin to affect mitochondrial function.	Metformin	282-291	nuclear receptor subfamily 4 group A member 1	Homo sapiens	150-155
34452975-5	2021	Using in silico modelling of metformin-NR4A1 interactions, Nr4a1-mutagenesis and a transfected HEK 293T cell functional assay for metformin-activated Nr4a1, we identified two Nr4a1 prolines, P505/P549 (mouse sequences corresponding to human P501/P546), as key residues for enabling metformin to affect mitochondrial function.	Metformin	282-291	nuclear receptor subfamily 4 group A member 1	Homo sapiens	175-180
34452975-6	2021	Our data indicate a critical role for Nr4a1 in metformin"s endothelial-protective effects, observed at micromolar concentrations, which activate AMPKinase but do not affect mitochondrial complex-I or complex-III oxygen consumption rates, as does 0.5 mM metformin.	Metformin	47-56	nuclear receptor subfamily 4 group A member 1	Homo sapiens	38-43
34452975-7	2021	Thus, therapeutic metformin concentrations, requiring the expression of Nr4a1, protect the vasculature from hyperglycaemia-induced dysfunction in addition to metformin"s action to enhance insulin action in diabetics.	Metformin	18-27	nuclear receptor subfamily 4 group A member 1	Homo sapiens	72-77
34452975-10	2021	However, this action of metformin requires the expression of the orphan nuclear receptor, NR4A1/Nur77.	Metformin	24-33	nuclear receptor subfamily 4 group A member 1	Homo sapiens	90-95
34452975-10	2021	However, this action of metformin requires the expression of the orphan nuclear receptor, NR4A1/Nur77.	Metformin	24-33	nuclear receptor subfamily 4 group A member 1	Homo sapiens	96-101
34481229-5	2021	SC proliferation-inhibiting effect of metformin exposure was regulated by decreasing adenosine triphosphate level and respiratory enzyme activity in the mitochondria; this process was possibly mediated by the adenosine monophosphate-activated protein kinase (AMPK)/tuberous sclerosis complex 2 (TSC2)/mammalian target of rapamycin (mTOR) signaling pathway, which was regulated by the down-expressed miR-1764 and by the decreased antioxidant enzyme activity and excessive reactive oxygen species generation.	Metformin	38-47	mechanistic target of rapamycin kinase	Homo sapiens	301-330
34481229-5	2021	SC proliferation-inhibiting effect of metformin exposure was regulated by decreasing adenosine triphosphate level and respiratory enzyme activity in the mitochondria; this process was possibly mediated by the adenosine monophosphate-activated protein kinase (AMPK)/tuberous sclerosis complex 2 (TSC2)/mammalian target of rapamycin (mTOR) signaling pathway, which was regulated by the down-expressed miR-1764 and by the decreased antioxidant enzyme activity and excessive reactive oxygen species generation.	Metformin	38-47	mechanistic target of rapamycin kinase	Homo sapiens	332-336
34481229-8	2021	Our findings suggest appropriate dose of exogenous 17beta-estradiol treatment can ameliorate the inhibitory effect of metformin on SC proliferation via the regulation of AMPK/TSC2/mTOR signaling pathway, this might reduce the risk of poor male fertility caused by the abuse of anti-diabetic agents.	Metformin	118-127	mechanistic target of rapamycin kinase	Homo sapiens	180-184
34479029-2	2021	The anti-diabetic agent metformin (MET) and the aspirin metabolite salicylate (SAL) are shown to activate AMP-activated protein kinase (AMPK), suppress de novo lipogenesis (DNL), the mammalian target of rapamycin (mTOR) pathway and reduce PrCa proliferation in-vitro.	Metformin	24-33	mechanistic target of rapamycin kinase	Homo sapiens	183-212
34479029-2	2021	The anti-diabetic agent metformin (MET) and the aspirin metabolite salicylate (SAL) are shown to activate AMP-activated protein kinase (AMPK), suppress de novo lipogenesis (DNL), the mammalian target of rapamycin (mTOR) pathway and reduce PrCa proliferation in-vitro.	Metformin	24-33	mechanistic target of rapamycin kinase	Homo sapiens	214-218
34713480-9	2022	A significant reduction in homoeostatic model assessment of insulin resistance (HOMA-IR) was seen with exenatide versus metformin (MD: -0.34; 95% CI: -0.65, -0.03; I2 = 0%, low-grade evidence).	Metformin	120-129	insulin	Homo sapiens	60-67
34745769-6	2021	Mechanistically, metformin induced activation of the JAK1/2/3/STAT5 and AKT/mTOR pathways in a p38 MAPK-dependent manner rather than an AMPK-dependent manner.	Metformin	17-26	Janus kinase 1	Homo sapiens	53-61
34745769-6	2021	Mechanistically, metformin induced activation of the JAK1/2/3/STAT5 and AKT/mTOR pathways in a p38 MAPK-dependent manner rather than an AMPK-dependent manner.	Metformin	17-26	AKT serine/threonine kinase 1	Homo sapiens	72-75
34745769-6	2021	Mechanistically, metformin induced activation of the JAK1/2/3/STAT5 and AKT/mTOR pathways in a p38 MAPK-dependent manner rather than an AMPK-dependent manner.	Metformin	17-26	mechanistic target of rapamycin kinase	Homo sapiens	76-80
34769067-0	2021	Increased Post-Hypoxic Oxidative Stress and Activation of the PERK Branch of the UPR in Trap1-Deficient Drosophila melanogaster Is Abrogated by Metformin.	Metformin	144-153	rolled	Drosophila melanogaster	62-66
34769067-12	2021	Metformin appears to rescue Trap1-deficiency after hypoxia mitigating ROS production and downregulating the pro-apoptotic PERK (protein kinase R-like ER kinase) arm of the UPR.	Metformin	0-9	rolled	Drosophila melanogaster	122-126
34769067-12	2021	Metformin appears to rescue Trap1-deficiency after hypoxia mitigating ROS production and downregulating the pro-apoptotic PERK (protein kinase R-like ER kinase) arm of the UPR.	Metformin	0-9	rolled	Drosophila melanogaster	128-159
34630670-0	2021	Metformin attenuates H2O2-induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway.	Metformin	0-9	thymoma viral proto-oncogene 1	Mus musculus	88-91
34630670-13	2021	In addition, experiments with SIRT3 knockdown indicated that metformin reverses H2O2-induced osteoblast apoptosis by upregulating the expression of SIRT3 via the PI3K/AKT pathway.	Metformin	61-70	thymoma viral proto-oncogene 1	Mus musculus	167-170
34986539-4	2021	After metformin treatment, the apoptosis rate of Caco-2 cells was decreased from (14.22+-2.34)% to 0.61)% (=3.119, <0.05), and the expression levels of tight junction protein-1 and claudin-1 increased (=5.172 and 3.546, both <0.05).	Metformin	6-15	tight junction protein 1	Homo sapiens	152-176
34689705-5	2022	Treatment of OZ rats with metformin, an activator of AMPK that blocks JNK activity, augments ZO-2 and claudin-1 expression in the liver, reduces the paracellular permeability of hepatocytes, and serum bile acid content.	Metformin	26-35	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	53-57
34670765-9	2021	CONCLUSIONS: Users of metformin and DPP-4 inhibitors had fewer adverse outcomes from COVID-19 compared with non-users, whereas insulin and sulphonylurea might predict a worse prognosis.	Metformin	22-31	insulin	Homo sapiens	127-134
34727651-9	2021	And after intervention with different doses of metformin, the lung organ coefficient, alveolitis and fibrosis scores, HYP content and the levels of TGF-beta1, TNF-alpha and IL-1beta were significantly decreased (P<0.05) .	Metformin	47-56	transforming growth factor, beta 1	Rattus norvegicus	148-157
34727651-9	2021	And after intervention with different doses of metformin, the lung organ coefficient, alveolitis and fibrosis scores, HYP content and the levels of TGF-beta1, TNF-alpha and IL-1beta were significantly decreased (P<0.05) .	Metformin	47-56	tumor necrosis factor	Rattus norvegicus	159-168
34727651-9	2021	And after intervention with different doses of metformin, the lung organ coefficient, alveolitis and fibrosis scores, HYP content and the levels of TGF-beta1, TNF-alpha and IL-1beta were significantly decreased (P<0.05) .	Metformin	47-56	interleukin 1 alpha	Rattus norvegicus	173-181
34736121-0	2021	Metformin reduces macrophage HIF1alpha-dependent proinflammatory signaling to restore brown adipocyte function in vitro.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	29-38
34736121-1	2021	Therapeutic potential of metformin in obese/diabetic patients has been associated to its ability to combat insulin resistance.	Metformin	25-34	insulin	Homo sapiens	107-114
34736121-5	2021	At the molecular level, metformin inhibits an inflammatory program executed by HIF1alpha in macrophages by inducing its degradation through the inhibition of mitochondrial complex I activity, thereby reducing oxygen consumption in a reactive oxygen species (ROS)-independent manner.	Metformin	24-33	hypoxia inducible factor 1 subunit alpha	Homo sapiens	79-88
34736121-7	2021	In conclusion, the impact of metformin on macrophages by suppressing a HIF1alpha-dependent proinflammatory program is likely responsible for a secondary beneficial effect on insulin-mediated glucose uptake and beta-adrenergic responses in brown adipocytes.	Metformin	29-38	hypoxia inducible factor 1 subunit alpha	Homo sapiens	71-80
34736121-7	2021	In conclusion, the impact of metformin on macrophages by suppressing a HIF1alpha-dependent proinflammatory program is likely responsible for a secondary beneficial effect on insulin-mediated glucose uptake and beta-adrenergic responses in brown adipocytes.	Metformin	29-38	insulin	Homo sapiens	174-181
34804675-4	2021	As metformin passes through the placenta, it is essential to know its consequence of leading to insulin resistance in the fetus as well as the impact on postnatal development.	Metformin	3-12	insulin	Homo sapiens	96-103
34745014-1	2021	Metformin is a drug used for the treatment of type 2 diabetes and disorders associated with insulin resistance.	Metformin	0-9	insulin	Homo sapiens	92-99
34486387-8	2021	While 0.1mM/L metformin upregulated the expression of BECLIN1 and LC3 I/II gene and inhibited the expression of mTOR and GSK3beta, contribute to reverse the osteogenesis inhibition of ASCs caused by high glucose.	Metformin	14-23	mechanistic target of rapamycin kinase	Homo sapiens	112-116
34385063-6	2021	Metformin (Met), as an AMPK activator, triggered autophagy and thus alleviated the inhibitory effect of Cr(VI) on NETs.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	23-27
34642298-0	2021	Metformin alleviates inflammation through suppressing FASN-dependent palmitoylation of Akt.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	87-90
34642298-6	2021	The reduction of FASN by metformin hinders Akt palmitoylation, which further disturbs Akt membrane attachment and its phosphorylation.	Metformin	25-34	AKT serine/threonine kinase 1	Homo sapiens	43-46
34642298-6	2021	The reduction of FASN by metformin hinders Akt palmitoylation, which further disturbs Akt membrane attachment and its phosphorylation.	Metformin	25-34	AKT serine/threonine kinase 1	Homo sapiens	86-89
34642298-7	2021	Metformin-mediated suppression of FASN/Akt pathway and its downstream MAPK signaling contributes to its anti-inflammatory role in macrophages.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	39-42
34626114-9	2022	Taken together, the present study suggested that poly I:C-injection led to aging-like phenomena in gut and metformin activated AMPK and SIRT1 to reduce NF-kappaB mediated inflammation and resist oxidative stress via enhanced expression of FoxO3a and PGC-1alpha, and finally delayed gut aging in vertebrates.	Metformin	107-116	forkhead box O3	Homo sapiens	239-245
34681615-8	2021	Carfilzomib led to an increased Bip expression and decreased AMPKalpha phosphorylation, while metformin coadministration partially decreased Bip expression and induced AMPKalpha phosphorylation, leading to enhanced myocardial LC3B-dependent autophagy.	Metformin	94-103	heat shock protein 5	Mus musculus	141-144
34626114-9	2022	Taken together, the present study suggested that poly I:C-injection led to aging-like phenomena in gut and metformin activated AMPK and SIRT1 to reduce NF-kappaB mediated inflammation and resist oxidative stress via enhanced expression of FoxO3a and PGC-1alpha, and finally delayed gut aging in vertebrates.	Metformin	107-116	PPARG coactivator 1 alpha	Homo sapiens	250-260
34670977-0	2021	Metformin Inhibits Transforming Growth Factor beta-Induced Fibrogenic Response of Human Dermal Fibroblasts and Suppresses Fibrosis in Keloid Spheroids.	Metformin	0-9	tumor necrosis factor	Homo sapiens	19-50
34690930-8	2021	However, Metformin, as a first-line medicine for the treatment of type 2 diabetes mellitus (T2DM), may be a potential drug benefiting diabetic patients with SARS-CoV-2 infection, probably via a suppression of mTOR signaling together with its anti-inflammatory and anti-fibrosis function in lung.	Metformin	9-18	mechanistic target of rapamycin kinase	Homo sapiens	209-213
34676202-11	2021	In metformin-treated samples, the CEBPA, TP53 and USF1 transcription factors appeared to be involved in the regulation of several factors (SOD1, SOD2, CAT, GLRX, GSTP1) blocking ROS.	Metformin	3-12	CCAAT enhancer binding protein alpha	Homo sapiens	34-39
34676202-11	2021	In metformin-treated samples, the CEBPA, TP53 and USF1 transcription factors appeared to be involved in the regulation of several factors (SOD1, SOD2, CAT, GLRX, GSTP1) blocking ROS.	Metformin	3-12	tumor protein p53	Homo sapiens	41-45
34676202-11	2021	In metformin-treated samples, the CEBPA, TP53 and USF1 transcription factors appeared to be involved in the regulation of several factors (SOD1, SOD2, CAT, GLRX, GSTP1) blocking ROS.	Metformin	3-12	superoxide dismutase 1	Homo sapiens	139-143
34676202-11	2021	In metformin-treated samples, the CEBPA, TP53 and USF1 transcription factors appeared to be involved in the regulation of several factors (SOD1, SOD2, CAT, GLRX, GSTP1) blocking ROS.	Metformin	3-12	catalase	Homo sapiens	151-154
34611097-0	2021	Metformin Inhibits Transforming Growth Factor beta-Induced Fibrogenic Response of Human Dermal Fibroblasts and Suppresses Fibrosis in Keloid Spheroids.	Metformin	0-9	tumor necrosis factor	Homo sapiens	19-50
34790753-0	2021	Metformin alleviates bevacizumab-induced vascular endothelial injury by up-regulating GDF15 and activating the PI3K/AKT/FOXO/PPARgamma signaling pathway.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	116-119
34790753-0	2021	Metformin alleviates bevacizumab-induced vascular endothelial injury by up-regulating GDF15 and activating the PI3K/AKT/FOXO/PPARgamma signaling pathway.	Metformin	0-9	peroxisome proliferator activated receptor gamma	Homo sapiens	125-134
34790753-10	2021	Conclusions: Metformin protected against bevacizumab-induced vascular endothelial injury via activation of GDF15 and the PI3K/AKT/FOXO/PPARgamma signaling pathway.	Metformin	13-22	AKT serine/threonine kinase 1	Homo sapiens	126-129
34790753-10	2021	Conclusions: Metformin protected against bevacizumab-induced vascular endothelial injury via activation of GDF15 and the PI3K/AKT/FOXO/PPARgamma signaling pathway.	Metformin	13-22	peroxisome proliferator activated receptor gamma	Homo sapiens	135-144
34076286-0	2021	Vitamin D status determines the impact of metformin on circulating prolactin levels in premenopausal women.	Metformin	42-51	prolactin	Homo sapiens	67-76
34626114-6	2022	The results of q-PCR analysis showed that metformin reduced NF-kappaB mediated inflammatory response including decreased level of pro-inflammatory cytokine IL-8 and increased expression of anti-inflammatory cytokine IL-10 in gut of the fish with natural aging and poly I:C-injected 6-month-old fish.	Metformin	42-51	C-X-C motif chemokine ligand 8	Homo sapiens	156-160
34626114-7	2022	Metformin also exhibited antioxidant effects, as it reduced ROS production which is associated with the upregulation of FoxO3a and PGC-1alpha in gut of 6-month-old fish with poly I:C-injection.	Metformin	0-9	forkhead box O3	Homo sapiens	120-126
34626114-7	2022	Metformin also exhibited antioxidant effects, as it reduced ROS production which is associated with the upregulation of FoxO3a and PGC-1alpha in gut of 6-month-old fish with poly I:C-injection.	Metformin	0-9	PPARG coactivator 1 alpha	Homo sapiens	131-141
34351835-4	2021	Drugs targeting mTOR and AMPK, such as sirolimus, rapamycin, and metformin, have shown some efficacy and tolerability in clinical trials on patients with SLE, but have not led to breakthroughs.	Metformin	65-74	mechanistic target of rapamycin kinase	Homo sapiens	16-20
34076286-3	2021	The aim of the current study was to investigate whether vitamin D status determines the impact of metformin on prolactin levels in premenopausal women with hyperprolactinaemia.	Metformin	98-107	prolactin	Homo sapiens	111-120
34076286-8	2021	Although metformin decreased glucose levels and improved insulin sensitivity in all treatment groups, this effect was more pronounced in groups 2 and 3.	Metformin	9-18	insulin	Homo sapiens	57-64
34076286-9	2021	Only in subjects with 25-hydroxyvitamin D levels within the reference range, metformin reduced prolactin levels.	Metformin	77-86	prolactin	Homo sapiens	95-104
34216041-0	2021	The impact of metformin on prolactin levels in postmenopausal women.	Metformin	14-23	prolactin	Homo sapiens	27-36
34216041-1	2021	WHAT IS KNOWN AND OBJECTIVE: Metformin-induced reduction in prolactin levels is more pronounced in users of hormonal contraception than in non-users.	Metformin	29-38	prolactin	Homo sapiens	60-69
34216041-8	2021	Although metformin reduced monomeric prolactin levels in both study groups, this effect was more pronounced in group 1 than in group 2.	Metformin	9-18	prolactin	Homo sapiens	37-46
34216041-9	2021	Only in group 1, metformin decreased total prolactin levels, while only in group 2 the drug reduced FSH levels.	Metformin	17-26	prolactin	Homo sapiens	43-52
34216041-11	2021	The impact of metformin on total and monomeric prolactin levels correlated with baseline prolactin levels and with the degree of improvement in insulin sensitivity.	Metformin	14-23	prolactin	Homo sapiens	47-56
34216041-11	2021	The impact of metformin on total and monomeric prolactin levels correlated with baseline prolactin levels and with the degree of improvement in insulin sensitivity.	Metformin	14-23	prolactin	Homo sapiens	89-98
34216041-11	2021	The impact of metformin on total and monomeric prolactin levels correlated with baseline prolactin levels and with the degree of improvement in insulin sensitivity.	Metformin	14-23	insulin	Homo sapiens	144-151
34396450-10	2021	Furthermore, NADPH oxidase 4 (NOX4) was downregulated by metformin at both the mRNA and protein levels, and adenosine 5"-monophosphate-activated protein kinase (AMPK) phosphorylation was increased by metformin.	Metformin	200-209	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	108-159
34660707-8	2021	Metformin treatment significantly inhibited the expression of YTHDC2 and circYTHDC2.	Metformin	0-9	YTH domain containing 2	Homo sapiens	62-68
34660707-11	2021	Taken together, these results suggest that the YTHDC2/circYTHDC2/TET2 pathway is an important target of metformin in preventing the progression of VSMCs dysfunction under high glucose.	Metformin	104-113	YTH domain containing 2	Homo sapiens	47-53
34605456-0	2021	Serum Vitamin B12 Levels in Patients with Type 2 Diabetes Mellitus on Metformin Compared to those Never on Metformin: A Cross-sectional Study from Bangladesh.	Metformin	70-79	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	14-17
34605456-2	2021	Metformin use is a known cause of B12 deficiency in patients with type 2 DM (T2DM).	Metformin	0-9	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	34-37
34605456-7	2021	Subjects in the metformin group had significantly lower B12 levels compared to the non-metformin group (448.5 (343.0-570.9) vs. 549.0 (487.5-847.0) pg/mL, median (IQR), p<0.001).	Metformin	16-25	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	56-59
34605456-7	2021	Subjects in the metformin group had significantly lower B12 levels compared to the non-metformin group (448.5 (343.0-570.9) vs. 549.0 (487.5-847.0) pg/mL, median (IQR), p<0.001).	Metformin	87-96	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	56-59
34605456-11	2021	B12 levels had weak negative correlation (r = -0.061, p = 0.624) with gram-years of metformin use.	Metformin	84-93	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	0-3
34605456-12	2021	Periodic screening for serum vitamin B12 levels should be done to identify metformin-induced B12 deficiency in T2DM, especially those with PN.	Metformin	75-84	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	93-96
34429755-0	2021	Metformin mitigates PLCepsilon gene expression and modulates the Notch1/Hes and androgen receptor signaling pathways in castration-resistant prostate cancer xenograft models.	Metformin	0-9	notch receptor 1	Homo sapiens	65-71
34429755-0	2021	Metformin mitigates PLCepsilon gene expression and modulates the Notch1/Hes and androgen receptor signaling pathways in castration-resistant prostate cancer xenograft models.	Metformin	0-9	androgen receptor	Homo sapiens	80-97
34429755-2	2021	Additionally, phorbol 12-myristate 13-acetate was used to activate PLC, and Jagged1 was used as a Notch activator to verify whether metformin could suppress CRPC development via the PLCepsilon/Notch1/AR pathways.	Metformin	132-141	notch receptor 1	Homo sapiens	193-199
34429755-2	2021	Additionally, phorbol 12-myristate 13-acetate was used to activate PLC, and Jagged1 was used as a Notch activator to verify whether metformin could suppress CRPC development via the PLCepsilon/Notch1/AR pathways.	Metformin	132-141	androgen receptor	Homo sapiens	200-202
34429755-3	2021	The results confirmed that metformin may serve critical roles in CRPC by significantly inhibiting the occurrence, growth and proliferation of CRPC tumors by decreasing PLCepsilon/Notch1 expression and AR nucleation.	Metformin	27-36	notch receptor 1	Homo sapiens	179-185
34429755-3	2021	The results confirmed that metformin may serve critical roles in CRPC by significantly inhibiting the occurrence, growth and proliferation of CRPC tumors by decreasing PLCepsilon/Notch1 expression and AR nucleation.	Metformin	27-36	androgen receptor	Homo sapiens	201-203
34478236-2	2021	The anticancer effect exerted by the pleiotropic drug metformin and the associated reduction in hypoxia-inducible factor 1alpha (HIF-1alpha) levels putatively mediated by MC1 inhibition led to the development of HIF-1alpha inhibitors, such as BAY87-2243, with a more specific MC1 targeting.	Metformin	54-63	hypoxia inducible factor 1 subunit alpha	Homo sapiens	96-127
34478236-2	2021	The anticancer effect exerted by the pleiotropic drug metformin and the associated reduction in hypoxia-inducible factor 1alpha (HIF-1alpha) levels putatively mediated by MC1 inhibition led to the development of HIF-1alpha inhibitors, such as BAY87-2243, with a more specific MC1 targeting.	Metformin	54-63	hypoxia inducible factor 1 subunit alpha	Homo sapiens	129-139
34599229-9	2021	Chronic metformin administration partially reversed oxidative damage in sucrose-fed animals, together with increased AMPK activation; probably by modulating BACE-1 and NFE2L2.	Metformin	8-17	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	117-121
34599229-9	2021	Chronic metformin administration partially reversed oxidative damage in sucrose-fed animals, together with increased AMPK activation; probably by modulating BACE-1 and NFE2L2.	Metformin	8-17	NFE2 like bZIP transcription factor 2	Rattus norvegicus	168-174
34680477-8	2021	Our results show that treatment with liraglutide, metformin or their combination ameliorates DKD by rectifying renal function tests and protecting against fibrosis paralleled by restored mRNA levels of nephrin, DUOX1 and 2, and reduced ROS production.	Metformin	50-59	dual oxidase 1	Rattus norvegicus	211-222
34396450-10	2021	Furthermore, NADPH oxidase 4 (NOX4) was downregulated by metformin at both the mRNA and protein levels, and adenosine 5"-monophosphate-activated protein kinase (AMPK) phosphorylation was increased by metformin.	Metformin	200-209	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	161-165
34396450-12	2021	It was also found that metformin upregulated the phosphorylation of AMPK and decreased the expression of NOX4.	Metformin	23-32	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	68-72
34396450-13	2021	Furthermore, pre-treatment with AMPK inhibitor compound-C could block the effect of metformin, indicated by increased NOX4 compared with metformin treatment alone.	Metformin	84-93	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	32-36
34396450-13	2021	Furthermore, pre-treatment with AMPK inhibitor compound-C could block the effect of metformin, indicated by increased NOX4 compared with metformin treatment alone.	Metformin	137-146	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	32-36
34396450-15	2021	In conclusion, the present study indicated that metformin activated AMPK to inhibit the expression of NOX4, leading to a decrease in myocardial oxidative damage and apoptosis, thus alleviating reperfusion injury.	Metformin	48-57	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	68-72
34638899-9	2021	The present results indicate a shift towards synergism in cells with mutant or null p53, treated with olaparib combined with metformin, providing a new approach to the treatment of gynecologic cancers.	Metformin	125-134	tumor protein p53	Homo sapiens	84-87
34664819-7	2021	Treatment of the BC mice with metformin alone and in combination with cimetidine and/or ibuprofen enhanced the frequency of Th1 cells, and IFN-gamma concentration, while it resulted in a decrease in the frequency of Treg cells, serum TGF-beta concentration, and the expression of FOXP3 and TGF-beta compared with un-treated BC mice.	Metformin	30-39	interferon gamma	Mus musculus	139-148
34584119-5	2021	Metformin upregulated the human antimicrobial peptides cathelicidin LL-37 and RNase7 via modulation of the TRPA1 channel and AMPK pathway.	Metformin	0-9	cathelicidin antimicrobial peptide	Homo sapiens	68-73
34584119-6	2021	Interestingly, metformin stimulation enriched both LL-37 and TRPA1 in lysosomes.	Metformin	15-24	cathelicidin antimicrobial peptide	Homo sapiens	51-56
34584119-8	2021	Moreover, metformin also triggered mRNA expression of the proinflammatory cytokines IL1B, CXCL8 and growth factor GDF15 in human uroepithelial cells.	Metformin	10-19	interleukin 1 beta	Homo sapiens	84-88
34584119-8	2021	Moreover, metformin also triggered mRNA expression of the proinflammatory cytokines IL1B, CXCL8 and growth factor GDF15 in human uroepithelial cells.	Metformin	10-19	C-X-C motif chemokine ligand 8	Homo sapiens	90-95
34684418-7	2021	Maternal metformin increased MyoD expression but decreased Ppargc1a, Drp1 and Mfn2 expression in SM of adult male and female offspring.	Metformin	9-18	PPARG coactivator 1 alpha	Rattus norvegicus	59-67
34684418-9	2021	Maternal metformin increased AMPK phosphorylation and decreased 4E-BP1 phosphorylation in SM of male and female offspring.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	29-33
34684418-9	2021	Maternal metformin increased AMPK phosphorylation and decreased 4E-BP1 phosphorylation in SM of male and female offspring.	Metformin	9-18	eukaryotic translation initiation factor 4E binding protein 1	Rattus norvegicus	64-70
34684418-10	2021	Our data demonstrate that maternal metformin during gestation and lactation can potentially overcome the negative effects of perinatal exposure to HF diet in offspring, by altering their myogenesis, mitochondrial biogenesis and dynamics through AMPK/mTOR pathways in SM.	Metformin	35-44	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	245-249
34564891-5	2022	Our results showed that topical application of metformin can effectively suppress the PDL-induced early stage of angiogenesis via inhibition of the AKT/mTOR/P70S6K pathway in animal models.	Metformin	47-56	AKT serine/threonine kinase 1	Rattus norvegicus	148-151
34593005-6	2021	METHODS: Metformin (Met) down-regulates NADH/NADPH, promotes the FAO of CD8+ T cells by activating AMPK, increases the number of CD8+ TCM, which boosts the long-term immune memory of tumor-bearing mice treated with PTT.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	99-103
34311050-0	2021	Metformin attenuates vascular pathology by increasing expression of insulin-degrading enzyme in a mixed model of cerebral amyloid angiopathy and type 2 diabetes mellitus.	Metformin	0-9	insulin degrading enzyme	Mus musculus	68-92
34311050-9	2021	Compared with controls, metformin-treated APP23-ob/ob mice had significantly reduced Abeta levels in the cerebral cortex (p < .05) and hippocampus (p < .05) and increased levels of IDE in the hippocampus (p < .01).	Metformin	24-33	insulin degrading enzyme	Mus musculus	181-184
34311050-10	2021	Our results indicate that metformin attenuates the severity of CAA by enhancing Abeta-cleaving IDE expression.	Metformin	26-35	insulin degrading enzyme	Mus musculus	95-98
34558242-15	2021	CONCLUSION: EA, metformin and EA plus metformin can improve cognitive ability and relieve SP formation in cerebral cortex and hippocampus in AD mice, which may be associated with their functions in down-regulating the expression of betaACE1 and up-regulating the expression of IDE.	Metformin	16-25	insulin degrading enzyme	Mus musculus	277-280
34558242-15	2021	CONCLUSION: EA, metformin and EA plus metformin can improve cognitive ability and relieve SP formation in cerebral cortex and hippocampus in AD mice, which may be associated with their functions in down-regulating the expression of betaACE1 and up-regulating the expression of IDE.	Metformin	38-47	insulin degrading enzyme	Mus musculus	277-280
34280460-0	2021	Metformin reduces oxandrolone- induced depression-like behavior in rats via modulating the expression of IL-1beta, IL-6, IL-10 and TNF-alpha.	Metformin	0-9	interleukin 1 alpha	Rattus norvegicus	105-113
34638615-2	2021	Even though the various therapeutic potential of metformin treatment has been reported, as well as the improvement of insulin sensitivity and glucose homeostasis, the mechanisms underlying those benefits are still not fully understood.	Metformin	49-58	insulin	Homo sapiens	118-125
34280460-0	2021	Metformin reduces oxandrolone- induced depression-like behavior in rats via modulating the expression of IL-1beta, IL-6, IL-10 and TNF-alpha.	Metformin	0-9	interleukin 6	Rattus norvegicus	115-119
34280460-0	2021	Metformin reduces oxandrolone- induced depression-like behavior in rats via modulating the expression of IL-1beta, IL-6, IL-10 and TNF-alpha.	Metformin	0-9	tumor necrosis factor	Rattus norvegicus	131-140
34630103-8	2021	Metformin significantly decreased CRP levels and DAS-28-CRP after 6 months compared to the control group (p-value <0.001).	Metformin	0-9	C-reactive protein	Homo sapiens	34-37
34630103-8	2021	Metformin significantly decreased CRP levels and DAS-28-CRP after 6 months compared to the control group (p-value <0.001).	Metformin	0-9	C-reactive protein	Homo sapiens	56-59
34630103-10	2021	Despite the significantly higher serum adiponectin in the metformin group at baseline, it was significantly reduced after 6 months in the metformin group with median percent change of -63.49% compared to the significant increase in the control group with median percent change of 92.40%.	Metformin	58-67	adiponectin, C1Q and collagen domain containing	Homo sapiens	39-50
34630103-10	2021	Despite the significantly higher serum adiponectin in the metformin group at baseline, it was significantly reduced after 6 months in the metformin group with median percent change of -63.49% compared to the significant increase in the control group with median percent change of 92.40%.	Metformin	138-147	adiponectin, C1Q and collagen domain containing	Homo sapiens	39-50
34546972-0	2021	Metformin inhibits hepatocellular carcinoma development by inducing apoptosis and pyroptosis through regulating FOXO3.	Metformin	0-9	forkhead box O3	Homo sapiens	112-117
34546972-13	2021	This effect of metformin is partially dependent on FOXO3 which can activate the transcription of NLRP3.	Metformin	15-24	forkhead box O3	Homo sapiens	51-56
34546972-13	2021	This effect of metformin is partially dependent on FOXO3 which can activate the transcription of NLRP3.	Metformin	15-24	NLR family pyrin domain containing 3	Homo sapiens	97-102
34572149-8	2021	In addition, metformin, a potential inhibitor of TLR4, also decreased expression of COX-2 and IL-6 induced by co-incubation with IL-26 and palmitate.	Metformin	13-22	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	84-89
34548527-2	2021	In addition to its antigluconeogenic and insulin-sensitizing properties, metformin has emerged as a potent inhibitor of the chronic inflammatory response of macrophages.	Metformin	73-82	insulin	Homo sapiens	41-48
34548527-3	2021	In particular, metformin treatment has been shown to reduce expression of interleukin (IL-) 1beta during long-term exposure to the pro-inflammatory stimulus lipopolysaccharide (LPS) through a reduction in reactive oxygen species (ROS), which decreases the levels of the hypoxia-inducible factor (HIF) 1-alpha, and through enhanced expression of IL-10.	Metformin	15-24	hypoxia inducible factor 1 subunit alpha	Homo sapiens	270-308
34572149-8	2021	In addition, metformin, a potential inhibitor of TLR4, also decreased expression of COX-2 and IL-6 induced by co-incubation with IL-26 and palmitate.	Metformin	13-22	interleukin 6	Homo sapiens	94-98
34573418-7	2021	Overexpression of G0S2 significantly induced apoptosis of macrophages in a dose-dependent manner and blunted the function of the crucial anti-apoptotic gene Bcl-2, which was significantly reduced by metformin.	Metformin	199-208	BCL2 apoptosis regulator	Homo sapiens	157-162
34576192-11	2021	Metformin and DCA inhibited mTOR complex I signaling through upregulated AMPK-independent REDD1.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	28-32
34528900-0	2021	Metformin-induced chemosensitization to cisplatin depends on P53 status and is inhibited by Jarid1b overexpression in non-small cell lung cancer cells.	Metformin	0-9	tumor protein p53	Homo sapiens	61-64
34528900-3	2021	Here we test if the presence of P53 could predict the activity of metformin as an adjuvant for cisplatin-based therapy in non-small cell lung cancer (NSCLC).	Metformin	66-75	tumor protein p53	Homo sapiens	32-35
34528900-7	2021	Metformin sensitized A549 and HCC 827 cells (but not H1299 and H358 cells) to cisplatin in a P53-dependent manner, changing its subcellular localization to the mitochondria.	Metformin	0-9	tumor protein p53	Homo sapiens	93-96
34528900-8	2021	Treatment with a sub-lethal dose of cisplatin increased Jarid1b expression, yet downregulated P53 levels, protecting A549Res cells from metformin-induced chemosensitization to cisplatin and favored a glycolytic phenotype.	Metformin	136-145	tumor protein p53	Homo sapiens	94-97
34528900-10	2021	In conclusion, metformin could potentially be used as an adjuvant for cisplatin-based therapy in NSCLC cells if wild type P53 is present.	Metformin	15-24	tumor protein p53	Homo sapiens	122-125
34116042-9	2021	High-dextrose and TM increased IRE1alpha and PERK phosphorylation and ATF6 and GRP78 expression, while treatment with metformin, liraglutide (a GLP-1 receptor agonist) and dapagliflozin (a SGLT-2 inhibitor), suppressed IRE1alpha and PERK phosphorylation as well as ATF6 and GRP78 expression.	Metformin	118-127	heat shock protein family A (Hsp70) member 5	Homo sapiens	79-84
34116042-9	2021	High-dextrose and TM increased IRE1alpha and PERK phosphorylation and ATF6 and GRP78 expression, while treatment with metformin, liraglutide (a GLP-1 receptor agonist) and dapagliflozin (a SGLT-2 inhibitor), suppressed IRE1alpha and PERK phosphorylation as well as ATF6 and GRP78 expression.	Metformin	118-127	heat shock protein family A (Hsp70) member 5	Homo sapiens	274-279
34568732-4	2021	Objective: To evaluate the effects of Gal and metformin (met) on the levels of glucose, insulin, testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sperm count, antioxidant status, and histological changes in the testes of diabetic mice induced by methylglyoxal (MGO).	Metformin	46-55	follicle stimulating hormone beta	Mus musculus	137-165
34568732-4	2021	Objective: To evaluate the effects of Gal and metformin (met) on the levels of glucose, insulin, testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sperm count, antioxidant status, and histological changes in the testes of diabetic mice induced by methylglyoxal (MGO).	Metformin	46-55	follicle stimulating hormone beta	Mus musculus	167-170
34495393-2	2021	RECENT FINDINGS: A large, multicenter, double-blind randomized controlled trial found that women with type 2 diabetes in pregnancy treated with metformin as an adjunct to insulin therapy had less gestational weight gain, insulin requirements, caesarian sections, macrosomia, and neonatal adiposity, but more neonates were small for gestational age (SGA) compared with insulin alone.	Metformin	144-153	insulin	Homo sapiens	221-228
34646376-1	2021	As a first-line treatment for diabetes, the insulin-sensitizing biguanide, metformin, regulates glucose levels and positively affects cardiovascular function in patients with diabetes and cardiovascular complications.	Metformin	75-84	insulin	Homo sapiens	44-51
34255745-0	2021	Inhibition of mTOR signaling and clinical activity of metformin in oral premalignant lesions.	Metformin	54-63	mechanistic target of rapamycin kinase	Homo sapiens	14-18
34255745-2	2021	Here, we conducted a single-arm, open label phase IIa clinical trial (NCT02581137) in individuals with oral premalignant lesions (OPL) to explore the potential of metformin to target PI3K/mTOR signaling for HNSCC prevention.	Metformin	163-172	mechanistic target of rapamycin kinase	Homo sapiens	188-192
34255745-11	2021	CONCLUSIONS: This is the first phase II trial of metformin in individuals with OPL, providing evidence that metformin administration results in encouraging histological responses and mTOR pathway modulation, thus supporting its further investigation as a chemopreventive agent.	Metformin	49-58	mechanistic target of rapamycin kinase	Homo sapiens	183-187
34255745-11	2021	CONCLUSIONS: This is the first phase II trial of metformin in individuals with OPL, providing evidence that metformin administration results in encouraging histological responses and mTOR pathway modulation, thus supporting its further investigation as a chemopreventive agent.	Metformin	108-117	mechanistic target of rapamycin kinase	Homo sapiens	183-187
34480113-9	2021	Furthermore, metformin ameliorated SCI-induced blockade of autophagic flux in the spinal cord, and enhanced the fusion of autophagosome and lysosome by inhibiting the AMPK-mTOR signaling pathway.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	167-171
34557403-11	2021	Finally, we showed that metformin can induce cell death in BL cells by stressing cellular metabolism through the induction of GLUT1, PKM2, and LDHA.	Metformin	24-33	lactate dehydrogenase A	Homo sapiens	143-147
34323698-2	2021	In this background, metformin, an insulin sensitizer"s neuroprotective effectiveness, has been established in the prior findings.	Metformin	20-29	insulin	Homo sapiens	34-41
34346315-0	2021	L-ergothioneine and its combination with metformin attenuates renal dysfunction in type-2 diabetic rat model by activating Nrf2 antioxidant pathway.	Metformin	41-50	NFE2 like bZIP transcription factor 2	Rattus norvegicus	123-127
34323699-0	2021	Evaluation of the effects of metformin as adenosine monophosphate-activated protein kinase activator on spatial learning and memory in a rat model of multiple sclerosis disease.	Metformin	29-38	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	42-90
34135015-2	2021	RESEARCH DESIGN AND METHODS: Glucagon was measured in three randomized, parallel, clinical studies: 1) 91 youth studied at baseline, after 12 months on metformin alone (MET) or glargine followed by metformin (G/M), and 3 months after treatment withdrawal; 2) 267 adults studied at the same time points and treated with MET, G/M, or liraglutide plus metformin (L+M) or given placebo (PLAC); and 3) 88 adults studied at baseline and after 12 and 24 months of LB or MET.	Metformin	198-207	glucagon	Homo sapiens	29-37
34135015-2	2021	RESEARCH DESIGN AND METHODS: Glucagon was measured in three randomized, parallel, clinical studies: 1) 91 youth studied at baseline, after 12 months on metformin alone (MET) or glargine followed by metformin (G/M), and 3 months after treatment withdrawal; 2) 267 adults studied at the same time points and treated with MET, G/M, or liraglutide plus metformin (L+M) or given placebo (PLAC); and 3) 88 adults studied at baseline and after 12 and 24 months of LB or MET.	Metformin	152-161	glucagon	Homo sapiens	29-37
34637373-9	2021	This could be achieved by a direct elevation of PGC-1alpha activity, a stabilization or modification of its upstream activators and inhibitors by chemical compounds, like 5-Aminoimidazole-4-carboxamide riboside, metformin, and resveratrol.	Metformin	212-221	PPARG coactivator 1 alpha	Homo sapiens	48-58
34296521-7	2021	Additionally, we found that metformin suppressed HLE-B3 cell senescence by improving lysosomal function and inactivating mTOR.	Metformin	28-37	mechanistic target of rapamycin kinase	Homo sapiens	121-125
34531248-0	2021	Mitochondrial reactive oxygen species trigger metformin-dependent antitumor immunity via activation of Nrf2/mTORC1/p62 axis in tumor-infiltrating CD8T lymphocytes.	Metformin	46-55	NFE2 like bZIP transcription factor 2	Homo sapiens	103-107
34671008-8	2021	Metformin, a known inhibitor of NETs formation, also decreased the FMLP-induced changes in neutrophils.	Metformin	0-9	formyl peptide receptor 1	Homo sapiens	67-71
34197898-0	2021	Metformin attenuates rotenone-induced oxidative stress and mitochondrial damage via the AKT/Nrf2 pathway.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	88-91
34197898-0	2021	Metformin attenuates rotenone-induced oxidative stress and mitochondrial damage via the AKT/Nrf2 pathway.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	92-96
34197898-6	2021	Furthermore, metformin upregulated PGC-1alpha, the master regulator of mitochondrial biogenesis and key antioxidant molecules, including glutathione and superoxide dismutase.	Metformin	13-22	PPARG coactivator 1 alpha	Homo sapiens	35-45
34197898-7	2021	We demonstrated that the drug exerted its cytoprotective effects by activating nuclear factor erythroid 2-related factor 2 (Nrf2)/heme-oxygenase (HO)-1 pathway, which in turn, is dependent on AKT activation by metformin.	Metformin	210-219	NFE2 like bZIP transcription factor 2	Homo sapiens	79-122
34197898-7	2021	We demonstrated that the drug exerted its cytoprotective effects by activating nuclear factor erythroid 2-related factor 2 (Nrf2)/heme-oxygenase (HO)-1 pathway, which in turn, is dependent on AKT activation by metformin.	Metformin	210-219	NFE2 like bZIP transcription factor 2	Homo sapiens	124-128
34197898-7	2021	We demonstrated that the drug exerted its cytoprotective effects by activating nuclear factor erythroid 2-related factor 2 (Nrf2)/heme-oxygenase (HO)-1 pathway, which in turn, is dependent on AKT activation by metformin.	Metformin	210-219	AKT serine/threonine kinase 1	Homo sapiens	192-195
34197898-8	2021	Thus, our results implicate that metformin provides neuroprotection against rotenone by inhibiting oxidative stress in the cells by inducing antioxidant system via upregulation of transcription mediated by Nrf2, thereby restoring the rotenone-induced mitochondrial dysfunction and energy deficit in the cells.	Metformin	33-42	NFE2 like bZIP transcription factor 2	Homo sapiens	206-210
34355850-0	2021	Metformin for pediatric obesity and insulin resistance: a retrospective study within an integrated health care system.	Metformin	0-9	insulin	Homo sapiens	36-43
34355850-10	2021	CONCLUSIONS: Metformin with lifestyle interventions significantly reduced weight, BMI, and BMI z score in pediatric patients with obesity and insulin resistance up to 24 months, compared with intensive and routine counseling alone.	Metformin	13-22	insulin	Homo sapiens	142-149
34502359-2	2021	Metformin, which is widely prescribed for type 2 diabetes mellitus (T2DM) patients, regulates blood sugar by inhibiting hepatic gluconeogenesis and promoting insulin sensitivity to facilitate glucose uptake by cells.	Metformin	0-9	insulin	Homo sapiens	158-165
34062070-0	2021	The role of AMPK/mTOR signaling pathway in anticancer activity of metformin.	Metformin	66-75	mechanistic target of rapamycin kinase	Homo sapiens	17-21
34343108-9	2021	CONCLUSION: Additional metformin therapy improved GV in adults with T1DM, as well as improving body composition and reducing insulin requirement.	Metformin	23-32	insulin	Homo sapiens	125-132
34502314-8	2021	Moreover, metformin resulted in reduced expression of COL3A1, alphaSMA and CD68 after 14 days of reperfusion.	Metformin	10-19	actin alpha 2, smooth muscle, aorta	Mus musculus	62-70
34427916-0	2022	Metformin accelerate wound healing by Akt phosphorylation of gingival fibroblast in insulin-resistant prediabetes mice.	Metformin	0-9	thymoma viral proto-oncogene 1	Mus musculus	38-41
34427916-13	2022	Metformin treatment significantly recovered the downregulated Akt phosphorylation and VEGF expression in high-glucose conditions.	Metformin	0-9	thymoma viral proto-oncogene 1	Mus musculus	62-65
34427916-14	2022	CONCLUSIONS: Metformin improved delayed gingival wound healing in insulin-resistant prediabetes by accelerating HGFs proliferation and migration via Akt phosphorylation in insulin signaling pathway.	Metformin	13-22	thymoma viral proto-oncogene 1	Mus musculus	149-152
34427916-14	2022	CONCLUSIONS: Metformin improved delayed gingival wound healing in insulin-resistant prediabetes by accelerating HGFs proliferation and migration via Akt phosphorylation in insulin signaling pathway.	Metformin	13-22	insulin	Homo sapiens	172-179
34514098-0	2021	Metformin inhibits gastric cancer cell proliferation by regulation of a novel Loc100506691-CHAC1 axis.	Metformin	0-9	ChaC glutathione specific gamma-glutamylcyclotransferase 1	Homo sapiens	91-96
34514098-8	2021	We concluded that anti-proliferative effects of metformin in gastric cancer may be partially caused by suppression of the Loc100506691-miR-26a-5p/miR-330-5p-CHAC1 axis.	Metformin	48-57	ChaC glutathione specific gamma-glutamylcyclotransferase 1	Homo sapiens	157-162
34135015-2	2021	RESEARCH DESIGN AND METHODS: Glucagon was measured in three randomized, parallel, clinical studies: 1) 91 youth studied at baseline, after 12 months on metformin alone (MET) or glargine followed by metformin (G/M), and 3 months after treatment withdrawal; 2) 267 adults studied at the same time points and treated with MET, G/M, or liraglutide plus metformin (L+M) or given placebo (PLAC); and 3) 88 adults studied at baseline and after 12 and 24 months of LB or MET.	Metformin	349-358	glucagon	Homo sapiens	29-37
34440224-5	2021	Metformin exerts anti-cancer properties by activating the MAPK pathway, inhibiting the PI3K/AKT/mTOR pathway, increasing tumor suppressor genes, inducing G2/M cycle arrest, and various other processes.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	92-95
34440224-5	2021	Metformin exerts anti-cancer properties by activating the MAPK pathway, inhibiting the PI3K/AKT/mTOR pathway, increasing tumor suppressor genes, inducing G2/M cycle arrest, and various other processes.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	96-100
34489707-5	2021	The modulating effects of empagliflozin and metformin on the AMPK/mTOR/NLRP3 axis and T cell polarization were delineated.	Metformin	44-53	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	61-65
34489707-5	2021	The modulating effects of empagliflozin and metformin on the AMPK/mTOR/NLRP3 axis and T cell polarization were delineated.	Metformin	44-53	NLR family, pyrin domain containing 3	Rattus norvegicus	71-76
34489707-9	2021	Interestingly, empagliflozin/metformin combination significantly enhanced AMPK phosphorylation and depressed mTOR and NLRP3 expression leading to a subsequent reduction in caspase-1 cleavage and inhibition of several inflammatory cytokines, including IL-1beta, and IL-18.	Metformin	29-38	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	74-78
34489707-9	2021	Interestingly, empagliflozin/metformin combination significantly enhanced AMPK phosphorylation and depressed mTOR and NLRP3 expression leading to a subsequent reduction in caspase-1 cleavage and inhibition of several inflammatory cytokines, including IL-1beta, and IL-18.	Metformin	29-38	NLR family, pyrin domain containing 3	Rattus norvegicus	118-123
34489707-9	2021	Interestingly, empagliflozin/metformin combination significantly enhanced AMPK phosphorylation and depressed mTOR and NLRP3 expression leading to a subsequent reduction in caspase-1 cleavage and inhibition of several inflammatory cytokines, including IL-1beta, and IL-18.	Metformin	29-38	interleukin 1 alpha	Rattus norvegicus	251-259
34489707-11	2021	Together, the current study reveals that the protective effects of empagliflozin and metformin against DSS-induced colitis are fundamentally mediated via enhancing AMPK phosphorylation.	Metformin	85-94	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	164-168
34484117-7	2021	Decreased FSHR expression and increased LHCGR expression were observed in F1 female rats of the PCOS-IR and PCOS-IR+Metformin groups, suggesting that FSHR and LHCGR dysfunction might promote the development of PCOS.	Metformin	116-125	luteinizing hormone/choriogonadotropin receptor	Rattus norvegicus	40-45
34484117-7	2021	Decreased FSHR expression and increased LHCGR expression were observed in F1 female rats of the PCOS-IR and PCOS-IR+Metformin groups, suggesting that FSHR and LHCGR dysfunction might promote the development of PCOS.	Metformin	116-125	luteinizing hormone/choriogonadotropin receptor	Rattus norvegicus	159-164
34384472-0	2021	Correction to: Decreased SFRP5 correlated with excessive metabolic inflammation in polycystic ovary syndrome could be reversed by metformin: implication of its role in dysregulated metabolism.	Metformin	130-139	secreted frizzled related protein 5	Homo sapiens	25-30
34407851-1	2021	BACKGROUND: Multiple oral insulin-sensitizing agents, such as metformin, thiazolidinediones, inositols, and berberine, have been proven safe and efficacious in improving the endocrine, metabolic, and reproductive abnormalities seen in polycystic ovary syndrome (PCOS), providing more options for healthcare providers and patients.	Metformin	62-71	insulin	Homo sapiens	26-33
34407851-11	2021	Thiazolidinediones, metformin + thiazolidinediones, and myo-inositol + D-chiro-inositol were associated with a lower insulin resistance index (HOMA-IR) compared with that in metformin alone (mean differences: - 0.72 (95% CI (- 1.11)-(- 0.34)) to - 0.89 (95% CI (- 1.460)-(- 0.32))).	Metformin	20-29	insulin	Homo sapiens	117-124
34407851-11	2021	Thiazolidinediones, metformin + thiazolidinediones, and myo-inositol + D-chiro-inositol were associated with a lower insulin resistance index (HOMA-IR) compared with that in metformin alone (mean differences: - 0.72 (95% CI (- 1.11)-(- 0.34)) to - 0.89 (95% CI (- 1.460)-(- 0.32))).	Metformin	174-183	insulin	Homo sapiens	117-124
34407851-13	2021	CONCLUSIONS: Ours is the first study to report that for women with PCOS, myo-inositol combined with D-chiro-inositol and metformin combined with thiazolidinediones appear superior to metformin alone in improving insulin resistance and decreasing total testosterone.	Metformin	121-130	insulin	Homo sapiens	212-219
34407851-13	2021	CONCLUSIONS: Ours is the first study to report that for women with PCOS, myo-inositol combined with D-chiro-inositol and metformin combined with thiazolidinediones appear superior to metformin alone in improving insulin resistance and decreasing total testosterone.	Metformin	183-192	insulin	Homo sapiens	212-219
34434111-0	2021	Metformin Attenuates Silica-Induced Pulmonary Fibrosis by Activating Autophagy via the AMPK-mTOR Signaling Pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	92-96
34381133-7	2021	Metformin-induced AMPK significantly ameliorated renal autophagic function, inhibited the partial EMT of RTECs, and attenuated TIF, all of which effectively prevented or delayed the onset of DN.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	18-22
34434111-5	2021	Metformin significantly reduced silica particle-induced inflammatory cytokines including transforming growth factor-beta1 (TGF-beta1), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in rat lung tissue and HBEC culture supernatant.	Metformin	0-9	transforming growth factor, beta 1	Rattus norvegicus	89-121
34434111-5	2021	Metformin significantly reduced silica particle-induced inflammatory cytokines including transforming growth factor-beta1 (TGF-beta1), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in rat lung tissue and HBEC culture supernatant.	Metformin	0-9	transforming growth factor, beta 1	Rattus norvegicus	123-132
34434111-5	2021	Metformin significantly reduced silica particle-induced inflammatory cytokines including transforming growth factor-beta1 (TGF-beta1), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in rat lung tissue and HBEC culture supernatant.	Metformin	0-9	tumor necrosis factor	Rattus norvegicus	135-162
34434111-5	2021	Metformin significantly reduced silica particle-induced inflammatory cytokines including transforming growth factor-beta1 (TGF-beta1), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in rat lung tissue and HBEC culture supernatant.	Metformin	0-9	tumor necrosis factor	Rattus norvegicus	164-173
34434111-5	2021	Metformin significantly reduced silica particle-induced inflammatory cytokines including transforming growth factor-beta1 (TGF-beta1), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in rat lung tissue and HBEC culture supernatant.	Metformin	0-9	interleukin 1 beta	Rattus norvegicus	179-196
34434111-5	2021	Metformin significantly reduced silica particle-induced inflammatory cytokines including transforming growth factor-beta1 (TGF-beta1), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in rat lung tissue and HBEC culture supernatant.	Metformin	0-9	interleukin 1 alpha	Rattus norvegicus	198-206
34434111-7	2021	Besides, metformin increased the expression levels of phosphorylated adenosine 5"-monophosphate (AMP)-activated protein kinase (p-AMPK), microtubule-associated protein (MAP) light chain 3B (LC3B) and Beclin1 proteins, and reduced levels of phosphorylated mammalian target of rapamycin (p-mTOR) and p62 proteins in vivo and in vitro.	Metformin	9-18	mechanistic target of rapamycin kinase	Homo sapiens	255-284
34434111-7	2021	Besides, metformin increased the expression levels of phosphorylated adenosine 5"-monophosphate (AMP)-activated protein kinase (p-AMPK), microtubule-associated protein (MAP) light chain 3B (LC3B) and Beclin1 proteins, and reduced levels of phosphorylated mammalian target of rapamycin (p-mTOR) and p62 proteins in vivo and in vitro.	Metformin	9-18	mechanistic target of rapamycin kinase	Homo sapiens	288-292
34439169-7	2021	Isotope tracing studies in SHMT1 knock-out cells confirmed that metformin decreased the SHMT2-channeled serine-to-formate flux and restricted the formate utilization in thymidylate synthesis upon overexpression of the metformin-unresponsive yeast equivalent of mitochondrial complex I (mCI).	Metformin	64-73	glycine hydroxymethyltransferase SHM1	Saccharomyces cerevisiae S288C	27-32
34422646-1	2021	Objectives: Anti-diabetic biguanide drugs such as metformin may have anti-tumorigenic effects by behaving as AMPK activators and mTOR inhibitors.	Metformin	50-59	mechanistic target of rapamycin kinase	Homo sapiens	129-133
34422646-2	2021	Metformin requires organic cation transporters (OCTs) for entry into cells, and NT-1044 is an AMPK activator designed to have greater affinity for two of these transporters, OCT1 and OCT3.	Metformin	0-9	solute carrier family 22 member 1	Homo sapiens	174-178
34422646-14	2021	As compared to placebo, NT-1044 and metformin inhibited endometrial tumor growth in obese and lean LKB1fl/flp53fl/fl mice.	Metformin	36-45	serine/threonine kinase 11	Mus musculus	99-103
34421608-0	2021	Metformin Potentiates the Effects of Anlotinib in NSCLC via AMPK/mTOR and ROS-Mediated Signaling Pathways.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	65-69
34421608-4	2021	Interesting, metformin also exerts broad anticancer effects through the activation of AMP-activated protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR).	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	140-169
34421608-4	2021	Interesting, metformin also exerts broad anticancer effects through the activation of AMP-activated protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR).	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	171-175
34434111-8	2021	These results suggest that metformin could inhibit silica-induced pulmonary fibrosis by activating autophagy through the AMPK-mTOR pathway.	Metformin	27-36	mechanistic target of rapamycin kinase	Homo sapiens	126-130
34421611-0	2021	Metformin Attenuates Bone Cancer Pain by Reducing TRPV1 and ASIC3 Expression.	Metformin	0-9	acid sensing ion channel subunit 3	Rattus norvegicus	60-65
34421611-7	2021	What"s more, intraperitoneally injection of Metformin or Vinorelbine markedly elevated the PWT of BCP rats, but reduced the expression of TRPV1 and ASIC3 in L4-6 DRGs and decreased the TRPV1 expression in SDH (*p < 0.05, **p < 0.01 vs. BCP + NS).	Metformin	44-53	acid sensing ion channel subunit 3	Rattus norvegicus	148-153
34421611-8	2021	Collectively, these results suggest an effective analgesic effect of Metformin on mechanical allodynia of BCP rats, which may be mediated by the downregulation of ASIC3 and TRPV1.	Metformin	69-78	acid sensing ion channel subunit 3	Rattus norvegicus	163-168
34185201-5	2021	The other major area of exploration in the present review is based on the new targets for the modulation of fetuin-A, like calorie restriction and novel pharmacological agents, such as rosuvastatin, metformin, and pioglitazone which are successfully implicated in the management of various liver-related complications.	Metformin	199-208	alpha 2-HS glycoprotein	Homo sapiens	108-116
34421608-7	2021	Moreover, anlotinib combined with metformin induced apoptosis and oxidative stress, which was associated with the activation of AMPK and inhibition of mTOR.	Metformin	34-43	mechanistic target of rapamycin kinase	Homo sapiens	151-155
34257723-0	2021	Metformin suppresses breast cancer growth via inhibition of cyclooxygenase-2.	Metformin	0-9	prostaglandin-endoperoxide synthase 2	Homo sapiens	60-76
34257723-6	2021	Additionally, metformin inhibited cyclooxygenase (COX)-2 expression.	Metformin	14-23	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	34-56
34257723-8	2021	Thus, the current data suggested that metformin may have potential value as a synergistic therapy targeting both the COX-2 and mTOR signaling pathways.	Metformin	38-47	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	117-122
34257723-8	2021	Thus, the current data suggested that metformin may have potential value as a synergistic therapy targeting both the COX-2 and mTOR signaling pathways.	Metformin	38-47	mechanistic target of rapamycin kinase	Homo sapiens	127-131
34302119-0	2021	Correction: Repurposing dextromethorphan and metformin for treating nicotine-induced cancer by directly targeting CHRNA7 to inhibit JAK2/STAT3/SOX2 signaling.	Metformin	45-54	signal transducer and activator of transcription 3	Homo sapiens	137-142
34326272-3	2021	U0126 was applied to inhibit ERK, and metformin or 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) was applied to cause AMP-activated protein kinase (AMPK) activation.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	126-154
34326272-3	2021	U0126 was applied to inhibit ERK, and metformin or 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) was applied to cause AMP-activated protein kinase (AMPK) activation.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	156-160
34326272-11	2021	For the mechanisms, activating AMPK with metformin (obese CCD rats) or AICAR (DRG neurons in a high-fat environment) not only inhibited the ERK-NOX4 pathway, but also improved oxidative stress and inflammation caused by high-fat.	Metformin	41-50	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	31-35
34326272-11	2021	For the mechanisms, activating AMPK with metformin (obese CCD rats) or AICAR (DRG neurons in a high-fat environment) not only inhibited the ERK-NOX4 pathway, but also improved oxidative stress and inflammation caused by high-fat.	Metformin	41-50	Eph receptor B1	Rattus norvegicus	140-143
34368369-1	2021	Objective: To investigate if PP2A plays a role in metformin-induced insulin sensitivity improvement in human skeletal muscle cells.	Metformin	50-59	insulin	Homo sapiens	68-75
34164906-6	2021	In metformin-treated cells, MALAT1 knock-down increased the Bax/Bcl2 ratio and enhanced p21 but decreased cyclin B1 expression.	Metformin	3-12	BCL2 associated X, apoptosis regulator	Homo sapiens	60-63
34164906-7	2021	The expression of Beclin1, VDAC1, LC3-II, CHOP and Bip was promoted in the cells received combinatorial treatment of metformin and MALAT1 knock-down.	Metformin	117-126	DNA damage inducible transcript 3	Homo sapiens	42-46
34164906-7	2021	The expression of Beclin1, VDAC1, LC3-II, CHOP and Bip was promoted in the cells received combinatorial treatment of metformin and MALAT1 knock-down.	Metformin	117-126	growth differentiation factor 10	Homo sapiens	51-54
34485814-0	2021	Cancer Antigen 15-3/Mucin 1 Levels in CCTG MA.32: A Breast Cancer Randomized Trial of Metformin vs Placebo.	Metformin	86-95	chaperonin containing TCP1 subunit 3	Homo sapiens	38-42
34304438-0	2021	(Effect of metformin and rosiglitazone in non-obese polycystic ovary syndrome women with insulin resistance).	Metformin	11-20	insulin	Homo sapiens	89-96
34304438-1	2021	Objective: To investigate effects of metformin and rosiglitazone in non-obese polycystic ovary syndrome (PCOS) women with insulin resistance.	Metformin	37-46	insulin	Homo sapiens	122-129
34304438-8	2021	After treatment for 6 months, fasting insulin level (metformin group (13.5+-5.1) mU/L, rosiglitazone group (12.7+-5.6) mU/L) and homeostasis model assessment-insulin resistance index (metformin group 3.0+-1.2, rosiglitazone group 2.8+-1.2) were decreased in both groups (all P<0.01).	Metformin	53-62	insulin	Homo sapiens	38-45
34304438-10	2021	For PCOS with insulin resistance, lifestyle plus insulin sensitizers such as metformin could improve their clinical symptoms, correct the biochemical and metabolic dysfunction.	Metformin	77-86	insulin	Homo sapiens	14-21
34304438-10	2021	For PCOS with insulin resistance, lifestyle plus insulin sensitizers such as metformin could improve their clinical symptoms, correct the biochemical and metabolic dysfunction.	Metformin	77-86	insulin	Homo sapiens	49-56
34335036-0	2021	Metformin-Insulin versus Metformin-Sulfonylurea Combination Therapies in Type 2 Diabetes: A Comparative Study of Glycemic Control and Risk of Cardiovascular Diseases in Addis Ababa, Ethiopia.	Metformin	0-9	insulin	Homo sapiens	10-17
34368369-9	2021	Conclusions: These results provided the first evidence that metformin can activate PP2A in human skeletal muscle cells derived from lean healthy insulin-sensitive participants and may help to understand metformin"s action in skeletal muscle in humans.	Metformin	60-69	insulin	Homo sapiens	145-152
34335036-1	2021	Objective: This study aimed to compare glycemic control and risk of cardiovascular outcomes of metformin-insulin versus metformin-sulfonylurea combination therapies in type 2 diabetes mellitus.	Metformin	95-104	insulin	Homo sapiens	105-112
34368251-2	2021	As metformin is an AMPK activator, we used a mouse vascular smooth muscle cell (VSMC) line and a Myh11-cre-EGFP mice to investigate whether metformin could inhibit the migration of VSMCs in vitro and in a wire-injury model in vivo.	Metformin	3-12	myosin, heavy polypeptide 11, smooth muscle	Mus musculus	97-102
34335036-6	2021	Results: Of the total participants enrolled, 50.5% (n = 162) were those who received metformin-insulin and 49.5% (n = 159) metformin-sulfonylurea combination therapies for a median of 48 months follow-up.	Metformin	85-94	insulin	Homo sapiens	95-102
34335036-7	2021	The reduction of Hb1Ac levels was comparable between the metformin-insulin (-1.04 +- 0.96%) and metformin-sulfonylurea (-1.02 +- 1.03%), p = 0.912.	Metformin	57-66	insulin	Homo sapiens	67-74
34335036-8	2021	Patients who received metformin-sulfonylurea had 4.3 times more likely to have achieved target HbA1c level compared to those who received metformin-insulin, p < 0.001, adjusted odds ratio (AOR) with 95% CI = 4.31(1.79-10.32).	Metformin	138-147	insulin	Homo sapiens	148-155
34335036-9	2021	Risk of composite cardiovascular outcomes was higher in metformin-insulin group (40.5% versus 34.0%), p = 0.021.	Metformin	56-65	insulin	Homo sapiens	66-73
34335036-12	2021	Conclusion: High proportion of patients who received metformin-sulfonylurea achieved target HbA1c level and had less composite cardiovascular outcomes compared to those who received metformin-insulin.	Metformin	182-191	insulin	Homo sapiens	192-199
34368251-11	2021	The data of ApoE-/- mice showed that increased plasma lipids and aggravated vascular smooth muscle cell infiltration into the atherosclerotic lesion in diabetic mice were observed Metformin alleviated diabetes-induced metabolic disorders and atherosclerosis and also reduced VSMC infiltration in atherosclerotic plaques, while the Pdlim5 phospho-abolished mutant that carried adenovirus S177A-Pdlim5 undermines the protective function of metformin.	Metformin	180-189	apolipoprotein E	Mus musculus	12-16
34368251-11	2021	The data of ApoE-/- mice showed that increased plasma lipids and aggravated vascular smooth muscle cell infiltration into the atherosclerotic lesion in diabetic mice were observed Metformin alleviated diabetes-induced metabolic disorders and atherosclerosis and also reduced VSMC infiltration in atherosclerotic plaques, while the Pdlim5 phospho-abolished mutant that carried adenovirus S177A-Pdlim5 undermines the protective function of metformin.	Metformin	438-447	apolipoprotein E	Mus musculus	12-16
34264978-0	2021	Metformin intervention ameliorates AS in ApoE-/- mice through restoring gut dysbiosis and anti-inflammation.	Metformin	0-9	apolipoprotein E	Mus musculus	41-45
34293835-6	2021	Insulin resistance, followed by thiazolidinediones, is central to the pathophysiology of PCOS, with metformin having nearly similar efficacy.	Metformin	100-109	insulin	Homo sapiens	0-7
34137729-3	2021	Metformin is used to decrease insulin resistance, and at present it is assumed to influence the effect of triiodothyronine, as well.	Metformin	0-9	insulin	Homo sapiens	30-37
34284806-0	2021	Decreased SFRP5 correlated with excessive metabolic inflammation in polycystic ovary syndrome could be reversed by metformin: implication of its role in dysregulated metabolism.	Metformin	115-124	secreted frizzled related protein 5	Homo sapiens	10-15
34284806-3	2021	We aimed to confirm the correlation between SFRP5, metabolic inflammation and PCOS, investigate the predictive value of SFRP5 for PCOS and the involvement of SFRP5 in metformin treated PCOS.	Metformin	167-176	secreted frizzled related protein 5	Homo sapiens	158-163
34284806-12	2021	Metformin promoted SFRP5 and decreased leptin, IL-6 and TNFalpha secretion in PCOS women with metabolic abnormality in a time dependent manner and with improved ovulation rate and pregnancy rate.	Metformin	0-9	secreted frizzled related protein 5	Homo sapiens	19-24
34284806-12	2021	Metformin promoted SFRP5 and decreased leptin, IL-6 and TNFalpha secretion in PCOS women with metabolic abnormality in a time dependent manner and with improved ovulation rate and pregnancy rate.	Metformin	0-9	interleukin 6	Homo sapiens	47-51
34284806-12	2021	Metformin promoted SFRP5 and decreased leptin, IL-6 and TNFalpha secretion in PCOS women with metabolic abnormality in a time dependent manner and with improved ovulation rate and pregnancy rate.	Metformin	0-9	tumor necrosis factor	Homo sapiens	56-64
34284806-14	2021	The reverse of serum SFRP5 by metformin indicated that SFRP5 participated in the improvment of follicular development by metformin.	Metformin	30-39	secreted frizzled related protein 5	Homo sapiens	21-26
34284806-14	2021	The reverse of serum SFRP5 by metformin indicated that SFRP5 participated in the improvment of follicular development by metformin.	Metformin	30-39	secreted frizzled related protein 5	Homo sapiens	55-60
34284806-14	2021	The reverse of serum SFRP5 by metformin indicated that SFRP5 participated in the improvment of follicular development by metformin.	Metformin	121-130	secreted frizzled related protein 5	Homo sapiens	55-60
34269008-4	2021	Results indicated that EGCG and metformin exhibited a synergistic effect on cell viability, migration, and proliferation, as well as signal transducer and activator of transcription 3/nuclear factor-kappaB (STAT3/NF-kappaB) pathway signaling and the production of inflammation cytokines.	Metformin	32-41	signal transducer and activator of transcription 3	Mus musculus	207-212
34269008-4	2021	Results indicated that EGCG and metformin exhibited a synergistic effect on cell viability, migration, and proliferation, as well as signal transducer and activator of transcription 3/nuclear factor-kappaB (STAT3/NF-kappaB) pathway signaling and the production of inflammation cytokines.	Metformin	32-41	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	213-222
34285531-1	2021	Purpose: The study aimed to compare the metabolic effects of an intensive dose of metformin alone among non-adherence patients with type 2 diabetes versus in combination with insulin among adherence patients.	Metformin	82-91	insulin	Homo sapiens	175-182
34326945-2	2021	Indeed, metformin is the most widely used oral insulin-sensitizing agent, being prescribed to more than 100 million people worldwide, including patients with prediabetes, insulin resistance, and polycystic ovary syndrome.	Metformin	8-17	insulin	Homo sapiens	47-54
34326945-2	2021	Indeed, metformin is the most widely used oral insulin-sensitizing agent, being prescribed to more than 100 million people worldwide, including patients with prediabetes, insulin resistance, and polycystic ovary syndrome.	Metformin	8-17	insulin	Homo sapiens	171-178
34335983-0	2021	CCDC65 as a new potential tumor suppressor induced by metformin inhibits activation of AKT1 via ubiquitination of ENO1 in gastric cancer.	Metformin	54-63	AKT serine/threonine kinase 1	Homo sapiens	87-91
34335983-10	2021	Finally, we observed that metformin, a new anti-cancer drug, can significantly induce CCDC65 to suppress ENO1-AKT1 complex-mediated cell proliferation and EMT signals and finally suppresses the malignant phenotypes of gastric cancer cells.	Metformin	26-35	AKT serine/threonine kinase 1	Homo sapiens	110-114
34335983-11	2021	Conclusion: These results firstly highlight a critical role of CCDC65 in suppressing ENO1-AKT1 pathway to reduce the progression of gastric cancer and reveals a new molecular mechanism for metformin in suppressing gastric cancer.	Metformin	189-198	AKT serine/threonine kinase 1	Homo sapiens	90-94
34335798-8	2021	Compared with the model group, the content of FBG decreased and the insulin level increased in the MSHC medium-dose (0.15 g/kg) and high-dose (0.45 g/kg) groups and metformin group after 4 weeks of drug administration (P < 0.05).	Metformin	165-174	insulin	Homo sapiens	68-75
34115964-0	2021	Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation.	Metformin	0-9	NLR family pyrin domain containing 3	Homo sapiens	70-75
34115964-3	2021	We show that metformin inhibited NLRP3 inflammasome activation and interleukin (IL)-1beta production in cultured and alveolar macrophages along with inflammasome-independent IL-6 secretion, thus attenuating lipopolysaccharide (LPS)- and SARS-CoV-2-induced ARDS.	Metformin	13-22	NLR family pyrin domain containing 3	Homo sapiens	33-38
34115964-3	2021	We show that metformin inhibited NLRP3 inflammasome activation and interleukin (IL)-1beta production in cultured and alveolar macrophages along with inflammasome-independent IL-6 secretion, thus attenuating lipopolysaccharide (LPS)- and SARS-CoV-2-induced ARDS.	Metformin	13-22	interleukin 6	Homo sapiens	174-178
34115964-4	2021	By targeting electron transport chain complex 1 and independently of AMP-activated protein kinase (AMPK) or NF-kappaB, metformin blocked LPS-induced and ATP-dependent mitochondrial (mt) DNA synthesis and generation of oxidized mtDNA, an NLRP3 ligand.	Metformin	119-128	NLR family pyrin domain containing 3	Homo sapiens	237-242
34307505-12	2021	Furthermore, we found that LOXL2 and LOXL4 was inhibited by metformin and losartan in HASMCs, which indicated that LOXL2 and LOXL4 are the potential targets that involved in the therapeutic effects of metformin and losartan on aortic or aneurysm expansion.	Metformin	201-210	lysyl oxidase like 2	Homo sapiens	27-32
34307505-12	2021	Furthermore, we found that LOXL2 and LOXL4 was inhibited by metformin and losartan in HASMCs, which indicated that LOXL2 and LOXL4 are the potential targets that involved in the therapeutic effects of metformin and losartan on aortic or aneurysm expansion.	Metformin	60-69	lysyl oxidase like 2	Homo sapiens	27-32
34307505-12	2021	Furthermore, we found that LOXL2 and LOXL4 was inhibited by metformin and losartan in HASMCs, which indicated that LOXL2 and LOXL4 are the potential targets that involved in the therapeutic effects of metformin and losartan on aortic or aneurysm expansion.	Metformin	60-69	lysyl oxidase like 2	Homo sapiens	115-120
34234193-3	2021	Metformin increased AMPK, p-AMPK (Thr172), FOXO3a, p-FOXO3a (Ser413), and MnSOD levels in HDF, but not in AsPC-1 cells.	Metformin	0-9	forkhead box O3	Homo sapiens	43-49
34234193-3	2021	Metformin increased AMPK, p-AMPK (Thr172), FOXO3a, p-FOXO3a (Ser413), and MnSOD levels in HDF, but not in AsPC-1 cells.	Metformin	0-9	forkhead box O3	Homo sapiens	53-59
34234193-4	2021	p-AMPK and p-FOXO3a also translocated from the cytosol to the nucleus by metformin in HDF, but not in AsPC-1 cells.	Metformin	73-82	forkhead box O3	Homo sapiens	13-19
34234193-10	2021	Our results suggest that metformin in cancer cells differentially regulates cellular ROS levels via AMPK-FOXO3a-MnSOD pathway and combination of metformin/apigenin exerts anticancer activity through DNA damage-induced apoptosis, autophagy and necroptosis by cancer cell-specific ROS amplification.	Metformin	25-34	superoxide dismutase 2, mitochondrial	Mus musculus	112-117
34231706-1	2021	OBJECTIVES: This study aimed to explore the efficacy of combination treatment with dendrobium mixture and metformin (Met) in diabetic cardiomyopathy (DCM) and its effects on NEAT1 and the Nrf2 signaling pathway.	Metformin	106-115	NFE2 like bZIP transcription factor 2	Rattus norvegicus	188-192
34307505-12	2021	Furthermore, we found that LOXL2 and LOXL4 was inhibited by metformin and losartan in HASMCs, which indicated that LOXL2 and LOXL4 are the potential targets that involved in the therapeutic effects of metformin and losartan on aortic or aneurysm expansion.	Metformin	201-210	lysyl oxidase like 2	Homo sapiens	115-120
34230143-0	2021	Inhibition of AKT Enhances the Sensitivity of NSCLC Cells to Metformin.	Metformin	61-70	AKT serine/threonine kinase 1	Homo sapiens	14-17
34230143-4	2021	RESULTS: Notably, metformin increased the phosphorylation of AKT at serine 473 using protein array screening.	Metformin	18-27	AKT serine/threonine kinase 1	Homo sapiens	61-64
34230143-5	2021	Metformin-induced AKT activation was markedly suppressed by siRNA targeting activating transcription factor 4 (ATF4) but not AMP-activated protein kinase alpha.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	18-21
34230143-6	2021	These results indicate that AKT activation by metformin was induced in an ATF4-dependent and AMPKalpha-independent manner.	Metformin	46-55	AKT serine/threonine kinase 1	Homo sapiens	28-31
34230143-7	2021	Treatment using metformin combined with MK-2206, an AKT inhibitor, or a siRNA for AKT markedly reduced the viability of cells compared with those cells treated with these agents alone.	Metformin	16-25	AKT serine/threonine kinase 1	Homo sapiens	52-55
34230143-7	2021	Treatment using metformin combined with MK-2206, an AKT inhibitor, or a siRNA for AKT markedly reduced the viability of cells compared with those cells treated with these agents alone.	Metformin	16-25	AKT serine/threonine kinase 1	Homo sapiens	82-85
34230143-9	2021	CONCLUSION: Inhibition of AKT can enhance the antitumor effect of metformin and would be a promising strategy to sensitize non-small-cell lung cancer to a combination of metformin with radiation or cisplatin.	Metformin	66-75	AKT serine/threonine kinase 1	Homo sapiens	26-29
34230143-9	2021	CONCLUSION: Inhibition of AKT can enhance the antitumor effect of metformin and would be a promising strategy to sensitize non-small-cell lung cancer to a combination of metformin with radiation or cisplatin.	Metformin	170-179	AKT serine/threonine kinase 1	Homo sapiens	26-29
34094535-2	2021	Metformin is an insulin-sensitizing agent, with multiple potential pharmacodynamic profiles.	Metformin	0-9	insulin	Homo sapiens	16-23
34243629-2	2021	Metformin improves insulin resistance (IR) by modulating metabolic mechanisms and mitochondrial biogenesis.	Metformin	0-9	insulin	Homo sapiens	19-26
34564972-3	2021	We evaluated the antitumoral effect of iRNA-PFK-1 and the combined therapy iRNA-PFK-1 + metformin in RKO p53-positive cells.	Metformin	88-97	tumor protein p53	Homo sapiens	105-108
34152528-2	2021	Metformin has in-vitro anti-cancer activity, through AMPK activation and mTOR inhibition.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	73-77
34218545-6	2021	In this regard, we clarify that it is valuable to consider the therapeutic effect of mTOR inhibitor drugs and metformin by its mTOR inhibition property in the treatment of COVID-19 patients.	Metformin	110-119	mechanistic target of rapamycin kinase	Homo sapiens	127-131
34197485-0	2021	The genetic association of the transcription factor NPAT with glycemic response to metformin involves regulation of fuel selection.	Metformin	83-92	nuclear protein in the AT region	Mus musculus	52-56
34239695-0	2021	Data-Driven Cluster Analysis of Oxidative Stress Indexes in relation to Vitamin D Level, Age, and Metabolic Control in Patients with Type 2 Diabetes on Metformin Therapy.	Metformin	152-161	renin binding protein	Homo sapiens	89-92
34197485-8	2021	In contrast, metformin regulation of respiratory exchange ratio (RER) was completely lost in animals lacking one allele of npat.	Metformin	13-22	nuclear protein in the AT region	Mus musculus	123-127
34197485-10	2021	In summary, we provide methodological advancements for the detection of NPAT, demonstrate that minor reductions in NPAT mRNA levels (20-40%) influence metformin regulation of RER, and propose that the association between NPAT SNPs and metformin response observed in GWAS, could be due to loss of metformin modification of cellular fuel usage.	Metformin	151-160	nuclear protein in the AT region	Mus musculus	115-119
34197485-10	2021	In summary, we provide methodological advancements for the detection of NPAT, demonstrate that minor reductions in NPAT mRNA levels (20-40%) influence metformin regulation of RER, and propose that the association between NPAT SNPs and metformin response observed in GWAS, could be due to loss of metformin modification of cellular fuel usage.	Metformin	235-244	nuclear protein in the AT region	Mus musculus	221-225
34197485-10	2021	In summary, we provide methodological advancements for the detection of NPAT, demonstrate that minor reductions in NPAT mRNA levels (20-40%) influence metformin regulation of RER, and propose that the association between NPAT SNPs and metformin response observed in GWAS, could be due to loss of metformin modification of cellular fuel usage.	Metformin	296-305	nuclear protein in the AT region	Mus musculus	115-119
34262962-0	2021	Metformin Inhibits Lipoteichoic Acid-Induced Oxidative Stress and Inflammation Through AMPK/NRF2/NF-kappaB Signaling Pathway in Bovine Mammary Epithelial Cells.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Bos taurus	92-96
34262962-10	2021	Importantly, metformin-induced activation of Nrf2 is AMP-activated protein kinase (AMPK)-dependent; as metformin-pretreated PBMECs activated AMPK signaling via the upregulation of phosphorylated AMPK levels, cell pretreatment with metformin also reversed the translocation of Nrf2 that was LTA inhibited.	Metformin	13-22	NFE2 like bZIP transcription factor 2	Bos taurus	45-49
34262962-10	2021	Importantly, metformin-induced activation of Nrf2 is AMP-activated protein kinase (AMPK)-dependent; as metformin-pretreated PBMECs activated AMPK signaling via the upregulation of phosphorylated AMPK levels, cell pretreatment with metformin also reversed the translocation of Nrf2 that was LTA inhibited.	Metformin	13-22	NFE2 like bZIP transcription factor 2	Bos taurus	276-280
34262962-10	2021	Importantly, metformin-induced activation of Nrf2 is AMP-activated protein kinase (AMPK)-dependent; as metformin-pretreated PBMECs activated AMPK signaling via the upregulation of phosphorylated AMPK levels, cell pretreatment with metformin also reversed the translocation of Nrf2 that was LTA inhibited.	Metformin	103-112	NFE2 like bZIP transcription factor 2	Bos taurus	45-49
34262962-10	2021	Importantly, metformin-induced activation of Nrf2 is AMP-activated protein kinase (AMPK)-dependent; as metformin-pretreated PBMECs activated AMPK signaling via the upregulation of phosphorylated AMPK levels, cell pretreatment with metformin also reversed the translocation of Nrf2 that was LTA inhibited.	Metformin	231-240	NFE2 like bZIP transcription factor 2	Bos taurus	45-49
34262962-10	2021	Importantly, metformin-induced activation of Nrf2 is AMP-activated protein kinase (AMPK)-dependent; as metformin-pretreated PBMECs activated AMPK signaling via the upregulation of phosphorylated AMPK levels, cell pretreatment with metformin also reversed the translocation of Nrf2 that was LTA inhibited.	Metformin	231-240	NFE2 like bZIP transcription factor 2	Bos taurus	276-280
34262962-11	2021	This convergence between AMPK and Nrf2 pathways is essential for the anti-inflammatory effect of metformin in LTA-stimulated PBMECs.	Metformin	97-106	NFE2 like bZIP transcription factor 2	Bos taurus	34-38
34262962-12	2021	Altogether, our results indicate that metformin exerts anti-inflammation and oxidative stress through regulation of AMPK/Nrf2/NF-kappaB signaling pathway, which highlights the role of AMPK as a potential therapeutic strategy for treatment of bovine mastitis.	Metformin	38-47	NFE2 like bZIP transcription factor 2	Bos taurus	121-125
34158423-5	2022	Emerging evidence showed that metformin possesses chemopreventive effects via both direct (e.g., adenosine monophosphate-activated protein kinase activation and subsequent inhibition of the mammalian target of rapamycin pathway) and indirect (e.g., modulation of the interaction between tumor cells and their microenvironment and gut microbiota) pathways.	Metformin	30-39	mechanistic target of rapamycin kinase	Homo sapiens	190-219
34157054-3	2021	Maintaining proper blood glucose levels using insulin and/or other oral antidiabetic drugs (such as Metformin) reduced the detrimental effects of COVID-19.	Metformin	100-109	insulin	Homo sapiens	46-53
34161263-10	2021	Finally, we found that dual MCT1/4 inhibition also sensitized LCLs to killing by the electron transport chain complex I inhibitors phenformin and metformin.	Metformin	146-155	solute carrier family 16 member 14	Homo sapiens	28-34
34154617-0	2021	Correction to: Metformin ameliorates scleroderma via inhibiting Th17 cells and reducing mTOR-STAT3 signaling in skin fibroblasts.	Metformin	15-24	mechanistic target of rapamycin kinase	Homo sapiens	88-92
34154617-0	2021	Correction to: Metformin ameliorates scleroderma via inhibiting Th17 cells and reducing mTOR-STAT3 signaling in skin fibroblasts.	Metformin	15-24	signal transducer and activator of transcription 3	Homo sapiens	93-98
34286169-0	2021	A Pilot Trial: Fish Oil and Metformin Effects on ApoB-Remnants and Triglycerides in Women With Polycystic Ovary Syndrome.	Metformin	28-37	apolipoprotein B	Homo sapiens	49-53
34286169-7	2021	Fasting plasma apoB48 was lowered 40% in FO-metformin and 15% in the FO groups from baseline to postintervention.	Metformin	44-53	apolipoprotein B	Homo sapiens	15-21
34286169-9	2021	Conclusion: The findings of this pilot trial show that high dose FO and FO-metformin combination therapy tend to lower fasting and postprandial plasma TG and ApoB-lipoprotein remnants compared with metformin; however, the study is limited by small sample size.	Metformin	75-84	apolipoprotein B	Homo sapiens	158-162
34139918-4	2022	Areas of ongoing investigation focus on metformin"s ability to activate adenosine monophosphate kinase (AMPK), in addition to its effect on Myc mRNA, monocarboxylate transporter 1 (MCT1), hypoxia-inducible factor 1 (HIF1), mammalian target of rapamycin (mTOR), and human epidermal growth factor receptor 2 (HER2).	Metformin	40-49	solute carrier family 16 member 1	Homo sapiens	150-179
34139918-4	2022	Areas of ongoing investigation focus on metformin"s ability to activate adenosine monophosphate kinase (AMPK), in addition to its effect on Myc mRNA, monocarboxylate transporter 1 (MCT1), hypoxia-inducible factor 1 (HIF1), mammalian target of rapamycin (mTOR), and human epidermal growth factor receptor 2 (HER2).	Metformin	40-49	solute carrier family 16 member 1	Homo sapiens	181-185
34139918-4	2022	Areas of ongoing investigation focus on metformin"s ability to activate adenosine monophosphate kinase (AMPK), in addition to its effect on Myc mRNA, monocarboxylate transporter 1 (MCT1), hypoxia-inducible factor 1 (HIF1), mammalian target of rapamycin (mTOR), and human epidermal growth factor receptor 2 (HER2).	Metformin	40-49	hypoxia inducible factor 1 subunit alpha	Homo sapiens	188-214
34139918-4	2022	Areas of ongoing investigation focus on metformin"s ability to activate adenosine monophosphate kinase (AMPK), in addition to its effect on Myc mRNA, monocarboxylate transporter 1 (MCT1), hypoxia-inducible factor 1 (HIF1), mammalian target of rapamycin (mTOR), and human epidermal growth factor receptor 2 (HER2).	Metformin	40-49	hypoxia inducible factor 1 subunit alpha	Homo sapiens	216-220
34139918-4	2022	Areas of ongoing investigation focus on metformin"s ability to activate adenosine monophosphate kinase (AMPK), in addition to its effect on Myc mRNA, monocarboxylate transporter 1 (MCT1), hypoxia-inducible factor 1 (HIF1), mammalian target of rapamycin (mTOR), and human epidermal growth factor receptor 2 (HER2).	Metformin	40-49	mechanistic target of rapamycin kinase	Homo sapiens	223-252
34139918-4	2022	Areas of ongoing investigation focus on metformin"s ability to activate adenosine monophosphate kinase (AMPK), in addition to its effect on Myc mRNA, monocarboxylate transporter 1 (MCT1), hypoxia-inducible factor 1 (HIF1), mammalian target of rapamycin (mTOR), and human epidermal growth factor receptor 2 (HER2).	Metformin	40-49	mechanistic target of rapamycin kinase	Homo sapiens	254-258
34139918-7	2022	The acquired knowledge about metformin properties has expanded the number of targets for drug discovery such as microRNA, hexokinase, adenylate cyclase, transcription factors, various cyclins, and copper.	Metformin	29-38	hexokinase 1	Homo sapiens	122-132
34211461-3	2021	Metformin, an antidiabetic drug and an inducer of AMPK, upregulated the level of SMILE in human intestinal epithelial cells and the number of SMILE-expressing cells in colon tissues from DSS-induced colitis mice compared to control mice.	Metformin	0-9	CREB/ATF bZIP transcription factor	Homo sapiens	81-86
34211461-3	2021	Metformin, an antidiabetic drug and an inducer of AMPK, upregulated the level of SMILE in human intestinal epithelial cells and the number of SMILE-expressing cells in colon tissues from DSS-induced colitis mice compared to control mice.	Metformin	0-9	CREB/ATF bZIP transcription factor	Homo sapiens	142-147
34211461-7	2021	Metformin increased the levels of SMILE, AMPK, and Foxp3 but decreased the number of interleukin (IL)-17-producing T cells among PBMCs from patients with UC.	Metformin	0-9	CREB/ATF bZIP transcription factor	Homo sapiens	34-39
34194474-9	2021	Carriers of reduced-function alleles of organic cation transporter 1 (OCT 1, encoded by SLC22A1) or reduced expression alleles of plasma membrane monoamine transporter (PMAT, encoded by SLC29A4) or serotonin transporter (SERT, encoded by SLC6A4) were associated with increased incidence of metformin-related gastrointestinal (GI) adverse effects.	Metformin	290-299	solute carrier family 22 member 1	Homo sapiens	40-68
34194474-9	2021	Carriers of reduced-function alleles of organic cation transporter 1 (OCT 1, encoded by SLC22A1) or reduced expression alleles of plasma membrane monoamine transporter (PMAT, encoded by SLC29A4) or serotonin transporter (SERT, encoded by SLC6A4) were associated with increased incidence of metformin-related gastrointestinal (GI) adverse effects.	Metformin	290-299	solute carrier family 22 member 1	Homo sapiens	70-75
34194474-9	2021	Carriers of reduced-function alleles of organic cation transporter 1 (OCT 1, encoded by SLC22A1) or reduced expression alleles of plasma membrane monoamine transporter (PMAT, encoded by SLC29A4) or serotonin transporter (SERT, encoded by SLC6A4) were associated with increased incidence of metformin-related gastrointestinal (GI) adverse effects.	Metformin	290-299	solute carrier family 22 member 1	Homo sapiens	88-95
34194474-9	2021	Carriers of reduced-function alleles of organic cation transporter 1 (OCT 1, encoded by SLC22A1) or reduced expression alleles of plasma membrane monoamine transporter (PMAT, encoded by SLC29A4) or serotonin transporter (SERT, encoded by SLC6A4) were associated with increased incidence of metformin-related gastrointestinal (GI) adverse effects.	Metformin	290-299	solute carrier family 6 member 4	Homo sapiens	198-219
34194474-9	2021	Carriers of reduced-function alleles of organic cation transporter 1 (OCT 1, encoded by SLC22A1) or reduced expression alleles of plasma membrane monoamine transporter (PMAT, encoded by SLC29A4) or serotonin transporter (SERT, encoded by SLC6A4) were associated with increased incidence of metformin-related gastrointestinal (GI) adverse effects.	Metformin	290-299	solute carrier family 6 member 4	Homo sapiens	221-225
34194474-9	2021	Carriers of reduced-function alleles of organic cation transporter 1 (OCT 1, encoded by SLC22A1) or reduced expression alleles of plasma membrane monoamine transporter (PMAT, encoded by SLC29A4) or serotonin transporter (SERT, encoded by SLC6A4) were associated with increased incidence of metformin-related gastrointestinal (GI) adverse effects.	Metformin	290-299	solute carrier family 6 member 4	Homo sapiens	238-244
34115034-2	2021	Metformin increases insulin sensitivity, but it is associated with unsatisfied benefits of weight loss.	Metformin	0-9	insulin	Homo sapiens	20-27
34203951-0	2021	The Anti-Tumor Effect of Lactococcus lactis Bacteria-Secreting Human Soluble TRAIL Can Be Enhanced by Metformin Both In Vitro and In Vivo in a Mouse Model of Human Colorectal Cancer.	Metformin	102-111	TNF superfamily member 10	Homo sapiens	77-82
34135572-0	2021	Metformin Decreases Insulin Resistance in Type 1 Diabetes Through Regulating P53 and RAP2A in vitro and in vivo (Retraction).	Metformin	0-9	insulin	Homo sapiens	20-27
34135572-0	2021	Metformin Decreases Insulin Resistance in Type 1 Diabetes Through Regulating P53 and RAP2A in vitro and in vivo (Retraction).	Metformin	0-9	tumor protein p53	Homo sapiens	77-80
34103538-12	2021	Significant improvements were seen in all metabolic factors, with 6 month standardized ratios (metformin/placebo) of 0.85 (insulin), 0.83 (HOMA), 0.80 (leptin), and 0.84 (hsCRP), with no qualitative interactions with baseline BMI or insulin.	Metformin	95-104	insulin	Homo sapiens	123-130
34268040-9	2021	Conclusion Combined therapy with metformin and MI plus DCI in women with PCOS and insulin resistance seems promising with the need for further studies with a greater sample size to evaluate the efficacy of this treatment.	Metformin	33-42	insulin	Homo sapiens	82-89
34163481-3	2021	The mechanisms by which metformin regulates the function of macrophages include AMPK, AMPK independent targets, NF-kappaB, ABCG5/8, Sirt1, FOXO1/FABP4 and HMGB1.	Metformin	24-33	nuclear factor kappa B subunit 1	Homo sapiens	112-121
34163481-3	2021	The mechanisms by which metformin regulates the function of macrophages include AMPK, AMPK independent targets, NF-kappaB, ABCG5/8, Sirt1, FOXO1/FABP4 and HMGB1.	Metformin	24-33	ATP binding cassette subfamily G member 5	Homo sapiens	123-130
34163481-3	2021	The mechanisms by which metformin regulates the function of macrophages include AMPK, AMPK independent targets, NF-kappaB, ABCG5/8, Sirt1, FOXO1/FABP4 and HMGB1.	Metformin	24-33	forkhead box O1	Homo sapiens	139-144
34149406-2	2021	Metformin could enhance the anticancer effects of standard antineoplastic agents (traditional chemotherapy drugs, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), or immune checkpoint inhibitors (ICIs)); however, it is unclear whether metformin can be combined with antineoplastic agents in the treatment of lung cancer.	Metformin	0-9	epidermal growth factor receptor	Homo sapiens	175-179
34149406-8	2021	Compared to standard antineoplastic agents alone (traditional chemotherapy drugs, EGFR-TKIs or ICIs), the antineoplastic agents combined with metformin significantly improved OS (HR 0.73, 95% CI 0.66-0.81, p < 0.00001) and PFS (HR 0.72, 95% CI 0.59-0.88, p = 0.001); a similar association was found in observational evidence.	Metformin	142-151	epidermal growth factor receptor	Homo sapiens	82-86
34386644-3	2021	We previously reported that MEK inhibitor trametinib increases the expression of epithelial-mesenchymal transition (EMT) regulators and melanoma cell motility, which are suppressed by addition of metformin in A375 melanoma cells.	Metformin	196-205	mitogen-activated protein kinase kinase 7	Homo sapiens	28-31
34386644-9	2021	Metformin, on the contrary, suppressed the expression of sparc, integrin alphaV, fibronectin and N-cadherin with the reduced cell motility.	Metformin	0-9	fibronectin 1	Homo sapiens	81-92
33929389-10	2021	Following metformin treatment, p-AMPK and p-eNOS expression increased, while p-mTOR expression decreased.	Metformin	10-19	nitric oxide synthase 3	Homo sapiens	44-48
34322416-0	2021	Serum vitamin B12 status of patients with type 2 diabetes mellitus on metformin: A single-center cross-sectional study from Bangladesh.	Metformin	70-79	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	14-17
34322416-1	2021	Background: Metformin use is a known cause of B12 deficiency in patients with type 2 DM (T2DM).	Metformin	12-21	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	46-49
34322416-3	2021	Objective: The present study aims to assess serum vitamin B12 levels in patients with T2DM on metformin.	Metformin	94-103	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	58-61
34322416-8	2021	Serum B12 levels had a strong negative correlation with duration of metformin use and gram-years of metformin use.	Metformin	68-77	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	6-9
34322416-8	2021	Serum B12 levels had a strong negative correlation with duration of metformin use and gram-years of metformin use.	Metformin	100-109	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	6-9
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	22-31	BCL2 associated X, apoptosis regulator	Homo sapiens	96-99
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	22-31	BCL2 apoptosis regulator	Homo sapiens	100-105
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	22-31	caspase 3	Homo sapiens	110-119
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	22-31	AKT serine/threonine kinase 1	Homo sapiens	342-345
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	22-31	mitogen-activated protein kinase 8	Homo sapiens	360-363
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	22-31	mitogen-activated protein kinase 1	Homo sapiens	421-424
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	22-31	AKT serine/threonine kinase 1	Homo sapiens	429-432
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	217-226	BCL2 associated X, apoptosis regulator	Homo sapiens	96-99
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	217-226	BCL2 apoptosis regulator	Homo sapiens	100-105
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	217-226	caspase 3	Homo sapiens	110-119
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	217-226	AKT serine/threonine kinase 1	Homo sapiens	342-345
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	217-226	mitogen-activated protein kinase 8	Homo sapiens	360-363
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	217-226	mitogen-activated protein kinase 1	Homo sapiens	421-424
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	217-226	AKT serine/threonine kinase 1	Homo sapiens	429-432
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	318-327	BCL2 associated X, apoptosis regulator	Homo sapiens	96-99
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	318-327	BCL2 apoptosis regulator	Homo sapiens	100-105
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	318-327	caspase 3	Homo sapiens	110-119
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	318-327	AKT serine/threonine kinase 1	Homo sapiens	342-345
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	318-327	mitogen-activated protein kinase 8	Homo sapiens	360-363
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	318-327	mitogen-activated protein kinase 1	Homo sapiens	421-424
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	318-327	AKT serine/threonine kinase 1	Homo sapiens	429-432
34078517-4	2021	These results suggest that a low concentration of metformin inhibits osteoclast differentiation through PI3K/Akt and MAPK/ERK signaling pathway; high concentrations of metformin promote osteoclast apoptosis through PI3K/Akt and ERK signaling pathway.	Metformin	50-59	AKT serine/threonine kinase 1	Homo sapiens	109-112
34078517-4	2021	These results suggest that a low concentration of metformin inhibits osteoclast differentiation through PI3K/Akt and MAPK/ERK signaling pathway; high concentrations of metformin promote osteoclast apoptosis through PI3K/Akt and ERK signaling pathway.	Metformin	50-59	mitogen-activated protein kinase 1	Homo sapiens	122-125
34078517-4	2021	These results suggest that a low concentration of metformin inhibits osteoclast differentiation through PI3K/Akt and MAPK/ERK signaling pathway; high concentrations of metformin promote osteoclast apoptosis through PI3K/Akt and ERK signaling pathway.	Metformin	50-59	AKT serine/threonine kinase 1	Homo sapiens	220-223
34078517-4	2021	These results suggest that a low concentration of metformin inhibits osteoclast differentiation through PI3K/Akt and MAPK/ERK signaling pathway; high concentrations of metformin promote osteoclast apoptosis through PI3K/Akt and ERK signaling pathway.	Metformin	50-59	mitogen-activated protein kinase 1	Homo sapiens	228-231
34078517-4	2021	These results suggest that a low concentration of metformin inhibits osteoclast differentiation through PI3K/Akt and MAPK/ERK signaling pathway; high concentrations of metformin promote osteoclast apoptosis through PI3K/Akt and ERK signaling pathway.	Metformin	168-177	AKT serine/threonine kinase 1	Homo sapiens	220-223
34078517-4	2021	These results suggest that a low concentration of metformin inhibits osteoclast differentiation through PI3K/Akt and MAPK/ERK signaling pathway; high concentrations of metformin promote osteoclast apoptosis through PI3K/Akt and ERK signaling pathway.	Metformin	168-177	mitogen-activated protein kinase 1	Homo sapiens	228-231
33929389-10	2021	Following metformin treatment, p-AMPK and p-eNOS expression increased, while p-mTOR expression decreased.	Metformin	10-19	mechanistic target of rapamycin kinase	Homo sapiens	79-83
33929389-12	2021	In conclusion, metformin can attenuate endothelial injuries and suppress EndMT of HCMECs under hypoxic conditions, owing to its ability to activate the AMPK pathway, increase p-AMPK/t-AMPK, and inhibit mTOR.	Metformin	15-24	mechanistic target of rapamycin kinase	Homo sapiens	202-206
34124444-0	2021	Proteomic Analysis Reveals That Metformin Suppresses PSMD2, STIP1, and CAP1 for Preventing Gastric Cancer AGS Cell Proliferation and Migration.	Metformin	32-41	proteasome 26S subunit ubiquitin receptor, non-ATPase 2	Homo sapiens	53-58
34124444-6	2021	Using small-scale quantitative proteomics, we identified 177 differentially expressed proteins upon metformin treatment; among these, nine proteins such as 26S proteasome non-ATPase regulatory subunit 2 (PSMD2), stress-induced phosphoprotein 1 (STIP1), and adenylyl cyclase-associated protein 1 (CAP1) were significantly altered.	Metformin	100-109	proteasome 26S subunit ubiquitin receptor, non-ATPase 2	Homo sapiens	156-202
34124444-6	2021	Using small-scale quantitative proteomics, we identified 177 differentially expressed proteins upon metformin treatment; among these, nine proteins such as 26S proteasome non-ATPase regulatory subunit 2 (PSMD2), stress-induced phosphoprotein 1 (STIP1), and adenylyl cyclase-associated protein 1 (CAP1) were significantly altered.	Metformin	100-109	proteasome 26S subunit ubiquitin receptor, non-ATPase 2	Homo sapiens	204-209
34123772-0	2021	Combination of Metformin, Sodium Oxamate and Doxorubicin Induces Apoptosis and Autophagy in Colorectal Cancer Cells via Downregulation HIF-1alpha.	Metformin	15-24	hypoxia inducible factor 1 subunit alpha	Homo sapiens	135-145
34113269-8	2021	We further hypothesize that (iv) reversing IR through lifestyle changes or the actions of insulin sensitizing medications such as metformin, or optimizing BBB function using vascular protective drugs, such as losartan, could provide novel strategies for the prevention or treatment of neuroprogressive BD.	Metformin	130-139	insulin	Homo sapiens	90-97
34064886-2	2021	Hepatic OCT1, intestinal OCT3, renal OCT2 on tubule basolateral membrane, and MATE1/2-K on tubule apical membrane coordinately work to control metformin disposition.	Metformin	143-152	solute carrier family 22 member 1	Homo sapiens	8-12
34064886-7	2021	Individual contributions of transporters to metformin disposition are renal OCT2   renal MATEs > intestinal OCT3 > hepatic OCT1 > intestinal PMAT.	Metformin	44-53	solute carrier family 22 member 1	Homo sapiens	123-127
34277866-0	2021	Efficacy of Photobiomodulation and Metformin on Diabetic Cell Line of Human Periodontal Ligament Stem Cells through Keap1/Nrf2/Ho-1 Pathway.	Metformin	35-44	kelch like ECH associated protein 1	Homo sapiens	116-121
34217162-8	2021	Four hub genes (C3, THBS1, CXCL1, and TTN) were identified after treatment of Metformin (P<0.05, T-test).	Metformin	78-87	thrombospondin 1	Homo sapiens	20-25
34141868-0	2021	Upregulation of endogenous TRAIL-elicited apoptosis is essential for metformin-mediated antitumor activity against TNBC and NSCLC.	Metformin	69-78	TNF superfamily member 10	Homo sapiens	27-32
34141868-4	2021	Here, we discovered that metformin increased TRAIL expression and induced apoptosis in triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC) cells.	Metformin	25-34	TNF superfamily member 10	Homo sapiens	45-50
34141868-6	2021	Metformin-upregulated TRAIL was secreted into conditioned medium (CM) and found to be functional, since the CM promoted TNBC cells undergoing apoptosis, which was abrogated by a recombinant TRAIL-R2-Fc chimera.	Metformin	0-9	TNF superfamily member 10	Homo sapiens	22-27
34141868-7	2021	Moreover, blockade of TRAIL binding to DR4/DR5 or specific knockdown of TRAIL expression significantly attenuated metformin-induced apoptosis.	Metformin	114-123	TNF superfamily member 10	Homo sapiens	22-27
34141868-7	2021	Moreover, blockade of TRAIL binding to DR4/DR5 or specific knockdown of TRAIL expression significantly attenuated metformin-induced apoptosis.	Metformin	114-123	TNF superfamily member 10	Homo sapiens	72-77
34141868-8	2021	Studies with a tumor xenograft model revealed that metformin not only significantly inhibited tumor growth but also elicited apoptosis and enhanced TRAIL expression in vivo.	Metformin	51-60	TNF superfamily member 10	Homo sapiens	148-153
34141868-9	2021	Collectively, we have demonstrated that upregulation of TRAIL and activation of death receptor signaling are pivotal for metformin-induced apoptosis in TNBC and NSCLC cells.	Metformin	121-130	TNF superfamily member 10	Homo sapiens	56-61
34141868-10	2021	Our studies identify a novel mechanism of action of metformin exhibiting potent antitumor activity via induction of endogenous TRAIL.	Metformin	52-61	TNF superfamily member 10	Homo sapiens	127-132
34074108-5	2021	LADA is treated early with insulin and combined with metformin in patients with a higher level of insulin resistance.	Metformin	53-62	insulin	Homo sapiens	98-105
34222065-15	2021	Metformin reduces FBXW7 and Fetuin-A levels.	Metformin	0-9	F-box and WD repeat domain containing 7	Homo sapiens	18-23
34222065-15	2021	Metformin reduces FBXW7 and Fetuin-A levels.	Metformin	0-9	alpha 2-HS glycoprotein	Homo sapiens	28-36
34277866-0	2021	Efficacy of Photobiomodulation and Metformin on Diabetic Cell Line of Human Periodontal Ligament Stem Cells through Keap1/Nrf2/Ho-1 Pathway.	Metformin	35-44	NFE2 like bZIP transcription factor 2	Homo sapiens	122-126
34277866-12	2021	Results: Photobiomodulation at 1, 2, and 3 J/cm2 combined with metformin significantly promoted diabetic cell lines of HPDLSCs viability (in MTT assay and ELISA reader of ROS, TNF-alpha, IL-10 results) and gene expression of Nrf2, Keap1, PIK3, and HO-1 levels (p< 0.05).	Metformin	63-72	tumor necrosis factor	Homo sapiens	176-185
34277866-12	2021	Results: Photobiomodulation at 1, 2, and 3 J/cm2 combined with metformin significantly promoted diabetic cell lines of HPDLSCs viability (in MTT assay and ELISA reader of ROS, TNF-alpha, IL-10 results) and gene expression of Nrf2, Keap1, PIK3, and HO-1 levels (p< 0.05).	Metformin	63-72	NFE2 like bZIP transcription factor 2	Homo sapiens	225-229
34277866-12	2021	Results: Photobiomodulation at 1, 2, and 3 J/cm2 combined with metformin significantly promoted diabetic cell lines of HPDLSCs viability (in MTT assay and ELISA reader of ROS, TNF-alpha, IL-10 results) and gene expression of Nrf2, Keap1, PIK3, and HO-1 levels (p< 0.05).	Metformin	63-72	kelch like ECH associated protein 1	Homo sapiens	231-236
34265779-7	2021	Variants on SLC47A1, SLC28A1, and ABCG2 likely impact the pharmacokinetics (PK) of metformin, while the role of the two latter can be related to insulin resistance and regulation of adipogenesis.	Metformin	83-92	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	34-39
34308109-0	2021	Assessment of vitamin B12 deficiency and B12 screening trends for patients on metformin: a retrospective cohort case review.	Metformin	78-87	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	22-25
34308109-0	2021	Assessment of vitamin B12 deficiency and B12 screening trends for patients on metformin: a retrospective cohort case review.	Metformin	78-87	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	41-44
34308109-1	2021	Objectives: Our study investigated the use of vitamin B12 testing in a large cohort of patients on metformin and assesses appropriateness and benefits of screening recommendations for vitamin B12 deficiency.	Metformin	99-108	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	54-57
34308109-4	2021	Primary outcome was incidence of B12 deficiency diagnosed in patients on metformin.	Metformin	73-82	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	33-36
34308109-5	2021	Secondary outcome was occurrence of B12 testing in the patient population on metformin.	Metformin	77-86	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	36-39
34308109-9	2021	Results: Of 13 489 patients on metformin, 6051 (44.9%) were tested for vitamin B12 deficiency, of which 202 (3.3%) tested positive (vs 2.2% of comparisons).	Metformin	31-40	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	79-82
34308109-14	2021	Conclusions: Based on our study"s findings of vitamin B12 deficiency in patients on metformin who are greater than 65 years old and have been using it for over 5 years, we recommend that physicians consider screening in these populations.	Metformin	84-93	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	54-57
34238029-0	2021	Metformin Antagonizes Ovarian Cancer Cells Malignancy Through MSLN Mediated IL-6/STAT3 Signaling.	Metformin	0-9	interleukin 6	Homo sapiens	76-80
34238029-0	2021	Metformin Antagonizes Ovarian Cancer Cells Malignancy Through MSLN Mediated IL-6/STAT3 Signaling.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	81-86
34238029-8	2021	On mechanism, metformin treatment remarkably reduced mesothelin (MSLN) expression, downregulated IL-6/STAT3 signaling activity, subsequently resulted in VEGF and TGFbeta1 expression.	Metformin	14-23	interleukin 6	Homo sapiens	97-101
34238029-8	2021	On mechanism, metformin treatment remarkably reduced mesothelin (MSLN) expression, downregulated IL-6/STAT3 signaling activity, subsequently resulted in VEGF and TGFbeta1 expression.	Metformin	14-23	signal transducer and activator of transcription 3	Homo sapiens	102-107
34238029-8	2021	On mechanism, metformin treatment remarkably reduced mesothelin (MSLN) expression, downregulated IL-6/STAT3 signaling activity, subsequently resulted in VEGF and TGFbeta1 expression.	Metformin	14-23	vascular endothelial growth factor A	Homo sapiens	153-157
34238029-8	2021	On mechanism, metformin treatment remarkably reduced mesothelin (MSLN) expression, downregulated IL-6/STAT3 signaling activity, subsequently resulted in VEGF and TGFbeta1 expression.	Metformin	14-23	transforming growth factor beta 1	Homo sapiens	162-170
34238029-10	2021	CONCLUSIONS: Collectively, our findings suggested that metformin exerts anticancer effects by suppressing ovarian cancer cell malignancy, which attributed to MSLN inhibition mediated IL6/STAT3 signaling and VEGF and TGFbeta1 downregulation.	Metformin	55-64	interleukin 6	Homo sapiens	183-186
34238029-10	2021	CONCLUSIONS: Collectively, our findings suggested that metformin exerts anticancer effects by suppressing ovarian cancer cell malignancy, which attributed to MSLN inhibition mediated IL6/STAT3 signaling and VEGF and TGFbeta1 downregulation.	Metformin	55-64	signal transducer and activator of transcription 3	Homo sapiens	187-192
34238029-10	2021	CONCLUSIONS: Collectively, our findings suggested that metformin exerts anticancer effects by suppressing ovarian cancer cell malignancy, which attributed to MSLN inhibition mediated IL6/STAT3 signaling and VEGF and TGFbeta1 downregulation.	Metformin	55-64	vascular endothelial growth factor A	Homo sapiens	207-211
34238029-10	2021	CONCLUSIONS: Collectively, our findings suggested that metformin exerts anticancer effects by suppressing ovarian cancer cell malignancy, which attributed to MSLN inhibition mediated IL6/STAT3 signaling and VEGF and TGFbeta1 downregulation.	Metformin	55-64	transforming growth factor beta 1	Homo sapiens	216-224
34347981-6	2021	Metformin has been used traditionally as a pillar of PCOS treatment, but even effective insulin sensitization therapy can contribute to side effects that reduce patient adherence and limit treatment effectiveness.	Metformin	0-9	insulin	Homo sapiens	88-95
34514769-3	2021	Some studies have shown that metformin causes weight loss in insulin-sensitive and insulin-resistant overweight and obese patients.	Metformin	29-38	insulin	Homo sapiens	61-68
34514769-3	2021	Some studies have shown that metformin causes weight loss in insulin-sensitive and insulin-resistant overweight and obese patients.	Metformin	29-38	insulin	Homo sapiens	83-90
34875861-4	2021	As a biguanide metformin improves glycemic control by inhibiting gluconeogenesis and increasing insulin-mediated glucose utilization in peripheral tissues.	Metformin	15-24	insulin	Homo sapiens	96-103
34875861-8	2021	The risk increases with renal impairment; therefore the metformin dose must be adjusted to the eGFR.	Metformin	56-65	epidermal growth factor receptor	Homo sapiens	95-99
35588955-0	2022	Metformin-ROS-Nrf2 connection in the host defense mechanism against oxidative stress, apoptosis, cancers, and ageing.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	14-18
35588955-4	2022	Although metformin"s effect against T2DM, cancers, and ageing, are believed mostly attributed to the activation of AMP-activated protein kinase (AMPK), the cellular responses involving metformin-ROS-Nrf2 axis might be another natural asset to improve healthspan and lifespan.	Metformin	9-18	NFE2 like bZIP transcription factor 2	Homo sapiens	199-203
35588955-4	2022	Although metformin"s effect against T2DM, cancers, and ageing, are believed mostly attributed to the activation of AMP-activated protein kinase (AMPK), the cellular responses involving metformin-ROS-Nrf2 axis might be another natural asset to improve healthspan and lifespan.	Metformin	185-194	NFE2 like bZIP transcription factor 2	Homo sapiens	199-203
35550195-0	2022	Metformin-induced downregulation of c-Met is a determinant of sensitivity in MDA-MB-468 breast cancer cells.	Metformin	0-9	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	36-41
35550195-5	2022	We found that metformin-induced inhibition of MDA-MB-468 cells was correlated with downregulation of c-Met at both protein and mRNA levels.	Metformin	14-23	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	101-106
35550195-6	2022	To understand the functional significance of c-Met downregulation in metformin-mediated tumor inhibition, we established control and c-Met overexpressing sublines of MDA-MB-468 cells (468/C and 468/Met) using lentiviral expression system.	Metformin	69-78	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	45-50
35550195-7	2022	We demonstrated that overexpression of c-Met significantly attenuated metformin induced inhibition of MDA-MB-468 cells.	Metformin	70-79	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	39-44
35550195-9	2022	Signal transduction analysis of the paired cell lines indicated that c-Met-induced activation of STAT3 and AKT1, and upregulation of Gab1 are related to c-Met-modulated metformin responsiveness.	Metformin	169-178	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	69-74
35550195-9	2022	Signal transduction analysis of the paired cell lines indicated that c-Met-induced activation of STAT3 and AKT1, and upregulation of Gab1 are related to c-Met-modulated metformin responsiveness.	Metformin	169-178	signal transducer and activator of transcription 3	Homo sapiens	97-102
35550195-9	2022	Signal transduction analysis of the paired cell lines indicated that c-Met-induced activation of STAT3 and AKT1, and upregulation of Gab1 are related to c-Met-modulated metformin responsiveness.	Metformin	169-178	AKT serine/threonine kinase 1	Homo sapiens	107-111
35550195-9	2022	Signal transduction analysis of the paired cell lines indicated that c-Met-induced activation of STAT3 and AKT1, and upregulation of Gab1 are related to c-Met-modulated metformin responsiveness.	Metformin	169-178	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	153-158
35550195-10	2022	These findings highlight c-Met as a potential key regulator of metformin-mediated inhibition of proliferation and stemness of breast cancer cells, indicating that c-Met overexpression may be a critical factor contributing to metformin resistance.	Metformin	63-72	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	25-30
35550195-10	2022	These findings highlight c-Met as a potential key regulator of metformin-mediated inhibition of proliferation and stemness of breast cancer cells, indicating that c-Met overexpression may be a critical factor contributing to metformin resistance.	Metformin	63-72	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	163-168
35550195-10	2022	These findings highlight c-Met as a potential key regulator of metformin-mediated inhibition of proliferation and stemness of breast cancer cells, indicating that c-Met overexpression may be a critical factor contributing to metformin resistance.	Metformin	225-234	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	25-30
35550195-10	2022	These findings highlight c-Met as a potential key regulator of metformin-mediated inhibition of proliferation and stemness of breast cancer cells, indicating that c-Met overexpression may be a critical factor contributing to metformin resistance.	Metformin	225-234	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	163-168
35550195-11	2022	The data also suggest that combination of metformin with c-Met inhibitors could be a useful strategy to improve metformin-mediated anti-cancer efficacies in breast cancer treatment.	Metformin	112-121	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	57-62
35286779-9	2022	However, catalase and glutathione peroxidase enzymes were significantly increased by metformin compared to the aging model.	Metformin	85-94	catalase	Mus musculus	9-17
35341746-0	2022	Metformin attenuates early brain injury after subarachnoid hemorrhage in rats via AMPK-dependent mitophagy.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	82-86
35286779-11	2022	Localization of B-cell lymphoma 2 (Bcl2) showed intense immunostaining in the uterus of CN- and metformin-treated groups, with mild immunostaining in aging model.	Metformin	96-105	B cell leukemia/lymphoma 2	Mus musculus	16-33
35286779-11	2022	Localization of B-cell lymphoma 2 (Bcl2) showed intense immunostaining in the uterus of CN- and metformin-treated groups, with mild immunostaining in aging model.	Metformin	96-105	B cell leukemia/lymphoma 2	Mus musculus	35-39
35286779-13	2022	Moreover, it may be concluded that metformin might ameliorate uterine dysfunctions by reducing oxidative stress, suppressing apoptosis, and increasing the survival/antiapoptotic protein Bcl2.	Metformin	35-44	B cell leukemia/lymphoma 2	Mus musculus	186-190
35142713-1	2022	PURPOSE: To determine the separated and combined effects of metformin and resistance exercise on glycemic control, insulin sensitivity and insulin-like growth factor 1 (IGF-1) in overweight/obese individuals with pre-and-T2DM.	Metformin	60-69	insulin	Homo sapiens	115-122
35341746-1	2022	Metformin is the most widely used drug to treat type 2 diabetes and its mitochondrial activity is through activation of adenosine monophosphate-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	120-168
35341746-1	2022	Metformin is the most widely used drug to treat type 2 diabetes and its mitochondrial activity is through activation of adenosine monophosphate-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	170-174
35341746-3	2022	The aim of this study was to investigate whether metformin could reduce early brain injury (EBI) after subarachnoid hemorrhage (SAH) by activating mitophagy and improving mitochondrial morphology through AMPK.	Metformin	49-58	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	204-208
35341746-11	2022	Metformin treatment after SAH promoted mitophagy in an AMPK-dependent manner.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	55-59
35341746-12	2022	In addition to the effects on mitophagy, we also found that metformin alleviated oxidative stress and apoptosis after SAH in an AMPK-dependent manner.	Metformin	60-69	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	128-132
35341746-14	2022	Metformin attenuated EBI after SAH in rats through AMPK-dependent signaling.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	51-55
35605453-8	2022	Mitophagy was altered in type 2 diabetic patients, evident in a decrease in the protein levels of PINK1 and Parkin in parallel to that of the mitochondrial biogenesis protein PGC1alpha, both of which effects were reversed by metformin.	Metformin	225-234	PPARG coactivator 1 alpha	Homo sapiens	175-184
35605453-10	2022	In addition, there was an increase in the serum levels of TNFalpha and IL-6 in type 2 diabetic patients and this was reversed with metformin treatment.	Metformin	131-140	tumor necrosis factor	Homo sapiens	58-66
35605453-10	2022	In addition, there was an increase in the serum levels of TNFalpha and IL-6 in type 2 diabetic patients and this was reversed with metformin treatment.	Metformin	131-140	interleukin 6	Homo sapiens	71-75
35142713-1	2022	PURPOSE: To determine the separated and combined effects of metformin and resistance exercise on glycemic control, insulin sensitivity and insulin-like growth factor 1 (IGF-1) in overweight/obese individuals with pre-and-T2DM.	Metformin	60-69	insulin like growth factor 1	Homo sapiens	139-167
35142713-1	2022	PURPOSE: To determine the separated and combined effects of metformin and resistance exercise on glycemic control, insulin sensitivity and insulin-like growth factor 1 (IGF-1) in overweight/obese individuals with pre-and-T2DM.	Metformin	60-69	insulin like growth factor 1	Homo sapiens	169-174
35142713-9	2022	Metformin decreased serum IGF-1 concentrations (P = 0.006) and RT did not reverse this reduction.	Metformin	0-9	insulin like growth factor 1	Homo sapiens	26-31
35398171-6	2022	Some markers of senescent cells (p21WAF1/Cip1, p16INK4A, and gammaH2AX) were also significantly upregulated by doxorubicin and then counteracted by metformin treatment.	Metformin	148-157	cyclin dependent kinase inhibitor 2A	Mus musculus	47-55
35398171-6	2022	Some markers of senescent cells (p21WAF1/Cip1, p16INK4A, and gammaH2AX) were also significantly upregulated by doxorubicin and then counteracted by metformin treatment.	Metformin	148-157	H2A.X variant histone	Mus musculus	61-70
35393769-5	2022	Here, we demonstrate that the combination of oral glycine and metformin with intravenous PMO enhances PMO activity, dystrophin restoration, extends lifespan, and improves body-wide function and phenotypic rescue of dystrophin /utrophin double knock-out (DKO) mice without any overt adverse effects.	Metformin	62-71	dystrophin, muscular dystrophy	Mus musculus	116-126
35393769-5	2022	Here, we demonstrate that the combination of oral glycine and metformin with intravenous PMO enhances PMO activity, dystrophin restoration, extends lifespan, and improves body-wide function and phenotypic rescue of dystrophin /utrophin double knock-out (DKO) mice without any overt adverse effects.	Metformin	62-71	dystrophin, muscular dystrophy	Mus musculus	215-225
35393769-5	2022	Here, we demonstrate that the combination of oral glycine and metformin with intravenous PMO enhances PMO activity, dystrophin restoration, extends lifespan, and improves body-wide function and phenotypic rescue of dystrophin /utrophin double knock-out (DKO) mice without any overt adverse effects.	Metformin	62-71	utrophin	Mus musculus	227-235
35143900-9	2022	A significant increase in Gal-3 S-glutathionylation was observed in metformin-treated db/db mice when compared to db/db mice alone.	Metformin	68-77	lectin, galactose binding, soluble 3	Mus musculus	26-31
35341775-0	2022	Metformin alleviates dexamethasone-induced apoptosis by regulating autophagy via AMPK/mTOR/p70S6K in osteoblasts.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	86-90
35341775-12	2022	Treatment with the autophagy inhibitor 3-methyladenine (3-MA) attenuated the effect of metformin on apoptosis, autophagy, and the AMPK/mTOR/p70S6K signaling pathway.	Metformin	87-96	mechanistic target of rapamycin kinase	Homo sapiens	135-139
35341775-14	2022	Furthermore, sh-AMPK transfection and the mTOR activator MHY1485 impaired metformin-mediated inhibition of osteoblast apoptosis and promotion of autophagy.	Metformin	74-83	mechanistic target of rapamycin kinase	Homo sapiens	42-46
35341775-15	2022	The AMPK/mTOR/p70S6K signaling pathway plays a role in metformin-mediated apoptosis suppression and autophagy promotion.	Metformin	55-64	mechanistic target of rapamycin kinase	Homo sapiens	9-13
35341775-16	2022	In conclusion, metformin can alleviate Dex-induced osteoblast apoptosis by inducing autophagy via the AMPK/mTOR/p70S6K pathway.	Metformin	15-24	mechanistic target of rapamycin kinase	Homo sapiens	107-111
35334358-12	2022	Inspiringly, we identified that disulfiram and metformin could augment gut Akkermansia abundance, reduce serum IFN-gamma level, inhibit macrophage pyroptosis in ovaries, therefore ameliorating PCOS.	Metformin	47-56	interferon gamma	Mus musculus	111-120
35217034-11	2022	In PCOS mice, Cap overexpression, Cap transactivation by metformin, or enhancing Cbl-CrkII binding improved insulin sensitivity and ovarian dysfunction (i.e., estrous cycle disruption, cyst-like follicle formation, and sex hormone dysregulation).	Metformin	57-66	insulin	Homo sapiens	108-115
35367225-9	2022	Metformin is a pleiotropic drug, modulating different targets such as AMPK, insulin signalling and many others.	Metformin	0-9	insulin	Homo sapiens	76-83
35620570-3	2022	Results: The empagliflozin-metformin combination increased levels of the antioxidants (TAS, SOD, and GPx up to 1.1-fold; P < 0.01), decreased the levels of prooxidants (AOPP and isoprostanes up to 1.2-fold, P < 0.01; AGE up to 1.5-fold, P < 0.01), and decreased inflammatory parameters (up to 1.5-fold, CRP P < 0.01; IL-6 P < 0.001).	Metformin	27-36	superoxide dismutase 1	Homo sapiens	92-95
35578807-1	2022	OBJECTIVE: This study aimed to determine whether chronic metformin use interferes with the improvements in insulin resistance (IR) and cardiorespiratory fitness with aerobic training in people with hyperglycemia and metabolic syndrome (MetS).	Metformin	57-66	insulin	Homo sapiens	107-114
35138021-7	2022	In the subgroup on metformin monotherapy (N=140), 45% subsequently required restart of insulin.	Metformin	19-28	insulin	Homo sapiens	87-94
35619086-0	2022	Role of human organic cation transporter-1 (OCT-1/SLC22A1) in modulating the response to metformin in patients with type 2 diabetes.	Metformin	89-98	solute carrier family 22 member 1	Homo sapiens	14-42
35619086-0	2022	Role of human organic cation transporter-1 (OCT-1/SLC22A1) in modulating the response to metformin in patients with type 2 diabetes.	Metformin	89-98	solute carrier family 22 member 1	Homo sapiens	44-49
35619086-0	2022	Role of human organic cation transporter-1 (OCT-1/SLC22A1) in modulating the response to metformin in patients with type 2 diabetes.	Metformin	89-98	solute carrier family 22 member 1	Homo sapiens	50-57
35619086-1	2022	BACKGROUND: Organic cation transporter 1 primarily governs the action of metformin in the liver.	Metformin	73-82	solute carrier family 22 member 1	Homo sapiens	12-40
35619086-3	2022	In light of this, it is crucial to obtain a greater understanding of the influence of OCT1 expression or polymorphism in the context of variable responses elicited by metformin treatment.	Metformin	167-176	solute carrier family 22 member 1	Homo sapiens	86-90
35619086-4	2022	RESULTS: We observed that the variable response to metformin in the responders and non-responders is independent of isoform variation and mRNA expression of OCT-1.	Metformin	51-60	solute carrier family 22 member 1	Homo sapiens	157-162
35619086-6	2022	Further, molecular docking provided us with an insight into the hotspot regions of OCT-1 for metformin binding.	Metformin	93-102	solute carrier family 22 member 1	Homo sapiens	83-88
35619086-8	2022	The 181T>C and 1222A>G changes were further found to alter OCT-1 structure in silico and affect metformin transport in vitro which was illustrated by their effect on the activation of AMPK, the marker for metformin activity.	Metformin	205-214	solute carrier family 22 member 1	Homo sapiens	59-64
35619086-9	2022	CONCLUSION: Taken together, our results corroborate the role of OCT-1 in the transport of metformin and also point at OCT1 genetic variations possibly affecting the transport of metformin into the cells and hence its subsequent action in responders and non-responders.	Metformin	90-99	solute carrier family 22 member 1	Homo sapiens	64-69
35619086-9	2022	CONCLUSION: Taken together, our results corroborate the role of OCT-1 in the transport of metformin and also point at OCT1 genetic variations possibly affecting the transport of metformin into the cells and hence its subsequent action in responders and non-responders.	Metformin	178-187	solute carrier family 22 member 1	Homo sapiens	118-122
35610639-0	2022	Metformin exerts an antitumor effect by inhibiting bladder cancer cell migration and growth, and promoting apoptosis through the PI3K/AKT/mTOR pathway.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	134-137
35610639-0	2022	Metformin exerts an antitumor effect by inhibiting bladder cancer cell migration and growth, and promoting apoptosis through the PI3K/AKT/mTOR pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	138-142
35610639-10	2022	Compared with that in the control group, the level of cleaved-caspase 3 and cleaved-PARP protein in the metformin group was increased in each treatment group, and the levels of p-mTOR, p-AKT, and p-PI3K decreased significantly compared with those in the control group (P < 0.05).	Metformin	104-113	poly(ADP-ribose) polymerase 1	Homo sapiens	84-88
35610639-10	2022	Compared with that in the control group, the level of cleaved-caspase 3 and cleaved-PARP protein in the metformin group was increased in each treatment group, and the levels of p-mTOR, p-AKT, and p-PI3K decreased significantly compared with those in the control group (P < 0.05).	Metformin	104-113	mechanistic target of rapamycin kinase	Homo sapiens	179-183
35610639-10	2022	Compared with that in the control group, the level of cleaved-caspase 3 and cleaved-PARP protein in the metformin group was increased in each treatment group, and the levels of p-mTOR, p-AKT, and p-PI3K decreased significantly compared with those in the control group (P < 0.05).	Metformin	104-113	AKT serine/threonine kinase 1	Homo sapiens	187-190
35587864-1	2022	Importance: Recent studies suggest that the diabetes drug metformin has a protective effect on open-angle glaucoma (OAG) and age-related macular degeneration (AMD).	Metformin	58-67	renin binding protein	Homo sapiens	125-128
35592896-0	2022	The effect of metformin on vitamin B12 levels in pediatric patients.	Metformin	14-23	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	35-38
35592896-2	2022	In adults, one well-documented side effect of metformin is vitamin B12 deficiency.	Metformin	46-55	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	67-70
35592896-4	2022	This study examined the changes of vitamin B12 levels in pediatric patients being treated with metformin administration.	Metformin	95-104	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	43-46
35592896-6	2022	The effects of varying doses of metformin on the mean vitamin B12 level were investigated at 6-month, 12-month, 24-month and 36-month intervals.	Metformin	32-41	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	62-65
35592896-7	2022	The degree of compliance of metformin intake on vitamin B12 level also was studied.	Metformin	28-37	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	56-59
35592896-9	2022	Mean vitamin B12 drop was only noticeable (p<0.05) in patients taking high dose of metformin with a good compliance.	Metformin	83-92	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	13-16
35592896-13	2022	Our findings suggest metformin treatment in children does not cause vitamin B12 deficiency; however, long-term treatment could reduce vitamin B12 levels when patients take a high dose consistently.	Metformin	21-30	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	142-145
35631186-0	2022	Vitamin B12 Deficiency in Patients with Diabetes on Metformin: Arab Countries.	Metformin	52-61	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	8-11
35631186-2	2022	AIM: The goal of this study was to review the published studies that were conducted to determine the relationship between metformin treatment for type 2 diabetes mellitus (T2DM) and vitamin B12 deficiency and to identify possible complications in this relationship.	Metformin	122-131	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	190-193
35631186-4	2022	RESULTS: Eleven studies were included in this review which indicated an association between taking metformin and B12 deficiency in patients with T2DM in Arab countries.	Metformin	99-108	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	113-116
35631186-5	2022	This B12 deficiency was found to be negatively associated with the dose and duration of metformin therapy.	Metformin	88-97	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	5-8
35631186-6	2022	The physician"s knowledge of current ADA recommendations regarding supplementation with and screening of the B12 level for T2DM patients on metformin was also found to have an effect.	Metformin	140-149	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	109-112
35631186-7	2022	CONCLUSION: Metformin therapy is associated with B12 deficiency among people with T2DM in Arabic countries.	Metformin	12-21	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	49-52
35631186-8	2022	Thus, diabetes must be managed in compliance with current guidelines and recommendations, and B12 levels must be routinely monitored, particularly in those who have been long-term takers of metformin, to ensure the suitable management of diabetes and its complications.	Metformin	190-199	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	94-97
35561893-0	2022	Metformin inhibits multiple myeloma serum-induced endothelial cell thrombosis by down-regulating miR-532.	Metformin	0-9	microRNA 532	Homo sapiens	97-104
35561893-10	2022	Based on the MM serum treatment, metformin decreased these expressions and inhibited the thrombin generation and protein C activation in HUVECs.	Metformin	33-42	coagulation factor II, thrombin	Homo sapiens	89-97
35561893-11	2022	However, miR-532 mimic reversed the effect of metformin and promoted the levels of thrombosis related indicators in HUVECs.	Metformin	46-55	microRNA 532	Homo sapiens	9-16
35561893-12	2022	Moreover, metformin activated the EPCR, ERK 1/2, p38 MAPK and NF-kappaB pathways but miR-532 mimic suppressed the activation of pathways.	Metformin	10-19	mitogen-activated protein kinase 3	Homo sapiens	40-47
35592685-10	2022	However, the SOD of the metformin group was higher than the control group, but the cyclin D was lower, while the SOD was higher than medium- and low-concentration groups in the high-concentration group, but the cyclin D was lower after cultured.	Metformin	24-33	superoxide dismutase 1	Homo sapiens	13-16
35592685-10	2022	However, the SOD of the metformin group was higher than the control group, but the cyclin D was lower, while the SOD was higher than medium- and low-concentration groups in the high-concentration group, but the cyclin D was lower after cultured.	Metformin	24-33	superoxide dismutase 1	Homo sapiens	113-116
35592685-11	2022	Conclusion: High-concentration metformin can reduce oxidative stress injury, increase the expression of SOD in CCRCC, and reduce cyclin D in CCRCC to inhibit proliferation and migration, which has optimistic prospects and application value in controlling the progression of CCRCC.	Metformin	31-40	superoxide dismutase 1	Homo sapiens	104-107
35620570-3	2022	Results: The empagliflozin-metformin combination increased levels of the antioxidants (TAS, SOD, and GPx up to 1.1-fold; P < 0.01), decreased the levels of prooxidants (AOPP and isoprostanes up to 1.2-fold, P < 0.01; AGE up to 1.5-fold, P < 0.01), and decreased inflammatory parameters (up to 1.5-fold, CRP P < 0.01; IL-6 P < 0.001).	Metformin	27-36	C-reactive protein	Homo sapiens	303-306
35620570-3	2022	Results: The empagliflozin-metformin combination increased levels of the antioxidants (TAS, SOD, and GPx up to 1.1-fold; P < 0.01), decreased the levels of prooxidants (AOPP and isoprostanes up to 1.2-fold, P < 0.01; AGE up to 1.5-fold, P < 0.01), and decreased inflammatory parameters (up to 1.5-fold, CRP P < 0.01; IL-6 P < 0.001).	Metformin	27-36	interleukin 6	Homo sapiens	317-321
35525318-4	2022	Available data suggest that metformin inhibits complex I of the mitochondrial electron transport chain, crucial gluconeogenic enzymes, and fatty acid synthesis that leads to a significant improvement in glucose tolerance and maintenance of insulin sensitivity during glucocorticoid treatment.	Metformin	28-37	insulin	Homo sapiens	240-247
35481401-0	2022	Metformin combats obesity by targeting FTO in an m6A-YTHDF2-dependent manner.	Metformin	0-9	glycoprotein m6a	Mus musculus	49-52
35481401-4	2022	Mechanically, we revealed that metformin could inhibit protein expression of FTO, leading to increased m6A methylation levels of cyclin D1 (Ccnd1) and cyclin dependent kinase 2 (Cdk2), two crucial regulators in cell cycle.	Metformin	31-40	glycoprotein m6a	Mus musculus	103-106
35571566-8	2022	In conclusion, our results stipulate that metformin inhibits inflammation through the adenosine 5"-monophosphate (AMP-) activated protein kinase pathway by inhibiting nuclear factor kappa beta (NF-kappaB).	Metformin	42-51	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	194-203
35470560-2	2022	Metformin (dimethyl-biguanide) is a first-line treatment for type II diabetes that, among other mechanisms, is involved in the activation of adenosine monophosphate activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	141-189
35227644-0	2022	Metformin increases the radiosensitivity of non-small cell lung cancer cells by destabilizing NRF2.	Metformin	0-9	nuclear factor, erythroid derived 2, like 2	Mus musculus	94-98
35227644-5	2022	Furthermore, we identified nuclear factor erythroid 2-related factor 2 (NRF2) as a critical target of radiosensitization effect of metformin, as the radiosensitization effect was abolished in NRF2 knockout cells.	Metformin	131-140	nuclear factor, erythroid derived 2, like 2	Mus musculus	27-70
35227644-5	2022	Furthermore, we identified nuclear factor erythroid 2-related factor 2 (NRF2) as a critical target of radiosensitization effect of metformin, as the radiosensitization effect was abolished in NRF2 knockout cells.	Metformin	131-140	nuclear factor, erythroid derived 2, like 2	Mus musculus	72-76
35227644-5	2022	Furthermore, we identified nuclear factor erythroid 2-related factor 2 (NRF2) as a critical target of radiosensitization effect of metformin, as the radiosensitization effect was abolished in NRF2 knockout cells.	Metformin	131-140	nuclear factor, erythroid derived 2, like 2	Mus musculus	192-196
35227644-6	2022	We also showed that metformin treatment increased the ubiquitination and proteasomal degradation of NRF2 through a KEAP1-independent mechanism.	Metformin	20-29	nuclear factor, erythroid derived 2, like 2	Mus musculus	100-104
35227644-8	2022	In an orthotopic transplanted tumor model in nude mice, metformin treatment reduced NRF2 levels and led to fewer lung tumor nodules.	Metformin	56-65	nuclear factor, erythroid derived 2, like 2	Mus musculus	84-88
35227644-10	2022	In conclusion, our results suggest that the degradation of NRF2 that is induced by metformin may play a pivotal role in radiosensitizing NSCLC cells and that metformin can be developed as a sensitizer of radiotherapy against lung cancer.	Metformin	83-92	nuclear factor, erythroid derived 2, like 2	Mus musculus	59-63
35227644-10	2022	In conclusion, our results suggest that the degradation of NRF2 that is induced by metformin may play a pivotal role in radiosensitizing NSCLC cells and that metformin can be developed as a sensitizer of radiotherapy against lung cancer.	Metformin	158-167	nuclear factor, erythroid derived 2, like 2	Mus musculus	59-63
35470560-2	2022	Metformin (dimethyl-biguanide) is a first-line treatment for type II diabetes that, among other mechanisms, is involved in the activation of adenosine monophosphate activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	191-195
35416588-10	2022	From univariate analysis performed within the group of individuals with T2DM, the likelihood of death following a COVID-19 recorded infection was lower in people taking metformin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i) or a glucagon-like peptide 1 (GLP-1) agonist.	Metformin	169-178	glucagon	Homo sapiens	237-260
35405526-0	2022	Metformin alleviates nickel-refining fumes-induced aerobic glycolysis via AMPK/GOLPH3 pathway in vitro and in vivo.	Metformin	0-9	golgi phosphoprotein 3	Homo sapiens	79-85
35405526-6	2022	Our findings indicated that Ni fumes expose evoked aerobic glycolysis by AMPK/GOLPH3, while metformin attenuated Ni particles-promoted GOLPH3-mediated aerobic glycolysis by p-AMPK expression increase.	Metformin	92-101	golgi phosphoprotein 3	Homo sapiens	135-141
35405526-11	2022	The results indicated that metformin decreased the protein levels of GOLPH3, LDHA, HK2, MCT-4 and improved p-AMPK expression.	Metformin	27-36	golgi phosphoprotein 3	Homo sapiens	69-75
35405526-11	2022	The results indicated that metformin decreased the protein levels of GOLPH3, LDHA, HK2, MCT-4 and improved p-AMPK expression.	Metformin	27-36	lactate dehydrogenase A	Homo sapiens	77-81
35405526-12	2022	Thus, our findings demonstrated metformin antagonized Ni-refining fumes-caused aerobic glycolysis via AMPK/GOLPH3.	Metformin	32-41	golgi phosphoprotein 3	Homo sapiens	107-113
35416588-10	2022	From univariate analysis performed within the group of individuals with T2DM, the likelihood of death following a COVID-19 recorded infection was lower in people taking metformin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i) or a glucagon-like peptide 1 (GLP-1) agonist.	Metformin	169-178	glucagon	Homo sapiens	262-267
35098553-4	2022	Therefore, this study is the first to assess the possible ameliorating effects of avocado and cinnamon extracts on streptozotocin (STZ)-induced disturbances in the gene expression of PDX1 and Ins1 in type-2 diabetic rats, in comparison to metformin.	Metformin	239-248	pancreatic and duodenal homeobox 1	Rattus norvegicus	183-187
35090865-1	2022	The aim of this study was to investigate the contributions of multiple transport mechanisms to the intestinal absorption of metformin, focusing on OCT3, PMAT, THTR2, SERT and OCTN2.	Metformin	124-133	solute carrier family 6 member 4	Homo sapiens	166-170
35090865-3	2022	Uptake studies with MDCKII cells expressing OCT3, PMAT, THTR2 or SERT confirmed that metformin is a substrate of these transporters.	Metformin	85-94	solute carrier family 6 member 4	Homo sapiens	65-69
35090865-6	2022	AG835, thiamine and paroxetine specifically inhibited PMAT-, THTR2- and SERT-mediated uptake of metformin, respectively.	Metformin	96-105	solute carrier family 6 member 4	Homo sapiens	72-76
35090865-7	2022	Using these inhibitors, the relative contributions of OCT3, PMAT, THTR2, SERT, OCTN2 and others to the intestinal permeation of metformin across Caco-2 cells were estimated to be 9.77%, 9.68%, 22.2%, 1.52%, 0% and 0.66%, respectively.	Metformin	128-137	solute carrier family 6 member 4	Homo sapiens	73-77
35489715-11	2022	Fatty acid oxidation inhibitor, etomoxir, decreased apical-to-basolateral export of medium-chain B-C12 and long-chain B-C16 fatty acids whereas CPT1 agonist, C75, and antidiabetic drug, metformin, increased apical-to-basolateral export.	Metformin	186-195	carnitine palmitoyltransferase 1A	Homo sapiens	144-148
35558742-12	2022	Interaction and subgroup analyses demonstrated that glucagon-like peptide-1 (GLP-1) was positively related to total energy (beta = 0.268, P = 0.033), carbohydrates intake, and insulin secretion (beta = 2,045.2, P = 0.003) only in the acarbose group, while systolic blood pressure (SBP) was negatively related to protein intake in the metformin group (beta = 23.21, P = 0.014).	Metformin	334-343	glucagon	Homo sapiens	52-75
35558742-12	2022	Interaction and subgroup analyses demonstrated that glucagon-like peptide-1 (GLP-1) was positively related to total energy (beta = 0.268, P = 0.033), carbohydrates intake, and insulin secretion (beta = 2,045.2, P = 0.003) only in the acarbose group, while systolic blood pressure (SBP) was negatively related to protein intake in the metformin group (beta = 23.21, P = 0.014).	Metformin	334-343	glucagon	Homo sapiens	77-82
35558742-13	2022	The results of this study showed that metformin and acarbose mainly exerted different interactive effects with dietary energy, carbohydrate, and protein intakes on GLP-1 secretion, insulin release, and SBP.	Metformin	38-47	glucagon	Homo sapiens	164-169
35558742-13	2022	The results of this study showed that metformin and acarbose mainly exerted different interactive effects with dietary energy, carbohydrate, and protein intakes on GLP-1 secretion, insulin release, and SBP.	Metformin	38-47	insulin	Homo sapiens	181-188
35528246-7	2022	The effects of p-cymene and metformin were studied on levels of glucose (Glu), lipid profile, liver enzymes, oxidative stress, and the expression of Akt, phospho-Akt, and mTOR (mammalian target of rapamycin) proteins, using biochemical, histological, and immunohistochemical analysis.	Metformin	28-37	AKT serine/threonine kinase 1	Homo sapiens	149-152
35528246-7	2022	The effects of p-cymene and metformin were studied on levels of glucose (Glu), lipid profile, liver enzymes, oxidative stress, and the expression of Akt, phospho-Akt, and mTOR (mammalian target of rapamycin) proteins, using biochemical, histological, and immunohistochemical analysis.	Metformin	28-37	AKT serine/threonine kinase 1	Homo sapiens	162-165
35528246-7	2022	The effects of p-cymene and metformin were studied on levels of glucose (Glu), lipid profile, liver enzymes, oxidative stress, and the expression of Akt, phospho-Akt, and mTOR (mammalian target of rapamycin) proteins, using biochemical, histological, and immunohistochemical analysis.	Metformin	28-37	mechanistic target of rapamycin kinase	Homo sapiens	171-175
35528246-7	2022	The effects of p-cymene and metformin were studied on levels of glucose (Glu), lipid profile, liver enzymes, oxidative stress, and the expression of Akt, phospho-Akt, and mTOR (mammalian target of rapamycin) proteins, using biochemical, histological, and immunohistochemical analysis.	Metformin	28-37	mechanistic target of rapamycin kinase	Homo sapiens	177-206
35545589-10	2022	Immunofluorescence experiments showed that compared with the noise exposure group, the fluorescence intensity of insulin-like growth factor 1 receptor (IGF1R) in the metformin+noise exposure group was increased, and the fluorescence intensity of eukaryotic translation initiation factor 4E binding protein 1 (eIF4EBP1) was decreased.	Metformin	166-175	eukaryotic translation initiation factor 4E binding protein 1	Rattus norvegicus	246-307
35625721-0	2022	Metformin Protects against Diabetic Cardiomyopathy: An Association between Desmin-Sarcomere Injury and the iNOS/mTOR/TIMP-1 Fibrosis Axis.	Metformin	0-9	nitric oxide synthase 2	Rattus norvegicus	107-111
35625721-9	2022	These findings demonstrate an association between damage of the cardiac contractile unit-desmin and sarcomere-and the iNOS/mTOR/TIMP-1/collagen axis of fibrosis in T2DM-induced cardiomyopathy, with metformin exhibiting beneficial cardiovascular pleiotropic effects.	Metformin	198-207	nitric oxide synthase 2	Homo sapiens	118-122
35625721-9	2022	These findings demonstrate an association between damage of the cardiac contractile unit-desmin and sarcomere-and the iNOS/mTOR/TIMP-1/collagen axis of fibrosis in T2DM-induced cardiomyopathy, with metformin exhibiting beneficial cardiovascular pleiotropic effects.	Metformin	198-207	mechanistic target of rapamycin kinase	Homo sapiens	123-127
35625721-9	2022	These findings demonstrate an association between damage of the cardiac contractile unit-desmin and sarcomere-and the iNOS/mTOR/TIMP-1/collagen axis of fibrosis in T2DM-induced cardiomyopathy, with metformin exhibiting beneficial cardiovascular pleiotropic effects.	Metformin	198-207	TIMP metallopeptidase inhibitor 1	Homo sapiens	128-134
35497918-0	2022	Correlation of Serum IGF-1R, VEGF, and ET Levels with Bone Mineral Density in Type 2 Diabetic Mellitus Patients Treated with Metformin Plus alpha-Glucosidase Inhibitors.	Metformin	125-134	major facilitator superfamily domain containing 11	Homo sapiens	39-41
35497918-7	2022	Alpha-glucosidase inhibitors plus metformin for primary T2DM can effectively manage blood glucose and reduce insulin resistance in patients, but the prediction of osteoporosis development remains to be further explored in large sample studies.	Metformin	34-43	insulin	Homo sapiens	109-116
35545589-10	2022	Immunofluorescence experiments showed that compared with the noise exposure group, the fluorescence intensity of insulin-like growth factor 1 receptor (IGF1R) in the metformin+noise exposure group was increased, and the fluorescence intensity of eukaryotic translation initiation factor 4E binding protein 1 (eIF4EBP1) was decreased.	Metformin	166-175	eukaryotic translation initiation factor 4E binding protein 1	Rattus norvegicus	309-317
35496297-11	2022	Metformin and TQ inhibited the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) signaling and induced apoptosis in tested cell lines and primary cells.	Metformin	0-9	nuclear factor kappa B subunit 1	Homo sapiens	95-104
35444236-6	2022	Administration of the well-known OXPHOS inhibitor metformin eradicated CML stem/progenitor cells and re-sensitized CD34+ CML cells to imatinib in vitro and in patient-derived tumor xenograft murine model.	Metformin	50-59	CD34 molecule	Homo sapiens	115-119
35454163-1	2022	Metformin is a synthetic biguanide that improves insulin sensitivity and reduces hepatic gluconeogenesis.	Metformin	0-9	insulin	Homo sapiens	49-56
35454163-8	2022	This suggests that metformin might be useful for patients with differentiated or poorly differentiated thyroid cancer and metabolic diseases such as insulin resistance or diabetes.	Metformin	19-28	insulin	Homo sapiens	149-156
35496297-14	2022	A combination of 1.25 mM metformin and 0.625 microM TQ increased the levels of cleaved poly (ADP-ribose) polymerase (PARP), decreased the levels of proliferation regulatory proteins, and inhibited protein kinase B (Akt) and NF-kappaB signaling in primary CLL cells.	Metformin	25-34	poly(ADP-ribose) polymerase 1	Homo sapiens	87-115
35496297-14	2022	A combination of 1.25 mM metformin and 0.625 microM TQ increased the levels of cleaved poly (ADP-ribose) polymerase (PARP), decreased the levels of proliferation regulatory proteins, and inhibited protein kinase B (Akt) and NF-kappaB signaling in primary CLL cells.	Metformin	25-34	poly(ADP-ribose) polymerase 1	Homo sapiens	117-121
35496297-14	2022	A combination of 1.25 mM metformin and 0.625 microM TQ increased the levels of cleaved poly (ADP-ribose) polymerase (PARP), decreased the levels of proliferation regulatory proteins, and inhibited protein kinase B (Akt) and NF-kappaB signaling in primary CLL cells.	Metformin	25-34	AKT serine/threonine kinase 1	Homo sapiens	215-218
35496297-14	2022	A combination of 1.25 mM metformin and 0.625 microM TQ increased the levels of cleaved poly (ADP-ribose) polymerase (PARP), decreased the levels of proliferation regulatory proteins, and inhibited protein kinase B (Akt) and NF-kappaB signaling in primary CLL cells.	Metformin	25-34	nuclear factor kappa B subunit 1	Homo sapiens	224-233
35090900-4	2022	We found that metformin exerted antidepressant effects on apoE4 mice, including reduced immobility time in TST and FST, and increased ratios of time and distance in the central area of OFT.	Metformin	14-23	thiosulfate sulfurtransferase, mitochondrial	Mus musculus	107-110
35498407-2	2022	Patients with this condition will eventually develop diabetes, presenting a variable response to insulin-sensitizers, such as metformin and thiazolidinediones, and high doses of insulin.	Metformin	126-135	insulin	Homo sapiens	97-104
35416184-2	2022	Previous experimental studies have shown that resveratrol and metformin, less specific activators of AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1), can effectively attenuate acute liver injury.	Metformin	62-71	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	101-129
35416184-2	2022	Previous experimental studies have shown that resveratrol and metformin, less specific activators of AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1), can effectively attenuate acute liver injury.	Metformin	62-71	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	131-135
35416184-2	2022	Previous experimental studies have shown that resveratrol and metformin, less specific activators of AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1), can effectively attenuate acute liver injury.	Metformin	62-71	sirtuin 1	Rattus norvegicus	141-150
35416184-2	2022	Previous experimental studies have shown that resveratrol and metformin, less specific activators of AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1), can effectively attenuate acute liver injury.	Metformin	62-71	sirtuin 1	Rattus norvegicus	152-157
35413055-5	2022	Furthermore, we evaluated the effect of brief Metformin treatment on sera of obese postmenopausal women and its impact on Akt and NF-kappaB activation.	Metformin	46-55	AKT serine/threonine kinase 1	Homo sapiens	122-125
35413055-10	2022	We further demonstrated that sera from post-Metformin obese women induced an increase in p38 phosphorylation, independent of insulin resistance.	Metformin	44-53	mitogen-activated protein kinase 14	Homo sapiens	89-92
35090900-7	2022	Moreover, the metformin administration increased the levels of transcriptional factor NRF-1 and TFAM, mtDNA, and most mitochondrial complex subunits in apoE-TR mice.	Metformin	14-23	nuclear respiratory factor 1	Mus musculus	86-91
35090900-7	2022	Moreover, the metformin administration increased the levels of transcriptional factor NRF-1 and TFAM, mtDNA, and most mitochondrial complex subunits in apoE-TR mice.	Metformin	14-23	apolipoprotein E	Mus musculus	152-156
35344434-3	2022	Using mouse models and human primary hepatocytes, we show that metformin, at clinically relevant doses, suppresses hepatic glucose production by activating a conserved regulatory pathway encompassing let-7, TET3, and a fetal isoform of hepatocyte nuclear factor 4 alpha (HNF4alpha).	Metformin	63-72	tet methylcytosine dioxygenase 3	Homo sapiens	207-211
35449816-7	2022	We showed that administration of TSJ or metformin prevented the increases in FBG level, serum Cr, BUN, TC, and TG level, and urine protein excretion in diabetic nephropathy.	Metformin	40-49	thyroglobulin	Rattus norvegicus	111-113
35449816-9	2022	TSJ or metformin markedly upregulated the level of nephrin and podocin, accompanied by evident enhancement of podocyte autophagy and activation of p-AMPK/p-ULK1 signaling in the diabetic nephropathy.	Metformin	7-16	NPHS2 stomatin family member, podocin	Rattus norvegicus	63-70
35449816-9	2022	TSJ or metformin markedly upregulated the level of nephrin and podocin, accompanied by evident enhancement of podocyte autophagy and activation of p-AMPK/p-ULK1 signaling in the diabetic nephropathy.	Metformin	7-16	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	149-153
35449816-9	2022	TSJ or metformin markedly upregulated the level of nephrin and podocin, accompanied by evident enhancement of podocyte autophagy and activation of p-AMPK/p-ULK1 signaling in the diabetic nephropathy.	Metformin	7-16	unc-51 like autophagy activating kinase 1	Rattus norvegicus	156-160
35396719-5	2022	Treating diabetic rats with metformin and forskolin resulted in significant improvement in sperm quality parameters, increased testosterone levels, reduced oxidative stress in blood and testicular tissue, and decreased blood sugar, and Bax to Bcl-2 ratio level.	Metformin	28-37	BCL2, apoptosis regulator	Rattus norvegicus	243-248
35462933-5	2022	For example, metformin promotes thermogenesis and alleviates obesity by activating the AMPK/alphaKG/PRDM16 signaling pathway; rosiglitazone alleviates obesity under the synergistic effect of PRDM16; resveratrol plays an antiobesity role by inducing the expression of PRDM16; liraglupeptide improves insulin resistance by inducing the expression of PRDM16; and mulberry leaves play an anti-inflammatory and antidiabetes role by activating the expression of brown fat cell marker genes (including PRDM16).	Metformin	13-22	insulin	Homo sapiens	299-306
35344434-3	2022	Using mouse models and human primary hepatocytes, we show that metformin, at clinically relevant doses, suppresses hepatic glucose production by activating a conserved regulatory pathway encompassing let-7, TET3, and a fetal isoform of hepatocyte nuclear factor 4 alpha (HNF4alpha).	Metformin	63-72	hepatocyte nuclear factor 4 alpha	Homo sapiens	236-269
35344434-3	2022	Using mouse models and human primary hepatocytes, we show that metformin, at clinically relevant doses, suppresses hepatic glucose production by activating a conserved regulatory pathway encompassing let-7, TET3, and a fetal isoform of hepatocyte nuclear factor 4 alpha (HNF4alpha).	Metformin	63-72	hepatocyte nuclear factor 4 alpha	Homo sapiens	271-280
35344434-5	2022	Our results thus reveal an important role of the hepatic let-7/TET3/HNF4alpha axis in mediating the therapeutic effects of metformin and suggest that targeting this axis may be a potential therapeutic for diabetes.	Metformin	123-132	tet methylcytosine dioxygenase 3	Mus musculus	63-67
35444557-0	2022	Metformin Inhibits Na+/H+ Exchanger NHE3 Resulting in Intestinal Water Loss.	Metformin	0-9	solute carrier family 9 (sodium/hydrogen exchanger), member 3	Mus musculus	36-40
35444557-5	2022	The goal of this study is to investigate whether metformin regulates NHE3 and inhibition of NHE3 contributes to metformin-induced diarrhea.	Metformin	49-58	solute carrier family 9 (sodium/hydrogen exchanger), member 3	Mus musculus	69-73
35444557-5	2022	The goal of this study is to investigate whether metformin regulates NHE3 and inhibition of NHE3 contributes to metformin-induced diarrhea.	Metformin	112-121	solute carrier family 9 (sodium/hydrogen exchanger), member 3	Mus musculus	92-96
35444557-7	2022	We found that metformin decreased intestinal water absorption mediated by NHE3.	Metformin	14-23	solute carrier family 9 (sodium/hydrogen exchanger), member 3	Mus musculus	74-78
35444557-9	2022	To determine the mechanism of metformin-mediated regulation of NHE3, we used intestinal epithelial cells.	Metformin	30-39	solute carrier family 9 (sodium/hydrogen exchanger), member 3	Mus musculus	63-67
35444557-10	2022	Metformin inhibited NHE3 activity and the effect of metformin on NHE3 was mimicked by a 5"-AMP-activated protein kinase (AMPK) activator and blocked by pharmacological inhibition of AMPK.	Metformin	0-9	solute carrier family 9 (sodium/hydrogen exchanger), member 3	Mus musculus	20-24
35444557-10	2022	Metformin inhibited NHE3 activity and the effect of metformin on NHE3 was mimicked by a 5"-AMP-activated protein kinase (AMPK) activator and blocked by pharmacological inhibition of AMPK.	Metformin	0-9	solute carrier family 9 (sodium/hydrogen exchanger), member 3	Mus musculus	65-69
35444557-10	2022	Metformin inhibited NHE3 activity and the effect of metformin on NHE3 was mimicked by a 5"-AMP-activated protein kinase (AMPK) activator and blocked by pharmacological inhibition of AMPK.	Metformin	52-61	solute carrier family 9 (sodium/hydrogen exchanger), member 3	Mus musculus	65-69
35444557-11	2022	Metformin increased phosphorylation and ubiquitination of NHE3, resulting in retrieval of NHE3 from the plasma membrane.	Metformin	0-9	solute carrier family 9 (sodium/hydrogen exchanger), member 3	Mus musculus	58-62
35444557-11	2022	Metformin increased phosphorylation and ubiquitination of NHE3, resulting in retrieval of NHE3 from the plasma membrane.	Metformin	0-9	solute carrier family 9 (sodium/hydrogen exchanger), member 3	Mus musculus	90-94
35379885-10	2022	In addition, we found that LXRalpha overexpression compromised the effect of metformin on PCSK9 levels and intracellular lipid droplet formation.	Metformin	77-86	nuclear receptor subfamily 1, group H, member 3	Mus musculus	27-35
35395467-7	2022	In addition, metformin therapy increased mitochondrial membrane potential, with a reduction in mitochondrial reactive oxygen species, MDA and SOD levels, and restored mitochondrial balance through enhanced expression of dynamin-related protein 1 (Drp1).	Metformin	13-22	dynamin 1-like	Mus musculus	220-245
35395467-7	2022	In addition, metformin therapy increased mitochondrial membrane potential, with a reduction in mitochondrial reactive oxygen species, MDA and SOD levels, and restored mitochondrial balance through enhanced expression of dynamin-related protein 1 (Drp1).	Metformin	13-22	dynamin 1-like	Mus musculus	247-251
35379885-0	2022	Metformin Ameliorates Hepatic Steatosis induced by olanzapine through inhibiting LXRalpha/PCSK9 pathway.	Metformin	0-9	nuclear receptor subfamily 1, group H, member 3	Mus musculus	81-89
35455439-3	2022	By reducing mitochondrial oxidative phosphorylation and adenosine triphosphate (ATP) production, metformin increased AMP (adenosine monophosphate)-activated protein kinase (AMPK) activity and altered cellular redox state with reduced glucagon activity, endogenous glucose production, lipogenesis, and protein synthesis.	Metformin	97-106	glucagon	Homo sapiens	234-242
35379885-11	2022	Taken together, our findings suggest that olanzapine enhances hepatic PCSK9 expression by upregulating LXRalpha, thereby increasing FAS and SCD1 expression as well as decreasing SCAD and PPARalpha, and promoting lipid accumulation, and, subsequently, NAFLD, which is ameliorated by metformin.	Metformin	282-291	nuclear receptor subfamily 1, group H, member 3	Mus musculus	103-111
34990285-9	2022	Furthermore, metformin decreased mRNA and protein expression of components of the Shh pathway including Shh, Ptch, Smo and Gli-1.	Metformin	13-22	patched 1	Homo sapiens	109-113
35530948-12	2022	Discussion: Although the relative low quality of randomized controlled trials (RCTs) and limited results made it difficult to draw a definite conclusion, our study showed that metformin treatment during pregnancy can reduce the risk of pregnancy complications but may have impacts on increasing SHBG levels and long-term BMI in offspring.	Metformin	176-185	sex hormone binding globulin	Homo sapiens	295-299
35286856-0	2022	Abeta-responsive metformin-based supramolecular synergistic nanodrugs for Alzheimer"s disease via enhancing microglial Abeta clearance.	Metformin	17-26	amyloid beta precursor protein	Homo sapiens	0-5
35286856-0	2022	Abeta-responsive metformin-based supramolecular synergistic nanodrugs for Alzheimer"s disease via enhancing microglial Abeta clearance.	Metformin	17-26	amyloid beta precursor protein	Homo sapiens	119-124
35286856-1	2022	Here, inspired by the concept of supramolecular inclusion complex, we successfully fabricate metformin (Met)-based supramolecular nanodrugs with the Abeta-responsive on-demand drug release for synergistic Alzheimer"s disease (AD) therapy via enhancing microglial Abeta clearance.	Metformin	93-102	amyloid beta precursor protein	Homo sapiens	149-154
35286856-1	2022	Here, inspired by the concept of supramolecular inclusion complex, we successfully fabricate metformin (Met)-based supramolecular nanodrugs with the Abeta-responsive on-demand drug release for synergistic Alzheimer"s disease (AD) therapy via enhancing microglial Abeta clearance.	Metformin	93-102	amyloid beta precursor protein	Homo sapiens	263-268
34990878-6	2022	In details, metformin plus exercise ameliorated the abnormal metabolic status and cartilage lesions, significantly increased aggrecan and collagen-II expression and decreased the expression of ADAMTS-4.	Metformin	12-21	a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 4	Mus musculus	193-201
35450869-8	2022	After adjusting for HbA1c, time <3 mmol/L was 2.1 (95% CI 0.9 to 4.7) and 5.5 (95% CI 2.4 to 12.6) times greater with sulphonylurea and insulin, respectively, than metformin alone.	Metformin	164-173	insulin	Homo sapiens	136-143
35351535-2	2022	Metformin sensitizes body cells to insulin, which may cause a reduction of atherogenic lipid fractions.	Metformin	0-9	insulin	Homo sapiens	35-42
35351535-8	2022	After 24-weeks, metformin therapy for the intervention group resulted in a significant decrease of HbA1c, CRP, UACR, total cholesterol and CIMT while Nrg-4 levels were increased compared with baseline levels (p<0.001) and with placebo group(p<0.001).	Metformin	16-25	C-reactive protein	Homo sapiens	106-109
35149444-6	2022	Of these, metformin, an insulin sensitizer used as oral hypoglycemic agent, is gaining popularity.	Metformin	10-19	insulin	Homo sapiens	24-31
35503642-9	2022	Recent literature highlights the positive effects of metformin, an insulin sensitizing drug that reduces the insulin proliferative stimulus on the endometrium.	Metformin	53-62	insulin	Homo sapiens	67-74
35503642-9	2022	Recent literature highlights the positive effects of metformin, an insulin sensitizing drug that reduces the insulin proliferative stimulus on the endometrium.	Metformin	53-62	insulin	Homo sapiens	109-116
35409282-0	2022	Metformin Treatment Regulates the Expression of Molecules Involved in Adiponectin and Insulin Signaling Pathways in Endometria from Women with Obesity-Associated Insulin Resistance and PCOS.	Metformin	0-9	adiponectin, C1Q and collagen domain containing	Homo sapiens	70-81
35431970-7	2022	Metformin significantly inhibited the IR-induced elevation of tumor necrosis factor-alpha in liver and heart tissue.	Metformin	0-9	tumor necrosis factor	Rattus norvegicus	62-89
35414608-0	2022	Metformin improves renal injury of MRL/lpr lupus-prone mice via the AMPK/STAT3 pathway.	Metformin	0-9	signal transducer and activator of transcription 3	Mus musculus	73-78
35414608-11	2022	Metformin administration decreased renal expression of necroptosis markers p-RIPK1 (phosphorylated receptor-interacting protein kinase 1) and p-MLKL, along with tubular injury marker KIM-1 (kidney injury molecule-1) in lupus mice.	Metformin	0-9	receptor (TNFRSF)-interacting serine-threonine kinase 1	Mus musculus	77-82
35414608-12	2022	In addition, metformin alleviated the necroptosis of HK-2 cells stimulated by LPS and TNF-alpha, evidencing by a decrease in the expression of necroptosis markers p-RIPK1, p-RIPK3 and p-MLKL, and the inflammasome-related markers NLRP3 (NLR family pyrin domain containing 3), ASC (apoptosis-associated speck-like protein containing a CARD), caspase-1.	Metformin	13-22	tumor necrosis factor	Mus musculus	86-95
35414608-12	2022	In addition, metformin alleviated the necroptosis of HK-2 cells stimulated by LPS and TNF-alpha, evidencing by a decrease in the expression of necroptosis markers p-RIPK1, p-RIPK3 and p-MLKL, and the inflammasome-related markers NLRP3 (NLR family pyrin domain containing 3), ASC (apoptosis-associated speck-like protein containing a CARD), caspase-1.	Metformin	13-22	receptor (TNFRSF)-interacting serine-threonine kinase 1	Mus musculus	165-170
35414608-12	2022	In addition, metformin alleviated the necroptosis of HK-2 cells stimulated by LPS and TNF-alpha, evidencing by a decrease in the expression of necroptosis markers p-RIPK1, p-RIPK3 and p-MLKL, and the inflammasome-related markers NLRP3 (NLR family pyrin domain containing 3), ASC (apoptosis-associated speck-like protein containing a CARD), caspase-1.	Metformin	13-22	PYD and CARD domain containing	Mus musculus	275-278
35414608-12	2022	In addition, metformin alleviated the necroptosis of HK-2 cells stimulated by LPS and TNF-alpha, evidencing by a decrease in the expression of necroptosis markers p-RIPK1, p-RIPK3 and p-MLKL, and the inflammasome-related markers NLRP3 (NLR family pyrin domain containing 3), ASC (apoptosis-associated speck-like protein containing a CARD), caspase-1.	Metformin	13-22	PYD and CARD domain containing	Mus musculus	280-337
35414608-13	2022	Mechanistically, metformin treatment upregulated p-AMPK (phosphorylated AMP-activated protein kinase) and downregulated p-STAT3 (phosphorylated signal transducer and activator of transcription 3) expression in the kidneys.	Metformin	17-26	signal transducer and activator of transcription 3	Mus musculus	122-127
35414608-13	2022	Mechanistically, metformin treatment upregulated p-AMPK (phosphorylated AMP-activated protein kinase) and downregulated p-STAT3 (phosphorylated signal transducer and activator of transcription 3) expression in the kidneys.	Metformin	17-26	signal transducer and activator of transcription 3	Mus musculus	144-194
35414608-14	2022	Moreover, AMPKalpha2 knockdown abolished the protective effects of metformin in vitro.	Metformin	67-76	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	10-20
35414608-15	2022	CONCLUSIONS: Metformin alleviated kidney injury in LN though suppressing renal necroptosis and inflammation via the AMPK/STAT3 pathway.	Metformin	13-22	signal transducer and activator of transcription 3	Mus musculus	121-126
35067907-6	2022	The exact action mechanism behind the glucose-lowering effect of metformin is not clear, but, presumably, metformin utilizes a broad spectrum of molecular mechanisms to control blood glucose including decreasing intestinal glucose absorption, inhibition of the hepatic gluconeogenesis, decreasing insulin resistance, etc.	Metformin	65-74	insulin	Homo sapiens	297-304
35067907-6	2022	The exact action mechanism behind the glucose-lowering effect of metformin is not clear, but, presumably, metformin utilizes a broad spectrum of molecular mechanisms to control blood glucose including decreasing intestinal glucose absorption, inhibition of the hepatic gluconeogenesis, decreasing insulin resistance, etc.	Metformin	106-115	insulin	Homo sapiens	297-304
35409282-0	2022	Metformin Treatment Regulates the Expression of Molecules Involved in Adiponectin and Insulin Signaling Pathways in Endometria from Women with Obesity-Associated Insulin Resistance and PCOS.	Metformin	0-9	insulin	Homo sapiens	86-93
35409282-0	2022	Metformin Treatment Regulates the Expression of Molecules Involved in Adiponectin and Insulin Signaling Pathways in Endometria from Women with Obesity-Associated Insulin Resistance and PCOS.	Metformin	0-9	insulin	Homo sapiens	162-169
35409282-3	2022	Metformin (MTF) treatment improves insulin signaling in endometrial tissues, but its mechanism is not fully understood.	Metformin	0-9	insulin	Homo sapiens	35-42
35409282-3	2022	Metformin (MTF) treatment improves insulin signaling in endometrial tissues, but its mechanism is not fully understood.	Metformin	11-14	insulin	Homo sapiens	35-42
35433698-7	2022	Furthermore, the biguanide diabetes drug metformin, treatment with which enhances autophagy via AMPK-mediated mTOR inactivation, has been reported to reduce the risk of EC.	Metformin	41-50	mechanistic target of rapamycin kinase	Homo sapiens	110-114
35387358-0	2022	Metformin Protects against Spinal Cord Injury and Cell Pyroptosis via AMPK/NLRP3 Inflammasome Pathway.	Metformin	0-9	NLR family, pyrin domain containing 3	Rattus norvegicus	75-80
35344814-4	2022	Metformin upregulated BAX activation with facilitation of BIM, BAD and PUMA; downregulated Bcl-2 and Bcl-xl, but did not affect Mcl-1.	Metformin	0-9	B cell leukemia/lymphoma 2	Mus musculus	91-96
35392573-0	2022	Metformin Protects Against Diabetes-Induced Cognitive Dysfunction by Inhibiting Mitochondrial Fission Protein DRP1.	Metformin	0-9	dynamin 1-like	Mus musculus	110-114
35387349-0	2022	Metformin Promotes Differentiation and Attenuates H2O2-Induced Oxidative Damage of Osteoblasts via the PI3K/AKT/Nrf2/HO-1 Pathway.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	108-111
35387349-0	2022	Metformin Promotes Differentiation and Attenuates H2O2-Induced Oxidative Damage of Osteoblasts via the PI3K/AKT/Nrf2/HO-1 Pathway.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	112-116
35387349-5	2022	The PI3K/AKT signaling pathway was revealed to play an essential role in the metformin-induced osteogenic process, as shown by RNA sequencing.	Metformin	77-86	AKT serine/threonine kinase 1	Homo sapiens	9-12
35387349-6	2022	We added LY294002 to inhibit the PI3K/AKT pathway, and the results indicated that the osteogenic effect of metformin was also blocked.	Metformin	107-116	AKT serine/threonine kinase 1	Homo sapiens	38-41
35387349-9	2022	Antioxidative Nrf2/HO-1 pathway, regarded as the downstream of PI3K/AKT pathway, was modulated by metformin in the protective process.	Metformin	98-107	NFE2 like bZIP transcription factor 2	Homo sapiens	14-18
35387349-9	2022	Antioxidative Nrf2/HO-1 pathway, regarded as the downstream of PI3K/AKT pathway, was modulated by metformin in the protective process.	Metformin	98-107	AKT serine/threonine kinase 1	Homo sapiens	68-71
35387349-11	2022	In conclusion, our study revealed that metformin promoted osteogenic differentiation and H2O2-induced oxidative damage of osteoblasts via the PI3K/AKT/Nrf2/HO-1 pathway.	Metformin	39-48	AKT serine/threonine kinase 1	Homo sapiens	147-150
35387349-11	2022	In conclusion, our study revealed that metformin promoted osteogenic differentiation and H2O2-induced oxidative damage of osteoblasts via the PI3K/AKT/Nrf2/HO-1 pathway.	Metformin	39-48	NFE2 like bZIP transcription factor 2	Homo sapiens	151-155
35306537-4	2022	Levels of phosphorylated IkBalpha and p65 significantly rose in mdx/mTR-/- dystrophic hearts and Wt1 expression declined in the epicardium of mdx/mTR-/- mice when nuclear factor kappaB (NF-kappaB) and inflammation were inhibited by metformin.	Metformin	232-241	nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha	Mus musculus	25-33
35306537-7	2022	Our study demonstrates that upregulation of Wt1 in epicardial cells contributes to fibrosis in dystrophic hearts and metformin-mediated inhibition of NF-kappaB can ameliorate the pathology, and thus showing clinical potential for dystrophic cardiomyopathy.	Metformin	117-126	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	150-159
35426808-0	2022	(Metformin and lipopolysaccharide regulate transcription of NFATc2 gene via the transcription factor RUNX2).	Metformin	1-10	RUNX family transcription factor 2	Homo sapiens	101-106
35337178-0	2022	Metformin Enhances TKI-Afatinib Cytotoxic Effect, Causing Downregulation of Glycolysis, Epithelial-Mesenchymal Transition, and EGFR-Signaling Pathway Activation in Lung Cancer Cells.	Metformin	0-9	epidermal growth factor receptor	Homo sapiens	127-131
35426808-11	2022	The mutation in the RUNX2 binding site on pGL3-1651 bp obviously reduced metformin- and LPS-induced enhancement of pGL3-1651bp transcription by 1.7 and 2 folds, respectively.	Metformin	73-82	RUNX family transcription factor 2	Homo sapiens	20-25
35426808-12	2022	CONCLUSION: pGL3-NFATc2-promoter can be transcribed and activated in 293F cells, and LPS and metformin can activate the transcription of pGL3- NFATc2-promoter in a RUNX2-dependent manner.	Metformin	93-102	RUNX family transcription factor 2	Homo sapiens	164-169
35345424-0	2022	Effects of Low-Dose Spironolactone Combined with Metformin or Either Drug Alone on Insulin Resistance in Patients with Polycystic Ovary Syndrome: A Pilot Study.	Metformin	49-58	insulin	Homo sapiens	83-90
35345424-2	2022	To compare the effects and safety of low-dose spironolactone combined with metformin or either drug alone on insulin resistance (IR) and functional improvement in patients with PCOS, this was a single-center, randomized, open-label, pilot study of patients with PCOS at the Third Affiliated Hospital of Guangzhou Medical University between 01/2014 and 01/2016.	Metformin	75-84	insulin	Homo sapiens	109-116
35328696-6	2022	After induction in an induction medium supplemented with metformin, Western blot and immunofluorescence results showed that GMSCs differentiated into neuron-like cells with a significantly enhanced expression of neuro-related markers, including Nestin (NES) and beta-Tubulin (TUJ1).	Metformin	57-66	nestin	Homo sapiens	245-251
35328696-6	2022	After induction in an induction medium supplemented with metformin, Western blot and immunofluorescence results showed that GMSCs differentiated into neuron-like cells with a significantly enhanced expression of neuro-related markers, including Nestin (NES) and beta-Tubulin (TUJ1).	Metformin	57-66	nestin	Homo sapiens	253-256
35328696-7	2022	Proteomics was used to construct protein profiles in neural differentiation, and the results showed that chitosan hydrogels containing metformin promoted the upregulation of neural regeneration-related proteins, including ATP5F1, ATP5J, NADH dehydrogenase (ubiquinone) Fe-S protein 3 (NDUFS3), and Glutamate Dehydrogenase 1 (GLUD1).	Metformin	135-144	ATP synthase peripheral stalk subunit F6	Homo sapiens	230-235
35326689-0	2022	In Vivo and In Vitro Enhanced Tumoricidal Effects of Metformin, Active Vitamin D3, and 5-Fluorouracil Triple Therapy against Colon Cancer by Modulating the PI3K/Akt/PTEN/mTOR Network.	Metformin	53-62	AKT serine/threonine kinase 1	Homo sapiens	161-164
35326689-0	2022	In Vivo and In Vitro Enhanced Tumoricidal Effects of Metformin, Active Vitamin D3, and 5-Fluorouracil Triple Therapy against Colon Cancer by Modulating the PI3K/Akt/PTEN/mTOR Network.	Metformin	53-62	mechanistic target of rapamycin kinase	Homo sapiens	170-174
35264157-12	2022	Further study showed that metformin blocked the cells in G1 phase by inducing phosphorylated YAP1 and reducing the expression of cyclin D1, CDK6, CDK4 and RB, which enhanced the chemosensitivity of cisplatin and activated the expression of cleaved caspase 3 in TGCTs.	Metformin	26-35	cyclin dependent kinase 6	Homo sapiens	140-144
35370636-12	2022	Notably, our data showed that the regulative effects of FPS, both in vivo and in vitro, on the key signaling molecules, such as p-AMPK and p-raptor, in the AMPK/mTORC1/NLRP3 signaling axis were superior to those of RAP, but similar to those of metformin, an AMPK agonist, in vitro.	Metformin	244-253	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	130-134
35370636-12	2022	Notably, our data showed that the regulative effects of FPS, both in vivo and in vitro, on the key signaling molecules, such as p-AMPK and p-raptor, in the AMPK/mTORC1/NLRP3 signaling axis were superior to those of RAP, but similar to those of metformin, an AMPK agonist, in vitro.	Metformin	244-253	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	156-160
35370636-12	2022	Notably, our data showed that the regulative effects of FPS, both in vivo and in vitro, on the key signaling molecules, such as p-AMPK and p-raptor, in the AMPK/mTORC1/NLRP3 signaling axis were superior to those of RAP, but similar to those of metformin, an AMPK agonist, in vitro.	Metformin	244-253	NLR family, pyrin domain containing 3	Rattus norvegicus	168-173
35278160-0	2022	Metformin Relieves Bortezomib-Induced Neuropathic Pain by Regulating AMPKa2-Mediated Autophagy in the Spinal Dorsal Horn.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	69-75
35278160-5	2022	BTZ treatment also reduced the expression of AMPKa2 in the dorsal horn, which was recovered by metformin treatment.	Metformin	95-104	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	45-51
35278160-10	2022	Our findings suggest that metformin may regulate AMPKa2-mediated autophagy in the dorsal horn and alleviate the behavioral hypersensitivity induced by BTZ.	Metformin	26-35	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	49-55
35264157-12	2022	Further study showed that metformin blocked the cells in G1 phase by inducing phosphorylated YAP1 and reducing the expression of cyclin D1, CDK6, CDK4 and RB, which enhanced the chemosensitivity of cisplatin and activated the expression of cleaved caspase 3 in TGCTs.	Metformin	26-35	caspase 3	Homo sapiens	248-257
35399475-0	2022	Frequency of Vitamin B12 Deficiency in Type 2 Diabetic Patients Taking Metformin.	Metformin	71-80	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	21-24
35399475-2	2022	Vitamin B12 malabsorption is one of the reported side effects of metformin.	Metformin	65-74	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	8-11
35399475-3	2022	Our study aims to assess the correlation of B12 deficiency in type 2 diabetics using metformin for their treatment.	Metformin	85-94	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	44-47
35399475-9	2022	Serum vitamin B12 levels were found to be declining with the increasing duration of metformin use (p-value: <0.0001).	Metformin	84-93	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	14-17
35399475-10	2022	Conclusion Our study found a significant effect of vitamin B12 deficiency in metformin-treated patients.	Metformin	77-86	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	59-62
35399475-11	2022	Therefore, it is prudent to recognize B12 deficiency as a potential side effect of long-term use of metformin.	Metformin	100-109	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	38-41
35249270-2	2022	Metformin is one of the oral medications typically used in type 2 diabetes mellitus to reduce insulin resistance.	Metformin	0-9	insulin	Homo sapiens	94-101
35249270-3	2022	We aimed to examine the effect of metformin on glycemic indices and insulin daily dosage in adolescents with T1DM.	Metformin	34-43	insulin	Homo sapiens	68-75
35249270-9	2022	RESULTS: The HbA1c level (p<0.001) and insulin dosage (p=0.04) were lower in the metformin group than in the placebo group after nine months.	Metformin	81-90	insulin	Homo sapiens	39-46
35249270-13	2022	CONCLUSIONS: Adjunctive metformin therapy reduces insulin dosage by inhibiting insulin resistance and weight gain.	Metformin	24-33	insulin	Homo sapiens	50-57
35249270-13	2022	CONCLUSIONS: Adjunctive metformin therapy reduces insulin dosage by inhibiting insulin resistance and weight gain.	Metformin	24-33	insulin	Homo sapiens	79-86
35131865-0	2022	The anti-diabetic drug metformin regulates voltage-gated sodium channel NaV1.7 via the ubiquitin-ligase NEDD4-2.	Metformin	23-32	sodium channel, voltage-gated, type IX, alpha	Mus musculus	72-78
35131865-7	2022	In mouse dorsal root ganglion (DRG) neurons, without changing the biophysical properties of Nav1.7, metformin significantly decreased Nav1.7 current densities, but not in Nedd4L knockout mice (SNS-Nedd4L-/- ).	Metformin	100-109	sodium channel, voltage-gated, type IX, alpha	Mus musculus	134-140
35131865-12	2022	We found that metformin acts through the activity of the E3-ubiquitin ligase NEDD4-2 to reduce cell surface expression and currents of voltage gated sodium channels (Navs), especially the Nav1.7 isoform.	Metformin	14-23	sodium channel, voltage-gated, type IX, alpha	Mus musculus	188-194
35241650-7	2022	Our findings identify AMPKalpha1-mediated mechanisms of intestine-BAT communication that may partially underlie the therapeutic effects of metformin.	Metformin	139-148	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	22-32
35434034-0	2022	Metformin reverses tamoxifen resistance through the lncRNA GAS5-medicated mTOR pathway in breast cancer.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	74-78
35434034-9	2022	Metformin had no significant effect on MCF-7R cells with lncRNA GAS5 knockdown but contrarily activated p-mTOR.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	106-110
35236827-0	2022	Metformin suppresses the growth of colorectal cancer by targeting INHBA to inhibit TGF-beta/PI3K/AKT signaling transduction.	Metformin	0-9	inhibin subunit beta A	Homo sapiens	66-71
35236827-0	2022	Metformin suppresses the growth of colorectal cancer by targeting INHBA to inhibit TGF-beta/PI3K/AKT signaling transduction.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	97-100
35236827-2	2022	Here, we revealed that metformin specifically suppressed the proliferation of CRC cells by causing G1/S arrest, and INHBA is a potential target for metformin to play an anti-proliferation effect in CRC.	Metformin	23-32	inhibin subunit beta A	Homo sapiens	116-121
35236827-2	2022	Here, we revealed that metformin specifically suppressed the proliferation of CRC cells by causing G1/S arrest, and INHBA is a potential target for metformin to play an anti-proliferation effect in CRC.	Metformin	148-157	inhibin subunit beta A	Homo sapiens	116-121
35236827-6	2022	In mechanism, INHBA is an important ligand of TGF-beta signaling and metformin blocked the activation of TGF-beta signaling by targeting INHBA, and then down-regulated the activity of PI3K/Akt pathway, leading to the reduction of cyclinD1 and cell cycle arrest.	Metformin	69-78	inhibin subunit beta A	Homo sapiens	14-19
35236827-6	2022	In mechanism, INHBA is an important ligand of TGF-beta signaling and metformin blocked the activation of TGF-beta signaling by targeting INHBA, and then down-regulated the activity of PI3K/Akt pathway, leading to the reduction of cyclinD1 and cell cycle arrest.	Metformin	69-78	inhibin subunit beta A	Homo sapiens	137-142
35236827-6	2022	In mechanism, INHBA is an important ligand of TGF-beta signaling and metformin blocked the activation of TGF-beta signaling by targeting INHBA, and then down-regulated the activity of PI3K/Akt pathway, leading to the reduction of cyclinD1 and cell cycle arrest.	Metformin	69-78	AKT serine/threonine kinase 1	Homo sapiens	189-192
35236827-7	2022	Together, these findings indicate that metformin down-regulates the expression of INHBA, then attenuating TGF-beta/PI3K/Akt signaling transduction, thus inhibiting the proliferation of CRC.	Metformin	39-48	inhibin subunit beta A	Homo sapiens	82-87
35236827-7	2022	Together, these findings indicate that metformin down-regulates the expression of INHBA, then attenuating TGF-beta/PI3K/Akt signaling transduction, thus inhibiting the proliferation of CRC.	Metformin	39-48	AKT serine/threonine kinase 1	Homo sapiens	120-123
35134385-4	2022	Metformin is a biguanide and the most commonly prescribed medication for type 2 diabetes Due to its pleiotropic properties, metformin"s potential disease-modifying effects are widely studied on different pathophysiological plyers of AD such as amyloid-beta (Abeta) production and clearance, tau phosphorylation, and neuroinflammation, in relevant in vitro and in vivo models.	Metformin	0-9	amyloid beta precursor protein	Homo sapiens	244-256
35134385-4	2022	Metformin is a biguanide and the most commonly prescribed medication for type 2 diabetes Due to its pleiotropic properties, metformin"s potential disease-modifying effects are widely studied on different pathophysiological plyers of AD such as amyloid-beta (Abeta) production and clearance, tau phosphorylation, and neuroinflammation, in relevant in vitro and in vivo models.	Metformin	0-9	amyloid beta precursor protein	Homo sapiens	258-263
35134385-4	2022	Metformin is a biguanide and the most commonly prescribed medication for type 2 diabetes Due to its pleiotropic properties, metformin"s potential disease-modifying effects are widely studied on different pathophysiological plyers of AD such as amyloid-beta (Abeta) production and clearance, tau phosphorylation, and neuroinflammation, in relevant in vitro and in vivo models.	Metformin	124-133	amyloid beta precursor protein	Homo sapiens	244-256
35134385-4	2022	Metformin is a biguanide and the most commonly prescribed medication for type 2 diabetes Due to its pleiotropic properties, metformin"s potential disease-modifying effects are widely studied on different pathophysiological plyers of AD such as amyloid-beta (Abeta) production and clearance, tau phosphorylation, and neuroinflammation, in relevant in vitro and in vivo models.	Metformin	124-133	amyloid beta precursor protein	Homo sapiens	258-263
35114355-4	2022	We further showed that metformin enhanced expression of lgg-1, daf-16, skn-1 and other genes known to regulate autophagy, longevity and oxidative stress in hSOD1 transgenic worms.	Metformin	23-32	Protein lgg-1	Caenorhabditis elegans	56-61
35114355-4	2022	We further showed that metformin enhanced expression of lgg-1, daf-16, skn-1 and other genes known to regulate autophagy, longevity and oxidative stress in hSOD1 transgenic worms.	Metformin	23-32	superoxide dismutase 1	Homo sapiens	156-161
35114355-5	2022	Accordingly, overexpression of lgg-1 or daf-16 attenuated the aging and pathological abnormalities of mutant human SOD1 worms, while genetic deletion of lgg-1 or daf-16 abolished the beneficial effects of metformin.	Metformin	205-214	superoxide dismutase 1	Homo sapiens	115-119
35114355-5	2022	Accordingly, overexpression of lgg-1 or daf-16 attenuated the aging and pathological abnormalities of mutant human SOD1 worms, while genetic deletion of lgg-1 or daf-16 abolished the beneficial effects of metformin.	Metformin	205-214	Protein lgg-1	Caenorhabditis elegans	153-158
35114355-6	2022	Collectively, we demonstrate that metformin protects against mutant SOD1-induced cytotoxicity in part through enhancement of autophagy and extends lifespan through daf-16 pathway.	Metformin	34-43	superoxide dismutase 1	Homo sapiens	68-72
35217236-0	2022	Sitagliptin/metformin improves the fertilization rate and embryo quality in polycystic ovary syndrome patients through increasing the expression of GDF9 and BMP15: A new alternative to metformin (a randomized trial).	Metformin	12-21	bone morphogenetic protein 15	Homo sapiens	157-162
35217236-9	2022	The mRNA expression and protein levels of GDF9 and BMP15 in the cumulus cells increased significantly in the sitaformin compared to metformin and sitagliptin groups.	Metformin	132-141	bone morphogenetic protein 15	Homo sapiens	51-56
35217236-11	2022	Sitaformin improves levels of GDF9 and BMP15 in PCOS compared to metformin and sitagliptin, which can increase the rate of fertilization and grade I embryos.	Metformin	65-74	bone morphogenetic protein 15	Homo sapiens	39-44
35203060-0	2022	Metformin alleviates chronic obstructive pulmonary disease and cigarette smoke extract-induced glucocorticoid resistance by activating the nuclear factor E2-related factor 2/heme oxygenase-1 signaling pathway.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	139-173
34380878-9	2022	The study also revealed that cognition-enhancing effects of metformin in aged animals were associated with the activation of the energy regulator adenosine monophosphate-activated protein kinase, diminished neuroinflammation, inhibition of the mammalian target of rapamycin signaling, and augmented autophagy in the hippocampus.	Metformin	60-69	mechanistic target of rapamycin kinase	Homo sapiens	244-273
35269852-3	2022	The insulin sensitizer metformin, one of the most prescribed oral antidiabetic drugs, has been suggested to function as an antitumoral agent, based on epidemiological and retrospective clinical data as well as preclinical studies showing an antiproliferative effect in cultured breast cancer cells and animal models.	Metformin	23-32	insulin	Homo sapiens	4-11
35228471-0	2022	Metformin ameliorates polycystic ovary syndrome in a rat model by decreasing excessive autophagy in ovarian granulosa cells via the PI3K/AKT/mTOR pathway.	Metformin	0-9	AKT serine/threonine kinase 1	Rattus norvegicus	137-140
35228471-5	2022	In the present study, we first treated a letrozole-induced PCOS rat model with metformin, detected the pathological recovery of PCOS, and then assessed the effects of metformin on H2O2-induced autophagy in ovarian granulosa cells (GCs) by detecting the level of oxidative stress and the expression of autophagy-associated proteins and key proteins in the PI3K/AKT/mTOR pathway.	Metformin	167-176	AKT serine/threonine kinase 1	Rattus norvegicus	360-363
35228471-6	2022	We demonstrated that metformin ameliorated PCOS in a rat model by downregulating autophagy in GCs, and metformin decreased the levels of oxidative stress and autophagy in H2O2-induced GCs and affected the PI3K/AKT/mTOR signaling pathway.	Metformin	21-30	AKT serine/threonine kinase 1	Rattus norvegicus	210-213
35228471-6	2022	We demonstrated that metformin ameliorated PCOS in a rat model by downregulating autophagy in GCs, and metformin decreased the levels of oxidative stress and autophagy in H2O2-induced GCs and affected the PI3K/AKT/mTOR signaling pathway.	Metformin	103-112	AKT serine/threonine kinase 1	Rattus norvegicus	210-213
35228471-7	2022	Taken together, our results indicate that metformin ameliorates PCOS in a rat model by decreasing excessive autophagy in GCs via the PI3K/AKT/mTOR pathway, and this study provides evidence for targeted reduction of excessive autophagy of ovarian granulosa cells and improvement of PCOS.	Metformin	42-51	AKT serine/threonine kinase 1	Rattus norvegicus	138-141
35143597-0	2022	Investigation of metformin hydrochloride-bovine serum albumin interaction by narrow-bore capillary zone electrophoresis.	Metformin	17-40	albumin	Homo sapiens	48-61
35143597-1	2022	A narrow-bore capillary (inner diameter = 2 mum) zone electrophoresis method was developed to study the interaction between metformin hydrochloride and bovine serum albumin.	Metformin	124-147	albumin	Homo sapiens	159-172
35196199-8	2022	Treatment of APOE-mice with metformin or trehalose ameliorated the loss of retinal function and reduced Bruch"s membrane thickening, enhancing LC3 and LAMP1 labeling in the ocular tissues and restoring LC3-II:LC3-I ratio to WT levels.	Metformin	28-37	apolipoprotein E	Mus musculus	13-17
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	apolipoprotein E	Homo sapiens	354-370
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	BCL2 like 1	Homo sapiens	408-414
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	BCL2 like 1	Homo sapiens	415-421
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	BCL2 like 1	Homo sapiens	423-434
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	glyceraldehyde-3-phosphate dehydrogenase	Homo sapiens	504-544
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	mechanistic target of rapamycin kinase	Homo sapiens	788-792
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	mitogen-activated protein kinase 14	Homo sapiens	1016-1022
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	mitogen-activated protein kinase 14	Homo sapiens	1023-1026
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	mitogen-activated protein kinase 14	Homo sapiens	1043-1078
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	tumor protein p53	Homo sapiens	1192-1196
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	tumor protein p53	Homo sapiens	1197-1202
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	tumor protein p53	Homo sapiens	1203-1206
35268272-9	2022	PWVcf and CRP were negatively correlated (r = 0.571) in the T2DM subjects treated with metformin in the AAA group.	Metformin	87-96	C-reactive protein	Homo sapiens	10-13
35268272-13	2022	The negative correlation between CRP and PWVcf in males with T2DM treated with metformin may indicate that metformin influences the arterial wall to decrease stiffness in subjects with AAA.	Metformin	79-88	C-reactive protein	Homo sapiens	33-36
35268272-13	2022	The negative correlation between CRP and PWVcf in males with T2DM treated with metformin may indicate that metformin influences the arterial wall to decrease stiffness in subjects with AAA.	Metformin	107-116	C-reactive protein	Homo sapiens	33-36
35434034-10	2022	Conclusions: Metformin can inhibit overactivation of the mTOR signaling pathway through upregulating lncRNA GAS5 expression, thereby inhibiting the growth and inducing the apoptosis of BC cells, providing a new clinical treatment for BC.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	57-61
35265081-6	2022	Treatment with metformin and vitamin D reduces HG-enhanced expression of TRAIL in CTLs and coherently protects 1.4E7 cells from TRAIL-mediated apoptosis.	Metformin	15-24	TNF superfamily member 10	Homo sapiens	73-78
35265081-6	2022	Treatment with metformin and vitamin D reduces HG-enhanced expression of TRAIL in CTLs and coherently protects 1.4E7 cells from TRAIL-mediated apoptosis.	Metformin	15-24	TNF superfamily member 10	Homo sapiens	128-133
35038549-7	2022	Moreover, metformin enhanced the reducing environment via further increasing the catalase activity and NAD(P)H level.	Metformin	10-19	catalase	Homo sapiens	81-89
35252207-6	2022	Currently, taking glucose sensitizing agents, including metformin, SGLT-2 inhibitor, and GLP-1 agonist, is an effective way of lowering insulin levels and controlling PDA development at the same time.	Metformin	56-65	insulin	Homo sapiens	136-143
35144596-1	2022	BACKGROUND: The current study was to evaluate the effects of canagliflozin and metformin on insulin resistance and visceral adipose tissue in people with newly-diagnosed type 2 diabetes.	Metformin	79-88	insulin	Homo sapiens	92-99
35222283-0	2022	Metformin Downregulates the Expression of Epidermal Growth Factor Receptor Independent of Lowering Blood Glucose in Oral Squamous Cell Carcinoma.	Metformin	0-9	epidermal growth factor receptor	Homo sapiens	42-74
35222283-5	2022	The patients were divided into groups according to whether they were taking metformin for the treatment of T2DM, and the expression of EGFR in different groups was compared.	Metformin	76-85	epidermal growth factor receptor	Homo sapiens	135-139
35222283-9	2022	Results: EGFR expression in T2DM patients with OSCC taking metformin was significantly lower than that in the non-metformin group.	Metformin	59-68	epidermal growth factor receptor	Homo sapiens	9-13
35222283-11	2022	In patients with recurrent OSCC with normal blood glucose, metformin remarkably reduced the expression of EGFR in recurrent OSCC tissues.	Metformin	59-68	epidermal growth factor receptor	Homo sapiens	106-110
35222283-12	2022	Conclusion: Metformin may regulate the expression of EGFR in a way that does not rely on lowering blood glucose.	Metformin	12-21	epidermal growth factor receptor	Homo sapiens	53-57
35038311-2	2022	Although metformin promotes weight loss and improves insulin sensitivity, its effect on intrahepatic triglyceride (IHTG) remains unclear.	Metformin	9-18	insulin	Homo sapiens	53-60
35038311-6	2022	RESULTS: Twelve weeks treatment with metformin resulted in a significant reduction in body weight and improved insulin sensitivity, but IHTG content and FA oxidation remained unchanged.	Metformin	37-46	insulin	Homo sapiens	111-118
35038311-9	2022	CONCLUSIONS: We demonstrate the mechanisms of action of metformin whereby it improves insulin sensitivity and promotes weight loss, without improvement in IHTG; these observations are partly, explained through increased hepatic DNL and a lack of change in fatty acid oxidation.	Metformin	56-65	insulin	Homo sapiens	86-93
35125086-8	2022	Coadministration of nimbolide with metformin and the chemotherapeutic drugs tamoxifen/cisplatin displayed higher efficacy than single agents in inhibiting IGF-1/PI3K/Akt/AR signaling.	Metformin	35-44	insulin like growth factor 1	Homo sapiens	155-160
35125086-8	2022	Coadministration of nimbolide with metformin and the chemotherapeutic drugs tamoxifen/cisplatin displayed higher efficacy than single agents in inhibiting IGF-1/PI3K/Akt/AR signaling.	Metformin	35-44	AKT serine/threonine kinase 1	Homo sapiens	166-169
35125086-8	2022	Coadministration of nimbolide with metformin and the chemotherapeutic drugs tamoxifen/cisplatin displayed higher efficacy than single agents in inhibiting IGF-1/PI3K/Akt/AR signaling.	Metformin	35-44	aldo-keto reductase family 1 member B	Homo sapiens	170-172
35044756-4	2022	In the mouse model, combined treatment (50 and 100 mg/kg metformin + anthocyanin groups) demonstrated synergistic restorative effects on the blood glucose level, insulin resistance, and organ damage in the liver, pancreas, and ileum.	Metformin	57-66	insulin	Homo sapiens	162-169
35044756-5	2022	Additionally, combined metformin and anthocyanin treatment suppressed protein tyrosine phosphatase 1B expression and regulated the PI3K/AKT/GSK3beta pathway.	Metformin	23-32	AKT serine/threonine kinase 1	Homo sapiens	136-139
35164292-11	2022	Prostatic expression of the mRNA of pro-inflammatory cytokines IL-6, IL1beta and TNF-alpha was down-regulated in metformin- and C. speciosus-treated rats.	Metformin	113-122	interleukin 1 alpha	Rattus norvegicus	69-76
35164292-11	2022	Prostatic expression of the mRNA of pro-inflammatory cytokines IL-6, IL1beta and TNF-alpha was down-regulated in metformin- and C. speciosus-treated rats.	Metformin	113-122	tumor necrosis factor	Rattus norvegicus	81-90
35164292-12	2022	The histological structure of the ventral prostate was preserved in metformin- and C. speciosus-treated diabetic rats with a significantly thicker epithelial cell layer and significant increase immunoexpression in Bcl-2 and Ki67.	Metformin	68-77	BCL2, apoptosis regulator	Rattus norvegicus	214-219
35139776-1	2022	As one of the most frequently prescribed antidiabetic drugs, metformin can lower glucose levels, improve insulin resistance manage body weight.	Metformin	61-70	insulin	Homo sapiens	105-112
35139776-5	2022	By activating farnesoid X receptor (FXR), metformin increases the expression of vascular endothelial growth factor-A (VEGF-A) and endothelial nitric oxide synthase (eNOS), improves the production of nitric oxide (NO) and decreases the production of ROS.	Metformin	42-51	vascular endothelial growth factor A	Homo sapiens	80-116
35139776-5	2022	By activating farnesoid X receptor (FXR), metformin increases the expression of vascular endothelial growth factor-A (VEGF-A) and endothelial nitric oxide synthase (eNOS), improves the production of nitric oxide (NO) and decreases the production of ROS.	Metformin	42-51	vascular endothelial growth factor A	Homo sapiens	118-124
35139776-5	2022	By activating farnesoid X receptor (FXR), metformin increases the expression of vascular endothelial growth factor-A (VEGF-A) and endothelial nitric oxide synthase (eNOS), improves the production of nitric oxide (NO) and decreases the production of ROS.	Metformin	42-51	nitric oxide synthase 3	Homo sapiens	130-163
35139776-5	2022	By activating farnesoid X receptor (FXR), metformin increases the expression of vascular endothelial growth factor-A (VEGF-A) and endothelial nitric oxide synthase (eNOS), improves the production of nitric oxide (NO) and decreases the production of ROS.	Metformin	42-51	nitric oxide synthase 3	Homo sapiens	165-169
35139776-7	2022	Thus, metformin appears to regulate islet microvascular endothelial cell (IMEC) proliferation, apoptosis and oxidative stress by activating the FXR/VEGF-A/eNOS pathway.	Metformin	6-15	vascular endothelial growth factor A	Homo sapiens	148-154
35139776-7	2022	Thus, metformin appears to regulate islet microvascular endothelial cell (IMEC) proliferation, apoptosis and oxidative stress by activating the FXR/VEGF-A/eNOS pathway.	Metformin	6-15	nitric oxide synthase 3	Homo sapiens	155-159
35156512-10	2022	Metformin notably reversed the decreased phosphorylated AMP-activated protein kinase (p-AMPK) and PGC-1alpha expressions in the liver of septic rats.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	88-92
35156512-10	2022	Metformin notably reversed the decreased phosphorylated AMP-activated protein kinase (p-AMPK) and PGC-1alpha expressions in the liver of septic rats.	Metformin	0-9	PPARG coactivator 1 alpha	Rattus norvegicus	98-108
35156512-11	2022	Metformin also inhibited PDK1, HIF-1alpha expression, including downstream inflammatory mediators, HMGB1 and TNF-alpha.	Metformin	0-9	pyruvate dehydrogenase kinase, isoenzyme 1	Mus musculus	25-29
35156512-11	2022	Metformin also inhibited PDK1, HIF-1alpha expression, including downstream inflammatory mediators, HMGB1 and TNF-alpha.	Metformin	0-9	tumor necrosis factor	Mus musculus	109-118
35282660-11	2022	Conclusions: Metformin use was associated with a lower prevalence of vulnerable plaque features in type 2 diabetic patients with CAD, especially insulin non-user.	Metformin	13-22	insulin	Homo sapiens	145-152
35100024-9	2022	Treatment with metformin activated AMPK, which inhibited salt-induced hepatic inflammatory memory and cardiovascular damage by lowering the H3K27ac level on SIRT3 promoter, and increased NRF2 binding ability to activate SIRT3 expression.	Metformin	15-24	nuclear factor, erythroid derived 2, like 2	Mus musculus	187-191
35120288-3	2022	We investigated metformin, an insulin sensitizer, to reverse IR and improve clinical outcomes in TRBD.	Metformin	16-25	insulin	Homo sapiens	30-37
35123389-11	2022	Metformin treatment reduced RIF1 levels, and partially improved ZGA activation status by rescuing epigenetic modification remodeling in oocytes and preimplantation embryos of obese mice.	Metformin	0-9	replication timing regulatory factor 1	Mus musculus	28-32
35123389-14	2022	CONCLUSION: Elevated RIF1 in oocytes caused by maternal obesity may mediate abnormal embryonic epigenetic remodeling and increase metabolic risk in offspring by regulating histone modifications on MuERV-L, which can be partially rescued by metformin treatment.	Metformin	240-249	replication timing regulatory factor 1	Mus musculus	21-25
35179472-7	2022	For overweight patients with cardiometabolic risk factors, including insulin resistance or dysglycemia, metformin may also be combined with contraception.	Metformin	104-113	insulin	Homo sapiens	69-76
35064693-0	2022	Metformin ameliorates chronic colitis in a mouse model by regulating interferon-gamma-producing lamina propria CD4+ T cells through AMPK activation.	Metformin	0-9	interferon gamma	Mus musculus	69-85
35064693-6	2022	We observed that metformin suppresses the frequency of interferon (IFN) -gamma-producing LP CD4+ T cells in vitro, which were regulated by AMPK activation, a process possibly induced by the inhibition of oxidative phosphorylation.	Metformin	17-26	interferon gamma	Mus musculus	55-78
35064693-9	2022	Our study demonstrates that metformin-induced AMPK activation in mucosal CD4+ T cells contributes to the improvement of IBD by suppressing IFN-gamma production.	Metformin	28-37	interferon gamma	Mus musculus	139-148
35528855-5	2022	This study aims to investigate the inhibitory effect of metformin on VISTA via AHR in melanoma cells (CHL-1, B16) and animal models.	Metformin	56-65	cell adhesion molecule L1 like	Homo sapiens	102-107
34545025-0	2022	Association of SLC22A1 rs622342 and ATM rs11212617 polymorphisms with metformin efficacy in patients with type 2 diabetes.	Metformin	70-79	solute carrier family 22 member 1	Homo sapiens	15-22
34545025-9	2022	Our results indicated that common variants of SLC22A1 rs622342 and ATM rs11212617 were associated with the efficacy of metformin in T2DM of Han nationality in Chaoshan China.	Metformin	119-128	solute carrier family 22 member 1	Homo sapiens	46-53
35153733-4	2021	Evidence from clinical studies has demonstrated that metformin use contributes to a lower risk of developing AD and better cognitive performance, which might be modified by interactors such as diabetic status and APOE-epsilon4 status.	Metformin	53-62	apolipoprotein E	Homo sapiens	213-217
35153733-5	2021	Previous mechanistic studies have gradually unveiled the effects of metformin on AD pathology and pathophysiology, including neuronal loss, neural dysfunction, amyloid-beta (Abeta) depositions, tau phosphorylation, chronic neuroinflammation, insulin resistance, impaired glucose metabolism and mitochondrial dysfunction.	Metformin	68-77	amyloid beta precursor protein	Homo sapiens	160-172
35153733-5	2021	Previous mechanistic studies have gradually unveiled the effects of metformin on AD pathology and pathophysiology, including neuronal loss, neural dysfunction, amyloid-beta (Abeta) depositions, tau phosphorylation, chronic neuroinflammation, insulin resistance, impaired glucose metabolism and mitochondrial dysfunction.	Metformin	68-77	amyloid beta precursor protein	Homo sapiens	174-179
35153733-5	2021	Previous mechanistic studies have gradually unveiled the effects of metformin on AD pathology and pathophysiology, including neuronal loss, neural dysfunction, amyloid-beta (Abeta) depositions, tau phosphorylation, chronic neuroinflammation, insulin resistance, impaired glucose metabolism and mitochondrial dysfunction.	Metformin	68-77	insulin	Homo sapiens	242-249
35088363-11	2022	This study revealed that metformin upregulated the expression of IGFBP-7 in the endometrium of human and mouse models of endometriosis.	Metformin	25-34	insulin like growth factor binding protein 7	Homo sapiens	65-72
35088363-12	2022	Metformin potentially affects endometrial receptivity of minimal/mild endometriosis by improving the expression of the endometrial receptivity marker IGFBP-7.	Metformin	0-9	insulin-like growth factor binding protein 7	Mus musculus	150-157
35158846-5	2022	The pleiotropic effects of metformin are mainly exerted through the activation of AMP-activated protein kinase, which is the key cellular energy homeostasis regulator that inhibits mTOR, a major autophagy suppressor.	Metformin	27-36	mechanistic target of rapamycin kinase	Homo sapiens	181-185
35079096-6	2022	Overexpression of anti-apoptotic Bcl-2 family members decrease both metformin effects.	Metformin	68-77	BCL2 apoptosis regulator	Homo sapiens	33-38
34676406-8	2022	Furthermore, in diabetic patients, Metformin treatment was associated with lower high-sensitivity C-reactive protein levels.	Metformin	35-44	C-reactive protein	Homo sapiens	98-116
35072253-4	2022	The mechanism of the antitumor action of metformin is pleiotropic and involves several signalling pathways, including AMPK/mTOR (mitogen activated protein kinase/mammalian target rapamycin), STAT3 (signal transducer and activator of transcription) and numerous factors: NF-KB (nuclear factor kappa), HIF-1 alpha (hypoxia inducible factor 1), IGF-1 (insulin-like growth factor-1), which affect cell proliferation and apoptosis.	Metformin	41-50	mechanistic target of rapamycin kinase	Homo sapiens	123-127
35072253-4	2022	The mechanism of the antitumor action of metformin is pleiotropic and involves several signalling pathways, including AMPK/mTOR (mitogen activated protein kinase/mammalian target rapamycin), STAT3 (signal transducer and activator of transcription) and numerous factors: NF-KB (nuclear factor kappa), HIF-1 alpha (hypoxia inducible factor 1), IGF-1 (insulin-like growth factor-1), which affect cell proliferation and apoptosis.	Metformin	41-50	signal transducer and activator of transcription 3	Homo sapiens	191-196
35072253-4	2022	The mechanism of the antitumor action of metformin is pleiotropic and involves several signalling pathways, including AMPK/mTOR (mitogen activated protein kinase/mammalian target rapamycin), STAT3 (signal transducer and activator of transcription) and numerous factors: NF-KB (nuclear factor kappa), HIF-1 alpha (hypoxia inducible factor 1), IGF-1 (insulin-like growth factor-1), which affect cell proliferation and apoptosis.	Metformin	41-50	hypoxia inducible factor 1 subunit alpha	Homo sapiens	300-311
35072253-4	2022	The mechanism of the antitumor action of metformin is pleiotropic and involves several signalling pathways, including AMPK/mTOR (mitogen activated protein kinase/mammalian target rapamycin), STAT3 (signal transducer and activator of transcription) and numerous factors: NF-KB (nuclear factor kappa), HIF-1 alpha (hypoxia inducible factor 1), IGF-1 (insulin-like growth factor-1), which affect cell proliferation and apoptosis.	Metformin	41-50	insulin like growth factor 1	Homo sapiens	342-347
35072253-4	2022	The mechanism of the antitumor action of metformin is pleiotropic and involves several signalling pathways, including AMPK/mTOR (mitogen activated protein kinase/mammalian target rapamycin), STAT3 (signal transducer and activator of transcription) and numerous factors: NF-KB (nuclear factor kappa), HIF-1 alpha (hypoxia inducible factor 1), IGF-1 (insulin-like growth factor-1), which affect cell proliferation and apoptosis.	Metformin	41-50	insulin like growth factor 1	Homo sapiens	349-377
35153777-5	2022	By histopathological and immunohistochemical analyses, metformin-treated mice showed a significant alleviation in airway inflammation, and in the parameters of airway remodeling including goblet cell hyperplasia, collagen deposition and airway smooth muscle hypertrophy compared to those in the OVA-challenged mice.	Metformin	55-64	serine (or cysteine) peptidase inhibitor, clade B, member 1, pseudogene	Mus musculus	295-298
35153777-8	2022	These results indicate that metformin ameliorates airway inflammation and remodeling in an OVA-induced chronic asthmatic model and its protective role could be associated with the restoration of AMPKalpha activity and decreased asthma-related angiogenesis.	Metformin	28-37	serine (or cysteine) peptidase inhibitor, clade B, member 1, pseudogene	Mus musculus	91-94
35163187-1	2022	Metformin is the most commonly used treatment to increase insulin sensitivity in insulin-resistant (IR) conditions such as diabetes, prediabetes, polycystic ovary syndrome, and obesity.	Metformin	0-9	insulin	Homo sapiens	58-65
35163187-1	2022	Metformin is the most commonly used treatment to increase insulin sensitivity in insulin-resistant (IR) conditions such as diabetes, prediabetes, polycystic ovary syndrome, and obesity.	Metformin	0-9	insulin	Homo sapiens	81-88
35163187-6	2022	Our aim is to provide a comprehensive review of the studies in this field in order to shed some light on the complex interactions between metformin action, GLUT4 expression, GLUT4 translocation, and the observed increase in peripheral insulin sensitivity.	Metformin	138-147	insulin	Homo sapiens	235-242
35153777-6	2022	We also observed elevated levels of multiple cytokines (IL-4, IL-5, IL-13, TNF-alpha, TGF-beta1 and MMP-9) in the bronchoalveolar lavage fluid, OVA-specific IgE in the serum and angiogenesis-related factors (VEGF, SDF-1 and CXCR4) in the plasma from asthmatic mice, while metformin reduced all these parameters.	Metformin	272-281	serine (or cysteine) peptidase inhibitor, clade B, member 1, pseudogene	Mus musculus	144-147
35153777-7	2022	Additionally, the activity of 5"-adenosine monophosphate-activated protein kinase a (AMPKalpha) in the lungs from OVA-challenged mice was remarkably lower than control ones, while after metformin treatment, the ratio of p-AMPKalpha to AMPKalpha was upregulated and new blood vessels in the sub-epithelial area as evidenced by CD31 staining were effectively suppressed.	Metformin	186-195	serine (or cysteine) peptidase inhibitor, clade B, member 1, pseudogene	Mus musculus	114-117
35158754-5	2022	Furthermore, we show that metformin repressed the proliferation of MLL/AF9 AML cells by inhibiting mitochondrial respiration.	Metformin	26-35	MLLT3 super elongation complex subunit	Homo sapiens	71-74
35158754-6	2022	Together, this study demonstrates that AML cells with an MLL/AF9 genotype have a high dependency on OXPHOS and could be therapeutically targeted by metformin.	Metformin	148-157	MLLT3 super elongation complex subunit	Homo sapiens	61-64
35095535-8	2021	In conclusion, our results demonstrate that metformin does not show beneficial effects on body weight or survival time but reduced the inflammatory response in a mouse model of NPC1 when combined with HPbetaCD.	Metformin	44-53	NPC intracellular cholesterol transporter 1	Mus musculus	177-181
34841901-9	2022	FUTURE DIRECTIONS: Among strategies to inhibit the NLRP3 inflammasome, Glyburide, Metformin, PPAR agonists and the DPP-4 inhibitor saxagliptin appear to be closest to clinical translation, as these drugs are already FDA approved for other indications.	Metformin	82-91	NLR family pyrin domain containing 3	Homo sapiens	51-56
35052471-9	2022	Quantitive PCR revealed that Diane-35 and metformin decreased androgen receptor (AR) expression but elevated GLUT4 expression.	Metformin	42-51	androgen receptor	Homo sapiens	62-79
35045841-0	2022	Effectiveness and safety of basal insulin therapy in type 2 diabetes mellitus patients with or without metformin observed in a national cohort in China.	Metformin	103-112	insulin	Homo sapiens	34-41
35045841-1	2022	BACKGROUND: Though many randomized control trials had examined the effectiveness and safety of taking insulin therapy with or without metformin, there are limited real-world data, especially among Chinese type 2 diabetes patients initiating basal insulin (BI) with uncontrolled hyperglycemia by oral agents.	Metformin	134-143	insulin	Homo sapiens	102-109
35045841-9	2022	After propensity score adjustment, multivariate regression analysis controlled with number of OADs, total insulin dose, physical activity and diet consumption showed that BI with metformin group had a slightly higher control rate of HbA1c <7.0 % (39.9 % vs. 36.4 %, P = 0.0011) at 6-month follow-up, and lower dose increment from baseline to 6-month (0.0064 vs. 0.0068 U/day/kg, P = 0.0035).	Metformin	179-188	insulin	Homo sapiens	106-113
35046683-5	2022	Efforts to improve insulin sensitivity by using pharmacological agents such as metformin are insufficient in resolving this problem.	Metformin	79-88	insulin	Homo sapiens	19-26
35052471-9	2022	Quantitive PCR revealed that Diane-35 and metformin decreased androgen receptor (AR) expression but elevated GLUT4 expression.	Metformin	42-51	androgen receptor	Homo sapiens	81-83
34994666-0	2022	AMPK/mTOR-mediated therapeutic effect of metformin on myocardial ischaemia reperfusion injury in diabetic rat.	Metformin	41-50	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	0-4
34994666-9	2022	Furthermore, the increasing protein levels of LC3-II, BECLIN 1, autophagy related 5 (ATG5) and AMP-activated protein kinase suggested activated autophagy-associated intracellular signalling AMPK and mTOR pathways upon DMBG treated.	Metformin	218-222	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	190-194
34983571-1	2022	BACKGROUND: Moving from the correlation between insulin-resistance and PCOS, metformin has been administered in some PCOS women improving ovulatory and metabolic functions and decreasing androgen levels.	Metformin	77-86	insulin	Homo sapiens	48-55
35072689-14	2022	After metformin treatment, phospho-AMPK was upregulated and the morphology of MG was well maintained.	Metformin	6-15	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	35-39
34714980-3	2022	Our previous study showed that metformin protected against the pathophysiology of AAA by reducing the activation of the PI3K/AKT/mTOR pathway.	Metformin	31-40	AKT serine/threonine kinase 1	Homo sapiens	125-128
34714980-3	2022	Our previous study showed that metformin protected against the pathophysiology of AAA by reducing the activation of the PI3K/AKT/mTOR pathway.	Metformin	31-40	mechanistic target of rapamycin kinase	Homo sapiens	129-133
34714980-10	2022	The Ang-II also induced the expression of Atg7, and metformin reversed this effect both in vivo and in vitro.	Metformin	52-61	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	4-10
35181615-8	2022	CONCLUSION: By targeting the Sirt1, EZH2 and CXCR4 pathways using relatively non-toxic adjuvant therapeutic agents such as metformin, melatonin, curcumin, sulforaphane, vitamin D3 and plerixafor, we should be able to target the biology of DLBCL.	Metformin	123-132	enhancer of zeste 2 polycomb repressive complex 2 subunit	Homo sapiens	36-40
35075807-0	2022	Metformin promotes histone deacetylation of optineurin and suppresses tumour growth through autophagy inhibition in ocular melanoma.	Metformin	0-9	optineurin	Homo sapiens	44-54
35075807-7	2022	Through high-throughput proteomics analysis, we revealed that optineurin (OPTN), which is a key candidate for autophagosome formation and maturation, was significantly downregulated after metformin treatment.	Metformin	188-197	optineurin	Homo sapiens	62-72
35075807-7	2022	Through high-throughput proteomics analysis, we revealed that optineurin (OPTN), which is a key candidate for autophagosome formation and maturation, was significantly downregulated after metformin treatment.	Metformin	188-197	optineurin	Mus musculus	74-78
35075807-10	2022	CONCLUSIONS: Overall, we revealed for the first time that metformin significantly inhibited the progression of ocular melanoma, and verified that metformin acted as an autophagy inhibitor through histone deacetylation of OPTN.	Metformin	146-155	optineurin	Homo sapiens	221-225
34375188-11	2022	RESULTS: Astaxanthin and metformin have anti-obesity and antioxidant actions and significantly decreased the weight of the body, glucose, insulin, triglycerides, total cholesterol, triglycerides and leptin, as well as plasma calprotectin & IL-6 and increased HDL-C and adiponectin.	Metformin	25-34	interleukin 6	Rattus norvegicus	240-244
35145895-7	2022	Results: The results showed that all AA extracts (100, 200, and 400 mg/kg) and metformin (250 mg/kg) significantly reduced the serum levels of free fatty acids, TNF-alpha, IL-6, LDL/HDL ratio, and HOMA-IR in diabetic mice compared to untreated diabetic mice (p<0.0001).	Metformin	79-88	tumor necrosis factor	Mus musculus	161-170
35145895-7	2022	Results: The results showed that all AA extracts (100, 200, and 400 mg/kg) and metformin (250 mg/kg) significantly reduced the serum levels of free fatty acids, TNF-alpha, IL-6, LDL/HDL ratio, and HOMA-IR in diabetic mice compared to untreated diabetic mice (p<0.0001).	Metformin	79-88	interleukin 6	Mus musculus	172-176
35145895-8	2022	Notably, the 400 mg/kg dose of cold-water extract was more effective than metformin in reduction of TNF-alpha and IL-6 (p<0.01 and p<0.05, respectively).	Metformin	74-83	tumor necrosis factor	Mus musculus	100-109
35145895-8	2022	Notably, the 400 mg/kg dose of cold-water extract was more effective than metformin in reduction of TNF-alpha and IL-6 (p<0.01 and p<0.05, respectively).	Metformin	74-83	interleukin 6	Mus musculus	114-118
34919671-0	2022	Hypothalamic miR-1983 Targets Insulin Receptor beta and the Insulin-mediated miR-1983 Increase Is Blocked by Metformin.	Metformin	109-118	microRNA 1983	Mus musculus	13-21
34919671-0	2022	Hypothalamic miR-1983 Targets Insulin Receptor beta and the Insulin-mediated miR-1983 Increase Is Blocked by Metformin.	Metformin	109-118	insulin	Homo sapiens	60-67
34919671-0	2022	Hypothalamic miR-1983 Targets Insulin Receptor beta and the Insulin-mediated miR-1983 Increase Is Blocked by Metformin.	Metformin	109-118	microRNA 1983	Mus musculus	77-85
34919671-5	2022	Levels of miR-1983 are normalized with metformin exposure in mouse hypothalamic neuronal cell culture.	Metformin	39-48	microRNA 1983	Mus musculus	10-18
33607930-1	2022	PURPOSE: To assess whether metformin is associated with dry age-related macular degeneration (dAMD) development.	Metformin	27-36	alpha methyl dopa-resistant	Drosophila melanogaster	94-98
33607930-4	2022	A time updating Cox proportional hazard regression was used to estimate the hazard ratio of dAMD incidence with metformin exposure.	Metformin	112-121	alpha methyl dopa-resistant	Drosophila melanogaster	92-96
33607930-8	2022	In the active versus prior use of metformin model, active use conferred an increased hazard of developing dAMD (HR, 1.08; 95% CI, 1.04-1.12) while prior use had a decreased hazard (HR, 0.95; 95% CI 0.92-0.98).	Metformin	34-43	alpha methyl dopa-resistant	Drosophila melanogaster	106-110
33607930-9	2022	The cumulative metformin dosage model showed a significant trend toward increased hazard of dAMD incidence with increasing cumulative dosage (p < 0.001), with the lowest dosage quartile having decreased hazard of dAMD incidence (HR, 0.95; 95% CI, 0.91-0.99) and the highest having increased hazard (HR, 1.07; 95% CI, 1.01-1.13).	Metformin	15-24	alpha methyl dopa-resistant	Drosophila melanogaster	92-96
33607930-9	2022	The cumulative metformin dosage model showed a significant trend toward increased hazard of dAMD incidence with increasing cumulative dosage (p < 0.001), with the lowest dosage quartile having decreased hazard of dAMD incidence (HR, 0.95; 95% CI, 0.91-0.99) and the highest having increased hazard (HR, 1.07; 95% CI, 1.01-1.13).	Metformin	15-24	alpha methyl dopa-resistant	Drosophila melanogaster	213-217
33607930-10	2022	CONCLUSIONS: Small, conflicting associations between metformin exposure and development of dAMD were observed depending on cumulative dosage and whether drug use was active, suggesting metformin did not substantially affect the development of dAMD.	Metformin	53-62	alpha methyl dopa-resistant	Drosophila melanogaster	91-95
33607930-10	2022	CONCLUSIONS: Small, conflicting associations between metformin exposure and development of dAMD were observed depending on cumulative dosage and whether drug use was active, suggesting metformin did not substantially affect the development of dAMD.	Metformin	185-194	alpha methyl dopa-resistant	Drosophila melanogaster	91-95
3149105-1	1988	Insulin binding to erythrocyte receptors was studied in 36 newly diagnosed male subjects with NIDDM, treated with diet alone (Group I; n = 10) or diet + glibenclamide (Group II; n = 12) or diet + glibenclamide + metformin (Group III; n = 14).	Metformin	212-221	insulin	Homo sapiens	0-7
35350904-0	2022	Plantamajoside promotes metformin-induced apoptosis, autophagy and proliferation arrest of liver cancer cells via suppressing Akt/GSK3beta signaling.	Metformin	24-33	AKT serine/threonine kinase 1	Homo sapiens	126-129
35350904-11	2022	Restoration of Akt/GSK3beta signaling by a constitutively activated myr-Akt1 abrogated the effects of PMS on metformin-treated liver cancer cells.	Metformin	109-118	AKT serine/threonine kinase 1	Homo sapiens	15-18
35350904-11	2022	Restoration of Akt/GSK3beta signaling by a constitutively activated myr-Akt1 abrogated the effects of PMS on metformin-treated liver cancer cells.	Metformin	109-118	AKT serine/threonine kinase 1	Homo sapiens	72-76
35005996-0	2022	Lasting Complete Clinical Response of a Recurring Cutaneous Squamous Cell Carcinoma With MEK Mutation and PIK3CA Amplification Achieved by Dual Trametinib and Metformin Therapy.	Metformin	159-168	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	106-112
34983210-4	2022	As a biguanide metformin improves glycemic control by inhibiting gluconeogenesis and increasing insulin-mediated glucose utilization in peripheral tissues.	Metformin	15-24	insulin	Homo sapiens	96-103
34983210-8	2022	The risk increases with renal impairment; therefore the metformin dose must be adjusted to the eGFR.	Metformin	56-65	epidermal growth factor receptor	Homo sapiens	95-99
35370738-6	2022	Conclusion: The pleiotropic actions of metformin associated with lower background cardiovascular risk may mediate some of these effects, for example reductions of insulin resistance, systemic inflammation and hypercoagulability.	Metformin	39-48	insulin	Homo sapiens	163-170
2523787-0	1989	The effects of metformin on adipocyte insulin action and metabolic control in obese subjects with type 2 diabetes.	Metformin	15-24	insulin	Homo sapiens	38-45
2648723-4	1989	Metformin treatment significantly reduced mean day-time plasma glucose levels (10.2 +/- 1.2 vs 11.4 +/- 1.2 mmol/l, P less than 0.01) without enhancing mean day-time plasma insulin (43 +/- 4 vs 50 +/- 7 mU/l, NS) or C-peptide levels (1.26 +/- 0.12 vs 1.38 +/- 0.18 nmol/l, NS).	Metformin	0-9	insulin	Homo sapiens	216-225
2648723-6	1989	The clamp study revealed that metformin treatment was associated with an enhanced insulin-mediated glucose utilization (370 +/- 38 vs 313 +/- 33 mg.m-2.min-1, P less than 0.01), whereas insulin-mediated suppression of hepatic glucose production was unchanged.	Metformin	30-39	insulin	Homo sapiens	82-89
2576469-0	1989	[Somatostatin-like activity (SLI) in the blood during metformin treatment of obese patients with diabetes mellitus type 2].	Metformin	54-63	SHC adaptor protein 2	Homo sapiens	29-32
2576469-8	1989	action of SLI secreted after metformin administration cannot be excluded.	Metformin	29-38	SHC adaptor protein 2	Homo sapiens	10-13
2702918-7	1989	Metformin, added to the usual treatment undergone by a diabetic treated with insulin, seems to affect platelet aggregation independently of other metabolic factors.	Metformin	0-9	insulin	Homo sapiens	77-84
3075902-2	1988	Metformin is an antihyperglycaemic agent which can be used to ameliorate insulin resistance.	Metformin	0-9	insulin	Homo sapiens	73-80
3075902-4	1988	Although metformin may increase insulin-receptor binding, its main effect appears to be directed at the postreceptor level of insulin action.	Metformin	9-18	insulin	Homo sapiens	32-39
34374879-8	2021	A significant interaction was found between the use of metformin and insulin in patients with T2DM (p = 0.018).	Metformin	55-64	insulin	Homo sapiens	69-76
34374879-12	2021	CONCLUSIONS: Metformin administration may be associated with reduced mortality in patients with surgically resected breast cancer, particularly in the HT+/HER2 Tx- group.	Metformin	13-22	erb-b2 receptor tyrosine kinase 2	Homo sapiens	155-159
3239906-0	1988	[Lipoatrophic diabetes with insulin resistance controlled by metformin].	Metformin	61-70	insulin	Homo sapiens	28-35
3126223-0	1987	Effects of metformin and glibenclamide on insulin receptors in fibroblasts and tumor cells in vitro.	Metformin	11-20	insulin	Homo sapiens	42-49
3126223-1	1987	The effects of the oral hypoglycemic agents metformin and glibenclamide on receptor binding of insulin and insulin-induced receptor down-regulation were studied in cultured normal human fibroblasts, human breast tumors (cell lines MCF-7 and T-47D) and a human colon tumor (cell line HCT-8) in order to identify differences in receptor regulation between normal and transformed cells.	Metformin	44-53	insulin	Homo sapiens	95-102
3126223-1	1987	The effects of the oral hypoglycemic agents metformin and glibenclamide on receptor binding of insulin and insulin-induced receptor down-regulation were studied in cultured normal human fibroblasts, human breast tumors (cell lines MCF-7 and T-47D) and a human colon tumor (cell line HCT-8) in order to identify differences in receptor regulation between normal and transformed cells.	Metformin	44-53	insulin	Homo sapiens	107-114
3126223-3	1987	Glibenclamide (2 microM) and metformin (1-10 microM) induced a 13-28% reduction in insulin receptor down regulation in fibroblasts exposed to 1.7 x 10(-8)M-insulin, the loss of binding on exposure to insulin decreasing from 55% to 40-48%.	Metformin	29-38	insulin	Homo sapiens	83-90
3126223-3	1987	Glibenclamide (2 microM) and metformin (1-10 microM) induced a 13-28% reduction in insulin receptor down regulation in fibroblasts exposed to 1.7 x 10(-8)M-insulin, the loss of binding on exposure to insulin decreasing from 55% to 40-48%.	Metformin	29-38	insulin	Homo sapiens	156-163
3329125-0	1987	[Value of combined subcutaneous infusion of insulin and metformin in 10 insulin-dependent obese diabetics].	Metformin	56-65	insulin	Homo sapiens	72-79
3745404-3	1986	In vitro exposure of rat adipose tissue to metformin for 20 h resulted in a significant increase in insulin binding (mean +/- SEM percent specific [125I]insulin bound per 10(5) adipocytes: control, 1.35 +/- 0.13; Met, 1.69 +/- 0.18; P less than 0.02).	Metformin	43-52	insulin	Homo sapiens	100-107
3115843-6	1987	Plasma insulin was lowered in obese non-diabetic subjects, without modification of the body weight, by a 24 hour fast or by treatment with Metformin.	Metformin	139-148	insulin	Homo sapiens	7-14
3115843-8	1987	Treatment for 15 days by 1.75 g Metformin (or placebo), on a weight maintaining diet, induced, in the Metformin group, a decrease in plasma insulin, triglyceride and PA Inhibitor activity and an increase in EFA, while no change was observed in the placebo group.	Metformin	32-41	insulin	Homo sapiens	140-147
3115843-8	1987	Treatment for 15 days by 1.75 g Metformin (or placebo), on a weight maintaining diet, induced, in the Metformin group, a decrease in plasma insulin, triglyceride and PA Inhibitor activity and an increase in EFA, while no change was observed in the placebo group.	Metformin	102-111	insulin	Homo sapiens	140-147
3310318-0	1987	Metformin decreases the high plasminogen activator inhibition capacity, plasma insulin and triglyceride levels in non-diabetic obese subjects.	Metformin	0-9	insulin	Homo sapiens	79-86
3817257-0	1986	Effect of metformin on peripheral insulin sensitivity in non insulin dependent diabetes mellitus.	Metformin	10-19	insulin	Homo sapiens	34-41
3817257-1	1986	To test whether metformin treatment might improve peripheral insulin sensitivity in non insulin dependent diabetes, we measured peripheral glucose uptake in 12 non insulin dependent diabetics before (A) and after 4 weeks (B) of metformin therapy (2 X 850 mg/day) by the hyperinsulinemic clamp technique (80 mU/m2/min).	Metformin	16-25	insulin	Homo sapiens	61-68
3817257-2	1986	In addition, insulin binding to monocytes was compared between A and B. Diabetic control, evaluated by measurement of fasting blood glucose and glycosylated hemoglobin, was significantly improved by metformin treatment (P less than 0.01).	Metformin	199-208	insulin	Homo sapiens	13-20
3552795-6	1987	In the basal state, metformin administration reduced plasma glucose levels from 172 +/- 14 to 103 +/- 9 mg/dl (P less than .005), hepatic glucose output (HGO) from 2.67 +/- 0.15 to 2.20 +/- 0.20 mg X kg-1 X min-1 (P less than .02), and forearm glucose uptake (FGU) from 0.106 +/- 0.18 to 0.039 +/- 0.016 mg X 100 ml-1 forearm X min-1 (P less than .005), whereas insulin (23 +/- 6 microU/ml) and lactate (1.56 +/- 0.18 mM) levels were unchanged.	Metformin	20-29	insulin	Homo sapiens	362-369
3552772-0	1987	Metformin enhances insulin binding to "in vitro" down regulated human fat cells.	Metformin	0-9	insulin	Homo sapiens	19-26
3552772-1	1987	Insulin binding to human adipose tissue from surgical patients was determined after three different preincubation conditions: a) 24 hrs in the presence or absence of 80 ng/ml insulin; b) 24 hrs in the presence of 80 ng/ml insulin or insulin plus 4 micrograms/ml metformin; c) 48 hrs pre-incubation as in b).	Metformin	262-271	insulin	Homo sapiens	0-7
3552772-2	1987	We found that insulin down regulated its own receptor after 24 hours pre-incubation; when metformin was present in the pre-incubation medium together with insulin, insulin binding to adipose tissue was significantly higher than in tissue exposed to insulin alone after 48 hrs pre-incubation; a similar effect of metformin was already seen after 24 hrs, but was not statistically significant.	Metformin	90-99	insulin	Homo sapiens	14-21
3552772-2	1987	We found that insulin down regulated its own receptor after 24 hours pre-incubation; when metformin was present in the pre-incubation medium together with insulin, insulin binding to adipose tissue was significantly higher than in tissue exposed to insulin alone after 48 hrs pre-incubation; a similar effect of metformin was already seen after 24 hrs, but was not statistically significant.	Metformin	312-321	insulin	Homo sapiens	14-21
3552772-2	1987	We found that insulin down regulated its own receptor after 24 hours pre-incubation; when metformin was present in the pre-incubation medium together with insulin, insulin binding to adipose tissue was significantly higher than in tissue exposed to insulin alone after 48 hrs pre-incubation; a similar effect of metformin was already seen after 24 hrs, but was not statistically significant.	Metformin	312-321	insulin	Homo sapiens	155-162
3552772-2	1987	We found that insulin down regulated its own receptor after 24 hours pre-incubation; when metformin was present in the pre-incubation medium together with insulin, insulin binding to adipose tissue was significantly higher than in tissue exposed to insulin alone after 48 hrs pre-incubation; a similar effect of metformin was already seen after 24 hrs, but was not statistically significant.	Metformin	312-321	insulin	Homo sapiens	155-162
3552772-2	1987	We found that insulin down regulated its own receptor after 24 hours pre-incubation; when metformin was present in the pre-incubation medium together with insulin, insulin binding to adipose tissue was significantly higher than in tissue exposed to insulin alone after 48 hrs pre-incubation; a similar effect of metformin was already seen after 24 hrs, but was not statistically significant.	Metformin	312-321	insulin	Homo sapiens	155-162
3552772-4	1987	This finding could explain discrepant results among studies dealing with the influence of metformin on insulin binding.	Metformin	90-99	insulin	Homo sapiens	103-110
3552772-5	1987	Moreover, these results could be useful in understanding the mechanism of action of metformin in insulin-resistant states, e.g. type II diabetes.	Metformin	84-93	insulin	Homo sapiens	97-104
3745404-3	1986	In vitro exposure of rat adipose tissue to metformin for 20 h resulted in a significant increase in insulin binding (mean +/- SEM percent specific [125I]insulin bound per 10(5) adipocytes: control, 1.35 +/- 0.13; Met, 1.69 +/- 0.18; P less than 0.02).	Metformin	43-52	insulin	Homo sapiens	153-160
3533670-0	1986	Effects of metformin treatment on erythrocyte insulin binding in normal weight subjects, in obese non diabetic subjects, in type 1 and type 2 diabetic patients.	Metformin	11-20	insulin	Homo sapiens	46-53
3533670-1	1986	We have evaluated the effects of metformin administration on erythrocyte insulin receptors in 21 subjects: 5 normal weight subjects, 5 obese non diabetics, 5 insulin-dependent diabetics (Type I) and 6 obese non insulin-dependent (Type II) diabetics.	Metformin	33-42	insulin	Homo sapiens	73-80
3533670-4	1986	Maximum specific insulin binding to erythrocytes increased after metformin in the normals (p less than 0.01), in the obese non diabetics (p less than 0.01) and in the obese Type 2 diabetics (p less than 0.005), but not in Type I diabetics.	Metformin	65-74	insulin	Homo sapiens	17-24
4046836-0	1985	Metformin improved insulin resistance in type I, insulin-dependent, diabetic patients.	Metformin	0-9	insulin	Homo sapiens	19-26
3552509-2	1987	The mechanism of action of metformin and other biguanides is not completely understood, but recent in vitro and in vivo studies suggest that metformin may act in part by both increasing the binding of insulin to its receptor and potentiating insulin action.	Metformin	27-36	insulin	Homo sapiens	201-208
3552509-2	1987	The mechanism of action of metformin and other biguanides is not completely understood, but recent in vitro and in vivo studies suggest that metformin may act in part by both increasing the binding of insulin to its receptor and potentiating insulin action.	Metformin	141-150	insulin	Homo sapiens	201-208
3552509-2	1987	The mechanism of action of metformin and other biguanides is not completely understood, but recent in vitro and in vivo studies suggest that metformin may act in part by both increasing the binding of insulin to its receptor and potentiating insulin action.	Metformin	141-150	insulin	Homo sapiens	242-249
3552515-0	1987	Effect of metformin on insulin-stimulated glucose turnover and insulin binding to receptors in type II diabetes.	Metformin	10-19	insulin	Homo sapiens	23-30
3552515-4	1987	With the same insulin infusion rates, glucose disposal was 4.94 +/- 0.55 (P less than .01) and 8.99 +/- 0.66 (P less than .01), respectively, after metformin treatment.	Metformin	148-157	insulin	Homo sapiens	14-21
3552515-6	1987	Insulin maximum binding to erythrocytes in diabetics was 9.6 +/- 4.2 and 5.8 +/- 2.6 X 10(9) cells (means +/- SD) before and after metformin treatment, respectively (NS).	Metformin	131-140	insulin	Homo sapiens	0-7
3552515-7	1987	Insulin maximum binding to monocytes in diabetics was 6.2 +/- 2.3 X 10(7) cells before and 5.0 +/- 1.6% after metformin.	Metformin	110-119	insulin	Homo sapiens	0-7
3552515-9	1987	Basal glucose and insulin concentrations decreased with metformin.	Metformin	56-65	insulin	Homo sapiens	18-25
4046836-0	1985	Metformin improved insulin resistance in type I, insulin-dependent, diabetic patients.	Metformin	0-9	insulin	Homo sapiens	49-56
4046836-2	1985	The aim of this was to measure the effect of metformin (850 mg/twice daily) on insulin sensitivity.	Metformin	45-54	insulin	Homo sapiens	79-86
4046836-6	1985	Metformin was therefore effective in improving the insulin action in type I diabetic patients, although its use in such circumstances requires consideration of several other factors.	Metformin	0-9	insulin	Homo sapiens	51-58
3908277-0	1985	Improvement of insulin action is an important part of the antidiabetic effect of metformin.	Metformin	81-90	insulin	Homo sapiens	15-22
3910491-0	1985	[Value of metformin-insulin association in the treatment of insulin- dependent diabetes].	Metformin	10-19	insulin	Homo sapiens	20-27
2578686-1	1985	We describe insulin binding and insulin-mediated RNA synthesis on seven human fibroblasts strains in culture initiated from skin biopsies in the presence of three oral antidiabetic agents, Metformin, Gliquidone, and a non-sulfonylurea antidiabetic drug (B X DF 591 ZW), which belong to different chemical classes.	Metformin	189-198	insulin	Homo sapiens	32-39
3908277-4	1985	Recent studies indicate that metformin treatment improves peripheral insulin action, which might occur both at the receptor level and/or at the postreceptor site.	Metformin	29-38	insulin	Homo sapiens	69-76
3908277-6	1985	Findings indicating that metformin might influence postreceptor sites of insulin action seem, therefore, to be more relevant than possible effects on insulin receptor binding.	Metformin	25-34	insulin	Homo sapiens	73-80
6376023-1	1984	We evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo.	Metformin	27-36	insulin	Homo sapiens	117-124
6397366-0	1984	Influence of metformin on metabolic effect of insulin in human adipose tissue in vitro.	Metformin	13-22	insulin	Homo sapiens	46-53
6397366-3	1984	When insulin was present, however, metformin stimulated glucose conversion into both triglycerides and CO2.	Metformin	35-44	insulin	Homo sapiens	5-12
6397366-6	1984	In conclusion, metformin seems to exert its effect on glucose metabolism by potentiating the action of insulin at a post-receptor level, possibly on the rate of glucose transport.	Metformin	15-24	insulin	Homo sapiens	103-110
6350337-0	1983	Metformin normalizes insulin binding to monocytes from obese nondiabetic subjects and obese type II diabetic patients.	Metformin	0-9	insulin	Homo sapiens	21-28
6350337-3	1983	After metformin administration, an increase in insulin binding to peripheral monocytes was observed in seven of eight obese nondiabetic subjects (3.57 +/- 0.43 to 4.69 +/- 0.59% bound at 10(7) monocytes, mean +/- SEM, P less than 0.01) and in all diabetic patients (3.21 +/- 0.21 to 5.22 +/- 0.34, P less than 0.01).	Metformin	6-15	insulin	Homo sapiens	47-54
6350337-6	1983	These studies indicate that metformin normalizes the binding of insulin to its receptor in obese subjects and diabetic patients.	Metformin	28-37	insulin	Homo sapiens	64-71
6345193-0	1983	Effect of metformin on blood glucose, insulin and C-peptide responses to glucagon in non-insulin dependent diabetics.	Metformin	10-19	insulin	Homo sapiens	50-59
6345193-8	1983	After treatment with metformin the hyperglycemia induced by glucagon was not influenced; nevertheless insulin and C-peptide plasma levels showed an evident reduction while CPR/IRI molar ratio was unchanged.	Metformin	21-30	insulin	Homo sapiens	102-109
6345193-8	1983	After treatment with metformin the hyperglycemia induced by glucagon was not influenced; nevertheless insulin and C-peptide plasma levels showed an evident reduction while CPR/IRI molar ratio was unchanged.	Metformin	21-30	insulin	Homo sapiens	114-123
2577974-0	1985	[Action of metformin in insulin resistance].	Metformin	11-20	insulin	Homo sapiens	24-31
6376023-5	1984	Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively.	Metformin	0-9	insulin	Homo sapiens	34-41
6376023-6	1984	Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects (+ 31%, P less than 0.05) and diabetic patients (+ 63%, P less than 0.01).	Metformin	0-9	insulin	Homo sapiens	44-51
6376023-9	1984	These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo.	Metformin	25-34	insulin	Homo sapiens	45-52
6734405-3	1984	In contrast the two biguanides tested, phenformin and metformin, increased insulin binding in all cell types by 44 to 101%.	Metformin	54-63	insulin	Homo sapiens	75-82
6390140-0	1984	[Effect of metformin on the metabolic action of insulin in human adipose tissue "in vitro" and "in vivo"].	Metformin	11-20	insulin	Homo sapiens	48-55
6373159-1	1984	A study was carried out to evaluate the acute effect of an intravenous injection of metformin on the fasting plasma concentrations of glucose, insulin, C-peptide, glucagon and growth hormone in 15 non-diabetic subjects.	Metformin	84-93	insulin	Homo sapiens	143-150
6373159-1	1984	A study was carried out to evaluate the acute effect of an intravenous injection of metformin on the fasting plasma concentrations of glucose, insulin, C-peptide, glucagon and growth hormone in 15 non-diabetic subjects.	Metformin	84-93	insulin	Homo sapiens	152-161
6373159-1	1984	A study was carried out to evaluate the acute effect of an intravenous injection of metformin on the fasting plasma concentrations of glucose, insulin, C-peptide, glucagon and growth hormone in 15 non-diabetic subjects.	Metformin	84-93	growth hormone 1	Homo sapiens	176-190
6360756-5	1983	Insulin binding to monocytes was nearly identical at all insulin concentrations tested in the placebo or metformin therapy phase.	Metformin	105-114	insulin	Homo sapiens	0-7
6360756-6	1983	These data indicate that the glucose-lowering potency of metformin in non-insulin-dependent diabetics cannot be associated with changes in receptor number or affinity.	Metformin	57-66	insulin	Homo sapiens	74-81
6347782-0	1983	Metformin reduces insulin requirement in Type 1 (insulin-dependent) diabetes.	Metformin	0-9	insulin	Homo sapiens	18-25
6347782-5	1983	There was a 25.8% reduction in insulin requirement during metformin management despite slightly lower blood glucose levels (5.25 +/- 0.20 versus 5.98 +/- 0.18 mmol/l, p less than 0.01).	Metformin	58-67	insulin	Homo sapiens	31-38
6347782-12	1983	It follows that metformin could be usefully administered to Type 1 diabetic patients with unimpaired liver and renal function to reduce their insulin requirement.	Metformin	16-25	insulin	Homo sapiens	142-149
6818080-4	1982	There was a significant increase in serum apolipoprotein A-I in obese females treated with calorie restriction and metformin and in non-obese females treated with carbohydrate restriction and glibenclamide.	Metformin	115-124	apolipoprotein A1	Homo sapiens	42-60
6376023-1	1984	We evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo.	Metformin	38-59	insulin	Homo sapiens	117-124
6376023-2	1984	Specific 125I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin.	Metformin	141-150	insulin	Homo sapiens	14-21
6749582-0	1982	Metformin reduces post-prandial insulin needs in type I (insulin-dependent) diabetic patients: assessment by the artificial pancreas.	Metformin	0-9	insulin	Homo sapiens	32-39
6749582-3	1982	We have studied the effect of metformin (850 mg) given at 08.00 h in diminishing insulin needs after a 60 g carbohydrate mixed meal taken at 12.00 h, using an artificial pancreas and a sequential analysis of the results.	Metformin	30-39	insulin	Homo sapiens	81-88
6749582-5	1982	After the eighth patient a 26% saving of insulin need was demonstrated in the metformin-treated group (p less than 0.01).	Metformin	78-87	insulin	Homo sapiens	41-48
6749582-6	1982	Metformin is thus effective in reducing post-prandial insulin needs in Type 1 diabetic patients, although its use in such circumstances requires consideration of several other issues.	Metformin	0-9	insulin	Homo sapiens	54-61
33830463-14	2021	The broad scope of the review includes the use of progesterone, metformin to reverse insulin resistance, and bariatric surgery or operative hysteroscopy.	Metformin	64-73	insulin	Homo sapiens	85-92
6751898-1	1982	The effect of the biguanide metformin (dimethyl-biguanide) on insulin binding in vitro to IM-9 lymphocytes and MCF-7 human breast cancer cells was studied.	Metformin	39-57	insulin	Homo sapiens	62-69
6751898-2	1982	Metformin significantly increased insulin binding to both cell types: maximum increment was 47.1 +/- 7.0% greater than control in IM-9 and 38.0 +/- 6.1% in MCF-7 cells.	Metformin	0-9	insulin	Homo sapiens	34-41
6751898-4	1982	When compared with phenformin, metformin was less active in increasing insulin binding to cultured cells, the ratio between the two drug responses being similar to that of their therapeutic dosage in patients.	Metformin	31-40	insulin	Homo sapiens	71-78
6751898-5	1982	Insulin binding increment due to metformin was reversible, was not dependent on new protein synthesis and was evident also in IM-9 lymphocytes that had been down-regulated by pre-incubation with insulin (10(-7) mol/l).	Metformin	33-42	insulin	Homo sapiens	0-7
6751898-5	1982	Insulin binding increment due to metformin was reversible, was not dependent on new protein synthesis and was evident also in IM-9 lymphocytes that had been down-regulated by pre-incubation with insulin (10(-7) mol/l).	Metformin	33-42	insulin	Homo sapiens	195-202
6751898-6	1982	This effect of metformin on insulin binding to receptors may contribute to the hypoglycaemic effect of this agent in patients.	Metformin	15-24	insulin	Homo sapiens	28-35
7033271-6	1982	Metformin was also effective in significantly enhancing insulin binding in both IM-9 and MCF-7 cells.	Metformin	0-9	insulin	Homo sapiens	56-63
1174086-9	1975	Even those test persons who did not lose weight under metformin showed lower proinsulin and insulin levels.	Metformin	54-63	insulin	Homo sapiens	77-87
1174086-9	1975	Even those test persons who did not lose weight under metformin showed lower proinsulin and insulin levels.	Metformin	54-63	insulin	Homo sapiens	80-87
4469884-0	1974	[Effects of treatment with glipizide-metformin on the behavior of blood sugar, insulin and lipids after intravenous administration of glucose in diabetic subjects].	Metformin	37-46	insulin	Homo sapiens	79-86
4995366-0	1971	[Experimental demonstration of the simulating action of biguanides (phenformin, metformin) on insulin secretion].	Metformin	80-89	insulin	Homo sapiens	94-101
5791574-0	1969	[Effect of dimethylbiguanide on sensitivity to exogenous insulin in nondiabetic subjects treated by hydrochlorothiazide].	Metformin	11-28	insulin	Homo sapiens	57-64
33850550-8	2021	Furthermore, metformin treatment significantly inhibited the generation of inflammatory cytokines, including TNF-alpha and IL-1beta in db/db mice.	Metformin	13-22	tumor necrosis factor	Mus musculus	109-118
33850550-10	2021	These findings suggested that metformin may reduce DN damage via regulation of the AMPK-mTOR-autophagy axis and indicated that metformin may be considered as a potential target in the treatment of DN.	Metformin	30-39	mechanistic target of rapamycin kinase	Homo sapiens	88-92
33850550-10	2021	These findings suggested that metformin may reduce DN damage via regulation of the AMPK-mTOR-autophagy axis and indicated that metformin may be considered as a potential target in the treatment of DN.	Metformin	127-136	mechanistic target of rapamycin kinase	Homo sapiens	88-92
33850553-0	2021	Metformin prevents PFKFB3-related aerobic glycolysis from enhancing collagen synthesis in lung fibroblasts by regulating AMPK/mTOR pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	126-130
33850553-11	2021	However, this inhibitory role of metformin on PFKFB3-meditaed aerobic glycolysis and collagen synthesis was prevented by treatments with 3BDO and compound C, which are specific mTOR activator and AMPK inhibitor, respectively.	Metformin	33-42	mechanistic target of rapamycin kinase	Homo sapiens	177-181
33850553-12	2021	Taken together, the findings from this study suggested that metformin may prevent PFKFB3-associated aerobic glycolysis from enhancing collagen synthesis in lung fibroblasts via regulating the AMPK/mTOR pathway.	Metformin	60-69	mechanistic target of rapamycin kinase	Homo sapiens	197-201
34057870-0	2021	Repurposing metformin for covid-19 complications in patients with type 2 diabetes and insulin resistance.	Metformin	12-21	insulin	Homo sapiens	86-93
34057870-9	2021	In this article, we argue that metformin has beneficial effects on Covid-19 infection in patients with type 2 diabetes and insulin resistance.	Metformin	31-40	insulin	Homo sapiens	123-130
33713207-5	2021	On the other hand, metformin, an anti-hyperglycemic drug that decreases serum levels of insulin and IGF-1, could have a protective role in the treatment of endocrine tumors.	Metformin	19-28	insulin	Homo sapiens	88-95
33713207-5	2021	On the other hand, metformin, an anti-hyperglycemic drug that decreases serum levels of insulin and IGF-1, could have a protective role in the treatment of endocrine tumors.	Metformin	19-28	insulin like growth factor 1	Homo sapiens	100-105
33838154-4	2021	In the present study, we originally found that the increased ROS induced by metformin was blunted in NFE2L1 knockdown cell line.	Metformin	76-85	NFE2 like bZIP transcription factor 1	Homo sapiens	101-107
33838154-5	2021	Furtherly by examining the effects of metformin on endogenous and exogenous NFE2L1, we also found metformin could not only inhibit the transcription of NFE2L1 gene, but also promote the degradation of NFE2L1 protein at the post-transcriptional level, whereas this effect can be reversed by high glucose.	Metformin	38-47	NFE2 like bZIP transcription factor 1	Homo sapiens	76-82
33838154-5	2021	Furtherly by examining the effects of metformin on endogenous and exogenous NFE2L1, we also found metformin could not only inhibit the transcription of NFE2L1 gene, but also promote the degradation of NFE2L1 protein at the post-transcriptional level, whereas this effect can be reversed by high glucose.	Metformin	98-107	NFE2 like bZIP transcription factor 1	Homo sapiens	76-82
33838154-5	2021	Furtherly by examining the effects of metformin on endogenous and exogenous NFE2L1, we also found metformin could not only inhibit the transcription of NFE2L1 gene, but also promote the degradation of NFE2L1 protein at the post-transcriptional level, whereas this effect can be reversed by high glucose.	Metformin	98-107	NFE2 like bZIP transcription factor 1	Homo sapiens	152-158
33838154-5	2021	Furtherly by examining the effects of metformin on endogenous and exogenous NFE2L1, we also found metformin could not only inhibit the transcription of NFE2L1 gene, but also promote the degradation of NFE2L1 protein at the post-transcriptional level, whereas this effect can be reversed by high glucose.	Metformin	98-107	NFE2 like bZIP transcription factor 1	Homo sapiens	152-158
33838154-6	2021	The inhibitory effect of metformin on NFE2L1 was investigated to occur through the N-terminal domain (NTD) of NFE2L1 protein, and its downregulation by metformin was in an AMP-activated protein kinase (AMPK)-independent manner.	Metformin	25-34	NFE2 like bZIP transcription factor 1	Homo sapiens	38-44
33838154-6	2021	The inhibitory effect of metformin on NFE2L1 was investigated to occur through the N-terminal domain (NTD) of NFE2L1 protein, and its downregulation by metformin was in an AMP-activated protein kinase (AMPK)-independent manner.	Metformin	25-34	NFE2 like bZIP transcription factor 1	Homo sapiens	110-116
33838154-6	2021	The inhibitory effect of metformin on NFE2L1 was investigated to occur through the N-terminal domain (NTD) of NFE2L1 protein, and its downregulation by metformin was in an AMP-activated protein kinase (AMPK)-independent manner.	Metformin	152-161	NFE2 like bZIP transcription factor 1	Homo sapiens	38-44
33838154-6	2021	The inhibitory effect of metformin on NFE2L1 was investigated to occur through the N-terminal domain (NTD) of NFE2L1 protein, and its downregulation by metformin was in an AMP-activated protein kinase (AMPK)-independent manner.	Metformin	152-161	NFE2 like bZIP transcription factor 1	Homo sapiens	110-116
33838154-7	2021	But the activation of AMPK signaling pathway by metformin in NFE2L1 knockdown HepG2 cells is reversed, indicating that NFE2L1 may be an important regulator of AMPK signal.	Metformin	48-57	NFE2 like bZIP transcription factor 1	Homo sapiens	61-67
33838154-7	2021	But the activation of AMPK signaling pathway by metformin in NFE2L1 knockdown HepG2 cells is reversed, indicating that NFE2L1 may be an important regulator of AMPK signal.	Metformin	48-57	NFE2 like bZIP transcription factor 1	Homo sapiens	119-125
34002012-10	2021	When cells were treated with metformin (an AMPK activator), the CRBN-induced activation of SMAD3 and upregulation of alpha-SMA and collagen expression were significantly suppressed, suggesting that increased TGF-beta1-induced activation of SMAD3 via CRBN overexpression is associated with AMPKalpha1 inactivation.	Metformin	29-38	cereblon	Mus musculus	64-68
34002012-10	2021	When cells were treated with metformin (an AMPK activator), the CRBN-induced activation of SMAD3 and upregulation of alpha-SMA and collagen expression were significantly suppressed, suggesting that increased TGF-beta1-induced activation of SMAD3 via CRBN overexpression is associated with AMPKalpha1 inactivation.	Metformin	29-38	actin alpha 2, smooth muscle, aorta	Mus musculus	117-126
34002012-10	2021	When cells were treated with metformin (an AMPK activator), the CRBN-induced activation of SMAD3 and upregulation of alpha-SMA and collagen expression were significantly suppressed, suggesting that increased TGF-beta1-induced activation of SMAD3 via CRBN overexpression is associated with AMPKalpha1 inactivation.	Metformin	29-38	cereblon	Mus musculus	250-254
34002012-10	2021	When cells were treated with metformin (an AMPK activator), the CRBN-induced activation of SMAD3 and upregulation of alpha-SMA and collagen expression were significantly suppressed, suggesting that increased TGF-beta1-induced activation of SMAD3 via CRBN overexpression is associated with AMPKalpha1 inactivation.	Metformin	29-38	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	289-299
34004440-0	2021	Metformin prevents BAFF activation of Erk1/2 from B-cell proliferation and survival by impeding mTOR-PTEN/Akt signaling pathway.	Metformin	0-9	mitogen-activated protein kinase 3	Homo sapiens	38-44
34004440-0	2021	Metformin prevents BAFF activation of Erk1/2 from B-cell proliferation and survival by impeding mTOR-PTEN/Akt signaling pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	96-100
34004440-0	2021	Metformin prevents BAFF activation of Erk1/2 from B-cell proliferation and survival by impeding mTOR-PTEN/Akt signaling pathway.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	106-109
34004440-4	2021	Here, we show that metformin attenuated human soluble BAFF (hsBAFF)-induced cell proliferation and survival by blocking the Erk1/2 pathway in normal and B-lymphoid (Raji) cells.	Metformin	19-28	mitogen-activated protein kinase 3	Homo sapiens	124-130
34004440-5	2021	Pretreatment with U0126, knockdown of Erk1/2, or expression of dominant negative MKK1 strengthened metformin"s inhibition of hsBAFF-activated Erk1/2 and B-cell proliferation/viability, whereas expression of constitutively active MKK1 rendered high resistance to metformin.	Metformin	99-108	mitogen-activated protein kinase 3	Homo sapiens	38-44
34004440-5	2021	Pretreatment with U0126, knockdown of Erk1/2, or expression of dominant negative MKK1 strengthened metformin"s inhibition of hsBAFF-activated Erk1/2 and B-cell proliferation/viability, whereas expression of constitutively active MKK1 rendered high resistance to metformin.	Metformin	99-108	mitogen-activated protein kinase 3	Homo sapiens	142-148
34004440-6	2021	Further investigation found that overexpression of wild type PTEN or ectopic expression of dominant negative Akt potentiated metformin"s suppression of hsBAFF-induced Erk1/2 activation and proliferation/viability in Raji cells, implying a PTEN/Akt-dependent mechanism involved.	Metformin	125-134	AKT serine/threonine kinase 1	Homo sapiens	109-112
34004440-6	2021	Further investigation found that overexpression of wild type PTEN or ectopic expression of dominant negative Akt potentiated metformin"s suppression of hsBAFF-induced Erk1/2 activation and proliferation/viability in Raji cells, implying a PTEN/Akt-dependent mechanism involved.	Metformin	125-134	mitogen-activated protein kinase 3	Homo sapiens	167-173
34004440-6	2021	Further investigation found that overexpression of wild type PTEN or ectopic expression of dominant negative Akt potentiated metformin"s suppression of hsBAFF-induced Erk1/2 activation and proliferation/viability in Raji cells, implying a PTEN/Akt-dependent mechanism involved.	Metformin	125-134	AKT serine/threonine kinase 1	Homo sapiens	244-247
34004440-7	2021	Furthermore, we noticed that metformin hindered hsBAFF-activated mTOR pathway in B cells.	Metformin	29-38	mechanistic target of rapamycin kinase	Homo sapiens	65-69
34004440-8	2021	Inhibition of mTOR with rapamycin or knockdown of mTOR enhanced metformin"s suppression of hsBAFF-induced phosphorylation of S6K1, PTEN, Akt, and Erk1/2, as well as B-cell proliferation/viability.	Metformin	64-73	mechanistic target of rapamycin kinase	Homo sapiens	14-18
34004440-8	2021	Inhibition of mTOR with rapamycin or knockdown of mTOR enhanced metformin"s suppression of hsBAFF-induced phosphorylation of S6K1, PTEN, Akt, and Erk1/2, as well as B-cell proliferation/viability.	Metformin	64-73	mechanistic target of rapamycin kinase	Homo sapiens	50-54
34004440-8	2021	Inhibition of mTOR with rapamycin or knockdown of mTOR enhanced metformin"s suppression of hsBAFF-induced phosphorylation of S6K1, PTEN, Akt, and Erk1/2, as well as B-cell proliferation/viability.	Metformin	64-73	AKT serine/threonine kinase 1	Homo sapiens	137-140
34004440-8	2021	Inhibition of mTOR with rapamycin or knockdown of mTOR enhanced metformin"s suppression of hsBAFF-induced phosphorylation of S6K1, PTEN, Akt, and Erk1/2, as well as B-cell proliferation/viability.	Metformin	64-73	mitogen-activated protein kinase 3	Homo sapiens	146-152
34004440-9	2021	These results indicate that metformin prevents BAFF activation of Erk1/2 from cell proliferation and survival by impeding mTOR-PTEN/Akt signaling pathway in normal and neoplastic B-lymphoid cells.	Metformin	28-37	mitogen-activated protein kinase 3	Homo sapiens	66-72
34004440-9	2021	These results indicate that metformin prevents BAFF activation of Erk1/2 from cell proliferation and survival by impeding mTOR-PTEN/Akt signaling pathway in normal and neoplastic B-lymphoid cells.	Metformin	28-37	mechanistic target of rapamycin kinase	Homo sapiens	122-126
34004440-9	2021	These results indicate that metformin prevents BAFF activation of Erk1/2 from cell proliferation and survival by impeding mTOR-PTEN/Akt signaling pathway in normal and neoplastic B-lymphoid cells.	Metformin	28-37	AKT serine/threonine kinase 1	Homo sapiens	132-135
33987977-0	2021	Metformin Carbon Dots for Promoting Periodontal Bone Regeneration via Activation of ERK/AMPK Pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	88-92
33990102-6	2021	The alteration of insulin signaling pathways, involved in gastrointestinal manifestations, carcinogenesis, muscle function, cognitive and endocrinological aspects, gain further relevance in the light of recent evidence of metformin efficacy in DM1.	Metformin	222-231	insulin	Homo sapiens	18-25
33982074-10	2021	Along with the upregulation of phosphorylated AMPKalpha and ACCalpha, metformin at 1.5 and 3 mM inactivated NF-kappaB signalling components (p65 and IkappaBalpha) and the inflammatory genes (TNFA, IL6, IL1B and COX-2) which were activated by BHBA.	Metformin	70-79	cytochrome c oxidase subunit II	Bos taurus	211-216
33982074-14	2021	Compared to BHBA treated cells, the protein expression of COX-2 and IL-1beta were decreased by the pretreatment with metformin, and the inhibitory effect of metformin was released by compound C. The bound of NF-kappaB onto IL1B promoter displayed higher in BHBA group and this was suppressed by pretreatment with metformin (P < 0.05).	Metformin	117-126	cytochrome c oxidase subunit II	Bos taurus	58-63
33980323-14	2021	Metformin suppresses the NF-kappaB/Snail/HK3 signaling axis that is activated by LPS and then inhibits LPS-induced metastasis.	Metformin	0-9	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	25-34
34007128-2	2021	The pleiotropic insulin-dependent and insulin-independent effects of metformin might inhibit pathways that are frequently amplified in neoplastic tissue.	Metformin	69-78	insulin	Homo sapiens	16-23
34007128-2	2021	The pleiotropic insulin-dependent and insulin-independent effects of metformin might inhibit pathways that are frequently amplified in neoplastic tissue.	Metformin	69-78	insulin	Homo sapiens	38-45
33444083-2	2021	Metformin is the recommended first choice of drug for the management of T2DM and is known to improve insulin sensitivity and prevents hyperglycemia by reducing chronic inflammation.	Metformin	0-9	insulin	Homo sapiens	101-108
33444083-8	2021	We observed that participants on 3000 mg/day dose of metformin had significantly lower levels of TNF-alpha (p < .001) and IFN-gamma (p = .014) compared to those on other dosages (1000 mg and 2000 mg/day).	Metformin	53-62	tumor necrosis factor	Homo sapiens	97-106
33444083-8	2021	We observed that participants on 3000 mg/day dose of metformin had significantly lower levels of TNF-alpha (p < .001) and IFN-gamma (p = .014) compared to those on other dosages (1000 mg and 2000 mg/day).	Metformin	53-62	interferon gamma	Homo sapiens	122-131
33444083-10	2021	After adjusting for age, gender, dose and duration of metformin use, we observed that participants who took higher doses of metformin had significantly reduced levels of TNF-alpha (beta = -0.0297, 95% CI = (-0.005 to -0.002) p < .001.	Metformin	54-63	tumor necrosis factor	Homo sapiens	170-179
33444083-10	2021	After adjusting for age, gender, dose and duration of metformin use, we observed that participants who took higher doses of metformin had significantly reduced levels of TNF-alpha (beta = -0.0297, 95% CI = (-0.005 to -0.002) p < .001.	Metformin	124-133	tumor necrosis factor	Homo sapiens	170-179
33444083-11	2021	Metformin dosage independently predicted reduced TNF-alpha levels with 14.4% variations in the metformin dosage levels.	Metformin	0-9	tumor necrosis factor	Homo sapiens	49-58
33444083-12	2021	Increased metformin dosage suppresses TNF-alpha levels in systemic circulation and hence might contribute to its beneficial effects.	Metformin	10-19	tumor necrosis factor	Homo sapiens	38-47
33947424-0	2021	Metformin ameliorates scleroderma via inhibiting Th17 cells and reducing mTOR-STAT3 signaling in skin fibroblasts.	Metformin	0-9	signal transducer and activator of transcription 3	Mus musculus	78-83
33947424-9	2021	These results suggest that metformin treatment has anti-inflammatory effects on lymphocytes via the inhibition of IL-17 and cytokines related to Th17 differentiation, such as IL-1beta, IL-6, and TNF-alpha.	Metformin	27-36	interleukin 6	Mus musculus	185-189
33947424-9	2021	These results suggest that metformin treatment has anti-inflammatory effects on lymphocytes via the inhibition of IL-17 and cytokines related to Th17 differentiation, such as IL-1beta, IL-6, and TNF-alpha.	Metformin	27-36	tumor necrosis factor	Mus musculus	195-204
33947424-10	2021	To investigate how metformin modulates the inflammatory process in skin fibroblasts, we measured mTOR-STAT3 signaling in skin fibroblasts and found that phosphorylated mTOR and phosphorylated STAT3 protein expression were decreased by metformin treatment.	Metformin	19-28	signal transducer and activator of transcription 3	Mus musculus	102-107
33947424-10	2021	To investigate how metformin modulates the inflammatory process in skin fibroblasts, we measured mTOR-STAT3 signaling in skin fibroblasts and found that phosphorylated mTOR and phosphorylated STAT3 protein expression were decreased by metformin treatment.	Metformin	19-28	signal transducer and activator of transcription 3	Mus musculus	192-197
33947424-11	2021	These results suggest that metformin has potential to treat scleroderma by inhibiting pro-inflammatory cytokines and anti-inflammatory activity mediated by mTOR-STAT3 signaling.	Metformin	27-36	signal transducer and activator of transcription 3	Mus musculus	161-166
6751898-0	1982	Effect of metformin on insulin binding to receptors in cultured human lymphocytes and cancer cells.	Metformin	10-19	insulin	Homo sapiens	23-30
6751898-1	1982	The effect of the biguanide metformin (dimethyl-biguanide) on insulin binding in vitro to IM-9 lymphocytes and MCF-7 human breast cancer cells was studied.	Metformin	28-37	insulin	Homo sapiens	62-69
428695-0	1979	Metformin in management of pregnant insulin-independent diabetics.	Metformin	0-9	insulin	Homo sapiens	36-43
455913-0	1979	[Effects of dimethylbiguanide (metformin) on peripheral insulin clearance and lipid biosynthesis in obese dyslipidemic subjects with and without diabetes mellitus].	Metformin	31-40	insulin	Homo sapiens	56-63
188698-6	1976	Basal plasma insulin was significantly reduced in all the patients following metformin treatment.	Metformin	77-86	insulin	Homo sapiens	13-20
33961875-0	2021	Metformin protects against neuroinflammation through integrated mechanisms of miR-141 and the NF-kB-mediated inflammasome pathway in a diabetic mouse model.	Metformin	0-9	microRNA 141	Mus musculus	78-85
33961875-5	2021	We hypothesised that Metformin (MF) regulates the miR-141/protein phosphatase 2A (PP2A) axis, and associated NF-kB-mediated inflammasome expression in diabetic mice brain.	Metformin	21-30	microRNA 141	Mus musculus	50-57
33580540-2	2021	Metformin is known to decrease interleukin-6 (IL-6) and tumor-necrosis alpha (TNFalpha), which appear to contribute to morbidity in COVID-19.	Metformin	0-9	interleukin 6	Homo sapiens	31-44
33580540-2	2021	Metformin is known to decrease interleukin-6 (IL-6) and tumor-necrosis alpha (TNFalpha), which appear to contribute to morbidity in COVID-19.	Metformin	0-9	interleukin 6	Homo sapiens	46-50
33580540-2	2021	Metformin is known to decrease interleukin-6 (IL-6) and tumor-necrosis alpha (TNFalpha), which appear to contribute to morbidity in COVID-19.	Metformin	0-9	tumor necrosis factor	Homo sapiens	78-86
33838541-4	2021	The use of metformin for chemoprevention has been shown to reduce CRC and adenoma incidence through the upregulation of AMPK, which causes cell cycle arrest in the Gap 1-S (G1-S) phase and inhibits the mTOR pathway, even potentially reversing the epithelial-mesenchymal transition.	Metformin	11-20	mechanistic target of rapamycin kinase	Homo sapiens	202-206
33745895-11	2021	SIGNIFICANCE: Our study indicated that pre-admitted metformin usage may have beneficial effects on COVID-19 with pre-existed type 2 diabetes, insulin should be used sparingly in the hospital stay.	Metformin	52-61	insulin	Homo sapiens	142-149
33915432-0	2021	Metformin attenuates atherosclerosis and plaque vulnerability by upregulating KLF2-mediated autophagy in apoE-/- mice.	Metformin	0-9	apolipoprotein E	Mus musculus	105-109
33915432-9	2021	In this study, we first investigated whether metformin could protect against atherogenesis via enhancing autophagy in high fat diet (HFD)-induced apoE-/- mice.	Metformin	45-54	apolipoprotein E	Mus musculus	146-150
33915432-11	2021	We show that metformin protected against HFD-induced atherosclerosis and enhanced plaque stability in apoE-/- mice.	Metformin	13-22	apolipoprotein E	Mus musculus	102-106
33714781-5	2021	Besides, metformin inhibits cystic fibrosis transmembrane conductance regulator (CFTR)-mediated fluids secretion and the mammalian target of rapamycin (mTOR)-involved cyst formation negatively regulated by AMPK in autosomal dominant polycystic kidney disease (APDKD).	Metformin	9-18	CF transmembrane conductance regulator	Homo sapiens	28-79
33714781-5	2021	Besides, metformin inhibits cystic fibrosis transmembrane conductance regulator (CFTR)-mediated fluids secretion and the mammalian target of rapamycin (mTOR)-involved cyst formation negatively regulated by AMPK in autosomal dominant polycystic kidney disease (APDKD).	Metformin	9-18	CF transmembrane conductance regulator	Homo sapiens	81-85
33859820-14	2021	However, obesity significantly increased serum AST levels in both the control and metformin treatment groups (P=0.01).	Metformin	82-91	glutamic-oxaloacetic transaminase 2	Rattus norvegicus	47-50
32770520-0	2021	Metformin Lowers Body Weight But Fails to Increase Insulin Sensitivity in Chronic Heart Failure Patients without Diabetes: a Randomized, Double-Blind, Placebo-Controlled Study.	Metformin	0-9	insulin	Homo sapiens	51-58
32770520-2	2021	However, it remains to be established whether these beneficial myocardial effects are associated with metformin-induced alterations in whole-body insulin sensitivity and substrate metabolism.	Metformin	102-111	insulin	Homo sapiens	146-153
32770520-7	2021	RESULTS: Compared with placebo, metformin treatment lowered mean glycated hemoglobin levels (absolute mean difference, - 0.2%; 95% CI - 0.3 to 0.0; p = 0.03), reduced body weight (- 2.8 kg; 95% CI - 5.0 to - 0.6; p = 0.02), and increased fasting glucagon levels (3.2 pmol L-1; 95% CI 0.4 to 6.0; p = 0.03).	Metformin	32-41	glucagon	Homo sapiens	246-254
33358075-9	2021	Metformin has been demonstrated to reduce cell-viability post-radiotherapy in both rectal and prostate cancer cell lines, with an enhanced effect in tumours with a p53 mutation and increased apoptosis post-radiotherapy for cervical cancer.	Metformin	0-9	tumor protein p53	Homo sapiens	164-167
33355497-0	2021	Metformin protects cardiomyocytes against oxygen-glucose deprivation injury by promoting autophagic flux through AMPK pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	113-117
33355497-5	2021	Moreover, metformin furtherly promoted autophagy by increasing the protein expression of LC3-II, ATG5, ATG7 and Beclin1, and by involving AMPK pathway during MI.	Metformin	10-19	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	138-142
33355497-9	2021	In addition, metformin augmented the protein level of Bcl-2 and diminished the protein levels of Bax and cleaved caspase-3.	Metformin	13-22	BCL2, apoptosis regulator	Rattus norvegicus	54-59
33355497-10	2021	Metformin also upregulated p-AMPK expression.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	29-33
33355497-11	2021	Nevertheless, the above-mentioned effects of metformin on H9c2 cells were remarkably eliminated by compound C (an AMPK inhibitor).	Metformin	45-54	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	114-118
33355497-12	2021	In summary, we displayed that metformin protected cardiomyocytes against OGD-induced injury and apoptosis by promoting autophagic flux through AMPK pathway.	Metformin	30-39	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	143-147
33838154-0	2021	Metformin leads to accumulation of reactive oxygen species by inhibiting the NFE2L1 expression in human hepatocellular carcinoma cells.	Metformin	0-9	NFE2 like bZIP transcription factor 1	Homo sapiens	77-83
33838154-3	2021	Here we provide evidence that metformin induces accumulation of ROS by inhibiting the expression of a core antioxidant transcription factor nuclear factor erythroid 2 like 1 (NFE2L1/Nrf1) in human hepatocellular carcinoma HepG2 cells.	Metformin	30-39	NFE2 like bZIP transcription factor 1	Homo sapiens	140-173
33838154-3	2021	Here we provide evidence that metformin induces accumulation of ROS by inhibiting the expression of a core antioxidant transcription factor nuclear factor erythroid 2 like 1 (NFE2L1/Nrf1) in human hepatocellular carcinoma HepG2 cells.	Metformin	30-39	NFE2 like bZIP transcription factor 1	Homo sapiens	175-181
34053175-8	2021	HUA directly inhibited the phosphorylation of Akt and the translocation of GLUT4 induced by insulin, which was blocked by metformin.	Metformin	122-131	thymoma viral proto-oncogene 1	Mus musculus	46-49
34053175-8	2021	HUA directly inhibited the phosphorylation of Akt and the translocation of GLUT4 induced by insulin, which was blocked by metformin.	Metformin	122-131	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	75-80
34053175-10	2021	As a result of these effects, in a mouse model of acute hyperuricaemia, metformin improved insulin tolerance and glucose tolerance, accompanied by increased AMPK phosphorylation, Akt phosphorylation and translocation of GLUT4 in myocardial tissues.	Metformin	72-81	thymoma viral proto-oncogene 1	Mus musculus	179-182
34053175-10	2021	As a result of these effects, in a mouse model of acute hyperuricaemia, metformin improved insulin tolerance and glucose tolerance, accompanied by increased AMPK phosphorylation, Akt phosphorylation and translocation of GLUT4 in myocardial tissues.	Metformin	72-81	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	220-225
34053455-0	2021	Metformin reduces androgen receptor and upregulates homeobox A10 expression in uterine endometrium in women with polycystic ovary syndrome.	Metformin	0-9	androgen receptor	Homo sapiens	18-35
34053455-5	2021	METHODS: In this study, we examined whether metformin affects androgen receptor (AR) and HOXA10 expression in PCOS endometrium in vivo and in human endometrial cell lines in vitro.	Metformin	44-53	androgen receptor	Homo sapiens	62-79
34041677-10	2021	Vildagliptin and metformin not only restored the above but also decreased the expression of IL-6, NFkappaB, SOCS-3 along with lipid accumulation.	Metformin	17-26	interleukin 6	Rattus norvegicus	92-96
34009437-6	2021	Obese pre-diabetics in metformin vs. placebo showed significant reduction in serum miR-195 and miR-27 (p < 0.05).	Metformin	23-32	microRNA 195	Homo sapiens	83-90
34009437-6	2021	Obese pre-diabetics in metformin vs. placebo showed significant reduction in serum miR-195 and miR-27 (p < 0.05).	Metformin	23-32	microRNA 27a	Homo sapiens	95-101
34009437-7	2021	Obese pre-diabetics in metformin vs. normoglycemics showed higher expression of serum miR-195 and miR-27 (p < 0.05).	Metformin	23-32	microRNA 195	Homo sapiens	86-93
34009437-7	2021	Obese pre-diabetics in metformin vs. normoglycemics showed higher expression of serum miR-195 and miR-27 (p < 0.05).	Metformin	23-32	microRNA 27a	Homo sapiens	98-104
34009437-11	2021	CONCLUSIONS: In obese pre-diabetics", metformin significantly reduces inflammation/oxidative stress, and miR-195 and miR-27, with reduction in LVM, IMT.	Metformin	38-47	microRNA 195	Homo sapiens	105-112
34009437-11	2021	CONCLUSIONS: In obese pre-diabetics", metformin significantly reduces inflammation/oxidative stress, and miR-195 and miR-27, with reduction in LVM, IMT.	Metformin	38-47	microRNA 27a	Homo sapiens	117-123
34009437-11	2021	CONCLUSIONS: In obese pre-diabetics", metformin significantly reduces inflammation/oxidative stress, and miR-195 and miR-27, with reduction in LVM, IMT.	Metformin	38-47	modulator of VRAC current 1	Homo sapiens	143-146
34004027-4	2021	The relationship between metformin clearance and eGFR metrics and gentamicin clearance was found to be linear suggesting that a proportional dose reduction based on GFR in patients with CKD is reasonable.	Metformin	25-34	epidermal growth factor receptor	Homo sapiens	49-53
33459895-12	2021	Women treated with metformin plus insulin had 201 (52.1%) obstetric complications versus 184 (47.7%) in insulin-only group, p = 0.22; and 112 (29.0%) neonatal complications versus 96 (24.9%), p = 0.19.	Metformin	19-28	insulin	Homo sapiens	104-111
33459895-13	2021	Patients treated with metformin plus insulin had similar GWG, excessive weight gain and insulin dose compared to the insulin-only group.	Metformin	22-31	insulin	Homo sapiens	88-95
33459895-13	2021	Patients treated with metformin plus insulin had similar GWG, excessive weight gain and insulin dose compared to the insulin-only group.	Metformin	22-31	insulin	Homo sapiens	88-95
33459895-14	2021	CONCLUSIONS: Women with GDM treated with insulin plus metformin had similar obstetric and neonatal complications, weight gained and insulin dose compared to those only treated with insulin.	Metformin	54-63	insulin	Homo sapiens	132-139
33459895-14	2021	CONCLUSIONS: Women with GDM treated with insulin plus metformin had similar obstetric and neonatal complications, weight gained and insulin dose compared to those only treated with insulin.	Metformin	54-63	insulin	Homo sapiens	132-139
33689478-4	2021	Commonly accepted mechanisms of metformin action include AMPK activation and inhibition of mTOR pathways, which are evaluated in multiple diseases.	Metformin	32-41	mechanistic target of rapamycin kinase	Homo sapiens	91-95
33645317-3	2021	NLRP3 inflammasome pathway was inhibited in pBOO rat bladders with the treatment of metformin in early phase.	Metformin	84-93	NLR family, pyrin domain containing 3	Rattus norvegicus	0-5
33524789-6	2021	First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3.	Metformin	32-41	mechanistic target of rapamycin kinase	Homo sapiens	154-158
33645317-4	2021	Metformin reduced the activity of NLRP3 in primary urothelial cells.	Metformin	0-9	NLR family, pyrin domain containing 3	Rattus norvegicus	34-39
33645317-6	2021	Treatment with metformin suppressed the activation of Smad3 and compensated the diminished autophagy in 9-week pBOO rat bladder.	Metformin	15-24	SMAD family member 3	Rattus norvegicus	54-59
33645317-8	2021	The anti-fibrotic effects of metformin on fibroblasts were diminished after silencing AMPK or LC3B.	Metformin	29-38	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	86-90
33524789-6	2021	First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3.	Metformin	32-41	mechanistic target of rapamycin kinase	Homo sapiens	218-222
33524789-6	2021	First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3.	Metformin	32-41	mitogen-activated protein kinase 1	Homo sapiens	255-259
33524789-6	2021	First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3.	Metformin	32-41	mitogen-activated protein kinase 1	Homo sapiens	260-263
33524789-6	2021	First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3.	Metformin	32-41	AKT serine/threonine kinase 1	Homo sapiens	273-276
33524789-7	2021	Secondly, some signaling pathways were involved in the process of metformin inhibiting autophagy, such as AMPK-related signaling pathways (AMPK/NF-kappaB and other undetermined AMPK-related signaling pathways), Hedgehog, miR-570-3p, miR-142-3p, and MiR-3127-5p.	Metformin	66-75	nuclear factor kappa B subunit 1	Homo sapiens	144-153
33524789-8	2021	Thirdly, two types of signaling pathways including PI3K/AKT/mTOR and endoplasmic reticulum (ER) stress could bidirectionally impact the effectiveness of metformin on autophagy.	Metformin	153-162	AKT serine/threonine kinase 1	Homo sapiens	56-59
33524789-8	2021	Thirdly, two types of signaling pathways including PI3K/AKT/mTOR and endoplasmic reticulum (ER) stress could bidirectionally impact the effectiveness of metformin on autophagy.	Metformin	153-162	mechanistic target of rapamycin kinase	Homo sapiens	60-64
33609419-8	2021	RESULTS: Treatment with metformin/rosiglitazone in MMTV-ErbB2/Leprdb/db mouse model reduced serum insulin levels, prolonged overall survival, decreased cumulative tumor incidence, and inhibited tumor progression.	Metformin	24-33	erb-b2 receptor tyrosine kinase 2	Homo sapiens	56-61
33609419-8	2021	RESULTS: Treatment with metformin/rosiglitazone in MMTV-ErbB2/Leprdb/db mouse model reduced serum insulin levels, prolonged overall survival, decreased cumulative tumor incidence, and inhibited tumor progression.	Metformin	24-33	insulin	Homo sapiens	98-105
33609419-10	2021	The tumor cells from MMTV-ErbB2/Leprdb/db transgenic mice treated with metformin had reprogrammed metabolism by reducing levels of both oxygen consumption and lactate production.	Metformin	71-80	erb-b2 receptor tyrosine kinase 2	Homo sapiens	26-31
33609419-12	2021	Moreover, metformin attenuated the mTOR/AKT signaling pathway and altered adipokine profiles.	Metformin	10-19	thymoma viral proto-oncogene 1	Mus musculus	40-43
33394543-5	2021	Metformin effect on eGFR slope was calculated using a mixed model-repeated measures (MMRM) analysis, and the number of lactic acidosis events was tabulated.	Metformin	0-9	epidermal growth factor receptor	Homo sapiens	20-24
33509804-10	2021	Colon polyps removed from the metformin-treated patients showed significantly lower mTOR signal (p-S6) expression than those from patients in the placebo arm.	Metformin	30-39	mechanistic target of rapamycin kinase	Homo sapiens	84-88
33515696-8	2021	Third, miR-27 was downregulated in cultured cells when CREB was decreased by siRNA or metformin treatment.	Metformin	86-95	cAMP responsive element binding protein 1	Mus musculus	55-59
32533543-1	2021	Metformin is widely used as a firstline therapy to improve insulin sensitivity in type 2 diabetes mellitus (T2DM) patients.	Metformin	0-9	insulin	Homo sapiens	59-66
33394543-8	2021	An improvement in eGFR slope was observed with metformin in the CKD stage 3B cohort in SAVOR, but not in other groups.	Metformin	47-56	epidermal growth factor receptor	Homo sapiens	18-22
33311577-3	2021	Here we found that background treatment with metformin diminished the SGLT2i-induced reductions in eGFR after 3 months of SGLT2i therapy in patients with type 2 diabetes and hypertension (-2.29 +- 0.90 vs -5.85 +- 1.27 mL/min/1.73 m2 for metformin users (n = 126) and nonusers (n = 97), respectively).	Metformin	45-54	epidermal growth factor receptor	Homo sapiens	99-103
33311577-3	2021	Here we found that background treatment with metformin diminished the SGLT2i-induced reductions in eGFR after 3 months of SGLT2i therapy in patients with type 2 diabetes and hypertension (-2.29 +- 0.90 vs -5.85 +- 1.27 mL/min/1.73 m2 for metformin users (n = 126) and nonusers (n = 97), respectively).	Metformin	238-247	epidermal growth factor receptor	Homo sapiens	99-103
33311577-6	2021	Next, we evaluated the interaction between metformin and RASis in the eGFR responses to SGLT2is.	Metformin	43-52	epidermal growth factor receptor	Homo sapiens	70-74
33311577-7	2021	Under no background treatment with RASis, metformin abrogated the eGFR response to SGLT2is, but this response was preserved when RASis had been given along with metformin (decreases of 0.75 +- 1.28 vs. 4.60 +- 1.15 mL/min/1.73 m2 in eGFR, p = 0.028).	Metformin	42-51	epidermal growth factor receptor	Homo sapiens	66-70
33311577-9	2021	In conclusion, metformin blunts the SGLT2i-induced decrease in eGFR, but coadministration of RASis ameliorates this response.	Metformin	15-24	epidermal growth factor receptor	Homo sapiens	63-67
33649784-11	2021	The pharmacological induction of autophagy with rapamycin or metformin attenuated the pro-migratory effects of IL-8.	Metformin	61-70	C-X-C motif chemokine ligand 8	Homo sapiens	111-115
34012924-0	2021	Imaging Metformin Efficacy as Add-On Therapy in Cells and Mouse Models of Human EGFR Glioblastoma.	Metformin	8-17	epidermal growth factor receptor	Homo sapiens	80-84
33858654-0	2021	Metformin regulates the Th17/Treg balance by glycolysis with TIGAR in hepatic ischemia-reperfusion injury.	Metformin	0-9	TP53 induced glycolysis regulatory phosphatase	Rattus norvegicus	61-66
33650273-1	2021	PURPOSE: Metformin is widely used as an insulin sensitizer in polycystic ovary syndrome (PCOS) patients.	Metformin	9-18	insulin	Homo sapiens	40-47
33858654-8	2021	RNA-seq results showed that TIGAR was a possible regulatory site of metformin.	Metformin	68-77	TP53 induced glycolysis regulatory phosphatase	Rattus norvegicus	28-33
33858654-9	2021	However, the protective effect and the regulating effect of Th17/Treg balance by metformin in TIGAR knock-out cells were disappeared.	Metformin	81-90	TP53 induced glycolysis regulatory phosphatase	Rattus norvegicus	94-99
33858654-10	2021	In conclusion, metformin could regulate TIGAR inhibit glycolysis then regulate Th17/Treg balance, inhibit the release of liver inflammatory factors, and finally play a role in inhibiting the occurrence of liver injury caused by ischemia-reperfusion.	Metformin	15-24	TP53 induced glycolysis regulatory phosphatase	Rattus norvegicus	40-45
34001842-0	2021	ZNF423 modulates the AMP-activated protein kinase pathway and metformin response in a single nucleotide polymorphisms, estrogen and selective estrogen receptor modulator dependent fashion.	Metformin	62-71	zinc finger protein 423	Mus musculus	0-6
34001842-8	2021	The ZNF423 rs9940645 SNP affects metformin response in breast cancer and could be a potential biomarker for tailoring the metformin treatment.	Metformin	33-42	zinc finger protein 423	Mus musculus	4-10
34001842-8	2021	The ZNF423 rs9940645 SNP affects metformin response in breast cancer and could be a potential biomarker for tailoring the metformin treatment.	Metformin	122-131	zinc finger protein 423	Mus musculus	4-10
33350292-0	2021	Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism.	Metformin	0-9	tumor protein p53	Homo sapiens	111-114
33350292-1	2021	AIM: In the present study we aimed to figure out the effect of metformin on the expression of AMPK-alpha, cyclin D1 and Tp53, and apoptosis in primary breast cancer cells (PBCCs).	Metformin	63-72	tumor protein p53	Homo sapiens	120-124
33350292-8	2021	25mM dose of metformin increased p53 expression significantly compared with the non-treated group.	Metformin	13-22	tumor protein p53	Homo sapiens	33-36
33350292-10	2021	CONCLUSION: Metformin can modulate cyclin D1 and p53 expression through AMPK-alpha independent mechanism in breast cancer cells, leading to cell proliferation inhibition and apoptosis induction.	Metformin	12-21	tumor protein p53	Homo sapiens	49-52
32791889-13	2021	Metformin treatment decreased the FRO- or SW1736-CM-induced STAT3 phosphorylation by AMPK phosphorylation.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	60-65
32667970-7	2021	Metformin at a clinically relevant concentration (10muM) evoked AMPK-dependent and ATF1-dependent increases in Hmox1, Nr1h2 (Lxrb), Abca1, Apoe, Igf1 and Pdgf, increases in several M2-markers and decreases in Nos2, in murine bone marrow macrophages.	Metformin	0-9	heme oxygenase 1	Mus musculus	111-116
33899646-1	2021	OBJECTIVE: To improve insulin action, most clinicians prescribe Metformin in patients with insulin resistance (IR).	Metformin	64-73	insulin	Homo sapiens	22-29
33899646-1	2021	OBJECTIVE: To improve insulin action, most clinicians prescribe Metformin in patients with insulin resistance (IR).	Metformin	64-73	insulin	Homo sapiens	91-98
33899646-4	2021	Therefore, we conducted a meta-analysis to determine if Metformin provides a benefit in conjunction with hypocaloric diets to improve insulin sensitivity in PCOS women.	Metformin	56-65	insulin	Homo sapiens	134-141
32667970-7	2021	Metformin at a clinically relevant concentration (10muM) evoked AMPK-dependent and ATF1-dependent increases in Hmox1, Nr1h2 (Lxrb), Abca1, Apoe, Igf1 and Pdgf, increases in several M2-markers and decreases in Nos2, in murine bone marrow macrophages.	Metformin	0-9	apolipoprotein E	Mus musculus	139-143
32667970-7	2021	Metformin at a clinically relevant concentration (10muM) evoked AMPK-dependent and ATF1-dependent increases in Hmox1, Nr1h2 (Lxrb), Abca1, Apoe, Igf1 and Pdgf, increases in several M2-markers and decreases in Nos2, in murine bone marrow macrophages.	Metformin	0-9	nitric oxide synthase 2, inducible	Mus musculus	209-213
33887146-10	2021	Conclusions: Metformin treatment was associated with significant decreases in BMI, fasting insulin, and HOMA-IR.	Metformin	13-22	insulin	Homo sapiens	91-98
33634460-10	2021	Metformin normalized the alterations in the expression of glucose metabolism-related genes (PGC-1alpha, G6pc, Pepck, Gck, PYGL, Gys2, PKLR, GLUT4) and insulin resistance-related genes (AdipoR1, AdipoR2) in the muscles and livers of rats induced by CORT.	Metformin	0-9	PPARG coactivator 1 alpha	Rattus norvegicus	92-102
33634460-10	2021	Metformin normalized the alterations in the expression of glucose metabolism-related genes (PGC-1alpha, G6pc, Pepck, Gck, PYGL, Gys2, PKLR, GLUT4) and insulin resistance-related genes (AdipoR1, AdipoR2) in the muscles and livers of rats induced by CORT.	Metformin	0-9	adiponectin receptor 1	Rattus norvegicus	185-192
33922757-0	2021	Metformin Protects against NMDA-Induced Retinal Injury through the MEK/ERK Signaling Pathway in Rats.	Metformin	0-9	Eph receptor B1	Rattus norvegicus	71-74
33922757-6	2021	The neuroprotective effect of metformin was abolished by compound C, an inhibitor of AMP-activated protein kinase (AMPK).	Metformin	30-39	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	85-113
33922757-6	2021	The neuroprotective effect of metformin was abolished by compound C, an inhibitor of AMP-activated protein kinase (AMPK).	Metformin	30-39	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	115-119
33922757-9	2021	These results suggest that metformin protects against NMDA-induced retinal neurotoxicity through activation of the AMPK and MEK/extracellular signal-regulated kinase (ERK) signaling pathways.	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	115-119
33922757-9	2021	These results suggest that metformin protects against NMDA-induced retinal neurotoxicity through activation of the AMPK and MEK/extracellular signal-regulated kinase (ERK) signaling pathways.	Metformin	27-36	Eph receptor B1	Rattus norvegicus	167-170
33893356-7	2021	In addition, co-treatment with metformin and UPA was associated with significant increase in the Bax and significant reduction in Bcl-2, PCNA, Cyclin-D1and ER-alpha as compared to treatment with UPA alone.	Metformin	31-40	BCL2, apoptosis regulator	Rattus norvegicus	130-135
33893356-7	2021	In addition, co-treatment with metformin and UPA was associated with significant increase in the Bax and significant reduction in Bcl-2, PCNA, Cyclin-D1and ER-alpha as compared to treatment with UPA alone.	Metformin	31-40	cyclin D1	Rattus norvegicus	143-152
33886150-7	2021	We found that cotreatment with metformin (30 mM) and pitavastatin (10 muM) significantly reduced cell viability; caused G0/G1 cell cycle arrest; upregulated the expression levels of Bax, PCNA, cleaved PARP-1, cleaved caspase-3, LC3 II, and p27 Kip1 /p21Cip1 ; and inhibited cell migration.	Metformin	31-40	BCL2 associated X, apoptosis regulator	Homo sapiens	182-185
33886150-7	2021	We found that cotreatment with metformin (30 mM) and pitavastatin (10 muM) significantly reduced cell viability; caused G0/G1 cell cycle arrest; upregulated the expression levels of Bax, PCNA, cleaved PARP-1, cleaved caspase-3, LC3 II, and p27 Kip1 /p21Cip1 ; and inhibited cell migration.	Metformin	31-40	poly(ADP-ribose) polymerase 1	Homo sapiens	201-207
33886150-7	2021	We found that cotreatment with metformin (30 mM) and pitavastatin (10 muM) significantly reduced cell viability; caused G0/G1 cell cycle arrest; upregulated the expression levels of Bax, PCNA, cleaved PARP-1, cleaved caspase-3, LC3 II, and p27 Kip1 /p21Cip1 ; and inhibited cell migration.	Metformin	31-40	caspase 3	Homo sapiens	217-226
33886150-7	2021	We found that cotreatment with metformin (30 mM) and pitavastatin (10 muM) significantly reduced cell viability; caused G0/G1 cell cycle arrest; upregulated the expression levels of Bax, PCNA, cleaved PARP-1, cleaved caspase-3, LC3 II, and p27 Kip1 /p21Cip1 ; and inhibited cell migration.	Metformin	31-40	cyclin dependent kinase inhibitor 1A	Homo sapiens	250-257
33886150-9	2021	Moreover, cotreating the cells with metformin (30 mM) and pitavastatin (10 muM) could preserve mitochondrial function, activate AMPK, and inhibit PI3K/mTOR than treatment with metformin or pitavastatin alone.	Metformin	36-45	mechanistic target of rapamycin kinase	Homo sapiens	151-155
33886150-10	2021	These findings clearly indicated that metformin plus pitavastatin had a synergistic anticancer effect on pancreatic cancer cells, potentially caused due to the activation of AMPK and inhibition of PI3K/mTOR signaling.	Metformin	38-47	mechanistic target of rapamycin kinase	Homo sapiens	202-206
33884414-0	2021	Effects of Behavioral Weight Loss and Metformin on Insulin-like Growth Factors in Cancer Survivors: A Randomized Trial.	Metformin	38-47	insulin	Homo sapiens	51-58
33884414-10	2021	Compared to the self-directed group, participants in metformin had significant decreases on IGF-1 (mean difference in change: -5.50 ng/ml, p=0.02) and IGF1:IGFBP3 molar ratio (mean difference in change: -0.0119, p=0.011) at 3 months.	Metformin	53-62	insulin like growth factor 1	Homo sapiens	92-97
33884414-10	2021	Compared to the self-directed group, participants in metformin had significant decreases on IGF-1 (mean difference in change: -5.50 ng/ml, p=0.02) and IGF1:IGFBP3 molar ratio (mean difference in change: -0.0119, p=0.011) at 3 months.	Metformin	53-62	insulin like growth factor 1	Homo sapiens	151-155
33884414-14	2021	CONCLUSIONS: In cancer survivors with obesity, metformin may have a short-term effect on IGF-1 reduction that wanes over time.	Metformin	47-56	insulin like growth factor 1	Homo sapiens	89-94
33967805-1	2021	Organic Cation Transporter 1 (OCT1, gene symbol: SLC22A1) is predominately expressed in human liver, localized in the basolateral membrane of hepatocytes and facilitates the uptake of endogenous compounds (e.g. serotonin, acetylcholine, thiamine), and widely prescribed drugs (e.g. metformin, fenoterol, morphine).	Metformin	282-291	solute carrier family 22 member 1	Homo sapiens	0-28
33967805-1	2021	Organic Cation Transporter 1 (OCT1, gene symbol: SLC22A1) is predominately expressed in human liver, localized in the basolateral membrane of hepatocytes and facilitates the uptake of endogenous compounds (e.g. serotonin, acetylcholine, thiamine), and widely prescribed drugs (e.g. metformin, fenoterol, morphine).	Metformin	282-291	solute carrier family 22 member 1	Homo sapiens	30-34
33967805-1	2021	Organic Cation Transporter 1 (OCT1, gene symbol: SLC22A1) is predominately expressed in human liver, localized in the basolateral membrane of hepatocytes and facilitates the uptake of endogenous compounds (e.g. serotonin, acetylcholine, thiamine), and widely prescribed drugs (e.g. metformin, fenoterol, morphine).	Metformin	282-291	solute carrier family 22 member 1	Homo sapiens	49-56
33997311-7	2021	KDM individuals on metformin treatment exhibited lower levels of TIMP-1, -2 and -4 at baseline and of TIMP-4 at post-treatment.	Metformin	19-28	TIMP metallopeptidase inhibitor 1	Homo sapiens	65-82
33997311-8	2021	Conclusions: TIMP levels were elevated in TB-DM, associated with disease severity and bacterial burden, correlated with HbA1c levels and modulated by duration of DM and metformin treatment.	Metformin	169-178	TIMP metallopeptidase inhibitor 1	Homo sapiens	13-17
33968030-6	2021	Mechanistically, metformin treatment modulated the phosphorylation of dynamin-related protein 1 (Drp-1) and mitochondrial fission 1 protein (FIS1), resulting in increased mass in effector T cells.	Metformin	17-26	dynamin 1-like	Mus musculus	70-95
33968030-6	2021	Mechanistically, metformin treatment modulated the phosphorylation of dynamin-related protein 1 (Drp-1) and mitochondrial fission 1 protein (FIS1), resulting in increased mass in effector T cells.	Metformin	17-26	dynamin 1-like	Mus musculus	97-102
33887240-13	2021	Hypoglycemic episodes were significantly more common in the insulin-treated group (55.9% vs 17.7% on metformin, OR 6.118, 95% CI 3.134-11.944, p 0.000).	Metformin	101-110	insulin	Homo sapiens	60-67
33953705-8	2021	ROS/RNS level was reduced in immune cells after metformin stimulation accompanied by induction of the FOXO3 targets mitochondrial superoxide dismutase and cytochrome c. Studies in Foxo3 deficient (Foxo3-/- ) mouse splenocytes confirmed that metformin mediates its effects via Foxo3 as it attenuates ROS/RNS in myeloid cells of wildtype (WT) but not of Foxo3-/- mice.	Metformin	241-250	forkhead box O3	Homo sapiens	102-107
33881795-7	2021	Among treatment visits where a single drug was prescribed, use of metformin declined from 57.0% of monotherapy in 2015 to 46.0% of monotherapy in 2019, while during the same period the share of monotherapy accounted for by Glucagon-like peptide -1 (GLP-1) agonists increased from 4.3% to 8.5% and the share accounted for by sodium-glucose cotransporter-2 (SGLT-2) inhibitors increased from 7.3% to 19.5%.	Metformin	66-75	glucagon	Homo sapiens	249-254
33881795-8	2021	Among treatment visits where metformin plus another drug was prescribed, the share of second line therapy accounted for by dipeptidyl peptidase-4 (DPP-4) inhibitors decreased from 21.9% of treatment visits in 2015 to 20.8% of treatment visits in 2019; sulfonylurea use declined from 45.2% to 32.7%, use of SGLT-2 inhibitors increased from 14.5% to 21.2% and use of GLP-1 agonists increased from 9.8% to 18.2%.	Metformin	29-38	glucagon	Homo sapiens	365-370
33876387-10	2021	While the expression of AKT in the AST group revealed a significant increase (P<0.05), it decreased in the metformin group.	Metformin	107-116	thymoma viral proto-oncogene 1	Mus musculus	24-27
33953705-2	2021	Here, we investigated if metformin can activate FOXO3 in human immune cells and affects the subsequent level of reactive oxygen/nitrogen species (ROS/RNS) in immune cells.	Metformin	25-34	forkhead box O3	Homo sapiens	48-53
33953705-7	2021	Metformin induced activation of AMPK (pT172) and FOXO3 (pS413).	Metformin	0-9	forkhead box O3	Homo sapiens	49-54
33302299-13	2021	Although currently no intervention can be universally recommended to reverse endometrial dysfunction in PCOS women, lifestyle modifications and metformin may improve underlying endometrial dysfunction and pregnancy outcomes in obese and/or insulin resistant patients.	Metformin	144-153	insulin	Homo sapiens	240-247
33865459-15	2021	Additionally, the expressions of PCK1 and ABAT were raised in HepG2 cells pre-treated with metformin and phenformin.	Metformin	91-100	4-aminobutyrate aminotransferase	Homo sapiens	42-46
33860870-10	2021	Metformin, metformin and ketamine, triciribine, LY294002, and torin2 reduced Akt and PI3K expression, peribronchial and perivascular inflammation, and increased expression of Foxp3.	Metformin	0-9	thymoma viral proto-oncogene 1	Mus musculus	77-80
33860870-10	2021	Metformin, metformin and ketamine, triciribine, LY294002, and torin2 reduced Akt and PI3K expression, peribronchial and perivascular inflammation, and increased expression of Foxp3.	Metformin	11-20	thymoma viral proto-oncogene 1	Mus musculus	77-80
33849997-5	2021	Metformin has beneficial effects in humans in tissues with high levels of mGPD such as pancreatic beta cells where mGPD is much higher than in liver.	Metformin	0-9	atypical chemokine receptor 1 (Duffy blood group)	Mus musculus	74-78
33854039-9	2021	Our results show that metformin improved dysglycemia and insulin sensitivity, independent of weight loss, in a young population with prediabetes/diabetes and psychosis spectrum illness, that is at extremely high risk of early cardiovascular mortality.	Metformin	22-31	insulin	Homo sapiens	57-64
33849997-5	2021	Metformin has beneficial effects in humans in tissues with high levels of mGPD such as pancreatic beta cells where mGPD is much higher than in liver.	Metformin	0-9	atypical chemokine receptor 1 (Duffy blood group)	Mus musculus	115-119
33849997-7	2021	For these and other reasons we used four different enzyme assays to reassess whether metformin inhibited mGPD.	Metformin	85-94	atypical chemokine receptor 1 (Duffy blood group)	Mus musculus	105-109
33849997-9	2021	If metformin actually inhibited mGPD, adverse effects in tissues where the level of mGPD is much higher than in liver could prevent metformin"s use as a diabetes medicine.	Metformin	3-12	atypical chemokine receptor 1 (Duffy blood group)	Mus musculus	32-36
33849997-9	2021	If metformin actually inhibited mGPD, adverse effects in tissues where the level of mGPD is much higher than in liver could prevent metformin"s use as a diabetes medicine.	Metformin	3-12	atypical chemokine receptor 1 (Duffy blood group)	Mus musculus	84-88
33849997-9	2021	If metformin actually inhibited mGPD, adverse effects in tissues where the level of mGPD is much higher than in liver could prevent metformin"s use as a diabetes medicine.	Metformin	132-141	atypical chemokine receptor 1 (Duffy blood group)	Mus musculus	32-36
33849997-9	2021	If metformin actually inhibited mGPD, adverse effects in tissues where the level of mGPD is much higher than in liver could prevent metformin"s use as a diabetes medicine.	Metformin	132-141	atypical chemokine receptor 1 (Duffy blood group)	Mus musculus	84-88
33854349-11	2021	The wound healing process in rats treated with insulin was more effective than in the metformin and control groups.	Metformin	86-95	insulin	Homo sapiens	47-54
33917520-9	2021	Systematic findings on the nine publications indicated metformin decreased insulin levels in four studies, FBS in one, BMI in two, Ki-67 in three studies, and HOMA-IR in two study.	Metformin	55-64	insulin	Homo sapiens	75-82
33513084-3	2021	Metformin is an AMP Kinase (AMPK) activator, the widest used anti-diabetic drug.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	16-26
33927970-6	2021	Furthermore, anti-diabetic drugs including metformin, thiazolidinediones, and glucagon-like peptide-1 (GLP-1) analogue could modulate IRS-1 phosphorylation, brain IR, PI3K/Akt insulin signaling pathway, and other pathologic processes of AD.	Metformin	43-52	AKT serine/threonine kinase 1	Homo sapiens	172-175
33927970-6	2021	Furthermore, anti-diabetic drugs including metformin, thiazolidinediones, and glucagon-like peptide-1 (GLP-1) analogue could modulate IRS-1 phosphorylation, brain IR, PI3K/Akt insulin signaling pathway, and other pathologic processes of AD.	Metformin	43-52	insulin	Homo sapiens	176-183
33513084-10	2021	Furthermore, our data demonstrate that metformin mediated activation of AMPK is responsible for poor homing and survival of BM-MSCs in the diabetic heart.	Metformin	39-48	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	72-76
33915682-2	2021	Pharmacological treatments for EMS include metformin, a biguanide antihyperglycemic agent also administered to people to help improve glucose tolerance and insulin sensitivity.	Metformin	43-52	insulin	Homo sapiens	156-163
33535788-0	2021	New Insight Into Metformin-Induced Cholesterol-Lowering Effect Crosstalk Between Glucose and Cholesterol Homeostasis via ChREBP (Carbohydrate-Responsive Element-Binding Protein)-Mediated PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Regulation.	Metformin	17-26	MLX interacting protein like	Homo sapiens	121-127
33439105-3	2021	Therefore, the aim of this study was to investigate whether metformin, an indirect AMPK activator, was effective in PCK rats.	Metformin	60-69	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	83-87
33439105-8	2021	Metformin increased the phosphorylation of AMPK and decreased the phosphorylation of mammalian target of rapamycin and extracellular signal-regulated kinase and the expression of cystic fibrosis transmembrane conductance regulator, aquaporin I, transforming growth factor-beta and type 1 collagen in the liver.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	85-114
33439105-9	2021	Conclusions Metformin slows the development of cyst formation and fibrosis with activation of AMPK and inhibition of signaling cascades responsible for cellular proliferation and fibrosis in the liver of PCK rats.	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	94-98
33109447-0	2021	Glycemic Impact of Metformin in Diabetes Caused by Heterozygous Insulin Gene Mutation R46Q.	Metformin	19-28	insulin	Homo sapiens	64-71
32761290-0	2021	Sex differences in changes of protein synthesis with rapamycin treatment are minimized when metformin is added to rapamycin.	Metformin	92-101	regulatory associated protein of MTOR, complex 1	Mus musculus	53-62
33642112-11	2021	Metformin alleviated transcription and secretion of IL-1beta, Tumor Necrosis Factor-alpha, and Fibroblast Growth Factor 2, expression and nuclear translocation of C/EBPbeta in this model.	Metformin	0-9	tumor necrosis factor	Mus musculus	62-89
33625942-0	2021	Metformin Alleviates Cisplatin-Induced Ototoxicity by Autophagy Induction Possibly via the AMPK/FOXO3a Pathway.	Metformin	0-9	forkhead box O3	Homo sapiens	96-102
33625942-10	2021	Notably, metformin activated autophagy and increased the expression levels of the adenosine monophosphate-activated protein kinase (AMPK) and the transcription factor Forkhead box protein O3 (FOXO3a), while cells with AMPK silencing displayed otherwise.	Metformin	9-18	forkhead box O3	Homo sapiens	167-190
33625942-10	2021	Notably, metformin activated autophagy and increased the expression levels of the adenosine monophosphate-activated protein kinase (AMPK) and the transcription factor Forkhead box protein O3 (FOXO3a), while cells with AMPK silencing displayed otherwise.	Metformin	9-18	forkhead box O3	Homo sapiens	192-198
33625942-11	2021	Our findings indicate that metformin alleviates cisplatin-induced ototoxicity possibly through AMPK/FOXO3a-mediated autophagy machinery.	Metformin	27-36	forkhead box O3	Homo sapiens	100-106
33915902-9	2021	In addition, metformin treatment increased the expression of monophosphate (AMP)-activated protein kinase (AMPK) and p53 in both HCT116 xenografts and colorectal cancer cell lines and decreased the expression of the urea cycle enzymes, including carbamoyl phosphate synthase 1 (CPS1), arginase 1 (ARG1), ornithine trans-carbamylase (OTC), and ODC.	Metformin	13-22	tumor protein p53	Homo sapiens	117-120
33915902-11	2021	These results demonstrate that metformin inhibited CRC cell proliferation via activating AMPK/p53 and that there was an association between metformin, urea cycle inhibition and a reduction in putrescine generation.	Metformin	31-40	tumor protein p53	Homo sapiens	94-97
33784336-15	2021	CONCLUSION: Vitamin B12 deficiency and diabetic neuropathy are very high among metformin-treated T2DM patients and it is associated with increased GPA, IFA, TNF-alpha and cardiometabolic risk factors (higher LDL and TC and lower HDL).	Metformin	79-88	glycophorin A (MNS blood group)	Homo sapiens	147-150
33784336-15	2021	CONCLUSION: Vitamin B12 deficiency and diabetic neuropathy are very high among metformin-treated T2DM patients and it is associated with increased GPA, IFA, TNF-alpha and cardiometabolic risk factors (higher LDL and TC and lower HDL).	Metformin	79-88	tumor necrosis factor	Homo sapiens	157-166
33781829-10	2021	After activation of AMPK by metformin, expressions of p-AMPKalpha, SIRT1 were significantly raised, while expressions of Beclin-1, LC3 II/I, p62, TNF-alpha, IL-6 were reduced, and the number of autophagosome was decreased significantly in caerulein-stimulated AR42J cells.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	20-24
33781829-10	2021	After activation of AMPK by metformin, expressions of p-AMPKalpha, SIRT1 were significantly raised, while expressions of Beclin-1, LC3 II/I, p62, TNF-alpha, IL-6 were reduced, and the number of autophagosome was decreased significantly in caerulein-stimulated AR42J cells.	Metformin	28-37	sirtuin 1	Rattus norvegicus	67-72
33781829-10	2021	After activation of AMPK by metformin, expressions of p-AMPKalpha, SIRT1 were significantly raised, while expressions of Beclin-1, LC3 II/I, p62, TNF-alpha, IL-6 were reduced, and the number of autophagosome was decreased significantly in caerulein-stimulated AR42J cells.	Metformin	28-37	interleukin 6	Rattus norvegicus	157-161
33517358-8	2021	Metformin, thalidomide and cytokines (IFN, tumor necrosis factor (TNF), interleukin-2 (IL-2) and others) have pleiomorphic activities, some of which can enhance tumorigenesis.	Metformin	0-9	tumor necrosis factor	Homo sapiens	43-64
33517358-8	2021	Metformin, thalidomide and cytokines (IFN, tumor necrosis factor (TNF), interleukin-2 (IL-2) and others) have pleiomorphic activities, some of which can enhance tumorigenesis.	Metformin	0-9	tumor necrosis factor	Homo sapiens	66-69
33517358-8	2021	Metformin, thalidomide and cytokines (IFN, tumor necrosis factor (TNF), interleukin-2 (IL-2) and others) have pleiomorphic activities, some of which can enhance tumorigenesis.	Metformin	0-9	interleukin 2	Homo sapiens	72-85
33517358-8	2021	Metformin, thalidomide and cytokines (IFN, tumor necrosis factor (TNF), interleukin-2 (IL-2) and others) have pleiomorphic activities, some of which can enhance tumorigenesis.	Metformin	0-9	interleukin 2	Homo sapiens	87-91
33382900-0	2021	TLR4-associated IRF-7 and NFkB signaling acts as a molecular link between androgen and metformin activities and cytokine synthesis in the PCOS endometrium.	Metformin	87-96	interferon regulatory factor 7	Homo sapiens	16-21
33382900-10	2021	CONCLUSION: Cytokine synthesis and increased endometrial inflammation in PCOS patients is coupled to androgen-induced TLR4/IRF-7/NFkB signaling, which is be inhibited by metformin treatment.	Metformin	170-179	interferon regulatory factor 7	Homo sapiens	123-128
33395696-8	2021	These abnormalities were ameliorated by pharmacological activation of UNC-51/ATG1, a FEZ1-activating kinase, with rapamycin and metformin.	Metformin	128-137	fasciculation and elongation protein zeta 1	Homo sapiens	85-89
33796404-9	2021	Metabolic modulation with metformin modifies the acetylation pattern in the B7-H6 promoter, impairing BRD4 binding, thereby inhibiting B7-H6 expression.	Metformin	26-35	bromodomain containing 4	Homo sapiens	102-106
33841337-7	2021	GLP1 RAs and metformin also had better therapeutic effects than other drugs as measured by the levels of ALT (liraglutide: -9.36 (95% Cl -18 to -0.34), metformin: -2.84 (95% CI -11.09 to 5.28)) and AST (liraglutide: -5.14 (95% CI -10.69 to 0.37), metformin: -2.39 (95% CI -7.55, 2.49)) and other biological indicators.	Metformin	13-22	solute carrier family 17 member 5	Homo sapiens	198-201
33759685-11	2021	In patients with impaired glucose metabolism and insulin resistance, Metformin should also be considered as part of treatment.	Metformin	69-78	insulin	Homo sapiens	49-56
33626869-9	2021	Ag2S QD nanomedicines improved the pharmacokinetic and pharmacodynamic properties of metformin and NMN by increasing their therapeutic potency, bypassing classical cellular uptake pathways, and demonstrated efficacy when drug alone was ineffective in aging mice.	Metformin	85-94	angiotensin II receptor, type 1a	Mus musculus	0-4
33752282-8	2021	The cell growth and Bcl-2 expression level suppressed under hypoxia were reversed with a decrease of the induced Hif-1alpha and Cav-1 levels after AMPK activation with metformin (1 mM) or phenformin (0.1 microM).	Metformin	168-177	BCL2 apoptosis regulator	Homo sapiens	20-25
33752282-8	2021	The cell growth and Bcl-2 expression level suppressed under hypoxia were reversed with a decrease of the induced Hif-1alpha and Cav-1 levels after AMPK activation with metformin (1 mM) or phenformin (0.1 microM).	Metformin	168-177	hypoxia inducible factor 1 subunit alpha	Homo sapiens	113-123
33752282-8	2021	The cell growth and Bcl-2 expression level suppressed under hypoxia were reversed with a decrease of the induced Hif-1alpha and Cav-1 levels after AMPK activation with metformin (1 mM) or phenformin (0.1 microM).	Metformin	168-177	caveolin 1	Homo sapiens	128-133
33757524-0	2021	Correction to: A combination of herbal compound (SPTC) along with exercise or metformin more efficiently alleviated diabetic complications through down-regulation of stress oxidative pathway upon activating Nrf2-Keap1 axis in AGE rich diet-induced type 2 diabetic mice.	Metformin	78-87	nuclear factor, erythroid derived 2, like 2	Mus musculus	207-211
33733926-3	2021	Additionally, GLUT4, AKT2 and AMPK were docked with catechin, epicatechin, kaempferol, metformin, quercetin and ursolic acid reportedly present in Potentilla fulgens.	Metformin	87-96	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	14-19
33728428-2	2021	OBJECTIVE: Evaluate the impact of metformin treatment during puberty, a critical window of cardiometabolic change, on insulin sensitivity (Si) and compensatory beta-cell response in youth with obesity.	Metformin	34-43	insulin	Homo sapiens	118-125
33841656-15	2021	In addition, metformin overcame progestin resistance by down-regulating Nrf2/LASS2 expression.	Metformin	13-22	NFE2 like bZIP transcription factor 2	Homo sapiens	72-76
33719959-10	2021	Compared with controls, metformin can effectively reduce serum fasting glucose and insulin levels and the HOMA-IR index in NAFLD patients at the 6-month follow-up.	Metformin	24-33	insulin	Homo sapiens	83-90
33719959-14	2021	CONCLUSION: Compared to the controls, metformin can effectively reduce the serum fasting glucose and insulin levels and the HOMA-IR index in NAFLD patients at the 6-month follow-up and ALT and the HOMA-IR index at the 12-month follow-up.	Metformin	38-47	insulin	Homo sapiens	101-108
33758522-6	2021	T2DM on metformin group had significantly higher Bad, Bax, and caspase-7 expression.	Metformin	8-17	BCL2 associated X, apoptosis regulator	Homo sapiens	54-57
33758522-8	2021	Metformin treatment significantly inhibited the expression of Bcl-10, Bid, and caspase-3 and upregulated Bad/Bax/caspase-7 pathway suggesting the activation of Bad/Bax/caspase-7 apoptotic pathway.	Metformin	0-9	BH3 interacting domain death agonist	Homo sapiens	70-73
33758522-8	2021	Metformin treatment significantly inhibited the expression of Bcl-10, Bid, and caspase-3 and upregulated Bad/Bax/caspase-7 pathway suggesting the activation of Bad/Bax/caspase-7 apoptotic pathway.	Metformin	0-9	caspase 3	Homo sapiens	79-88
33758522-8	2021	Metformin treatment significantly inhibited the expression of Bcl-10, Bid, and caspase-3 and upregulated Bad/Bax/caspase-7 pathway suggesting the activation of Bad/Bax/caspase-7 apoptotic pathway.	Metformin	0-9	BCL2 associated X, apoptosis regulator	Homo sapiens	109-112
33758522-8	2021	Metformin treatment significantly inhibited the expression of Bcl-10, Bid, and caspase-3 and upregulated Bad/Bax/caspase-7 pathway suggesting the activation of Bad/Bax/caspase-7 apoptotic pathway.	Metformin	0-9	BCL2 associated X, apoptosis regulator	Homo sapiens	164-167
33690729-5	2021	Metformin is an insulin-sensitizing biguanide drug, commonly used in the treatment of type II diabetes mellitus, especially in obese patients.	Metformin	0-9	insulin	Homo sapiens	16-23
33690729-7	2021	Direct anti-cancer effects of metformin target signaling pathways that are involved in cellular growth and proliferation, e.g. the AKT/PKB/mTOR pathway.	Metformin	30-39	AKT serine/threonine kinase 1	Homo sapiens	131-138
33690729-7	2021	Direct anti-cancer effects of metformin target signaling pathways that are involved in cellular growth and proliferation, e.g. the AKT/PKB/mTOR pathway.	Metformin	30-39	mechanistic target of rapamycin kinase	Homo sapiens	139-143
33690729-18	2021	However, further investigations are necessary to confirm the observations and conclusions drawn from the presented data after metformin administration, especially for proteins that were regulated in a favorable way, i.e. AKT3, CCND2, CD63, CD81, GFAP, IL5, IL17A, IRF4, PI3, and VTCN1.	Metformin	126-135	cyclin D2	Homo sapiens	227-232
33831975-6	2022	Metformin may reduce the risk of BPH by inhibiting the insulin-like growth factor 1 pathway and some but not all studies suggest a protective role of metformin on the risk of PCa.	Metformin	0-9	insulin like growth factor 1	Homo sapiens	55-83
33516778-12	2021	The inverse association with ER-positive cancer was stronger for longer duration (>=10 year) metformin use (HR 0.62; 95% CI, 0.38-1.01; P for trend=0.09).	Metformin	93-102	estrogen receptor 1	Homo sapiens	29-31
33516778-14	2021	CONCLUSION: Our findings suggest that associations between T2D and breast cancer may differ by hormone receptor status and that associations between T2D and ER-positive breast cancer may be reduced by long-term metformin use.	Metformin	211-220	estrogen receptor 1	Homo sapiens	157-159
33788730-3	2021	MATERIALS AND METHODS: Metformin with trametinib and paclitaxel was tested for effects on cell viability, signaling molecules in MAPK and mTOR pathways, factors involved in epithelial-mesenchymal transition (EMT), and cell motility.	Metformin	23-32	mitogen-activated protein kinase 1	Homo sapiens	129-133
33788730-4	2021	RESULTS: The combination of metformin with trametinib and paclitaxel showed differential growth inhibitory effects; synergistic effects were observed in a cell line in which metformin suppresses ERK activity, whereas the combination showed antagonistic effects in a cell line with metformin-induced ERK activation.	Metformin	28-37	mitogen-activated protein kinase 1	Homo sapiens	195-198
33788730-4	2021	RESULTS: The combination of metformin with trametinib and paclitaxel showed differential growth inhibitory effects; synergistic effects were observed in a cell line in which metformin suppresses ERK activity, whereas the combination showed antagonistic effects in a cell line with metformin-induced ERK activation.	Metformin	28-37	mitogen-activated protein kinase 1	Homo sapiens	299-302
33666871-9	2021	Compared with the model group, IL-6 and visfatin levels were significantly decreased in the acupuncture and metformin groups (P<0.05).	Metformin	108-117	interleukin 6	Rattus norvegicus	31-35
32462317-10	2021	Restoration of the insulin signaling pathway, IRS/Akt/GLUT4 protein expression, was demonstrated in hesperidin and metformin-treated groups (p < 0.05).	Metformin	115-124	AKT serine/threonine kinase 1	Rattus norvegicus	50-53
33147367-0	2021	Cytotoxicity of metformin against HT29 colon cancer cells contributes to mitochondrial Sirt3 upregulation.	Metformin	16-25	sirtuin 3	Homo sapiens	87-92
33147367-2	2021	In this study, the effect of metformin, an antidiabetic with anticancer properties, has been evaluated on mitochondrial functionality markers, cell death pathways, and SIRT3 enzyme activity in the colon cancer cell line, HT-29, and human embryonic kidney cells (HEK 293).	Metformin	29-38	sirtuin 3	Homo sapiens	168-173
33147367-7	2021	Results from SIRT3 activity and expression showed that metformin increased its activity and expression in cancer cells.	Metformin	55-64	sirtuin 3	Homo sapiens	13-18
33147367-8	2021	In conclusion, metformin in HT-29 cells disturbed the mitochondrial activity via increased ROS levels and SIRT3 activity, and these rapid modifications may play a key role in its cytotoxic property.	Metformin	15-24	sirtuin 3	Homo sapiens	106-111
33538080-3	2021	First, metformin reduced mRNA levels of TGF-beta1 in gastric cancer cells, in parallel to the decrease of its protein abundance.	Metformin	7-16	transforming growth factor beta 1	Homo sapiens	40-49
33538080-6	2021	Third, metformin suppressed firefly luciferase activity whose transcription was driven by TGF-beta1 promoter.	Metformin	7-16	transforming growth factor beta 1	Homo sapiens	90-99
33538080-7	2021	In accordance, deletion of the putative binding site of Smad3 in the TGF-beta1 promoter region severely impaired the promoter activity and response to metformin.	Metformin	151-160	transforming growth factor beta 1	Homo sapiens	69-78
33538080-8	2021	Fourth, in support of our in vitro study, clinical treatment of type 2 diabetes with metformin significantly reduced the plasma level of TGF-beta1.	Metformin	85-94	transforming growth factor beta 1	Homo sapiens	137-146
33475696-0	2021	Association of Metformin Use With Age-Related Macular Degeneration: A Case-Control Study.	Metformin	15-24	renin binding protein	Homo sapiens	34-37
33475696-2	2021	The common antidiabetic drug metformin has been shown to have protective outcomes in multiple age-associated diseases and may have the potential to protect against the development of AMD.	Metformin	29-38	renin binding protein	Homo sapiens	94-97
32241082-8	2021	Results: Sub-toxic doses of metformin enhanced nilotinib efficacy by reducing Bcl-xL expression, which induces apoptosis in CML cells.	Metformin	28-37	BCL2 like 1	Homo sapiens	78-84
32241082-11	2021	Furthermore, metformin was effective in decreasing phosphorylated JNK levels, restoring nilotinib sensitivity.	Metformin	13-22	mitogen-activated protein kinase 8	Homo sapiens	66-69
32241082-12	2021	Combined treatment with nilotinib and metformin was more effective than combined treatment with nilotinib and a JNK inhibitor in terms of cell proliferation inhibition.	Metformin	38-47	mitogen-activated protein kinase 8	Homo sapiens	112-115
33412215-9	2021	SIGNIFICANCE: These results suggested that metformin modulated HG-induced endothelial ROS via the AMPKalpha/Lin-28/OGG1 pathway.	Metformin	43-52	lin-28 homolog A	Homo sapiens	108-114
33495648-3	2021	We have generated a novel Fbxo48 inhibitory compound, BC1618, whose potency in stimulating Ampk-dependent signaling greatly exceeds 5-aminoimidazole-4-carboxamide-1-beta-ribofuranoside (AICAR) or metformin.	Metformin	196-205	F-box protein 48	Mus musculus	26-32
33047165-10	2021	Metformin significantly attenuated diabetes-related histopathological ocular deteriorations in the cornea, lens, sclera, ciliary body, iris, conjunctiva, retina, and optic nerve partly by restoring serum TNF-alpha, VEGF, claudin-1, and glutathione/malondialdehyde ratios without significantly affecting the fasting blood glucose levels or body weight in these hyperglycemic rats.	Metformin	0-9	tumor necrosis factor	Rattus norvegicus	204-213
33141769-0	2021	Metformin Inhibits Transforming Growth Factor beta-Induced Fibrogenic Response of Human Dermal Fibroblasts and Suppresses Fibrosis in Keloid Spheroids.	Metformin	0-9	tumor necrosis factor	Homo sapiens	19-50
33141769-7	2021	In addition, the expression levels of collagen types I and III, fibronectin, and elastin were significantly reduced in keloid spheroids after treatment with metformin (100 mM).	Metformin	157-166	fibronectin 1	Homo sapiens	64-75
33535788-6	2021	Metformin decreased the expression of ChREBP and inhibited its transcriptional activity by blocking its nuclear translocation attributed to the decreased intracellular glucose and glucose metabolites levels.	Metformin	0-9	MLX interacting protein like	Homo sapiens	38-44
33535788-8	2021	CONCLUSIONS: Collectively, we revealed a new mechanism of action of metformin in cholesterol-lowering and identified a novel crosstalk signal between glucose and cholesterol homeostasis via ChREBP-mediated PCSK9 regulation.	Metformin	68-77	MLX interacting protein like	Homo sapiens	190-196
33650651-0	2021	Metformin inhibits mTOR and c-Myc by decreasing YAP protein expression in OSCC cells.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	19-23
33650651-9	2021	In addition, compared to the control treatment, metformin treatment decreased the protein levels of YAP, mTOR, p-mTOR and c-Myc.	Metformin	48-57	mechanistic target of rapamycin kinase	Homo sapiens	105-109
33535788-0	2021	New Insight Into Metformin-Induced Cholesterol-Lowering Effect Crosstalk Between Glucose and Cholesterol Homeostasis via ChREBP (Carbohydrate-Responsive Element-Binding Protein)-Mediated PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Regulation.	Metformin	17-26	MLX interacting protein like	Homo sapiens	129-176
33650651-9	2021	In addition, compared to the control treatment, metformin treatment decreased the protein levels of YAP, mTOR, p-mTOR and c-Myc.	Metformin	48-57	mechanistic target of rapamycin kinase	Homo sapiens	113-117
33650651-10	2021	The overexpression of YAP alleviated the inhibitory effect of metformin on the protein expression of mTOR, p-mTOR and c-Myc.	Metformin	62-71	mechanistic target of rapamycin kinase	Homo sapiens	101-105
33608415-9	2021	Metformin resulted in a modest decrease in BMI (range of mean values: -2.70 to 1.30 vs -1.12 to 1.90), BMI z score (range of mean values: -0.37 to -0.03 vs -0.22 to 0.15), and homeostatic model assessment of insulin resistance (range of mean values: -3.74 to 1.00 vs -1.40 to 2.66).	Metformin	0-9	insulin	Homo sapiens	208-215
33650651-10	2021	The overexpression of YAP alleviated the inhibitory effect of metformin on the protein expression of mTOR, p-mTOR and c-Myc.	Metformin	62-71	mechanistic target of rapamycin kinase	Homo sapiens	109-113
33650651-11	2021	The combination of metformin and verteporfin markedly enhanced the effects of metformin on the protein expression of mTOR, p-mTOR and c-Myc.	Metformin	19-28	mechanistic target of rapamycin kinase	Homo sapiens	117-121
33650651-11	2021	The combination of metformin and verteporfin markedly enhanced the effects of metformin on the protein expression of mTOR, p-mTOR and c-Myc.	Metformin	19-28	mechanistic target of rapamycin kinase	Homo sapiens	125-129
33650651-11	2021	The combination of metformin and verteporfin markedly enhanced the effects of metformin on the protein expression of mTOR, p-mTOR and c-Myc.	Metformin	78-87	mechanistic target of rapamycin kinase	Homo sapiens	117-121
33650651-11	2021	The combination of metformin and verteporfin markedly enhanced the effects of metformin on the protein expression of mTOR, p-mTOR and c-Myc.	Metformin	78-87	mechanistic target of rapamycin kinase	Homo sapiens	125-129
33650651-12	2021	Therefore, the results of the present study suggest that metformin suppresses OSCC by inhibiting YAP protein expression and by suppressing the YAP-mediated effects of metformin on the protein expression of mTOR and c-Myc.	Metformin	57-66	mechanistic target of rapamycin kinase	Homo sapiens	206-210
33650651-12	2021	Therefore, the results of the present study suggest that metformin suppresses OSCC by inhibiting YAP protein expression and by suppressing the YAP-mediated effects of metformin on the protein expression of mTOR and c-Myc.	Metformin	167-176	mechanistic target of rapamycin kinase	Homo sapiens	206-210
33141412-7	2021	Surprisingly, our results demonstrated that the treatment in which we applied the combination of quercetin and metformin significantly reversed these changes and had a pronounced effect on the endometrial implant size and gene expression levels of mTOR and autophagy markers in ectopic endometrium.	Metformin	111-120	mechanistic target of rapamycin kinase	Homo sapiens	248-252
33608415-12	2021	CONCLUSIONS: With this systematic review of RCTs, we suggest that metformin has modest but favorable effects on weight and insulin resistance and a tolerable safety profile among children and adolescents with obesity.	Metformin	66-75	insulin	Homo sapiens	123-130
32951988-1	2021	PURPOSE: Metformin, an insulin sensitizer, is the most common first-line antidiabetic therapy.	Metformin	9-18	insulin	Homo sapiens	23-30
33652909-8	2021	The cell-based analysis further indicated that metformin treatment regulated p38/JNK pathway to reduce Cyclin D1 and Bcl-2 expressions.	Metformin	47-56	mitogen-activated protein kinase 14	Homo sapiens	77-80
33652909-8	2021	The cell-based analysis further indicated that metformin treatment regulated p38/JNK pathway to reduce Cyclin D1 and Bcl-2 expressions.	Metformin	47-56	mitogen-activated protein kinase 8	Homo sapiens	81-84
33652909-8	2021	The cell-based analysis further indicated that metformin treatment regulated p38/JNK pathway to reduce Cyclin D1 and Bcl-2 expressions.	Metformin	47-56	BCL2 apoptosis regulator	Homo sapiens	117-122
33652909-9	2021	In addition, metformin activated the pathways of AMPKalpha and MEK/ERK to phosphorylate p27(Thr198) and reduce mTOR phosphorylation in cells.	Metformin	13-22	mitogen-activated protein kinase kinase 7	Homo sapiens	63-66
33652909-9	2021	In addition, metformin activated the pathways of AMPKalpha and MEK/ERK to phosphorylate p27(Thr198) and reduce mTOR phosphorylation in cells.	Metformin	13-22	mitogen-activated protein kinase 1	Homo sapiens	67-70
33652909-9	2021	In addition, metformin activated the pathways of AMPKalpha and MEK/ERK to phosphorylate p27(Thr198) and reduce mTOR phosphorylation in cells.	Metformin	13-22	dynactin subunit 6	Homo sapiens	88-91
33652909-9	2021	In addition, metformin activated the pathways of AMPKalpha and MEK/ERK to phosphorylate p27(Thr198) and reduce mTOR phosphorylation in cells.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	111-115
33622853-7	2021	Metformin or fructo-oligosaccharide supplementation significantly restored A. muciniphila and AHR ligands in sucralose-consuming mice, consequently ameliorating NAFLD.IMPORTANCE Our findings indicate that the gut-liver signaling axis contributes to saccharin/sucralose consumption-induced NAFLD.	Metformin	0-9	aryl-hydrocarbon receptor	Mus musculus	94-97
33671767-6	2021	The insulin-induced accumulation of MG and S-d-lactoylglutathione were efficiently removed by the treatment of metformin, possibly via affecting the glyoxalase system.	Metformin	111-120	insulin	Homo sapiens	4-11
33718411-6	2021	CRP, LDH, and D-dimer serum levels were also lowered in metformin-treated patients compared to non-metformin treated patients (p = 0.0001).	Metformin	56-65	C-reactive protein	Homo sapiens	0-3
33606350-5	2022	RESULTS: Metformin increased implant osteointegration in a rat model and promoted the osteogenic capacity of DM-BMSCs via the AMPK/BMP/Smad signalling pathway, and 125 muM was the optimal concentration; however, concentrations over 200 microM, metformin showed an inhibitory effect on DM-BMSCs.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	126-130
33594488-3	2021	Metformin treatment had a small but positive effect on bone quality in the peripheral skeleton, reduced weight gain, and resulted in a more beneficial body composition compared with placebo in insulin-treated patients with type 2 diabetes.	Metformin	0-9	insulin	Homo sapiens	193-200
33594488-6	2021	METHODS: This was a sub-study of the Copenhagen Insulin and Metformin Therapy trial, which was a double-blinded randomized placebo-controlled trial assessing 18-month treatment with metformin compared with placebo, in combination with different insulin regimens in patients with type 2 diabetes mellitus (T2DM).	Metformin	182-191	insulin	Homo sapiens	48-55
33594488-14	2021	CONCLUSION: Metformin treatment had a small positive effect on BMC and BMD in the peripheral skeleton and reduced weight gain compared with placebo in insulin-treated patients with T2DM.	Metformin	12-21	insulin	Homo sapiens	151-158
33578894-4	2021	Metformin suppressed the expression of H3K4 methyltransferases MLL1, MLL2, and WDR82.	Metformin	0-9	lysine (K)-specific methyltransferase 2B	Mus musculus	69-73
33658930-0	2020	Diffusion Mechanism Modeling of Metformin in Human Organic Cationic Amino Acid Transporter one and Functional Impact of S189L, R206C, and G401S Mutation.	Metformin	32-41	solute carrier family 38 member 7	Homo sapiens	68-90
33658930-9	2020	Metformin efficacy considerably varies from one patient to another; this may be largely attributed to the presence of mutations on the SLC22A1 gene.	Metformin	0-9	solute carrier family 22 member 1	Homo sapiens	135-142
33658930-10	2020	This study aims at proposing a potential structural model for metformin-hOCT1 (SLC22A1) transporter interaction, as well as the identification of the effect of mutations G401S (rs34130495), S189L (rs34104736), and R206C (616C > T) of the SLC22A1 gene at the topological and electronic structure levels on the channel surfaces, from a chemical viewpoint.	Metformin	62-71	solute carrier family 22 member 1	Homo sapiens	72-77
33658930-10	2020	This study aims at proposing a potential structural model for metformin-hOCT1 (SLC22A1) transporter interaction, as well as the identification of the effect of mutations G401S (rs34130495), S189L (rs34104736), and R206C (616C > T) of the SLC22A1 gene at the topological and electronic structure levels on the channel surfaces, from a chemical viewpoint.	Metformin	62-71	solute carrier family 22 member 1	Homo sapiens	79-86
33613693-1	2021	Background: The aim of this study was to improve activity over single human epidermal growth factor receptor 2 (HER2)-blockade sequential neaodjuvant regimens for HER2-positive breast cancer, by exploiting the concomitant administration of trastuzumab, taxane and anthracycline, while restraining cardiac toxicity with use of liposomal doxorubicin, and by adding metformin, based on preliminary evidence of antitumor activity.	Metformin	363-372	erb-b2 receptor tyrosine kinase 2	Homo sapiens	112-116
33561991-1	2021	AIMS: To examine the association of polymorphisms belonging to SLC22A1, SP1, PRPF31, NBEA, SCNN1B, CPA6 and CAPN10 genes with glycaemic response to metformin and sulphonylureas (SU) combination therapy among South African adults with diabetes mellitus type 2 (T2DM).	Metformin	148-157	calpain 10	Homo sapiens	108-114
33562646-0	2021	Metformin and Androgen Receptor-Axis-Targeted (ARAT) Agents Induce Two PARP-1-Dependent Cell Death Pathways in Androgen-Sensitive Human Prostate Cancer Cells.	Metformin	0-9	poly(ADP-ribose) polymerase 1	Homo sapiens	71-77
33562646-1	2021	We explored whether the anti-prostate cancer (PC) activity of the androgen receptor-axis-targeted agents (ARATs) abiraterone and enzalutamide is enhanced by metformin.	Metformin	157-166	androgen receptor	Homo sapiens	66-83
33562646-4	2021	Metformin decreased AR and ARv7 expression and induced cleaved PARP-1-associated death in both cell lines.	Metformin	0-9	poly(ADP-ribose) polymerase 1	Homo sapiens	63-69
33562646-8	2021	Finally, metformin and metformin/ARAT combinations increased lysosomal permeability resulting in cathepsin G-mediated PARP-1 cleavage and cell death.	Metformin	9-18	poly(ADP-ribose) polymerase 1	Homo sapiens	118-124
33562646-8	2021	Finally, metformin and metformin/ARAT combinations increased lysosomal permeability resulting in cathepsin G-mediated PARP-1 cleavage and cell death.	Metformin	23-32	poly(ADP-ribose) polymerase 1	Homo sapiens	118-124
33562646-9	2021	In conclusion, metformin enhances the efficacy of abiraterone and enzalutamide via two PARP-1-dependent, caspase 3-independent pathways, providing a rationale to evaluate these combinations in castration-sensitive PC.	Metformin	15-24	poly(ADP-ribose) polymerase 1	Homo sapiens	87-93
33562646-9	2021	In conclusion, metformin enhances the efficacy of abiraterone and enzalutamide via two PARP-1-dependent, caspase 3-independent pathways, providing a rationale to evaluate these combinations in castration-sensitive PC.	Metformin	15-24	caspase 3	Homo sapiens	105-114
33443781-10	2021	Additional analysis demonstrated that metformin treatment in late middle age increased adenosine monophosphate-activated protein kinase activation, reduced proinflammatory cytokine levels, and the mammalian target of rapamycin signaling, and enhanced autophagy in the hippocampus.	Metformin	38-47	mechanistic target of rapamycin kinase	Homo sapiens	197-226
33524231-7	2021	Lipopolysaccharide and transforming growth factor beta1-treated HK2 cells showed lower tubular expression of proinflammatory and fibrogenesis markers upon co-culture with metformin-treated CKD MSCs than with untreated CKD MSCs, suggestive of enhanced paracrine action of CKD MSCs mediated by metformin.	Metformin	171-180	transforming growth factor beta 1	Homo sapiens	23-55
33524231-7	2021	Lipopolysaccharide and transforming growth factor beta1-treated HK2 cells showed lower tubular expression of proinflammatory and fibrogenesis markers upon co-culture with metformin-treated CKD MSCs than with untreated CKD MSCs, suggestive of enhanced paracrine action of CKD MSCs mediated by metformin.	Metformin	292-301	transforming growth factor beta 1	Homo sapiens	23-55
33135396-3	2021	In this review, we will discuss how the "obesity-insulin-testosterone" connection and the abnormal production of bioactive oestrogen - as a result of the conversion of the androgens by aromatase and the estrone reconversion by sulfatase-, may affect the response to hormone therapy and the outcome of postmenopausal breast cancer patients, and how a combined therapy including metformin, anti-inflammatory drugs, and aromatase/sulfatase inhibitors could successfully improve patient"s outcome.	Metformin	377-386	arylsulfatase family member H	Homo sapiens	427-436
33148437-6	2021	However, studies have shown that metformin is also able to target several other ageing pathways, thereby inhibiting mammalian target of rapamycin (mTOR), increasing AMPK activity and improving DNA repair.	Metformin	33-42	mechanistic target of rapamycin kinase	Homo sapiens	116-145
33148437-6	2021	However, studies have shown that metformin is also able to target several other ageing pathways, thereby inhibiting mammalian target of rapamycin (mTOR), increasing AMPK activity and improving DNA repair.	Metformin	33-42	mechanistic target of rapamycin kinase	Homo sapiens	147-151
33262120-8	2021	AMPK activation by metformin reduced adipocyte-mediated exosome release and mitigated fatty liver development in WT and liver specific Prkaalpha1 -/- mice.	Metformin	19-28	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	135-145
33273042-1	2021	OBJECTIVE: To compare the long-term efficacy of initiating therapy with metformin/pioglitazone/exenatide in patients with new-onset type 2 diabetes mellitus (T2DM) versus sequential addition of metformin followed by glipizide and insulin.	Metformin	72-81	insulin	Homo sapiens	230-237
33270043-13	2021	Additional analyses showed a null association for other antidiabetic drugs, but significant interactions between metformin and insulin, sulfonylurea and pioglitazone, respectively, were noted.	Metformin	113-122	insulin	Homo sapiens	127-134
32594364-0	2021	Novel complementary coloprotective effects of metformin and MCC950 by modulating HSP90/NLRP3 interaction and inducing autophagy in rats.	Metformin	46-55	heat shock protein 90 alpha family class A member 1	Rattus norvegicus	81-86
32594364-0	2021	Novel complementary coloprotective effects of metformin and MCC950 by modulating HSP90/NLRP3 interaction and inducing autophagy in rats.	Metformin	46-55	NLR family, pyrin domain containing 3	Rattus norvegicus	87-92
32594364-8	2021	This pharmacological activity might be attributed to interrupting the priming signal of the NLRP3 inflammasome activation through inactivating Toll-like receptor 4 (TLR4)/nuclear transcription factor kappa-B (NF-kappaB) signalling (effect of metformin) as well as interrupting the activation signal through potent inhibition of NLRP3 expression and caspase-1 (effect of MCC950).	Metformin	242-251	NLR family, pyrin domain containing 3	Rattus norvegicus	92-97
32594364-8	2021	This pharmacological activity might be attributed to interrupting the priming signal of the NLRP3 inflammasome activation through inactivating Toll-like receptor 4 (TLR4)/nuclear transcription factor kappa-B (NF-kappaB) signalling (effect of metformin) as well as interrupting the activation signal through potent inhibition of NLRP3 expression and caspase-1 (effect of MCC950).	Metformin	242-251	toll-like receptor 4	Rattus norvegicus	143-163
32594364-8	2021	This pharmacological activity might be attributed to interrupting the priming signal of the NLRP3 inflammasome activation through inactivating Toll-like receptor 4 (TLR4)/nuclear transcription factor kappa-B (NF-kappaB) signalling (effect of metformin) as well as interrupting the activation signal through potent inhibition of NLRP3 expression and caspase-1 (effect of MCC950).	Metformin	242-251	toll-like receptor 4	Rattus norvegicus	165-169
32594364-10	2021	Moreover, the metformin/MCC950 leads to the induction of autophagy by AMP-activated protein kinase (AMPK)-dependent mechanisms leading to the accumulation of Beclin-1 and a substantial decline in the levels of p62 SQSTM1 (effect of metformin).	Metformin	14-23	sequestosome 1	Rattus norvegicus	214-220
32594364-11	2021	The observed impeding effect on HSP90 along with inducing autophagy (effect of metformin) suggests that NLRP3 is prone to autophagic degradation.	Metformin	79-88	NLR family, pyrin domain containing 3	Rattus norvegicus	104-109
32951009-10	2021	HPA axis activity as determined by corticotropin-releasing hormone in the median eminence and serum corticosterone was decreased by metformin in a dose-dependent manner, and so was norepinephrine (NE) in the paraventricular nucleus.	Metformin	132-141	corticotropin releasing hormone	Rattus norvegicus	35-66
33527807-6	2021	Combination therapy of Evogliptin and Metformin lowers blood glucose via augmentation of insulin secretion, suppression of glucagon secretion, and insulin sensitization.	Metformin	38-47	glucagon	Homo sapiens	123-131
33337344-9	2021	Treatment with either empagliflozin or metformin lowered expression of the dysfunction marker genes ex vivo, which correlated with improved glycemic control, and increased insulin release in vivo.	Metformin	39-48	insulin	Homo sapiens	172-179
33337344-11	2021	Improving islet endothelial function through strategies such as empagliflozin/metformin treatment may provide an effective approach for improving insulin release in human type 2 diabetes.	Metformin	78-87	insulin	Homo sapiens	146-153
33352227-3	2021	Metformin, a first-line oral antidiabetic agent for type 2 diabetes mellitus (T2DM), not only reduces blood glucose levels and improves insulin sensitivity and exerts cardioprotective effects but also shows benefits against cancers, cardiovascular diseases, and other diverse diseases and regulates angiogenesis.	Metformin	0-9	insulin	Homo sapiens	136-143
32990500-0	2021	Metformin prevents brain injury after cardiopulmonary resuscitation by inhibiting the endoplasmic reticulum stress response and activating AMPK-mediated autophagy.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	139-143
32990500-7	2021	Metformin enhanced AMPK-induced autophagy activation.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	19-23
32990500-8	2021	AMPK and autophagy inhibitors removed the metformin neuroprotective effect.	Metformin	42-51	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	0-4
33563734-0	2021	Vitamin B12 deficiency in patients with type 2 diabetes mellitus using metformin and the associated factors in Saudi Arabia.	Metformin	71-80	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	8-11
33889509-0	2021	Concurrent use of metformin enhances the efficacy of EGFR-TKIs in patients with advanced EGFR-mutant non-small cell lung cancer-an option for overcoming EGFR-TKI resistance.	Metformin	18-27	epidermal growth factor receptor	Homo sapiens	53-57
33889509-0	2021	Concurrent use of metformin enhances the efficacy of EGFR-TKIs in patients with advanced EGFR-mutant non-small cell lung cancer-an option for overcoming EGFR-TKI resistance.	Metformin	18-27	epidermal growth factor receptor	Homo sapiens	89-93
33889509-7	2021	Metformin can also augment apoptosis effect of these TKI-resistant cells to EGFR-TKIs.	Metformin	0-9	epidermal growth factor receptor	Homo sapiens	76-80
33889509-11	2021	Further analysis revealed that metformin obviously prolonged the median PFS2 of osimertinib treatment among patients who progressed to prior line EGFR-TKIs due to secondary EGFR T790M mutation (cohort B).	Metformin	31-40	epidermal growth factor receptor	Homo sapiens	146-150
33889509-11	2021	Further analysis revealed that metformin obviously prolonged the median PFS2 of osimertinib treatment among patients who progressed to prior line EGFR-TKIs due to secondary EGFR T790M mutation (cohort B).	Metformin	31-40	epidermal growth factor receptor	Homo sapiens	173-177
33889509-12	2021	Conclusions: Our study suggest that concurrent use of metformin could be beneficial to EGFR-mutant NSCLC patients treated with either first-line EGFR-TKIs or second-line osimertinib.	Metformin	54-63	epidermal growth factor receptor	Homo sapiens	87-91
33889509-12	2021	Conclusions: Our study suggest that concurrent use of metformin could be beneficial to EGFR-mutant NSCLC patients treated with either first-line EGFR-TKIs or second-line osimertinib.	Metformin	54-63	epidermal growth factor receptor	Homo sapiens	145-149
33517853-0	2021	Metformin attenuates ischemia/reperfusion-induced apoptosis of cardiac cells by downregulation of p53/microRNA-34a via activation SIRT1.	Metformin	0-9	sirtuin 1	Rattus norvegicus	130-135
33517853-4	2021	Metformin also reduced apoptosis, the expression of apoptosis associated proteins and miR-34a, which resulted in corresponding changes of Bcl-2 expression.	Metformin	0-9	BCL2, apoptosis regulator	Rattus norvegicus	138-143
33563734-1	2021	OBJECTIVES: To assess the presence of vitamin B12 deficiency among metformin users and associated factors in patients with type 2 diabetes mellitus.	Metformin	67-76	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	46-49
33665047-10	2021	In one-third of the patients, down-titration of the insulin dose was done, indicating the insulin-sparing effect with the addition of the glimepiride and metformin combination.	Metformin	154-163	insulin	Homo sapiens	90-97
33563734-5	2021	The vitamin B12 deficiency and borderline levels were strongly associated with the dose of metformin.	Metformin	91-100	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	12-15
33563734-6	2021	Patients taking doses of metformin more than 1000 mg had lower levels of vitamin B12.	Metformin	25-34	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	81-84
33563734-8	2021	CONCLUSION: Our findings show a low prevalence of vitamin B12 deficiency in type 2 diabetic patients taking metformin.	Metformin	108-117	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	58-61
33510216-5	2021	Metformin increased expression of Slc2a1 (GLUT1), decreased expression of Slc2a2 (GLUT2) and Slc5a1 (SGLT1) whilst increasing GLUT-dependent glucose uptake and glycolytic rate as observed by live cell imaging of genetically encoded metabolite sensors and measurement of oxygen consumption and extracellular acidification rates.	Metformin	0-9	solute carrier family 1 (glial high affinity glutamate transporter), member 3	Mus musculus	42-46
33520106-0	2021	Metformin regulates inflammation and fibrosis in diabetic kidney disease through TNC/TLR4/NF-kappaB/miR-155-5p inflammatory loop.	Metformin	0-9	toll-like receptor 4	Rattus norvegicus	85-89
33430738-12	2022	CONCLUSION: Collectively, this study has demonstrated a decrease in blood glucose levels and a rise in insulin-levels and thus a consequent prophylactic effects in metformin-given STZ-induced diabetic rats.	Metformin	164-173	insulin	Homo sapiens	103-110
33323505-7	2021	Absence of PTP-PEST also blocked hypoxia-induced autophagy (LC3 degradation and puncta formation) which was rescued by AMPK activator, metformin (500 microM).	Metformin	135-144	protein tyrosine phosphatase non-receptor type 12	Homo sapiens	11-19
33488583-9	2020	In LT patients, addition of metformin increased the peripheral percentage of CD4+Treg and CD8+Treg cells and decreased CD4+Th17.	Metformin	28-37	CD4 molecule	Homo sapiens	77-80
33488583-9	2020	In LT patients, addition of metformin increased the peripheral percentage of CD4+Treg and CD8+Treg cells and decreased CD4+Th17.	Metformin	28-37	CD4 molecule	Homo sapiens	119-122
33412927-9	2021	RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Based on available evidence from RCTs in this meta-analysis, metformin decreased CRP level.	Metformin	110-119	C-reactive protein	Homo sapiens	130-133
33412927-11	2021	CONCLUSION: The present study evidences that therapy with metformin can reduces CRP level significantly in T2D patients compared to other inflammatory markers.	Metformin	58-67	C-reactive protein	Homo sapiens	80-83
33413067-4	2021	In patients with T2DM, metformin lowers mean glycated haemoglobin (HbA1c) levels by 1.1-1.2% as monotherapy, by 0.6-0.83 % as an add-on therapy to insulin, and by 0.9- 0.95 % as add-on therapy to other oral agents.	Metformin	23-32	insulin	Homo sapiens	147-154
32548833-7	2021	Recently, metformin has been used more commonly in diabetic pregnant women in cases when insulin cannot be prescribed, after its safety has been proven.	Metformin	10-19	insulin	Homo sapiens	89-96
33603170-0	2021	Repurposing dextromethorphan and metformin for treating nicotine-induced cancer by directly targeting CHRNA7 to inhibit JAK2/STAT3/SOX2 signaling.	Metformin	33-42	signal transducer and activator of transcription 3	Homo sapiens	125-130
33510179-7	2021	Metformin increased the AMPK and FOXO3 and induced phosphorylation of activating FOXO3 in iCCA cells.	Metformin	0-9	forkhead box O3	Homo sapiens	33-38
33510179-7	2021	Metformin increased the AMPK and FOXO3 and induced phosphorylation of activating FOXO3 in iCCA cells.	Metformin	0-9	forkhead box O3	Homo sapiens	81-86
33510179-11	2021	In conclusion, Metformin reverts the mesenchymal and EMT traits in iCCA by activating AMPK-FOXO3 related pathways suggesting it might have therapeutic implications.	Metformin	15-24	forkhead box O3	Homo sapiens	91-96
33569379-0	2020	Metformin Reverses the Enhanced Myocardial SR/ER-Mitochondria Interaction and Impaired Complex I-Driven Respiration in Dystrophin-Deficient Mice.	Metformin	0-9	dystrophin, muscular dystrophy	Mus musculus	119-129
33681180-7	2020	Moreover, treatment with metformin can increase sorafenib sensitivity through AMPK activation in EGFR-overexpressed liver cancer cells.	Metformin	25-34	epidermal growth factor receptor	Homo sapiens	97-101
33271062-5	2021	RIPK1-deficient cells are unable to cope with energetic stress and are vulnerable to low glucose levels and metformin.	Metformin	108-117	receptor (TNFRSF)-interacting serine-threonine kinase 1	Mus musculus	0-5
33477154-0	2022	PROLACTIN RESPONSE TO METFORMIN IN CABERGOLINE-RESISTANT PROLACTINOMAS: A PILOT STUDY.	Metformin	22-31	prolactin	Homo sapiens	0-9
33477154-3	2022	Metformin, a biguanide widely used in the treatment of diabetes mellitus, has been shown to reduce prolactin secretion in various pituitary tumor cell lineages both in vitro and in vivo and in human pituitary adenomas in vitro.	Metformin	0-9	prolactin	Homo sapiens	99-108
33477154-4	2022	The aim of this study is to test the effects of metformin addition to cabergoline treatment on prolactin levels in patients with resistant prolactinomas.	Metformin	48-57	prolactin	Homo sapiens	95-104
33477154-12	2022	Two patients were considered partial responders for exhibiting prolactin decreases >=50% at a single time point during metformin.	Metformin	119-128	prolactin	Homo sapiens	63-72
33477154-13	2022	CONCLUSION: Metformin addition to ongoing high dose cabergoline treatment in patients with cabergoline-resistant prolactinomas failed to show a consistent inhibitory effect in serum prolactin levels.	Metformin	12-21	prolactin	Homo sapiens	113-122
33477996-5	2021	The potential anti-cancer activity of metformin is based on two principal effects: first, its capacity for lowering circulating insulin levels with indirect endocrine effects that may impact on tumor cell proliferation; second, its direct influence on many pro-cancer signaling pathways that are key drivers of BC aggressiveness.	Metformin	38-47	insulin	Homo sapiens	128-135
33468193-0	2021	A combination of herbal compound (SPTC) along with exercise or metformin more efficiently alleviated diabetic complications through down-regulation of stress oxidative pathway upon activating Nrf2-Keap1 axis in AGE rich diet-induced type 2 diabetic mice.	Metformin	63-72	nuclear factor, erythroid derived 2, like 2	Mus musculus	192-196
33468193-7	2021	RESULTS: SPTC + exercise and SPTC + metformin reduced diabetic complications like gain weight, water and calorie intake, blood glucose, insulin, and GLUT4 content more efficiently than each treatment.	Metformin	36-45	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	149-154
33537296-0	2020	Metformin Induces Apoptosis and Inhibits Notch1 in Malignant Pleural Mesothelioma Cells.	Metformin	0-9	notch receptor 1	Homo sapiens	41-47
33537296-9	2020	In this study, the anti-proliferative effect of metformin on MPM cells and the putative involvement of Notch1 as a mediator of metformin activities, were investigated.	Metformin	127-136	notch receptor 1	Homo sapiens	103-109
33537296-11	2020	Furthermore, metformin treatment hampered MPM cell proliferation and enhanced the apoptotic process, accompanied by decreased Notch1 activation.	Metformin	13-22	notch receptor 1	Homo sapiens	126-132
33157041-8	2021	The beneficial effects of using both the naringenin and metformin along with the lower dose of doxorubicin were evident from the reduced dose-related body weight loss and increase in cytokines (TNF-alpha and IL-1beta) compared to a large dose of doxorubicin alone.	Metformin	56-65	tumor necrosis factor	Mus musculus	194-203
33143871-9	2021	In conclusion, metformin reduced high glucose-induced ER stress and inflammation by inhibiting the interaction between caveolin1 and AMPKalpha, suggesting that the caveolin1/AMPKalpha complex may be a potential therapeutic target for metformin.	Metformin	234-243	caveolin 1	Rattus norvegicus	164-173
33861440-1	2021	Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, for which the insulin sensitizer metformin has been used therapeutically.	Metformin	119-128	insulin	Homo sapiens	100-107
32951587-5	2021	In this review, we summarize the chemosensitization effects of metformin and focus primarily on its molecular mechanisms in enhancing the sensitivity of multiple chemotherapeutic drugs, through targeting of mTOR, ERK/P70S6K, NF-kappaB/HIF-1alpha, and mitogenactivated protein kinase (MAPK) signaling pathways, as well as by down-regulating the expression of CSC genes and pyruvate kinase isoenzyme M2 (PKM2).	Metformin	63-72	mechanistic target of rapamycin kinase	Homo sapiens	207-211
32951587-5	2021	In this review, we summarize the chemosensitization effects of metformin and focus primarily on its molecular mechanisms in enhancing the sensitivity of multiple chemotherapeutic drugs, through targeting of mTOR, ERK/P70S6K, NF-kappaB/HIF-1alpha, and mitogenactivated protein kinase (MAPK) signaling pathways, as well as by down-regulating the expression of CSC genes and pyruvate kinase isoenzyme M2 (PKM2).	Metformin	63-72	mitogen-activated protein kinase 1	Homo sapiens	213-216
32951587-5	2021	In this review, we summarize the chemosensitization effects of metformin and focus primarily on its molecular mechanisms in enhancing the sensitivity of multiple chemotherapeutic drugs, through targeting of mTOR, ERK/P70S6K, NF-kappaB/HIF-1alpha, and mitogenactivated protein kinase (MAPK) signaling pathways, as well as by down-regulating the expression of CSC genes and pyruvate kinase isoenzyme M2 (PKM2).	Metformin	63-72	hypoxia inducible factor 1 subunit alpha	Homo sapiens	235-245
33143871-0	2021	Metformin alleviates high glucose-induced ER stress and inflammation by inhibiting the interaction between caveolin1 and AMPKalpha in rat astrocytes.	Metformin	0-9	caveolin 1	Rattus norvegicus	107-116
33143871-7	2021	Moreover, metformin inhibited the formation of caveolin1/AMPKalpha complex.	Metformin	10-19	caveolin 1	Rattus norvegicus	47-56
33143871-9	2021	In conclusion, metformin reduced high glucose-induced ER stress and inflammation by inhibiting the interaction between caveolin1 and AMPKalpha, suggesting that the caveolin1/AMPKalpha complex may be a potential therapeutic target for metformin.	Metformin	15-24	caveolin 1	Rattus norvegicus	119-128
33227290-9	2021	We therefore hypothesised that the effect of metformin in vivo was not due to direct cytotoxicity on cancer cells, but by modulation of IGF-1 expression.	Metformin	45-54	insulin like growth factor 1	Homo sapiens	136-141
33143871-9	2021	In conclusion, metformin reduced high glucose-induced ER stress and inflammation by inhibiting the interaction between caveolin1 and AMPKalpha, suggesting that the caveolin1/AMPKalpha complex may be a potential therapeutic target for metformin.	Metformin	15-24	caveolin 1	Rattus norvegicus	164-173
33143871-9	2021	In conclusion, metformin reduced high glucose-induced ER stress and inflammation by inhibiting the interaction between caveolin1 and AMPKalpha, suggesting that the caveolin1/AMPKalpha complex may be a potential therapeutic target for metformin.	Metformin	234-243	caveolin 1	Rattus norvegicus	119-128
33007330-0	2021	FGFR1 overexpression renders breast cancer cells resistant to metformin through activation of IRS1/ERK signaling.	Metformin	62-71	fibroblast growth factor receptor 1	Homo sapiens	0-5
33007330-5	2021	To investigate the effect of FGFR1 overexpression on metformin-induced inhibition of breast cancer cells, we demonstrated that FGFR1 overexpression rendered MCF-7 and T47D cells resistant to metformin.	Metformin	53-62	fibroblast growth factor receptor 1	Homo sapiens	29-34
33007330-5	2021	To investigate the effect of FGFR1 overexpression on metformin-induced inhibition of breast cancer cells, we demonstrated that FGFR1 overexpression rendered MCF-7 and T47D cells resistant to metformin.	Metformin	53-62	fibroblast growth factor receptor 1	Homo sapiens	127-132
33007330-5	2021	To investigate the effect of FGFR1 overexpression on metformin-induced inhibition of breast cancer cells, we demonstrated that FGFR1 overexpression rendered MCF-7 and T47D cells resistant to metformin.	Metformin	191-200	fibroblast growth factor receptor 1	Homo sapiens	127-132
33007330-6	2021	In particular, we found that, in addition to AKT and ERK1/2 activation, FGFR1-induced activation of IRS1 and IGF1R, key regulators connecting metabolism and cancer, was associated with metformin resistance.	Metformin	185-194	fibroblast growth factor receptor 1	Homo sapiens	72-77
33007330-7	2021	Targeting IRS with IRS1 KO or IRS inhibitor NT157 significantly sensitized FGFR1 overexpressing cells to metformin.	Metformin	105-114	isoleucyl-tRNA synthetase 1	Homo sapiens	10-13
33007330-7	2021	Targeting IRS with IRS1 KO or IRS inhibitor NT157 significantly sensitized FGFR1 overexpressing cells to metformin.	Metformin	105-114	isoleucyl-tRNA synthetase 1	Homo sapiens	19-22
33007330-7	2021	Targeting IRS with IRS1 KO or IRS inhibitor NT157 significantly sensitized FGFR1 overexpressing cells to metformin.	Metformin	105-114	fibroblast growth factor receptor 1	Homo sapiens	75-80
33007330-8	2021	Combination of NT157 with metformin induced enhanced inhibition of p-IGF1R, p-ERK1/2 and p-mTOR.	Metformin	26-35	mitogen-activated protein kinase 3	Homo sapiens	78-84
33007330-8	2021	Combination of NT157 with metformin induced enhanced inhibition of p-IGF1R, p-ERK1/2 and p-mTOR.	Metformin	26-35	mechanistic target of rapamycin kinase	Homo sapiens	91-95
33217690-11	2021	However, metformin co-administration significantly decreased the levels of TNF-alpha, IL-6 and IL-1beta while increased the level of IL-10 in epididymal white adipose tissue compared to olanzapine-treated rats.	Metformin	9-18	tumor necrosis factor	Rattus norvegicus	75-84
33217690-11	2021	However, metformin co-administration significantly decreased the levels of TNF-alpha, IL-6 and IL-1beta while increased the level of IL-10 in epididymal white adipose tissue compared to olanzapine-treated rats.	Metformin	9-18	interleukin 6	Rattus norvegicus	86-90
33217690-11	2021	However, metformin co-administration significantly decreased the levels of TNF-alpha, IL-6 and IL-1beta while increased the level of IL-10 in epididymal white adipose tissue compared to olanzapine-treated rats.	Metformin	9-18	interleukin 1 alpha	Rattus norvegicus	95-103
32972040-6	2021	In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)-negative breast cancer.	Metformin	157-166	estrogen receptor 1	Homo sapiens	211-228
32940848-2	2021	Metformin has been shown to have antitumor effects by lowering serum levels of the mitogen insulin and having pleiotropic effects on cancer cell signaling pathways.	Metformin	0-9	insulin	Homo sapiens	91-98
33191800-5	2021	Metformin treatment was negatively associated with p53-AP in T2DM patients.	Metformin	0-9	tumor protein p53	Homo sapiens	51-54
32972040-6	2021	In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)-negative breast cancer.	Metformin	157-166	estrogen receptor 1	Homo sapiens	230-232
32972040-9	2021	Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.	Metformin	35-44	estrogen receptor 1	Homo sapiens	101-103
33268288-9	2021	Moreover, western blotting assay revealed that metformin could decrease Hcy-induced expression of Bax and cleaved caspase3, and increase the expression of Bcl-2.	Metformin	47-56	BCL2 associated X, apoptosis regulator	Homo sapiens	98-101
33861440-3	2021	Given that metformin acts as an ovulation inducing agent and both curcumin and metformin can reduce insulin resistance, the aim of the current study was to evaluate the effect of metformin with and without curcumin nanomicelles in the treatment of women with polycystic ovary syndrome.	Metformin	79-88	insulin	Homo sapiens	100-107
33861440-3	2021	Given that metformin acts as an ovulation inducing agent and both curcumin and metformin can reduce insulin resistance, the aim of the current study was to evaluate the effect of metformin with and without curcumin nanomicelles in the treatment of women with polycystic ovary syndrome.	Metformin	79-88	insulin	Homo sapiens	100-107
33861440-13	2021	This study showed that curcumin has a synergistic effect with metformin in the improvement of insulin resistance and lipid profile in patients with PCOS.	Metformin	62-71	insulin	Homo sapiens	94-101
33268288-9	2021	Moreover, western blotting assay revealed that metformin could decrease Hcy-induced expression of Bax and cleaved caspase3, and increase the expression of Bcl-2.	Metformin	47-56	caspase 3	Homo sapiens	114-122
33268288-9	2021	Moreover, western blotting assay revealed that metformin could decrease Hcy-induced expression of Bax and cleaved caspase3, and increase the expression of Bcl-2.	Metformin	47-56	BCL2 apoptosis regulator	Homo sapiens	155-160
32987433-12	2021	Interestingly, we found that the combination of metformin with docetaxel significantly down-regulated the mRNA levels of Gli1, Gli2, and TWIST1 in the AGS gastric cancer cell line compared to docetaxel alone.	Metformin	48-57	GLI family zinc finger 2	Homo sapiens	127-131
32987433-12	2021	Interestingly, we found that the combination of metformin with docetaxel significantly down-regulated the mRNA levels of Gli1, Gli2, and TWIST1 in the AGS gastric cancer cell line compared to docetaxel alone.	Metformin	48-57	twist family bHLH transcription factor 1	Homo sapiens	137-143
33279861-5	2021	The protein profiles at baseline were attenuated during guideline-based diabetes treatment and several plasma proteins associated with metformin medication independently of metabolic variables, such as circulating EPCAM.	Metformin	135-144	epithelial cell adhesion molecule	Homo sapiens	214-219
31234219-0	2021	The Impact of Ethinyl Estradiol on Metformin Action on Prolactin Levels in Women with Hyperprolactinemia.	Metformin	35-44	prolactin	Homo sapiens	55-64
33487223-0	2021	Retraction notice to "The antineoplastic drug metformin downregulates YAP by interfering with IRF-1 binding to the YAP promoter in NSCLC" [EBioMedicine 37 (2018) 188-204].	Metformin	46-55	interferon regulatory factor 1	Homo sapiens	94-99
33970481-5	2021	Results from available studies have shown that metformin therapy in patients with type 2 diabetes mellitus and heart failure was associated with improved clinical outcomes when compared with other oral antidiabetic agents, insulin, or lifestyle management.	Metformin	47-56	insulin	Homo sapiens	223-230
33365058-0	2021	Metformin alleviates beta-glycerophosphate-induced calcification of vascular smooth muscle cells via AMPK/mTOR-activated autophagy.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	106-110
33365058-6	2021	Metformin increased the number of autophagosomes, green fluorescent LC3 puncta and the levels of LC3II/I, beclin 1, alpha-SMA and phosphorylated (p)-AMPK in the VSMCs that were treated with beta-glycerophosphate when compared to controls; whereas, calcium deposition and the expression levels of RUNX2 and p-mTOR were found to be decreased.	Metformin	0-9	actin alpha 1, skeletal muscle	Homo sapiens	116-125
33365058-6	2021	Metformin increased the number of autophagosomes, green fluorescent LC3 puncta and the levels of LC3II/I, beclin 1, alpha-SMA and phosphorylated (p)-AMPK in the VSMCs that were treated with beta-glycerophosphate when compared to controls; whereas, calcium deposition and the expression levels of RUNX2 and p-mTOR were found to be decreased.	Metformin	0-9	RUNX family transcription factor 2	Homo sapiens	296-301
33365058-6	2021	Metformin increased the number of autophagosomes, green fluorescent LC3 puncta and the levels of LC3II/I, beclin 1, alpha-SMA and phosphorylated (p)-AMPK in the VSMCs that were treated with beta-glycerophosphate when compared to controls; whereas, calcium deposition and the expression levels of RUNX2 and p-mTOR were found to be decreased.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	308-312
33365058-8	2021	The results of the present study suggested that metformin may alleviate beta-glycerophosphate-induced calcification of VSMCs, which may be attributed to the activation of AMPK/mTOR signaling pathway-dependent autophagy.	Metformin	48-57	mechanistic target of rapamycin kinase	Homo sapiens	176-180
33161784-4	2021	Areas covered: The authors review literature on metformin treatment in Parkinson"s disease, Huntington"s disease and other neurological diseases of the CNS along with neuroprotective effects of AMPK activation and suppression of the mammalian target of rapamycin (mTOR) pathway on peripheral neuropathy and neuropathic pain.	Metformin	48-57	mechanistic target of rapamycin kinase	Homo sapiens	264-268
31234219-1	2021	BACKGROUND: Metformin reduced prolactin levels only in women with hyperprolactinemia.	Metformin	12-21	prolactin	Homo sapiens	30-39
31234219-8	2021	Metformin reduced plasma glucose levels and improved insulin sensitivity but the latter effect was stronger in women receiving oral contraceptive pills than in women not using any contraception.	Metformin	0-9	insulin	Homo sapiens	53-60
31234219-9	2021	Although metformin treatment decreased plasma prolactin levels in both study groups, this effect was stronger in women taking oral contraceptive pills.	Metformin	9-18	prolactin	Homo sapiens	46-55
33212505-0	2021	Does metformin improve the efficacy of standard epidermal growth factor receptor-tyrosine kinase inhibitor treatment for patients with advanced non-small-cell lung cancer?	Metformin	5-14	epidermal growth factor receptor	Homo sapiens	48-80
33212505-2	2021	The question addressed was whether metformin improved the efficacy of standard epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment for patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer.	Metformin	35-44	epidermal growth factor receptor	Homo sapiens	139-143
33212505-2	2021	The question addressed was whether metformin improved the efficacy of standard epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment for patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer.	Metformin	35-44	epidermal growth factor receptor	Homo sapiens	177-209
33212505-2	2021	The question addressed was whether metformin improved the efficacy of standard epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment for patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer.	Metformin	35-44	epidermal growth factor receptor	Homo sapiens	211-215
33212505-5	2021	We concluded that the addition of metformin to EGFR-TKI might improve the survival of patients with EGFR-mutated non-small-cell lung cancer and diabetes mellitus type 2.	Metformin	34-43	epidermal growth factor receptor	Homo sapiens	100-104
33212505-6	2021	However, for non-diabetic non-small-cell lung cancer patients with EGFR mutation, the efficiency of additional metformin in EGFR-TKI treatment remains unclear because of the conflicting results of only 2 available studies.	Metformin	111-120	epidermal growth factor receptor	Homo sapiens	124-128
33232684-1	2021	OBJECTIVES: The COVID-19 pandemic presents an urgent need to investigate whether existing drugs can enhance or even worsen prognosis; metformin, a known mammalian target of rapamycin (m-TOR) inhibitor, has been identified as a potential agent.	Metformin	134-143	mechanistic target of rapamycin kinase	Homo sapiens	153-182
33232684-1	2021	OBJECTIVES: The COVID-19 pandemic presents an urgent need to investigate whether existing drugs can enhance or even worsen prognosis; metformin, a known mammalian target of rapamycin (m-TOR) inhibitor, has been identified as a potential agent.	Metformin	134-143	RAR related orphan receptor C	Homo sapiens	186-189
33232684-11	2021	These findings suggest a relative survival benefit in nursing home residents on metformin, potentially through its mTOR inhibition effects.	Metformin	80-89	mechanistic target of rapamycin kinase	Homo sapiens	115-119
31234219-11	2021	The changes in plasma prolactin correlated with their baseline insulin sensitivity and the effect of metformin on insulin sensitivity.	Metformin	101-110	prolactin	Homo sapiens	22-31
31234219-11	2021	The changes in plasma prolactin correlated with their baseline insulin sensitivity and the effect of metformin on insulin sensitivity.	Metformin	101-110	insulin	Homo sapiens	114-121
33187870-10	2021	Metformin treatment reverted LMNA, LMNC, and p53 expression levels to normal levels.	Metformin	0-9	tumor protein p53	Homo sapiens	45-48
33576490-1	2021	The main mechanism of gestational diabetes mellitus (GDM) is insulin resistance, therefore using metformin as a medicine reducing insulin resistance appears to be promising.	Metformin	97-106	insulin	Homo sapiens	61-68
33576490-1	2021	The main mechanism of gestational diabetes mellitus (GDM) is insulin resistance, therefore using metformin as a medicine reducing insulin resistance appears to be promising.	Metformin	97-106	insulin	Homo sapiens	130-137
33601368-0	2021	Metformin Inhibits Abdominal Aortic Aneurysm Formation through the Activation of the AMPK/mTOR Signaling Pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	85-89
32994182-5	2021	In cultured mouse mammary and human breast cancer cells, metformin suppressed DPP-4 inhibitor KR62436 (KR)-induced EMT and cell migration via suppression of the mTOR pathway associated with AMPK activation.	Metformin	57-66	mechanistic target of rapamycin kinase	Homo sapiens	161-165
34017786-3	2021	Therefore, he escaped from insulin injection and was able to treat with metformin.	Metformin	72-81	insulin	Homo sapiens	27-34
32657143-8	2021	In the metformin treated group, the expression of Bax and PUMA genes was enhanced while the expression of Bcl-2, hTERT, mTOR, and p53 genes declined.	Metformin	7-16	BCL2 associated X, apoptosis regulator	Homo sapiens	50-53
32994182-3	2021	Metformin has been shown to inhibit the mTOR signaling pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	40-44
32994182-4	2021	In this study, we investigated whether metformin mitigates breast cancer metastasis induced by a DPP-4 inhibitor via suppression of mTOR signaling.	Metformin	39-48	mechanistic target of rapamycin kinase	Homo sapiens	132-136
33262823-0	2021	Metformin inhibits epithelial-mesenchymal transition of oral squamous cell carcinoma via the mTOR/HIF-1alpha/PKM2/STAT3 pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	93-97
33262823-0	2021	Metformin inhibits epithelial-mesenchymal transition of oral squamous cell carcinoma via the mTOR/HIF-1alpha/PKM2/STAT3 pathway.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	98-108
33262823-0	2021	Metformin inhibits epithelial-mesenchymal transition of oral squamous cell carcinoma via the mTOR/HIF-1alpha/PKM2/STAT3 pathway.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	114-119
33262823-9	2021	Moreover, metformin reversed EMT in OSCC by inhibiting the mTOR-associated HIF-1alpha/PKM2/STAT3 signaling pathway.	Metformin	10-19	mechanistic target of rapamycin kinase	Homo sapiens	59-63
33262823-9	2021	Moreover, metformin reversed EMT in OSCC by inhibiting the mTOR-associated HIF-1alpha/PKM2/STAT3 signaling pathway.	Metformin	10-19	hypoxia inducible factor 1 subunit alpha	Homo sapiens	75-85
33262823-9	2021	Moreover, metformin reversed EMT in OSCC by inhibiting the mTOR-associated HIF-1alpha/PKM2/STAT3 signaling pathway.	Metformin	10-19	signal transducer and activator of transcription 3	Homo sapiens	91-96
32657143-8	2021	In the metformin treated group, the expression of Bax and PUMA genes was enhanced while the expression of Bcl-2, hTERT, mTOR, and p53 genes declined.	Metformin	7-16	BCL2 apoptosis regulator	Homo sapiens	106-111
32657143-8	2021	In the metformin treated group, the expression of Bax and PUMA genes was enhanced while the expression of Bcl-2, hTERT, mTOR, and p53 genes declined.	Metformin	7-16	mechanistic target of rapamycin kinase	Homo sapiens	120-124
32657143-8	2021	In the metformin treated group, the expression of Bax and PUMA genes was enhanced while the expression of Bcl-2, hTERT, mTOR, and p53 genes declined.	Metformin	7-16	tumor protein p53	Homo sapiens	130-133
32657143-9	2021	Although all treatments induced apoptosis, the combination of curcumin and metformin showed the maximum level of apoptosis, cytotoxicity, and expression of Bax gene.	Metformin	75-84	BCL2 associated X, apoptosis regulator	Homo sapiens	156-159
32862004-0	2021	Protective effect of metformin on BPA-induced liver toxicity in rats through upregulation of cystathionine beta synthase and cystathionine gamma lyase expression.	Metformin	21-30	cystathionine beta synthase	Rattus norvegicus	93-120
32674107-5	2021	METHODS: In MH7A cells, cell proliferation and the IL-6-mediated signaling pathway following administration of LMT-28 and metformin combination was analyzed through MTT assay and Western blotting.	Metformin	122-131	interleukin 6	Homo sapiens	51-55
32674107-8	2021	RESULTS: Combination treatment with LMT-28 and metformin diminished proliferation of MH7A cells and IL-6-mediated gp130, STAT3, and ERK signaling more than in individual treatments.	Metformin	47-56	interleukin 6	Homo sapiens	100-104
32674107-8	2021	RESULTS: Combination treatment with LMT-28 and metformin diminished proliferation of MH7A cells and IL-6-mediated gp130, STAT3, and ERK signaling more than in individual treatments.	Metformin	47-56	signal transducer and activator of transcription 3	Homo sapiens	121-126
32674107-9	2021	Furthermore, the differentiation of CD4+ T cells into Th17 cells was attenuated more by combination treatment with LMT-28 and metformin than individual treatments.	Metformin	126-135	CD4 molecule	Homo sapiens	36-39
32674107-12	2021	CONCLUSION: Combination treatment with LMT-28 and metformin significantly ameliorates arthritic symptoms in CIA by suppressing Th17 differentiation and IL-6 signaling.	Metformin	50-59	interleukin 6	Homo sapiens	152-156
33017649-8	2021	Cumulative evidence from these RCTs supported the blood glucose lowering effects of metformin, in addition to promoting weight loss, ameliorating insulin resistance, and reducing pro-inflammatory markers such as interleukin-6 and tumor necrosis factor-alpha in patients with metabolic syndrome.	Metformin	84-93	insulin	Homo sapiens	146-153
33017649-8	2021	Cumulative evidence from these RCTs supported the blood glucose lowering effects of metformin, in addition to promoting weight loss, ameliorating insulin resistance, and reducing pro-inflammatory markers such as interleukin-6 and tumor necrosis factor-alpha in patients with metabolic syndrome.	Metformin	84-93	interleukin 6	Homo sapiens	212-225
33017649-8	2021	Cumulative evidence from these RCTs supported the blood glucose lowering effects of metformin, in addition to promoting weight loss, ameliorating insulin resistance, and reducing pro-inflammatory markers such as interleukin-6 and tumor necrosis factor-alpha in patients with metabolic syndrome.	Metformin	84-93	tumor necrosis factor	Homo sapiens	230-257
32862004-10	2021	Additionally, metformin significantly increased cystathionine beta synthase (CBS) and cystathionine gamma lyase (CSE), thus reducing serum levels of homocysteine and increasing hepatic levels of cysteine and glutathione in BPA-treated rats.	Metformin	14-23	cystathionine beta synthase	Rattus norvegicus	48-75
32862004-10	2021	Additionally, metformin significantly increased cystathionine beta synthase (CBS) and cystathionine gamma lyase (CSE), thus reducing serum levels of homocysteine and increasing hepatic levels of cysteine and glutathione in BPA-treated rats.	Metformin	14-23	cystathionine beta synthase	Rattus norvegicus	77-80
33347618-1	2020	BACKGROUND: The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation (IVF) cycles has been widely studied.	Metformin	59-68	insulin	Homo sapiens	23-30
33408792-7	2021	Results: Different from ICIs that conformationally block PD-L1 on cancer cell membrane, MS NPs directly reduced the PD-L1 level via metformin to achieve immunotherapy.	Metformin	132-141	CD274 molecule	Sus scrofa	116-121
33411680-9	2020	In vivo, administration of metformin increased the levels of lncRNA-ANRIL, suppressed VSMC phenotypic switching, and prevented the development of atherosclerotic plaque in Apoe-/- mice fed with western diet.	Metformin	27-36	apolipoprotein E	Mus musculus	172-176
33411680-10	2020	These protective effects of metformin were abolished by infecting Apoe-/- mice with adenovirus expressing lncRNA-ANRIL shRNA.	Metformin	28-37	apolipoprotein E	Mus musculus	66-70
33069361-0	2020	Metformin ameliorates skeletal muscle atrophy in Grx1 KO mice by regulating intramuscular lipid accumulation and glucose utilization.	Metformin	0-9	glutaredoxin	Mus musculus	49-53
33069361-9	2020	However, intraperitoneal injection of metformin for 15 consecutive days ameliorated skeletal muscle atrophy caused by Grx1 deficiency to a certain extent.	Metformin	38-47	glutaredoxin	Mus musculus	118-122
33069361-10	2020	Taken together, these findings indicate that Grx1 deficiency might induce skeletal muscle atrophy by regulating the intramuscular lipid deposition and glucose utilization, which could be attenuated by metformin.	Metformin	201-210	glutaredoxin	Mus musculus	45-49
33334002-6	2020	Because increased insulin secretion enhances ovarian androgen production, short-term treatment with metformin and other hypoglycemic agents results in significant weight loss, favorable metabolic changes, and testosterone reduction.	Metformin	100-109	insulin	Homo sapiens	18-25
32516360-10	2020	Of note, either nicotine treatment or activation of AMPK by intracerebroventricular infusion of metformin reduced LPS-induced impairment of fear memory reconsolidation, and ameliorated inflammation factor TNF-alpha and IL-1beta as well as the expression of CRTC1.	Metformin	96-105	tumor necrosis factor	Homo sapiens	205-214
32859615-8	2020	Compared with control, exercise and metformin reduced sTNF-alphaR2: -13.1% (95% CI: -22.9, -1.0) and IL-6: -38.7% (95% CI: -52.3, -18.9); but did not change hs-CRP: -20.5% (95% CI: -44.0, 12.7).	Metformin	36-45	C-reactive protein	Homo sapiens	160-163
32777157-0	2020	Metformin andbetter survival in Type 2 Diabetes patients with NSCLC during EGFR-TKI Treatment: implications of miR-146a?	Metformin	0-9	epidermal growth factor receptor	Homo sapiens	75-79
32979417-6	2020	Baseline total and VLDL triglycerides, VLDL cholesterol, and apolipoprotein B to A-1 ratio (apoB/apoA-1) associated positively with BW, more strongly in the metformin group.	Metformin	157-166	apolipoprotein B	Homo sapiens	61-77
32979417-6	2020	Baseline total and VLDL triglycerides, VLDL cholesterol, and apolipoprotein B to A-1 ratio (apoB/apoA-1) associated positively with BW, more strongly in the metformin group.	Metformin	157-166	apolipoprotein B	Homo sapiens	92-96
33426334-0	2020	PSTi8 with metformin ameliorates perimenopause induced steatohepatitis associated ER stress by regulating SIRT-1/SREBP-1c axis.	Metformin	11-20	sirtuin 1	Rattus norvegicus	106-112
33297431-12	2020	For patients with DM and COVID-19 who require hospitalization, insulin-based treatment is recommended with cessation of metformin and SGLT2i.	Metformin	120-129	insulin	Homo sapiens	63-70
33533444-0	2020	Assessment of Interaction of Human OCT 1-3 Proteins and Metformin Using Silico Analyses.	Metformin	56-65	solute carrier family 22 member 1	Homo sapiens	35-42
33533444-1	2020	Metformin, a drug frequently used by diabetic patients as the first-line treatment worldwide, is positively charged and is transported into the cell through human organic cation transporter (hOCT 1-3) proteins.	Metformin	0-9	solute carrier family 22 member 1	Homo sapiens	191-199
33533444-2	2020	We aimed to mimic the cellular uptake of metformin by hOCT1-3 with various bioinformatics methods and tools.	Metformin	41-50	solute carrier family 22 member 1	Homo sapiens	54-61
33533444-6	2020	We simulated the OCT1-3 and metformin docking and also validated the docking procedure with other substrates of HOCT1-3 proteins.	Metformin	28-37	solute carrier family 22 member 1	Homo sapiens	112-119
32808185-8	2020	The expression level of TMPRSS2 was increased noticeably with a number of medications such as metformin.	Metformin	94-103	transmembrane serine protease 2	Homo sapiens	24-31
32103411-0	2020	Co-administration of Selenium Nanoparticles and Metformin Abrogate Testicular Oxidative Injury by Suppressing Redox Imbalance, Augmenting Sperm Quality and Nrf2 Protein Expression in Streptozotocin-Induced Diabetic Rats.	Metformin	48-57	NFE2 like bZIP transcription factor 2	Rattus norvegicus	156-160
33328161-3	2020	The purpose of this analysis was to determine whether intensive lifestyle intervention (ILS) or metformin changed circulating SHBG and if resultant changes influenced diabetes risk in the Diabetes Prevention Program (DPP).	Metformin	96-105	sex hormone binding globulin	Homo sapiens	126-130
33037045-1	2020	The most commonly used oral antidiabetic drug metformin is a substrate of the hepatic uptake transporter OCT1 (SLC22A1).	Metformin	46-55	solute carrier family 22 member 1	Homo sapiens	105-109
32970287-2	2020	This study set up to determine the effect of metformin on miR223 expression and content of AKT/GLUT4 proteins in insulin resistant signaling in 3T3L1 cells and adipocyte of human diabetic patients.	Metformin	45-54	insulin	Homo sapiens	113-120
33037045-1	2020	The most commonly used oral antidiabetic drug metformin is a substrate of the hepatic uptake transporter OCT1 (SLC22A1).	Metformin	46-55	solute carrier family 22 member 1	Homo sapiens	111-118
33037045-10	2020	In conclusion, the contribution of human OCT1 to the cellular uptake of thiamine and especially of metformin may be much lower than that of mouse OCT1.	Metformin	99-108	solute carrier family 22 member 1	Homo sapiens	41-45
33037045-13	2020	Significance Statement OCT1 is a major hepatic uptake transporter of metformin and thiamine, but we report strong differences in the affinity for both compounds between human and mouse OCT1.	Metformin	69-78	solute carrier family 22 member 1	Homo sapiens	23-27
33037045-14	2020	Consequently, intrahepatic metformin concentrations could be much higher in mice than in humans, impacting metformin actions and representing a strong limitation of using rodent animal models for predictions of OCT1-related pharmacokinetics and efficacy in humans.	Metformin	27-36	solute carrier family 22 member 1	Homo sapiens	211-215
33037045-15	2020	Furthermore, OCT1 transmembrane helices TMH2 and TMH3 were identified to confer the observed species-specific differences in metformin affinity.	Metformin	125-134	solute carrier family 22 member 1	Homo sapiens	13-17
32970287-0	2020	Metformin downregulates miR223 expression in insulin-resistant 3T3L1 cells and human diabetic adipose tissue.	Metformin	0-9	insulin	Homo sapiens	45-52
32970287-2	2020	This study set up to determine the effect of metformin on miR223 expression and content of AKT/GLUT4 proteins in insulin resistant signaling in 3T3L1 cells and adipocyte of human diabetic patients.	Metformin	45-54	thymoma viral proto-oncogene 1	Mus musculus	91-94
32970287-2	2020	This study set up to determine the effect of metformin on miR223 expression and content of AKT/GLUT4 proteins in insulin resistant signaling in 3T3L1 cells and adipocyte of human diabetic patients.	Metformin	45-54	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	95-100
33093887-3	2020	The present study aimed to evaluate the therapeutic effect of metformin, an AMPK activator, in a monocrotaline (MCT)-induced PH rat model.	Metformin	62-71	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	76-80
33169942-7	2020	Furthermore, we found that metformin suppressed ALP activity and mineralization of the cells, an event that was attenuated by the dominant negative mutant of AMPK and mimicked by its constitutively active mutant.	Metformin	27-36	alopecia, recessive	Mus musculus	48-51
32706919-9	2020	In both study arms, metformin reduced plasma glucose levels and improved insulin sensitivity but this effect was stronger in subjects receiving vitamin D.	Metformin	20-29	insulin	Homo sapiens	73-80
33049108-10	2020	Moreover, metformin treatment enhanced the expression of pro-angiogenic/osteogenic growth factors BMP2 and VEGF but reduced the osteoclastogenic factor RANKL/OPG expression in SHEDs.	Metformin	10-19	vascular endothelial growth factor A	Homo sapiens	107-111
33024029-0	2020	Inhibition of EZH2 enhances the antitumor efficacy of metformin in prostate cancer.	Metformin	54-63	enhancer of zeste 2 polycomb repressive complex 2 subunit	Homo sapiens	14-18
33024029-4	2020	Mechanistically, we identify that metformin can reduce EZH2"s expression through upregulating miR-26a-5p, which is antagonized by androgen receptor (AR).	Metformin	34-43	enhancer of zeste 2 polycomb repressive complex 2 subunit	Homo sapiens	55-59
33024029-4	2020	Mechanistically, we identify that metformin can reduce EZH2"s expression through upregulating miR-26a-5p, which is antagonized by androgen receptor (AR).	Metformin	34-43	androgen receptor	Homo sapiens	130-147
33024029-4	2020	Mechanistically, we identify that metformin can reduce EZH2"s expression through upregulating miR-26a-5p, which is antagonized by androgen receptor (AR).	Metformin	34-43	androgen receptor	Homo sapiens	149-151
33024029-6	2020	Although metformin can remove AR from the miR-26a-5p promoter, the interaction between AR and EZH2, which usually exists in androgen-refractory PCa cells, strongly impedes the removal.	Metformin	9-18	androgen receptor	Homo sapiens	30-32
33024029-7	2020	However, GSK126 can inhibit the methyltransferase-dependent interaction between AR and EZH2, thus restoring metformin"s efficacy in androgen-refractory PCa cells.	Metformin	108-117	androgen receptor	Homo sapiens	80-82
33024029-7	2020	However, GSK126 can inhibit the methyltransferase-dependent interaction between AR and EZH2, thus restoring metformin"s efficacy in androgen-refractory PCa cells.	Metformin	108-117	enhancer of zeste 2 polycomb repressive complex 2 subunit	Homo sapiens	87-91
33024029-8	2020	Collectively, our finding suggests that the combination of metformin and GSK126 would be an effective approach for future PCa therapy, and particularly effective for AR-positive CRPC.	Metformin	59-68	androgen receptor	Homo sapiens	166-168
33174032-0	2020	Metformin protects high glucose-cultured cardiomyocytes from oxidative stress by promoting NDUFA13 expression and mitochondrial biogenesis via the AMPK signaling pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	147-151
33174032-3	2020	Metformin, an AMP-activated protein kinase (AMPK) activator, protects cardiomyocytes from oxidative stress by improving mitochondrial function; however, the exact underlying mechanisms are not completely understood.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	14-42
33174032-3	2020	Metformin, an AMP-activated protein kinase (AMPK) activator, protects cardiomyocytes from oxidative stress by improving mitochondrial function; however, the exact underlying mechanisms are not completely understood.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	44-48
33174032-10	2020	In addition, metformin stimulated mitochondrial biogenesis, as indicated by increased expression levels of mitochondrial genes (NDUFA1, NDUFA2, NDUFA13 and manganese superoxide dismutase) and mitochondrial biogenesis-related transcription factors [peroxisome proliferator-activated receptor-gamma coactivator-1alpha, nuclear respiratory factor (NRF)-1, and NRF-2] in the metformin + HG group compared with the HG group.	Metformin	13-22	NADH:ubiquinone oxidoreductase subunit A2	Rattus norvegicus	136-142
33174032-10	2020	In addition, metformin stimulated mitochondrial biogenesis, as indicated by increased expression levels of mitochondrial genes (NDUFA1, NDUFA2, NDUFA13 and manganese superoxide dismutase) and mitochondrial biogenesis-related transcription factors [peroxisome proliferator-activated receptor-gamma coactivator-1alpha, nuclear respiratory factor (NRF)-1, and NRF-2] in the metformin + HG group compared with the HG group.	Metformin	13-22	PPARG coactivator 1 alpha	Rattus norvegicus	248-315
33174032-10	2020	In addition, metformin stimulated mitochondrial biogenesis, as indicated by increased expression levels of mitochondrial genes (NDUFA1, NDUFA2, NDUFA13 and manganese superoxide dismutase) and mitochondrial biogenesis-related transcription factors [peroxisome proliferator-activated receptor-gamma coactivator-1alpha, nuclear respiratory factor (NRF)-1, and NRF-2] in the metformin + HG group compared with the HG group.	Metformin	13-22	nuclear respiratory factor 1	Rattus norvegicus	317-351
33174032-10	2020	In addition, metformin stimulated mitochondrial biogenesis, as indicated by increased expression levels of mitochondrial genes (NDUFA1, NDUFA2, NDUFA13 and manganese superoxide dismutase) and mitochondrial biogenesis-related transcription factors [peroxisome proliferator-activated receptor-gamma coactivator-1alpha, nuclear respiratory factor (NRF)-1, and NRF-2] in the metformin + HG group compared with the HG group.	Metformin	13-22	NFE2 like bZIP transcription factor 2	Rattus norvegicus	357-362
33174032-11	2020	Moreover, metformin promoted mitochondrial NDUFA13 protein expression via the AMPK signaling pathway, which was abolished by pretreatment with the AMPK inhibitor, Compound C. The results suggested that metformin protected cardiomyocytes against HG-induced oxidative stress via a mechanism involving AMPK, NDUFA13 and mitochondrial biogenesis.	Metformin	10-19	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	78-82
33174032-11	2020	Moreover, metformin promoted mitochondrial NDUFA13 protein expression via the AMPK signaling pathway, which was abolished by pretreatment with the AMPK inhibitor, Compound C. The results suggested that metformin protected cardiomyocytes against HG-induced oxidative stress via a mechanism involving AMPK, NDUFA13 and mitochondrial biogenesis.	Metformin	10-19	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	147-151
33174032-11	2020	Moreover, metformin promoted mitochondrial NDUFA13 protein expression via the AMPK signaling pathway, which was abolished by pretreatment with the AMPK inhibitor, Compound C. The results suggested that metformin protected cardiomyocytes against HG-induced oxidative stress via a mechanism involving AMPK, NDUFA13 and mitochondrial biogenesis.	Metformin	10-19	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	147-151
33174032-11	2020	Moreover, metformin promoted mitochondrial NDUFA13 protein expression via the AMPK signaling pathway, which was abolished by pretreatment with the AMPK inhibitor, Compound C. The results suggested that metformin protected cardiomyocytes against HG-induced oxidative stress via a mechanism involving AMPK, NDUFA13 and mitochondrial biogenesis.	Metformin	202-211	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	78-82
33174032-11	2020	Moreover, metformin promoted mitochondrial NDUFA13 protein expression via the AMPK signaling pathway, which was abolished by pretreatment with the AMPK inhibitor, Compound C. The results suggested that metformin protected cardiomyocytes against HG-induced oxidative stress via a mechanism involving AMPK, NDUFA13 and mitochondrial biogenesis.	Metformin	202-211	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	147-151
33174032-11	2020	Moreover, metformin promoted mitochondrial NDUFA13 protein expression via the AMPK signaling pathway, which was abolished by pretreatment with the AMPK inhibitor, Compound C. The results suggested that metformin protected cardiomyocytes against HG-induced oxidative stress via a mechanism involving AMPK, NDUFA13 and mitochondrial biogenesis.	Metformin	202-211	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	147-151
33385163-4	2020	CDC25B depletion leads to metformin resistance by inhibiting metformin-induced AMPK activation.	Metformin	26-35	cell division cycle 25B	Homo sapiens	0-6
33385163-4	2020	CDC25B depletion leads to metformin resistance by inhibiting metformin-induced AMPK activation.	Metformin	61-70	cell division cycle 25B	Homo sapiens	0-6
32859615-8	2020	Compared with control, exercise and metformin reduced sTNF-alphaR2: -13.1% (95% CI: -22.9, -1.0) and IL-6: -38.7% (95% CI: -52.3, -18.9); but did not change hs-CRP: -20.5% (95% CI: -44.0, 12.7).	Metformin	36-45	interleukin 6	Homo sapiens	101-105
32544018-6	2020	Results: After six months, the fasting insulin, glucose/insulin ratio, and homeostatic model assessment estimates for insulin resistance were significantly improved in metformin group.	Metformin	168-177	insulin	Homo sapiens	39-46
32544018-6	2020	Results: After six months, the fasting insulin, glucose/insulin ratio, and homeostatic model assessment estimates for insulin resistance were significantly improved in metformin group.	Metformin	168-177	insulin	Homo sapiens	56-63
32544018-6	2020	Results: After six months, the fasting insulin, glucose/insulin ratio, and homeostatic model assessment estimates for insulin resistance were significantly improved in metformin group.	Metformin	168-177	insulin	Homo sapiens	56-63
32544018-9	2020	Conclusion: Metformin, associated with vaginal ring, improves the insulin and carbohydrate metabolism.	Metformin	12-21	insulin	Homo sapiens	66-73
32822526-9	2020	Metformin reduced glucose levels and glycated haemoglobin, improved insulin sensitivity and decreased thyrotrophin levels.	Metformin	0-9	insulin	Homo sapiens	68-75
32822526-11	2020	In levothyroxine-treated patients, metformin slightly reduced prolactin levels.	Metformin	35-44	prolactin	Homo sapiens	62-71
32822526-13	2020	The thyrotrophin-lowering effect of metformin correlated with the improvement in insulin sensitivity and in levothyroxine-treated women with the changes in prolactin levels.	Metformin	36-45	insulin	Homo sapiens	81-88
32866967-11	2020	Metformin also reduced A4 (p=0.036), T (p=0.023) and SHBG (p=0.010) levels through pregnancy in mothers with a male foetus.	Metformin	0-9	sex hormone binding globulin	Homo sapiens	53-57
33126079-4	2020	In addition, activation of AMPK by metformin inhibited S1P-induced ASMCs proliferation by suppressing STAT3 phosphorylation and therefore suppression of PLK1 and ID2 protein expression.	Metformin	35-44	signal transducer and activator of transcription 3	Homo sapiens	102-107
33303055-0	2020	Metformin protects chondrocytes against IL-1beta induced injury by regulation of the AMPK/NF-kappa B signaling pathway.	Metformin	0-9	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	90-100
33303055-7	2020	Furthermore, the results showed that metformin blocked the NF-kappa B pathway in IL-1beta-induced ATDC5 cells via activation of AMP-activated protein kinase (AMPK).	Metformin	37-46	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	59-69
33303055-8	2020	These results indicated that metformin protected chondrocytes against IL-1beta-induced injury, possibly by regulation of the AMPK/NF-kappa B signaling pathway.	Metformin	29-38	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	130-140
33489797-0	2020	Metformin reverses chemoresistance in non-small cell lung cancer via accelerating ubiquitination-mediated degradation of Nrf2.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	121-125
33489797-3	2020	Metformin-mediated downregulation of Nrf2 plays a pivotal role in overcoming drug resistance in NSCLC cells.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	37-41
33489797-6	2020	Co-immunoprecipitation (co-IP) and Phos-tag assays were used to explore the mechanism of metformin-mediated Nrf2 suppression.	Metformin	89-98	NFE2 like bZIP transcription factor 2	Homo sapiens	108-112
33489797-8	2020	Results: Metformin was observed to synergistically augment cisplatin-induced cytotoxicity by strongly inhibiting the level of Nrf2, thereby weakening the antioxidant system and detoxification ability of Nrf2 and enhancing ROS-mediated apoptosis in NSCLC.	Metformin	9-18	NFE2 like bZIP transcription factor 2	Homo sapiens	126-130
33489797-8	2020	Results: Metformin was observed to synergistically augment cisplatin-induced cytotoxicity by strongly inhibiting the level of Nrf2, thereby weakening the antioxidant system and detoxification ability of Nrf2 and enhancing ROS-mediated apoptosis in NSCLC.	Metformin	9-18	NFE2 like bZIP transcription factor 2	Homo sapiens	203-207
33489797-10	2020	Mechanistically, metformin extensively dephosphorylates Nrf2 by attenuating the interaction between Nrf2 and extracellular signal-regulated kinases 1/2 (ERK1/2), which then restores its polyubiquitination and accelerates its proteasomal degradation.	Metformin	17-26	NFE2 like bZIP transcription factor 2	Homo sapiens	56-60
33489797-10	2020	Mechanistically, metformin extensively dephosphorylates Nrf2 by attenuating the interaction between Nrf2 and extracellular signal-regulated kinases 1/2 (ERK1/2), which then restores its polyubiquitination and accelerates its proteasomal degradation.	Metformin	17-26	NFE2 like bZIP transcription factor 2	Homo sapiens	100-104
33489797-10	2020	Mechanistically, metformin extensively dephosphorylates Nrf2 by attenuating the interaction between Nrf2 and extracellular signal-regulated kinases 1/2 (ERK1/2), which then restores its polyubiquitination and accelerates its proteasomal degradation.	Metformin	17-26	mitogen-activated protein kinase 1	Homo sapiens	109-151
33489797-10	2020	Mechanistically, metformin extensively dephosphorylates Nrf2 by attenuating the interaction between Nrf2 and extracellular signal-regulated kinases 1/2 (ERK1/2), which then restores its polyubiquitination and accelerates its proteasomal degradation.	Metformin	17-26	mitogen-activated protein kinase 3	Homo sapiens	153-159
33489797-12	2020	Conclusions: Our findings illustrate the mechanism of metformin-mediated Nrf2 degradation through posttranslational modifications (PTMs), which weakens the ROS defense system in NSCLC.	Metformin	54-63	NFE2 like bZIP transcription factor 2	Homo sapiens	73-77
32970287-8	2020	In contrast the IRS/PI3-K/AKT pathway signaling components, Akt and GLUT4 increased in insulin-resistant 3T3L1 adipocytes and human diabetic adipose tissue after three months of metformin treatment.	Metformin	178-187	isoleucyl-tRNA synthetase 1	Homo sapiens	16-19
32970287-8	2020	In contrast the IRS/PI3-K/AKT pathway signaling components, Akt and GLUT4 increased in insulin-resistant 3T3L1 adipocytes and human diabetic adipose tissue after three months of metformin treatment.	Metformin	178-187	AKT serine/threonine kinase 1	Homo sapiens	26-29
32970287-8	2020	In contrast the IRS/PI3-K/AKT pathway signaling components, Akt and GLUT4 increased in insulin-resistant 3T3L1 adipocytes and human diabetic adipose tissue after three months of metformin treatment.	Metformin	178-187	AKT serine/threonine kinase 1	Homo sapiens	60-63
32970287-9	2020	CONCLUSIONS: Metformin reduced insulin resistance in adipocytes by reduction of miR223 expression and improving of IRS/Akt/GLUT4 signaling pathways.	Metformin	13-22	insulin	Homo sapiens	31-38
32970287-9	2020	CONCLUSIONS: Metformin reduced insulin resistance in adipocytes by reduction of miR223 expression and improving of IRS/Akt/GLUT4 signaling pathways.	Metformin	13-22	isoleucyl-tRNA synthetase 1	Homo sapiens	115-118
32970287-9	2020	CONCLUSIONS: Metformin reduced insulin resistance in adipocytes by reduction of miR223 expression and improving of IRS/Akt/GLUT4 signaling pathways.	Metformin	13-22	AKT serine/threonine kinase 1	Homo sapiens	119-122
33243251-8	2020	Insulin and the insulin sensitizers rosiglitazone and metformin prevent in part the RD-induced cone loss in vivo, despite the persistence of inflammation CONCLUSION: Our results describe a new mechanism by which inflammation induces cone death in RD, likely through cone starvation due to the downregulation of RdCVF that could be reversed by insulin.	Metformin	54-63	insulin	Homo sapiens	16-23
33200330-1	2020	Metformin is an activator of the AMPK and Nrf2 pathways which are important in the pathology of several complex pulmonary diseases with unmet medical needs.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	42-46
33294120-8	2020	Metformin inhibited apoptosis through regulating cooperation of the mitochondrion-associated ER membranes and the insulin (PI3K/AKT) signaling pathway.	Metformin	0-9	insulin	Gallus gallus	114-121
33294120-10	2020	Additionally, metformin activated PI3K/AKT that suppressed activation of BAD (downstream of the insulin signaling pathway) in the atretic follicles.	Metformin	14-23	insulin	Gallus gallus	96-103
33575476-0	2021	Metformin enhances anti-cancer effects of cisplatin in meningioma through AMPK-mTOR signaling pathways.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	79-83
33575476-5	2021	Additionally, metformin activated adenosine monophosphate activated protein kinase (AMPK) and repressed the mammalian target of rapamycin (mTOR) signaling pathways via an AMPK-dependent mechanism.	Metformin	14-23	mechanistic target of rapamycin kinase	Homo sapiens	108-137
33575476-5	2021	Additionally, metformin activated adenosine monophosphate activated protein kinase (AMPK) and repressed the mammalian target of rapamycin (mTOR) signaling pathways via an AMPK-dependent mechanism.	Metformin	14-23	mechanistic target of rapamycin kinase	Homo sapiens	139-143
33575476-8	2021	These results demonstrate metformin enhanced the anti-cancer effect of cisplatin in meningioma in vitro and in vivo, an effect mediated through the activation of AMPK and repression of mTOR signaling pathways.	Metformin	26-35	mechanistic target of rapamycin kinase	Homo sapiens	185-189
33269063-9	2020	In the acarbose group, a lower baseline area under the curve of glucagon-like peptide 1 (AUCGLP-1) was associated with a high DeltaWHtR (odds ratio [OR] = 0.796, P < 0.001), while a higher baseline AUCGLP-1 was associated with a high DeltaWHtR in the patients treated with metformin (OR = 1.133, P = 0.025).	Metformin	273-282	glucagon	Homo sapiens	64-87
33197121-7	2022	Of the non-insulin agents, metformin was consistently the most frequently dispensed agent, with a rapid growth in metformin combination tablets.	Metformin	27-36	insulin	Homo sapiens	11-18
32877649-9	2020	Marjoram alone or in combination with metformin prominently decreased the IL-6 level and improved the levels of ovarian SOD and GPx enzymes (P-value<0.05).	Metformin	38-47	interleukin 6	Rattus norvegicus	74-78
33172126-0	2020	Medroxyprogesterone Reverses Tolerable Dose Metformin-Induced Inhibition of Invasion via Matrix Metallopeptidase-9 and Transforming Growth Factor-beta1 in KLE Endometrial Cancer Cells.	Metformin	44-53	transforming growth factor beta 1	Homo sapiens	119-151
33172126-6	2020	Changes of MMP-9 and TGF-beta1 according to combinations of MPA and metformin were similar to those of invasion in KLE cells.	Metformin	68-77	transforming growth factor beta 1	Homo sapiens	21-30
33172126-8	2020	Anti-invasive effect of metformin in KLE cells was completely reversed by the addition of MPA; this might be associated with MMP-9 and TGF-beta1.	Metformin	24-33	transforming growth factor beta 1	Homo sapiens	135-144
33520876-8	2020	In the present study, metabolic rate and hepatic clearance changed to 0.0112 +- 0.0008 and 6.2 +- 0.1 ml/min in the type-1 diabetic group treated with insulin plus metformin, and 0.0149 +- 0.0012 and 6.03 +- 0.06 ml/min in the insulin-receiving type-2 diabetic rats.	Metformin	164-173	insulin	Homo sapiens	227-234
33152427-0	2021	Huangkui capsule in combination with metformin ameliorates diabetic nephropathy via the Klotho/TGF-beta1/p38MAPK signaling pathway.	Metformin	37-46	transforming growth factor, beta 1	Rattus norvegicus	95-104
32601731-7	2020	Metformin was able to stabilise insulin sensitivity in every stratified sub-cohort except one.	Metformin	0-9	insulin	Homo sapiens	32-39
32601731-11	2020	Metformin was able to stabilise insulin sensitivity and was more effective in persons with more pronounced IFG.	Metformin	0-9	insulin	Homo sapiens	32-39
33208304-5	2020	Serum FN3K protein and AGE levels were assessed by ELISA in patients with COPD exacerbations receiving metformin.	Metformin	103-112	fructosamine 3 kinase	Homo sapiens	6-10
33208304-10	2020	Metformin enhanced systemic levels of FN3K in COPD subjects independent of their high-expression or low-expression status.	Metformin	0-9	fructosamine 3 kinase	Homo sapiens	38-42
33208304-11	2020	DISCUSSION: The data highlight that low and high FN3K expressors exist within our study cohort and metformin induces FN3K levels, highlighting a potential mechanism to reduce the risk of CVD comorbidity and mortality.	Metformin	99-108	fructosamine 3 kinase	Homo sapiens	117-121
32934682-0	2020	Metformin attenuates renal interstitial fibrosis through upregulation of Deptor in unilateral ureteral obstruction in rats.	Metformin	0-9	DEP domain containing MTOR-interacting protein	Rattus norvegicus	73-79
32934682-13	2020	In conclusion, the present results suggested that metformin attenuated RIF of UUO rats, and the mechanism of action was found to be associated with the increase in Deptor expression and inhibition of the mTOR/p70S6K pathway in the kidneys of UUO rats.	Metformin	50-59	DEP domain containing MTOR-interacting protein	Rattus norvegicus	164-170
33051086-0	2020	Metformin inhibits the inflammatory and oxidative stress response induced by skin UVB-irradiation and provides 4-hydroxy-2-nonenal and nitrotyrosine formation and p53 protein activation.	Metformin	0-9	tumor protein p53	Homo sapiens	163-166
33194937-8	2020	Metformin"s mechanisms of actions are complex but clearly involve secondary lowering of circulating insulin.	Metformin	0-9	insulin	Homo sapiens	100-107
33081077-0	2020	Metformin Reduces NGF-Induced Tumour Promoter Effects in Epithelial Ovarian Cancer Cells.	Metformin	0-9	nerve growth factor	Homo sapiens	18-21
33081077-3	2020	We previously reported that metformin prevents NGF-induced proliferation and angiogenic potential of EOC cells.	Metformin	28-37	nerve growth factor	Homo sapiens	47-50
33081077-4	2020	In this study, we sought to obtain a better understanding of the mechanism(s) by which metformin blocks these NGF-induced effects in EOC cells.	Metformin	87-96	nerve growth factor	Homo sapiens	110-113
33081077-6	2020	Metformin decreased the NGF-induced transcriptional activity of MYC and beta-catenin/T-cell factor/lymphoid enhancer-binding factor (TCF-Lef), as well as the expression of c-MYC, survivin and VEGF in EOC cells, while it increased miR-23b and miR-145 levels.	Metformin	0-9	nerve growth factor	Homo sapiens	24-27
33081077-6	2020	Metformin decreased the NGF-induced transcriptional activity of MYC and beta-catenin/T-cell factor/lymphoid enhancer-binding factor (TCF-Lef), as well as the expression of c-MYC, survivin and VEGF in EOC cells, while it increased miR-23b and miR-145 levels.	Metformin	0-9	vascular endothelial growth factor A	Homo sapiens	192-196
32750367-12	2020	All doses of metformin improved brain pathologies in rats with cardiac I/R injury possibly via activating cerebral AMPK.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	115-119
33066102-2	2020	Previously, we reported that metformin reduced SUV39H1, a histone methyltransferase of H3 Lys9, to inhibit the migration of PCa cells.	Metformin	29-38	SUV39H1 histone lysine methyltransferase	Homo sapiens	47-54
33162888-0	2020	Metformin Ameliorates Gestational Diabetes Mellitus-Induced Endothelial Dysfunction via Downregulation of p65 and Upregulation of Nrf2.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	130-134
33025801-11	2021	Metformin slightly reduced expression in ADAMTS5 (beta = 0.34, P = 0.04), HIF-1a (beta = 0.39, P = 0.04), IL4 (beta = 0.30, P = 0.02), MMP1 (beta = 0.47, P < 0.01), and SOX9 (beta = 0.37, P = 0.03).	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	74-80
33025801-11	2021	Metformin slightly reduced expression in ADAMTS5 (beta = 0.34, P = 0.04), HIF-1a (beta = 0.39, P = 0.04), IL4 (beta = 0.30, P = 0.02), MMP1 (beta = 0.47, P < 0.01), and SOX9 (beta = 0.37, P = 0.03).	Metformin	0-9	interleukin 4	Homo sapiens	106-109
32783890-0	2020	Microbial Imidazole Propionate Affects Responses to Metformin through p38gamma-Dependent Inhibitory AMPK Phosphorylation.	Metformin	52-61	mitogen-activated protein kinase 12	Mus musculus	70-78
32783890-7	2020	Finally, we identify imidazole propionate-activated p38gamma as a novel kinase for Akt and demonstrate that p38gamma kinase activity mediates the inhibitory action of imidazole propionate on metformin.	Metformin	191-200	mitogen-activated protein kinase 12	Mus musculus	52-60
32783890-7	2020	Finally, we identify imidazole propionate-activated p38gamma as a novel kinase for Akt and demonstrate that p38gamma kinase activity mediates the inhibitory action of imidazole propionate on metformin.	Metformin	191-200	mitogen-activated protein kinase 12	Mus musculus	108-116
32480429-10	2020	Conversely, the AMPK activator metformin or the mTORC1 inhibitor rapamycin reversed the effects of FL on the alterations of autophagy, hypertrophy and apoptosis in cardiomyocytes induced by Ang II.	Metformin	31-40	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	16-20
32480429-10	2020	Conversely, the AMPK activator metformin or the mTORC1 inhibitor rapamycin reversed the effects of FL on the alterations of autophagy, hypertrophy and apoptosis in cardiomyocytes induced by Ang II.	Metformin	31-40	angiotensinogen	Rattus norvegicus	190-196
33149857-9	2020	Generally, metabolic memory increased p53 and acetyl-P53 and decreased SIRT1 proteins in HUVECs, which were reversed by alpha-mangostin and metformin.	Metformin	140-149	tumor protein p53	Homo sapiens	38-41
32589349-0	2020	Effects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells.	Metformin	11-20	mechanistic target of rapamycin kinase	Homo sapiens	72-76
31903641-8	2020	In both groups, metformin reduced glucose levels, homeostasis model assessment 1 of insulin resistance index (HOMA1-IR), thyrotropin levels and Jostel"s thyrotropin index, as well as increased SPINA-GT.	Metformin	16-25	insulin	Homo sapiens	84-91
32384961-7	2020	RT-qPCR and immunoblotting were used to detect the effects of metformin on the expression of TXNIP and autophagy associated genes-BECN1 and LC3B in the sciatic nerves of pain model mice.	Metformin	62-71	thioredoxin interacting protein	Mus musculus	93-98
32384961-12	2020	However, metformin intervention resulted in significant up-regulation of TXNIP and autophagy related indexes, and augmented the threshold of thermal sensitivity and mechanical tingling.	Metformin	9-18	thioredoxin interacting protein	Mus musculus	73-78
32384961-15	2020	In contrast, metformin promotes the expression of TXNIP and autophagy of cells thereby inhibiting neural sensitivity and thus results in pain relief.	Metformin	13-22	thioredoxin interacting protein	Mus musculus	50-55
33153458-10	2020	Our initial attempt to reduce insulin resistance with metformin and pioglitazone was not effective, possibly because of inadequate insulinemia.	Metformin	54-63	insulin	Homo sapiens	30-37
32858129-8	2020	Furthermore, compared with cTBI, the administration of metformin at day 3-10 or day 5-28 after cTBI significantly elevated the expression of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and growth associated protein 43 (an axonal regeneration marker) and the number of vascular branch points and decreased the area of glial scar and the number of amoeboid microglia in the peri-infarct area at day 14 or 28 postinjury.	Metformin	55-64	growth associated protein 43	Mus musculus	216-244
32843330-8	2020	Next, using the REF approach, we predicted the in vivo metformin CLh,s,in using OCT1-transporter expressing HEK293 cells or plated human hepatocytes.	Metformin	55-64	solute carrier family 22 member 1	Homo sapiens	80-84
32843330-12	2020	Significance Statement This study is the first to use OCT1-expressing cells and plated hepatocytes to compare proteomics-informed REF approach with the traditional MGPGL approach to predict hepatic uptake CL of metformin in humans.	Metformin	211-220	solute carrier family 22 member 1	Homo sapiens	54-58
32519799-0	2020	Metformin scavenges formaldehyde and attenuates formaldehyde-induced bovine serum albumin crosslinking and cellular DNA damage.	Metformin	0-9	albumin	Homo sapiens	76-89
32870322-0	2020	Metformin improves depressive-like symptoms in mice via inhibition of peripheral and central NF-kappaB-NLRP3 inflammation activation.	Metformin	0-9	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	93-102
32870322-6	2020	We further found that metformin significantly suppressed NLRP3 inflammasome activation, subsequent caspase-1 cleavage, and interleukin-1beta secretion in both peripheral macrophages and central hippocampus.	Metformin	22-31	interleukin 1 beta	Mus musculus	123-140
32893983-11	2020	Cyclic PIP synthesis is activated by biguanides as metformin two to four-fold and by antihypertensive drugs two-fold.	Metformin	51-60	prolactin induced protein	Rattus norvegicus	7-10
32239671-3	2020	Treatment of colorectal cancer (CRC)-derived cells (SW-480 and HT-29) with 2.0 mM metformin promoted a redistribution of cytosolic E-cadherin to de novo formed puncta along the length of the contacting membranes of these cells.	Metformin	82-91	cadherin 1	Homo sapiens	131-141
32239671-6	2020	Western blot analysis of lysates of CRC-derived cells revealed a substantial metformin-induced increase in the level of p120-catenin as well as E-cadherin phosphorylation on Ser838/840 , a modification associated with beta-catenin/E-cadherin interaction.	Metformin	77-86	cadherin 1	Homo sapiens	231-241
32239671-7	2020	These modifications in E-cadherin, p120-catenin and beta-catenin localization suggest that metformin induces rebuilding of AJs in CRC-derived cells.	Metformin	91-100	cadherin 1	Homo sapiens	23-33
32679167-13	2020	In sum, we have concluded that progranulin can be a key mediator in epilepsy, and the anti-inflammatory action of metformin in status epilepticus is through increasing the secretion of IL-10 and inhibiting IL-1 beta and astrogliosis.	Metformin	114-123	interleukin 1 alpha	Rattus norvegicus	206-215
32428991-4	2020	The United Kingdom Prospective Diabetes Study (UKPDS) demonstrated that metformin not only had hypoglycemic action equivalent to sulfonylureas (SU) and insulin but also significantly lowered mortality and incidence of cardiovascular disease compared with SU or insulin treatment (1) while exerting a cardioprotective effect that lasted 10 years after the study ended (2).	Metformin	72-81	insulin	Homo sapiens	261-268
32934724-3	2020	As a traditional insulin sensitizer and newly discovered anticancer agent, metformin directly and indirectly inhibits the development of EC.	Metformin	75-84	insulin	Homo sapiens	17-24
32934724-4	2020	The direct mechanisms of metformin include inhibition of the LKB1-AMP-activated protein kinase-mTOR, PI3K-Akt and insulin-like growth factor 1-related signaling pathways, which reduces the proliferation and promotes the apoptosis of EC cells.	Metformin	25-34	mechanistic target of rapamycin kinase	Homo sapiens	95-99
32934724-4	2020	The direct mechanisms of metformin include inhibition of the LKB1-AMP-activated protein kinase-mTOR, PI3K-Akt and insulin-like growth factor 1-related signaling pathways, which reduces the proliferation and promotes the apoptosis of EC cells.	Metformin	25-34	AKT serine/threonine kinase 1	Homo sapiens	106-109
32934724-4	2020	The direct mechanisms of metformin include inhibition of the LKB1-AMP-activated protein kinase-mTOR, PI3K-Akt and insulin-like growth factor 1-related signaling pathways, which reduces the proliferation and promotes the apoptosis of EC cells.	Metformin	25-34	insulin like growth factor 1	Homo sapiens	114-142
32934724-5	2020	In the indirect mechanism, metformin increases the insulin sensitivity of body tissues and decreases circulating insulin levels.	Metformin	27-36	insulin	Homo sapiens	51-58
32934724-5	2020	In the indirect mechanism, metformin increases the insulin sensitivity of body tissues and decreases circulating insulin levels.	Metformin	27-36	insulin	Homo sapiens	113-120
32739430-7	2020	To further investigate the mechanism of the synergetic activity of metformin/salicylate, we used CRISPR to generate mutant alleles of the scaffolding subunit of AMPK, aakb-1/AMPKbeta1.	Metformin	67-76	AMPKBI domain-containing protein	Caenorhabditis elegans	167-173
32739430-10	2020	Interestingly, only aakb-2/AMPKbeta2 is required for the synergistic action of metformin/salicylate to reduce polyQ aggregation.	Metformin	79-88	AMPKBI domain-containing protein	Caenorhabditis elegans	20-26
33065544-9	2020	The expression of genes related to steroidogenesis such as FSHR, STAR, CYP11A1, HSD3B, and progesterone secretion was significantly decreased in response to metformin treatment in a dose-dependent manner.	Metformin	157-166	follicle stimulating hormone receptor	Gallus gallus	59-63
32994049-5	2020	These metformin effects result in the improvement of insulin sensitivity and glucose utilization in extrahepatic tissues.	Metformin	6-15	insulin	Homo sapiens	53-60
33149616-0	2020	Metformin Combined with 4SC-202 Inhibited the Migration and Invasion of OSCC via STAT3/TWIST1.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	81-86
33149616-0	2020	Metformin Combined with 4SC-202 Inhibited the Migration and Invasion of OSCC via STAT3/TWIST1.	Metformin	0-9	twist family bHLH transcription factor 1	Homo sapiens	87-93
33149616-8	2020	Importantly, the expression of TWIST1 was suppressed by metformin and 4SC-202, while the invasion and migration inhibitory effects of metformin and 4SC-202 were countered by the overexpression of TWIST1.	Metformin	56-65	twist family bHLH transcription factor 1	Homo sapiens	31-37
33149616-8	2020	Importantly, the expression of TWIST1 was suppressed by metformin and 4SC-202, while the invasion and migration inhibitory effects of metformin and 4SC-202 were countered by the overexpression of TWIST1.	Metformin	134-143	twist family bHLH transcription factor 1	Homo sapiens	196-202
33149616-9	2020	In addition, the phosphorylation level of STAT3 decreased after the administration of metformin or/and 4SC-202.	Metformin	86-95	signal transducer and activator of transcription 3	Homo sapiens	42-47
33149616-11	2020	Conclusion: Metformin and 4SC-202 suppressed the invasion and migration of OSCC through inhibition of STAT3/TWIST1, and this scheme can serve as a novel therapeutic strategy for OSCC.	Metformin	12-21	signal transducer and activator of transcription 3	Homo sapiens	102-107
33149616-11	2020	Conclusion: Metformin and 4SC-202 suppressed the invasion and migration of OSCC through inhibition of STAT3/TWIST1, and this scheme can serve as a novel therapeutic strategy for OSCC.	Metformin	12-21	twist family bHLH transcription factor 1	Homo sapiens	108-114
33126710-10	2020	In agreement with the changes on mitochondrial morphology, the ERK-Akt signal axis dependent Drp-1 phosphorylation at S616 (an index of mitochondrial fission) under NaIO3 treatment was blocked by A769662, but not by metformin.	Metformin	216-225	mitogen-activated protein kinase 1	Homo sapiens	63-66
33126710-10	2020	In agreement with the changes on mitochondrial morphology, the ERK-Akt signal axis dependent Drp-1 phosphorylation at S616 (an index of mitochondrial fission) under NaIO3 treatment was blocked by A769662, but not by metformin.	Metformin	216-225	AKT serine/threonine kinase 1	Homo sapiens	67-70
33116117-8	2020	Metformin significantly modulated the profiles of the SASP elicited by LY2835219 by inhibiting the mTOR and stat3 pathways.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	99-103
33116117-8	2020	Metformin significantly modulated the profiles of the SASP elicited by LY2835219 by inhibiting the mTOR and stat3 pathways.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	108-113
33116117-10	2020	Furthermore, results showed that the stemness inhibition by metformin was associated with blockade of the IL6-stat3 axis.	Metformin	60-69	interleukin 6	Homo sapiens	106-109
33116117-10	2020	Furthermore, results showed that the stemness inhibition by metformin was associated with blockade of the IL6-stat3 axis.	Metformin	60-69	signal transducer and activator of transcription 3	Homo sapiens	110-115
33116117-11	2020	Survival analysis demonstrated that overexpression of IL6 and stemness markers was associated with poor survival in HNSCC patients, indicating that including metformin to target these proteins might improve patient prognosis.	Metformin	158-167	interleukin 6	Homo sapiens	54-57
33268575-18	2020	Metformin effectively reduced H/R-induced apoptosis (P=0.013), mitoSOX release (P<0.001), HIF-1alpha, PGC1alpha and apoptosis-related protein expression, recovered the cell viability (P<0.001), and reduced myocardial infarction (P=0.003).	Metformin	0-9	PPARG coactivator 1 alpha	Rattus norvegicus	102-111
33108409-0	2020	Metformin partially reverses the inhibitory effect of co-culture with ER-/PR-/HER2+ breast cancer cells on biomarkers of monocyte antitumor activity.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	78-82
33204328-13	2020	Notably, inhibiting the OXPHOS system with metformin delayed the proliferative capacity of OSCC cells cultured in the ITGB2-expressing CAFs medium.	Metformin	43-52	integrin subunit beta 2	Homo sapiens	118-123
33553026-5	2020	Result: In the glucose-free treatments, metformin and silymarin decreased the levels of AST, ALT, and ALP enzymes in the blood.	Metformin	40-49	PDZ and LIM domain 3b	Danio rerio	102-105
33030392-0	2021	Metformin rescues muscle function in BAG3 myofibrillar myopathy models.	Metformin	0-9	BAG cochaperone 3	Homo sapiens	37-41
33030392-7	2021	Further evaluation demonstrated metformin is not only able to bring about the removal of protein aggregates in zebrafish and human myoblasts but is also able to rescue the fiber disintegration and swimming deficit observed in the bag3 -/- fish.	Metformin	32-41	BAG cochaperone 3	Homo sapiens	230-234
33030392-8	2021	Therefore, repurposing metformin provides a promising therapy for BAG3 myopathy.	Metformin	23-32	BAG cochaperone 3	Homo sapiens	66-70
30572719-3	2020	Notably, protein levels of SIRT1, SIRT3, and SIRT4 were higher in patients with DR compared with controls after adjusting for diabetes duration and taking metformin (p = .001 for SIRT1; p = .001 for SIRT3; p = .005 for SIRT4).	Metformin	155-164	sirtuin 4	Homo sapiens	45-50
32621957-2	2020	Since pretreatment with metformin attenuated both cardiac and cerebral I/R injury via AMP-activated protein kinase (AMPK) pathways, we hypothesized that metformin given after ischemia mitigates both cardiac and brain pathologies following cardiac I/R.	Metformin	24-33	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	86-114
32621957-2	2020	Since pretreatment with metformin attenuated both cardiac and cerebral I/R injury via AMP-activated protein kinase (AMPK) pathways, we hypothesized that metformin given after ischemia mitigates both cardiac and brain pathologies following cardiac I/R.	Metformin	24-33	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	116-120
32621957-2	2020	Since pretreatment with metformin attenuated both cardiac and cerebral I/R injury via AMP-activated protein kinase (AMPK) pathways, we hypothesized that metformin given after ischemia mitigates both cardiac and brain pathologies following cardiac I/R.	Metformin	153-162	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	86-114
32621957-2	2020	Since pretreatment with metformin attenuated both cardiac and cerebral I/R injury via AMP-activated protein kinase (AMPK) pathways, we hypothesized that metformin given after ischemia mitigates both cardiac and brain pathologies following cardiac I/R.	Metformin	153-162	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	116-120
32621957-13	2020	In conclusion, metformin given during ischemia preferentially provides neuroprotection against brain mitochondrial dysfunction, apoptosis, microglial activation, and dendritic spine loss in an AMPK-independent manner following cardiac I/R injury.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	193-197
32800853-0	2020	Activation of AMPK/aPKCzeta/CREB pathway by metformin is associated with upregulation of GDNF and dopamine.	Metformin	44-53	protein kinase C, zeta	Mus musculus	19-27
32800853-0	2020	Activation of AMPK/aPKCzeta/CREB pathway by metformin is associated with upregulation of GDNF and dopamine.	Metformin	44-53	cAMP responsive element binding protein 1	Mus musculus	28-32
32800853-6	2020	We further investigated the role of the neurotrophic factors in the activation of TH and observed that both BDNF and GDNF-induction were essential for metformin-induced TH activation.	Metformin	151-160	glial cell derived neurotrophic factor	Homo sapiens	117-121
32800853-7	2020	We found that the AMPK/aPKCzeta/CREB pathway was essential for metformin-induced GDNF upregulation and TH activation.	Metformin	63-72	protein kinase C, zeta	Mus musculus	23-31
32800853-7	2020	We found that the AMPK/aPKCzeta/CREB pathway was essential for metformin-induced GDNF upregulation and TH activation.	Metformin	63-72	cAMP responsive element binding protein 1	Mus musculus	32-36
32800853-7	2020	We found that the AMPK/aPKCzeta/CREB pathway was essential for metformin-induced GDNF upregulation and TH activation.	Metformin	63-72	glial cell derived neurotrophic factor	Homo sapiens	81-85
32713411-0	2020	Effects of metformin on epicardial adipose tissue and atrial electromechanical delay of obese children with insulin resistance.	Metformin	11-20	insulin	Homo sapiens	108-115
32713411-3	2020	AIM: This study aims to demonstrate the effects of metformin on epicardial adipose tissue and electromechanical delay in patients using metformin for insulin resistance.	Metformin	51-60	insulin	Homo sapiens	150-157
32713411-3	2020	AIM: This study aims to demonstrate the effects of metformin on epicardial adipose tissue and electromechanical delay in patients using metformin for insulin resistance.	Metformin	136-145	insulin	Homo sapiens	150-157
32713411-4	2020	MATERIALS AND METHODS: A total of 30 patients using metformin for insulin resistance were included in the study.	Metformin	52-61	insulin	Homo sapiens	66-73
32861747-5	2020	Transfection of mir-181c, one of the positive regulators of Akt and mTOR, lead to an increase in the cell resistance to both mTOR inhibitors, rapamycin, and metformin, which correlated with Raptor overexpression and activation of Akt/AP-1 signaling.	Metformin	157-166	AKT serine/threonine kinase 1	Homo sapiens	60-63
32861747-5	2020	Transfection of mir-181c, one of the positive regulators of Akt and mTOR, lead to an increase in the cell resistance to both mTOR inhibitors, rapamycin, and metformin, which correlated with Raptor overexpression and activation of Akt/AP-1 signaling.	Metformin	157-166	mechanistic target of rapamycin kinase	Homo sapiens	68-72
32861747-5	2020	Transfection of mir-181c, one of the positive regulators of Akt and mTOR, lead to an increase in the cell resistance to both mTOR inhibitors, rapamycin, and metformin, which correlated with Raptor overexpression and activation of Akt/AP-1 signaling.	Metformin	157-166	AKT serine/threonine kinase 1	Homo sapiens	230-233
33271428-1	2020	Metformin remains the first-line drug treatment for type 2 diabetes (T2D) in most guidelines not only because it achieves significant reduction in HbA1c but also because of a wealth of clinical experience regarding its safety and observational data that has shown that metformin use is associated with lower mortality rates when compared to sulphonylureas or insulin.	Metformin	0-9	insulin	Homo sapiens	359-366
33271428-1	2020	Metformin remains the first-line drug treatment for type 2 diabetes (T2D) in most guidelines not only because it achieves significant reduction in HbA1c but also because of a wealth of clinical experience regarding its safety and observational data that has shown that metformin use is associated with lower mortality rates when compared to sulphonylureas or insulin.	Metformin	269-278	insulin	Homo sapiens	359-366
32621159-0	2020	Neuroprotective effects of metformin on traumatic brain injury in rats is associated with the AMP-activated protein kinase signaling pathway.	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	94-122
32621159-1	2020	Metformin is an activator of AMP-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	29-57
32621159-1	2020	Metformin is an activator of AMP-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	59-63
32621159-12	2020	Furthermore, the p-AMPK/AMPK ratio was increased by metformin administration compare to TBI or Vehicle groups (p < 0.0001).	Metformin	52-61	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	19-23
32621159-12	2020	Furthermore, the p-AMPK/AMPK ratio was increased by metformin administration compare to TBI or Vehicle groups (p < 0.0001).	Metformin	52-61	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	24-28
32621159-13	2020	Inhibition of AMPK by compound C abolished Metformin neuroprotective effects (P < 0.05 compared to Met 200 group).	Metformin	43-52	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	14-18
32621159-14	2020	This study suggests that metformin inhibits TBI-mediated secondary injury via phosphorylation of AMPK and improves neurobehavioral function following TBI, which provides a potential therapeutic opportunity in the treatment of TBI.	Metformin	25-34	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	97-101
32945402-0	2020	Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS-AKT-mTOR axis.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	106-109
32945402-0	2020	Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS-AKT-mTOR axis.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	110-114
32945402-8	2020	Furthermore, metformin significantly scavenged reactive oxygen species (ROS) induced by high glucose levels, and regulated the ROS-AKT-mTOR axis inhibited by high glucose levels, suggesting the protective effects of metformin against high glucose levels via regulation of the ROS-AKT-mTOR axis.	Metformin	13-22	AKT serine/threonine kinase 1	Homo sapiens	131-134
32945402-8	2020	Furthermore, metformin significantly scavenged reactive oxygen species (ROS) induced by high glucose levels, and regulated the ROS-AKT-mTOR axis inhibited by high glucose levels, suggesting the protective effects of metformin against high glucose levels via regulation of the ROS-AKT-mTOR axis.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	135-139
32945402-8	2020	Furthermore, metformin significantly scavenged reactive oxygen species (ROS) induced by high glucose levels, and regulated the ROS-AKT-mTOR axis inhibited by high glucose levels, suggesting the protective effects of metformin against high glucose levels via regulation of the ROS-AKT-mTOR axis.	Metformin	13-22	AKT serine/threonine kinase 1	Homo sapiens	280-283
32945402-8	2020	Furthermore, metformin significantly scavenged reactive oxygen species (ROS) induced by high glucose levels, and regulated the ROS-AKT-mTOR axis inhibited by high glucose levels, suggesting the protective effects of metformin against high glucose levels via regulation of the ROS-AKT-mTOR axis.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	284-288
32945402-8	2020	Furthermore, metformin significantly scavenged reactive oxygen species (ROS) induced by high glucose levels, and regulated the ROS-AKT-mTOR axis inhibited by high glucose levels, suggesting the protective effects of metformin against high glucose levels via regulation of the ROS-AKT-mTOR axis.	Metformin	216-225	AKT serine/threonine kinase 1	Homo sapiens	131-134
32945402-8	2020	Furthermore, metformin significantly scavenged reactive oxygen species (ROS) induced by high glucose levels, and regulated the ROS-AKT-mTOR axis inhibited by high glucose levels, suggesting the protective effects of metformin against high glucose levels via regulation of the ROS-AKT-mTOR axis.	Metformin	216-225	mechanistic target of rapamycin kinase	Homo sapiens	135-139
32945402-8	2020	Furthermore, metformin significantly scavenged reactive oxygen species (ROS) induced by high glucose levels, and regulated the ROS-AKT-mTOR axis inhibited by high glucose levels, suggesting the protective effects of metformin against high glucose levels via regulation of the ROS-AKT-mTOR axis.	Metformin	216-225	AKT serine/threonine kinase 1	Homo sapiens	280-283
32945402-8	2020	Furthermore, metformin significantly scavenged reactive oxygen species (ROS) induced by high glucose levels, and regulated the ROS-AKT-mTOR axis inhibited by high glucose levels, suggesting the protective effects of metformin against high glucose levels via regulation of the ROS-AKT-mTOR axis.	Metformin	216-225	mechanistic target of rapamycin kinase	Homo sapiens	284-288
32853957-0	2020	Oxidative stress and TGF-beta1 induction by metformin in MCF-7 and MDA-MB-231 human breast cancer cells are accompanied with the downregulation of genes related to cell proliferation, invasion and metastasis.	Metformin	44-53	transforming growth factor beta 1	Homo sapiens	21-30
32853957-1	2020	High doses of metformin induces oxidative stress (OS) and transforming growth factor beta1 (TGF-beta1) in breast cancer cells, which was associated with increased cancer stem cell population, local invasion, liver metastasis and treatment resistance.	Metformin	14-23	transforming growth factor beta 1	Homo sapiens	58-90
32853957-1	2020	High doses of metformin induces oxidative stress (OS) and transforming growth factor beta1 (TGF-beta1) in breast cancer cells, which was associated with increased cancer stem cell population, local invasion, liver metastasis and treatment resistance.	Metformin	14-23	transforming growth factor beta 1	Homo sapiens	92-101
32853957-2	2020	Considering the impact of TGF- beta1 and OS in breast cancer and the interrelation between these two pathways, the objective of this work was to investigate the effects of consecutive metformin treatments, at a non-cytotoxic dosage, in TGF- beta1 targets in MCF-7 and MDA-MB-231 cells.	Metformin	184-193	transforming growth factor beta 1	Homo sapiens	236-246
32853964-10	2020	Meanwhile, the inhibitory effect of metformin on estrogen-induced cell proliferation was respectively blunted or partly reversed by knockdown of ERalpha or ERbeta.	Metformin	36-45	estrogen receptor 1	Homo sapiens	145-152
32853964-10	2020	Meanwhile, the inhibitory effect of metformin on estrogen-induced cell proliferation was respectively blunted or partly reversed by knockdown of ERalpha or ERbeta.	Metformin	36-45	estrogen receptor 1	Homo sapiens	156-162
32853964-11	2020	Altogether, ERalpha and ERbeta have different expression patterns in the progression of EC either facilitating or suppressing cell proliferation through regulating the expression of CyclinD1 and p21 in EC cells, and may also mediate the inhibitory effect of metformin on estrogen-induced EC cells proliferation.	Metformin	258-267	estrogen receptor 1	Homo sapiens	12-19
32853964-11	2020	Altogether, ERalpha and ERbeta have different expression patterns in the progression of EC either facilitating or suppressing cell proliferation through regulating the expression of CyclinD1 and p21 in EC cells, and may also mediate the inhibitory effect of metformin on estrogen-induced EC cells proliferation.	Metformin	258-267	estrogen receptor 1	Homo sapiens	24-30
32715434-0	2020	Influence of metformin on HIF-1 pathway in multiple myeloma.	Metformin	13-22	hypoxia inducible factor 1 subunit alpha	Homo sapiens	26-31
32715434-5	2020	METHODS: The Western Blot and RT-PCR techniques were applied to analyze the influence of metformin on HIF-1 pathway in MM cells.	Metformin	89-98	hypoxia inducible factor 1 subunit alpha	Homo sapiens	102-107
32715434-8	2020	RESULTS: Our results showed, for the first time, that metformin inhibits HIF-1 signaling in MM cells.	Metformin	54-63	hypoxia inducible factor 1 subunit alpha	Homo sapiens	73-78
32715434-9	2020	Moreover, we demonstrated the effect of metformin to be mainly oxygen dependent, since the HIF-1 pathway was not significantly affected by metformin in anoxic conditions as well as after application of hypoxic mimicking compound, CoCl2.	Metformin	40-49	hypoxia inducible factor 1 subunit alpha	Homo sapiens	91-96
32715434-11	2020	CONCLUSIONS: Taken together, our study indicates metformin as a promising candidate for developing new treatment strategies exploiting HIF-1 signaling inhibition to enhance the overall anti-MM effect of currently used therapies, that may considerably benefit MM patients.	Metformin	49-58	hypoxia inducible factor 1 subunit alpha	Homo sapiens	135-140
32863184-9	2020	While data show that PPARdelta levels were increased by the drug metformin, PPARdelta was not necessary for metformin-induced protection from light damage.	Metformin	65-74	peroxisome proliferator activator receptor delta	Mus musculus	21-30
32991321-8	2020	Finally, metformin, an anti-aging agent, activated the YAP-CDK6 pathway and suppressed D-gal-induced senescence of C6 cells.	Metformin	9-18	cyclin dependent kinase 6	Homo sapiens	59-63
32912901-0	2020	AMPK regulation of Raptor and TSC2 mediate metformin effects on transcriptional control of anabolism and inflammation.	Metformin	43-52	regulatory associated protein of MTOR, complex 1	Mus musculus	19-25
32800550-6	2020	Inhibition of AMPK by siRNA adversely affected the anti-calcification effects of metformin, resveratrol, and exendin-4 and reversed the reduction of the expression of Rankl by metformin and exendin-4 in the Pi-treated VSMCs.	Metformin	176-185	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	14-18
32912901-5	2020	Metformin treatment of primary hepatocytes and intact murine liver requires AMPK regulation of both RAPTOR and TSC2 to fully inhibit mTORC1, and this regulation is critical for both the translational and transcriptional response to metformin.	Metformin	0-9	regulatory associated protein of MTOR, complex 1	Mus musculus	100-106
32979921-0	2020	Metformin may adversely affect orthostatic blood pressure recovery in patients with type 2 diabetes: substudy from the placebo-controlled Copenhagen Insulin and Metformin Therapy (CIMT) trial.	Metformin	0-9	insulin	Homo sapiens	149-156
32979921-10	2020	CONCLUSIONS: Eighteen months of metformin treatment in combination with insulin compared with insulin alone increased early drop in OBP indicating an adverse effect of metformin on CAN independent of vitamin B12, MMA HbA1c.	Metformin	168-177	insulin	Homo sapiens	72-79
32800550-0	2020	Metformin, resveratrol, and exendin-4 inhibit high phosphate-induced vascular calcification via AMPK-RANKL signaling.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	96-100
32800550-5	2020	Metformin, resveratrol, and exendin-4 reduced the expression of osteoblast differentiation-associated factors, such as runt-related transcription factor 2, bone morphogenic protein-2, p-small mothers against decapentaplegic 1/5/8, and Rankl.	Metformin	0-9	RUNX family transcription factor 2	Rattus norvegicus	119-154
32800550-6	2020	Inhibition of AMPK by siRNA adversely affected the anti-calcification effects of metformin, resveratrol, and exendin-4 and reversed the reduction of the expression of Rankl by metformin and exendin-4 in the Pi-treated VSMCs.	Metformin	81-90	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	14-18
33001414-10	2021	Metformin was associated with increased OR (CI) for AKI, 1.07 (1.02-1.12), equally to sulfonylurea, 1.10 (1.03-1.18) and DPP-4i, 1.11 (1.02-1.20), but not insulin, 0.99 (0.93-1.05).	Metformin	0-9	insulin	Homo sapiens	155-162
32967076-0	2020	Systemic Oxidative Stress and Visceral Adipose Tissue Mediators of NLRP3 Inflammasome and Autophagy Are Reduced in Obese Type 2 Diabetic Patients Treated with Metformin.	Metformin	159-168	NLR family pyrin domain containing 3	Homo sapiens	67-72
32967076-5	2020	Patients treated with metformin showed decreased levels of all analyzed serum pro-inflammatory markers (TNFalpha, IL6, IL1beta and MCP1) and a downwards trend in IL18 levels associated with a lower production of oxidative stress markers in leukocytes (mitochondrial ROS and myeloperoxidase (MPO)).	Metformin	22-31	tumor necrosis factor	Homo sapiens	104-112
32967076-5	2020	Patients treated with metformin showed decreased levels of all analyzed serum pro-inflammatory markers (TNFalpha, IL6, IL1beta and MCP1) and a downwards trend in IL18 levels associated with a lower production of oxidative stress markers in leukocytes (mitochondrial ROS and myeloperoxidase (MPO)).	Metformin	22-31	interleukin 6	Homo sapiens	114-117
32967076-5	2020	Patients treated with metformin showed decreased levels of all analyzed serum pro-inflammatory markers (TNFalpha, IL6, IL1beta and MCP1) and a downwards trend in IL18 levels associated with a lower production of oxidative stress markers in leukocytes (mitochondrial ROS and myeloperoxidase (MPO)).	Metformin	22-31	myeloperoxidase	Homo sapiens	274-289
32967076-5	2020	Patients treated with metformin showed decreased levels of all analyzed serum pro-inflammatory markers (TNFalpha, IL6, IL1beta and MCP1) and a downwards trend in IL18 levels associated with a lower production of oxidative stress markers in leukocytes (mitochondrial ROS and myeloperoxidase (MPO)).	Metformin	22-31	myeloperoxidase	Homo sapiens	291-294
32967076-7	2020	This downregulation of both the NLRP3 inflammasome and autophagy in VAT may be associated with the improved inflammatory profile and leukocyte homeostasis seen in obese T2D patients treated with metformin with respect to MHO subjects and endorses the cardiometabolic protective effect of this drug.	Metformin	195-204	NLR family pyrin domain containing 3	Homo sapiens	32-37
32943543-7	2020	Addition of metformin following ADT induced apoptosis, attenuated mTOR activation by ADT, reduced senescent cell number in vitro and inhibited tumor growth in PC PDX models.	Metformin	12-21	mechanistic target of rapamycin kinase	Homo sapiens	66-70
32800550-7	2020	These data suggest that metformin, resveratrol, and exendin-4 ameliorate Pi-induced vascular calcification by inhibiting osteoblast differentiation of VSMCs, which is mediated by AMPK.	Metformin	24-33	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	179-183
32940892-6	2021	Moreover, the patients on metformin showed lower levels of vascular cell adhesion molecule (VCAM)1 (26.6 +- 1.4 vs. 35.03 +- 3.1 ng/mL, p = 0.014) and higher expression of miR-126-3p/U6sno (11.39 +- 2.8 vs. 4.26 +- 0.9, p = 0.006), a known post-transcriptional down regulator of TF and VCAM1.	Metformin	26-35	vascular cell adhesion molecule 1	Homo sapiens	59-98
32646922-7	2020	However, metformin reprogrammed the TIME towards "infiltrated-inflamed" and increased the numbers of infiltrated CD8+ cytotoxic T-lymphocyte and CD20+ B-lymphocyte.	Metformin	9-18	keratin 20	Homo sapiens	145-149
32646922-10	2020	In ESCC mouse model, short-term metformin treatment reprogrammed the TIME in a similar fashion to humans, whereas long-term treatment further shifted the TIME towards an active state (e.g., reduction in CD4+ FoxP3+ Tregs) and inhibited ESCC growth.	Metformin	32-41	CD4 molecule	Homo sapiens	203-206
32646922-11	2020	In both humans and mice, metformin triggered AMPK activation and STAT3 inactivation, and altered the production of effector cytokines (i.e. TNF-alpha, IFN-gamma, IL-10) in the immune cells.	Metformin	25-34	signal transducer and activator of transcription 3	Mus musculus	65-70
32646922-11	2020	In both humans and mice, metformin triggered AMPK activation and STAT3 inactivation, and altered the production of effector cytokines (i.e. TNF-alpha, IFN-gamma, IL-10) in the immune cells.	Metformin	25-34	tumor necrosis factor	Homo sapiens	140-149
32646922-11	2020	In both humans and mice, metformin triggered AMPK activation and STAT3 inactivation, and altered the production of effector cytokines (i.e. TNF-alpha, IFN-gamma, IL-10) in the immune cells.	Metformin	25-34	interferon gamma	Homo sapiens	151-160
32619406-7	2020	Furthermore, we identify that metformin-stimulated AMPK signaling converges at FOXO3 to stimulate SETD2 expression.	Metformin	30-39	SET domain containing 2	Mus musculus	98-103
32927432-0	2020	Metformin suppresses Nrf2-mediated chemoresistance in hepatocellular carcinoma cells by increasing glycolysis.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	21-25
32927432-3	2020	Here we provide evidence in HepG2 hepatocellular carcinoma cells that metformin sensitizes cisplatin-resistant HepG2 cells (HepG2/DDP) through increasing cellular glycolysis and suppressing Nrf2-dependent transcription.	Metformin	70-79	NFE2 like bZIP transcription factor 2	Homo sapiens	190-194
32927432-6	2020	Elevated glycolysis was required for metformin to regulate Nrf2-dependent transcription and cisplatin sensitivity, as inhibition of glycolysis with 2-Deoxy-D-glucose (2-DG) significantly mitigates the beneficial effect of metformin.	Metformin	37-46	NFE2 like bZIP transcription factor 2	Homo sapiens	59-63
32940892-6	2021	Moreover, the patients on metformin showed lower levels of vascular cell adhesion molecule (VCAM)1 (26.6 +- 1.4 vs. 35.03 +- 3.1 ng/mL, p = 0.014) and higher expression of miR-126-3p/U6sno (11.39 +- 2.8 vs. 4.26 +- 0.9, p = 0.006), a known post-transcriptional down regulator of TF and VCAM1.	Metformin	26-35	vascular cell adhesion molecule 1	Homo sapiens	286-291
32911743-11	2020	Metformin treatment increased p-AMPK and decreased mTOR (pS6) expression; these effects were reversed by addition of mevalonate.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	51-55
33014814-0	2020	Metformin Overcomes Acquired Resistance to EGFR TKIs in EGFR-Mutant Lung Cancer via AMPK/ERK/NF-kappaB Signaling Pathway.	Metformin	0-9	epidermal growth factor receptor	Homo sapiens	43-47
33014814-0	2020	Metformin Overcomes Acquired Resistance to EGFR TKIs in EGFR-Mutant Lung Cancer via AMPK/ERK/NF-kappaB Signaling Pathway.	Metformin	0-9	epidermal growth factor receptor	Homo sapiens	56-60
33014814-0	2020	Metformin Overcomes Acquired Resistance to EGFR TKIs in EGFR-Mutant Lung Cancer via AMPK/ERK/NF-kappaB Signaling Pathway.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	89-92
33014814-0	2020	Metformin Overcomes Acquired Resistance to EGFR TKIs in EGFR-Mutant Lung Cancer via AMPK/ERK/NF-kappaB Signaling Pathway.	Metformin	0-9	nuclear factor kappa B subunit 1	Homo sapiens	93-102
33014814-5	2020	The most commonly used antidiabetic drug metformin has demonstrated antitumor effects associated with NF-kappaB inhibition.	Metformin	41-50	nuclear factor kappa B subunit 1	Homo sapiens	102-111
33014814-9	2020	Metformin inhibited proliferation and promoted apoptosis of lung cancer cells, especially those with acquired EGFR TKI resistance.	Metformin	0-9	epidermal growth factor receptor	Homo sapiens	110-114
33014814-10	2020	Moreover, metformin reversed and delayed acquired resistance to EGFR TKIs as well as suppressed cancer stemness in EGFR-mutant lung cancer.	Metformin	10-19	epidermal growth factor receptor	Homo sapiens	64-68
33014814-10	2020	Moreover, metformin reversed and delayed acquired resistance to EGFR TKIs as well as suppressed cancer stemness in EGFR-mutant lung cancer.	Metformin	10-19	epidermal growth factor receptor	Homo sapiens	115-119
33014814-11	2020	Mechanistically, those effects of metformin were associated with activation of AMPK, resulting in the inhibition of downstream ERK/NF-kappaB signaling.	Metformin	34-43	mitogen-activated protein kinase 1	Homo sapiens	127-130
33014814-11	2020	Mechanistically, those effects of metformin were associated with activation of AMPK, resulting in the inhibition of downstream ERK/NF-kappaB signaling.	Metformin	34-43	nuclear factor kappa B subunit 1	Homo sapiens	131-140
33014814-12	2020	Conclusions: Our data provided novel and further molecular rationale and preclinical data to support combination of metformin with EGFR TKIs to treat EGFR-mutant lung cancer patients, especially those with acquired resistance.	Metformin	116-125	epidermal growth factor receptor	Homo sapiens	150-154
32917052-5	2020	The change in plasma vaspin level in response to metformin therapy was parallel with the improving of insulin resistance/sensitivity parameters.	Metformin	49-58	serpin family A member 12	Homo sapiens	21-27
32917052-5	2020	The change in plasma vaspin level in response to metformin therapy was parallel with the improving of insulin resistance/sensitivity parameters.	Metformin	49-58	insulin	Homo sapiens	102-109
32917052-9	2020	Multifactorial discriminant analysis revealed that irisin and vaspin plasma levels contribute clinically relevant information concerning the effectiveness of metformin treatment in T2D patients.	Metformin	158-167	serpin family A member 12	Homo sapiens	62-68
32913271-6	2020	The disturbance of the link between metabolism and immune function in CD8 + PD-1 + T cells in T2D was proved by recovery of antigen-specific and non-specific cytokine production via metformin-mediated increase in glycolytic activity.	Metformin	182-191	MHC class I antigen 1	Sus scrofa	76-80
32921782-4	2020	The insulin sensitizing actions of metformin encouraged many investigators and physician to use it as the key drug in these conditions for both prevention and treatment.	Metformin	35-44	insulin	Homo sapiens	4-11
32266492-1	2020	AIM: The present study aimed to evaluate the combined effect of both dose and duration of metformin therapy on vitamin B12 levels in patients with type 2 diabetes mellitus (T2D).	Metformin	90-99	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	119-122
32266492-5	2020	RESULTS: Vitamin B12 levels < 200 pg/ml and between 200 and 300 pg/ml were noted among 24.5% and 34.5% metformin users, respectively; this was significantly higher than among non-metformin users (17.3% and 22.6%, respectively) [P < 0.001].	Metformin	103-112	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	17-20
32266492-5	2020	RESULTS: Vitamin B12 levels < 200 pg/ml and between 200 and 300 pg/ml were noted among 24.5% and 34.5% metformin users, respectively; this was significantly higher than among non-metformin users (17.3% and 22.6%, respectively) [P < 0.001].	Metformin	179-188	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	17-20
32590170-12	2020	Local administration of metformin-HCl substantially down-regulated the expression of fibrosis-involved genes: transforming growth factor (TGF-beta1), collagen type 1 (Col-I), fibronectin, collagen type 3 (Col-III), and alpha-smooth muscle actin (alpha-SMA).	Metformin	24-37	transforming growth factor, beta 1	Rattus norvegicus	110-147
32887578-8	2020	The metformin group had a lower risk of primary cesarean section (aOR = 0.57; 95% CI, 0.40-0.82) and congenital malformations (aOR, 0.51; 95% CI; 0.27-0.94) and similar risk for the other outcomes as compared with the insulin group.	Metformin	4-13	insulin	Homo sapiens	218-225
33042621-0	2020	Metformin activates the STING/IRF3/IFN-beta pathway by inhibiting AKT phosphorylation in pancreatic cancer.	Metformin	0-9	thymoma viral proto-oncogene 1	Mus musculus	66-69
33042621-4	2020	Metformin also activated the STING/IRF3/IFN-beta pathway by inhibiting AKT signaling in PDAC cells.	Metformin	0-9	thymoma viral proto-oncogene 1	Mus musculus	71-74
32741222-8	2020	In addition, metformin also reduced the levels of thyroid stimulating hormone (TSH), homeostasis model assessment of insulin resistance (HOMA-IR) in patients with HT and SH (HT: p TSH = .000 and p HOMA-IR = .000; SH: p TSH = .000 and p HOMA-IR = .000, respectively).	Metformin	13-22	insulin	Homo sapiens	117-124
32472692-5	2020	KEY RESULTS: Metformin alleviated radiation-induced acute and chronic intestinal toxicity by optimising mitophagy which was AMPK-dependent.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	124-128
32390336-9	2020	CONCLUSIONS: Metformin with insulin has the potential to retard the progression of atherosclerosis and provides better metabolic control in patients with T1DM, and thus, providing a potential therapeutic strategy for patients with T1DM on reducing CVD risks.	Metformin	13-22	insulin	Homo sapiens	28-35
32700188-1	2020	INTRODUCTION: International guidelines recommend treatment with a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist for treatment intensification in type 2 diabetes mellitus (T2DM) patients with progression on metformin.	Metformin	262-271	glucagon	Homo sapiens	119-142
32869837-0	2020	Metformin inhibits the growth of ovarian cancer cells by promoting the Parkin-induced p53 ubiquitination.	Metformin	0-9	tumor protein p53	Homo sapiens	86-89
32869837-10	2020	Further, up-regulated Parkin expression promoted the ubiquitination and degradation of p53, and metformin inhibited the expression of p53 to suppress the proliferation of chemo-resistant ovarian cancer cells.	Metformin	96-105	tumor protein p53	Homo sapiens	134-137
32869837-11	2020	Mechanistically, metformin could inhibit the growth of ovarian cancer cells by promoting the Parkin-induced p53 ubiquitination.	Metformin	17-26	tumor protein p53	Homo sapiens	108-111
32869837-12	2020	Altogether, our study demonstrated an inhibitory role of metformin in the growth of chemo-resistant cancer cells through promoting the Parkin-induced p53 ubiquitination, which provides a novel mechanism of metformin for treating ovarian cancer.	Metformin	57-66	tumor protein p53	Homo sapiens	150-153
32869837-12	2020	Altogether, our study demonstrated an inhibitory role of metformin in the growth of chemo-resistant cancer cells through promoting the Parkin-induced p53 ubiquitination, which provides a novel mechanism of metformin for treating ovarian cancer.	Metformin	206-215	tumor protein p53	Homo sapiens	150-153
31863557-0	2020	A randomised, double-blind, placebo-controlled trial of metformin on myocardial efficiency in insulin-resistant chronic heart failure patients without diabetes.	Metformin	56-65	insulin	Homo sapiens	94-101
31863557-1	2020	AIMS: The present study tested the hypothesis that metformin treatment may increase myocardial efficiency (stroke work/myocardial oxygen consumption) in insulin-resistant patients with heart failure and reduced ejection fraction (HFrEF) without diabetes.	Metformin	51-60	insulin	Homo sapiens	153-160
33277829-7	2020	Insulin-raising drugs, including exogenous insulin, increased cancer risks, while drugs potentiating insulin sensitivity like metformin reduced cancer risks.	Metformin	126-135	insulin	Homo sapiens	101-108
32522567-11	2020	Combined administration of metformin and anti-PD-1 antibody efficiently inhibited the growth of LKB1-intact tumors, whereas no obvious suppression was observed in LKB1-deficient tumors.	Metformin	27-36	serine/threonine kinase 11	Mus musculus	96-100
33376686-5	2020	Results: Metformin therapy led to significant reduction of fasting insulin and insulin resistance (IR) with an increment in the insulin sensitivity (P < 0.01).	Metformin	9-18	insulin	Homo sapiens	67-74
33376686-5	2020	Results: Metformin therapy led to significant reduction of fasting insulin and insulin resistance (IR) with an increment in the insulin sensitivity (P < 0.01).	Metformin	9-18	insulin	Homo sapiens	79-86
33376686-7	2020	Metformin plus TA therapy reduced fasting blood glucose, glycated hemoglobin, and IR and showed increment in the insulin sensitivity (P < 0.01) with insignificant effect on fasting insulin (P = 0.09) compared with metformin monotherapy.	Metformin	0-9	insulin	Homo sapiens	113-120
32522567-13	2020	Activation of LKB1-AMPK with metformin improves the therapeutic effect of PD-1 blockade in NSCLC with wild-type LKB1.	Metformin	29-38	serine/threonine kinase 11	Mus musculus	14-18
32522567-13	2020	Activation of LKB1-AMPK with metformin improves the therapeutic effect of PD-1 blockade in NSCLC with wild-type LKB1.	Metformin	29-38	serine/threonine kinase 11	Mus musculus	112-116
32959498-7	2020	Metformin increased the levels of p-AMPK and PGC-1alpha, a downstream AMPK target which regulates mitochondrial biogenesis, at P4, P10, and P21 in hyperoxia pups.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	34-40
32959498-7	2020	Metformin increased the levels of p-AMPK and PGC-1alpha, a downstream AMPK target which regulates mitochondrial biogenesis, at P4, P10, and P21 in hyperoxia pups.	Metformin	0-9	PPARG coactivator 1 alpha	Rattus norvegicus	45-55
32959498-7	2020	Metformin increased the levels of p-AMPK and PGC-1alpha, a downstream AMPK target which regulates mitochondrial biogenesis, at P4, P10, and P21 in hyperoxia pups.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	36-40
32959498-12	2020	The AMPK activator, metformin improves AMPK function and alveolar and vascular growth in this rat pup model of hyperoxia-induced lung injury.	Metformin	20-29	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	4-8
32959498-12	2020	The AMPK activator, metformin improves AMPK function and alveolar and vascular growth in this rat pup model of hyperoxia-induced lung injury.	Metformin	20-29	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	39-43
32863218-0	2020	Metformin alleviates lead-induced mitochondrial fragmentation via AMPK/Nrf2 activation in SH-SY5Y cells.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	71-75
32863218-6	2020	Further investigation confirmed that nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor managing antioxidative function, and its downstream antioxidant detoxifying enzyme were activated by metformin, resulting in the inhibition of the Pb-caused oxidative stress.	Metformin	213-222	NFE2 like bZIP transcription factor 2	Homo sapiens	37-80
32863218-6	2020	Further investigation confirmed that nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor managing antioxidative function, and its downstream antioxidant detoxifying enzyme were activated by metformin, resulting in the inhibition of the Pb-caused oxidative stress.	Metformin	213-222	NFE2 like bZIP transcription factor 2	Homo sapiens	82-86
32863218-7	2020	Moreover, Nrf2 mediated the protection of metformin against mitochondrial fragmentation induced by Pb exposure, while knockdown of Nrf2 abrogated the protective effect.	Metformin	42-51	NFE2 like bZIP transcription factor 2	Homo sapiens	10-14
32863218-9	2020	To conclude, metformin could ameliorate Pb-induced mitochondrial fragmentation via antioxidative effects originated from AMPK/Nrf2 pathway activation, promoting energy supply and cell survival.	Metformin	13-22	NFE2 like bZIP transcription factor 2	Homo sapiens	126-130
32190918-6	2020	We also found that metformin increased the immunoreactivity of synaptophysin, sirtuin-1, AMP-activated protein kinase (AMPK) and brain-derived neuronal factor (BDNF), which are important plasticity markers.	Metformin	19-28	sirtuin 1	Rattus norvegicus	78-87
33081905-12	2020	The possible mechanism is that metformin could inhibit cytokine storm via suppressing interleukin-6 (IL-6) signaling, prevent the process of lung fibrosis, suppress endocytosis, thereby elevating angiotensin converting enzyme 2 (ACE2) expression.	Metformin	31-40	interleukin 6	Homo sapiens	101-105
32872293-0	2020	Metformin Derivative HL156A Reverses Multidrug Resistance by Inhibiting HOXC6/ERK1/2 Signaling in Multidrug-Resistant Human Cancer Cells.	Metformin	0-9	mitogen-activated protein kinase 3	Homo sapiens	78-84
32278041-7	2020	Compared to controls, metformin significantly reduced body mass index (BMI) (WMD: -0.71 kg/m2, 95 % CI = [-1.40, -0.02], P =  0.04, I2 = 1.8%) and serum aspartate aminotransferase (AST) (WMD: -6.97 U/L, 95 % CI = [-12.59, -1.35], P =  0.01, I2 = 64.5%).	Metformin	22-31	solute carrier family 17 member 5	Homo sapiens	153-179
32278041-7	2020	Compared to controls, metformin significantly reduced body mass index (BMI) (WMD: -0.71 kg/m2, 95 % CI = [-1.40, -0.02], P =  0.04, I2 = 1.8%) and serum aspartate aminotransferase (AST) (WMD: -6.97 U/L, 95 % CI = [-12.59, -1.35], P =  0.01, I2 = 64.5%).	Metformin	22-31	solute carrier family 17 member 5	Homo sapiens	181-184
32867201-7	2020	Our results showed that the combination of the two compounds is able to counteract the appearance of an adipogenic phenotype, indicating a feedforward regulation on vitamin D metabolism by metformin, acting on CYP27B1 and CYP3A4.	Metformin	189-198	cytochrome P450 family 27 subfamily B member 1	Homo sapiens	210-217
32867201-7	2020	Our results showed that the combination of the two compounds is able to counteract the appearance of an adipogenic phenotype, indicating a feedforward regulation on vitamin D metabolism by metformin, acting on CYP27B1 and CYP3A4.	Metformin	189-198	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	222-228
33081905-12	2020	The possible mechanism is that metformin could inhibit cytokine storm via suppressing interleukin-6 (IL-6) signaling, prevent the process of lung fibrosis, suppress endocytosis, thereby elevating angiotensin converting enzyme 2 (ACE2) expression.	Metformin	31-40	interleukin 6	Homo sapiens	86-99
33042258-7	2020	Pharmacological mTORC1 inhibition by RAD001 and metformin increased internalization of [177Lu]Lu-PP-F11N in A431/CCKBR and in AR42J cells.	Metformin	48-57	cholecystokinin B receptor	Rattus norvegicus	113-118
32825834-7	2020	The Cancer Genome Atlas dataset, an L1000 microarray with Gene Set Enrichment Analysis (GSEA) analysis, Western blot analysis and an animal model were used to study the activity of the AKT/mTOR pathway in response to the synergistic effects of neoadjuvant metformin combined with chemotherapy.	Metformin	256-265	AKT serine/threonine kinase 1	Homo sapiens	185-188
32825834-7	2020	The Cancer Genome Atlas dataset, an L1000 microarray with Gene Set Enrichment Analysis (GSEA) analysis, Western blot analysis and an animal model were used to study the activity of the AKT/mTOR pathway in response to the synergistic effects of neoadjuvant metformin combined with chemotherapy.	Metformin	256-265	mechanistic target of rapamycin kinase	Homo sapiens	189-193
32825834-9	2020	The protein profile induced by low- concentration metformin in ovarian cancer predominantly involved the AKT/mTOR pathway.	Metformin	50-59	AKT serine/threonine kinase 1	Homo sapiens	105-108
32825834-9	2020	The protein profile induced by low- concentration metformin in ovarian cancer predominantly involved the AKT/mTOR pathway.	Metformin	50-59	mechanistic target of rapamycin kinase	Homo sapiens	109-113
32825760-4	2020	Among the latter, the antidiabetic drug metformin exerts antitumor activity via the activation of AMPK and the subsequent inhibition of mTOR signaling.	Metformin	40-49	mechanistic target of rapamycin kinase	Homo sapiens	136-140
32825760-6	2020	We have demonstrated metformin"s ability to enhance the cytostatic activity of the tamoxifen and rapamycin on both parent MCF-7 cells and MCF-7-resistant derivates mediated via the suppression of mTOR signaling and growth-related transcriptional factors.	Metformin	21-30	mechanistic target of rapamycin kinase	Homo sapiens	196-200
32825760-8	2020	Similarly, the stimulation of apoptosis under metformin/tamoxifen co-treatment was shown to occur in the MCF-7 cells after steroid depletion as well as in the ERalpha-negative MDA-MB-231 cells.	Metformin	46-55	estrogen receptor 1	Homo sapiens	159-166
32825760-10	2020	Moreover, the combination of metformin with tamoxifen induces the apoptotic death in the ERalpha-negative breast cancer cells opening the additional perspectives in the treatment of estrogen-independent breast tumors.	Metformin	29-38	estrogen receptor 1	Homo sapiens	89-96
32974359-6	2020	The objective of this review article is to provide an overview of the pathophysiology of PH related to left heart disease (PH-LHD), outline the proposed pathophysiologic mechanism of insulin resistance in heart failure and PH-LHD, and evaluate the role metformin may have in heart failure and PH-LHD.	Metformin	253-262	insulin	Homo sapiens	183-190
32974191-0	2020	Matrix Stiffness-Upregulated MicroRNA-17-5p Attenuates the Intervention Effects of Metformin on HCC Invasion and Metastasis by Targeting the PTEN/PI3K/Akt Pathway.	Metformin	83-92	AKT serine/threonine kinase 1	Homo sapiens	151-154
32974191-11	2020	For HCC cells grown on the same-stiffness substrate, metformin remarkably upregulated PTEN expression and suppressed the activation of the PI3K/Akt/MMP pathway, but no effect on integrin beta1 expression.	Metformin	53-62	AKT serine/threonine kinase 1	Homo sapiens	144-147
32974191-12	2020	Importantly, the increase in fold of PTEN expression and decrease in folds of Akt phosphorylation level and MMP2 and MMP9 expressions in the treated HCC cells with metformin on 16-kPa stiffness substrate were evidently weakened compared with those in the controls on the 6-kPa stiffness substrate.	Metformin	164-173	AKT serine/threonine kinase 1	Homo sapiens	78-81
32974191-13	2020	Conclusions: Increased matrix stiffness significantly attenuates the inhibitory effect of metformin on HCC invasion and metastasis, and a common pathway of PTEN/PI3K/Akt/MMPs activated by mechanical stiffness signal and inactivated by metformin contributes to matrix stiffness-caused metformin resistance.	Metformin	235-244	AKT serine/threonine kinase 1	Homo sapiens	166-169
32974191-13	2020	Conclusions: Increased matrix stiffness significantly attenuates the inhibitory effect of metformin on HCC invasion and metastasis, and a common pathway of PTEN/PI3K/Akt/MMPs activated by mechanical stiffness signal and inactivated by metformin contributes to matrix stiffness-caused metformin resistance.	Metformin	235-244	AKT serine/threonine kinase 1	Homo sapiens	166-169
32841254-9	2020	The expression of SOX9 and RunX2 were also decreased by hyperglycemia and metformin treatment.	Metformin	74-83	RUNX family transcription factor 2	Rattus norvegicus	27-32
32841254-12	2020	Treatment of NH with metformin was able to mediate increased levels of TNF-alpha, IL-10 and IL-17, whereas for H an increase of TNF-alpha and IL-17 was detected in the 24- or 48-hour after stimulation with LPS.	Metformin	21-30	tumor necrosis factor	Rattus norvegicus	71-80
32841254-13	2020	Ligature was able to induce increased levels of TNF-alpha and IL-17 in both NH and H. This study revealed the negative impact of hyperglycemia and/or treatment with metformin in the bone repair via inhibition of transcription factors associated with osteoblastic differentiation.	Metformin	165-174	tumor necrosis factor	Rattus norvegicus	48-57
32470453-7	2020	Subsequently, overwhelming evidence showed that both metformin and aspirin can ameliorate T-cell mediated inflammation by inducing regulatory T-cells (Tregs) polarisation, inhibiting T-cell trafficking and activation as well as signal transducer and activator of transcription (STAT)3 signalling.	Metformin	53-62	signal transducer and activator of transcription 3	Homo sapiens	228-284
32470453-8	2020	As a plausible mechanism to mediate T-cell function, metformin showed enhanced potential to regulate mechanistic targets of rapamycin (mTOR), STAT5 and adenosine-monophosphate-activated protein kinase (AMPK) signalling pathways.	Metformin	53-62	mechanistic target of rapamycin kinase	Homo sapiens	101-133
32470453-8	2020	As a plausible mechanism to mediate T-cell function, metformin showed enhanced potential to regulate mechanistic targets of rapamycin (mTOR), STAT5 and adenosine-monophosphate-activated protein kinase (AMPK) signalling pathways.	Metformin	53-62	mechanistic target of rapamycin kinase	Homo sapiens	135-139
32806648-6	2020	We, thus, developed a new therapeutic approach to inhibit EGFR and hypoxia by combination treatment with metformin and gefitinib that sensitized TNBC cells to cisplatin and led to the inhibition of both CD44+/CD24- and ALDH+ CSCs.	Metformin	105-114	epidermal growth factor receptor	Homo sapiens	58-62
32606000-6	2020	The anti-diabetic drug metformin suppressed insulin-induced hepatic Cyclin D1 expression and protected against obese/diabetic hepatocarcinogenesis.	Metformin	23-32	insulin	Homo sapiens	44-51
32806648-6	2020	We, thus, developed a new therapeutic approach to inhibit EGFR and hypoxia by combination treatment with metformin and gefitinib that sensitized TNBC cells to cisplatin and led to the inhibition of both CD44+/CD24- and ALDH+ CSCs.	Metformin	105-114	CD24 molecule	Homo sapiens	209-213
32780768-4	2020	The longitudinal blood-derived transcriptome analysis revealed metformin-induced differential expression of novel and previously described genes involved in cholesterol homeostasis (SLC46A1 and LRP1), cancer development (CYP1B1, STAB1, CCR2, TMEM176B), and immune responses (CD14, CD163) after administration of metformin for three months.	Metformin	63-72	LDL receptor related protein 1	Homo sapiens	194-198
32780768-4	2020	The longitudinal blood-derived transcriptome analysis revealed metformin-induced differential expression of novel and previously described genes involved in cholesterol homeostasis (SLC46A1 and LRP1), cancer development (CYP1B1, STAB1, CCR2, TMEM176B), and immune responses (CD14, CD163) after administration of metformin for three months.	Metformin	63-72	C-C motif chemokine receptor 2	Homo sapiens	236-240
32758236-9	2020	Metformin reduced mortality in both preserved or reduced EF after adjustment with HF therapies such as angiotensin converting enzyme inhibitors (ACEi) and beta-blockers (beta = - 0.2 [95% CI - 0.3 to - 0.1], p = 0.02).	Metformin	0-9	angiotensin I converting enzyme	Homo sapiens	103-132
32641388-0	2020	Metformin and 2-Deoxyglucose Collaboratively Suppress Human CD4+ T Cell Effector Functions and Activation-Induced Metabolic Reprogramming.	Metformin	0-9	CD4 molecule	Homo sapiens	60-63
32641388-4	2020	In this study, we report that metformin + 2-DG treatment more potently suppressed IFN-gamma production and cell proliferation in activated primary human CD4+ T cells than either metformin or 2-DG treatment alone.	Metformin	30-39	interferon gamma	Homo sapiens	82-91
32641388-4	2020	In this study, we report that metformin + 2-DG treatment more potently suppressed IFN-gamma production and cell proliferation in activated primary human CD4+ T cells than either metformin or 2-DG treatment alone.	Metformin	30-39	CD4 molecule	Homo sapiens	153-156
32641388-5	2020	The effects of metformin + 2-DG on human T cells were accompanied by significant remodeling of activation-induced metabolic transcriptional programs, in part because of suppression of key transcriptional regulators MYC and HIF-1A.	Metformin	15-24	hypoxia inducible factor 1 subunit alpha	Homo sapiens	223-229
32755965-5	2020	Treatment with corticosteroids, metformin and hydroxychloroquine allowed withdrawal of insulin therapy, with stabilisation of glycaemia and diminished signs of insulin resistance; however, morning fasting hypoglycaemic episodes persisted.	Metformin	32-41	insulin	Homo sapiens	87-94
32755965-5	2020	Treatment with corticosteroids, metformin and hydroxychloroquine allowed withdrawal of insulin therapy, with stabilisation of glycaemia and diminished signs of insulin resistance; however, morning fasting hypoglycaemic episodes persisted.	Metformin	32-41	insulin	Homo sapiens	160-167
32755965-10	2020	Treatment with metformin, hydroxychloroquine and methotrexate ameliorated extreme insulin resistance.	Metformin	15-24	insulin	Homo sapiens	82-89
32758236-11	2020	Metformin treatment with insulin, ACEi and beta-blocker therapy were also shown to have a reduction in mortality (insulin p = 0.002; ACEi p < 0.001; beta-blocker p = 0.017), whereas female gender was associated with worse outcomes (p < 0.001).	Metformin	0-9	insulin	Homo sapiens	25-32
32758236-11	2020	Metformin treatment with insulin, ACEi and beta-blocker therapy were also shown to have a reduction in mortality (insulin p = 0.002; ACEi p < 0.001; beta-blocker p = 0.017), whereas female gender was associated with worse outcomes (p < 0.001).	Metformin	0-9	insulin	Homo sapiens	114-121
32743772-6	2020	Clearance of MDR1-mediated digoxin, OAT3-mediated furosemide, and OCT2-mediated metformin increased by 3.04-fold, 1.47-fold, and 1.26-fold, respectively.	Metformin	80-89	malic enzyme complex, mitochondrial	Mus musculus	13-17
32743772-6	2020	Clearance of MDR1-mediated digoxin, OAT3-mediated furosemide, and OCT2-mediated metformin increased by 3.04-fold, 1.47-fold, and 1.26-fold, respectively.	Metformin	80-89	POU domain, class 2, transcription factor 2	Mus musculus	66-70
32568826-9	2020	In addition, we found that metformin-mediated apoptosis occurred via degradation of the cellular FADD-like interleukin-1beta-converting enzyme inhibitory protein (c-FLIP) by facilitating ubiquitin/proteasome-mediated c-FLIPL degradation.	Metformin	27-36	CASP8 and FADD like apoptosis regulator	Homo sapiens	163-169
32748870-3	2020	In this context, the antidiabetic drug metformin is able to inhibit mTOR, providing a rationale for the use of metformin and everolimus in combination.	Metformin	39-48	mechanistic target of rapamycin kinase	Homo sapiens	68-72
32748870-3	2020	In this context, the antidiabetic drug metformin is able to inhibit mTOR, providing a rationale for the use of metformin and everolimus in combination.	Metformin	111-120	mechanistic target of rapamycin kinase	Homo sapiens	68-72
32748870-7	2020	In a PAN-NET cell line, metformin did not affect Akt phosphorylation; conversely, it significantly decreased Akt phosphorylation in a PNT cell line.	Metformin	24-33	AKT serine/threonine kinase 1	Homo sapiens	109-112
32748870-8	2020	Using everolimus-resistant NET cells, we confirmed that metformin maintained its effects, acting by two different pathways: Akt-dependent or independent, depending on the cell type, with both leading to mTOR suppression.	Metformin	56-65	AKT serine/threonine kinase 1	Homo sapiens	124-127
32748870-8	2020	Using everolimus-resistant NET cells, we confirmed that metformin maintained its effects, acting by two different pathways: Akt-dependent or independent, depending on the cell type, with both leading to mTOR suppression.	Metformin	56-65	mechanistic target of rapamycin kinase	Homo sapiens	203-207
32828146-8	2021	Metformin has been used to evaluate their potential modulatory effects on cells treated with TNF-alpha.	Metformin	0-9	tumor necrosis factor	Homo sapiens	93-102
32828146-11	2021	The TNF-alpha-induced expression of inflammatory cytokines and protease and growth factor genes in MH7A cells was downregulated by metformin.	Metformin	131-140	tumor necrosis factor	Homo sapiens	4-13
32568826-9	2020	In addition, we found that metformin-mediated apoptosis occurred via degradation of the cellular FADD-like interleukin-1beta-converting enzyme inhibitory protein (c-FLIP) by facilitating ubiquitin/proteasome-mediated c-FLIPL degradation.	Metformin	27-36	CASP8 and FADD like apoptosis regulator	Homo sapiens	217-224
32409919-5	2020	Therefore, we analyzed the induction of insulin resistance (IR) in the Huh7 cell line using an overdosage of insulin and treatment with metformin for its reversal, with the purpose of establishing an insulin resistance model useful for metabolic and pharmacological studies.	Metformin	136-145	insulin	Homo sapiens	40-47
32472157-3	2020	Hepatic and renal uptake of metformin is mediated by organic cation transporter 1 (OCT1) and OCT2, respectively, and its renal excretion by multidrug and toxin extrusion 1 (MATE1) and MATE2-K.	Metformin	28-37	solute carrier family 22 member 1	Homo sapiens	53-81
32409919-8	2020	Moreover, treatment of Huh7-IR with 0.5, 1 or 2 mM of metformin by 24 h decreased the biomarkers associated with an insulin-resistant state.	Metformin	54-63	insulin	Homo sapiens	116-123
32472157-3	2020	Hepatic and renal uptake of metformin is mediated by organic cation transporter 1 (OCT1) and OCT2, respectively, and its renal excretion by multidrug and toxin extrusion 1 (MATE1) and MATE2-K.	Metformin	28-37	solute carrier family 22 member 1	Homo sapiens	83-87
32472157-5	2020	METHODS: Inhibitory effects of peficitinib and its metabolite H2 on metformin uptake into human OCT1/2- and MATE1/2-K-expressing cells were assessed in vitro.	Metformin	68-77	solute carrier family 22 member 1	Homo sapiens	96-102
32472157-9	2020	RESULTS: Peficitinib, but not H2, inhibited metformin uptake into OCT1- and MATE1/2-K-expressing cells.	Metformin	44-53	solute carrier family 22 member 1	Homo sapiens	66-70
32742376-5	2020	In HCT116 cells expressing wild-type (wt) TP53, SIRT inhibitors were found to act antagonistically with multiple chemotherapeutic agents (cisplatin, 5-fluorouracil, oxaliplatin, gefitinib, LY294002 and metformin), and decreased the anti-tumor effects of these agents.	Metformin	202-211	tumor protein p53	Homo sapiens	42-46
32767342-3	2020	While the efficacy of metformin in reducing insulin resistance and decreasing androgen level has been widely validated, there is no agreement on the dose of metformin to be used.	Metformin	22-31	insulin	Homo sapiens	44-51
32742327-0	2020	Metformin attenuates cardiac remodeling in mice through the Nrf2/Keap1 signaling pathway.	Metformin	0-9	nuclear factor, erythroid derived 2, like 2	Mus musculus	60-64
32551505-5	2020	The assay is capable of simultaneously quantifying multiple endogenous compounds, including IBC, thiamine, N1-methylnicotinamide (1-NMN), creatinine, carnitine, and metformin, a substrate for OCT1/2 and MATE1/2K in clinical studies.	Metformin	165-174	solute carrier family 22 member 1	Homo sapiens	192-198
32592239-0	2020	Metformin suppresses HIF-1alpha expression in cancer-associated fibroblasts to prevent tumor-stromal cross talk in breast cancer.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	21-31
32792943-8	2020	The presence of metformin also sensitized NSCLC cells to celecoxib-induced apoptosis by activating caspase-9, -8, -3, and -7, upregulating the pro-apoptotic proteins Bad and Bax, and downregulating the antiapoptotic proteins Bcl-xl and Bcl-2.	Metformin	16-25	BCL2 associated X, apoptosis regulator	Homo sapiens	174-177
32792943-8	2020	The presence of metformin also sensitized NSCLC cells to celecoxib-induced apoptosis by activating caspase-9, -8, -3, and -7, upregulating the pro-apoptotic proteins Bad and Bax, and downregulating the antiapoptotic proteins Bcl-xl and Bcl-2.	Metformin	16-25	BCL2 like 1	Homo sapiens	225-231
32792943-8	2020	The presence of metformin also sensitized NSCLC cells to celecoxib-induced apoptosis by activating caspase-9, -8, -3, and -7, upregulating the pro-apoptotic proteins Bad and Bax, and downregulating the antiapoptotic proteins Bcl-xl and Bcl-2.	Metformin	16-25	BCL2 apoptosis regulator	Homo sapiens	236-241
32389830-13	2020	Additionally, metformin could affect the interactions of ZO-1 with p-Src/Cx43 via decrease the abnormal cAMP level after pacing (84.04 +- 4.58 vs. 69.34 +- 4.5 nmol/L, P<0.001).	Metformin	14-23	tight junction protein 1	Canis lupus familiaris	57-61
32274915-5	2020	Metformin seems to be safe and presents evident positive effects on insulin sensitivity, but long-term and consistent data are still missing to establish its role in the paediatric population and the possible effectiveness of other emergent treatments such as glucagon-like peptide-1 (GLP-1) analogues, dipeptidylpeptidase-4 (DPP-4) inhibitors, dual inhibitors of SGLT1 and SGLT2 and weight loss drugs.	Metformin	0-9	insulin	Homo sapiens	68-75
32274915-5	2020	Metformin seems to be safe and presents evident positive effects on insulin sensitivity, but long-term and consistent data are still missing to establish its role in the paediatric population and the possible effectiveness of other emergent treatments such as glucagon-like peptide-1 (GLP-1) analogues, dipeptidylpeptidase-4 (DPP-4) inhibitors, dual inhibitors of SGLT1 and SGLT2 and weight loss drugs.	Metformin	0-9	glucagon	Homo sapiens	285-290
32274915-5	2020	Metformin seems to be safe and presents evident positive effects on insulin sensitivity, but long-term and consistent data are still missing to establish its role in the paediatric population and the possible effectiveness of other emergent treatments such as glucagon-like peptide-1 (GLP-1) analogues, dipeptidylpeptidase-4 (DPP-4) inhibitors, dual inhibitors of SGLT1 and SGLT2 and weight loss drugs.	Metformin	0-9	solute carrier family 5 member 1	Homo sapiens	364-369
32418411-9	2020	Insulin resistance is becoming an increasingly studied target for therapy, most evidence stemming from the time-honoured metformin use.	Metformin	121-130	insulin	Homo sapiens	0-7
32758336-12	2020	As the diabetic MODY-5 patient (mutation of HNF1B, Val2Leu) was on low dose Riomet  while eliminating insulin gradually, a simple analytical method for metformin assay was recommended to ensure its concentration before use as it is not approved yet by the Egyptian QC labs.	Metformin	76-82	HNF1 homeobox B	Homo sapiens	16-22
32758336-12	2020	As the diabetic MODY-5 patient (mutation of HNF1B, Val2Leu) was on low dose Riomet  while eliminating insulin gradually, a simple analytical method for metformin assay was recommended to ensure its concentration before use as it is not approved yet by the Egyptian QC labs.	Metformin	76-82	HNF1 homeobox B	Homo sapiens	44-49
32758336-12	2020	As the diabetic MODY-5 patient (mutation of HNF1B, Val2Leu) was on low dose Riomet  while eliminating insulin gradually, a simple analytical method for metformin assay was recommended to ensure its concentration before use as it is not approved yet by the Egyptian QC labs.	Metformin	152-161	HNF1 homeobox B	Homo sapiens	16-22
32758336-12	2020	As the diabetic MODY-5 patient (mutation of HNF1B, Val2Leu) was on low dose Riomet  while eliminating insulin gradually, a simple analytical method for metformin assay was recommended to ensure its concentration before use as it is not approved yet by the Egyptian QC labs.	Metformin	152-161	HNF1 homeobox B	Homo sapiens	44-49
32758336-12	2020	As the diabetic MODY-5 patient (mutation of HNF1B, Val2Leu) was on low dose Riomet  while eliminating insulin gradually, a simple analytical method for metformin assay was recommended to ensure its concentration before use as it is not approved yet by the Egyptian QC labs.	Metformin	152-161	insulin	Homo sapiens	102-109
32903813-0	2020	Eye Drops of Metformin Prevents Fibrosis After Glaucoma Filtration Surgery in Rats via Activating AMPK/Nrf2 Signaling Pathway.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	98-102
32903813-0	2020	Eye Drops of Metformin Prevents Fibrosis After Glaucoma Filtration Surgery in Rats via Activating AMPK/Nrf2 Signaling Pathway.	Metformin	13-22	NFE2 like bZIP transcription factor 2	Rattus norvegicus	103-107
32903813-8	2020	Besides, the inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2)/AMP-activated protein kinase (AMPK) and the competition of organic cation transporters (OCTs) effectively reduced the anti-fibrotic capability of metformin.	Metformin	224-233	NFE2 like bZIP transcription factor 2	Rattus norvegicus	27-70
32903813-8	2020	Besides, the inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2)/AMP-activated protein kinase (AMPK) and the competition of organic cation transporters (OCTs) effectively reduced the anti-fibrotic capability of metformin.	Metformin	224-233	NFE2 like bZIP transcription factor 2	Homo sapiens	72-76
32903813-9	2020	Together, this experiment indicates that metformin enters into HConFs cell with OCTs, which can protect against filtrating blebs scar formation in SD rats of GFS via activating AMPK/Nrf2 axis and the downregulation of profibrogenic and inflammatory biomarkers.	Metformin	41-50	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	177-181
32903813-9	2020	Together, this experiment indicates that metformin enters into HConFs cell with OCTs, which can protect against filtrating blebs scar formation in SD rats of GFS via activating AMPK/Nrf2 axis and the downregulation of profibrogenic and inflammatory biomarkers.	Metformin	41-50	NFE2 like bZIP transcription factor 2	Rattus norvegicus	182-186
32447330-12	2020	Off GH, insulin requirements reduced to zero, allowing Metformin monotherapy.	Metformin	55-64	insulin	Homo sapiens	8-15
32801814-9	2020	A combination of drugs showed that the expression of TNF-alpha was almost the same as for metformin alone.	Metformin	90-99	tumor necrosis factor	Homo sapiens	53-62
32703218-10	2020	On the contrary, the activation of AMPK by metformin (Met) or 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) could overcome the KRAS-induced resistance to the anti-EGFR antibody in vivo and in vitro.	Metformin	43-52	epidermal growth factor receptor	Homo sapiens	171-175
32703218-10	2020	On the contrary, the activation of AMPK by metformin (Met) or 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) could overcome the KRAS-induced resistance to the anti-EGFR antibody in vivo and in vitro.	Metformin	54-57	epidermal growth factor receptor	Homo sapiens	171-175
32801686-1	2020	Introduction: Metformin is an ideal candidate to treat the liver tumor with insulin resistance because of its good performance in the treatment of type 2 diabetes and the advantage in cancer therapy.	Metformin	14-23	insulin	Homo sapiens	76-83
33520816-6	2020	Females consuming only metformin and metformin with other drugs, showed a positive association of HOMA-IR with cholesterol and a negative association with adiponectin.	Metformin	23-32	adiponectin, C1Q and collagen domain containing	Homo sapiens	155-166
32639009-7	2020	Further, activation of AMPK by metformin normalized endothelial-dependent vasodilation and decreased the blood pressure of hCRPtg rats.	Metformin	31-40	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	23-27
32639009-9	2020	Treatment with metformin or a synthetic AMPK activator may be a potential strategy for vaso-dysfunction and hypertension in patients with high hCRP levels.	Metformin	15-24	C-reactive protein	Homo sapiens	143-147
33520816-6	2020	Females consuming only metformin and metformin with other drugs, showed a positive association of HOMA-IR with cholesterol and a negative association with adiponectin.	Metformin	37-46	adiponectin, C1Q and collagen domain containing	Homo sapiens	155-166
32765083-0	2020	Metformin Induces Autophagy via the AMPK-mTOR Signaling Pathway in Human Hepatocellular Carcinoma Cells.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	41-45
32765083-2	2020	Our study was designed to determine the effect of metformin on the cell autophagy and autophagic flux via the AMPK-mTOR signaling pathway in human hepatocellular carcinoma (HCC) cells.	Metformin	50-59	mechanistic target of rapamycin kinase	Homo sapiens	115-119
32765083-8	2020	In metformin-induced autophagy, AMPK expression was activated, and the phosphorylation levels of mTOR and p70 S6 Kinase were inhibited.	Metformin	3-12	mechanistic target of rapamycin kinase	Homo sapiens	97-101
32765083-11	2020	Conclusion: Metformin could induce the autophagy, autophagic flux, and activate the AMPK-mTOR signaling pathway in human HCC cells.	Metformin	12-21	mechanistic target of rapamycin kinase	Homo sapiens	89-93
32652973-2	2020	We studied whether metformin treatment has favorable or unfavorable effects on inflammatory markers and insulin-like growth factor-binding protein 1 (IGFBP-1) in GDM patients compared with insulin, and whether these markers associate with major maternal or fetal clinical outcomes.	Metformin	19-28	insulin	Homo sapiens	104-111
32660025-11	2020	An analysis of a subgroup of participants taking metformin showed a decrease in fasting plasma glucose, HbA1c, insulin resistance, and zonulin; an increase in plasma butyrate concentrations; and an enrichment of microbial butyrate-producing pathways in the probiotic group but not in the placebo group.	Metformin	49-58	insulin	Homo sapiens	111-118
32371063-0	2020	NLRP3 inflammasome drives inflammation in high fructose fed diabetic rat liver: Effect of resveratrol and metformin.	Metformin	106-115	NLR family, pyrin domain containing 3	Rattus norvegicus	0-5
32660025-11	2020	An analysis of a subgroup of participants taking metformin showed a decrease in fasting plasma glucose, HbA1c, insulin resistance, and zonulin; an increase in plasma butyrate concentrations; and an enrichment of microbial butyrate-producing pathways in the probiotic group but not in the placebo group.	Metformin	49-58	haptoglobin	Homo sapiens	135-142
32371063-6	2020	Further we investigated the role of NLRP3 inflammasome on T2DM induced liver inflammation and effect of resveratrol and metformin treatment on NLRP3 inflammasome driven inflammatory response.	Metformin	120-129	NLR family, pyrin domain containing 3	Rattus norvegicus	143-148
32670541-4	2020	Although insulin sensitising agents such as metformin have been traditionally used for managing metabolic aspects of PCOS, their efficacy is low in terms of weight reduction and cardiovascular risk reduction compared with newer agents such as incretin mimetics and SGLT2 inhibitors.	Metformin	44-53	insulin	Homo sapiens	9-16
32695253-7	2020	Metformin treatment significantly increased the above protein expressions and slightly increased TXNIP expression.	Metformin	0-9	thioredoxin interacting protein	Homo sapiens	97-102
32695253-15	2020	Metformin exerted its protection against oxidative stress possibly via activating AMPK/Sirt1 and increasing TXNIP.	Metformin	0-9	thioredoxin interacting protein	Homo sapiens	108-113
32631421-0	2020	Metformin inhibits cervical cancer cell proliferation by modulating PI3K/Akt-induced major histocompatibility complex class I-related chain A gene expression.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	73-76
32631421-9	2020	RESULTS: Metformin inhibited cervical cancer cell proliferation, cervical cancer xenograft growth, expression of PCNA, p-PI3K and p-Akt.	Metformin	9-18	AKT serine/threonine kinase 1	Homo sapiens	132-135
32631421-11	2020	In addition, metformin upregulated the expression of DDR-1 and p53 in human cervical cancer cells.	Metformin	13-22	tumor protein p53	Homo sapiens	63-66
32631421-12	2020	Furthermore, metformin also regulated the mRNA and protein expression of MICA and HSP70 on the surface of human cervical cancer cells via the PI3K/Akt pathway, enhancing NK cell cytotoxicity.	Metformin	13-22	AKT serine/threonine kinase 1	Homo sapiens	147-150
32629460-7	2020	Patients using metformin and a dipeptidyl peptidase-4 inhibitors have a higher probability of success than do patients using metformin and a sulfonylurea, and patients using insulin and metformin have a higher probability of success than do patients using insulin alone.	Metformin	15-24	insulin	Homo sapiens	256-263
32060931-6	2020	Deterministic simulations from the model for a typical individual suggest that metformin doses of 250-500mg post-dialysis and 250mg given once daily should maintain median metformin plasma concentrations below 5mg L-1 .	Metformin	79-88	immunoglobulin kappa variable 1-16	Homo sapiens	214-217
32690574-0	2020	Glucagon-like peptide 1 agonists for treatment of patients with type 2 diabetes who fail metformin monotherapy: systematic review and meta-analysis of economic evaluation studies.	Metformin	89-98	glucagon	Homo sapiens	0-23
32402265-2	2020	Of note, the antiaging drug metformin reverses this autophagy defect and rejuvenates CD4+ T cell function.	Metformin	28-37	CD4 molecule	Homo sapiens	85-88
32443237-6	2020	Metformin significantly attenuated the production of IL-6, mitochondrial damage, cell viability and LDH activity by limiting TLRs/MyD88/NF-kappaB pathway.	Metformin	0-9	interleukin 6	Mus musculus	53-57
32533334-11	2020	Furthermore, IFNgamma expression appeared to be increased in response to metformin (p = 0.08).	Metformin	73-82	interferon gamma	Homo sapiens	13-21
32080865-0	2020	Combination of metformin and berberine represses the apoptosis of sebocytes in high-fat diet-induced diabetic hamsters and an insulin-treated human cell line.	Metformin	15-24	insulin	Homo sapiens	126-133
32080865-8	2020	Sebocytes isolated from high-fat diet-induced diabetic hamsters and insulin-treated human sebocytes displayed elevated cell death rates, which were attenuated by berberine and metformin treatments.	Metformin	176-185	insulin	Homo sapiens	68-75
32080865-9	2020	Further studies showed that the effects of metformin and berberine on cellular apoptosis were mediated via the Bik pathway.	Metformin	43-52	BCL2 interacting killer	Homo sapiens	111-114
32443237-6	2020	Metformin significantly attenuated the production of IL-6, mitochondrial damage, cell viability and LDH activity by limiting TLRs/MyD88/NF-kappaB pathway.	Metformin	0-9	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	136-145
32779431-9	2020	The expression levels of claudin 3 (Cldn3) and claudin 5 (Cldn5) were increased following treatment with metformin.	Metformin	105-114	claudin 3	Rattus norvegicus	25-34
32443237-7	2020	The siRNA against AMPKalpha2 or negative control were transfected to RAW264.7 cells to identify whether metformin protects PM2.5-induced cytotoxicity in an AMPKalpha2-dependent manner.	Metformin	104-113	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	156-166
32779431-9	2020	The expression levels of claudin 3 (Cldn3) and claudin 5 (Cldn5) were increased following treatment with metformin.	Metformin	105-114	claudin 3	Rattus norvegicus	36-41
32443237-8	2020	Pretreatment with metformin significantly attenuated PM2.5 induced decreasing of cell viability and increased LDH activity, as well as inhibited the TLRs/MyD88/NF-kappaB pathway in both siControl or siAMPKalpha2 cells.	Metformin	18-27	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	160-169
32443237-9	2020	Taken together, our results indicate that metformin protects against PM2.5-induced mitochondrial damage and cell cytotoxicity by inhibiting TLRs/MyD88/NF-kappaB signaling pathway in an AMPKalpha2 independent manner.	Metformin	42-51	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	151-160
32443237-9	2020	Taken together, our results indicate that metformin protects against PM2.5-induced mitochondrial damage and cell cytotoxicity by inhibiting TLRs/MyD88/NF-kappaB signaling pathway in an AMPKalpha2 independent manner.	Metformin	42-51	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	185-195
33099954-0	2020	Metformin induces apoptosis of melanoma B16 cells via PI3K/Akt/mTOR signaling pathways.	Metformin	0-9	thymoma viral proto-oncogene 1	Mus musculus	59-62
32229782-17	2020	Metformin exerted strong PI3K/Akt/mTOR pathway inactivation effects after 24-hour exposure (increasing pAMPK p<0.01, decreasing pAkt, p<0.01; and pS6, p<0.05).	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	30-33
32229782-17	2020	Metformin exerted strong PI3K/Akt/mTOR pathway inactivation effects after 24-hour exposure (increasing pAMPK p<0.01, decreasing pAkt, p<0.01; and pS6, p<0.05).	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	34-38
33099954-1	2020	PURPOSE: To investigate the influences of metformin on the proliferation and apoptosis of mouse melanoma B16 cells through regulating the phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway.	Metformin	42-51	thymoma viral proto-oncogene 1	Mus musculus	201-204
33099954-1	2020	PURPOSE: To investigate the influences of metformin on the proliferation and apoptosis of mouse melanoma B16 cells through regulating the phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway.	Metformin	42-51	mechanistic target of rapamycin kinase	Homo sapiens	206-235
33099954-1	2020	PURPOSE: To investigate the influences of metformin on the proliferation and apoptosis of mouse melanoma B16 cells through regulating the phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway.	Metformin	42-51	mechanistic target of rapamycin kinase	Homo sapiens	237-241
33099954-9	2020	CONCLUSIONS: Metformin can inhibit the proliferation of mouse melanoma B16 cells and induce their apoptosis probably through its regulation on the PI3K/AKT/mTOR signaling pathway in cells.	Metformin	13-22	thymoma viral proto-oncogene 1	Mus musculus	152-155
32229588-6	2020	Moreover, further results indicated that metformin suppresses Gm15622 and alleviates NAFLD-associated lipid deposition in mice.	Metformin	41-50	predicted gene 15622	Mus musculus	62-69
31868971-0	2020	Relationship between metformin use and vitamin B12 status in patients with type 2 diabetes in Japan.	Metformin	21-30	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	47-50
31868971-1	2020	AIMS/INTRODUCTION: Metformin therapy has been associated with vitamin B12 (VB12) deficiency, but information regarding this adverse effect in Asian populations is limited.	Metformin	19-28	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	70-73
32627027-0	2020	Metformin inhibits TGF-beta1-induced epithelial-mesenchymal transition and liver metastasis of pancreatic cancer cells.	Metformin	0-9	transforming growth factor beta 1	Homo sapiens	19-28
32342619-7	2020	The significant improvements found only in the metformin group were body mass index, fasting blood glucose, high-sensitivity C-reactive protein and 10-year risk of coronary heart disease (Framingham heart study) (P = 0.0004, P = 0.049, P = 0.035 and P = 0.029); whereas that only in the placebo group was high density lipoprotein cholesterol.	Metformin	47-56	C-reactive protein	Homo sapiens	125-143
32627027-9	2020	The cells stimulated with TGF-beta1 acquired an elongated and fusiform morphology, which was inhibited by metformin.	Metformin	106-115	transforming growth factor beta 1	Homo sapiens	26-35
32627027-10	2020	The wound healing assay revealed that metformin significantly suppressed the TGF-beta1-stimulated migration of pancreatic cancer cells.	Metformin	38-47	transforming growth factor beta 1	Homo sapiens	77-86
32627027-11	2020	Following treatment with metformin, E-cadherin expression (epithelial marker) was upregulated, and the levels of mesenchymal markers were downregulated, which had been increased by TGF-beta1 in these cells.	Metformin	25-34	cadherin 1	Homo sapiens	36-46
32627027-11	2020	Following treatment with metformin, E-cadherin expression (epithelial marker) was upregulated, and the levels of mesenchymal markers were downregulated, which had been increased by TGF-beta1 in these cells.	Metformin	25-34	transforming growth factor beta 1	Homo sapiens	181-190
32627027-12	2020	Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells.	Metformin	145-154	transforming growth factor beta 1	Homo sapiens	25-34
32627027-12	2020	Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells.	Metformin	145-154	AKT serine/threonine kinase 1	Homo sapiens	61-64
32627027-12	2020	Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells.	Metformin	145-154	mechanistic target of rapamycin kinase	Homo sapiens	65-94
32627027-12	2020	Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells.	Metformin	145-154	mechanistic target of rapamycin kinase	Homo sapiens	96-100
32627027-12	2020	Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells.	Metformin	145-154	transforming growth factor beta 1	Homo sapiens	191-200
32627027-12	2020	Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells.	Metformin	145-154	AKT serine/threonine kinase 1	Homo sapiens	307-310
32627027-12	2020	Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells.	Metformin	145-154	mechanistic target of rapamycin kinase	Homo sapiens	311-315
32627027-12	2020	Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells.	Metformin	172-181	transforming growth factor beta 1	Homo sapiens	25-34
32627027-12	2020	Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells.	Metformin	172-181	AKT serine/threonine kinase 1	Homo sapiens	61-64
32627027-12	2020	Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells.	Metformin	172-181	mechanistic target of rapamycin kinase	Homo sapiens	65-94
32627027-12	2020	Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells.	Metformin	172-181	mechanistic target of rapamycin kinase	Homo sapiens	96-100
32627027-12	2020	Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells.	Metformin	172-181	transforming growth factor beta 1	Homo sapiens	191-200
32627027-12	2020	Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells.	Metformin	172-181	AKT serine/threonine kinase 1	Homo sapiens	307-310
32627027-12	2020	Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells.	Metformin	172-181	mechanistic target of rapamycin kinase	Homo sapiens	311-315
32627027-14	2020	On the whole, the findings of the present study suggest that metformin inhibits EMT and cancer metastasis through the Smad or Akt/mTOR pathway.	Metformin	61-70	AKT serine/threonine kinase 1	Homo sapiens	126-129
32627027-14	2020	On the whole, the findings of the present study suggest that metformin inhibits EMT and cancer metastasis through the Smad or Akt/mTOR pathway.	Metformin	61-70	mechanistic target of rapamycin kinase	Homo sapiens	130-134
32610645-6	2020	Further analyses showed that metformin treatment increased the activities of superoxide dismutase, catalase and glutathione peroxidase and reduced lipid peroxidation.	Metformin	29-38	catalase	Mus musculus	99-107
32537703-0	2020	Metformin and/or low dose radiation reduces cardiotoxicity and apoptosis induced by cyclophosphamide through SIRT-1/SOD and BAX/Bcl-2 pathways in rats.	Metformin	0-9	sirtuin 1	Rattus norvegicus	109-115
32537703-0	2020	Metformin and/or low dose radiation reduces cardiotoxicity and apoptosis induced by cyclophosphamide through SIRT-1/SOD and BAX/Bcl-2 pathways in rats.	Metformin	0-9	BCL2, apoptosis regulator	Rattus norvegicus	128-133
32222530-0	2020	Metformin enhances the sensitivity of colorectal cancer cells to cisplatin through ROS-mediated PI3K/Akt signaling pathway.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	101-104
32222530-6	2020	Moreover, NAC could recover the downregulation of p-PI3K and p-Akt treated with combination of metformin and cisplatin, which subsequently activated the PI3K/Akt signaling pathway.	Metformin	95-104	AKT serine/threonine kinase 1	Homo sapiens	63-66
32222530-7	2020	Taken together, our results demonstrated that metformin enhanced the sensitivity of CRC cells to cisplatin through ROS-mediated PI3K/Akt signaling pathway.	Metformin	46-55	AKT serine/threonine kinase 1	Homo sapiens	133-136
32556103-6	2020	Moreover, lowering UA using benzbromarone (a uricosuric agent) or metformin-induced activation of AMPK expression significantly attenuated UA-induced FFA metabolism impairment and adipose beiging suppression, which subsequently alleviated serum FFA elevation and insulin resistance in HUA mice.	Metformin	66-75	insulin	Homo sapiens	263-270
32607520-13	2020	This sex-specific finding is consistent with metformin reducing TNF-alpha in females over males, and suggests that metformin conveys protection in Covid-19 through TNF-alpha effects.	Metformin	45-54	tumor necrosis factor	Homo sapiens	64-73
32607520-13	2020	This sex-specific finding is consistent with metformin reducing TNF-alpha in females over males, and suggests that metformin conveys protection in Covid-19 through TNF-alpha effects.	Metformin	115-124	tumor necrosis factor	Homo sapiens	164-173
32556103-7	2020	Taken together, these observations confirm that UA is involved in the aetiology of metabolic abnormalities in adipose tissue by regulating leptin-AMPK pathway,and metformin could lessen HUA-induced serum FFA elevation and insulin resistance by improving adipose tissue function via AMPK activation.	Metformin	163-172	insulin	Homo sapiens	222-229
32591547-2	2020	Our previous reports showed that high-fat-diet (HFD)-fed mice with liver-specific knockout of both AMPK catalytic alpha1 and alpha2 subunits exhibited significantly higher fasting blood glucose levels and produced more glucose than floxed AMPK catalytic alpha1 and alpha2 mice after long-term metformin treatment, and that metformin promotes the formation of the functional AMPK alphabetagamma heterotrimeric complex.	Metformin	293-302	ST3 beta-galactoside alpha-2,3-sialyltransferase 5	Mus musculus	125-131
32591547-2	2020	Our previous reports showed that high-fat-diet (HFD)-fed mice with liver-specific knockout of both AMPK catalytic alpha1 and alpha2 subunits exhibited significantly higher fasting blood glucose levels and produced more glucose than floxed AMPK catalytic alpha1 and alpha2 mice after long-term metformin treatment, and that metformin promotes the formation of the functional AMPK alphabetagamma heterotrimeric complex.	Metformin	323-332	ST3 beta-galactoside alpha-2,3-sialyltransferase 5	Mus musculus	125-131
32728616-0	2020	Insulin and Metformin Control Cell Proliferation by Regulating TDG-Mediated DNA Demethylation in Liver and Breast Cancer Cells.	Metformin	12-21	thymine DNA glycosylase	Homo sapiens	63-66
32728616-8	2020	These findings demonstrate that c-Myc activates, whereas AMPK inhibits, TDG-mediated DNA demethylation of the SREBP1 promoter in insulin-promoted and metformin-suppressed cancer progression, respectively.	Metformin	150-159	thymine DNA glycosylase	Homo sapiens	72-75
32575674-0	2020	rs622342 in SLC22A1, CYP2C9*2 and CYP2C9*3 and Glycemic Response in Individuals with Type 2 Diabetes Mellitus Receiving Metformin/Sulfonylurea Combination Therapy: 6-Month Follow-Up Study.	Metformin	120-129	solute carrier family 22 member 1	Homo sapiens	12-19
32575674-11	2020	CONCLUSION: The combination of metformin/sulfonylurea therapy led to the maximum glycemic control in individuals with T2DM carrying AA or AC genotypes in SLC22A1 and *1*3 in CYP2C9.	Metformin	31-40	solute carrier family 22 member 1	Homo sapiens	154-161
32606866-0	2020	Intronic Variants in OCT1 are Associated with All-Cause and Cardiovascular Mortality in Metformin Users with Type 2 Diabetes.	Metformin	88-97	solute carrier family 22 member 1	Homo sapiens	21-25
32606866-7	2020	Results: In a multivariate Cox regression analysis adjusted for classical cardiovascular risk factors, 4 intronic OCT1 SNPs were significantly associated with all-cause and cardiovascular mortality in individuals with T2DM on metformin therapy.	Metformin	226-235	solute carrier family 22 member 1	Homo sapiens	114-118
32606866-8	2020	Conclusion: According to their OCT1 genotype, some individuals with T2DM on metformin therapy might be prone to an increased risk of cardiovascular death.	Metformin	76-85	solute carrier family 22 member 1	Homo sapiens	31-35
32625081-2	2020	Metformin is an oral drug that is being evaluated to treat GDM, obesity-associated insulin resistance, and polycystic ovary syndrome (PCOS) during pregnancy.	Metformin	0-9	insulin	Homo sapiens	83-90
32556103-0	2020	Metformin alleviates hyperuricaemia-induced serum FFA elevation and insulin resistance by inhibiting adipocyte hypertrophy and reversing suppressed white adipose tissue beiging.	Metformin	0-9	insulin	Homo sapiens	68-75
32606605-0	2020	Metformin Decreases Insulin Resistance in Type 1 Diabetes Through Regulating p53 and RAP2A in vitro and in vivo.	Metformin	0-9	insulin	Homo sapiens	20-27
32606605-0	2020	Metformin Decreases Insulin Resistance in Type 1 Diabetes Through Regulating p53 and RAP2A in vitro and in vivo.	Metformin	0-9	tumor protein p53	Homo sapiens	77-80
32606605-2	2020	This study was set out to explore the molecular mechanism of metformin in the treatment of T1D insulin resistance.	Metformin	61-70	insulin	Homo sapiens	95-102
32606605-4	2020	Insulin resistance model rats and cells were constructed and treated with metformin respectively.	Metformin	74-83	insulin	Homo sapiens	0-7
32625081-4	2020	In this line of thought, improving the metabolic status of the pregnant mother by using metformin should avoid the consequences of insulin resistance on the offspring"s fetal and postnatal development.	Metformin	88-97	insulin	Homo sapiens	131-138
32606605-8	2020	Metformin could effectively improve insulin resistance and inflammatory response while down-regulating p53 and up-regulating RAP2A.	Metformin	0-9	insulin	Homo sapiens	36-43
32606605-8	2020	Metformin could effectively improve insulin resistance and inflammatory response while down-regulating p53 and up-regulating RAP2A.	Metformin	0-9	tumor protein p53	Homo sapiens	103-106
32546267-0	2020	Metformin inhibits intracranial aneurysm formation and progression by regulating vascular smooth muscle cell phenotype switching via the AMPK/ACC pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	137-141
32606605-10	2020	Conclusion: Metformin improves T1D insulin resistance and inflammatory response through p53/RAP2A pathway, and the regulation of p53/RAP2A pathway is conducive to improving the efficacy of metformin in the treatment of insulin resistance.	Metformin	12-21	insulin	Homo sapiens	35-42
32606605-10	2020	Conclusion: Metformin improves T1D insulin resistance and inflammatory response through p53/RAP2A pathway, and the regulation of p53/RAP2A pathway is conducive to improving the efficacy of metformin in the treatment of insulin resistance.	Metformin	12-21	tumor protein p53	Homo sapiens	88-91
32606605-10	2020	Conclusion: Metformin improves T1D insulin resistance and inflammatory response through p53/RAP2A pathway, and the regulation of p53/RAP2A pathway is conducive to improving the efficacy of metformin in the treatment of insulin resistance.	Metformin	189-198	insulin	Homo sapiens	35-42
32606605-10	2020	Conclusion: Metformin improves T1D insulin resistance and inflammatory response through p53/RAP2A pathway, and the regulation of p53/RAP2A pathway is conducive to improving the efficacy of metformin in the treatment of insulin resistance.	Metformin	189-198	tumor protein p53	Homo sapiens	129-132
32606605-10	2020	Conclusion: Metformin improves T1D insulin resistance and inflammatory response through p53/RAP2A pathway, and the regulation of p53/RAP2A pathway is conducive to improving the efficacy of metformin in the treatment of insulin resistance.	Metformin	189-198	insulin	Homo sapiens	219-226
32546267-8	2020	RESULTS: Metformin decreased the incidence and rupture rate of IA in the rat model and induced a switch in VSMC phenotype from contractile to synthetic through activation of the AMPK/ACC pathway, as evidenced by upregulation of VSMC-specific genes and decreased levels of pro-inflammatory cytokines.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	178-182
32566257-6	2020	Our results indicated that metformin increased the AMPK phosphorylation, but decreased the Akt phosphorylation.	Metformin	27-36	thymoma viral proto-oncogene 1	Mus musculus	91-94
32566257-10	2020	In conclusion, this study indicates a potential therapeutic effect of metformin on Tsc1 deletion-induced kidney pathology, although currently metformin is primarily prescribed to treat patients with type 2 diabetes.	Metformin	70-79	TSC complex subunit 1	Homo sapiens	83-87
32626781-11	2020	Finally, the levels of IL-1beta, TNF-alpha, Bax, and caspase-3 were also decreased in both treated groups (metformin and green coffee) when compared to the diabetic group.	Metformin	107-116	interleukin 1 alpha	Rattus norvegicus	23-31
32626781-11	2020	Finally, the levels of IL-1beta, TNF-alpha, Bax, and caspase-3 were also decreased in both treated groups (metformin and green coffee) when compared to the diabetic group.	Metformin	107-116	tumor necrosis factor	Rattus norvegicus	33-42
32595491-11	2020	Furthermore, the expression levels of CACNA1C mRNA and Cav1.2 were decreased in the metformin group.	Metformin	84-93	calcium channel, voltage-dependent, L type, alpha 1C subunit	Mus musculus	38-45
32595491-11	2020	Furthermore, the expression levels of CACNA1C mRNA and Cav1.2 were decreased in the metformin group.	Metformin	84-93	calcium channel, voltage-dependent, L type, alpha 1C subunit	Mus musculus	55-61
32444490-1	2020	Metastatic colorectal cancer (mCRC) patients have poor overall survival despite using irinotecan- or oxaliplatin-based chemotherapy combined with anti-EGFR (epidermal growth factor receptor) drugs, especially those with the oncogene mutation of KRAS Metformin has been reported as a potentially novel antitumor agent in many experiments, but its therapeutic activity is discrepant and controversial so far.	Metformin	250-259	epidermal growth factor receptor	Homo sapiens	157-189
32587614-15	2020	Conclusions: The use of insulin-sensitizing agents, such as metformin and inositols, along with lifestyle interventions may improve the metabolic profile in PCOS women.	Metformin	60-69	insulin	Homo sapiens	24-31
32596370-7	2020	Subsequently, metformin, a first-line clinical drug for T2DM treatment, was found to improve the osteogenic differentiation potential of BMSCs from T2DM patients via the BMP-4/Smad/Runx2 signaling pathway.	Metformin	14-23	RUNX family transcription factor 2	Homo sapiens	181-186
32243780-6	2020	However, metformin treatment still increases KLF4 levels and suppresses progenitor proliferation.	Metformin	9-18	Kruppel-like factor 4 (gut)	Mus musculus	45-49
32243780-7	2020	Thus, AMPK activates KLF4 in progenitors to reduce self-renewal and promote PC fate, whereas AMPK-PGC1alpha activation within the PC lineage promotes maturation, providing a potential suggestion for why metformin increases acid secretion and reduces gastric cancer risk in humans.	Metformin	203-212	PPARG coactivator 1 alpha	Homo sapiens	98-107
32493421-17	2020	The mechanistic studies indicated that the therapeutic effects of Diane-35 plus metformin treatment in the PCOS rats may be associated with the regulation of glycolysis-related mediators including PKM2, LDH-A and SIRT1.	Metformin	80-89	sirtuin 1	Rattus norvegicus	213-218
32572457-3	2020	Metformin, a commonly used oral antidiabetic drug, is known to elicit its action through 5" adenosine monophosphate-activated protein kinase (AMPK), a cellular metabolic regulator; however, its effect on Kir4.1 channels is unknown.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	142-146
32572457-11	2020	In rMC-1 cells, AMPK activation via AICAR and metformin resulted in increased Kir4.1 and intermediate core clock component Bmal-1 protein expression.	Metformin	46-55	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	16-20
32550106-0	2020	Metformin attenuates TGF-beta1-induced pulmonary fibrosis through inhibition of transglutaminase 2 and subsequent TGF-beta pathways.	Metformin	0-9	transforming growth factor beta 1	Homo sapiens	21-30
32550106-0	2020	Metformin attenuates TGF-beta1-induced pulmonary fibrosis through inhibition of transglutaminase 2 and subsequent TGF-beta pathways.	Metformin	0-9	transglutaminase 2	Homo sapiens	80-98
32550106-1	2020	The purpose of this study was to confirm whether metformin can attenuate TGF-beta1-induced pulmonary fibrosis through inhibition of transglutaminase 2 (TG2) and subsequent TGF-beta pathways.	Metformin	49-58	transforming growth factor beta 1	Homo sapiens	73-82
32550106-1	2020	The purpose of this study was to confirm whether metformin can attenuate TGF-beta1-induced pulmonary fibrosis through inhibition of transglutaminase 2 (TG2) and subsequent TGF-beta pathways.	Metformin	49-58	transglutaminase 2	Homo sapiens	132-150
32550106-1	2020	The purpose of this study was to confirm whether metformin can attenuate TGF-beta1-induced pulmonary fibrosis through inhibition of transglutaminase 2 (TG2) and subsequent TGF-beta pathways.	Metformin	49-58	transglutaminase 2	Homo sapiens	152-155
32550106-7	2020	Our results showed that metformin concentration-dependently inhibited the proliferation and promoted the apoptosis of TGF-beta1-stimulated HFL-1 cells.	Metformin	24-33	transforming growth factor beta 1	Homo sapiens	118-127
32550106-8	2020	The protein expressions of TG2, Col I and alpha-SMA stimulated by TGF-beta1 were decreased after metformin intervention, which was confirmed in both siRNAs and plasmids treatment conditions.	Metformin	97-106	transglutaminase 2	Homo sapiens	27-30
32550106-8	2020	The protein expressions of TG2, Col I and alpha-SMA stimulated by TGF-beta1 were decreased after metformin intervention, which was confirmed in both siRNAs and plasmids treatment conditions.	Metformin	97-106	actin alpha 1, skeletal muscle	Homo sapiens	42-51
32550106-8	2020	The protein expressions of TG2, Col I and alpha-SMA stimulated by TGF-beta1 were decreased after metformin intervention, which was confirmed in both siRNAs and plasmids treatment conditions.	Metformin	97-106	transforming growth factor beta 1	Homo sapiens	66-75
32550106-11	2020	Taken together, our results demonstrated that metformin can attenuate TGF-beta1-induced pulmonary fibrosis, at least partly, through inhibition of TG2 and subsequent TGF-beta pathways.	Metformin	46-55	transforming growth factor beta 1	Homo sapiens	70-79
32550106-11	2020	Taken together, our results demonstrated that metformin can attenuate TGF-beta1-induced pulmonary fibrosis, at least partly, through inhibition of TG2 and subsequent TGF-beta pathways.	Metformin	46-55	transglutaminase 2	Homo sapiens	147-150
32020414-1	2020	PURPOSE: To determine the separated and combined effects of metformin and exercise on insulin sensitivity and free-living glycemic control in overweight individuals with prediabetes/type 2 diabetes (T2DM).	Metformin	60-69	insulin	Homo sapiens	86-93
31721026-9	2020	The metformin-treated group had a significant reduction of body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C), but the control group did not.	Metformin	4-13	component of oligomeric golgi complex 2	Homo sapiens	85-120
31721026-9	2020	The metformin-treated group had a significant reduction of body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C), but the control group did not.	Metformin	4-13	component of oligomeric golgi complex 2	Homo sapiens	122-127
32048878-12	2020	AMPK agonists, A769662 and metformin increased the mitochondrial complex proteins and number, in vitro angiogenesis and Jag1 levels and decreased DLL4 levels in PPHN PAEC.	Metformin	27-36	protein jagged-1	Ovis aries	120-124
31840936-12	2020	Metformin or AICAR presence decreased spontaneous production of IL-6, IL-8 and MCP-1 in RA synovial explants and SFCs (n=5-7).	Metformin	0-9	interleukin 6	Homo sapiens	64-68
31840936-12	2020	Metformin or AICAR presence decreased spontaneous production of IL-6, IL-8 and MCP-1 in RA synovial explants and SFCs (n=5-7).	Metformin	0-9	C-X-C motif chemokine ligand 8	Homo sapiens	70-74
32268788-9	2020	Early treatment with treprostinil in SU5416/Obese ZSF1 rats lowered pulmonary pressures, and a late treatment with treprostinil together with metformin improved pulmonary artery acceleration time to ejection time ratio and tricuspid annular plane systolic excursion with AMPK (AMP-activated protein kinase) activation in skeletal muscle and the right ventricle.	Metformin	142-151	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	271-275
32268788-9	2020	Early treatment with treprostinil in SU5416/Obese ZSF1 rats lowered pulmonary pressures, and a late treatment with treprostinil together with metformin improved pulmonary artery acceleration time to ejection time ratio and tricuspid annular plane systolic excursion with AMPK (AMP-activated protein kinase) activation in skeletal muscle and the right ventricle.	Metformin	142-151	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	277-305
32270948-0	2020	Metformin Attenuates Ischemia/Reperfusion Injury of Fatty Liver in Rats Through Inhibition of the TLR4-NF-kappaB Axis Background: Donor organs for liver transplantation may often have fatty liver disease, which confers a higher sensitivity to ischemia/reperfusion (I/R) injury.	Metformin	0-9	toll-like receptor 4	Rattus norvegicus	98-102
32270948-9	2020	In addition, metformin significantly attenuated IL-6, IL-1beta, and TNF-alpha production and increased the expression of active caspase-3 and Bax in the liver (p<0.05).	Metformin	13-22	interleukin 6	Rattus norvegicus	48-52
32270948-9	2020	In addition, metformin significantly attenuated IL-6, IL-1beta, and TNF-alpha production and increased the expression of active caspase-3 and Bax in the liver (p<0.05).	Metformin	13-22	interleukin 1 alpha	Rattus norvegicus	54-62
32270948-9	2020	In addition, metformin significantly attenuated IL-6, IL-1beta, and TNF-alpha production and increased the expression of active caspase-3 and Bax in the liver (p<0.05).	Metformin	13-22	tumor necrosis factor	Rattus norvegicus	68-77
32270948-10	2020	Mechanistically, metformin suppressed the activation of TLR4/NF-kappaB signaling (p<0.05), resulting in a decreased inflammatory response and apoptosis.	Metformin	17-26	toll-like receptor 4	Rattus norvegicus	56-60
32270948-11	2020	Conclusions: Our findings demonstrated that metformin attenuated I/R injury in fatty liver disease via the TLR4/NF-kappaB axis, suggesting that metformin could have potential therapeutic applications in I/R injury associated with liver transplantation.	Metformin	44-53	toll-like receptor 4	Rattus norvegicus	107-111
32270948-11	2020	Conclusions: Our findings demonstrated that metformin attenuated I/R injury in fatty liver disease via the TLR4/NF-kappaB axis, suggesting that metformin could have potential therapeutic applications in I/R injury associated with liver transplantation.	Metformin	144-153	toll-like receptor 4	Rattus norvegicus	107-111
31961463-8	2020	This effect of metformin was also significant in non-obese (51.4 versus 24.3%, OR 3.28, 95% CI 1.22-8.84, P = 0.02) and insulin-sensitive (54.8 versus 28.6%, OR 3.04, 95% CI 1.03-8.97, P = 0.04) subgroups of AEH women.	Metformin	15-24	insulin	Homo sapiens	120-127
32247208-8	2020	Additionally, compared to women prescribed metformin, all-cause mortality hazard was elevated among women prescribed sulfonylurea (HR = 1.44; 95 %CI 1.06, 1.94) or insulin (HR = 1.54; 95 %CI 1.12, 2.11).	Metformin	43-52	insulin	Homo sapiens	164-171
32248666-0	2020	Metformin revert insulin-induced oxaliplatin resistance by activating mitochondrial apoptosis pathway in human colon cancer HCT116 cells.	Metformin	0-9	insulin	Homo sapiens	17-24
32248666-3	2020	This study aimed to elucidate the underlying mechanism by which metformin reverts insulin-induced oxaliplatin resistance in human colon cancer HCT116 cells.	Metformin	64-73	insulin	Homo sapiens	82-89
32248666-13	2020	The AMPK/Erk signaling pathway experiments revealed that the upregulation of Bcl-2 induced by insulin through Erk phosphorylation was inhibited by metformin and that such inhibition could be mitigated by the inhibition of AMPK.	Metformin	147-156	mitogen-activated protein kinase 1	Homo sapiens	9-12
32248666-13	2020	The AMPK/Erk signaling pathway experiments revealed that the upregulation of Bcl-2 induced by insulin through Erk phosphorylation was inhibited by metformin and that such inhibition could be mitigated by the inhibition of AMPK.	Metformin	147-156	BCL2 apoptosis regulator	Homo sapiens	77-82
32248666-13	2020	The AMPK/Erk signaling pathway experiments revealed that the upregulation of Bcl-2 induced by insulin through Erk phosphorylation was inhibited by metformin and that such inhibition could be mitigated by the inhibition of AMPK.	Metformin	147-156	insulin	Homo sapiens	94-101
32248666-13	2020	The AMPK/Erk signaling pathway experiments revealed that the upregulation of Bcl-2 induced by insulin through Erk phosphorylation was inhibited by metformin and that such inhibition could be mitigated by the inhibition of AMPK.	Metformin	147-156	mitogen-activated protein kinase 1	Homo sapiens	110-113
32248666-14	2020	CONCLUSIONS: Insulin-induced oxaliplatin resistance was reversed by metformin-mediated AMPK activation.	Metformin	68-77	insulin	Homo sapiens	13-20
31792920-10	2020	Alpha-mangostin (1.25 muM) and metformin (50 muM) reversed the toxic effects of high glucose in HUVECs.	Metformin	31-40	latexin	Homo sapiens	45-48
32734128-2	2020	In NSCLC cells, metformin suppresses PI3K/AKT/mTOR signaling pathway, but effect of metformin on RAS/ RAF/MEK/ERK signaling pathway is controversial; several studies showed the inhibition of ERK activity, while others demonstrated the activation of ERK in response to metformin exposure.	Metformin	16-25	AKT serine/threonine kinase 1	Homo sapiens	42-45
32734128-2	2020	In NSCLC cells, metformin suppresses PI3K/AKT/mTOR signaling pathway, but effect of metformin on RAS/ RAF/MEK/ERK signaling pathway is controversial; several studies showed the inhibition of ERK activity, while others demonstrated the activation of ERK in response to metformin exposure.	Metformin	16-25	mechanistic target of rapamycin kinase	Homo sapiens	46-50
32734128-2	2020	In NSCLC cells, metformin suppresses PI3K/AKT/mTOR signaling pathway, but effect of metformin on RAS/ RAF/MEK/ERK signaling pathway is controversial; several studies showed the inhibition of ERK activity, while others demonstrated the activation of ERK in response to metformin exposure.	Metformin	84-93	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	102-105
32734128-2	2020	In NSCLC cells, metformin suppresses PI3K/AKT/mTOR signaling pathway, but effect of metformin on RAS/ RAF/MEK/ERK signaling pathway is controversial; several studies showed the inhibition of ERK activity, while others demonstrated the activation of ERK in response to metformin exposure.	Metformin	84-93	mitogen-activated protein kinase kinase 7	Homo sapiens	106-109
32734128-2	2020	In NSCLC cells, metformin suppresses PI3K/AKT/mTOR signaling pathway, but effect of metformin on RAS/ RAF/MEK/ERK signaling pathway is controversial; several studies showed the inhibition of ERK activity, while others demonstrated the activation of ERK in response to metformin exposure.	Metformin	84-93	mitogen-activated protein kinase 1	Homo sapiens	110-113
32734128-2	2020	In NSCLC cells, metformin suppresses PI3K/AKT/mTOR signaling pathway, but effect of metformin on RAS/ RAF/MEK/ERK signaling pathway is controversial; several studies showed the inhibition of ERK activity, while others demonstrated the activation of ERK in response to metformin exposure.	Metformin	84-93	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	102-105
32734128-2	2020	In NSCLC cells, metformin suppresses PI3K/AKT/mTOR signaling pathway, but effect of metformin on RAS/ RAF/MEK/ERK signaling pathway is controversial; several studies showed the inhibition of ERK activity, while others demonstrated the activation of ERK in response to metformin exposure.	Metformin	84-93	mitogen-activated protein kinase kinase 7	Homo sapiens	106-109
32734128-2	2020	In NSCLC cells, metformin suppresses PI3K/AKT/mTOR signaling pathway, but effect of metformin on RAS/ RAF/MEK/ERK signaling pathway is controversial; several studies showed the inhibition of ERK activity, while others demonstrated the activation of ERK in response to metformin exposure.	Metformin	84-93	mitogen-activated protein kinase 1	Homo sapiens	110-113
32734128-3	2020	Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	32-35
32734128-3	2020	Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect.	Metformin	0-9	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	127-130
32734128-3	2020	Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect.	Metformin	0-9	mitogen-activated protein kinase kinase 7	Homo sapiens	131-134
32734128-3	2020	Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	135-138
32734128-3	2020	Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	214-217
32734128-3	2020	Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	218-222
32734128-3	2020	Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect.	Metformin	72-81	mitogen-activated protein kinase 1	Homo sapiens	32-35
32734128-3	2020	Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect.	Metformin	72-81	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	127-130
32734128-3	2020	Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect.	Metformin	72-81	mitogen-activated protein kinase kinase 7	Homo sapiens	131-134
32734128-3	2020	Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect.	Metformin	72-81	mitogen-activated protein kinase 1	Homo sapiens	135-138
32734128-3	2020	Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect.	Metformin	72-81	AKT serine/threonine kinase 1	Homo sapiens	214-217
32734128-3	2020	Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect.	Metformin	72-81	mechanistic target of rapamycin kinase	Homo sapiens	218-222
32734128-4	2020	The present study tested the combination therapy of metformin and trametinib by monitoring the alterations of regulatory effector proteins of cell signaling pathways and the effect of the combination on cell viability in NCI-H2087 NSCLC cells with NRAS and BRAF mutations.	Metformin	52-61	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	257-261
32734128-5	2020	We show that metformin alone blocks PI3K/AKT/mTOR signaling pathway but induces the activation and phosphorylation of ERK.	Metformin	13-22	AKT serine/threonine kinase 1	Homo sapiens	41-44
32734128-5	2020	We show that metformin alone blocks PI3K/AKT/mTOR signaling pathway but induces the activation and phosphorylation of ERK.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	45-49
32734128-5	2020	We show that metformin alone blocks PI3K/AKT/mTOR signaling pathway but induces the activation and phosphorylation of ERK.	Metformin	13-22	mitogen-activated protein kinase 1	Homo sapiens	118-121
32734128-7	2020	These findings suggest that the efficacy of metformin and trametinib combination therapy may depend on the alteration of ERK activity induced by metformin and specific cellular context of cancer cells.	Metformin	44-53	mitogen-activated protein kinase 1	Homo sapiens	121-124
32734128-7	2020	These findings suggest that the efficacy of metformin and trametinib combination therapy may depend on the alteration of ERK activity induced by metformin and specific cellular context of cancer cells.	Metformin	145-154	mitogen-activated protein kinase 1	Homo sapiens	121-124
32449697-8	2020	In the metformin group, VCAM-1 EMPs (p<0.001) increased significantly after 12 weeks of treatment, whereas all other EMPs remained unchanged.	Metformin	7-16	vascular cell adhesion molecule 1	Homo sapiens	24-30
31883148-8	2020	Furthermore, transport of cationic drugs, metformin and paclitaxel in HepG2 cells was blunted by OCT inhibitors, suggesting that hOCT1 and hOCT3 expressed in HepG2 cells exhibit notable impacts on cationic drug actions.	Metformin	42-51	solute carrier family 22 member 1	Homo sapiens	129-134
32546267-3	2020	Metformin is a 5" AMP-activated protein kinase (AMPK) agonist that has a protective effect on vasculature.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	18-46
32546267-3	2020	Metformin is a 5" AMP-activated protein kinase (AMPK) agonist that has a protective effect on vasculature.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	48-52
32360359-5	2020	Recent studies have shown that metformin decreases ACTH secretion from pituitary and reduces ACTH-stimulated adrenal secretion.	Metformin	31-40	proopiomelanocortin	Homo sapiens	51-55
32360359-13	2020	The ACTH concentration response curve (CRC) was half-log shifted and a ~30 % reduction in maximum receptor response (Rmax) to ACTH in presence of metformin was observed.	Metformin	146-155	proopiomelanocortin	Homo sapiens	126-130
32360359-5	2020	Recent studies have shown that metformin decreases ACTH secretion from pituitary and reduces ACTH-stimulated adrenal secretion.	Metformin	31-40	proopiomelanocortin	Homo sapiens	93-97
32360359-15	2020	qRT-PCR analyses showed that metformin decreased ACTH induced MC2R expression.	Metformin	29-38	proopiomelanocortin	Homo sapiens	49-53
32360359-12	2020	We found a significant inhibition of ACTH induced MC2R activation and signaling with 10 mM metformin.	Metformin	91-100	proopiomelanocortin	Homo sapiens	37-41
32360359-19	2020	However, a log shift of EC50 of ACTH stimulation on MC3R was observed with metformin treatment.	Metformin	75-84	proopiomelanocortin	Homo sapiens	32-36
32360359-13	2020	The ACTH concentration response curve (CRC) was half-log shifted and a ~30 % reduction in maximum receptor response (Rmax) to ACTH in presence of metformin was observed.	Metformin	146-155	proopiomelanocortin	Homo sapiens	4-8
32360359-24	2020	Our study may explain how metformin helps in weight loss and attenuates the excess response to ACTH in androgen excess disorders such as PCOS and CAH.	Metformin	26-35	proopiomelanocortin	Homo sapiens	95-99
32048246-0	2020	Metformin accelerates myelin recovery and ameliorates behavioral deficits in the animal model of multiple sclerosis via adjustment of AMPK/Nrf2/mTOR signaling and maintenance of endogenous oligodendrogenesis during brain self-repairing period.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	139-143
32048246-0	2020	Metformin accelerates myelin recovery and ameliorates behavioral deficits in the animal model of multiple sclerosis via adjustment of AMPK/Nrf2/mTOR signaling and maintenance of endogenous oligodendrogenesis during brain self-repairing period.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	144-148
32048246-4	2020	RESULTS: MET remarkably increased the localization of precursor OLGs (NG2+/O4+ cells) and subsequently the renewal of mature OLGs (MOG+ cells) in the corpus callosum via AMPK/mammalian target of rapamycin (mTOR) pathway.	Metformin	9-12	mechanistic target of rapamycin kinase	Homo sapiens	175-204
32048246-4	2020	RESULTS: MET remarkably increased the localization of precursor OLGs (NG2+/O4+ cells) and subsequently the renewal of mature OLGs (MOG+ cells) in the corpus callosum via AMPK/mammalian target of rapamycin (mTOR) pathway.	Metformin	9-12	mechanistic target of rapamycin kinase	Homo sapiens	206-210
32048246-5	2020	Moreover, we observed a significant elevation in the antioxidant responses, especially in mature OLGs (MOG+/nuclear factor erythroid 2-related factor 2 (Nrf2+) cells) after MET intervention.	Metformin	173-176	NFE2 like bZIP transcription factor 2	Homo sapiens	153-157
32048246-9	2020	CONCLUSIONS: Altogether, our study reveals that MET effectively induces lesion reduction and elevated molecular processes that support myelin recovery via direct activation of AMPK and indirect regulation of AMPK/Nrf2/mTOR pathway in OLGs.	Metformin	48-51	NFE2 like bZIP transcription factor 2	Homo sapiens	213-217
32048246-9	2020	CONCLUSIONS: Altogether, our study reveals that MET effectively induces lesion reduction and elevated molecular processes that support myelin recovery via direct activation of AMPK and indirect regulation of AMPK/Nrf2/mTOR pathway in OLGs.	Metformin	48-51	mechanistic target of rapamycin kinase	Homo sapiens	218-222
32452405-11	2020	DISCUSSION: Low dose combination metformin and sulfasalazine reduced cytotrophoblast sFlt-1 and sENG secretion, increased VEGFalpha expression and reduced TNFalpha induced endothelin-1 expression in primary endothelial cells.	Metformin	33-42	vascular endothelial growth factor A	Homo sapiens	122-131
32452405-11	2020	DISCUSSION: Low dose combination metformin and sulfasalazine reduced cytotrophoblast sFlt-1 and sENG secretion, increased VEGFalpha expression and reduced TNFalpha induced endothelin-1 expression in primary endothelial cells.	Metformin	33-42	tumor necrosis factor	Homo sapiens	155-163
32452405-11	2020	DISCUSSION: Low dose combination metformin and sulfasalazine reduced cytotrophoblast sFlt-1 and sENG secretion, increased VEGFalpha expression and reduced TNFalpha induced endothelin-1 expression in primary endothelial cells.	Metformin	33-42	endothelin 1	Homo sapiens	172-184
31904843-8	2020	RESULTS: Metformin enhanced the immunomodulatory functions of Ad-MSCs including IDO, IL-10 and TGF-beta.	Metformin	9-18	interleukin 10	Mus musculus	85-90
31904843-9	2020	Metformin upregulated the expression of p-AMPK, p-STAT1 and inhibited the expression of p-STAT3, p-mTOR in Ad-MSCs.	Metformin	0-9	signal transducer and activator of transcription 3	Mus musculus	90-95
31904843-10	2020	STAT1 inhibition by siRNA strongly diminished IDO, IL-10, TGF-beta in metformin-treated Ad-MSCs.	Metformin	70-79	interleukin 10	Mus musculus	51-56
32189544-9	2020	Furthermore, 50mg/kg metformin markedly down-regulated the expression of proinflammatory cytokines (TNF-alpha and IL-1beta) and ER stress related genes (ATF4, ATF6, XBP1, Grp78 and CHOP) in rotenone-induced PD mice.	Metformin	21-30	tumor necrosis factor	Mus musculus	100-109
32189544-9	2020	Furthermore, 50mg/kg metformin markedly down-regulated the expression of proinflammatory cytokines (TNF-alpha and IL-1beta) and ER stress related genes (ATF4, ATF6, XBP1, Grp78 and CHOP) in rotenone-induced PD mice.	Metformin	21-30	activating transcription factor 4	Mus musculus	153-157
32189544-9	2020	Furthermore, 50mg/kg metformin markedly down-regulated the expression of proinflammatory cytokines (TNF-alpha and IL-1beta) and ER stress related genes (ATF4, ATF6, XBP1, Grp78 and CHOP) in rotenone-induced PD mice.	Metformin	21-30	X-box binding protein 1	Mus musculus	165-169
32189544-9	2020	Furthermore, 50mg/kg metformin markedly down-regulated the expression of proinflammatory cytokines (TNF-alpha and IL-1beta) and ER stress related genes (ATF4, ATF6, XBP1, Grp78 and CHOP) in rotenone-induced PD mice.	Metformin	21-30	heat shock protein 5	Mus musculus	171-176
32897197-1	2020	OBJECTIVE: To clarify the molecular signaling mechanism underlying the inhibitory effect of metformin on transforming growth factor-beta1 (TGF-beta1)-stimulated collagen I production in rat biliary fibroblasts.	Metformin	92-101	transforming growth factor, beta 1	Rattus norvegicus	105-137
32897197-1	2020	OBJECTIVE: To clarify the molecular signaling mechanism underlying the inhibitory effect of metformin on transforming growth factor-beta1 (TGF-beta1)-stimulated collagen I production in rat biliary fibroblasts.	Metformin	92-101	transforming growth factor, beta 1	Rattus norvegicus	139-148
32897197-6	2020	The activated AMPK by metformin dose-dependently inhibited TGF-beta1-induced collagen I production.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	14-18
32897197-6	2020	The activated AMPK by metformin dose-dependently inhibited TGF-beta1-induced collagen I production.	Metformin	22-31	transforming growth factor, beta 1	Rattus norvegicus	59-68
32897197-8	2020	Activation of AMPK by metformin significantly reduced TGF-beta1-induced collagen I production by suppressing Smad3-driven CTGF expression (P < 0.01), and the application of Compound C reversed such changes in the fibroblasts (P < 0.01).	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	14-18
32897197-8	2020	Activation of AMPK by metformin significantly reduced TGF-beta1-induced collagen I production by suppressing Smad3-driven CTGF expression (P < 0.01), and the application of Compound C reversed such changes in the fibroblasts (P < 0.01).	Metformin	22-31	transforming growth factor, beta 1	Rattus norvegicus	54-63
32897197-8	2020	Activation of AMPK by metformin significantly reduced TGF-beta1-induced collagen I production by suppressing Smad3-driven CTGF expression (P < 0.01), and the application of Compound C reversed such changes in the fibroblasts (P < 0.01).	Metformin	22-31	SMAD family member 3	Rattus norvegicus	109-114
32897197-9	2020	CONCLUSIONS: Metformin inhibits TGF-beta1-stimulated collagen I production by activating AMPK and inhibiting Smad3- driven CTGF expression in rat biliary fibroblasts.	Metformin	13-22	transforming growth factor, beta 1	Rattus norvegicus	32-41
32897197-9	2020	CONCLUSIONS: Metformin inhibits TGF-beta1-stimulated collagen I production by activating AMPK and inhibiting Smad3- driven CTGF expression in rat biliary fibroblasts.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	89-93
32897197-9	2020	CONCLUSIONS: Metformin inhibits TGF-beta1-stimulated collagen I production by activating AMPK and inhibiting Smad3- driven CTGF expression in rat biliary fibroblasts.	Metformin	13-22	SMAD family member 3	Rattus norvegicus	109-114
32463794-2	2020	Metformin is capable of suppressing one of the molecular triggers of the proinflammatory and prothrombotic processes of urban PM air pollution, namely the mitochondrial ROS/Ca2+ release-activated Ca2+ channels (CRAC)/IL-6 cascade.	Metformin	0-9	interleukin 6	Homo sapiens	217-221
32463794-3	2020	Given the linkage between mitochondrial functionality, ion channels, and inflamm-aging, the ability of metformin to target mitochondrial electron transport and prevent ROS/CRAC-mediated IL-6 release might illuminate new therapeutic avenues to quell the raging of the cytokine and thrombotic-like storms that are the leading causes of COVID-19 morbidity and mortality in older people.	Metformin	103-112	interleukin 6	Homo sapiens	186-190
32460900-9	2020	We further show that this increase is associated with elevated ERK1/2 and Akt signalling and can be rescued by metformin treatment.	Metformin	111-120	mitogen-activated protein kinase 3	Homo sapiens	63-69
32460900-9	2020	We further show that this increase is associated with elevated ERK1/2 and Akt signalling and can be rescued by metformin treatment.	Metformin	111-120	AKT serine/threonine kinase 1	Homo sapiens	74-77
32843973-9	2020	Metformin treatment suppressed the diabetes-induced AKT/mTOR pathway activation and tumor growth.	Metformin	0-9	thymoma viral proto-oncogene 1	Mus musculus	52-55
32456272-1	2020	Insulin resistance is a central mediating factor of the metabolic syndrome (MetS), with exercise training and metformin proven antidotes to insulin resistance.	Metformin	110-119	insulin	Homo sapiens	140-147
32446297-13	2020	Oral administration of a HMG-CoA reductase inhibitor, simvastatin, or an AMPK activator, metformin, to young HFD offspring reversed maternal HFD-programmed increase in AT1R and decreases in SIRT1, PGC-1alpha and TFAM; alleviated ROS production in RVLM, and attenuated sympathoexcitation and hypertension.	Metformin	89-98	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	73-77
32446297-13	2020	Oral administration of a HMG-CoA reductase inhibitor, simvastatin, or an AMPK activator, metformin, to young HFD offspring reversed maternal HFD-programmed increase in AT1R and decreases in SIRT1, PGC-1alpha and TFAM; alleviated ROS production in RVLM, and attenuated sympathoexcitation and hypertension.	Metformin	89-98	sirtuin 1	Rattus norvegicus	190-195
32446297-13	2020	Oral administration of a HMG-CoA reductase inhibitor, simvastatin, or an AMPK activator, metformin, to young HFD offspring reversed maternal HFD-programmed increase in AT1R and decreases in SIRT1, PGC-1alpha and TFAM; alleviated ROS production in RVLM, and attenuated sympathoexcitation and hypertension.	Metformin	89-98	PPARG coactivator 1 alpha	Rattus norvegicus	197-207
32442232-17	2020	Metformin-exposed neonates were born lighter (-73.92 g, 95% CI -114.79 to -33.06 g, p < 0.001) with reduced risk of macrosomia (OR 0.60, 95% CI 0.45-0.79, p < 0.001) than insulin-exposed neonates.	Metformin	0-9	insulin	Homo sapiens	171-178
32442232-20	2020	Metformin-exposed neonates had decreased ponderal index (-0.13 kg/m3, 95% CI -0.26 to -0.00, p = 0.04) and reduced head (-0.21, 95% CI -0.39 to -0.03, p = 0.03) and chest circumferences (-0.34 cm, 95% CI -0.62 to -0.05, p = 0.02) versus the insulin-treated group.	Metformin	0-9	insulin	Homo sapiens	241-248
32455555-4	2020	In case of metformin and verapamil, organic cation transporter (OCT) 1 and 2 primarily mediate metformin distribution to the liver and its elimination into urine, whereas cytochrome P450 is responsible for the hepatic metabolism of verapamil.	Metformin	11-20	solute carrier family 22 member 1	Homo sapiens	36-76
32455555-4	2020	In case of metformin and verapamil, organic cation transporter (OCT) 1 and 2 primarily mediate metformin distribution to the liver and its elimination into urine, whereas cytochrome P450 is responsible for the hepatic metabolism of verapamil.	Metformin	95-104	solute carrier family 22 member 1	Homo sapiens	36-76
32433500-8	2020	Metformin treatment on male diabetic placental explant activated AMPK and stimulated PGC-1alpha expression, concomitant with increased H3K27 acetylation and decreased PGC-1alpha promoter methylation.	Metformin	0-9	PPARG coactivator 1 alpha	Homo sapiens	85-95
32433500-8	2020	Metformin treatment on male diabetic placental explant activated AMPK and stimulated PGC-1alpha expression, concomitant with increased H3K27 acetylation and decreased PGC-1alpha promoter methylation.	Metformin	0-9	PPARG coactivator 1 alpha	Homo sapiens	167-177
32547075-7	2020	Western blotting, cell proliferation, cell migration and invasion were used to verify that metformin enhances autophagy in GC cells through the AMPK-mTOR signalling pathway.	Metformin	91-100	mechanistic target of rapamycin kinase	Homo sapiens	149-153
32547075-13	2020	Furthermore, we verified that metformin can upregulate beclin1-mediated autophagy to inhibit GC cells through the AMPK-mTOR signalling pathway.	Metformin	30-39	mechanistic target of rapamycin kinase	Homo sapiens	119-123
32443566-2	2020	The current consensus is that metformin exerts indirect pleiotropy on core metabolic hallmarks of aging, such as the insulin/insulin-like growth factor 1 and AMP-activated protein kinase/mammalian Target Of Rapamycin signaling pathways, downstream of its primary inhibitory effect on mitochondrial respiratory complex I. Alternatively, but not mutually exclusive, metformin can exert regulatory effects on components of the biologic machinery of aging itself such as chromatin-modifying enzymes.	Metformin	30-39	mechanistic target of rapamycin kinase	Homo sapiens	187-216
32550202-10	2020	Results: Treatment with metformin/donepezil combination significantly reduced the activities of AchE, BchE as well as levels of malondialdehyde, TNF-alpha and IL-6, while the activities of SOD, GPx and catalase were significantly increased in the brain.	Metformin	24-33	tumor necrosis factor	Rattus norvegicus	145-154
32550202-10	2020	Results: Treatment with metformin/donepezil combination significantly reduced the activities of AchE, BchE as well as levels of malondialdehyde, TNF-alpha and IL-6, while the activities of SOD, GPx and catalase were significantly increased in the brain.	Metformin	24-33	interleukin 6	Rattus norvegicus	159-163
32550202-10	2020	Results: Treatment with metformin/donepezil combination significantly reduced the activities of AchE, BchE as well as levels of malondialdehyde, TNF-alpha and IL-6, while the activities of SOD, GPx and catalase were significantly increased in the brain.	Metformin	24-33	catalase	Rattus norvegicus	202-210
32202622-10	2020	While in-vitro treatment with metformin alone increased Snail and decreased Claudin 1, N-cadherin and alpha-SMA proteins, concomitant treatment with metformin and E2 increased the expression of CK 8 and Snail proteins and decreased the expression of Claudin 1, ZO-1, Slug and alpha-SMA proteins.	Metformin	30-39	actin alpha 1, skeletal muscle	Homo sapiens	102-111
32202622-10	2020	While in-vitro treatment with metformin alone increased Snail and decreased Claudin 1, N-cadherin and alpha-SMA proteins, concomitant treatment with metformin and E2 increased the expression of CK 8 and Snail proteins and decreased the expression of Claudin 1, ZO-1, Slug and alpha-SMA proteins.	Metformin	30-39	tight junction protein 1	Homo sapiens	261-265
32202622-10	2020	While in-vitro treatment with metformin alone increased Snail and decreased Claudin 1, N-cadherin and alpha-SMA proteins, concomitant treatment with metformin and E2 increased the expression of CK 8 and Snail proteins and decreased the expression of Claudin 1, ZO-1, Slug and alpha-SMA proteins.	Metformin	30-39	actin alpha 1, skeletal muscle	Homo sapiens	276-285
32202622-10	2020	While in-vitro treatment with metformin alone increased Snail and decreased Claudin 1, N-cadherin and alpha-SMA proteins, concomitant treatment with metformin and E2 increased the expression of CK 8 and Snail proteins and decreased the expression of Claudin 1, ZO-1, Slug and alpha-SMA proteins.	Metformin	149-158	actin alpha 1, skeletal muscle	Homo sapiens	102-111
32202622-10	2020	While in-vitro treatment with metformin alone increased Snail and decreased Claudin 1, N-cadherin and alpha-SMA proteins, concomitant treatment with metformin and E2 increased the expression of CK 8 and Snail proteins and decreased the expression of Claudin 1, ZO-1, Slug and alpha-SMA proteins.	Metformin	149-158	tight junction protein 1	Homo sapiens	261-265
32202622-10	2020	While in-vitro treatment with metformin alone increased Snail and decreased Claudin 1, N-cadherin and alpha-SMA proteins, concomitant treatment with metformin and E2 increased the expression of CK 8 and Snail proteins and decreased the expression of Claudin 1, ZO-1, Slug and alpha-SMA proteins.	Metformin	149-158	actin alpha 1, skeletal muscle	Homo sapiens	276-285
32407182-5	2020	Cell viability was reduced by 50% after 24 h. Data showed that metformin treatment down-regulated YAP and TAZ (p = .002) expressions and enhanced YAP phosphorylation (p < .001).	Metformin	63-72	tafazzin, phospholipid-lysophospholipid transacylase	Homo sapiens	106-109
32407182-8	2020	This study showed the effects of metformin on the inhibition of oncogenic YAP and TAZ in the proliferation of melanoma cells.	Metformin	33-42	tafazzin, phospholipid-lysophospholipid transacylase	Homo sapiens	82-85
32483456-12	2020	However, we find that metformin-stimulated aPKC-CBP pathway decreases Mgll expression to recover these deficits in 3xTg-AD.	Metformin	22-31	protein kinase C, zeta	Mus musculus	43-47
32523353-10	2020	Metformin decreased the UCA1 expression and further inhibited the proliferation and promoted the apoptosis of the colon cancer cells, which were associated with inactivation of the PI3K/AKT and ERK signaling pathways in vitro and in the tumor tissues obtained from the mice.	Metformin	0-9	thymoma viral proto-oncogene 1	Mus musculus	186-189
32523353-10	2020	Metformin decreased the UCA1 expression and further inhibited the proliferation and promoted the apoptosis of the colon cancer cells, which were associated with inactivation of the PI3K/AKT and ERK signaling pathways in vitro and in the tumor tissues obtained from the mice.	Metformin	0-9	mitogen-activated protein kinase 1	Mus musculus	194-197
32518807-9	2020	After metformin treatment, expression of interleukin 6 (IL-6), TNF-alpha, and IL-1beta were significantly downregulated in RA-FLSs; however, increased expression of p-AMPK-alpha1, protein kinase A (PKA)-alpha1, and HAPLN1 (hyaluronan and proteoglycan link protein 1) was observed.	Metformin	6-15	interleukin 6	Homo sapiens	41-54
32518807-9	2020	After metformin treatment, expression of interleukin 6 (IL-6), TNF-alpha, and IL-1beta were significantly downregulated in RA-FLSs; however, increased expression of p-AMPK-alpha1, protein kinase A (PKA)-alpha1, and HAPLN1 (hyaluronan and proteoglycan link protein 1) was observed.	Metformin	6-15	interleukin 6	Homo sapiens	56-60
32518807-9	2020	After metformin treatment, expression of interleukin 6 (IL-6), TNF-alpha, and IL-1beta were significantly downregulated in RA-FLSs; however, increased expression of p-AMPK-alpha1, protein kinase A (PKA)-alpha1, and HAPLN1 (hyaluronan and proteoglycan link protein 1) was observed.	Metformin	6-15	tumor necrosis factor	Homo sapiens	63-72
32454819-0	2020	SLC22A1 rs622342 Polymorphism Predicts Insulin Resistance Improvement in Patients with Type 2 Diabetes Mellitus Treated with Metformin: A Cross-Sectional Study.	Metformin	125-134	solute carrier family 22 member 1	Homo sapiens	0-7
32454819-0	2020	SLC22A1 rs622342 Polymorphism Predicts Insulin Resistance Improvement in Patients with Type 2 Diabetes Mellitus Treated with Metformin: A Cross-Sectional Study.	Metformin	125-134	insulin	Homo sapiens	39-46
32454819-1	2020	Background: Metformin is the most widely used oral antidiabetic agent and can reduce insulin resistance (IR) effectively.	Metformin	12-21	insulin	Homo sapiens	85-92
32454819-2	2020	Organic cation transporter 1 (encoded by SLC22A1) is responsible for the transport of metformin, and ataxia-telangiectasia-mutated (ATM) is a gene relating to the DNA repair and cell cycle control.	Metformin	86-95	solute carrier family 22 member 1	Homo sapiens	0-28
32454819-2	2020	Organic cation transporter 1 (encoded by SLC22A1) is responsible for the transport of metformin, and ataxia-telangiectasia-mutated (ATM) is a gene relating to the DNA repair and cell cycle control.	Metformin	86-95	solute carrier family 22 member 1	Homo sapiens	41-48
32454819-3	2020	The aim of this study was to evaluate if the genetic variants in SLC22A1 rs622342 and ATM rs11212617 could be effective predictors of islet function improvement in patients with type 2 diabetes mellitus (T2DM) on metformin treatment.	Metformin	213-222	solute carrier family 22 member 1	Homo sapiens	65-72
32454819-12	2020	Conclusions: The variant of rs622342 could be a predictor of insulin sensitivity in patients with T2DM treated with metformin.	Metformin	116-125	insulin	Homo sapiens	61-68
32312819-7	2020	Furthermore, glutamine deprivation, as well as the antimetabolic drugs 2-deoxyglucose and metformin, also promoted the release of IL-6 and IL-8.	Metformin	90-99	interleukin 6	Homo sapiens	130-134
32312819-7	2020	Furthermore, glutamine deprivation, as well as the antimetabolic drugs 2-deoxyglucose and metformin, also promoted the release of IL-6 and IL-8.	Metformin	90-99	C-X-C motif chemokine ligand 8	Homo sapiens	139-143
32404018-7	2020	In addition, metformin significantly (p < .05) reduced hyperglycemia, glycated hemoglobin (HbA1 c), malondialdehyde (MDA), high sensitivity C-reactive protein (hs-CRP), and interleukin-6 blood levels induced by diabetes.	Metformin	13-22	C-reactive protein	Rattus norvegicus	140-158
32404018-7	2020	In addition, metformin significantly (p < .05) reduced hyperglycemia, glycated hemoglobin (HbA1 c), malondialdehyde (MDA), high sensitivity C-reactive protein (hs-CRP), and interleukin-6 blood levels induced by diabetes.	Metformin	13-22	C-reactive protein	Rattus norvegicus	163-166
32404018-7	2020	In addition, metformin significantly (p < .05) reduced hyperglycemia, glycated hemoglobin (HbA1 c), malondialdehyde (MDA), high sensitivity C-reactive protein (hs-CRP), and interleukin-6 blood levels induced by diabetes.	Metformin	13-22	interleukin 6	Rattus norvegicus	173-186
32249610-1	2020	Metformin, an AMP-activated protein kinase (AMPK) activator, has been shown in previous studies to reduce kidney fibrosis in different models of experimental chronic kidney disease (CKD).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	14-42
32249610-1	2020	Metformin, an AMP-activated protein kinase (AMPK) activator, has been shown in previous studies to reduce kidney fibrosis in different models of experimental chronic kidney disease (CKD).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	44-48
32249610-9	2020	In addition, treatment with metformin was also able to activate kidney AMPK and therefore improve mitochondrial biogenesis.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	71-75
32249610-10	2020	It was concluded that metformin can arrest the progression of established kidney disease in the Nx model, likely via the activation of AMPK.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	135-139
32495169-0	2020	Restoration of beta-Adrenergic Signaling and Activity of Akt-Kinase and AMP-Activated Protein Kinase with Metformin in the Myocardium of Diabetic Rats.	Metformin	106-115	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	72-100
32251713-3	2020	Metformin inhibited QGP-1 cell proliferation in a dose- and time-dependent manner, at concentrations similar to those achievable in treated patients (-31 +- 12%, p < 0.05 vs basal at 100 muM).	Metformin	0-9	latexin	Homo sapiens	187-190
32251713-5	2020	Both octreotide and metformin induced AIP up-regulation.	Metformin	20-29	aryl hydrocarbon receptor interacting protein	Homo sapiens	38-41
32251713-6	2020	AIP silencing abolished the reduction of mTOR phosphorylation induced by metformin and octreotide.	Metformin	73-82	aryl hydrocarbon receptor interacting protein	Homo sapiens	0-3
32251713-6	2020	AIP silencing abolished the reduction of mTOR phosphorylation induced by metformin and octreotide.	Metformin	73-82	mechanistic target of rapamycin kinase	Homo sapiens	41-45
32251713-7	2020	Moreover, metformin decreased HSP70, increased Zac1 and AhR expression; these effects were abolished in AIP silenced QGP-1 cells.	Metformin	10-19	aryl hydrocarbon receptor interacting protein	Homo sapiens	104-107
32251713-8	2020	In conclusion, metformin acts as an anticancer agent in PAN-NET cells, its activity is mediated by AIP and its interacting proteins.	Metformin	15-24	aryl hydrocarbon receptor interacting protein	Homo sapiens	99-102
32495169-2	2020	Metformin normalized the ratio of adenylyl cyclase effects of beta1/2- and beta3-agonists in the myocardial membranes, that is reduced in DM2, and restored phosphorylation of Akt-kinase by Ser473 and AMPK by Thr172 in the myocardium of diabetic rats.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	200-204
32146661-6	2020	By calculating the light screening effect of environmental factors, it is found that the presence of NO3- and Cl- had a greater excitation effect on ROS than the screening effect, and generally promoted the photolysis rates of MEF from 90.3 to 193.5% and from 16.1 to 80.6% during the 6-h reaction process, respectively.	Metformin	227-230	NBL1, DAN family BMP antagonist	Homo sapiens	101-104
32092034-7	2020	We observed that dapagliflozin or metformin mitigated the enhanced expression of renal gluconeogenic enzymes, PEPCK, G6Pase and FBPase, as well as improved glucose tolerance and renal function in obese rats.	Metformin	34-43	fructose-bisphosphatase 2	Rattus norvegicus	128-134
32495867-0	2020	Metformin reduces pancreatic cancer cell proliferation and increases apoptosis through MTOR signaling pathway and its dose-effect relationship.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	87-91
32495867-10	2020	Moreover, Metformin treatment groups (0, 20, and 40 mM) had more apoptotic PANC-1 cells, higher expression levels of pro-apoptosis proteins Caspase-3 and Bax and lower expression levels of anti-apoptosis protein Bcl-2 and the mTOR pathway-related proteins PI3K, p-Akt, and p-mTOR in cells than Control group (p<0.05).	Metformin	10-19	caspase 3	Homo sapiens	140-149
32495867-10	2020	Moreover, Metformin treatment groups (0, 20, and 40 mM) had more apoptotic PANC-1 cells, higher expression levels of pro-apoptosis proteins Caspase-3 and Bax and lower expression levels of anti-apoptosis protein Bcl-2 and the mTOR pathway-related proteins PI3K, p-Akt, and p-mTOR in cells than Control group (p<0.05).	Metformin	10-19	BCL2 associated X, apoptosis regulator	Homo sapiens	154-157
32495867-10	2020	Moreover, Metformin treatment groups (0, 20, and 40 mM) had more apoptotic PANC-1 cells, higher expression levels of pro-apoptosis proteins Caspase-3 and Bax and lower expression levels of anti-apoptosis protein Bcl-2 and the mTOR pathway-related proteins PI3K, p-Akt, and p-mTOR in cells than Control group (p<0.05).	Metformin	10-19	BCL2 apoptosis regulator	Homo sapiens	212-217
32495867-10	2020	Moreover, Metformin treatment groups (0, 20, and 40 mM) had more apoptotic PANC-1 cells, higher expression levels of pro-apoptosis proteins Caspase-3 and Bax and lower expression levels of anti-apoptosis protein Bcl-2 and the mTOR pathway-related proteins PI3K, p-Akt, and p-mTOR in cells than Control group (p<0.05).	Metformin	10-19	mechanistic target of rapamycin kinase	Homo sapiens	226-230
32495867-10	2020	Moreover, Metformin treatment groups (0, 20, and 40 mM) had more apoptotic PANC-1 cells, higher expression levels of pro-apoptosis proteins Caspase-3 and Bax and lower expression levels of anti-apoptosis protein Bcl-2 and the mTOR pathway-related proteins PI3K, p-Akt, and p-mTOR in cells than Control group (p<0.05).	Metformin	10-19	AKT serine/threonine kinase 1	Homo sapiens	264-267
32495867-10	2020	Moreover, Metformin treatment groups (0, 20, and 40 mM) had more apoptotic PANC-1 cells, higher expression levels of pro-apoptosis proteins Caspase-3 and Bax and lower expression levels of anti-apoptosis protein Bcl-2 and the mTOR pathway-related proteins PI3K, p-Akt, and p-mTOR in cells than Control group (p<0.05).	Metformin	10-19	mechanistic target of rapamycin kinase	Homo sapiens	275-279
32495867-11	2020	CONCLUSIONS: Metformin modulates the mTOR signaling pathway to reduce the proliferation of pancreatic cancer cell, but increase their apoptosis.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	37-41
32471963-9	2020	RESULT: Our study showed that NIH 3T3 and RAW 264.7 coculture treated with metformin has higher collagen expression, but lower IL-6 mRNA expression compares to those on co-culture without treatment.	Metformin	75-84	interleukin 6	Mus musculus	127-131
32127372-6	2020	Uptake of the OCT1 substrate metformin in SCHH was decreased by T0901317 treatment.	Metformin	29-38	solute carrier family 22 member 1	Homo sapiens	14-18
32127372-7	2020	Effects of decreased OCT1 levels on metformin were simulated using a physiologically-based pharmacokinetic (PBPK) model.	Metformin	36-45	solute carrier family 22 member 1	Homo sapiens	21-25
32471963-10	2020	CONCLUSION: Metformin increases fibrosis markers in LPS and high glucose-induced NIH 3T3 and RAW 264.7 coculture despite its ability to improve IL-6 mRNA expression.	Metformin	12-21	interleukin 6	Mus musculus	144-148
32410849-0	2020	Pioglitazone Metformin Complex Improves Polycystic Ovary Syndrome Comorbid Psychological Distress via Inhibiting NLRP3 Inflammasome Activation: A Prospective Clinical Study.	Metformin	13-22	NLR family pyrin domain containing 3	Homo sapiens	113-118
32203160-6	2020	Together, our results suggest that p21WAF1/CIP1 overexpression is essential in the development of protumorigenic microenvironment induced by NCOA5 deficiency and metformin prevents HCC development via alleviating p21WAF1/CIP1 overexpression and protumorigenic microenvironment.	Metformin	162-171	cyclin dependent kinase inhibitor 1A	Homo sapiens	221-225
32330868-0	2020	Metformin protects against intestinal ischemia-reperfusion injury and cell pyroptosis via TXNIP-NLRP3-GSDMD pathway.	Metformin	0-9	thioredoxin interacting protein	Homo sapiens	90-95
32330868-0	2020	Metformin protects against intestinal ischemia-reperfusion injury and cell pyroptosis via TXNIP-NLRP3-GSDMD pathway.	Metformin	0-9	NLR family pyrin domain containing 3	Homo sapiens	96-101
32330868-11	2020	Importantly, Metformin reduced pyroptosis-related proteins, including NLRP3, cleaved caspase-1, and the N-terminus of GSDMD.	Metformin	13-22	NLR family pyrin domain containing 3	Homo sapiens	70-75
32330868-11	2020	Importantly, Metformin reduced pyroptosis-related proteins, including NLRP3, cleaved caspase-1, and the N-terminus of GSDMD.	Metformin	13-22	caspase 1	Homo sapiens	85-94
32330868-13	2020	We also discovered that Metformin suppressed the expression of TXNIP and the interaction between TXNIP and NLRP3.	Metformin	24-33	thioredoxin interacting protein	Homo sapiens	63-68
32330868-13	2020	We also discovered that Metformin suppressed the expression of TXNIP and the interaction between TXNIP and NLRP3.	Metformin	24-33	thioredoxin interacting protein	Homo sapiens	97-102
32330868-13	2020	We also discovered that Metformin suppressed the expression of TXNIP and the interaction between TXNIP and NLRP3.	Metformin	24-33	NLR family pyrin domain containing 3	Homo sapiens	107-112
32330868-15	2020	In conclusion, we believe that Metformin protects against intestinal I/R injury in a TXNIP-NLRP3-GSDMD-dependent manner.	Metformin	31-40	thioredoxin interacting protein	Homo sapiens	85-90
32330868-15	2020	In conclusion, we believe that Metformin protects against intestinal I/R injury in a TXNIP-NLRP3-GSDMD-dependent manner.	Metformin	31-40	NLR family pyrin domain containing 3	Homo sapiens	91-96
32327628-8	2020	Metformin was significantly superior to placebo with regards to decrease in body weight, body mass index, glycated hemoglobin A1c, fasting insulin, and homeostasis model assessment-insulin resistance (P = 0.002-0.01), but not regarding changes in waist circumference, waist-to-hip rate, leptin, fasting glucose, and blood pressure (P = 0.07-0.33).	Metformin	0-9	insulin	Homo sapiens	139-146
32327628-8	2020	Metformin was significantly superior to placebo with regards to decrease in body weight, body mass index, glycated hemoglobin A1c, fasting insulin, and homeostasis model assessment-insulin resistance (P = 0.002-0.01), but not regarding changes in waist circumference, waist-to-hip rate, leptin, fasting glucose, and blood pressure (P = 0.07-0.33).	Metformin	0-9	insulin	Homo sapiens	181-188
32368117-13	2020	Plasma SFRP5 levels were increased after 12-week metformin treatment (201.0+-34.8 pg/mL vs 213.1+-34.4 pg/mL, P<0.05), while insulin resistance was alleviated (ln(HOMA-IR): 1.35+-0.55 vs 1.07+-0.49, P<0.01).	Metformin	49-58	secreted frizzled related protein 5	Homo sapiens	7-12
32350854-10	2020	When cells were pretreated with metformin, caveolin-1 expression was induced and promoted T-DM1 uptake and enhanced cell toxicity.	Metformin	32-41	caveolin 1	Homo sapiens	43-53
32368014-7	2020	Upregulated Bcl-2 and downregulated Bax were observed in propofol-treated HT-22 cells following metformin administration.	Metformin	96-105	B cell leukemia/lymphoma 2	Mus musculus	12-17
32377293-0	2020	Metformin Ameliorates Abeta Pathology by Insulin-Degrading Enzyme in a Transgenic Mouse Model of Alzheimer"s Disease.	Metformin	0-9	insulin degrading enzyme	Mus musculus	41-65
32377293-5	2020	In this study, we tried to figure out whether metformin could activate insulin-degrading enzyme (IDE) to ameliorate Abeta-induced pathology.	Metformin	46-55	insulin degrading enzyme	Mus musculus	71-95
32377293-5	2020	In this study, we tried to figure out whether metformin could activate insulin-degrading enzyme (IDE) to ameliorate Abeta-induced pathology.	Metformin	46-55	insulin degrading enzyme	Mus musculus	97-100
32377293-9	2020	Metformin decreased oxidative stress (malondialdehyde and superoxide dismutase) and neuroinflammation (IL-1beta and IL-6) in APP/PS1 mice.	Metformin	0-9	interleukin 6	Mus musculus	116-120
32377293-13	2020	Metformin increased the protein levels of p-AMPK and IDE in the brain of APP/PS1 mice, which might be the key mechanism of metformin on AD.	Metformin	0-9	insulin degrading enzyme	Mus musculus	53-56
32377293-13	2020	Metformin increased the protein levels of p-AMPK and IDE in the brain of APP/PS1 mice, which might be the key mechanism of metformin on AD.	Metformin	123-132	insulin degrading enzyme	Mus musculus	53-56
32362869-7	2020	The expressions of sirtuin 1 (SIRT1) and hypoxia-inducible factor 1-alpha (HIF-1alpha) in diabetic testes were also upregulated by metformin or LBP treatment.	Metformin	131-140	sirtuin 1	Rattus norvegicus	19-28
32362869-7	2020	The expressions of sirtuin 1 (SIRT1) and hypoxia-inducible factor 1-alpha (HIF-1alpha) in diabetic testes were also upregulated by metformin or LBP treatment.	Metformin	131-140	sirtuin 1	Rattus norvegicus	30-35
32248762-11	2020	Metformin may exert its effects by normalizing myocardial AMPK and mammalian target-of-rapamycin activities, improving fatty acid oxidation, and reducing oxidative stress.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	67-96
32382466-12	2020	After the second lengthy dialysis, the patient"s condition improved significantly and he was discharged on hospital day 12, with the diagnosis of metformin-associated lactic acidosis (MALA) in the setting of acute tubular necrosis from gastrointestinal fluid loss accompanied by the continued use of an angiotensin-converting enzyme inhibitor.	Metformin	146-155	angiotensin I converting enzyme	Homo sapiens	303-332
32004528-10	2020	In conclusion, MET and IFX ameliorated the TNF-alpha worsening effect on IR in rat renal tissues by regulating insulin signaling.	Metformin	15-18	tumor necrosis factor	Rattus norvegicus	43-52
32017937-4	2020	Metformin is the most often used oral glucose-lowering agent; its beneficial properties include lowering insulin resistance, weight reduction and cardioprotection.	Metformin	0-9	insulin	Homo sapiens	105-112
31789625-9	2020	Metformin downregulated the levels of p-NF-kappaB p65, p-Erk1/2, p-AKT, and p-mTOR proteins.	Metformin	0-9	mitogen-activated protein kinase 3	Homo sapiens	57-63
31789625-9	2020	Metformin downregulated the levels of p-NF-kappaB p65, p-Erk1/2, p-AKT, and p-mTOR proteins.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	67-70
31789625-9	2020	Metformin downregulated the levels of p-NF-kappaB p65, p-Erk1/2, p-AKT, and p-mTOR proteins.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	78-82
31789625-12	2020	Our discovery revealed that metformin, via increasing the expression of microRNA-7 mediated by AMPK, regulates the AKT/mTOR, MAPK/Erk, and NF-kappaB signaling pathways, thereby suppressing A549 cell growth, migration, and invasion.	Metformin	28-37	AKT serine/threonine kinase 1	Homo sapiens	115-118
31789625-12	2020	Our discovery revealed that metformin, via increasing the expression of microRNA-7 mediated by AMPK, regulates the AKT/mTOR, MAPK/Erk, and NF-kappaB signaling pathways, thereby suppressing A549 cell growth, migration, and invasion.	Metformin	28-37	mechanistic target of rapamycin kinase	Homo sapiens	119-123
31789625-12	2020	Our discovery revealed that metformin, via increasing the expression of microRNA-7 mediated by AMPK, regulates the AKT/mTOR, MAPK/Erk, and NF-kappaB signaling pathways, thereby suppressing A549 cell growth, migration, and invasion.	Metformin	28-37	mitogen-activated protein kinase 3	Homo sapiens	125-129
31789625-12	2020	Our discovery revealed that metformin, via increasing the expression of microRNA-7 mediated by AMPK, regulates the AKT/mTOR, MAPK/Erk, and NF-kappaB signaling pathways, thereby suppressing A549 cell growth, migration, and invasion.	Metformin	28-37	mitogen-activated protein kinase 1	Homo sapiens	130-133
32014566-9	2020	Concomitantly, the hippocampal synaptic density and MAP2 and PSD95 immunoreactivity were significantly reduced by sevoflurane exposure but showed partial recovery in the metformin-pretreated group.	Metformin	170-179	microtubule-associated protein 2	Mus musculus	52-56
31821581-0	2020	Metformin alleviates renal injury in diabetic rats by inducing Sirt1/FoxO1 autophagic signal axis.	Metformin	0-9	sirtuin 1	Rattus norvegicus	63-68
31821581-6	2020	Sirt1 inhibitor EX527 and metformin were used to observe whether the protective effect of metformin on DN kidney was achieved through Sirt1/FoxO1 autophagic signaling pathway.	Metformin	90-99	sirtuin 1	Rattus norvegicus	134-139
31821581-8	2020	Sirt1 inhibitor could block the protective effect of metformin on kidney of diabetic rats, suggesting that metformin could alleviate kidney injury in diabetic rats by inducing Sirt1/FoxO1 autophagy signal axis.	Metformin	53-62	sirtuin 1	Rattus norvegicus	0-5
31821581-8	2020	Sirt1 inhibitor could block the protective effect of metformin on kidney of diabetic rats, suggesting that metformin could alleviate kidney injury in diabetic rats by inducing Sirt1/FoxO1 autophagy signal axis.	Metformin	53-62	sirtuin 1	Rattus norvegicus	176-181
31821581-8	2020	Sirt1 inhibitor could block the protective effect of metformin on kidney of diabetic rats, suggesting that metformin could alleviate kidney injury in diabetic rats by inducing Sirt1/FoxO1 autophagy signal axis.	Metformin	107-116	sirtuin 1	Rattus norvegicus	0-5
31821581-8	2020	Sirt1 inhibitor could block the protective effect of metformin on kidney of diabetic rats, suggesting that metformin could alleviate kidney injury in diabetic rats by inducing Sirt1/FoxO1 autophagy signal axis.	Metformin	107-116	sirtuin 1	Rattus norvegicus	176-181
31821581-9	2020	So metformin could alleviate renal injury in diabetic rats, which may be achieved by regulating Sirt1/FoxO1 autophagic signaling pathway and inducing renal autophagy.	Metformin	3-12	sirtuin 1	Rattus norvegicus	96-101
32022731-5	2020	Also, the homeostasis model assessment-insulin resistance has been independently associated with disease-free survival, suggesting that improving the glycemic control may improve the prognosis in this group of patients.Epidemiological studies revealed that cancer patients with diabetes mellitus have less cancer-related mortality after antiglycemic treatment, opening the option to include antiglycolytic agents, such as metformin, in the therapeutic plan.	Metformin	422-431	insulin	Homo sapiens	39-46
31802616-0	2020	Effects of Treatment With Metformin and/or Sitagliptin on Beta-cell Function and Insulin Resistance in Prediabetic Women With Previous Gestational Diabetes.	Metformin	26-35	insulin	Homo sapiens	81-88
31802616-6	2020	MET+SITA gave a greater increase of first phase(2-10 min) insulin secretion and arginine-stimulated response (720.3+-299.0 to 995.5+-370.3 pmol/l and 3.2+-0.6 to 4.8+-1.0 pmol/min, respectively, both p&lt;0.05) compared to MET and SITA.	Metformin	0-3	insulin	Homo sapiens	58-65
31802616-7	2020	Similarly, MET+SITA was more effective in increasing OGTT-based glucose sensitivity (55.7+-11.3 to 108+-56.2 pmol x min-1 m-2 x mM-1 ; p=0.04) and insulin sensitivity (M/I: 2.2+-0.5 to 4.6+-1.3 mg/kg/min/muIU/min/ml; p=0.04; Matsuda Index (SI): 3.1+-0.4 to 5.7+-1.1; p=0.03) as compared to either MET or SITA.	Metformin	11-14	insulin	Homo sapiens	147-154
31802616-10	2020	CONCLUSION: This study shows that MET+SITA is superior to SITA and MET monotherapy on beta-cell function and insulin sensitivity improvement in IGR women with previous GDM and it may offer a potential pharmacologic intervention to reduce risk of T2D in this high-risk population.	Metformin	34-37	insulin	Homo sapiens	109-116
32368117-14	2020	Conclusion: Metformin reduced circulating levels of secreted frizzled-related protein 5 and improved pathophysiological parameters of T2DM.	Metformin	12-21	secreted frizzled related protein 5	Homo sapiens	52-87
31742716-6	2020	Metformin significantly increased insulin sensitivity (51%) as well as disposition index (97%) and decreased mixed-meal tolerance test peak glucose concentrations (8%) in women with gestational diabetes mellitus after adjustment for gestational age-dependent effects; however, in women with T2DM metformin only significantly affected peak glucose concentrations (22%) and had no significant effect on any other parameters.	Metformin	0-9	insulin	Homo sapiens	34-41
32004509-0	2020	Metformin rescues Parkin protein expression and mitophagy in high glucose-challenged human renal epithelial cells by inhibiting NF-kappaB via PP2A activation.	Metformin	0-9	nuclear factor kappa B subunit 1	Homo sapiens	128-137
32004509-10	2020	Metformin increased PRKN gene transcription while reducednuclear factor kappa B (NF-kappaB) activation but not that of p53 or ATF4.	Metformin	0-9	nuclear factor kappa B subunit 1	Homo sapiens	81-90
32243405-2	2020	Studies have demonstrated that metformin can reduce liver glucose in PCOS, lower testosterone levels and increase peripheral insulin sensitivity.	Metformin	31-40	insulin	Homo sapiens	125-132
32258099-12	2020	Further study revealed that metformin may attenuate the phosphorylation of the Stat3 and the Bcl-2 expression, which was restored by IL-6 partly in EC109 cells but not HEECs.	Metformin	28-37	signal transducer and activator of transcription 3	Homo sapiens	79-84
32138474-3	2020	Metformin can be used safely when the estimated glomerular filtration rate (eGFR) is >= 45 mL/min/1.73 m2.	Metformin	0-9	CD59 molecule (CD59 blood group)	Homo sapiens	94-99
32138474-4	2020	If the eGFR is between 30 and 44 mL/min/1.73 m2, metformin treatment should not be started.	Metformin	49-58	CD59 molecule (CD59 blood group)	Homo sapiens	36-41
32138474-6	2020	Metformin is contraindicated when the eGFR is < 30 mL/min/1.73 m2.	Metformin	0-9	CD59 molecule (CD59 blood group)	Homo sapiens	54-59
32138474-8	2020	During procedures involving intravenous administration of ICM, metformin should be discontinued starting the day of the procedures and up to 48 hours postprocedures if the eGFR is < 60 mL/min/1.73 m2.	Metformin	63-72	CD59 molecule (CD59 blood group)	Homo sapiens	188-193
32207597-0	2021	Study of effect of metformin on expression levels of TNF-alpha and IL-18 in animal models of polycystic ovary syndrome.	Metformin	19-28	tumor necrosis factor	Homo sapiens	53-62
32258099-12	2020	Further study revealed that metformin may attenuate the phosphorylation of the Stat3 and the Bcl-2 expression, which was restored by IL-6 partly in EC109 cells but not HEECs.	Metformin	28-37	BCL2 apoptosis regulator	Homo sapiens	93-98
32258099-12	2020	Further study revealed that metformin may attenuate the phosphorylation of the Stat3 and the Bcl-2 expression, which was restored by IL-6 partly in EC109 cells but not HEECs.	Metformin	28-37	interleukin 6	Homo sapiens	133-137
32258099-15	2020	Therefore, the Stat3/Bcl-2 pathway-mediated apoptosis underlies the cell-type-specific drug sensitivity, suggesting metformin possesses a therapeutic activity and selectivity on esophageal cancer.	Metformin	116-125	signal transducer and activator of transcription 3	Homo sapiens	15-20
32258099-15	2020	Therefore, the Stat3/Bcl-2 pathway-mediated apoptosis underlies the cell-type-specific drug sensitivity, suggesting metformin possesses a therapeutic activity and selectivity on esophageal cancer.	Metformin	116-125	BCL2 apoptosis regulator	Homo sapiens	21-26
31874168-6	2020	We further indicated that treatment with the FDA-approved drug metformin normalized the hyperactive Akt-mTOR signaling, and attenuated pain-related hypersensitivity in Cntnap2-/- mice.	Metformin	63-72	thymoma viral proto-oncogene 1	Mus musculus	100-103
32001268-8	2020	The anti-diabetic effects of SPIONs may be mediated through its effect on (i) hepatic peroxisome proliferator-activated receptor gamma coactivator 1-alpha content, which induced by SPIONs treatment in a dose-dependent manner, (ii) adipocytokines as SPIONs treated diabetic rats showed significantly higher levels of adiponectin and lower retinol binding protein 4 compared to untreated diabetic rats, (iii) lipid profile as SPIONs treatment significantly corrected the lipid profile in a dose-dependent manner and to a similar extent as metformin or even better.	Metformin	537-546	PPARG coactivator 1 alpha	Rattus norvegicus	86-154
32157481-8	2021	Effective modulation of some heart failure-related outcomes with metformin treatment was related to its beneficial effects in ameliorating insulin resistance and blocking pro-inflammatory markers such as the aging-associated cytokine CCL11 (C-C motif chemokine ligand 11).	Metformin	65-74	insulin	Homo sapiens	139-146
32183017-4	2020	We have also evaluated the ability of metformin (Metf), an antidiabetic type II compound that acts through inhibition of the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway to sensitize resistant cells to PDT.	Metformin	38-47	mechanistic target of rapamycin kinase	Homo sapiens	161-190
32183017-4	2020	We have also evaluated the ability of metformin (Metf), an antidiabetic type II compound that acts through inhibition of the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway to sensitize resistant cells to PDT.	Metformin	38-47	mechanistic target of rapamycin kinase	Homo sapiens	192-196
32157481-8	2021	Effective modulation of some heart failure-related outcomes with metformin treatment was related to its beneficial effects in ameliorating insulin resistance and blocking pro-inflammatory markers such as the aging-associated cytokine CCL11 (C-C motif chemokine ligand 11).	Metformin	65-74	C-C motif chemokine ligand 11	Homo sapiens	234-239
32157481-8	2021	Effective modulation of some heart failure-related outcomes with metformin treatment was related to its beneficial effects in ameliorating insulin resistance and blocking pro-inflammatory markers such as the aging-associated cytokine CCL11 (C-C motif chemokine ligand 11).	Metformin	65-74	C-C motif chemokine ligand 11	Homo sapiens	241-270
31977586-11	2020	Taken together, metformin mitigates LPS-induced depressive-like behavior in mice by regulating the expression level of Lcn-2 and inflammation-related molecules, including IL-1beta, IL-6 and vWF.Video abstract: http://links.lww.com/WNR/A568.	Metformin	16-25	interleukin 6	Mus musculus	181-185
32156062-4	2020	A multivariate analysis showed that exposure to either metformin or to insulin was associated with a lower risk of LC-specific mortality, and this approached statistical significance (HR 0.82, 95% CI 0.72-92 for metformin and HR 0.65, 95% CI 0.44-95 for insulin).	Metformin	55-64	insulin	Homo sapiens	254-261
32156062-4	2020	A multivariate analysis showed that exposure to either metformin or to insulin was associated with a lower risk of LC-specific mortality, and this approached statistical significance (HR 0.82, 95% CI 0.72-92 for metformin and HR 0.65, 95% CI 0.44-95 for insulin).	Metformin	212-221	insulin	Homo sapiens	71-78
31874705-3	2020	Metformin is a first-line medication for treatment of type 2 diabetes which is known to activate AMPK and induce autophagy through the inhibition of mammalian target of rapamycin (mTOR1) signaling.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	149-178
32194991-3	2020	Although metformin reportedly inhibits mature IL-1beta secretion via NLRP3 inflammasome in macrophages of T2DM patients, it remains unclear whether it affects skin inflammation in psoriasis.	Metformin	9-18	NLR family pyrin domain containing 3	Homo sapiens	69-74
32194991-5	2020	This stimulation induced the upregulation of pro-IL-1beta mRNA and protein levels, and subsequently mature IL-1beta secretion, which was inhibited by metformin treatment.	Metformin	150-159	interleukin 1 beta	Homo sapiens	45-57
32194991-6	2020	To further reveal the mechanism involved, we examined how metformin treatment affected NLRP3 inflammasome activated by TNF-alpha and IL-17A stimulation.	Metformin	58-67	NLR family pyrin domain containing 3	Homo sapiens	87-92
32194991-6	2020	To further reveal the mechanism involved, we examined how metformin treatment affected NLRP3 inflammasome activated by TNF-alpha and IL-17A stimulation.	Metformin	58-67	tumor necrosis factor	Homo sapiens	119-128
32194991-8	2020	Furthermore, inhibitors of AMPK and SIRT1 abrogated the downregulation of caspase-1 induced by metformin treatment, indicating that AMPK and SIRT1 are essential for the inhibitory effect on NLRP3 inflammasome in NHEKs.	Metformin	95-104	caspase 1	Homo sapiens	74-83
32194991-8	2020	Furthermore, inhibitors of AMPK and SIRT1 abrogated the downregulation of caspase-1 induced by metformin treatment, indicating that AMPK and SIRT1 are essential for the inhibitory effect on NLRP3 inflammasome in NHEKs.	Metformin	95-104	NLR family pyrin domain containing 3	Homo sapiens	190-195
31654523-12	2020	CONCLUSIONS: In an increasing but changing population of gestational diabetes women in our region, with more heredity and non-Scandinavian origin, but with fewer smokers, metabolic control has improved with maintained favorable pregnancy outcomes, with more frequent use of Metformin and substantially less use of insulin treatment.	Metformin	274-283	insulin	Homo sapiens	314-321
32194991-10	2020	Metformin treatment inhibited upregulation of IL-36gamma, CXCL1, CXCL2, CCL20, S100A7, S100A8 and S100A9 mRNA and protein levels induced by TNF-alpha and IL-17A stimulation.	Metformin	0-9	tumor necrosis factor	Homo sapiens	140-149
32355824-9	2020	All of the 10 hub genes (CCNA2, CCNB1, MAD2L1, BU1B, RACGAP1, CHEK1, BUB1, ASPM, NCAPG and TTK) have a strong association with lower overall survival in liver cancer patients and four genes (CCNA2, CCNB1, CHEK1 and BUB1) have reduced expression in metformin-treated samples.	Metformin	248-257	cyclin A2	Homo sapiens	25-30
31815765-7	2020	In addition, metformin reduced the phosphorylation of receptor tyrosine kinases, especially Tie-2, ALK, PYK, EphA4, and EphA10, as well as angiogenesis-related proteins, including RANTES, TGF-beta, and TIMP-1.	Metformin	13-22	phosphorylase kinase regulatory subunit alpha 2	Homo sapiens	104-107
31815765-7	2020	In addition, metformin reduced the phosphorylation of receptor tyrosine kinases, especially Tie-2, ALK, PYK, EphA4, and EphA10, as well as angiogenesis-related proteins, including RANTES, TGF-beta, and TIMP-1.	Metformin	13-22	transforming growth factor beta 1	Homo sapiens	188-196
31815765-7	2020	In addition, metformin reduced the phosphorylation of receptor tyrosine kinases, especially Tie-2, ALK, PYK, EphA4, and EphA10, as well as angiogenesis-related proteins, including RANTES, TGF-beta, and TIMP-1.	Metformin	13-22	TIMP metallopeptidase inhibitor 1	Homo sapiens	202-208
32355824-9	2020	All of the 10 hub genes (CCNA2, CCNB1, MAD2L1, BU1B, RACGAP1, CHEK1, BUB1, ASPM, NCAPG and TTK) have a strong association with lower overall survival in liver cancer patients and four genes (CCNA2, CCNB1, CHEK1 and BUB1) have reduced expression in metformin-treated samples.	Metformin	248-257	Rac GTPase activating protein 1	Homo sapiens	53-60
32355824-9	2020	All of the 10 hub genes (CCNA2, CCNB1, MAD2L1, BU1B, RACGAP1, CHEK1, BUB1, ASPM, NCAPG and TTK) have a strong association with lower overall survival in liver cancer patients and four genes (CCNA2, CCNB1, CHEK1 and BUB1) have reduced expression in metformin-treated samples.	Metformin	248-257	checkpoint kinase 1	Homo sapiens	62-67
32355824-9	2020	All of the 10 hub genes (CCNA2, CCNB1, MAD2L1, BU1B, RACGAP1, CHEK1, BUB1, ASPM, NCAPG and TTK) have a strong association with lower overall survival in liver cancer patients and four genes (CCNA2, CCNB1, CHEK1 and BUB1) have reduced expression in metformin-treated samples.	Metformin	248-257	cyclin A2	Homo sapiens	191-196
32355824-9	2020	All of the 10 hub genes (CCNA2, CCNB1, MAD2L1, BU1B, RACGAP1, CHEK1, BUB1, ASPM, NCAPG and TTK) have a strong association with lower overall survival in liver cancer patients and four genes (CCNA2, CCNB1, CHEK1 and BUB1) have reduced expression in metformin-treated samples.	Metformin	248-257	checkpoint kinase 1	Homo sapiens	205-210
31786336-6	2020	Metformin ameliorated palmitate-induced necrosis and apoptosis (decreased caspase-3/7 activity by 52% and 57% respectively) in HepG2 cells.	Metformin	0-9	caspase 3	Homo sapiens	74-85
31922237-0	2020	Metformin attenuates the D-galactose-induced aging process via the UPR through the AMPK/ERK1/2 signaling pathways.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	83-87
31864213-3	2020	Metformin can inhibit the PI3K/Akt signaling pathway and synergizes with Nelfinavir to inhibit the proliferation and invasion of cervical cancer cells.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	31-34
31864213-8	2020	We also found that metformin up-regulated the expression of the tumor suppressor IGFBP7 to inhibit the proliferation and invasion of cervical cancer cells.	Metformin	19-28	insulin like growth factor binding protein 7	Homo sapiens	81-87
31949084-7	2020	CONCLUSIONS: In patients with type 2 diabetes, GIP infusion on top of treatment with metformin and a long-acting GLP-1R agonist did not affect energy intake, appetite, or energy expenditure but increased plasma glucose compared with placebo.	Metformin	85-94	gastric inhibitory polypeptide	Homo sapiens	47-50
31955370-1	2020	INTRODUCTION: The aim of our study was to determine the effect of metformin administration on juvenile type 1 diabetes mellitus and atherosclerosis in apolipoprotein E null (ApoE-/-) mice and to explore the mechanism involved.	Metformin	66-75	apolipoprotein E	Mus musculus	151-167
31971473-6	2020	Consistent with our hypothesis, spinal AMPK activation with 2-deoxyglucose (2-DG) or metformin blocked 5-HT7, but not 5-HT2A receptor-induced pMF; in both cases, pMF inhibition was reversed by spinal administration of the AMPK inhibitor compound C. Thus, AMPK differentially regulates cellular mechanisms of serotonin-induced phrenic motor plasticity.	Metformin	85-94	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	39-43
31971473-6	2020	Consistent with our hypothesis, spinal AMPK activation with 2-deoxyglucose (2-DG) or metformin blocked 5-HT7, but not 5-HT2A receptor-induced pMF; in both cases, pMF inhibition was reversed by spinal administration of the AMPK inhibitor compound C. Thus, AMPK differentially regulates cellular mechanisms of serotonin-induced phrenic motor plasticity.	Metformin	85-94	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	222-226
31971473-6	2020	Consistent with our hypothesis, spinal AMPK activation with 2-deoxyglucose (2-DG) or metformin blocked 5-HT7, but not 5-HT2A receptor-induced pMF; in both cases, pMF inhibition was reversed by spinal administration of the AMPK inhibitor compound C. Thus, AMPK differentially regulates cellular mechanisms of serotonin-induced phrenic motor plasticity.	Metformin	85-94	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	222-226
31975558-2	2020	Metformin besides being an insulin sensitizer also induces autophagy; however, its effect on mitophagy and NLRP3 activation in patients with T2DM still remains elusive.	Metformin	0-9	NLR family pyrin domain containing 3	Homo sapiens	107-112
31975558-6	2020	However, multivariate ANCOVA divulged that mRNA and protein expression of mitophagy markers, NLRP3 and p-AMPKalpha (T172), were significantly increased only with metformin therapy.	Metformin	162-171	NLR family pyrin domain containing 3	Homo sapiens	93-98
31922237-3	2020	In this study, we aimed to cells to investigate whether metformin protects against age-related pathologies and to elucidate the underlying mechanisms; specifically, we focused on the role of unfolded protein response (UPR) via the AMPK/ERK1/2 signaling pathways.	Metformin	56-65	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	231-235
31922237-7	2020	We found that metformin treatment markedly affected the UPR and the AMPK/ERK1/2 signaling pathway, and maintained the auditory brainstem response (ABR) threshold during the aging process.	Metformin	14-23	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	68-72
31922237-8	2020	The results indicated that the regulation of the UPR and AMPK/ERK1/2 signaling pathway by metformin significantly attenuated hearing loss, cell apoptosis and age-related neurodegeneration.	Metformin	90-99	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	57-61
32276896-4	2020	For evaluating the anticancerous effects of different dilutions of Metformin (0.5muM -100muM) we used 4 different cancerous cells lines; MCF-7, HT-29, MDA-MB-231 and Hela.	Metformin	67-76	latexin	Homo sapiens	81-84
32068959-2	2020	Aging-related pathways such as mTOR and AMPK, which are major targets of anti-aging interventions including rapamcyin, metformin, and exercise, either directly regulate or intersect with metabolic pathways.	Metformin	119-128	mechanistic target of rapamycin kinase	Homo sapiens	31-35
31593243-7	2020	Among the T2DM patients, insulin usage increased the risk of CRC (aHR = 1.86, 95% CI = 1.58-0-2.19) after adjustment for age, sex, urbanization level, comorbidities, metformin usage and examinations; nevertheless, metformin decreased the risk of CRC (aHR = 0.65, 95% CI = 0.54-0.77) after adjustment for age, sex, urbanization level, comorbidities, insulin usage and examinations.	Metformin	166-175	insulin	Homo sapiens	25-32
31593243-7	2020	Among the T2DM patients, insulin usage increased the risk of CRC (aHR = 1.86, 95% CI = 1.58-0-2.19) after adjustment for age, sex, urbanization level, comorbidities, metformin usage and examinations; nevertheless, metformin decreased the risk of CRC (aHR = 0.65, 95% CI = 0.54-0.77) after adjustment for age, sex, urbanization level, comorbidities, insulin usage and examinations.	Metformin	214-223	insulin	Homo sapiens	25-32
31926250-2	2020	Metformin, a classic hypoglycemic drug for diabetes recently delivered us a new identity that it exerted anti-tumor activity through suppressing mTOR in various tumors.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	145-149
32094377-0	2020	Metformin-induced suppression of IFN-alpha via mTORC1 signalling following seasonal vaccination is associated with impaired antibody responses in type 2 diabetes.	Metformin	0-9	interferon alpha 1	Homo sapiens	33-42
32863988-6	2020	Results: After 6 months, the myeloperoxidase activity was significantly lower and gradually decreased in the Intervention group by about 40%, compared to the baseline measurement (p = 0.015) and compared to the Metformin group (p = 0.001).	Metformin	211-220	myeloperoxidase	Homo sapiens	29-44
31653514-12	2020	Metformin reduced plasma TNFalpha levels and decreased tissue expression of COX2 and NOX2 (which were positively correlated), without affecting SOD1 and SOD2.	Metformin	0-9	tumor necrosis factor	Rattus norvegicus	25-33
32104542-0	2020	Metformin Reduces the Senescence of Renal Tubular Epithelial Cells in Diabetic Nephropathy via the MBNL1/miR-130a-3p/STAT3 Pathway.	Metformin	0-9	muscleblind like splicing factor 1	Mus musculus	99-104
32104542-0	2020	Metformin Reduces the Senescence of Renal Tubular Epithelial Cells in Diabetic Nephropathy via the MBNL1/miR-130a-3p/STAT3 Pathway.	Metformin	0-9	signal transducer and activator of transcription 3	Mus musculus	117-122
32104542-5	2020	Metformin was able to reduce senescence by upregulating the expression of RNA-binding protein MBNL1 and miR-130a-3p and reducing STAT3 expression.	Metformin	0-9	muscleblind like splicing factor 1	Mus musculus	94-99
32104542-5	2020	Metformin was able to reduce senescence by upregulating the expression of RNA-binding protein MBNL1 and miR-130a-3p and reducing STAT3 expression.	Metformin	0-9	signal transducer and activator of transcription 3	Mus musculus	129-134
32104542-8	2020	Meanwhile, metformin (200 mg/kg/day) could increase the expression of MBNL1 and miR-130a-3p and decreased STAT3 expression, thus reducing this senescence in db/db mice.	Metformin	11-20	muscleblind like splicing factor 1	Mus musculus	70-75
32104542-8	2020	Meanwhile, metformin (200 mg/kg/day) could increase the expression of MBNL1 and miR-130a-3p and decreased STAT3 expression, thus reducing this senescence in db/db mice.	Metformin	11-20	signal transducer and activator of transcription 3	Mus musculus	106-111
32104542-9	2020	Our results suggest that metformin reduces the senescence of renal tubular epithelial cells in diabetic nephropathy via the MBNL1/miR-130a-3p/STAT3 pathway, which provided new ideas for the therapy of this disease.	Metformin	25-34	muscleblind like splicing factor 1	Mus musculus	124-129
32104542-9	2020	Our results suggest that metformin reduces the senescence of renal tubular epithelial cells in diabetic nephropathy via the MBNL1/miR-130a-3p/STAT3 pathway, which provided new ideas for the therapy of this disease.	Metformin	25-34	signal transducer and activator of transcription 3	Mus musculus	142-147
32099330-9	2020	Metformin and TUG1 knockdown via small interfering RNA both inhibited proliferation and migration while promoted autophagy via the AMPK/mTOR pathway in vascular wall cells.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	136-140
32099330-11	2020	Conclusion: Taken together, our data demonstrate that metformin might function to prevent AS by activating the AMPK/mTOR pathway via lncRNA TUG1.	Metformin	54-63	mechanistic target of rapamycin kinase	Homo sapiens	116-120
31944526-11	2020	Notably, metformin treatment disrupted p62-RIP1-RIP3 complexes and effectively repressed I/R-induced necroptosis in aged hearts, ultimately reducing mortality in this model.	Metformin	9-18	receptor (TNFRSF)-interacting serine-threonine kinase 1	Mus musculus	43-47
31420971-0	2020	Endogenous testosterone determines metformin action on prolactin levels in hyperprolactinaemic men: A pilot study.	Metformin	35-44	prolactin	Homo sapiens	55-64
31420971-1	2020	Metformin was found to reduce elevated prolactin levels in women but not in men.	Metformin	0-9	prolactin	Homo sapiens	39-48
31420971-6	2020	Although metformin reduced plasma glucose levels and improved insulin sensitivity in both groups, this effect was stronger in participants with low testosterone levels.	Metformin	9-18	insulin	Homo sapiens	62-69
31818851-2	2020	The signaling pathway activated by metformin (LKB1/AMPK/mTOR) is implicated in tumor suppression in ApcMin/+ mice via metformin-induced reduction in polyp burden, increased ratio of pAMPK/AMPK, decreased pmTOR/mTOR ratio, and decreased pS6Ser235/S6Ser235 ratio in polyps.	Metformin	35-44	serine/threonine kinase 11	Mus musculus	46-50
31818851-2	2020	The signaling pathway activated by metformin (LKB1/AMPK/mTOR) is implicated in tumor suppression in ApcMin/+ mice via metformin-induced reduction in polyp burden, increased ratio of pAMPK/AMPK, decreased pmTOR/mTOR ratio, and decreased pS6Ser235/S6Ser235 ratio in polyps.	Metformin	118-127	serine/threonine kinase 11	Mus musculus	46-50
31830378-0	2020	Combination of aloin and metformin enhances the antitumor effect by inhibiting the growth and invasion and inducing apoptosis and autophagy in hepatocellular carcinoma through PI3K/AKT/mTOR pathway.	Metformin	25-34	AKT serine/threonine kinase 1	Homo sapiens	181-184
31830378-0	2020	Combination of aloin and metformin enhances the antitumor effect by inhibiting the growth and invasion and inducing apoptosis and autophagy in hepatocellular carcinoma through PI3K/AKT/mTOR pathway.	Metformin	25-34	mechanistic target of rapamycin kinase	Homo sapiens	185-189
31830378-9	2020	Both the in vitro and in vivo results showed that aloin and MET alone as well as combination treatment activated the PI3K/AKT/mTOR pathway.	Metformin	60-63	AKT serine/threonine kinase 1	Homo sapiens	122-125
31830378-9	2020	Both the in vitro and in vivo results showed that aloin and MET alone as well as combination treatment activated the PI3K/AKT/mTOR pathway.	Metformin	60-63	mechanistic target of rapamycin kinase	Homo sapiens	126-130
31830378-10	2020	Overall, our research demonstrated that the concomitant treatment with aloin and MET enhances the antitumor effect by inhibiting the growth and invasion as well as inducing apoptosis and autophagy in HCC through PI3K/AKT/mTOR pathway.	Metformin	81-84	AKT serine/threonine kinase 1	Homo sapiens	217-220
31830378-10	2020	Overall, our research demonstrated that the concomitant treatment with aloin and MET enhances the antitumor effect by inhibiting the growth and invasion as well as inducing apoptosis and autophagy in HCC through PI3K/AKT/mTOR pathway.	Metformin	81-84	mechanistic target of rapamycin kinase	Homo sapiens	221-225
31989218-8	2020	In contrast, in the celastrol and celastrol + metformin groups, the apoptotic potential was amplified, as revealed by the increase in the caspase-9 and caspase-3 levels and Bax:BCL-2 ratio.	Metformin	46-55	B cell leukemia/lymphoma 2	Mus musculus	177-182
31989218-9	2020	In addition to their repressive effect on the gene expression of NFkappaBp65, TNFR and TLR4, metformin and celastrol inhibited phosphorylation-induced activation of IkappaBkappaB and NFkappaBp65 and decreased IkappaBalpha degradation.	Metformin	93-102	nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha	Mus musculus	209-221
31989218-11	2020	In conclusion, by inhibiting NLRP3 inflammasome and its prerequisite NFkappaB signalling, simultaneous administration of metformin and celastrol appears to have additive benefits in the treatment of HCC compared to cela monotherapy.	Metformin	121-130	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	69-77
31570268-3	2020	The antidiabetic drug metformin inhibits both MAPK and PI3K/mTOR pathway signaling.	Metformin	22-31	mechanistic target of rapamycin kinase	Homo sapiens	60-64
31423743-8	2020	Mechanistically, our results demonstrated that autophagy activation by AMPK activator metformin or mTOR inhibitor rapamycin obviously promotes cell survival and autophagy flux, improved mitochondrial ultrastructure, and reduced expression of Cyt-C and caspase-3 in CORT-induced PC12 cells.	Metformin	86-95	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	71-75
31595635-5	2020	CONCLUSION: A single event of insulin-induced hypoglycaemia led to an increase in markers of platelet activation and coagulation in people with early stages of type 2 diabetes on metformin therapy.	Metformin	179-188	insulin	Homo sapiens	30-37
31974043-0	2020	rs622342A>C in SLC22A1 is associated with metformin pharmacokinetics and glycemic response.	Metformin	42-51	solute carrier family 22 member 1	Homo sapiens	15-22
31974043-1	2020	Polymorphisms in SLC22A1 lead to variability in metformin clinical efficacy.	Metformin	48-57	solute carrier family 22 member 1	Homo sapiens	17-24
31974043-7	2020	The rs622342A>C in SLC22A1 may be associated with metformin pharmacokinetics and variability in therapeutic efficacy.	Metformin	50-59	solute carrier family 22 member 1	Homo sapiens	19-26
32097995-3	2020	Metformin can be used safely when the estimated glomerular filtration rate (eGFR) is >=45 mL/min/1.73 m2.	Metformin	0-9	CD59 molecule (CD59 blood group)	Homo sapiens	93-98
32097995-4	2020	If the eGFR is between 30 and 44 mL/min/1.73 m2, metformin treatment should not be started.	Metformin	49-58	CD59 molecule (CD59 blood group)	Homo sapiens	36-41
32097995-6	2020	Metformin is contraindicated when the eGFR is <30 mL/min/1.73 m2.	Metformin	0-9	CD59 molecule (CD59 blood group)	Homo sapiens	53-58
32097995-8	2020	During procedures involving intravenous administration of ICM, metformin should be discontinued starting the day of the procedures and up to 48 hours post-procedures if the eGFR is <60 mL/min/1.73 m2.	Metformin	63-72	CD59 molecule (CD59 blood group)	Homo sapiens	188-193
31950354-5	2020	Pooled results showed that metformin had significant effects on total cholesterol (mean change -6.57 mg/dl; 95% CI -9.66, -3.47; P = 0.000) and LDL-c (mean change -4.69 mg/dl; 95% CI -7.38, -2.00; P = 0.001), but insignificant effects on HDL-c (mean change -4.33 mg/dl; 95% CI -9.62, 0.96; P = 0.109) and triglyceride (mean change -0.85 mg/dl; 95% CI -0.36, 2.06; P = 0.169).	Metformin	27-36	component of oligomeric golgi complex 2	Homo sapiens	144-149
31950354-10	2020	CONCLUSION: This meta-analysis revealed that metformin could reduce total cholesterol and LDL-c in nondiabetic adults.	Metformin	45-54	component of oligomeric golgi complex 2	Homo sapiens	90-95
31822926-4	2020	Documented evidence for prevention of CAD is available for the control of hypertension using angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB) and calcium antagonists, for the treatment of hypercholesterolemia using statins, ezetimibe and proprotein convertase subtilisin-kexin type 9 (PCSK-9) inhibitors and for the treatment of type 2 diabetes mellitus with metformin, sodium-glucose transporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists.	Metformin	394-403	angiotensin I converting enzyme	Homo sapiens	93-122
31822926-4	2020	Documented evidence for prevention of CAD is available for the control of hypertension using angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB) and calcium antagonists, for the treatment of hypercholesterolemia using statins, ezetimibe and proprotein convertase subtilisin-kexin type 9 (PCSK-9) inhibitors and for the treatment of type 2 diabetes mellitus with metformin, sodium-glucose transporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists.	Metformin	394-403	angiotensin I converting enzyme	Homo sapiens	124-127
32067218-12	2020	Metformin treatment elevates serum MANF levels and alleviates insulin resistance and hyperandrogenism in PCOS women.	Metformin	0-9	insulin	Homo sapiens	62-69
31894313-0	2020	Metformin alleviates endometrial hyperplasia through the UCA1/miR-144/TGF-beta1/AKT signaling pathway.	Metformin	0-9	microRNA 144	Homo sapiens	62-69
31894313-0	2020	Metformin alleviates endometrial hyperplasia through the UCA1/miR-144/TGF-beta1/AKT signaling pathway.	Metformin	0-9	transforming growth factor beta 1	Homo sapiens	70-79
31894313-0	2020	Metformin alleviates endometrial hyperplasia through the UCA1/miR-144/TGF-beta1/AKT signaling pathway.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	80-83
31894313-6	2020	By contrast, Met reduced cell viability, promoted cell apoptosis, and reduced the expression levels of UCA1, TGF-beta and p-AKT, while upregulating the expression of miR-144 and active Caspase-3 in a dose-dependent manner.	Metformin	13-16	transforming growth factor beta 1	Homo sapiens	109-117
31894313-6	2020	By contrast, Met reduced cell viability, promoted cell apoptosis, and reduced the expression levels of UCA1, TGF-beta and p-AKT, while upregulating the expression of miR-144 and active Caspase-3 in a dose-dependent manner.	Metformin	13-16	AKT serine/threonine kinase 1	Homo sapiens	124-127
31894313-6	2020	By contrast, Met reduced cell viability, promoted cell apoptosis, and reduced the expression levels of UCA1, TGF-beta and p-AKT, while upregulating the expression of miR-144 and active Caspase-3 in a dose-dependent manner.	Metformin	13-16	microRNA 144	Homo sapiens	166-173
31894313-6	2020	By contrast, Met reduced cell viability, promoted cell apoptosis, and reduced the expression levels of UCA1, TGF-beta and p-AKT, while upregulating the expression of miR-144 and active Caspase-3 in a dose-dependent manner.	Metformin	13-16	caspase 3	Homo sapiens	185-194
31894313-11	2020	In conclusion, the current study suggested that Met reduces the risk of EH by reducing the expression levels of UCA1, TGF-beta and p-AKT, while increasing the levels of miR-144 and active Caspase-3 in a dose-dependent manner.	Metformin	48-51	transforming growth factor beta 1	Homo sapiens	118-126
31894313-11	2020	In conclusion, the current study suggested that Met reduces the risk of EH by reducing the expression levels of UCA1, TGF-beta and p-AKT, while increasing the levels of miR-144 and active Caspase-3 in a dose-dependent manner.	Metformin	48-51	AKT serine/threonine kinase 1	Homo sapiens	133-136
31894313-11	2020	In conclusion, the current study suggested that Met reduces the risk of EH by reducing the expression levels of UCA1, TGF-beta and p-AKT, while increasing the levels of miR-144 and active Caspase-3 in a dose-dependent manner.	Metformin	48-51	microRNA 144	Homo sapiens	169-176
31894313-11	2020	In conclusion, the current study suggested that Met reduces the risk of EH by reducing the expression levels of UCA1, TGF-beta and p-AKT, while increasing the levels of miR-144 and active Caspase-3 in a dose-dependent manner.	Metformin	48-51	caspase 3	Homo sapiens	188-197
32405365-3	2020	We aimed to investigate the combination therapeutic effect of these cells with insulin and metformin on neuropeptide Y, melanocortin-4 receptor, and leptin receptor genes expression in TID.	Metformin	91-100	neuropeptide Y	Rattus norvegicus	104-118
31389032-7	2020	In both study groups, metformin decreased plasma glucose levels and improved insulin sensitivity.	Metformin	22-31	insulin	Homo sapiens	77-84
31389032-9	2020	Metformin-induced changes in thyrotropin and Jostel"s index correlated with their baseline values, baseline levels of testosterone, and with the effect of treatment on insulin sensitivity.	Metformin	0-9	insulin	Homo sapiens	168-175
31389032-10	2020	In men with neither low or normal testosterone levels, metformin affected free thyroid hormones, prolactin, testosterone, gonadotropins, and SPINA-GD.	Metformin	55-64	prolactin	Homo sapiens	97-106
31476446-0	2020	Recuperative effect of metformin loaded Polydopamine Nanoformulation promoting EZH2 mediated proteasomal degradation of phospho-alpha-Synuclein in Parkinson"s disease model.	Metformin	23-32	enhancer of zeste 2 polycomb repressive complex 2 subunit	Homo sapiens	79-83
31705064-5	2020	Interestingly, metformin decreased omental metastasis at least partially by inhibiting MCP-1 secretion from adipocytes independent of direct effects on cancer cells.	Metformin	15-24	mast cell protease 1	Mus musculus	87-92
32190375-0	2020	Vitamin B12 Deficiency in Diabetic Patients on Metformin Therapy: A cross-sectional study from Oman.	Metformin	47-56	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	8-11
32190375-1	2020	Objectives: This study aimed to determine the prevalence of vitamin B12 deficiency amongst diabetic patients on metformin therapy.	Metformin	112-121	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	68-71
32190375-6	2020	The mean daily dose of metformin was highest among vitamin B12 deficient group (1,981 +- 222 mg; P = 0.004).	Metformin	23-32	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	59-62
32190375-7	2020	Conclusion: The prevalence of vitamin B12 deficiency is considerable among diabetic patients on metformin therapy.	Metformin	96-105	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	38-41
32023702-18	2020	The expression of B-lymphocyte lymphoma-related protein, cytochrome c, and caspase-3 protein in HepG2 cells was decreased after treatment with low and high-dose metformin, while B-cell lymphoma 2 was increased (P < 0.05).	Metformin	161-170	cytochrome c, somatic	Homo sapiens	57-69
32099330-0	2020	Metformin Activates the AMPK-mTOR Pathway by Modulating lncRNA TUG1 to Induce Autophagy and Inhibit Atherosclerosis.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	29-33
32023702-18	2020	The expression of B-lymphocyte lymphoma-related protein, cytochrome c, and caspase-3 protein in HepG2 cells was decreased after treatment with low and high-dose metformin, while B-cell lymphoma 2 was increased (P < 0.05).	Metformin	161-170	caspase 3	Homo sapiens	75-84
31945013-6	2020	In addition, metformin treatment decreased p16INK4a levels in OA chondrocytes, and enhanced polarization of AMPK and inhibition of mTORC1 in OA mice and chondrocytes in a dose-dependent manner.	Metformin	13-22	cyclin dependent kinase inhibitor 2A	Mus musculus	43-51
31963528-0	2020	PPARalpha-Dependent Modulation by Metformin of the Expression of OCT-2 and MATE-1 in the Kidney of Mice.	Metformin	34-43	peroxisome proliferator activated receptor alpha	Mus musculus	0-9
31963528-0	2020	PPARalpha-Dependent Modulation by Metformin of the Expression of OCT-2 and MATE-1 in the Kidney of Mice.	Metformin	34-43	POU domain, class 2, transcription factor 2	Mus musculus	65-70
31963528-3	2020	Hereby, we provide evidence that points towards the metformin-dependent upregulation of OCT-2 and MATE-1 in the kidney via the transcription factor proliferator-activated receptor alpha (PPARalpha).	Metformin	52-61	POU domain, class 2, transcription factor 2	Mus musculus	88-93
31963528-3	2020	Hereby, we provide evidence that points towards the metformin-dependent upregulation of OCT-2 and MATE-1 in the kidney via the transcription factor proliferator-activated receptor alpha (PPARalpha).	Metformin	52-61	peroxisome proliferator activated receptor alpha	Mus musculus	187-196
31963528-4	2020	Treatment of wild type mice with metformin led to the upregulation of the expression of OCT-2 and MATE-1 by 34% and 157%, respectively.	Metformin	33-42	POU domain, class 2, transcription factor 2	Mus musculus	88-93
31963528-5	2020	An analysis in a kidney tubular cell line revealed that metformin upregulated PPARalpha and OCT-2 expression by 37% and 299% respectively.	Metformin	56-65	peroxisome proliferator activated receptor alpha	Mus musculus	78-87
31963528-5	2020	An analysis in a kidney tubular cell line revealed that metformin upregulated PPARalpha and OCT-2 expression by 37% and 299% respectively.	Metformin	56-65	POU domain, class 2, transcription factor 2	Mus musculus	92-97
31963528-6	2020	MK-886, a PPARalpha antagonist, abrogated the OCT-2 upregulation by metformin and reduced MATE-1 expression.	Metformin	68-77	peroxisome proliferator activated receptor alpha	Mus musculus	10-19
31963528-6	2020	MK-886, a PPARalpha antagonist, abrogated the OCT-2 upregulation by metformin and reduced MATE-1 expression.	Metformin	68-77	POU domain, class 2, transcription factor 2	Mus musculus	46-51
31963528-8	2020	PPARalpha knockout mice failed to upregulate both the expression of OCT-2 and MATE-1 in the kidney upon metformin treatment, supporting the PPARalpha-dependent metformin upregulation of the transporters in this organ.	Metformin	160-169	peroxisome proliferator activated receptor alpha	Mus musculus	140-149
31963528-9	2020	Taken together, our data sheds light on the metformin-induced mechanism of transporter modulation in the kidney, via PPARalpha, and this effect may have implications for drug safety and efficacy.	Metformin	44-53	peroxisome proliferator activated receptor alpha	Mus musculus	117-126
31963541-0	2020	Metformin Mitigates Nickel-Elicited Angiopoietin-Like Protein 4 Expression via HIF-1alpha for Lung Tumorigenesis.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	79-89
31963541-5	2020	The expression of ANGPTL4 and HIF-1alpha induced by NiCl2 were significantly repressed after metformin treatment.	Metformin	93-102	hypoxia inducible factor 1 subunit alpha	Homo sapiens	30-40
31963541-9	2020	Additionally, metformin has the ability to prevent NiCl2-induced ANGPTL4 through inhibiting HIF-1alpha expression and its binding activity.	Metformin	14-23	hypoxia inducible factor 1 subunit alpha	Homo sapiens	92-102
31945013-8	2020	METHODS: The effects of metformin on cartilage degradation and chondrocyte aging was determined in a destabilization of the medial meniscus (DMM)-induced OA mouse model and in IL-1beta-treated mouse chondrocytes and cartilage explants.	Metformin	24-33	interleukin 1 beta	Mus musculus	176-184
31647955-0	2020	Metformin alleviates oxidative stress and enhances autophagy in diabetic kidney disease via AMPK/SIRT1-FoxO1 pathway.	Metformin	0-9	sirtuin 1	Rattus norvegicus	97-102
31647955-3	2020	We found that metformin effectively alleviated the disorders of glycolipid metabolism, renal function injury in diabetic rats, and relieved oxidative stress, enhanced autophagy and slowed down abnormal cell proliferation in high glucose cultured RMCs through AMPK/SIRT1-FoxO1 pathway, indicating the protective role of metformin against the pathological process of DKD.	Metformin	14-23	sirtuin 1	Rattus norvegicus	264-269
31936857-2	2020	We study in jejunum the relation between insulin signalling and insulin resistance in morbidly obese subjects with low (MO-low-IR) or with high insulin resistance (MO-high-IR), and with type 2 diabetes treated with metformin (MO-metf-T2DM)), and the effect of insulin/leptin on intestinal epithelial cells (IEC).	Metformin	215-224	insulin	Homo sapiens	41-48
31715142-0	2020	Metformin promotes osteogenic differentiation and protects against oxidative stress-induced damage in periodontal ligament stem cells via activation of the Akt/Nrf2 signaling pathway.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	156-159
31715142-0	2020	Metformin promotes osteogenic differentiation and protects against oxidative stress-induced damage in periodontal ligament stem cells via activation of the Akt/Nrf2 signaling pathway.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	160-164
31715142-5	2020	This positive effect was associated with activation of Akt signaling by metformin.	Metformin	72-81	AKT serine/threonine kinase 1	Homo sapiens	55-58
31715142-7	2020	In addition, metformin was found to activate the Nrf2 signaling pathway in PDLSCs, and knockdown of Nrf2 by siRNA impaired the protective effect of metformin.	Metformin	13-22	NFE2 like bZIP transcription factor 2	Homo sapiens	49-53
31715142-7	2020	In addition, metformin was found to activate the Nrf2 signaling pathway in PDLSCs, and knockdown of Nrf2 by siRNA impaired the protective effect of metformin.	Metformin	148-157	NFE2 like bZIP transcription factor 2	Homo sapiens	49-53
31715142-7	2020	In addition, metformin was found to activate the Nrf2 signaling pathway in PDLSCs, and knockdown of Nrf2 by siRNA impaired the protective effect of metformin.	Metformin	148-157	NFE2 like bZIP transcription factor 2	Homo sapiens	100-104
31998447-5	2020	In this study, we found that the administration of metformin improved functional recovery after SCI through reducing neuronal cell apoptosis and repairing neurites by stabilizing microtubules via PI3K/Akt signaling pathway.	Metformin	51-60	AKT serine/threonine kinase 1	Homo sapiens	201-204
31906986-0	2020	Metformin-repressed miR-381-YAP-snail axis activity disrupts NSCLC growth and metastasis.	Metformin	0-9	snail family transcriptional repressor 1	Homo sapiens	32-37
31906986-4	2020	However, the molecular mechanism underpinning how metformin-induced upregulation of miR-381 directly targets YAP or its interactions with the epithelial-mesenchymal transition (EMT) marker protein Snail in NSCLC is still unknown.	Metformin	50-59	snail family transcriptional repressor 1	Homo sapiens	197-202
31906986-16	2020	Furthermore, miR-381, YAP, and Snail constitute the miR-381-YAP-Snail signal axis, which is repressed by metformin, and enhances cancer cell invasiveness by directly regulating EMT.	Metformin	105-114	snail family transcriptional repressor 1	Homo sapiens	31-36
31906986-16	2020	Furthermore, miR-381, YAP, and Snail constitute the miR-381-YAP-Snail signal axis, which is repressed by metformin, and enhances cancer cell invasiveness by directly regulating EMT.	Metformin	105-114	snail family transcriptional repressor 1	Homo sapiens	64-69
31906986-17	2020	CONCLUSIONS: Metformin-induced repression of miR-381-YAP-Snail axis activity disrupts NSCLC growth and metastasis.	Metformin	13-22	snail family transcriptional repressor 1	Homo sapiens	57-62
31998447-6	2020	Inhibiting the PI3K/Akt pathway with LY294002 partly reversed the therapeutic effects of metformin on SCI in vitro and vivo.	Metformin	89-98	AKT serine/threonine kinase 1	Homo sapiens	20-23
31998447-7	2020	Furthermore, metformin treatment weakened the excessive activation of oxidative stress and improved the mitochondrial function by activating the nuclear factor erythroid-related factor 2 (Nrf2) transcription and binding to the antioxidant response element (ARE).	Metformin	13-22	NFE2 like bZIP transcription factor 2	Homo sapiens	145-186
32021253-0	2020	Metformin Inhibits Proliferation of Human Thyroid Cancer TPC-1 Cells by Decreasing LRP2 to Suppress the JNK Pathway.	Metformin	0-9	two pore segment channel 1	Homo sapiens	57-62
31998447-7	2020	Furthermore, metformin treatment weakened the excessive activation of oxidative stress and improved the mitochondrial function by activating the nuclear factor erythroid-related factor 2 (Nrf2) transcription and binding to the antioxidant response element (ARE).	Metformin	13-22	NFE2 like bZIP transcription factor 2	Homo sapiens	188-192
32021253-0	2020	Metformin Inhibits Proliferation of Human Thyroid Cancer TPC-1 Cells by Decreasing LRP2 to Suppress the JNK Pathway.	Metformin	0-9	mitogen-activated protein kinase 8	Homo sapiens	104-107
32021253-1	2020	Objective: To uncover the potential effect of metformin on proliferation and apoptosis of thyroid cancer TPC-1 cell line, and the underlying mechanism.	Metformin	46-55	two pore segment channel 1	Homo sapiens	105-110
31998447-10	2020	Taken together, these results revealed that the role of metformin in nerve regeneration after SCI was probably related to stabilization of microtubules and inhibition of the excessive activation of Akt-mediated Nrf2/ARE pathway-regulated oxidative stress and mitochondrial dysfunction.	Metformin	56-65	AKT serine/threonine kinase 1	Homo sapiens	198-201
32021253-2	2020	Methods: Viability, apoptosis and LRP2 level in TPC-1 cells treated with different doses of metformin for different time points were determined.	Metformin	92-101	two pore segment channel 1	Homo sapiens	48-53
31998447-10	2020	Taken together, these results revealed that the role of metformin in nerve regeneration after SCI was probably related to stabilization of microtubules and inhibition of the excessive activation of Akt-mediated Nrf2/ARE pathway-regulated oxidative stress and mitochondrial dysfunction.	Metformin	56-65	NFE2 like bZIP transcription factor 2	Homo sapiens	211-215
32021253-3	2020	Besides, protein levels of p-JNK1 and c-Jun N-terminal kinases (JNK) in metformin-treated TPC-1 cells were detected by Western blot.	Metformin	72-81	mitogen-activated protein kinase 8	Homo sapiens	29-33
32021253-3	2020	Besides, protein levels of p-JNK1 and c-Jun N-terminal kinases (JNK) in metformin-treated TPC-1 cells were detected by Western blot.	Metformin	72-81	mitogen-activated protein kinase 8	Homo sapiens	29-32
31892560-10	2020	Furthermore, the angiogenic related protein TIMP-1 was down-regulated, and its miRNA expression was altered by metformin in QGP-1 cells.	Metformin	111-120	TIMP metallopeptidase inhibitor 1	Homo sapiens	44-50
32021253-3	2020	Besides, protein levels of p-JNK1 and c-Jun N-terminal kinases (JNK) in metformin-treated TPC-1 cells were detected by Western blot.	Metformin	72-81	two pore segment channel 1	Homo sapiens	90-95
32021253-4	2020	Regulatory effects of LRP2 on the JNK pathway and cell viability in metformin-treated TPC-1 cells were assessed.	Metformin	68-77	two pore segment channel 1	Homo sapiens	86-91
32021253-5	2020	Results: Viability in TPC-1 cells gradually decreased with the treatment of increased doses of metformin either for 24 h or 48 h. The apoptotic rate was concentration-dependently elevated by metformin treatment.	Metformin	95-104	two pore segment channel 1	Homo sapiens	22-27
32021253-5	2020	Results: Viability in TPC-1 cells gradually decreased with the treatment of increased doses of metformin either for 24 h or 48 h. The apoptotic rate was concentration-dependently elevated by metformin treatment.	Metformin	191-200	two pore segment channel 1	Homo sapiens	22-27
32021253-6	2020	Relative levels of LRP2 and p-JNK1 were concentration-dependently downregulated by metformin treatment.	Metformin	83-92	mitogen-activated protein kinase 8	Homo sapiens	30-34
32021253-7	2020	In addition, overexpression of LRP2 partially abolished the inhibitory effect of metformin on the viability of TPC-1 cells.	Metformin	81-90	two pore segment channel 1	Homo sapiens	111-116
32021253-8	2020	Conclusion: Metformin treatment suppresses the proliferative ability and induces apoptosis of TPC-1 cells by downregulating LRP2 to block the JNK pathway.	Metformin	12-21	two pore segment channel 1	Homo sapiens	94-99
32021253-8	2020	Conclusion: Metformin treatment suppresses the proliferative ability and induces apoptosis of TPC-1 cells by downregulating LRP2 to block the JNK pathway.	Metformin	12-21	mitogen-activated protein kinase 8	Homo sapiens	142-145
31948119-7	2020	Both chamomile extract and metformin decreased MDA (p &lt; 0.05) and increased GPx and CAT (p &lt; 0.01).	Metformin	27-36	catalase	Rattus norvegicus	87-90
31902918-6	2020	Furthermore, metformin also enhanced autophagic flux, inhibited the phosphorylation of the serine/threonine protein kinase (AKT)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs) related protein levels and the level of miR-221 in LPS-stimulated RAW264.7 cells.	Metformin	13-22	AKT serine/threonine kinase 1	Homo sapiens	124-127
31786229-10	2020	Meanwhile, pre-treated with either the specific Cdk5-inhibitor (roscovitine) or the antidiabetic AMPK-alpha2-inhibitor (metformin) could restore the alterations in neuronal protein expression.	Metformin	120-129	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	97-108
31715372-11	2020	Relative to the diabetic control, treatments with omega-3 or metformin caused significant elevations in hepatic glycogen, total alkaline phosphatase (TALP), osteocalcin, PTH, estradiol, and calcium; however, significant decreases in TRAP and glucose.	Metformin	61-70	bone gamma-carboxyglutamate protein	Rattus norvegicus	157-168
31715372-11	2020	Relative to the diabetic control, treatments with omega-3 or metformin caused significant elevations in hepatic glycogen, total alkaline phosphatase (TALP), osteocalcin, PTH, estradiol, and calcium; however, significant decreases in TRAP and glucose.	Metformin	61-70	parathyroid hormone	Rattus norvegicus	170-173
31902918-4	2020	In the present study, we found that metformin reduced the production of nitric oxide (NO) and the level of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.	Metformin	36-45	tumor necrosis factor	Mus musculus	141-174
31902918-6	2020	Furthermore, metformin also enhanced autophagic flux, inhibited the phosphorylation of the serine/threonine protein kinase (AKT)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs) related protein levels and the level of miR-221 in LPS-stimulated RAW264.7 cells.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	129-158
31902918-4	2020	In the present study, we found that metformin reduced the production of nitric oxide (NO) and the level of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.	Metformin	36-45	interleukin 6	Mus musculus	204-208
31902918-6	2020	Furthermore, metformin also enhanced autophagic flux, inhibited the phosphorylation of the serine/threonine protein kinase (AKT)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs) related protein levels and the level of miR-221 in LPS-stimulated RAW264.7 cells.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	160-164
31006835-7	2020	Results of the subgroup analyses showed that insulin, glucose, and BMI decreased more significantly when the duration of administering metformin intervention was above 4 weeks.	Metformin	135-144	insulin	Homo sapiens	45-52
31694905-8	2020	Interference with both oxidative phosphorylation (metformin, oligomycin) and beta-oxidation of fatty acids (etomoxir) enhanced the antitumor efficacy of c-MET inhibition.	Metformin	50-59	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	153-158
31006835-9	2020	CONCLUSIONS: Breast cancer patients receiving metformin as treatment for diabetes showed significant reduction in levels of insulin, fasting glucose, CRP, HOMA, leptin, BMI, and Ki-67.	Metformin	46-55	insulin	Homo sapiens	124-131
31006835-9	2020	CONCLUSIONS: Breast cancer patients receiving metformin as treatment for diabetes showed significant reduction in levels of insulin, fasting glucose, CRP, HOMA, leptin, BMI, and Ki-67.	Metformin	46-55	C-reactive protein	Homo sapiens	150-153
31662305-0	2020	Insulin Sensitivity and Renal Hemodynamic Function in Metformin-Treated Adults With Type 2 Diabetes and Preserved Renal Function.	Metformin	54-63	insulin	Homo sapiens	0-7
30663560-4	2020	Regarding antidiabetic medication, metformin, gliclazide, pioglitazone, exenatide and dapagliflozin exert a beneficial effect on Endothelial Function (EF); glimepiride and glibenclamide, dipeptidyl peptidase-4 inhibitors and liraglutide have a neutral effect, while studies examining the effect of insulin analogues, empagliflozin and canagliflozin on EF are limited.	Metformin	35-44	insulin	Homo sapiens	298-305
32407269-10	2020	CONCLUSION: The interaction between rs72552763 and rs622342 in OCT1, and rs12943590 in MATE2 suggested an important role of these polymorphisms in metformin response in T2D Mexican Mestizo population.	Metformin	147-156	solute carrier family 22 member 1	Homo sapiens	63-67
31969093-0	2020	Pharmacological strategies for insulin sensitivity: thiazolidinediones and metformin.	Metformin	75-84	insulin	Homo sapiens	31-38
31969093-7	2020	OBJECTIVE: The aim of this study was to review TZD and metformin as pharmacological treatments for insulin resistance associated with obesity and cancer.	Metformin	55-64	insulin	Homo sapiens	99-106
31662305-13	2020	CONCLUSIONS: For the first time, we demonstrate that impaired insulin sensitivity is associated with intrarenal hemodynamic dysfunction by gold standard techniques in adults with T2D treated with metformin monotherapy.	Metformin	196-205	insulin	Homo sapiens	62-69
31853319-10	2020	In conclusion, insulin combined with metformin is more effective than insulin alone in reducing serum Cys C and Hcy levels, with significant effect on the improvement of maternal and neonatal outcomes.	Metformin	37-46	insulin	Homo sapiens	70-77
32769032-3	2020	Metformin regulates insulin responsive gene and helps to achieve glycemic control however, no extensive study reported about its role against glycation induced oxidative stress and vascular inflammation.	Metformin	0-9	insulin	Homo sapiens	20-27
32769032-8	2020	RESULTS: Metformin showed maximum percent declined from baseline to three months therapy in levels of fructosamine, beta-amyloid, sRAGE, inflammatory cytokines (IL-6, TNF-alpha) and percent increment in esRAGE and antioxidants levels.	Metformin	9-18	interleukin 6	Homo sapiens	161-165
32769032-8	2020	RESULTS: Metformin showed maximum percent declined from baseline to three months therapy in levels of fructosamine, beta-amyloid, sRAGE, inflammatory cytokines (IL-6, TNF-alpha) and percent increment in esRAGE and antioxidants levels.	Metformin	9-18	tumor necrosis factor	Homo sapiens	167-176
31718828-1	2020	OBJECTIVE: To compare the effects of metformin, rosiglitazone, and their combination in obese polycystic ovary syndrome (PCOS) patients with insulin resistance.	Metformin	37-46	insulin	Homo sapiens	141-148
32396212-5	2020	Metformin is taken by many patients before pregnancy due to both previously diagnosed type 2 diabetes and in the treatment of prediabetes, obesity and polycystic ovary syndrome (PCOS) as part of therapy for insulin resistance.	Metformin	0-9	insulin	Homo sapiens	207-214
31892847-0	2020	Metformin induces cell cycle arrest, apoptosis and autophagy through ROS/JNK signaling pathway in human osteosarcoma.	Metformin	0-9	mitogen-activated protein kinase 8	Homo sapiens	73-76
31892847-5	2020	Further research indicated the induction of apoptosis and autophagy triggered by metformin could remarkably attenuate after the treatment of ROS scavenger NAC and JNK inhibitor SP600125.	Metformin	81-90	mitogen-activated protein kinase 8	Homo sapiens	163-166
31892847-6	2020	Additionally, our results showed that NAC-suppressed JNK/c-Jun signaling pathway could have been activated through metformin treatment.	Metformin	115-124	mitogen-activated protein kinase 8	Homo sapiens	53-56
31892847-8	2020	Thus, we propose that metformin could induce cell cycle arrest as well as programmed cell death, including apoptosis and autophagy, through ROS-dependent JNK/c-Jun cascade in human osteosarcoma.	Metformin	22-31	mitogen-activated protein kinase 8	Homo sapiens	154-157
31521867-0	2020	Metformin ameliorates stress-induced depression-like behaviors via enhancing the expression of BDNF by activating AMPK/CREB-mediated histone acetylation.	Metformin	0-9	cAMP responsive element binding protein 1	Mus musculus	119-123
31521867-7	2020	At a molecular level, metformin significantly upregulated the expression of the brain-derived neurotrophic factor (BDNF) by increasing the histone acetylation along with the BDNF promoter, which was attributed to the activation of AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB).	Metformin	22-31	cAMP responsive element binding protein 1	Mus musculus	271-308
31521867-7	2020	At a molecular level, metformin significantly upregulated the expression of the brain-derived neurotrophic factor (BDNF) by increasing the histone acetylation along with the BDNF promoter, which was attributed to the activation of AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB).	Metformin	22-31	cAMP responsive element binding protein 1	Mus musculus	310-314
32538851-8	2020	DNLA and metformin treatments decreased amyloid-beta1-42, AbetaPP, PS1, and BACE1, while increasing IDE and neprilysin for Abeta clearance.	Metformin	9-18	insulin degrading enzyme	Mus musculus	100-103
33442187-0	2020	Prevalence of Vitamin B12 Deficiency and its Associated Factors among Patients with Type 2 Diabetes Mellitus on Metformin from a District in Malaysia.	Metformin	112-121	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	22-25
33442187-1	2020	Introduction: Vitamin B12 deficiency is more common among metformin-treated subjects although the prevalence is variable.	Metformin	58-67	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	22-25
33442187-3	2020	The aim of this study is to determine the prevalence of vitamin B12 deficiency and its associated factors among patients with type 2 diabetes mellitus (DM) who are on metformin.	Metformin	167-176	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	64-67
33442187-7	2020	Results: The prevalence of vitamin B12 deficiency among metformin-treated patients with type 2 DM patients was 28.3% (n=58).	Metformin	56-65	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	35-38
33442187-9	2020	The non-Malay population was at a higher risk for metformin-associated vitamin B12 deficiency [adjusted odds ratio (OR) 3.86, 95% CI: 1.836 to 8.104, p<0.001].	Metformin	50-59	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	79-82
33442187-10	2020	Duration of metformin use of more than five years showed increased risk for metformin-associated vitamin B12 deficiency (adjusted OR 2.06, 95% CI: 1.003 to 4.227, p=0.049).	Metformin	12-21	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	105-108
33442187-10	2020	Duration of metformin use of more than five years showed increased risk for metformin-associated vitamin B12 deficiency (adjusted OR 2.06, 95% CI: 1.003 to 4.227, p=0.049).	Metformin	76-85	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	105-108
33442187-11	2020	Conclusion: Our study suggests that the prevalence of vitamin B12 deficiency among patients with type 2 diabetes mellitus on metformin in our population is substantial.	Metformin	125-134	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	62-65
33184242-11	2020	We found Metformin pre-treatment attenuated human and rat cardiomyocytes apoptosis, HMGB1, TNFalpha and IL-6 release and ROS production that were induced by high-glucose stimulation, and these effects of metformin could be blocked by okadaic acid treatment.	Metformin	9-18	tumor necrosis factor	Rattus norvegicus	91-99
33184242-11	2020	We found Metformin pre-treatment attenuated human and rat cardiomyocytes apoptosis, HMGB1, TNFalpha and IL-6 release and ROS production that were induced by high-glucose stimulation, and these effects of metformin could be blocked by okadaic acid treatment.	Metformin	9-18	interleukin 6	Rattus norvegicus	104-108
33184242-11	2020	We found Metformin pre-treatment attenuated human and rat cardiomyocytes apoptosis, HMGB1, TNFalpha and IL-6 release and ROS production that were induced by high-glucose stimulation, and these effects of metformin could be blocked by okadaic acid treatment.	Metformin	204-213	tumor necrosis factor	Rattus norvegicus	91-99
33184242-11	2020	We found Metformin pre-treatment attenuated human and rat cardiomyocytes apoptosis, HMGB1, TNFalpha and IL-6 release and ROS production that were induced by high-glucose stimulation, and these effects of metformin could be blocked by okadaic acid treatment.	Metformin	204-213	interleukin 6	Rattus norvegicus	104-108
33184242-13	2020	Metformin pre-treatment reduced NF-kappaB activation in human and rat cardiomyocytes apoptosis that was elicited by high-glucose stimulation, and this effect of metformin could be blocked by okadaic acid treatment.	Metformin	0-9	nuclear factor kappa B subunit 1	Homo sapiens	32-41
33184242-13	2020	Metformin pre-treatment reduced NF-kappaB activation in human and rat cardiomyocytes apoptosis that was elicited by high-glucose stimulation, and this effect of metformin could be blocked by okadaic acid treatment.	Metformin	161-170	nuclear factor kappa B subunit 1	Homo sapiens	32-41
31385363-3	2020	Metformin also upregulates peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha).	Metformin	0-9	PPARG coactivator 1 alpha	Homo sapiens	27-94
31385363-3	2020	Metformin also upregulates peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha).	Metformin	0-9	PPARG coactivator 1 alpha	Homo sapiens	96-106
31385363-5	2020	Because BCAA catabolic enzyme content is regulated by PGC-1alpha, we hypothesized metformin may alter BCAA catabolism.	Metformin	82-91	PPARG coactivator 1 alpha	Homo sapiens	54-64
31385363-9	2020	Supraphysiological metformin upregulated PGC-1alpha mRNA expression along with related downstream targets, yet the reduced expression of electron transport chain components as well as basal and peak cell metabolism.	Metformin	19-28	PPARG coactivator 1 alpha	Homo sapiens	41-51
31385363-10	2020	Supraphysiological metformin also suppressed branched-chain aminotransferase 2 (BCAT2) and branched-chain-alpha-keto acid dehydrogenase E1a (BCKDHa) mRNA expression as well as BCAT2 protein expression and BCKDHa activity, which was accompanied by decreased Kruppel-like factor 15 protein expression.	Metformin	19-28	branched chain amino acid transaminase 2	Homo sapiens	45-78
31385363-10	2020	Supraphysiological metformin also suppressed branched-chain aminotransferase 2 (BCAT2) and branched-chain-alpha-keto acid dehydrogenase E1a (BCKDHa) mRNA expression as well as BCAT2 protein expression and BCKDHa activity, which was accompanied by decreased Kruppel-like factor 15 protein expression.	Metformin	19-28	branched chain amino acid transaminase 2	Homo sapiens	80-85
31385363-10	2020	Supraphysiological metformin also suppressed branched-chain aminotransferase 2 (BCAT2) and branched-chain-alpha-keto acid dehydrogenase E1a (BCKDHa) mRNA expression as well as BCAT2 protein expression and BCKDHa activity, which was accompanied by decreased Kruppel-like factor 15 protein expression.	Metformin	19-28	branched chain amino acid transaminase 2	Homo sapiens	176-181
32601620-2	2020	Anti-neoplastic effects of metformin are believed through many mechanisms including activation of AMP-activated protein kinase, which controls mammalian target of rapamycin (mTOR) growth regulatory pathway.	Metformin	27-36	mechanistic target of rapamycin kinase	Homo sapiens	143-172
32601620-2	2020	Anti-neoplastic effects of metformin are believed through many mechanisms including activation of AMP-activated protein kinase, which controls mammalian target of rapamycin (mTOR) growth regulatory pathway.	Metformin	27-36	mechanistic target of rapamycin kinase	Homo sapiens	174-178
31102492-7	2020	RESULTS: In parallel with the suppression of interleukin-6 and tumor necrosis factor-alpha production in resting and lipopolysaccharide-stimulated macrophages, metformin could induce an increase in Dicer and most miRNAs.	Metformin	160-169	interleukin 6	Mus musculus	45-58
31102492-7	2020	RESULTS: In parallel with the suppression of interleukin-6 and tumor necrosis factor-alpha production in resting and lipopolysaccharide-stimulated macrophages, metformin could induce an increase in Dicer and most miRNAs.	Metformin	160-169	tumor necrosis factor	Mus musculus	63-90
31711841-5	2020	The most frequently prescribed medications added to metformin were sulfonylurea and basal insulin accounting for 51% (1724/3413) and 37% (1268/3413) respectively.	Metformin	52-61	insulin	Homo sapiens	90-97
31711841-8	2020	CONCLUSION AND RELEVANCE: Type 2 diabetes patients treated with sulfonylurea, basal insulin and GLP-1 agonist as an add on to metformin had significant reductions in HbA1c.	Metformin	126-135	insulin	Homo sapiens	84-91
31753516-0	2020	Intracanal Metformin Promotes Healing of Apical Periodontitis via Suppressing Inducible Nitric Oxide Synthase Expression and Monocyte Recruitment.	Metformin	11-20	nitric oxide synthase 2	Homo sapiens	78-109
31753516-10	2020	RESULTS: Metformin suppressed LPS-induced iNOS and NO production by monocytes.	Metformin	9-18	nitric oxide synthase 2	Rattus norvegicus	42-46
31753516-11	2020	More importantly, metformin inhibited LPS-enhanced CCL-2 synthesis through modulation of the iNOS/NO pathway.	Metformin	18-27	nitric oxide synthase 2	Rattus norvegicus	93-97
31753516-12	2020	Intracanal metformin reduced bone resorption associated with apical periodontitis and suppressed iNOS expression and monocyte recruitment.	Metformin	11-20	nitric oxide synthase 2	Rattus norvegicus	97-101
31753516-14	2020	Suppression of monocyte recruitment through modulation of iNOS expression and NO production is an important mechanism underlying the beneficial effect of metformin.	Metformin	154-163	nitric oxide synthase 2	Rattus norvegicus	58-62
30820523-2	2020	In mice, when metformin treatment (Met) is added to the mTOR inhibitor rapamycin (Rap), median and maximal life span is extended to a greater degree than with Rap or Met alone.	Metformin	14-23	regulatory associated protein of MTOR, complex 1	Mus musculus	71-80
30820523-2	2020	In mice, when metformin treatment (Met) is added to the mTOR inhibitor rapamycin (Rap), median and maximal life span is extended to a greater degree than with Rap or Met alone.	Metformin	14-23	regulatory associated protein of MTOR, complex 1	Mus musculus	82-85
30820523-2	2020	In mice, when metformin treatment (Met) is added to the mTOR inhibitor rapamycin (Rap), median and maximal life span is extended to a greater degree than with Rap or Met alone.	Metformin	14-23	regulatory associated protein of MTOR, complex 1	Mus musculus	159-162
30864661-0	2020	Brain Protein Synthesis Rates in the UM-HET3 Mouse Following Treatment with Rapamycin or Rapamycin with Metformin.	Metformin	104-113	regulatory associated protein of MTOR, complex 1	Mus musculus	89-98
30864661-1	2020	Treatment with the mTOR inhibitor, rapamycin (RAP), alone and in combination with the antidiabetic drug, metformin (RAP+MET), extends lifespan in mice.	Metformin	105-114	regulatory associated protein of MTOR, complex 1	Mus musculus	116-119
30888034-3	2020	Metformin is a widely used, well-tolerated drug that improves insulin sensitivity and displays anti-inflammatory properties.	Metformin	0-9	insulin	Homo sapiens	62-69
32341701-7	2020	The intervention with metformin in diabetic rats inhibited the mammalian target of rapamycin mRNA expression and caused an increase in the transcriptional activity of the Foxp3 gene in parapancreatic adipose tissue.	Metformin	22-31	mechanistic target of rapamycin kinase	Homo sapiens	63-92
31634770-0	2020	Inhibition of midkine by metformin can contribute to its anticancer effects in malignancies: A proposal mechanism of action of metformin in context of endometrial cancer prevention and therapy.	Metformin	25-34	midkine	Homo sapiens	14-21
31634770-0	2020	Inhibition of midkine by metformin can contribute to its anticancer effects in malignancies: A proposal mechanism of action of metformin in context of endometrial cancer prevention and therapy.	Metformin	127-136	midkine	Homo sapiens	14-21
31634770-8	2020	Given the opposite relationship between the actions of metformin and MK, we hypothesize that metformin may act like a novel MK inhibitor in some malignancies.	Metformin	93-102	midkine	Homo sapiens	69-71
31634770-8	2020	Given the opposite relationship between the actions of metformin and MK, we hypothesize that metformin may act like a novel MK inhibitor in some malignancies.	Metformin	93-102	midkine	Homo sapiens	124-126
31634770-9	2020	We also discuss the possible relationship between metformin and MK in the context of EC, the most common gynecological cancer worldwide, which incidence is rising rapidly, in parallel with the increase in obesity, T2DM and insulin resistance.	Metformin	50-59	midkine	Homo sapiens	64-66
31634770-10	2020	In this respect, the therapeutic use of metformin may improve the survival of EC or other cancers, via inhibiting or overcoming the unwanted effects of MK in carcinogenesis.	Metformin	40-49	midkine	Homo sapiens	152-154
31718828-13	2020	CONCLUSION(S): Considering the benefits of metformin on weight loss, high-dose metformin (1,500 mg/day) along with lifestyle modification should be recommended for obese, insulin-resistant women with PCOS.	Metformin	79-88	insulin	Homo sapiens	171-178
32258978-2	2020	We have recently reported that the antidiabetic drug metformin exerts antitumor effects on ESCC by inhibition of nuclear factor kappa B (NF-kappaB) nuclear translocation.	Metformin	53-62	nuclear factor kappa B subunit 1	Homo sapiens	113-135
31816435-0	2020	The influence of metformin on IGF-1 levels in humans: A systematic review and meta-analysis.	Metformin	17-26	insulin like growth factor 1	Homo sapiens	30-35
31816435-1	2020	BACKGROUND: A meta-analysis is needed to comprehensively consolidate findings from the influence of metformin on IGF-1 levels.	Metformin	100-109	insulin like growth factor 1	Homo sapiens	113-118
31816435-2	2020	The present study was conducted with the objective to accurately evaluate the influence of metformin intake on IGF-1 levels via a meta-analysis of randomized controlled trials.	Metformin	91-100	insulin like growth factor 1	Homo sapiens	111-116
31816435-4	2020	Weighted mean difference (WMD) with the 95 % CI were applied for estimating the effects of metformin on serum IGF-1 levels.	Metformin	91-100	insulin like growth factor 1	Homo sapiens	110-115
31816435-6	2020	Pooled results demonstrated an overall non-significant decline in IGF-1 following metformin intake (WMD: -8.292 ng/ml, 95 % CI: -20.248, 3.664, p = 0.174) with heterogeneity among (p = 0.000,I2 = 87.1 %).	Metformin	82-91	insulin like growth factor 1	Homo sapiens	66-71
31816435-8	2020	Moreover, in age 18 < years older metformin intake (WMD: 15.125 ng/ml, 95 % CI: 5.522, 24.729, I2 = 92.5 %) significantly increased IGF-1 than 18 <= years older (WMD:-1.038 ng/ml, 95 % CI: -3.578,1.502,I2 = 78.0 %).	Metformin	34-43	insulin like growth factor 1	Homo sapiens	132-137
31816435-9	2020	Following dose-response evaluation, metformin intake reduced IGF-1 (coefficient for dose-response analysis= -13.14, P = 0.041 and coefficient for liner analysis= -0.066, P = 0.038) significantly based on treatment duration.	Metformin	36-45	insulin like growth factor 1	Homo sapiens	61-66
31816435-10	2020	CONCLUSION: We found in children, intervention duration <12 weeks yielded significant reductions in IGF-1, whilst paradoxically, in participants >18 years old, metformin intake significantly increased IGF-1.	Metformin	160-169	insulin like growth factor 1	Homo sapiens	201-206
31669973-5	2020	After PM2.5 exposure, the AMPKalpha2-/- mice developed more severe lung injury and cardiac dysfunction than were developed in the WT mice; however the administration of metformin was effective in attenuating PM2.5-induced lung injury and cardiac dysfunction in both the WT and AMPKalpha2-/- mice.	Metformin	169-178	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	26-36
31669973-5	2020	After PM2.5 exposure, the AMPKalpha2-/- mice developed more severe lung injury and cardiac dysfunction than were developed in the WT mice; however the administration of metformin was effective in attenuating PM2.5-induced lung injury and cardiac dysfunction in both the WT and AMPKalpha2-/- mice.	Metformin	169-178	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	277-287
32460059-1	2020	Metformin is an anti-diabetic drug known to have anticancer activity by inhibiting mechanistic target of rapamycin (mTOR); however, other molecular mechanisms may also be involved.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	83-114
32460059-1	2020	Metformin is an anti-diabetic drug known to have anticancer activity by inhibiting mechanistic target of rapamycin (mTOR); however, other molecular mechanisms may also be involved.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	116-120
32460059-2	2020	In this study, we examined the effects of metformin on the activity of receptor tyrosine kinases of the TAM (TYRO3, AXL, and MERTK) family, which have important roles in leukemia cell growth.	Metformin	42-51	Myeloproliferative syndrome, transient (transient abnormal myelopoiesis)	Homo sapiens	104-107
32460059-2	2020	In this study, we examined the effects of metformin on the activity of receptor tyrosine kinases of the TAM (TYRO3, AXL, and MERTK) family, which have important roles in leukemia cell growth.	Metformin	42-51	TYRO3 protein tyrosine kinase	Homo sapiens	109-114
32460059-3	2020	The results indicated that metformin suppressed the in vitro growth of four leukemia cell lines, OCI/AML2, OCI/AML3, THP-1, and K562, in a dose-dependent manner, which corresponded to the downregulation of the expression and phosphorylation of AXL and inhibition of its downstream targets such as phosphorylation of STAT3.	Metformin	27-36	RUNX family transcription factor 2	Homo sapiens	111-115
32460059-3	2020	The results indicated that metformin suppressed the in vitro growth of four leukemia cell lines, OCI/AML2, OCI/AML3, THP-1, and K562, in a dose-dependent manner, which corresponded to the downregulation of the expression and phosphorylation of AXL and inhibition of its downstream targets such as phosphorylation of STAT3.	Metformin	27-36	GLI family zinc finger 2	Homo sapiens	117-122
32460059-3	2020	The results indicated that metformin suppressed the in vitro growth of four leukemia cell lines, OCI/AML2, OCI/AML3, THP-1, and K562, in a dose-dependent manner, which corresponded to the downregulation of the expression and phosphorylation of AXL and inhibition of its downstream targets such as phosphorylation of STAT3.	Metformin	27-36	signal transducer and activator of transcription 3	Homo sapiens	316-321
32460059-5	2020	Given that metformin also downregulated expression of TYRO3 and phosphorylation of MERTK, these findings indicate that anti-leukemic effects exerted by metformin could be partly due to the inhibition of TAM kinases.	Metformin	11-20	TYRO3 protein tyrosine kinase	Homo sapiens	54-59
32460059-5	2020	Given that metformin also downregulated expression of TYRO3 and phosphorylation of MERTK, these findings indicate that anti-leukemic effects exerted by metformin could be partly due to the inhibition of TAM kinases.	Metformin	11-20	Myeloproliferative syndrome, transient (transient abnormal myelopoiesis)	Homo sapiens	203-206
32460059-5	2020	Given that metformin also downregulated expression of TYRO3 and phosphorylation of MERTK, these findings indicate that anti-leukemic effects exerted by metformin could be partly due to the inhibition of TAM kinases.	Metformin	152-161	TYRO3 protein tyrosine kinase	Homo sapiens	54-59
32460059-5	2020	Given that metformin also downregulated expression of TYRO3 and phosphorylation of MERTK, these findings indicate that anti-leukemic effects exerted by metformin could be partly due to the inhibition of TAM kinases.	Metformin	152-161	Myeloproliferative syndrome, transient (transient abnormal myelopoiesis)	Homo sapiens	203-206
32460059-6	2020	Thus, metformin has a clinical potential for patients with leukemia cells positive for AXL and the other TAM proteins as well as activated mTOR.	Metformin	6-15	Myeloproliferative syndrome, transient (transient abnormal myelopoiesis)	Homo sapiens	105-108
32460059-6	2020	Thus, metformin has a clinical potential for patients with leukemia cells positive for AXL and the other TAM proteins as well as activated mTOR.	Metformin	6-15	mechanistic target of rapamycin kinase	Homo sapiens	139-143
31474154-0	2020	Co-Treatment with Sulforaphane and Nano-Metformin Molecules Accelerates Apoptosis in HER2+ Breast Cancer Cells by Inhibiting Key Molecules.	Metformin	40-49	erb-b2 receptor tyrosine kinase 2	Homo sapiens	85-89
31501521-6	2020	Human clinical surveys also linked the expression of TR4, lncTASR, and AXL to the RCC survival, and results from multiple RCC cell lines revealed that targeting this newly identified TR4-mediated signaling with small molecules, including tretinoin, metformin, or TR4-shRNAs, all led to increase the sunitinib sensitivity to better suppress the RCC progression, and our preclinical study using the in vivo mouse model further proved tretinoin had a better synergistic effect to increase sunitinib sensitivity to suppress RCC progression.	Metformin	249-258	nuclear receptor subfamily 2 group C member 2	Homo sapiens	183-186
31501521-6	2020	Human clinical surveys also linked the expression of TR4, lncTASR, and AXL to the RCC survival, and results from multiple RCC cell lines revealed that targeting this newly identified TR4-mediated signaling with small molecules, including tretinoin, metformin, or TR4-shRNAs, all led to increase the sunitinib sensitivity to better suppress the RCC progression, and our preclinical study using the in vivo mouse model further proved tretinoin had a better synergistic effect to increase sunitinib sensitivity to suppress RCC progression.	Metformin	249-258	nuclear receptor subfamily 2 group C member 2	Homo sapiens	183-186
31667980-1	2020	Previous randomized and observational studies on the efficacy of metformin in pregnancy to reduce incident gestational diabetes mellitus (GDM) in women at high risk (obesity, polycystic ovary syndrome [PCOS], or pregestational insulin resistance) have been conflicting and several groups are planning further randomized controlled trials (RCTs) to answer this question conclusively.	Metformin	65-74	insulin	Homo sapiens	227-234
33191721-2	2020	AIM OF THE STUDY: The aim of the study was to compare the impact of normoglycemia and hyperglycemia with doses of metformin on vivacity and prolifer-ation of cancer cell lines (MCF-7, MCF-7/DX, A549, CCRF/CEM, THP-1, NHDF).	Metformin	114-123	GLI family zinc finger 2	Homo sapiens	210-215
31283677-8	2020	KRAS, GRB2, PCK2, BCL2L1, INSL3, DOK3, and PTPN1 were among the most significantly upregulated genes in both immunosuppression and diabetes subsets and were appropriately reverted by metformin as confirmed in vitro.	Metformin	183-192	growth factor receptor bound protein 2	Homo sapiens	6-10
31283677-8	2020	KRAS, GRB2, PCK2, BCL2L1, INSL3, DOK3, and PTPN1 were among the most significantly upregulated genes in both immunosuppression and diabetes subsets and were appropriately reverted by metformin as confirmed in vitro.	Metformin	183-192	BCL2 like 1	Homo sapiens	18-24
31678650-0	2020	Metformin inhibited homocysteine-induced upregulation of endothelin receptors through the Sirt1/NF-kappaB signaling pathway in vascular smooth muscle cells.	Metformin	0-9	sirtuin 1	Rattus norvegicus	90-95
31678650-10	2020	The results showed that Met could significantly inhibit the Hcy-induced upregulation of endothelin receptors (including ETA and ETB receptor) protein expression and endothelin receptor-mediated vasoconstriction, and it recovered the Hcy-induced decrease in silent information regulator 1 (Sirt1) in a dosage-dependent manner in SMA.	Metformin	24-27	sirtuin 1	Rattus norvegicus	257-287
31678650-10	2020	The results showed that Met could significantly inhibit the Hcy-induced upregulation of endothelin receptors (including ETA and ETB receptor) protein expression and endothelin receptor-mediated vasoconstriction, and it recovered the Hcy-induced decrease in silent information regulator 1 (Sirt1) in a dosage-dependent manner in SMA.	Metformin	24-27	sirtuin 1	Rattus norvegicus	289-294
31678650-11	2020	However, Nic (a Sirt1 inhibitor) recovered the levels of Met-inhibited endothelin receptors and acetylated p65.	Metformin	57-60	sirtuin 1	Rattus norvegicus	16-21
31678650-12	2020	Furthermore, the in vivo results showed that Met not only significantly the inhibited HHcy-induced upregulation of endothelin receptors and acetylated p65 but also recovered the HHcy-induced decrease in Sirt1 in a dosage-dependent manner in SMA.	Metformin	45-48	synaptotagmin 1	Rattus norvegicus	151-154
31678650-12	2020	Furthermore, the in vivo results showed that Met not only significantly the inhibited HHcy-induced upregulation of endothelin receptors and acetylated p65 but also recovered the HHcy-induced decrease in Sirt1 in a dosage-dependent manner in SMA.	Metformin	45-48	sirtuin 1	Rattus norvegicus	203-208
31678650-15	2020	In conclusion, these data demonstrated that Met inhibited the Hcy-induced increase in endothelin receptor expression by activating Sirt1 and then inhibiting NF-kappaB in VSMCs.	Metformin	44-47	sirtuin 1	Rattus norvegicus	131-136
32258978-2	2020	We have recently reported that the antidiabetic drug metformin exerts antitumor effects on ESCC by inhibition of nuclear factor kappa B (NF-kappaB) nuclear translocation.	Metformin	53-62	nuclear factor kappa B subunit 1	Homo sapiens	137-146
31950065-5	2019	GPR40 was involved in metformin reversing metabolic inflammation key marker TLR4 activation-mediated beta-cell injury.	Metformin	22-31	toll-like receptor 4	Rattus norvegicus	76-80
31851935-0	2019	Mesothelial Cell HIF1alpha Expression Is Metabolically Downregulated by Metformin to Prevent Oncogenic Tumor-Stromal Crosstalk.	Metformin	72-81	hypoxia inducible factor 1 subunit alpha	Homo sapiens	17-26
31851935-3	2019	Metformin interrupts bidirectional signaling between tumor and mesothelial cells by blocking OvCa cell TGF-beta signaling and mesothelial cell production of CCL2 and IL-8.	Metformin	0-9	C-X-C motif chemokine ligand 8	Homo sapiens	166-170
31851935-5	2019	Through repressing this TCA enzyme and its metabolite, succinate, metformin activated prolyl hydroxylases (PHDs), resulting in the degradation of hypoxia-inducible factor 1alpha (HIF1alpha) in mesothelial cells.	Metformin	66-75	hypoxia inducible factor 1 subunit alpha	Homo sapiens	146-177
31851935-5	2019	Through repressing this TCA enzyme and its metabolite, succinate, metformin activated prolyl hydroxylases (PHDs), resulting in the degradation of hypoxia-inducible factor 1alpha (HIF1alpha) in mesothelial cells.	Metformin	66-75	hypoxia inducible factor 1 subunit alpha	Homo sapiens	179-188
31851935-6	2019	Disruption of HIF1alpha-driven IL-8 signaling in mesothelial cells by metformin results in reduced OvCa invasion in an organotypic 3D model.	Metformin	70-79	hypoxia inducible factor 1 subunit alpha	Homo sapiens	14-23
31851935-6	2019	Disruption of HIF1alpha-driven IL-8 signaling in mesothelial cells by metformin results in reduced OvCa invasion in an organotypic 3D model.	Metformin	70-79	C-X-C motif chemokine ligand 8	Homo sapiens	31-35
31934270-0	2019	Metformin Protects against Oxidative Stress Injury Induced by Ischemia/Reperfusion via Regulation of the lncRNA-H19/miR-148a-3p/Rock2 Axis.	Metformin	0-9	Rho-associated coiled-coil containing protein kinase 2	Mus musculus	128-133
31934270-13	2019	The expression of lncRNA-H19 and Rock2 could be downregulated with metformin in vivo and in vitro.	Metformin	67-76	Rho-associated coiled-coil containing protein kinase 2	Mus musculus	33-38
31934270-14	2019	In conclusion, our study confirmed that metformin exerts neuroprotective effects by regulating ischemic stroke-induced oxidative stress injury via the lncRNA-H19/miR-148a-3p/Rock2 axis.	Metformin	40-49	Rho-associated coiled-coil containing protein kinase 2	Mus musculus	174-179
31626790-0	2019	Metformin attenuates hepatoma cell proliferation by decreasing glycolytic flux through the HIF-1alpha/PFKFB3/PFK1 pathway.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	91-101
31705902-3	2019	Clinical evidence now suggests that most of metformin benefits originate from its actions in the gut, involving hormone signaling by glucagon-like peptide 1 and peptide YY.	Metformin	44-53	glucagon	Homo sapiens	133-156
31705902-3	2019	Clinical evidence now suggests that most of metformin benefits originate from its actions in the gut, involving hormone signaling by glucagon-like peptide 1 and peptide YY.	Metformin	44-53	peptide YY	Homo sapiens	161-171
32224233-5	2020	In diabetic patients, oral antidiabetic drugs (glyburide, metformin or pioglitazone) reduced circulating levels fractalkine and E-selectin (both P < .05), without affecting vascular responses (all P > .05).	Metformin	58-67	C-X3-C motif chemokine ligand 1	Homo sapiens	112-123
31626790-10	2019	Mechanistically, PFKFB3,a potent allosteric activator of PFK1, was markedly suppressed through inhibiting hypoxia-induced factor 1 (HIF-1alpha) accumulation mediated by metformin.	Metformin	169-178	hypoxia inducible factor 1 subunit alpha	Homo sapiens	132-142
31626790-11	2019	SIGNIFICANCE: Taken together these data indicate that HIF-1alpha/PFKFB3/PFK1 regulatory axis is a vital determinant of glucose metabolic reprogramming in hepatocellular carcinoma, which gives new insights into the action of metformin in combatting liver cancer.	Metformin	224-233	hypoxia inducible factor 1 subunit alpha	Homo sapiens	54-64
31821361-1	2019	BACKGROUND: Metformin treatment (1000-2000 mg/day) over 6 months in pubertal children and/or adolescents with obesity and hyperinsulinism is associated with a reduction in body mass index (BMI) and the insulin resistance index (HOMA-IR).	Metformin	12-21	insulin	Homo sapiens	127-134
31462593-0	2019	Glucose-responsive Insulinoma with Insulin Hypersecretion Suppressed by Metformin.	Metformin	72-81	insulin	Homo sapiens	19-26
31462593-1	2019	In type 2 diabetes mellitus, metformin suppresses excessive insulin secretion in relation to the intake of glucose.	Metformin	29-38	insulin	Homo sapiens	60-67
31821361-7	2019	The effect of metformin on the reduction of BMI-SDS, leptin, leptin-to-HMW adiponectin ratio, hsCRP, and liver fat seemed to be maintained after completing the 24 months of treatment.	Metformin	14-23	adiponectin, C1Q and collagen domain containing	Homo sapiens	75-86
31805999-0	2019	PTPRD-inactivation-induced CXCL8 promotes angiogenesis and metastasis in gastric cancer and is inhibited by metformin.	Metformin	108-117	C-X-C motif chemokine ligand 8	Homo sapiens	27-32
31811400-2	2019	RECENT FINDINGS: There has been increasing interest in the use of non-insulin agents, primarily metformin and glyburide (which both cross the placenta).	Metformin	96-105	insulin	Homo sapiens	70-77
31801093-6	2019	Inducible binding of 250 proteins following metformin treatment is observed, 44% of which proteins bind in a manner requiring LKB1.	Metformin	44-53	serine/threonine kinase 11	Mus musculus	126-130
31801093-7	2019	Beyond AMPK, metformin activates protein kinase D and MAPKAPK2 in an LKB1-independent manner, revealing additional kinases that may mediate aspects of metformin response.	Metformin	13-22	MAP kinase-activated protein kinase 2	Mus musculus	54-62
31801093-7	2019	Beyond AMPK, metformin activates protein kinase D and MAPKAPK2 in an LKB1-independent manner, revealing additional kinases that may mediate aspects of metformin response.	Metformin	13-22	serine/threonine kinase 11	Mus musculus	69-73
31870092-0	2019	Metformin Inhibit Cervical Cancer Migration by Suppressing the FAK/Akt Signaling Pathway.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	67-70
31415212-3	2019	Metformin improves insulin resistance and metabolic function.	Metformin	0-9	insulin	Homo sapiens	19-26
31870092-7	2019	The suppression of migration mediated through the regulatory proteins such as focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (Akt), Rac1 and RhoA after metformin treatment.	Metformin	164-173	AKT serine/threonine kinase 1	Homo sapiens	138-141
31870092-7	2019	The suppression of migration mediated through the regulatory proteins such as focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (Akt), Rac1 and RhoA after metformin treatment.	Metformin	164-173	ras homolog family member A	Homo sapiens	153-157
31870092-8	2019	CONCLUSION: Metformin displays antimigration effects in cervical cancer cells by inhibiting filopodia and lamellipodia formation through the suppression of FAK, Akt and its downstream Rac1 and RhoA protein.	Metformin	12-21	AKT serine/threonine kinase 1	Homo sapiens	161-164
31870092-8	2019	CONCLUSION: Metformin displays antimigration effects in cervical cancer cells by inhibiting filopodia and lamellipodia formation through the suppression of FAK, Akt and its downstream Rac1 and RhoA protein.	Metformin	12-21	ras homolog family member A	Homo sapiens	193-197
31628524-8	2019	Metformin effectively inhibited the increase of IGF-1 and maintained the IGFBP-1.	Metformin	0-9	insulin like growth factor 1	Homo sapiens	48-53
31583436-1	2019	PURPOSE: Metformin activates AMP-related pathways leading to inactivation of mammalian target of rapamycin (mTOR) and suppression of its downstream effectors, crucial for cancer growth.	Metformin	9-18	mechanistic target of rapamycin kinase	Homo sapiens	77-106
31583436-1	2019	PURPOSE: Metformin activates AMP-related pathways leading to inactivation of mammalian target of rapamycin (mTOR) and suppression of its downstream effectors, crucial for cancer growth.	Metformin	9-18	mechanistic target of rapamycin kinase	Homo sapiens	108-112
31413010-1	2019	PURPOSE: Preclinical and retrospective studies suggested a role for metformin in sensitizing diabetic non-small cell lung cancer (NSCLC) patients to epidermal growth factor receptor(EGFR) tyrosine kinase inhibitors(TKIs).	Metformin	68-77	epidermal growth factor receptor	Homo sapiens	182-186
31550676-6	2019	In additionally, metformin could enhance the phosphorylation of AMPK, reduce STAT3 phosphorylation levels, and down-regulate the inhibitory function of G-MDSCs in vitro.	Metformin	17-26	signal transducer and activator of transcription 3	Mus musculus	77-82
31413010-0	2019	Combination of metformin and gefitinib as first-line therapy for non-diabetic advanced NSCLC patients with EGFR mutations: A randomized, double-blind phase 2 trial.	Metformin	15-24	epidermal growth factor receptor	Homo sapiens	107-111
31413010-1	2019	PURPOSE: Preclinical and retrospective studies suggested a role for metformin in sensitizing diabetic non-small cell lung cancer (NSCLC) patients to epidermal growth factor receptor(EGFR) tyrosine kinase inhibitors(TKIs).	Metformin	68-77	epidermal growth factor receptor	Homo sapiens	149-181
31620963-0	2019	Metformin-induced AMPK activation stimulates remyelination through induction of neurotrophic factors, downregulation of NogoA and recruitment of Olig2+ precursor cells in the cuprizone murine model of multiple sclerosis.	Metformin	0-9	oligodendrocyte transcription factor 2	Mus musculus	145-150
31620963-7	2019	RESULTS: Our finding indicated that consumption of metformin during the recovery period potentially induced an active form of AMPK (p-AMPK) and promoted repopulation of mature OLGs (MOG+ cells, MBP+ cells) in CC through up-regulation of BDNF, CNTF, and NGF as well as down-regulation of NogoA and recruitment of Olig2+ precursor cells.	Metformin	51-60	oligodendrocyte transcription factor 2	Mus musculus	312-317
31856288-0	2019	Factors Associated with the Need for Insulin as a Complementary Treatment to Metformin in Gestational Diabetes Mellitus.	Metformin	77-86	insulin	Homo sapiens	37-44
31633875-0	2019	The displacement study of 99m Tc-DTPA-Human serum albumin binding in presence of furosemide and metformin by using equilibrium dialysis and molecular docking.	Metformin	96-105	albumin	Homo sapiens	50-57
31744691-8	2019	Metformin promoted the expression of p-AMPK, P53, P21CIP1 and P27KIP1, while inhibited the expression of CDK4 and CyclinD1.	Metformin	0-9	cyclin dependent kinase inhibitor 1A	Homo sapiens	50-57
32694673-6	2019	In primary mouse hepatocytes, metformin stimulates the secretion of GDF15 by increasing the expression of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP; also known as DDIT3).	Metformin	30-39	activating transcription factor 4	Mus musculus	106-139
32694673-6	2019	In primary mouse hepatocytes, metformin stimulates the secretion of GDF15 by increasing the expression of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP; also known as DDIT3).	Metformin	30-39	activating transcription factor 4	Mus musculus	141-145
32694673-7	2019	In wild-type mice fed a high-fat diet, oral administration of metformin increases serum GDF15 and reduces food intake, body mass, fasting insulin and glucose intolerance; these effects are eliminated in GDF15 null mice.	Metformin	62-71	insulin	Homo sapiens	138-145
31127593-7	2019	Fasting plasma glucose, serum high-density lipoprotein and indices of insulin sensitivity significantly improved in metformin group.	Metformin	116-125	insulin	Homo sapiens	70-77
31545909-0	2019	Fuzhu jiangtang granules combined with metformin reduces insulin resistance in skeletal muscle of diabetic rats via PI3K/Akt signaling.	Metformin	39-48	AKT serine/threonine kinase 1	Rattus norvegicus	121-124
31833226-8	2019	Also whole-body insulin sensitivity was enhanced by 4 days metformin treatment, that is reduced fasting plasma insulin and HOMA-IR.	Metformin	59-68	insulin	Homo sapiens	16-23
31833226-8	2019	Also whole-body insulin sensitivity was enhanced by 4 days metformin treatment, that is reduced fasting plasma insulin and HOMA-IR.	Metformin	59-68	insulin	Homo sapiens	111-118
31852643-6	2019	In animal model, The staining of alpha-SMA showed smooth muscle cells migrated to the intima or even to the lipid area from the media of aorta in CTL group compared to the Met group.	Metformin	172-175	actin alpha 2, smooth muscle, aorta	Mus musculus	33-42
31780804-0	2019	Full title: High glucose protects mesenchymal stem cells from metformin-induced apoptosis through the AMPK-mediated mTOR pathway.	Metformin	62-71	mechanistic target of rapamycin kinase	Homo sapiens	116-120
31780804-6	2019	In this study, we found that metformin induces MSC apoptosis during intensive glucose control, while high glucose (standard glucose control) could significantly reverse its adverse effect in an AMPK-mTOR pathway dependent manner.	Metformin	29-38	mechanistic target of rapamycin kinase	Homo sapiens	199-203
31788033-9	2019	As compared MET to HFD, differential expressed proteins in WAT and BAT were mainly assigned to the pathways of EIF2 signaling and mitochondrial dysfunction, respectively.	Metformin	12-15	eukaryotic translation initiation factor 2, subunit 2 (beta)	Mus musculus	111-115
31788033-10	2019	In the pathways, CPT1a in WAT, CPT1b and CPT2 in BAT were down-regulated by metformin significantly.	Metformin	76-85	carnitine palmitoyltransferase 2	Mus musculus	41-45
31772144-0	2019	Metformin decreases LPS-induced inflammatory response in rabbit annulus fibrosus stem/progenitor cells by blocking HMGB1 release.	Metformin	0-9	high mobility group protein B1	Oryctolagus cuniculus	115-120
31772144-7	2019	Following addition of metformin to LPS-containing medium, HMGB1 was retained in the nuclei of AFSCs and the production of PGE2 and HMGB1 was reduced.	Metformin	22-31	high mobility group protein B1	Oryctolagus cuniculus	58-63
31772144-7	2019	Following addition of metformin to LPS-containing medium, HMGB1 was retained in the nuclei of AFSCs and the production of PGE2 and HMGB1 was reduced.	Metformin	22-31	high mobility group protein B1	Oryctolagus cuniculus	131-136
31772144-9	2019	The findings indicated that metformin exerted an anti-inflammatory effect by blocking the HMGB1 translocation and by inhibiting catabolic production and cell senescence in AFSCs.	Metformin	28-37	high mobility group protein B1	Oryctolagus cuniculus	90-95
31886264-3	2019	Metformin relies on organic cation transporters (OCT1), a polyspecific cell membrane of the solute carrier 22A (SLC22A) gene family, to facilitate its intracellular uptake and action on complex I of the respiratory chain of mitochondria.	Metformin	0-9	solute carrier family 22 member 1	Homo sapiens	49-53
31886264-7	2019	Metformin phosphorylates extracellular signal-regulated kinase (ERK), stimulates endothelial and inducible nitric oxide synthases (e/iNOS), inhibits the GSK3beta/Wnt/beta-catenin pathway, and promotes osteogenic differentiation of osteoblasts.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	25-62
31886264-7	2019	Metformin phosphorylates extracellular signal-regulated kinase (ERK), stimulates endothelial and inducible nitric oxide synthases (e/iNOS), inhibits the GSK3beta/Wnt/beta-catenin pathway, and promotes osteogenic differentiation of osteoblasts.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	64-67
31886264-7	2019	Metformin phosphorylates extracellular signal-regulated kinase (ERK), stimulates endothelial and inducible nitric oxide synthases (e/iNOS), inhibits the GSK3beta/Wnt/beta-catenin pathway, and promotes osteogenic differentiation of osteoblasts.	Metformin	0-9	nitric oxide synthase 2	Homo sapiens	133-137
31693269-11	2019	After adjustment, metformin was associated with reduced absolute risk of planned elective c-section (RD = -2.3, 95% CI, -4.3 to -0.3), large for gestational age (RD = -3.7, 95% CI, -5.5 to -1.8), and neonatal hypoglycemia (RD = -5.0, 95% CI, -6.9 to -3.2) compared with insulin.	Metformin	18-27	insulin	Homo sapiens	270-277
31849810-6	2019	Clinically, evidence for involvement of insulin signaling pathways in DM1 is based on the increased incidence of insulin resistance seen in clinical practice and recent trial evidence of beneficial effects of metformin on muscle function.	Metformin	209-218	insulin	Homo sapiens	40-47
31886264-8	2019	The effect of metformin on hyperglycemia decreases intracellular reactive oxygen species (ROS) and advanced glycation end-products (AGEs) in collagen, and reduced serum levels of insulin-like growth factors (IGF-1) were beneficial for bone formation.	Metformin	14-23	insulin like growth factor 1	Homo sapiens	208-213
31828167-2	2019	It remains to be fully elucidated whether the use of metformin, an insulin sensitizer, and/or sulfonylureas, insulin secretagogues, affects cancer incidence in subjects with type 2 diabetes mellitus.	Metformin	53-62	insulin	Homo sapiens	67-74
31562866-0	2019	PlGF signaling and macrophage repolarization contribute to the anti-neoplastic effect of metformin.	Metformin	89-98	placental growth factor	Homo sapiens	0-4
31562866-2	2019	Metformin has been reported to have an inhibitory effect on PlGF expression in a breast cancer model.	Metformin	0-9	placental growth factor	Homo sapiens	60-64
31562866-3	2019	However, little is known about whether the anti-neoplastic activity of metformin is contributed by its inhibitory effect on PlGF expression.	Metformin	71-80	placental growth factor	Homo sapiens	124-128
31562866-8	2019	Metformin significantly decreased the secretion and mRNA levels of PlGF, which greatly contributed to its inhibitory effect on the proliferation of breast cancer cells with high P1GF expression.	Metformin	0-9	placental growth factor	Homo sapiens	67-71
31562866-11	2019	These findings indicated that both autocrine and paracrine PlGF signaling and macrophage repolarization are involved in the progression of breast cancer, which could be targeted by metformin.	Metformin	181-190	placental growth factor	Homo sapiens	59-63
31563650-9	2019	Meanwhile in rats with NAFLD: i) metformin inhibited hepatic total cholesterol and TGF-beta, increased diarrhea frequency, and slightly decreased liver steatosis, and fibrosis; ii) 4-hydroxychalcone decreased IL-6, TNF-alpha and TGF-beta, increased IL-10, and markedly decreased liver steatosis and fibrosis; and iii) co-treatment markedly decreased food intake, total caloric intake, and body weight, increased diarrhea; increased IL-10, showing and intermediate effect on decrease TNF-alpha, TGF-beta, liver steatosis and fibrosis.	Metformin	33-42	transforming growth factor, beta 1	Rattus norvegicus	83-91
31563650-9	2019	Meanwhile in rats with NAFLD: i) metformin inhibited hepatic total cholesterol and TGF-beta, increased diarrhea frequency, and slightly decreased liver steatosis, and fibrosis; ii) 4-hydroxychalcone decreased IL-6, TNF-alpha and TGF-beta, increased IL-10, and markedly decreased liver steatosis and fibrosis; and iii) co-treatment markedly decreased food intake, total caloric intake, and body weight, increased diarrhea; increased IL-10, showing and intermediate effect on decrease TNF-alpha, TGF-beta, liver steatosis and fibrosis.	Metformin	33-42	interleukin 6	Rattus norvegicus	209-213
31563650-9	2019	Meanwhile in rats with NAFLD: i) metformin inhibited hepatic total cholesterol and TGF-beta, increased diarrhea frequency, and slightly decreased liver steatosis, and fibrosis; ii) 4-hydroxychalcone decreased IL-6, TNF-alpha and TGF-beta, increased IL-10, and markedly decreased liver steatosis and fibrosis; and iii) co-treatment markedly decreased food intake, total caloric intake, and body weight, increased diarrhea; increased IL-10, showing and intermediate effect on decrease TNF-alpha, TGF-beta, liver steatosis and fibrosis.	Metformin	33-42	tumor necrosis factor	Rattus norvegicus	215-224
31563650-9	2019	Meanwhile in rats with NAFLD: i) metformin inhibited hepatic total cholesterol and TGF-beta, increased diarrhea frequency, and slightly decreased liver steatosis, and fibrosis; ii) 4-hydroxychalcone decreased IL-6, TNF-alpha and TGF-beta, increased IL-10, and markedly decreased liver steatosis and fibrosis; and iii) co-treatment markedly decreased food intake, total caloric intake, and body weight, increased diarrhea; increased IL-10, showing and intermediate effect on decrease TNF-alpha, TGF-beta, liver steatosis and fibrosis.	Metformin	33-42	transforming growth factor, beta 1	Rattus norvegicus	229-237
31563650-9	2019	Meanwhile in rats with NAFLD: i) metformin inhibited hepatic total cholesterol and TGF-beta, increased diarrhea frequency, and slightly decreased liver steatosis, and fibrosis; ii) 4-hydroxychalcone decreased IL-6, TNF-alpha and TGF-beta, increased IL-10, and markedly decreased liver steatosis and fibrosis; and iii) co-treatment markedly decreased food intake, total caloric intake, and body weight, increased diarrhea; increased IL-10, showing and intermediate effect on decrease TNF-alpha, TGF-beta, liver steatosis and fibrosis.	Metformin	33-42	tumor necrosis factor	Rattus norvegicus	483-492
31563650-9	2019	Meanwhile in rats with NAFLD: i) metformin inhibited hepatic total cholesterol and TGF-beta, increased diarrhea frequency, and slightly decreased liver steatosis, and fibrosis; ii) 4-hydroxychalcone decreased IL-6, TNF-alpha and TGF-beta, increased IL-10, and markedly decreased liver steatosis and fibrosis; and iii) co-treatment markedly decreased food intake, total caloric intake, and body weight, increased diarrhea; increased IL-10, showing and intermediate effect on decrease TNF-alpha, TGF-beta, liver steatosis and fibrosis.	Metformin	33-42	transforming growth factor, beta 1	Rattus norvegicus	229-237
32090192-11	2020	Conclusions: The combination of exercise and metformin statistically significantly improved insulin and associated metabolic markers, as compared to the control arm, with potential greater effect than either exercise or metformin alone though power limited formal synergy testing.	Metformin	45-54	insulin	Homo sapiens	92-99
31686542-4	2022	Importantly, miR-33b mimic inhibited the increasing effects of metformin on the expression of CPT1 and CROT.Conclusion: These findings suggest that metformin attenuates high glucose-induced lipid accumulation in HepG2 cell by downregulating the expression of miR-33b.	Metformin	63-72	carnitine O-octanoyltransferase	Homo sapiens	103-107
31703101-5	2019	Significantly elevated faecal sIgA levels during administration of metformin, and its correlation with the expression of genes associated with immune response (CXCR4, HLA-DQA1, MAP3K14, TNFRSF21, CCL4, ACVR1B, PF4, EPOR, CXCL8) supports a novel hypothesis of strong association between metformin and intestinal immune system, and for the first time provide evidence for altered RNA expression as a contributing mechanism of metformin"s action.	Metformin	67-76	C-X-C motif chemokine ligand 8	Homo sapiens	221-226
31070566-8	2019	After 12 months of metformin treatment, the T allele was associated with 25.9% lower fasting insulin levels (95% CI 10.9-38.3%, p = 0.002) and 29.1% lower HOMA-IR index (95% CI 10.1-44.1%, p = 0.005), after adjustment for baseline values.	Metformin	19-28	insulin	Homo sapiens	93-100
31070566-11	2019	Our results suggest that the TCF7L2 rs7903146 variant affects markers of insulin resistance and glycemic response to metformin in newly diagnosed patients with T2D within the first year of metformin treatment.	Metformin	189-198	insulin	Homo sapiens	73-80
31433832-7	2019	Further, we demonstrate that metformin can suppress CD54 expression on CD4+ T cells by inhibiting NF-kappaB/p65 phosphorylation.	Metformin	29-38	CD4 molecule	Homo sapiens	71-74
31686542-2	2022	To investigate the potential role of miR-33b in lipid accumulation, the mimic of the miR-33b was transfected into HepG2 cells.Results: We found that metformin reduces high glucose-induced lipid accumulation in HepG2 cells through inhibiting of SREBP1c and FAS and increasing the expression of CPT1 and CROT.	Metformin	149-158	carnitine palmitoyltransferase 1A	Homo sapiens	293-297
31686542-2	2022	To investigate the potential role of miR-33b in lipid accumulation, the mimic of the miR-33b was transfected into HepG2 cells.Results: We found that metformin reduces high glucose-induced lipid accumulation in HepG2 cells through inhibiting of SREBP1c and FAS and increasing the expression of CPT1 and CROT.	Metformin	149-158	carnitine O-octanoyltransferase	Homo sapiens	302-306
31686542-4	2022	Importantly, miR-33b mimic inhibited the increasing effects of metformin on the expression of CPT1 and CROT.Conclusion: These findings suggest that metformin attenuates high glucose-induced lipid accumulation in HepG2 cell by downregulating the expression of miR-33b.	Metformin	63-72	carnitine palmitoyltransferase 1A	Homo sapiens	94-98
31686542-4	2022	Importantly, miR-33b mimic inhibited the increasing effects of metformin on the expression of CPT1 and CROT.Conclusion: These findings suggest that metformin attenuates high glucose-induced lipid accumulation in HepG2 cell by downregulating the expression of miR-33b.	Metformin	148-157	carnitine palmitoyltransferase 1A	Homo sapiens	94-98
31686542-4	2022	Importantly, miR-33b mimic inhibited the increasing effects of metformin on the expression of CPT1 and CROT.Conclusion: These findings suggest that metformin attenuates high glucose-induced lipid accumulation in HepG2 cell by downregulating the expression of miR-33b.	Metformin	148-157	carnitine O-octanoyltransferase	Homo sapiens	103-107
31693892-2	2019	Metformin, a first-line antidiabetic drug, functions mainly by improving patients" hyperglycemia and insulin resistance.	Metformin	0-9	insulin	Homo sapiens	101-108
31647106-18	2019	Meta-analyses of effect modifications showed a positive interaction between baseline insulin levels and treatment effects on live birth in the comparison between CC plus metformin and CC (interaction RR 1.03, 95% CI 1.01-1.06).	Metformin	170-179	insulin	Homo sapiens	85-92
31647106-21	2019	Treatment effects of letrozole are influenced by baseline serum levels of total testosterone, while those of CC plus metformin are affected by baseline serum levels of insulin.	Metformin	117-126	insulin	Homo sapiens	168-175
31693892-6	2019	Furthermore, HFD-fed-mice with liver-specific knockout of AMPKalpha1/2 subunits exhibit higher blood glucose levels when treated with metformin.	Metformin	134-143	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	58-70
31395589-7	2019	CONCLUSIONS: The odds of having a TN rather than ER+/HER2- breast cancer is greater for women with type II diabetes, and particularly for those who were users of metformin.	Metformin	162-171	erb-b2 receptor tyrosine kinase 2	Homo sapiens	53-57
31220411-3	2019	We found that metformin decreased the cell apoptosis rate and death, ratio of Bcl-2/Bax, and expression of NR2A and NR2B, and increased the expression of LC3 in Abeta25-35 -treated SH-SY5Y cells.	Metformin	14-23	BCL2 apoptosis regulator	Homo sapiens	78-83
31220411-3	2019	We found that metformin decreased the cell apoptosis rate and death, ratio of Bcl-2/Bax, and expression of NR2A and NR2B, and increased the expression of LC3 in Abeta25-35 -treated SH-SY5Y cells.	Metformin	14-23	BCL2 associated X, apoptosis regulator	Homo sapiens	84-87
31220411-3	2019	We found that metformin decreased the cell apoptosis rate and death, ratio of Bcl-2/Bax, and expression of NR2A and NR2B, and increased the expression of LC3 in Abeta25-35 -treated SH-SY5Y cells.	Metformin	14-23	glutamate ionotropic receptor NMDA type subunit 2A	Homo sapiens	107-111
31518877-0	2019	Metformin inhibited Nod-like receptor protein 3 inflammasomes activation and suppressed diabetes-accelerated atherosclerosis in apoE-/- mice.	Metformin	0-9	apolipoprotein E	Mus musculus	128-132
31518877-10	2019	CONCLUSIONS: Metformin inhibited NLRP3 inflammasomes activation and suppressed diabetes-accelerated atherosclerosis in apoE-/- mice, which at least partially through activation of AMPK and regulation of thioredoxin-1/thioredoxin-interacting protein.	Metformin	13-22	apolipoprotein E	Mus musculus	119-123
31698699-7	2019	Additionally, treatment with metformin and 2DG (5 mM) inhibited the Akt/mTOR pathway and down-regulated the cell-cycle-related proteins such as p-cyclin B1 (S147) and cyclins D1 and D2 when compared to cells that were treated with either 2DG or metformin alone.	Metformin	29-38	thymoma viral proto-oncogene 1	Mus musculus	68-71
31427432-3	2019	Following a 30 minute preincubation with an inhibitor, approximately 50-fold higher inhibition potency was observed for Cyclosporine (CsA) against OCT1-mediated uptake of metformin as compared to coincubation, with IC50 values of 0.43 +- 0.12 and 21.6 +- 4.5 muM, respectively.	Metformin	171-180	solute carrier family 22 member 1	Homo sapiens	147-151
31395589-7	2019	CONCLUSIONS: The odds of having a TN rather than ER+/HER2- breast cancer is greater for women with type II diabetes, and particularly for those who were users of metformin.	Metformin	162-171	estrogen receptor 1	Homo sapiens	49-51
31427432-8	2019	A short (30 min) exposure to 10 muM CsA produced long-lasting (at least 120 min) inhibition of the OCT1-mediated uptake of metformin in OCT1-HEK293 cells, which was likely attributable to the retention of CsA in the cells, as shown by the fact that inhibitory cellular concentrations of CsA are maintained long after the removal of the compound from incubation buffer.	Metformin	123-132	solute carrier family 22 member 1	Homo sapiens	99-103
31427432-8	2019	A short (30 min) exposure to 10 muM CsA produced long-lasting (at least 120 min) inhibition of the OCT1-mediated uptake of metformin in OCT1-HEK293 cells, which was likely attributable to the retention of CsA in the cells, as shown by the fact that inhibitory cellular concentrations of CsA are maintained long after the removal of the compound from incubation buffer.	Metformin	123-132	solute carrier family 22 member 1	Homo sapiens	136-140
31511257-6	2019	In vivo inhibition of OCT2/MATE2-K by a single dose of DX-619 in cynomolgus monkeys resulted in the elevation of the area under the curve of m1A (1.72-fold) as well as metformin (2.18-fold).	Metformin	168-177	POU domain, class 2, transcription factor 2	Mus musculus	22-26
31427432-12	2019	For the first time, we observed a 50-fold increase in CsA inhibitory potency against OCT1-mediated transport of metformin following a preincubation step.	Metformin	112-121	solute carrier family 22 member 1	Homo sapiens	85-89
30989649-0	2019	Metformin treatment alleviates polycystic ovary syndrome by decreasing the expression of MMP-2 and MMP-9 via H19/miR-29b-3p and AKT/mTOR/autophagy signaling pathways.	Metformin	0-9	AKT serine/threonine kinase 1	Rattus norvegicus	128-131
31683341-0	2019	Treatment with Metformin and Combination of Metformin Plus Pioglitazone on Serum Levels of IL-6 and IL-8 in Polycystic Ovary Syndrome: A Randomized Clinical Trial.	Metformin	44-53	interleukin 6	Homo sapiens	91-95
31683341-0	2019	Treatment with Metformin and Combination of Metformin Plus Pioglitazone on Serum Levels of IL-6 and IL-8 in Polycystic Ovary Syndrome: A Randomized Clinical Trial.	Metformin	44-53	C-X-C motif chemokine ligand 8	Homo sapiens	100-104
31683341-14	2019	Combination of metformin and pioglitazone therapy was more effective as compared to metformin alone in reducing the levels of IL-6 and IL-8 as well as insulin resistance in PCOS.	Metformin	15-24	interleukin 6	Homo sapiens	126-130
31683341-14	2019	Combination of metformin and pioglitazone therapy was more effective as compared to metformin alone in reducing the levels of IL-6 and IL-8 as well as insulin resistance in PCOS.	Metformin	15-24	C-X-C motif chemokine ligand 8	Homo sapiens	135-139
31683341-14	2019	Combination of metformin and pioglitazone therapy was more effective as compared to metformin alone in reducing the levels of IL-6 and IL-8 as well as insulin resistance in PCOS.	Metformin	15-24	insulin	Homo sapiens	151-158
31683341-14	2019	Combination of metformin and pioglitazone therapy was more effective as compared to metformin alone in reducing the levels of IL-6 and IL-8 as well as insulin resistance in PCOS.	Metformin	84-93	interleukin 6	Homo sapiens	126-130
31683341-14	2019	Combination of metformin and pioglitazone therapy was more effective as compared to metformin alone in reducing the levels of IL-6 and IL-8 as well as insulin resistance in PCOS.	Metformin	84-93	C-X-C motif chemokine ligand 8	Homo sapiens	135-139
31369842-0	2019	Inhibition of neointima hyperplasia by the combined therapy of linagliptin and metformin via AMPK/Nox4 signaling in diabetic rats.	Metformin	79-88	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	93-97
31369842-11	2019	Linagliptin and metformin were synergistical to target AMPK/Nox4 signal pathway in VSMCs incubated with HG and in the cardia artery of diabetic rats, which was superior to the monotherapy.	Metformin	16-25	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	55-59
31369842-12	2019	CONCLUSIONS: We demonstrated that the potential protection of the combined use of linagliptin and metformin on VSMC remodeling through AMPK/Nox4 signal pathway, resulting in the improvement of neointima hyperplasia in diabetic rats.	Metformin	98-107	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	135-139
30988378-0	2019	Metformin inhibits IL-6 signaling by decreasing IL-6R expression on multiple myeloma cells.	Metformin	0-9	interleukin 6	Homo sapiens	19-23
31486833-3	2019	Particularly, evidence is accumulating regarding the synergistic association between metformin and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs).	Metformin	85-94	epidermal growth factor receptor	Homo sapiens	99-131
31486833-3	2019	Particularly, evidence is accumulating regarding the synergistic association between metformin and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs).	Metformin	85-94	epidermal growth factor receptor	Homo sapiens	133-137
31486833-14	2019	Conclusions and Relevance: To our knowledge, this is the first study to prospectively show that the addition of metformin to standard EGFR-TKIs therapy in patients with advanced lung adenocarcinoma significantly improves PFS.	Metformin	112-121	epidermal growth factor receptor	Homo sapiens	134-138
30988378-0	2019	Metformin inhibits IL-6 signaling by decreasing IL-6R expression on multiple myeloma cells.	Metformin	0-9	interleukin 6 receptor	Homo sapiens	48-53
30599813-3	2019	The endometrium of metformin-treated group (metformin-treated patients with PCOS) and the control group (non-metformin-treated patients with PCOS) were analyzed for the expression of homeobox A10 (HOXA10) and integrin beta-3 (ITGB3) and differential micro RNA (miRNA) expression profiles.	Metformin	19-28	integrin subunit beta 3	Homo sapiens	209-224
30599813-3	2019	The endometrium of metformin-treated group (metformin-treated patients with PCOS) and the control group (non-metformin-treated patients with PCOS) were analyzed for the expression of homeobox A10 (HOXA10) and integrin beta-3 (ITGB3) and differential micro RNA (miRNA) expression profiles.	Metformin	19-28	integrin subunit beta 3	Homo sapiens	226-231
30988378-6	2019	Metformin specifically decreased IL-6R expression which is mediated via AMPK, mTOR, and miR34a.	Metformin	0-9	interleukin 6 receptor	Homo sapiens	33-38
30599813-5	2019	Furthermore, we verified the effects of metformin on the expression of HOXA10 and ITGB3, and regulatory effects of miR-1910-3p and miR-491-3p on HOXA10 and ITGB3 using Ishikawa cell line.	Metformin	40-49	integrin subunit beta 3	Homo sapiens	82-87
30599813-6	2019	Metformin induced a significant dose-dependent upregulation of HOXA10 and ITGB3.	Metformin	0-9	integrin subunit beta 3	Homo sapiens	74-79
30599813-13	2019	Metformin likely improves endometrial receptivity through downregulating the expression of miR-491-3p and miR-1910-3p, thereby increasing the expression of HOXA10 and ITGB3 in the endometrium of PCOS women.	Metformin	0-9	integrin subunit beta 3	Homo sapiens	167-172
30988378-6	2019	Metformin specifically decreased IL-6R expression which is mediated via AMPK, mTOR, and miR34a.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	78-82
31781324-0	2019	Metformin Activates the Protective Effects of the AMPK Pathway in Acute Lung Injury Caused by Paraquat Poisoning.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	50-54
31781324-1	2019	Objective: To observe whether metformin (MET) plays a protective role in acute lung injury (ALI) induced by paraquat (PQ) poisoning in rats by activating the AMPK/NF-kappaB signaling pathway.	Metformin	30-39	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	158-162
31781324-1	2019	Objective: To observe whether metformin (MET) plays a protective role in acute lung injury (ALI) induced by paraquat (PQ) poisoning in rats by activating the AMPK/NF-kappaB signaling pathway.	Metformin	41-44	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	158-162
31857506-9	2019	:  Conclusion: The metformin treatment is effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effect to reduce the antipsychotic-induced insulin resistance appears earlier than the effect to improve dyslipidemia.	Metformin	19-28	insulin	Homo sapiens	104-111
31857506-9	2019	:  Conclusion: The metformin treatment is effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effect to reduce the antipsychotic-induced insulin resistance appears earlier than the effect to improve dyslipidemia.	Metformin	19-28	insulin	Homo sapiens	175-182
31695491-11	2019	Finally, several common drugs including metformin were observed to up-regulate the expression of TIPARP.	Metformin	40-49	TCDD inducible poly(ADP-ribose) polymerase	Homo sapiens	97-103
31651584-0	2019	Discovering metformin-induced vitamin B12 deficiency in patients with type 2 diabetes in primary care.	Metformin	12-21	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	38-41
31651584-1	2019	BACKGROUND: Although metformin is the preferred initial pharmacological choice in type 2 diabetes, there is evidence that reveals a link between metformin use and vitamin B12 deficiency.	Metformin	145-154	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	171-174
31651584-2	2019	The American Diabetes Association (ADA) has recently recommended periodic measurement of B12 levels for all patients on metformin.	Metformin	120-129	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	89-92
31651584-10	2019	Results may encourage other providers to follow the ADA guidelines for monitoring vitamin B12 levels for patients taking metformin.	Metformin	121-130	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	90-93
31610847-9	2019	Treatment with an anti-diabetes drug, Metformin, reversed Abeta-induced metabolic defects, reduced protein aggregation and normalized lifespan of GRU102.	Metformin	38-47	amyloid beta precursor protein	Homo sapiens	58-63
31737069-11	2019	Results: In HepG2 cells, metformin dose-dependently enhanced the transcriptional activity of FXR and MAFG and inhibited the expression of CYP8B1.	Metformin	25-34	MAF bZIP transcription factor G	Homo sapiens	101-105
31737069-11	2019	Results: In HepG2 cells, metformin dose-dependently enhanced the transcriptional activity of FXR and MAFG and inhibited the expression of CYP8B1.	Metformin	25-34	cytochrome P450 family 8 subfamily B member 1	Homo sapiens	138-144
31405334-0	2019	Metformin and sitagliptin combination therapy ameliorates polycystic ovary syndrome with insulin resistance through upregulation of lncRNA H19.	Metformin	0-9	insulin	Homo sapiens	89-96
31781324-4	2019	Results: Compared with the PQ group, the MET treatment group showed significantly (1) reduced lung wet/dry ratio (W/D: 4.67 +- 0.31 vs. 5.45 +- 0.40, P &lt; 0.001), (2) reduced pathological changes in lung tissue, (3) decreased MDA levels (nmol/mg prot: 2.70 +- 0.19 vs. 3.08 +- 0.15, P &lt; 0.001) and increased SOD and GSH-Px activities (U/mg prot: 76.17 +- 5.22 vs. 45.23 +- 6.58, 30.40 +- 2.84 vs. 21.00 +- 3.20; all P &lt; 0.001) in lung tissue homogenate, (4) reduced levels of IL-1beta, IL-6, and TNF-alpha in lung tissue homogenates (pg/mL: 47.87 +- 5.06 vs. 66.77 +- 6.55; 93.03 +- 7.41 vs. 107.39 +- 9.81; 75.73 +- 6.08 vs. 89.12 +- 8.94; all P &lt; 0.001), (5) increased activity of RLE-6TN cells (%: 0.69 +- 0.09, 0.76 +- 0.06, and 0.58 +- 0.03 vs. 0.50 +- 0.05; all P &lt; 0.05), (6) decreased protein levels of phospho-NF-kappaBp65 in lung homogenates and RLE-6TN cells (p-NF-kappaB/NF-kappaB: 0.47 +- 0.09 vs. 0.81 +- 0.13; 0.26 +- 0.07 vs. 0.79 +- 0.13; all P &lt; 0.01), and (7) upregulated protein expression of phospho-AMPK in lung homogenates and RLE-6TN cells (p-AMPK/AMPK: 0.88 +- 0.05 vs. 0.36 +- 0.12; 0.93 +- 0.03 vs. 0.56 +- 0.15; all P &lt; 0.01).	Metformin	41-44	interleukin 1 beta	Rattus norvegicus	484-492
31781324-4	2019	Results: Compared with the PQ group, the MET treatment group showed significantly (1) reduced lung wet/dry ratio (W/D: 4.67 +- 0.31 vs. 5.45 +- 0.40, P &lt; 0.001), (2) reduced pathological changes in lung tissue, (3) decreased MDA levels (nmol/mg prot: 2.70 +- 0.19 vs. 3.08 +- 0.15, P &lt; 0.001) and increased SOD and GSH-Px activities (U/mg prot: 76.17 +- 5.22 vs. 45.23 +- 6.58, 30.40 +- 2.84 vs. 21.00 +- 3.20; all P &lt; 0.001) in lung tissue homogenate, (4) reduced levels of IL-1beta, IL-6, and TNF-alpha in lung tissue homogenates (pg/mL: 47.87 +- 5.06 vs. 66.77 +- 6.55; 93.03 +- 7.41 vs. 107.39 +- 9.81; 75.73 +- 6.08 vs. 89.12 +- 8.94; all P &lt; 0.001), (5) increased activity of RLE-6TN cells (%: 0.69 +- 0.09, 0.76 +- 0.06, and 0.58 +- 0.03 vs. 0.50 +- 0.05; all P &lt; 0.05), (6) decreased protein levels of phospho-NF-kappaBp65 in lung homogenates and RLE-6TN cells (p-NF-kappaB/NF-kappaB: 0.47 +- 0.09 vs. 0.81 +- 0.13; 0.26 +- 0.07 vs. 0.79 +- 0.13; all P &lt; 0.01), and (7) upregulated protein expression of phospho-AMPK in lung homogenates and RLE-6TN cells (p-AMPK/AMPK: 0.88 +- 0.05 vs. 0.36 +- 0.12; 0.93 +- 0.03 vs. 0.56 +- 0.15; all P &lt; 0.01).	Metformin	41-44	interleukin 6	Rattus norvegicus	494-498
31781324-4	2019	Results: Compared with the PQ group, the MET treatment group showed significantly (1) reduced lung wet/dry ratio (W/D: 4.67 +- 0.31 vs. 5.45 +- 0.40, P &lt; 0.001), (2) reduced pathological changes in lung tissue, (3) decreased MDA levels (nmol/mg prot: 2.70 +- 0.19 vs. 3.08 +- 0.15, P &lt; 0.001) and increased SOD and GSH-Px activities (U/mg prot: 76.17 +- 5.22 vs. 45.23 +- 6.58, 30.40 +- 2.84 vs. 21.00 +- 3.20; all P &lt; 0.001) in lung tissue homogenate, (4) reduced levels of IL-1beta, IL-6, and TNF-alpha in lung tissue homogenates (pg/mL: 47.87 +- 5.06 vs. 66.77 +- 6.55; 93.03 +- 7.41 vs. 107.39 +- 9.81; 75.73 +- 6.08 vs. 89.12 +- 8.94; all P &lt; 0.001), (5) increased activity of RLE-6TN cells (%: 0.69 +- 0.09, 0.76 +- 0.06, and 0.58 +- 0.03 vs. 0.50 +- 0.05; all P &lt; 0.05), (6) decreased protein levels of phospho-NF-kappaBp65 in lung homogenates and RLE-6TN cells (p-NF-kappaB/NF-kappaB: 0.47 +- 0.09 vs. 0.81 +- 0.13; 0.26 +- 0.07 vs. 0.79 +- 0.13; all P &lt; 0.01), and (7) upregulated protein expression of phospho-AMPK in lung homogenates and RLE-6TN cells (p-AMPK/AMPK: 0.88 +- 0.05 vs. 0.36 +- 0.12; 0.93 +- 0.03 vs. 0.56 +- 0.15; all P &lt; 0.01).	Metformin	41-44	tumor necrosis factor	Rattus norvegicus	504-513
31781324-4	2019	Results: Compared with the PQ group, the MET treatment group showed significantly (1) reduced lung wet/dry ratio (W/D: 4.67 +- 0.31 vs. 5.45 +- 0.40, P &lt; 0.001), (2) reduced pathological changes in lung tissue, (3) decreased MDA levels (nmol/mg prot: 2.70 +- 0.19 vs. 3.08 +- 0.15, P &lt; 0.001) and increased SOD and GSH-Px activities (U/mg prot: 76.17 +- 5.22 vs. 45.23 +- 6.58, 30.40 +- 2.84 vs. 21.00 +- 3.20; all P &lt; 0.001) in lung tissue homogenate, (4) reduced levels of IL-1beta, IL-6, and TNF-alpha in lung tissue homogenates (pg/mL: 47.87 +- 5.06 vs. 66.77 +- 6.55; 93.03 +- 7.41 vs. 107.39 +- 9.81; 75.73 +- 6.08 vs. 89.12 +- 8.94; all P &lt; 0.001), (5) increased activity of RLE-6TN cells (%: 0.69 +- 0.09, 0.76 +- 0.06, and 0.58 +- 0.03 vs. 0.50 +- 0.05; all P &lt; 0.05), (6) decreased protein levels of phospho-NF-kappaBp65 in lung homogenates and RLE-6TN cells (p-NF-kappaB/NF-kappaB: 0.47 +- 0.09 vs. 0.81 +- 0.13; 0.26 +- 0.07 vs. 0.79 +- 0.13; all P &lt; 0.01), and (7) upregulated protein expression of phospho-AMPK in lung homogenates and RLE-6TN cells (p-AMPK/AMPK: 0.88 +- 0.05 vs. 0.36 +- 0.12; 0.93 +- 0.03 vs. 0.56 +- 0.15; all P &lt; 0.01).	Metformin	41-44	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	1038-1042
31781324-4	2019	Results: Compared with the PQ group, the MET treatment group showed significantly (1) reduced lung wet/dry ratio (W/D: 4.67 +- 0.31 vs. 5.45 +- 0.40, P &lt; 0.001), (2) reduced pathological changes in lung tissue, (3) decreased MDA levels (nmol/mg prot: 2.70 +- 0.19 vs. 3.08 +- 0.15, P &lt; 0.001) and increased SOD and GSH-Px activities (U/mg prot: 76.17 +- 5.22 vs. 45.23 +- 6.58, 30.40 +- 2.84 vs. 21.00 +- 3.20; all P &lt; 0.001) in lung tissue homogenate, (4) reduced levels of IL-1beta, IL-6, and TNF-alpha in lung tissue homogenates (pg/mL: 47.87 +- 5.06 vs. 66.77 +- 6.55; 93.03 +- 7.41 vs. 107.39 +- 9.81; 75.73 +- 6.08 vs. 89.12 +- 8.94; all P &lt; 0.001), (5) increased activity of RLE-6TN cells (%: 0.69 +- 0.09, 0.76 +- 0.06, and 0.58 +- 0.03 vs. 0.50 +- 0.05; all P &lt; 0.05), (6) decreased protein levels of phospho-NF-kappaBp65 in lung homogenates and RLE-6TN cells (p-NF-kappaB/NF-kappaB: 0.47 +- 0.09 vs. 0.81 +- 0.13; 0.26 +- 0.07 vs. 0.79 +- 0.13; all P &lt; 0.01), and (7) upregulated protein expression of phospho-AMPK in lung homogenates and RLE-6TN cells (p-AMPK/AMPK: 0.88 +- 0.05 vs. 0.36 +- 0.12; 0.93 +- 0.03 vs. 0.56 +- 0.15; all P &lt; 0.01).	Metformin	41-44	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	1084-1088
31781324-4	2019	Results: Compared with the PQ group, the MET treatment group showed significantly (1) reduced lung wet/dry ratio (W/D: 4.67 +- 0.31 vs. 5.45 +- 0.40, P &lt; 0.001), (2) reduced pathological changes in lung tissue, (3) decreased MDA levels (nmol/mg prot: 2.70 +- 0.19 vs. 3.08 +- 0.15, P &lt; 0.001) and increased SOD and GSH-Px activities (U/mg prot: 76.17 +- 5.22 vs. 45.23 +- 6.58, 30.40 +- 2.84 vs. 21.00 +- 3.20; all P &lt; 0.001) in lung tissue homogenate, (4) reduced levels of IL-1beta, IL-6, and TNF-alpha in lung tissue homogenates (pg/mL: 47.87 +- 5.06 vs. 66.77 +- 6.55; 93.03 +- 7.41 vs. 107.39 +- 9.81; 75.73 +- 6.08 vs. 89.12 +- 8.94; all P &lt; 0.001), (5) increased activity of RLE-6TN cells (%: 0.69 +- 0.09, 0.76 +- 0.06, and 0.58 +- 0.03 vs. 0.50 +- 0.05; all P &lt; 0.05), (6) decreased protein levels of phospho-NF-kappaBp65 in lung homogenates and RLE-6TN cells (p-NF-kappaB/NF-kappaB: 0.47 +- 0.09 vs. 0.81 +- 0.13; 0.26 +- 0.07 vs. 0.79 +- 0.13; all P &lt; 0.01), and (7) upregulated protein expression of phospho-AMPK in lung homogenates and RLE-6TN cells (p-AMPK/AMPK: 0.88 +- 0.05 vs. 0.36 +- 0.12; 0.93 +- 0.03 vs. 0.56 +- 0.15; all P &lt; 0.01).	Metformin	41-44	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	1084-1088
31346700-4	2019	By acting on IL-6 expression, metformin might have a positive impact on the main molecular pathways strictly connected with pathogenesis and biological features of ovarian cancer.	Metformin	30-39	interleukin 6	Homo sapiens	13-17
31814932-7	2019	D supplementation with metformin improved menstrual regularity and follicular maturation and significant decreases in serum insulin levels, homeostasis model of assessment-insulin resistance (HOMA-IR) and fasting blood sugar (FBS) and also significant rises on quantitative insulin sensitivity check index (QUICKI) at two studies.	Metformin	23-32	insulin	Homo sapiens	124-131
31814932-7	2019	D supplementation with metformin improved menstrual regularity and follicular maturation and significant decreases in serum insulin levels, homeostasis model of assessment-insulin resistance (HOMA-IR) and fasting blood sugar (FBS) and also significant rises on quantitative insulin sensitivity check index (QUICKI) at two studies.	Metformin	23-32	insulin	Homo sapiens	172-179
31814932-7	2019	D supplementation with metformin improved menstrual regularity and follicular maturation and significant decreases in serum insulin levels, homeostasis model of assessment-insulin resistance (HOMA-IR) and fasting blood sugar (FBS) and also significant rises on quantitative insulin sensitivity check index (QUICKI) at two studies.	Metformin	23-32	insulin	Homo sapiens	172-179
31405334-6	2019	Our results showed that co-treatment with TECOS and DMBG attenuated the induced apoptosis and insulin resistance (IR) in PCOS model cells, and improved reproductive hormone disorders, ovarian polycystic changes, and IR of PCOS rats.	Metformin	52-56	insulin	Homo sapiens	94-101
31405334-8	2019	Furthermore, co-treatment with TECOS and DMBG induced H19 expression via suppressing the PI3K/AKT-DNMT1 pathway.	Metformin	41-45	AKT serine/threonine kinase 1	Rattus norvegicus	94-97
31021474-5	2019	Clinical cardiovascular protection with metformin is supported by three randomized outcomes trials (in newly diagnosed and late stage insulin-treated type 2 diabetes patients) and a wealth of observational data.	Metformin	40-49	insulin	Homo sapiens	134-141
31087796-13	2019	In low-quality evidence in adults, meta-analyses demonstrated that metformin was better than placebo for BMI (MD -0.48 [-0.94, -0.02], P = 0.04); metformin was better than COCP for fasting insulin (MD 4.00 [2.59, 5.41], P = 0.00001), whereas COCP was better than metformin for irregular cycles (MD 12.49 [1.34, 116.62], P = 0.03).	Metformin	67-76	insulin	Homo sapiens	189-196
31319131-6	2019	We found that the metformin pretreatment alleviated the lung injury and decreased the levels of TNF-a, IL-1beta and IL-6 in the bronchoalveolar lavage fluid (BALF) and in lung tissues, as well as the levels of NLRP3, NLRC4 and cleaved caspase-1 associated with LPS-induced ALI in old mice.	Metformin	18-27	tumor necrosis factor	Mus musculus	96-101
31583022-0	2019	Metformin paradoxically worsens insulin resistance in SHORT syndrome.	Metformin	0-9	insulin	Homo sapiens	32-39
31583022-2	2019	Methods: We attempted to test the efficacy metformin in a female patient with SHORT syndrome by measuring glucose and insulin during an extended Oral Glucose Tolerance Test (OGTT) in a 21-year old patient (BMI 17.5 kg/m2), who presented for endocrine assessment with a history of amenorrhoea.	Metformin	43-52	insulin	Homo sapiens	118-125
31583022-8	2019	Insulin concentrations remained above upper assay detection limit also at 180 min of OGTT on metformin treatment (> 1000 microIU/ml versus 100.6 microIU/ml without metformin).	Metformin	93-102	insulin	Homo sapiens	0-7
31583022-8	2019	Insulin concentrations remained above upper assay detection limit also at 180 min of OGTT on metformin treatment (> 1000 microIU/ml versus 100.6 microIU/ml without metformin).	Metformin	164-173	insulin	Homo sapiens	0-7
31518991-0	2019	Vitamin B12 deficiency and diabetic neuropathy in patients taking metformin: a cross-sectional study.	Metformin	66-75	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	8-11
31518991-1	2019	OBJECTIVE: Vitamin B12 deficiency resulting from metformin use has been demonstrated in multiple studies.	Metformin	49-58	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	19-22
31518991-2	2019	In this study, we aimed to evaluate the prevalence of Vitamin B12 deficiency in patients with chronic metformin use and the relationship between vitamin B12 deficiency and diabetic neuropathy.	Metformin	102-111	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	62-65
31518991-10	2019	Those taking a higher metformin dose had lower levels of vitamin B12 (coefficient -0.061; CI 95% -0.09-0.024).	Metformin	22-31	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	65-68
31518991-14	2019	Higher doses of metformin and male sex were factors related to lower levels of vitamin B12.	Metformin	16-25	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	87-90
31319131-6	2019	We found that the metformin pretreatment alleviated the lung injury and decreased the levels of TNF-a, IL-1beta and IL-6 in the bronchoalveolar lavage fluid (BALF) and in lung tissues, as well as the levels of NLRP3, NLRC4 and cleaved caspase-1 associated with LPS-induced ALI in old mice.	Metformin	18-27	interleukin 1 beta	Mus musculus	103-111
31319131-6	2019	We found that the metformin pretreatment alleviated the lung injury and decreased the levels of TNF-a, IL-1beta and IL-6 in the bronchoalveolar lavage fluid (BALF) and in lung tissues, as well as the levels of NLRP3, NLRC4 and cleaved caspase-1 associated with LPS-induced ALI in old mice.	Metformin	18-27	interleukin 6	Mus musculus	116-120
31319131-6	2019	We found that the metformin pretreatment alleviated the lung injury and decreased the levels of TNF-a, IL-1beta and IL-6 in the bronchoalveolar lavage fluid (BALF) and in lung tissues, as well as the levels of NLRP3, NLRC4 and cleaved caspase-1 associated with LPS-induced ALI in old mice.	Metformin	18-27	toll-like receptor 4	Mus musculus	261-264
31319131-9	2019	The results demonstrated that the efficacy of metformin was reduced when using the AMPK pharmacological inhibitor compound C or AMPKalpha1 expression was knocked down in RAW 264.7 cells.	Metformin	46-55	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	128-138
31319131-10	2019	In conclusion, our data indicated that metformin may inhibit NLRC4 inflammasome activation in LPS-induced ALI in old mice through AMPK signaling, and further understanding of the AMPK/NLRC4 axis may provide a novel therapeutic strategy for LPS-induced ALI in the future.	Metformin	39-48	toll-like receptor 4	Mus musculus	94-97
31319131-10	2019	In conclusion, our data indicated that metformin may inhibit NLRC4 inflammasome activation in LPS-induced ALI in old mice through AMPK signaling, and further understanding of the AMPK/NLRC4 axis may provide a novel therapeutic strategy for LPS-induced ALI in the future.	Metformin	39-48	toll-like receptor 4	Mus musculus	240-243
31012983-0	2019	Altered Glycemic Control Associated With Polymorphisms in the SLC22A1 (OCT1) Gene in a Mexican Population With Type 2 Diabetes Mellitus Treated With Metformin: A Cohort Study.	Metformin	149-158	solute carrier family 22 member 1	Homo sapiens	62-69
31081406-6	2019	The fasting glucose, insulin, and glucose/insulin ratio, HOMA-IR, glucose, and insulin AUC 120 were significantly improved in metformin group.	Metformin	126-135	insulin	Homo sapiens	21-94
31081406-10	2019	In conclusion, metformin, associated with vaginal ring, improves the insulin and carbohydrate metabolism, reduces the body weight and android fat distribution.	Metformin	15-24	insulin	Homo sapiens	69-76
31408647-3	2019	Indeed, lowering glucose and/or insulin levels pharmacologically appears to reduce cancer risk and progression, as has been demonstrated for the biguanide metformin in observational studies.	Metformin	155-164	insulin	Homo sapiens	32-39
31742116-5	2019	Prolactin serum levels were higher in glyburide-treated patients compared with metformin-treated patients (P &lt; 0.01).	Metformin	79-88	prolactin	Homo sapiens	0-9
31742116-7	2019	Metformin but not glyburide reduced prolactin levels due to the improvement of insulin resistance.	Metformin	0-9	prolactin	Homo sapiens	36-45
31742116-7	2019	Metformin but not glyburide reduced prolactin levels due to the improvement of insulin resistance.	Metformin	0-9	insulin	Homo sapiens	79-86
31012983-0	2019	Altered Glycemic Control Associated With Polymorphisms in the SLC22A1 (OCT1) Gene in a Mexican Population With Type 2 Diabetes Mellitus Treated With Metformin: A Cohort Study.	Metformin	149-158	solute carrier family 22 member 1	Homo sapiens	71-75
31012983-1	2019	The organic cation transporters OCT1 and OCT2 and the multidrug and toxin extrusion transporter MATE1, encoded by the SLC22A1, SLC22A2, and SLC47A1 genes, respectively, are responsible for the absorption of metformin in enterocytes, hepatocytes, and kidney cells.	Metformin	207-216	solute carrier family 22 member 1	Homo sapiens	32-36
31012983-1	2019	The organic cation transporters OCT1 and OCT2 and the multidrug and toxin extrusion transporter MATE1, encoded by the SLC22A1, SLC22A2, and SLC47A1 genes, respectively, are responsible for the absorption of metformin in enterocytes, hepatocytes, and kidney cells.	Metformin	207-216	solute carrier family 22 member 1	Homo sapiens	118-125
31012983-2	2019	The aim of this study was to evaluate whether genetic variations in the SLC22A1, SLC22A2, and SLC47A1 genes could be associated with an altered response to metformin in patients with type 2 diabetes mellitus.	Metformin	156-165	solute carrier family 22 member 1	Homo sapiens	72-79
31324647-2	2019	AMPK can be activated directly using positive allosteric modulators, as well as indirectly through the upregulation of upstream kinases, such as liver kinase B1 (LKB1), which is a mechanism of action of metformin.	Metformin	203-212	serine/threonine kinase 11	Mus musculus	145-160
31686756-0	2019	Irisin as a Novel Marker for Insulin Resistance in Iraqi Women with Polycystic Ovary Syndrome Before and After Metformin Therapy.	Metformin	111-120	insulin	Homo sapiens	29-36
31437793-1	2019	Metformin, the most widely used medicine for type 2 diabetes, displays anti-inflammatory functions via activating AMP-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	114-142
31437793-1	2019	Metformin, the most widely used medicine for type 2 diabetes, displays anti-inflammatory functions via activating AMP-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	144-148
31437793-7	2019	While metformin treatment in vitro showed little effect on inducible Treg, metformin strongly inhibited Th17 cell differentiation through the increase of reactive oxygen species and AMPK.	Metformin	75-84	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	182-186
31324647-2	2019	AMPK can be activated directly using positive allosteric modulators, as well as indirectly through the upregulation of upstream kinases, such as liver kinase B1 (LKB1), which is a mechanism of action of metformin.	Metformin	203-212	serine/threonine kinase 11	Mus musculus	162-166
31593087-5	2019	Cox proportional hazard regression analysis revealed the lower rate of admission for subjects under combination therapy (adjusted hazard ratio of 0.275; 95% confidence interval = 0.136-0.557, P < .001).Patients with RA and T2DM receiving the combination of COX-2 inhibitors and metformin were associated with lower admission rate than those on COX-2 inhibitors alone, and this effect may be attributed to the decrease in the levels of proinflammatory factors.	Metformin	278-287	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	257-262
31439934-7	2019	Furthermore, the gastrointestinal tract also has a major role in metformin action through modulation of glucose-lowering hormone glucagon-like peptide 1 and the intestinal bile acid pool and alterations in gut microbiota composition.	Metformin	65-74	glucagon	Homo sapiens	129-152
31255569-0	2019	Corrigendum to "Metformin affects macrophages" phenotype and improves the activity of glutathione peroxidase, superoxide dismutase, catalase and decreases malondialdehyde concentration in a partially AMPK-independent manner in LPS-stimulated human monocytes/macrophages"" [Pharmacol.	Metformin	16-25	catalase	Homo sapiens	132-140
31335763-7	2019	CONCLUSIONS: In conclusion, our study revealed new therapeutic potential of metformin to attenuate calcineurin inhibitor-induced renal fibrosis, which was closely related to the suppression of MEK/ERK1/2 pathway.	Metformin	76-85	calcineurin binding protein 1	Rattus norvegicus	99-120
31607288-7	2019	Metformin inhibited the expression of GLUT1, LDHA, ALDOA, PDK1, and PGK1 genes of K562 cells (P&lt;0.05) showing a dose-dependent manner(r=0.83,r=0.80,r=0.72,r=0.76,r=0.73,respectively).	Metformin	0-9	lactate dehydrogenase A	Homo sapiens	45-49
31607288-8	2019	Metformin inhibited the expression of P-Akt, P-S6, GLUT1, LDHA proteins of K562 cells(P&lt;0.05), showing a dose-dependent relationship(r=0.80,r=0.92,r=0.83,r=0.92,respectively).	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	40-43
31607288-8	2019	Metformin inhibited the expression of P-Akt, P-S6, GLUT1, LDHA proteins of K562 cells(P&lt;0.05), showing a dose-dependent relationship(r=0.80,r=0.92,r=0.83,r=0.92,respectively).	Metformin	0-9	lactate dehydrogenase A	Homo sapiens	58-62
31607288-10	2019	PI3K/Akt/mTOR signaling pathway may be one of the molecular mechanisms of metformin on k562 cells.	Metformin	74-83	AKT serine/threonine kinase 1	Homo sapiens	5-8
31607288-10	2019	PI3K/Akt/mTOR signaling pathway may be one of the molecular mechanisms of metformin on k562 cells.	Metformin	74-83	mechanistic target of rapamycin kinase	Homo sapiens	9-13
31570103-15	2019	Prediabetic never-metformin-users showed higher inflammatory tone and leptin to adiponectin ratio in pericoronary fat compared to current-metformin-users (P &lt; 0.001).	Metformin	18-27	adiponectin, C1Q and collagen domain containing	Homo sapiens	80-91
31570103-18	2019	Metformin by reducing inflammatory tone and leptin to adiponectin ratio in pericoronary fat may improve prognosis in prediabetic patients with AMI.	Metformin	0-9	adiponectin, C1Q and collagen domain containing	Homo sapiens	54-65
31121159-11	2019	Moreover, the increased level of phosphorylation of Akt and GSK3beta in the frontal cortex induced by MK-801 was normalized by metformin.	Metformin	127-136	AKT serine/threonine kinase 1	Rattus norvegicus	52-55
31526389-0	2019	Effects of metformin and Exenatide on insulin resistance and AMPKalpha-SIRT1 molecular pathway in PCOS rats.	Metformin	11-20	sirtuin 1	Rattus norvegicus	61-76
31526389-8	2019	CONCLUSIONS: Both metformin and exenatide can improve the reproductive and endocrine functions of rats with PCOS via the AMPKalpha-SIRT1 pathway, which may be the molecular mechanism for IR in PCOS and could possibly serve as a therapeutic target.	Metformin	18-27	sirtuin 1	Rattus norvegicus	121-136
31583050-12	2019	A further mechanistic analysis revealed that metformin ameliorated the high-fat-diet-induced injury to the BTB structure and permeability and restored the disordered BTB-related proteins, which might be associated with an improvement in oxidative stress and a recovery of NF-kappaB activity in Sertoli cells (SCs).	Metformin	45-54	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	272-281
31348945-0	2019	Metformin reduces fibrosis factors in insulin resistant and hypertrophied adipocyte via integrin/ERK, collagen VI, apoptosis, and necrosis reduction.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	97-100
31348945-8	2019	Metformin caused reduction of activity of integrin/ERK pathway in Metformin treated insulin resistant and hypertrophied adipocytes compared to untreated group.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	51-54
31348945-8	2019	Metformin caused reduction of activity of integrin/ERK pathway in Metformin treated insulin resistant and hypertrophied adipocytes compared to untreated group.	Metformin	66-75	mitogen-activated protein kinase 1	Homo sapiens	51-54
31348946-7	2019	However, there is a growing understanding that Metformin demonstrates its anti-epileptic effect mainly via ameliorating brain oxidative damage, activation of AMPK, inhibition of mTOR pathway, downregulation of alpha-synuclein, reducing apoptosis, downregulation of BDNF and TrkB level.	Metformin	47-56	mechanistic target of rapamycin kinase	Homo sapiens	178-182
31474368-4	2019	We show that microbes integrate cues from metformin and the diet through the phosphotransferase signaling pathway that converges on the transcriptional regulator Crp.	Metformin	42-51	C-reactive protein	Homo sapiens	162-165
31233747-6	2019	Additionally, metformin demonstrates anti-apoptotic effects, most likely by inhibiting mitochondrial permeability transition pore (mPTP) opening, and anti-inflammatory effects, by JNK inhibition.	Metformin	14-23	mitogen-activated protein kinase 8	Homo sapiens	180-183
31326727-0	2019	Liraglutide in combination with metformin may improve the atherogenic lipid profile and decrease C-reactive protein level in statin treated obese patients with coronary artery disease and newly diagnosed type 2 diabetes: A randomized trial.	Metformin	32-41	C-reactive protein	Homo sapiens	97-115
31442575-7	2019	Metformin and Liraglutide were shown to elicit significantly greater release of TNFa, IL-6, and GM-CSF, while Sitagliptin had a lesser effect on pro-inflammatory cytokine production.	Metformin	0-9	tumor necrosis factor	Homo sapiens	80-84
31442575-7	2019	Metformin and Liraglutide were shown to elicit significantly greater release of TNFa, IL-6, and GM-CSF, while Sitagliptin had a lesser effect on pro-inflammatory cytokine production.	Metformin	0-9	interleukin 6	Homo sapiens	86-90
31326727-12	2019	The combination of liraglutide and metformin reduced the total LDL subfractions, primarily by reducing the most atherogenic subfraction LDL5, and reduced CRP but not TNF-alpha.	Metformin	35-44	tumor necrosis factor	Homo sapiens	166-175
31278880-9	2019	Therefore, metformin and phenformin may represent a novel strategy for the treatment of chemoresistant rectal cancer by targeting signal transducer and activator of transcription 3 and transforming growth factor-beta/Smad signaling.	Metformin	11-20	signal transducer and activator of transcription 3	Homo sapiens	130-180
31135975-1	2019	The diabetes mellitus (DM) drug metformin targets mechanistic/mammalian target of rapamycin and inhibits lymphoma growth in vitro.	Metformin	32-41	mechanistic target of rapamycin kinase	Homo sapiens	62-91
31326458-1	2019	AIM: The aim of this study was to analyze the efficacy, insulin sensitivity and safety in the event of administering sulfonylurea-based drugs and metformin in combination with basal insulin.	Metformin	146-155	insulin	Homo sapiens	56-63
31581911-0	2019	Metformin inhibits angiogenesis of endothelial progenitor cells via miR-221-mediated p27 expression and autophagy.	Metformin	0-9	dynactin subunit 6	Homo sapiens	85-88
31581911-4	2019	Metformin increased p27 and LC3II expression and AMP-activated protein kinase (AMPK) phosphorylation, and decreased p62 expression, while miR-221 overexpression reversed the effects of metformin.	Metformin	0-9	dynactin subunit 6	Homo sapiens	20-23
31195189-6	2019	Metformin prevented atrophy of myelinated axons, and reduced expression of inflammatory mediators (interleukin-1beta, inducible nitric oxide synthase and nitric oxide).	Metformin	0-9	interleukin 1 beta	Mus musculus	99-116
31121610-0	2019	Effect of Metformin Treatment on Insulin Resistance Markers, and Circulating Irisin in Women with Polycystic Ovarian Syndrome (PCOS).	Metformin	10-19	insulin	Homo sapiens	33-40
31120617-0	2019	RasGRP1 is a target for VEGF to induce angiogenesis and involved in the endothelial-protective effects of metformin under high glucose in HUVECs.	Metformin	106-115	vascular endothelial growth factor A	Homo sapiens	24-28
31120617-4	2019	Furthermore, we investigate whether RasGRP1-dependent VEGF signaling was downregulated under high glucose conditions mimicking diabetes and required for the endothelial protective action of metformin in human umbilical vein endothelial cells (HUVECs).	Metformin	190-199	vascular endothelial growth factor A	Homo sapiens	54-58
31120617-8	2019	The expression of VEGF, RasGRP1, and AKT phosphorylation was downregulated in HUVECs exposed to high glucose compared with normal glucose, whereas metformin upregulated the RasGRP1-dependent VEGF signaling and ameliorates the impaired angiogenesis caused by high glucose.	Metformin	147-156	vascular endothelial growth factor A	Homo sapiens	191-195
30615306-0	2019	Associations between metformin use and vitamin B12 levels, anemia, and neuropathy in patients with diabetes: a meta-analysis.	Metformin	21-30	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	47-50
30615306-3	2019	This meta-analyses reviewed all available studies on associations between metformin use and vitamin B12 levels, anemia, and neuropathy in diabetic patients.	Metformin	74-83	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	100-103
30615306-7	2019	Compared with diabetic patients not taking metformin, patients taking metformin had a significantly higher risk of vitamin B12 deficiency (RR 2.09; 95% CI 1.49, 2.93; P < 0.0001; I2  = 64%) and significantly lower serum vitamin B12 concentrations (MD -63.70; 95% CI -74.35, -53.05] pM; P < 0.00001; I2  = 87%), which depended on dose and duration of treatment.	Metformin	70-79	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	123-126
30615306-7	2019	Compared with diabetic patients not taking metformin, patients taking metformin had a significantly higher risk of vitamin B12 deficiency (RR 2.09; 95% CI 1.49, 2.93; P < 0.0001; I2  = 64%) and significantly lower serum vitamin B12 concentrations (MD -63.70; 95% CI -74.35, -53.05] pM; P < 0.00001; I2  = 87%), which depended on dose and duration of treatment.	Metformin	70-79	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	228-231
30615306-8	2019	Metformin use was also associated with significantly greater percentage decrease in serum vitamin B12 concentrations from baseline in diabetic patients (MD -14.68%; 95% CI -17.98%, -11.39%; P < 0.00001; I2  = 33%).	Metformin	0-9	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	98-101
30615306-10	2019	CONCLUSIONS: Metformin use led to significantly lowered vitamin B12 concentrations and significantly higher risk of vitamin B12 deficiency in diabetic patients.	Metformin	13-22	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	64-67
30615306-10	2019	CONCLUSIONS: Metformin use led to significantly lowered vitamin B12 concentrations and significantly higher risk of vitamin B12 deficiency in diabetic patients.	Metformin	13-22	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	124-127
30615306-12	2019	Annual vitamin B12 assessment in diabetic patients taking metformin is recommended.	Metformin	58-67	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	15-18
30945296-9	2019	RESULTS: We found that metformin treatment can robustly ameliorate periodontal infection and tissue destruction and reduce blood glucose and serum IL-1beta levels in mice with diabetic periodontitis.	Metformin	23-32	interleukin 1 beta	Mus musculus	147-155
30945296-10	2019	Moreover, gingival tissue exhibited less macrophage infiltration and decreased expression of Nek7, NLRP3, caspase-1, and mammalian target of rapamycin (mTOR), which were simultaneously observed in RAW 264.7 cell models stimulated with metformin.	Metformin	235-244	mechanistic target of rapamycin kinase	Homo sapiens	121-150
31273790-4	2019	We examined metformin"s regulation of angiopoietin-like 3 (ANGPTL3), a liver-derived secretory protein with LPL inhibitory property.	Metformin	12-21	angiopoietin like 3	Homo sapiens	59-66
31273790-0	2019	AMPK-SIRT1-independent inhibition of ANGPTL3 gene expression is a potential lipid-lowering mechanism of metformin.	Metformin	104-113	angiopoietin like 3	Homo sapiens	37-44
31273790-4	2019	We examined metformin"s regulation of angiopoietin-like 3 (ANGPTL3), a liver-derived secretory protein with LPL inhibitory property.	Metformin	12-21	angiopoietin like 3	Homo sapiens	38-57
31273790-5	2019	METHODS: Using HepG2 cells, a human hepatocyte cell line, the effects of metformin on ANGPTL3 gene and protein expression were determined.	Metformin	73-82	angiopoietin like 3	Homo sapiens	86-93
31273790-6	2019	The role of AMPK-SIRT1 pathway in metformin regulation of ANGPTL3 was determined using pharmacological, RNAi and reporter assays.	Metformin	34-43	angiopoietin like 3	Homo sapiens	58-65
31273790-7	2019	Metformin regulation of ANGPTL3 expression was also examined in sodium palmitate-induced insulin resistance.	Metformin	0-9	angiopoietin like 3	Homo sapiens	24-31
31273790-8	2019	KEY FINDINGS: Metformin and pharmacological activators of AMPK and SIRT1 inhibited the expression of ANGPTL3 in HepG2 cells.	Metformin	14-23	angiopoietin like 3	Homo sapiens	101-108
31273790-10	2019	AMPK-SIRT1 activators and metformin exhibited distinct effects on the expression of ANGPTL3 gene luciferase reporter.	Metformin	26-35	angiopoietin like 3	Homo sapiens	84-91
31273790-11	2019	Sodium palmitate-induced insulin resistance in cells resulted in increased ANGPTL3 gene expression which was suppressed by pretreatment with metformin.	Metformin	141-150	angiopoietin like 3	Homo sapiens	75-82
31273790-12	2019	CONCLUSIONS: Metformin inhibits ANGPTL3 expression in the liver in an AMPK-SIRT1-independent manner as a potential mechanism to regulate LPL and lower plasma lipids.	Metformin	13-22	angiopoietin like 3	Homo sapiens	32-39
31181215-0	2019	PPP1R3C mediates metformin-inhibited hepatic gluconeogenesis.	Metformin	17-26	protein phosphatase 1, regulatory subunit 3C	Mus musculus	0-7
31181215-3	2019	Here, we aimed to explore the role of PPP1R3C in metformin-mediated inhibition of hepatic gluconeogenesis.	Metformin	49-58	protein phosphatase 1, regulatory subunit 3C	Mus musculus	38-45
31181215-7	2019	RESULTS: Metformin and adenovirus-mediated activation of AMPK suppressed 8-Br-cAMP-stimulated Ppp1r3c mRNA expression in primary mouse hepatocytes.	Metformin	9-18	protein phosphatase 1, regulatory subunit 3C	Mus musculus	94-101
31181215-12	2019	CONCLUSION: Metformin-activated AMPK decreases hepatic PPP1R3C expression, leading to the suppression of hepatic gluconeogenesis through blocking cAMP-stimulated TORC2 dephosphorylation.	Metformin	12-21	protein phosphatase 1, regulatory subunit 3C	Mus musculus	55-62
31270521-2	2019	We report here on heat active hydrogel formation by mixing graphene oxide (GO) or carboxyl enriched reduced graphene oxide (rGO-COOH) with metformin hydrochloride, an insulin sensitizer drug currently used as the first line therapy to treat patients with type 2 diabetes.	Metformin	139-162	insulin	Homo sapiens	167-174
31548957-12	2019	About 44% patients in Group 1 (metformin) had increased insulin levels initially (>20 muU/ml), which were decreased to 16% after three months of metformin therapy.	Metformin	31-40	insulin	Homo sapiens	56-63
31548957-14	2019	Conclusion: It has been concluded from this study that metformin significantly lowers insulin levels in patients with PCOS; in both obese and nonobese; which points towards its potential usefulness in treatment of PCOS patients, though it had no significant effect on body mass index in 12 weeks.	Metformin	55-64	insulin	Homo sapiens	86-93
31467666-0	2019	Metformin represses the pathophysiology of AAA by suppressing the activation of PI3K/AKT/mTOR/autophagy pathway in ApoE-/- mice.	Metformin	0-9	thymoma viral proto-oncogene 1	Mus musculus	85-88
31467666-0	2019	Metformin represses the pathophysiology of AAA by suppressing the activation of PI3K/AKT/mTOR/autophagy pathway in ApoE-/- mice.	Metformin	0-9	apolipoprotein E	Mus musculus	115-119
31467666-9	2019	In addition, metformin significantly suppressed the activation of the PI3K/AKT/mToR pathway and decreased the mRNA and protein levels of LC3B and Beclin1, which were induced by Ang-II.	Metformin	13-22	thymoma viral proto-oncogene 1	Mus musculus	75-78
31467666-9	2019	In addition, metformin significantly suppressed the activation of the PI3K/AKT/mToR pathway and decreased the mRNA and protein levels of LC3B and Beclin1, which were induced by Ang-II.	Metformin	13-22	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	177-183
31467666-11	2019	Interestingly, the cell proliferation, apoptosis, migration and autophagy of vascular smooth muscle cells (VSMCs) induced by Ang-II were also decreased following metformin treatment.	Metformin	162-171	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	125-131
31467666-13	2019	Conclusions: Metformin represses the pathophysiology of AAA by inhibiting the activation of PI3K/AKT/mTOR/autophagy pathway.	Metformin	13-22	thymoma viral proto-oncogene 1	Mus musculus	97-100
31501716-4	2019	In this study, fecal microbiota transplantation (FMT) using fecal material from metformin-treated mice was found to upregulate the expression of GLP-1 and pattern-recognition receptors TLR1 and TLR4 for the improvement in hyperglycemia caused by a high-fat diet.	Metformin	80-89	toll-like receptor 4	Mus musculus	194-198
31150647-0	2019	Metformin inhibits PPARdelta agonist-mediated tumor growth by reducing Glut1 and SLC1A5 expressions of cancer cells.	Metformin	0-9	peroxisome proliferator activator receptor delta	Mus musculus	19-28
31150647-0	2019	Metformin inhibits PPARdelta agonist-mediated tumor growth by reducing Glut1 and SLC1A5 expressions of cancer cells.	Metformin	0-9	solute carrier family 1 (neutral amino acid transporter), member 5	Mus musculus	81-87
31391459-0	2019	Correction: H19 lncRNA alters methylation and expression of Hnf4alpha in the liver of metformin-exposed fetuses.	Metformin	86-95	hepatocyte nuclear factor 4 alpha	Homo sapiens	60-69
31386659-10	2019	Neonates born to metformin-treated mothers had lower birth weights (mean difference -107.7 g, 95% CI -182.3 to -32.7, I2 = 83%, p = 0.005) and lower ponderal indices (mean difference -0.13 kg/m3, 95% CI -0.26 to 0.00, I2 = 0%, p = 0.04) than neonates of insulin-treated mothers.	Metformin	17-26	insulin	Homo sapiens	254-261
31386659-17	2019	Limited evidence (1 study with data treated as 2 cohorts) suggested that adiposity indices (abdominal [p = 0.02] and visceral [p = 0.03] fat volumes) may be higher in children born to metformin-treated compared to insulin-treated mothers.	Metformin	184-193	insulin	Homo sapiens	214-221
31386659-19	2019	CONCLUSIONS: Following intrauterine exposure to metformin for treatment of maternal GDM, neonates are significantly smaller than neonates whose mothers were treated with insulin during pregnancy.	Metformin	48-57	insulin	Homo sapiens	170-177
31132357-5	2019	The results suggested metformin decreased the inflammatory response by reducing the expression of proinflammatory cytokines (TNF-alpha, IL-1beta and IL-6), myeloperoxidase activity, and malondialdehyde levels.	Metformin	22-31	tumor necrosis factor	Rattus norvegicus	125-134
31132357-5	2019	The results suggested metformin decreased the inflammatory response by reducing the expression of proinflammatory cytokines (TNF-alpha, IL-1beta and IL-6), myeloperoxidase activity, and malondialdehyde levels.	Metformin	22-31	interleukin 1 beta	Rattus norvegicus	136-144
31132357-5	2019	The results suggested metformin decreased the inflammatory response by reducing the expression of proinflammatory cytokines (TNF-alpha, IL-1beta and IL-6), myeloperoxidase activity, and malondialdehyde levels.	Metformin	22-31	interleukin 6	Rattus norvegicus	149-153
31132357-7	2019	Interestingly, with the presence of the AMPK inhibitor (Compound C), metformin presented impairment of its gastroprotective action.	Metformin	69-78	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	40-44
31132357-8	2019	The gastroprotective effect of metformin might be related to the activation of the AMPK pathway.	Metformin	31-40	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	83-87
31324361-4	2019	Metformin"s main antineoplastic mechanism of action is thought to be mediated through inhibition of mammalian target of rapamycin, inhibition of hypoxia-inducible factor 1 (HIF-1) alpha, and activation of p53.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	100-129
31324361-4	2019	Metformin"s main antineoplastic mechanism of action is thought to be mediated through inhibition of mammalian target of rapamycin, inhibition of hypoxia-inducible factor 1 (HIF-1) alpha, and activation of p53.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	173-185
31324361-4	2019	Metformin"s main antineoplastic mechanism of action is thought to be mediated through inhibition of mammalian target of rapamycin, inhibition of hypoxia-inducible factor 1 (HIF-1) alpha, and activation of p53.	Metformin	0-9	tumor protein p53	Homo sapiens	205-208
31195189-6	2019	Metformin prevented atrophy of myelinated axons, and reduced expression of inflammatory mediators (interleukin-1beta, inducible nitric oxide synthase and nitric oxide).	Metformin	0-9	nitric oxide synthase 2, inducible	Mus musculus	118-149
31195189-7	2019	However, treatment with 200 mg of metformin was more effective in increasing neurotrophic (myelin basic protein and neural growth factor), angiogenic (vascular endothelial growth factor) and anti-inflammatory (inhibitor kappa B-alpha and interleukin 10) factors.	Metformin	34-43	interleukin 10	Mus musculus	238-252
31047842-12	2019	Upon restoration of WT-TP53 activity in MIA-PaCa-2 cells, an altered sensitivity to the combination of certain NAX compounds and metformin was observed compared to the parental cells which normally lack WT-TP53.	Metformin	129-138	tumor protein p53	Homo sapiens	23-27
31047842-12	2019	Upon restoration of WT-TP53 activity in MIA-PaCa-2 cells, an altered sensitivity to the combination of certain NAX compounds and metformin was observed compared to the parental cells which normally lack WT-TP53.	Metformin	129-138	tumor protein p53	Homo sapiens	206-210
30973968-1	2019	AIMS: Metformin is first-line treatment of type 2 diabetes mellitus and reduces cardiovascular events in patients with insulin resistance and type 2 diabetes.	Metformin	6-15	insulin	Homo sapiens	119-126
31154939-15	2019	Metformin treatment decreased inflammation, IL-6 levels, STAT3 activation, and human PA smooth muscle cell proliferation.	Metformin	0-9	interleukin 6	Homo sapiens	44-48
31154939-15	2019	Metformin treatment decreased inflammation, IL-6 levels, STAT3 activation, and human PA smooth muscle cell proliferation.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	57-62
31154939-16	2019	In vivo, in the supracoronary aortic banding+MetS animals, reducing IL-6, either by anti-IL-6 antibody or metformin treatment, reversed pulmonary vascular remodeling and improve PH due to LHD.	Metformin	106-115	interleukin 6	Homo sapiens	68-72
31155146-9	2019	Metformin monotherapy (29.5%) was most commonly prescribed in patients with an HbA1c level of <7%; metformin combination (31.7%), in patients with an HbA1c level of 7%-<8%; and insulin-containing treatment, in patients with HbA1c levels of 8%-<9% (28.1%) and >=9% (38.4%).	Metformin	0-9	insulin	Homo sapiens	177-184
31136032-0	2019	Hyperglycemia induces NF-kappaB activation and MCP-1 expression via downregulating GLP-1R expression in rat mesangial cells: inhibition by metformin.	Metformin	139-148	mast cell protease 1-like 1	Rattus norvegicus	47-52
31346998-12	2019	(3) After treatment with metformin for 6 months, serum insulin levels decreased, and sOB-R levels increased significantly (P<0.01).	Metformin	25-34	insulin	Homo sapiens	55-62
31237133-0	2019	Effectiveness and Safety of Adding Basal Insulin Glargine in Patients with Type 2 Diabetes Mellitus Exhibiting Inadequate Response to Metformin and DPP-4 Inhibitors with or without Sulfonylurea.	Metformin	134-143	insulin	Homo sapiens	41-48
31237133-1	2019	BACKGROUND: We aimed to investigate the effectiveness and safety of adding basal insulin to initiating dipeptidyl peptidase-4 (DPP-4) inhibitor and metformin and/or sulfonylurea (SU) in achieving the target glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes mellitus (T2DM).	Metformin	148-157	insulin	Homo sapiens	81-88
31237133-12	2019	CONCLUSION: The combination add-on therapy of insulin glargine, on metformin and DPP-4 inhibitors with or without SU was safe and efficient in reducing HbA1c levels and thus, is a preferable option in managing T2DM patients exhibiting dysglycemia despite the use of OADs.	Metformin	67-76	insulin	Homo sapiens	46-53
31188026-6	2019	Results: In the primary analysis, both ATM and OCT1 showed significant effects of genotype on change in body mass index z-scores, the primary outcome measure, during the first 16 weeks of treatment with metformin.	Metformin	203-212	solute carrier family 22 member 1	Homo sapiens	47-51
31152309-12	2019	Metformin showed significant increase in AST and creatinine which was reserved in NS group.	Metformin	0-9	solute carrier family 17 member 5	Homo sapiens	41-44
30806102-9	2019	l-Carnitine may act synergistically with metformin for improvement of reproductive performance, insulin resistance, and lipid profile in clomiphene-resistant obese PCOS women.	Metformin	41-50	insulin	Homo sapiens	96-103
30989716-12	2019	We also discuss the activation of AMP activated protein kinase (AMPK) by the most widely used drug for type 2 diabetes, metformin, which exerts a dual negative regulatory effect on mTOR and BMP signaling, suggesting that metformin is a promising drug treatment for HO.	Metformin	120-129	mechanistic target of rapamycin kinase	Homo sapiens	181-185
30989716-12	2019	We also discuss the activation of AMP activated protein kinase (AMPK) by the most widely used drug for type 2 diabetes, metformin, which exerts a dual negative regulatory effect on mTOR and BMP signaling, suggesting that metformin is a promising drug treatment for HO.	Metformin	221-230	mechanistic target of rapamycin kinase	Homo sapiens	181-185
30938764-0	2019	Metformin Improves Peripheral Insulin Sensitivity in Youth With Type 1 Diabetes.	Metformin	0-9	insulin	Homo sapiens	30-37
30938764-2	2019	We previously demonstrated that adolescents with type 1 diabetes have adipose, hepatic, and muscle IR, and that metformin lowers daily insulin dose, suggesting improved IR.	Metformin	112-121	insulin	Homo sapiens	135-142
31176103-0	2019	Alpha lipoic acid and metformin alleviates experimentally induced insulin resistance and cognitive deficit by modulation of TLR2 signalling.	Metformin	22-31	insulin	Homo sapiens	66-73
31307011-7	2019	Preclinical evidence suggests that the primary direct mechanisms of metformin action include inhibition of mitochondrial oxidative phosphorylation via inhibition of both mitochondrial complex I and mitochondrial glycerophosphate dehydrogenase, leading to metabolic stress.	Metformin	68-77	glycerol-3-phosphate dehydrogenase 2	Homo sapiens	198-242
31603875-14	2019	Conclusions: High prevalence of vitamin B12 deficiency was observed in metformin-treated patients with type 2 diabetes.	Metformin	71-80	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	40-43
31173255-8	2019	In addition, compared with the control group, metformin significantly enhanced the activity of caspase-3, increased the expression of AMPK/pAMPK/Bax proteins and reduced the expression of mTOR/Bcl-2 proteins (P&lt;0.05).	Metformin	46-55	caspase 3	Homo sapiens	95-104
31173255-8	2019	In addition, compared with the control group, metformin significantly enhanced the activity of caspase-3, increased the expression of AMPK/pAMPK/Bax proteins and reduced the expression of mTOR/Bcl-2 proteins (P&lt;0.05).	Metformin	46-55	BCL2 associated X, apoptosis regulator	Homo sapiens	145-148
31173255-8	2019	In addition, compared with the control group, metformin significantly enhanced the activity of caspase-3, increased the expression of AMPK/pAMPK/Bax proteins and reduced the expression of mTOR/Bcl-2 proteins (P&lt;0.05).	Metformin	46-55	mechanistic target of rapamycin kinase	Homo sapiens	188-192
31173255-8	2019	In addition, compared with the control group, metformin significantly enhanced the activity of caspase-3, increased the expression of AMPK/pAMPK/Bax proteins and reduced the expression of mTOR/Bcl-2 proteins (P&lt;0.05).	Metformin	46-55	BCL2 apoptosis regulator	Homo sapiens	193-198
31173255-10	2019	Metformin may inhibit glioma cell proliferation, migration and invasion, and promote its apoptosis; the effects may be associated with the AMPK/mTOR signaling pathway and oxidative stress.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	144-148
31197747-9	2019	Metformin and glyburide pretreatment normalized the LPS-induced IL-1beta secretion in the control and diabetic cultures.	Metformin	0-9	interleukin 1 beta	Rattus norvegicus	64-72
31176103-0	2019	Alpha lipoic acid and metformin alleviates experimentally induced insulin resistance and cognitive deficit by modulation of TLR2 signalling.	Metformin	22-31	toll like receptor 2	Homo sapiens	124-128
31176103-10	2019	Combination of ALA (100 mg/kg, ip) with metformin (100 mg/kg, ip) exhibited a potentiating effect in improving cognitive performance and insulin signalling.	Metformin	40-49	insulin	Homo sapiens	137-144
31160534-3	2019	In this study, we report that in CD4+ T cells from human healthy controls and human systemic lupus erythematosus patients, metformin inhibits the transcription of IFN-stimulated genes (ISGs) after IFN-alpha treatment.	Metformin	123-132	interferon alpha 1	Homo sapiens	197-206
31250538-9	2019	Other studies have suggested that metformin regulates monocyte maturation through signal transducer and activator of transcription 3 (STAT3) activation, as also indicated by our results.	Metformin	34-43	signal transducer and activator of transcription 3	Mus musculus	82-132
31250538-9	2019	Other studies have suggested that metformin regulates monocyte maturation through signal transducer and activator of transcription 3 (STAT3) activation, as also indicated by our results.	Metformin	34-43	signal transducer and activator of transcription 3	Mus musculus	134-139
31160539-0	2019	Metformin Promotes Anxiolytic and Antidepressant-Like Responses in Insulin-Resistant Mice by Decreasing Circulating Branched-Chain Amino Acids.	Metformin	0-9	insulin	Homo sapiens	67-74
31337349-0	2019	Metformin reverses mesenchymal phenotype of primary breast cancer cells through STAT3/NF-kappaB pathways.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	80-85
31337349-0	2019	Metformin reverses mesenchymal phenotype of primary breast cancer cells through STAT3/NF-kappaB pathways.	Metformin	0-9	nuclear factor kappa B subunit 1	Homo sapiens	86-95
31337349-14	2019	CONCLUSION: These results suggest that MTF inhibits IL-6-induced EMT, cell proliferation, and migration of primary breast cancer cells by preventing the activation of STAT3 and NF-kappaB.	Metformin	39-42	interleukin 6	Homo sapiens	52-56
31337349-14	2019	CONCLUSION: These results suggest that MTF inhibits IL-6-induced EMT, cell proliferation, and migration of primary breast cancer cells by preventing the activation of STAT3 and NF-kappaB.	Metformin	39-42	signal transducer and activator of transcription 3	Homo sapiens	167-172
31337349-14	2019	CONCLUSION: These results suggest that MTF inhibits IL-6-induced EMT, cell proliferation, and migration of primary breast cancer cells by preventing the activation of STAT3 and NF-kappaB.	Metformin	39-42	nuclear factor kappa B subunit 1	Homo sapiens	177-186
31268904-0	2019	Metformin improved oxidized low-density lipoprotein-impaired mitochondrial function and increased glucose uptake involving Akt-AS160 pathway in raw264.7 macrophages.	Metformin	0-9	thymoma viral proto-oncogene 1	Mus musculus	123-126
31268904-9	2019	RESULTS: Metformin improved Ox-LDL-impaired anti-inflammatory phenotype in raw264.7 macrophages as shown by up-regulated transcription of anti-inflammatory markers including interleukin 10 (0.76 +- 0.04 vs. 0.94 +- 0.01, P = 0.003) and Resistin-like molecule alpha (0.67 +- 0.08 vs. 1.78 +- 0.34, P = 0.030).	Metformin	9-18	interleukin 10	Mus musculus	174-188
31268904-11	2019	Moreover, metformin-mediated Akt activation increased Akt substrate of 160 kDa (AS160) phosphorylation (0.51 +- 0.04 vs. 1.03 +- 0.03, P = 0.0041), promoted membrane translocation of glucose transporter 1, and increased glucose influx into the cells (4.78 +- 0.04 vs. 5.47 +- 0.01, P &lt; 0.001).	Metformin	10-19	thymoma viral proto-oncogene 1	Mus musculus	29-32
31293042-9	2019	Metformin treatment at 10 muM did not affect PDLSC proliferation, while at 50 and 100 muM, metformin time-dependently enhanced PDLSC proliferation and significantly increased cell numbers after 5 and 7 days of stimulation (P &lt;  0.05).	Metformin	0-9	latexin	Homo sapiens	26-29
31284427-0	2019	Metformin Enhances Nomegestrol Acetate Suppressing Growth of Endometrial Cancer Cells and May Correlate to Downregulating mTOR Activity In Vitro and In Vivo.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	122-126
31284427-7	2019	Metformin significantly increased the inhibitory effect of and apoptosis induced by NOMAC and strengthened the depressive effect of NOMAC on activity of mTOR and its downstream substrates, compared to their treatment alone (p &lt; 0.05).	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	153-157
31284427-8	2019	In xenograft tumor tissues, metformin (100 mg/kg) enhanced the suppressive effect of NOMAC (100 mg/kg) on mTOR signaling and increased the average concentration of NOMAC by nearly 1.6 times compared to NOMAC treatment alone.	Metformin	28-37	mechanistic target of rapamycin kinase	Homo sapiens	106-110
31278260-4	2019	In this study, we show that the first-line antidiabetic drug metformin exerts potent antifibrotic effects in the lung by modulating metabolic pathways, inhibiting TGFbeta1 action, suppressing collagen formation, activating PPARgamma signaling and inducing lipogenic differentiation in lung fibroblasts derived from IPF patients.	Metformin	61-70	transforming growth factor beta 1	Homo sapiens	163-171
31278260-4	2019	In this study, we show that the first-line antidiabetic drug metformin exerts potent antifibrotic effects in the lung by modulating metabolic pathways, inhibiting TGFbeta1 action, suppressing collagen formation, activating PPARgamma signaling and inducing lipogenic differentiation in lung fibroblasts derived from IPF patients.	Metformin	61-70	peroxisome proliferator activated receptor gamma	Homo sapiens	223-232
30445633-0	2019	Metformin suppresses the esophageal carcinogenesis in rats treated with NMBzA through inhibiting AMPK/mTOR signaling pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	97-101
30445633-8	2019	Immunohistochemistry and western blotting showed that without interfering the metabolism of NMBzA, metformin inhibited the inflammation of esophagi via reducing the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6).	Metformin	99-108	nitric oxide synthase 2	Rattus norvegicus	180-211
30445633-8	2019	Immunohistochemistry and western blotting showed that without interfering the metabolism of NMBzA, metformin inhibited the inflammation of esophagi via reducing the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6).	Metformin	99-108	nitric oxide synthase 2	Rattus norvegicus	213-217
30445633-8	2019	Immunohistochemistry and western blotting showed that without interfering the metabolism of NMBzA, metformin inhibited the inflammation of esophagi via reducing the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6).	Metformin	99-108	interleukin 6	Rattus norvegicus	249-262
30445633-8	2019	Immunohistochemistry and western blotting showed that without interfering the metabolism of NMBzA, metformin inhibited the inflammation of esophagi via reducing the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6).	Metformin	99-108	interleukin 6	Rattus norvegicus	264-268
30445633-9	2019	Treatment of metformin led to activation of AMP-activated protein kinase (AMPK) and attenuated signaling of the downstream molecules such as p-mTOR, p-p70S6K and cyclin D1 expression both in vivo and in vitro.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	44-72
30445633-9	2019	Treatment of metformin led to activation of AMP-activated protein kinase (AMPK) and attenuated signaling of the downstream molecules such as p-mTOR, p-p70S6K and cyclin D1 expression both in vivo and in vitro.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	143-147
30445633-9	2019	Treatment of metformin led to activation of AMP-activated protein kinase (AMPK) and attenuated signaling of the downstream molecules such as p-mTOR, p-p70S6K and cyclin D1 expression both in vivo and in vitro.	Metformin	13-22	cyclin D1	Rattus norvegicus	162-171
30445633-10	2019	Taken together, our study demonstrated that metformin suppressed the carcinogenesis of ESCC through inhibiting AMPK/mammalian target of the rapamycin (mTOR) signaling pathway, resulting in its chemopreventive effects on the carcinogenesis of ESCC.	Metformin	44-53	mechanistic target of rapamycin kinase	Homo sapiens	151-155
31293042-9	2019	Metformin treatment at 10 muM did not affect PDLSC proliferation, while at 50 and 100 muM, metformin time-dependently enhanced PDLSC proliferation and significantly increased cell numbers after 5 and 7 days of stimulation (P &lt;  0.05).	Metformin	91-100	latexin	Homo sapiens	86-89
31293042-10	2019	In addition, 50 muM metformin exhibited a maximal effect on migration, ALP activity, and mineral deposition (P &lt;  0.05).	Metformin	20-29	latexin	Homo sapiens	16-19
31293042-10	2019	In addition, 50 muM metformin exhibited a maximal effect on migration, ALP activity, and mineral deposition (P &lt;  0.05).	Metformin	20-29	alkaline phosphatase, placental	Homo sapiens	71-74
31293042-11	2019	Furthermore, 50 muM metformin significantly upregulated the gene expression levels of ALP, BSP, OPN, OCN, and Runx2 and the protein expression of ALP and Runx2 (P &lt;  0.05).	Metformin	20-29	latexin	Homo sapiens	16-19
31293042-11	2019	Furthermore, 50 muM metformin significantly upregulated the gene expression levels of ALP, BSP, OPN, OCN, and Runx2 and the protein expression of ALP and Runx2 (P &lt;  0.05).	Metformin	20-29	alkaline phosphatase, placental	Homo sapiens	86-89
31293042-11	2019	Furthermore, 50 muM metformin significantly upregulated the gene expression levels of ALP, BSP, OPN, OCN, and Runx2 and the protein expression of ALP and Runx2 (P &lt;  0.05).	Metformin	20-29	integrin binding sialoprotein	Homo sapiens	91-94
31293042-11	2019	Furthermore, 50 muM metformin significantly upregulated the gene expression levels of ALP, BSP, OPN, OCN, and Runx2 and the protein expression of ALP and Runx2 (P &lt;  0.05).	Metformin	20-29	bone gamma-carboxyglutamate protein	Homo sapiens	101-104
31293042-11	2019	Furthermore, 50 muM metformin significantly upregulated the gene expression levels of ALP, BSP, OPN, OCN, and Runx2 and the protein expression of ALP and Runx2 (P &lt;  0.05).	Metformin	20-29	RUNX family transcription factor 2	Homo sapiens	110-115
31293042-11	2019	Furthermore, 50 muM metformin significantly upregulated the gene expression levels of ALP, BSP, OPN, OCN, and Runx2 and the protein expression of ALP and Runx2 (P &lt;  0.05).	Metformin	20-29	alkaline phosphatase, placental	Homo sapiens	146-149
31293042-11	2019	Furthermore, 50 muM metformin significantly upregulated the gene expression levels of ALP, BSP, OPN, OCN, and Runx2 and the protein expression of ALP and Runx2 (P &lt;  0.05).	Metformin	20-29	RUNX family transcription factor 2	Homo sapiens	154-159
31028998-0	2019	Metformin inhibits the proliferation of rheumatoid arthritis fibroblast-like synoviocytes through IGF-IR/PI3K/AKT/m-TOR pathway.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	110-113
31273547-4	2019	The effects of high glucose and DMBG on klotho and the mTOR pathway in MDCK cells were analyzed at the cellular level.	Metformin	32-36	klotho	Canis lupus familiaris	40-46
31273547-8	2019	Therefore, klotho plays an important role in the mechanism by which DMBG inhibits the mTOR pathway to protect renal function.	Metformin	68-72	klotho	Canis lupus familiaris	11-17
31028998-0	2019	Metformin inhibits the proliferation of rheumatoid arthritis fibroblast-like synoviocytes through IGF-IR/PI3K/AKT/m-TOR pathway.	Metformin	0-9	RAR related orphan receptor C	Homo sapiens	116-119
31028998-6	2019	More importantly, metformin induced G2/M cell cycle phase arrest in RA-FLS via the IGF-IR/PI3K/AKT/ m-TOR pathway and inhibited m-TOR phosphorylation through both the IGF-IR/PI3K/AKT signaling pathways thereby further upregulating and down-regulating p70s6k and 4E-BP1 phosphorylation, respectively; however, metformin was found not to induce apoptosis in RA-FLSs.	Metformin	18-27	AKT serine/threonine kinase 1	Homo sapiens	95-98
31028998-6	2019	More importantly, metformin induced G2/M cell cycle phase arrest in RA-FLS via the IGF-IR/PI3K/AKT/ m-TOR pathway and inhibited m-TOR phosphorylation through both the IGF-IR/PI3K/AKT signaling pathways thereby further upregulating and down-regulating p70s6k and 4E-BP1 phosphorylation, respectively; however, metformin was found not to induce apoptosis in RA-FLSs.	Metformin	18-27	mechanistic target of rapamycin kinase	Homo sapiens	100-105
31028998-6	2019	More importantly, metformin induced G2/M cell cycle phase arrest in RA-FLS via the IGF-IR/PI3K/AKT/ m-TOR pathway and inhibited m-TOR phosphorylation through both the IGF-IR/PI3K/AKT signaling pathways thereby further upregulating and down-regulating p70s6k and 4E-BP1 phosphorylation, respectively; however, metformin was found not to induce apoptosis in RA-FLSs.	Metformin	18-27	mechanistic target of rapamycin kinase	Homo sapiens	128-133
31028998-6	2019	More importantly, metformin induced G2/M cell cycle phase arrest in RA-FLS via the IGF-IR/PI3K/AKT/ m-TOR pathway and inhibited m-TOR phosphorylation through both the IGF-IR/PI3K/AKT signaling pathways thereby further upregulating and down-regulating p70s6k and 4E-BP1 phosphorylation, respectively; however, metformin was found not to induce apoptosis in RA-FLSs.	Metformin	18-27	AKT serine/threonine kinase 1	Homo sapiens	179-182
31028998-8	2019	Moreover, IGF-IR/PI3K/AKT m-TOR signaling pathway can be regulated by metformin.	Metformin	70-79	AKT serine/threonine kinase 1	Homo sapiens	22-25
31028998-8	2019	Moreover, IGF-IR/PI3K/AKT m-TOR signaling pathway can be regulated by metformin.	Metformin	70-79	RAR related orphan receptor C	Homo sapiens	28-31
30959417-10	2019	Data indicated that the protective effect of SF or metformin in insulin resistant HepG2 cells involves inhibition of oxidant processes and that the combination of agents may prove more effective therapeutically.	Metformin	51-60	insulin	Homo sapiens	64-71
31336028-0	2019	Combination of metformin and luteolin synergistically protects carbon tetrachloride-induced hepatotoxicity: Mechanism involves antioxidant, anti-inflammatory, antiapoptotic, and Nrf2/HO-1 signaling pathway.	Metformin	15-24	NFE2 like bZIP transcription factor 2	Rattus norvegicus	178-182
30959417-8	2019	Treatment of insulin resistant cells with SF or metformin alone decreased levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6); whereas antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) activity, as well as total antioxidant capacity (T-AOC) ability increased.	Metformin	48-57	insulin	Homo sapiens	13-20
30959417-8	2019	Treatment of insulin resistant cells with SF or metformin alone decreased levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6); whereas antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) activity, as well as total antioxidant capacity (T-AOC) ability increased.	Metformin	48-57	tumor necrosis factor	Homo sapiens	138-159
30959417-8	2019	Treatment of insulin resistant cells with SF or metformin alone decreased levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6); whereas antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) activity, as well as total antioxidant capacity (T-AOC) ability increased.	Metformin	48-57	tumor necrosis factor	Homo sapiens	161-170
31180536-0	2019	Metformin induces TPC-1 cell apoptosis through endoplasmic reticulum stress-associated pathways in vitro and in vivo.	Metformin	0-9	two pore segment channel 1	Homo sapiens	18-23
30959417-8	2019	Treatment of insulin resistant cells with SF or metformin alone decreased levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6); whereas antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) activity, as well as total antioxidant capacity (T-AOC) ability increased.	Metformin	48-57	interleukin 6	Homo sapiens	176-189
30959417-8	2019	Treatment of insulin resistant cells with SF or metformin alone decreased levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6); whereas antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) activity, as well as total antioxidant capacity (T-AOC) ability increased.	Metformin	48-57	interleukin 6	Homo sapiens	191-195
30959417-8	2019	Treatment of insulin resistant cells with SF or metformin alone decreased levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6); whereas antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) activity, as well as total antioxidant capacity (T-AOC) ability increased.	Metformin	48-57	catalase	Homo sapiens	257-265
30959417-8	2019	Treatment of insulin resistant cells with SF or metformin alone decreased levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6); whereas antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) activity, as well as total antioxidant capacity (T-AOC) ability increased.	Metformin	48-57	catalase	Homo sapiens	267-270
31298351-7	2019	CONCLUSIONS: The results of this study suggest that the addition of the low-dose slow-release metformin in insulin-resistant patients with normogonadotropic infertility improves the efficacy of FSH therapy.	Metformin	94-103	insulin	Homo sapiens	107-114
31037926-0	2019	Impact of Metformin and Pioglitazone on Serum Level of Tumor Necrosis Factor-Alpha and Lipid Profiles during Implantation Window in Diabetic Rats.	Metformin	10-19	tumor necrosis factor	Rattus norvegicus	55-82
31037926-13	2019	In metformin treated group, TNF-alpha serum level was also significantly higher than pioglitazone treated group (P&lt;0.001).	Metformin	3-12	tumor necrosis factor	Rattus norvegicus	28-37
31037926-15	2019	Conclusion: Metformin and pioglitazone have similar effects on glucose, lipid profiles and TNF-alpha serum levels.	Metformin	12-21	tumor necrosis factor	Rattus norvegicus	91-100
31060005-8	2019	Transcription factor (TF)-target network analysis revealed that metformin regulated gene expression potentially via TFs including Tp53, Est1, Sp1 and Hif1alpha.	Metformin	64-73	sulfotransferase family 1E member 1	Rattus norvegicus	136-140
30664704-3	2019	The objective of this study is to investigate the effect of metformin on angiotensin II (Ang II)-induced hypertension and cardiovascular diseases.	Metformin	60-69	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	73-87
30664704-3	2019	The objective of this study is to investigate the effect of metformin on angiotensin II (Ang II)-induced hypertension and cardiovascular diseases.	Metformin	60-69	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	89-95
30664704-5	2019	Mice infused with angiotensin II displayed an increase in blood pressure associated with enhanced vascular endoplasmic reticulum (ER) stress markers, which were blunted after metformin treatment.	Metformin	175-184	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	18-32
31082618-0	2019	Metformin inhibits beta-catenin phosphorylation on Ser-552 through an AMPK/PI3K/Akt pathway in colorectal cancer cells.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	80-83
31082618-4	2019	Here we report that a non-canonical Ser552 phosphorylation in beta-catenin, which promotes its nuclear accumulation and transcriptional activity, is blocked by metformin via AMPK-mediated PI3K/Akt signaling inhibition.	Metformin	160-169	AKT serine/threonine kinase 1	Homo sapiens	193-196
31620350-10	2019	PRL serum level was high in glyburide-treated patients as compared with metformin-treated patients (P = 0.002).	Metformin	72-81	prolactin	Homo sapiens	0-3
31620350-12	2019	Diabetic pharmacotherapy mainly metformin reduced PRL serum level in patients with T2DM through amelioration of IR.	Metformin	32-41	prolactin	Homo sapiens	50-53
31180536-3	2019	The present study explored the effect and the underlying mechanisms of metformin on human thyroid cancer TPC-1 cells.	Metformin	71-80	two pore segment channel 1	Homo sapiens	105-110
30759215-0	2019	Metformin Triggers PYY Secretion in Human Gut Mucosa.	Metformin	0-9	peptide YY	Homo sapiens	19-22
30759215-2	2019	Recent clinical studies show that metformin increases plasma levels of the anorectic gut hormone, peptide YY (PYY), but whether this is through a direct effect on the gut is unknown.	Metformin	34-43	peptide YY	Homo sapiens	98-108
30759215-2	2019	Recent clinical studies show that metformin increases plasma levels of the anorectic gut hormone, peptide YY (PYY), but whether this is through a direct effect on the gut is unknown.	Metformin	34-43	peptide YY	Homo sapiens	110-113
30759215-3	2019	OBJECTIVE: We hypothesized that exposure of human gut mucosal tissue to metformin would acutely trigger PYY secretion.	Metformin	72-81	peptide YY	Homo sapiens	104-107
31180536-4	2019	Following treatment of TPC-1 cells with different concentrations of metformin, cell proliferation and apoptosis were analyzed by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively.	Metformin	68-77	two pore segment channel 1	Homo sapiens	23-28
30759215-8	2019	RESULTS: Metformin increased PYY secretion from both ileal (P < 0.05) and colonic (P < 0.001) epithelia.	Metformin	9-18	peptide YY	Homo sapiens	29-32
30759215-9	2019	Both basal and metformin-induced PYY secretion were unchanged across body mass index or in tissues obtained from individuals with type 2 diabetes.	Metformin	15-24	peptide YY	Homo sapiens	33-36
30759215-10	2019	Metformin-dependent PYY secretion was blocked by inhibitors of the plasma membrane monoamine transporter (PMAT) and the serotonin reuptake transporter (SERT), as well as by an inhibitor of AMP kinase (AMPK).	Metformin	0-9	peptide YY	Homo sapiens	20-23
31180536-7	2019	In addition, treatment with metformin increased the expression of Bip, CHOP and caspase-12 in vitro, activating endoplasmic reticulum (ER) stress.	Metformin	28-37	heat shock protein family A (Hsp70) member 5	Homo sapiens	66-69
30759215-10	2019	Metformin-dependent PYY secretion was blocked by inhibitors of the plasma membrane monoamine transporter (PMAT) and the serotonin reuptake transporter (SERT), as well as by an inhibitor of AMP kinase (AMPK).	Metformin	0-9	solute carrier family 6 member 4	Homo sapiens	120-150
30759215-10	2019	Metformin-dependent PYY secretion was blocked by inhibitors of the plasma membrane monoamine transporter (PMAT) and the serotonin reuptake transporter (SERT), as well as by an inhibitor of AMP kinase (AMPK).	Metformin	0-9	solute carrier family 6 member 4	Homo sapiens	152-156
30759215-11	2019	CONCLUSIONS: This is a report of a direct action of metformin on the gut epithelium to trigger PYY secretion in humans, occurring via cell internalization through PMAT and SERT and intracellular activation of AMPK.	Metformin	52-61	peptide YY	Homo sapiens	95-98
30759215-11	2019	CONCLUSIONS: This is a report of a direct action of metformin on the gut epithelium to trigger PYY secretion in humans, occurring via cell internalization through PMAT and SERT and intracellular activation of AMPK.	Metformin	52-61	solute carrier family 6 member 4	Homo sapiens	172-176
31180536-7	2019	In addition, treatment with metformin increased the expression of Bip, CHOP and caspase-12 in vitro, activating endoplasmic reticulum (ER) stress.	Metformin	28-37	DNA damage inducible transcript 3	Homo sapiens	71-75
31180536-10	2019	Finally, treatment with metformin inhibited thyroid cancer growth and increased the expression of Bip and CHOP in a TPC-1 cell xenograft model.	Metformin	24-33	heat shock protein family A (Hsp70) member 5	Homo sapiens	98-101
31180536-10	2019	Finally, treatment with metformin inhibited thyroid cancer growth and increased the expression of Bip and CHOP in a TPC-1 cell xenograft model.	Metformin	24-33	DNA damage inducible transcript 3	Homo sapiens	106-110
31180536-10	2019	Finally, treatment with metformin inhibited thyroid cancer growth and increased the expression of Bip and CHOP in a TPC-1 cell xenograft model.	Metformin	24-33	two pore segment channel 1	Homo sapiens	116-121
30761687-9	2019	In the adjusted Cox proportional regression analysis, metformin was associated with a decreased risk of CLRD mortality in the overall population (HR: 0.39, 95% CI: 0.15-0.99) and among participants with baseline CLRD (HR: 0.30, 95% CI: 0.10-0.93), after adjusting for age, gender, race/ethnicity, cigarette smoking, body mass index, current asthma and chronic obstructive pulmonary disease (COPD), insulin and other diabetic medications, and glycohaemoglobin level.	Metformin	54-63	insulin	Homo sapiens	398-405
31463247-2	2019	One standard first-line treatment for diabetes is metformin, which was reported to increase the risk for vitamin B12 deficiency.	Metformin	50-59	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	113-116
31463247-3	2019	We wanted to determine the prevalence of vitamin B12 deficiency in metformin-treated type 2 diabetes mellitus patients.	Metformin	67-76	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	49-52
31463247-18	2019	Thus, there is a need for doctors involved in the management of diabetes to keep abreast with guidelines and current recommendations and routinely monitor vitamin B12 levels particularly those who were on long-term takers of metformin and the elderly patients to optimize management of diabetes and its complications.	Metformin	225-234	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	163-166
31142603-7	2019	Our data show that metformin increased IL-10 and IDO expression in Ad-hMSCs and decreased high-mobility group box 1 protein, IL-1beta, and IL-6 expression.	Metformin	19-28	interleukin 1 beta	Rattus norvegicus	125-133
31142603-7	2019	Our data show that metformin increased IL-10 and IDO expression in Ad-hMSCs and decreased high-mobility group box 1 protein, IL-1beta, and IL-6 expression.	Metformin	19-28	interleukin 6	Rattus norvegicus	139-143
31142603-9	2019	In cocultures, metformin-stimulated Ad-hMSCs inhibited the mRNA expression of RUNX2, COL X, VEGF, MMP1, MMP3, and MMP13 in IL-1beta-stimulated OA chondrocytes and increased the expression of TIMP1 and TIMP3.	Metformin	15-24	RUNX family transcription factor 2	Rattus norvegicus	78-83
31142603-9	2019	In cocultures, metformin-stimulated Ad-hMSCs inhibited the mRNA expression of RUNX2, COL X, VEGF, MMP1, MMP3, and MMP13 in IL-1beta-stimulated OA chondrocytes and increased the expression of TIMP1 and TIMP3.	Metformin	15-24	interleukin 1 beta	Rattus norvegicus	123-131
31341409-0	2019	Metformin Inhibits Epithelial-to-Mesenchymal Transition of Keloid Fibroblasts via the HIF-1alpha/PKM2 Signaling Pathway.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	86-96
30975793-8	2019	OCT1-mediated uptake was prominent for class 2/4 compounds (e.g., metformin).	Metformin	66-75	solute carrier family 22 member 1	Homo sapiens	0-4
31004727-8	2019	RESULTS: LJ substantially inhibited MATE1-mediated metformin uptake in vitro.	Metformin	51-60	solute carrier family 47 member 1	Rattus norvegicus	36-41
31004727-11	2019	It could be due to the reduced MATE1-mediated metformin efflux from hepatocytes to bile by MATE1 inhibition in liver.	Metformin	46-55	solute carrier family 47 member 1	Rattus norvegicus	31-36
31004727-11	2019	It could be due to the reduced MATE1-mediated metformin efflux from hepatocytes to bile by MATE1 inhibition in liver.	Metformin	46-55	solute carrier family 47 member 1	Rattus norvegicus	91-96
31341409-8	2019	Metformin significantly inhibited the expression of HIF-1alpha and partially abolished hypoxia-induced EMT.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	52-62
31341409-10	2019	Conclusions: Metformin abolishes hypoxia-induced EMT in KFs by inhibiting the HIF-1alpha/PKM2 signaling pathway.	Metformin	13-22	hypoxia inducible factor 1 subunit alpha	Homo sapiens	78-88
30851273-0	2019	Metformin reduced NLRP3 inflammasome activity in Ox-LDL stimulated macrophages through adenosine monophosphate activated protein kinase and protein phosphatase 2A.	Metformin	0-9	NLR family pyrin domain containing 3	Homo sapiens	18-23
30851273-3	2019	This research aimed to elucidate whether and how metformin affects NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activity in oxidized low-density lipoprotein (ox-LDL) stimulated macrophages.	Metformin	49-58	NLR family pyrin domain containing 3	Homo sapiens	105-110
30851273-10	2019	In the results, upregulation of NLRP3 protein expression and NLRP3 inflammasome activation induced by ox-LDL treatment in macrophages were significantly attenuated by metformin treatment.	Metformin	167-176	NLR family pyrin domain containing 3	Homo sapiens	32-37
30851273-10	2019	In the results, upregulation of NLRP3 protein expression and NLRP3 inflammasome activation induced by ox-LDL treatment in macrophages were significantly attenuated by metformin treatment.	Metformin	167-176	NLR family pyrin domain containing 3	Homo sapiens	61-66
30851273-12	2019	Inhibition of PP2A significantly restored NLRP3 and pro-IL-1beta protein expression level downregulated by metformin in ox-LDL-stimulated macrophages.	Metformin	107-116	NLR family pyrin domain containing 3	Homo sapiens	42-47
30851273-12	2019	Inhibition of PP2A significantly restored NLRP3 and pro-IL-1beta protein expression level downregulated by metformin in ox-LDL-stimulated macrophages.	Metformin	107-116	interleukin 1 beta	Homo sapiens	52-64
30851273-14	2019	Our data showed Metformin reduced NLRP3 protein expression and NLRP3 inflammasome activation in ox-LDL-stimulated macrophages through AMPK and PP2A.	Metformin	16-25	NLR family pyrin domain containing 3	Homo sapiens	34-39
30851273-14	2019	Our data showed Metformin reduced NLRP3 protein expression and NLRP3 inflammasome activation in ox-LDL-stimulated macrophages through AMPK and PP2A.	Metformin	16-25	NLR family pyrin domain containing 3	Homo sapiens	63-68
30767126-16	2019	There is a need to inculcate GLP-1 analogs and SGLT2 inhibitors that reduce major CV events and heart failure hospitalizations (alongside lifestyle management and metformin) in the treatment of patients with diabetes and CV disease.	Metformin	163-172	glucagon	Homo sapiens	29-34
31244286-0	2019	Metformin Modulates Cyclin D1 and P53 Expression to Inhibit Cell Proliferation and to Induce Apoptosis in Cervical Cancer Cell Lines.	Metformin	0-9	tumor protein p53	Homo sapiens	34-37
31244286-12	2019	Moreover, 30 mM or higher doses of metformin increase significantly p53 expression (p< 0.001).	Metformin	35-44	tumor protein p53	Homo sapiens	68-71
31244286-14	2019	Conclusion: Metformin can modulate cyclin D1 and p53 expression in HeLa cancer cell line, leadingto inhibition of cell proliferation and induction of apoptosis.	Metformin	12-21	tumor protein p53	Homo sapiens	49-52
30885951-0	2019	Variation in the Plasma Membrane Monoamine Transporter (PMAT) (Encoded by SLC29A4) and Organic Cation Transporter 1 (OCT1) (Encoded by SLC22A1) and Gastrointestinal Intolerance to Metformin in Type 2 Diabetes: An IMI DIRECT Study.	Metformin	180-189	solute carrier family 22 member 1	Homo sapiens	87-115
30885951-0	2019	Variation in the Plasma Membrane Monoamine Transporter (PMAT) (Encoded by SLC29A4) and Organic Cation Transporter 1 (OCT1) (Encoded by SLC22A1) and Gastrointestinal Intolerance to Metformin in Type 2 Diabetes: An IMI DIRECT Study.	Metformin	180-189	solute carrier family 22 member 1	Homo sapiens	117-121
30885951-3	2019	We hypothesized that reduced transport of metformin via the plasma membrane monoamine transporter (PMAT) and organic cation transporter 1 (OCT1) could increase the risk of severe gastrointestinal adverse effects.	Metformin	42-51	solute carrier family 22 member 1	Homo sapiens	109-137
30885951-3	2019	We hypothesized that reduced transport of metformin via the plasma membrane monoamine transporter (PMAT) and organic cation transporter 1 (OCT1) could increase the risk of severe gastrointestinal adverse effects.	Metformin	42-51	solute carrier family 22 member 1	Homo sapiens	139-143
31020710-9	2019	Expression of phosphorylated AMPK was increased and that of phosphorylated mammalian target of rapamycin (mTOR) was decreased after exposure to tHA plus metformin.	Metformin	153-162	mechanistic target of rapamycin kinase	Homo sapiens	75-104
31020710-9	2019	Expression of phosphorylated AMPK was increased and that of phosphorylated mammalian target of rapamycin (mTOR) was decreased after exposure to tHA plus metformin.	Metformin	153-162	mechanistic target of rapamycin kinase	Homo sapiens	106-110
31210335-8	2019	Both mRNA and protein levels of TLR4 in VSMCs were upregulated after 500 mug/L LPS induction for 24 h, which were remarkably reversed by the treatment of different concentrations of metformin.	Metformin	182-191	toll-like receptor 4	Rattus norvegicus	32-36
31210335-9	2019	Knockdown of TLR4 remarkably inhibited LPS-induced inflammatory response in VSMCs, manifesting as decreased levels of MCP1, TNF-alpha and IL-6, which were further downregulated after combination treatment of TLR4 knockdown and 20 mM metformin.	Metformin	233-242	toll-like receptor 4	Rattus norvegicus	13-17
31210335-11	2019	GW9662 treatment resulted in elevated expressions of MCP-1, TNF-alpha and IL-6, which were reversed by metformin treatment.	Metformin	103-112	tumor necrosis factor	Rattus norvegicus	60-69
31210335-11	2019	GW9662 treatment resulted in elevated expressions of MCP-1, TNF-alpha and IL-6, which were reversed by metformin treatment.	Metformin	103-112	interleukin 6	Rattus norvegicus	74-78
31210335-12	2019	CONCLUSIONS: Metformin can effectively inhibit the mRNA and protein expressions of IL-6, MCP-1, and TNF-alpha in LPS-induced VSMCs.	Metformin	13-22	interleukin 6	Rattus norvegicus	83-87
31210335-12	2019	CONCLUSIONS: Metformin can effectively inhibit the mRNA and protein expressions of IL-6, MCP-1, and TNF-alpha in LPS-induced VSMCs.	Metformin	13-22	tumor necrosis factor	Rattus norvegicus	100-109
31210335-13	2019	The anti-inflammatory effects of metformin inhibit the inflammatory response through downregulating rely on the downregulation of TLR4 expression and upregulation ofng PPAR-gamma activity.	Metformin	33-42	toll-like receptor 4	Rattus norvegicus	130-134
31002375-0	2019	[Corrigendum] Metformin suppresses hypoxia-induced migration via the HIF-1alpha/VEGF pathway in gallbladder cancer in vitro and in vivo.	Metformin	14-23	hypoxia inducible factor 1 subunit alpha	Homo sapiens	69-79
31002375-0	2019	[Corrigendum] Metformin suppresses hypoxia-induced migration via the HIF-1alpha/VEGF pathway in gallbladder cancer in vitro and in vivo.	Metformin	14-23	vascular endothelial growth factor A	Homo sapiens	80-84
31164926-11	2019	Post-prandial insulin and glucose was reduced by metformin in combination with liraglutide and differed, but not significantly different from placebo, moreover, glucagon concentration was unaffected.	Metformin	49-58	insulin	Homo sapiens	14-21
31258748-0	2019	Role of p53 Family Proteins in Metformin Anti-Cancer Activities.	Metformin	31-40	tumor protein p53	Homo sapiens	8-11
31258748-7	2019	We also aimed to discuss the role of p53 family proteins in metformin-mediated suppression of cancer growth and survival.	Metformin	60-69	tumor protein p53	Homo sapiens	37-40
31118410-7	2019	Although AMPK activation by metformin did not reduce serum UA levels in hyperuricemic rats, it significantly alleviated HUA-induced renal tubular injury and NKA signaling impairment in vivo with effects similar to those of febuxostat.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	9-13
31118051-2	2019	Although Metformin has antiproliferative and proapoptotic effects on breast cancer, the heterogenous nature of this disease affects the response to metformin leading to the activation of pro-invasive signalling pathways that are mediated by the focal adhesion kinase PYK2 in pure HER2 phenotype breast cancer.	Metformin	148-157	erb-b2 receptor tyrosine kinase 2	Homo sapiens	280-284
31118051-4	2019	The activation of PYK2 by metformin in pure HER2 phenotype (HER2+/ER-/PR-) cell lines was investigated by microarrays, quantitative real time PCR and immunoblotting.	Metformin	26-35	erb-b2 receptor tyrosine kinase 2	Homo sapiens	44-48
31118051-4	2019	The activation of PYK2 by metformin in pure HER2 phenotype (HER2+/ER-/PR-) cell lines was investigated by microarrays, quantitative real time PCR and immunoblotting.	Metformin	26-35	erb-b2 receptor tyrosine kinase 2	Homo sapiens	60-64
31118051-5	2019	Cell migration and invasion PYK2-mediated and in response to metformin were determined by wound healing and invasion assays using HER2+/ER-/PR- PYK2 knockdown cell lines.	Metformin	61-70	erb-b2 receptor tyrosine kinase 2	Homo sapiens	130-134
31118051-8	2019	The effect of PYK2 and metformin on tumour initiation and invasion of HER2+/ER-/PR- breast cancer stem-like cells was performed using the in vitro stem cell proliferation and invasion assays.	Metformin	23-32	erb-b2 receptor tyrosine kinase 2	Homo sapiens	70-74
31118051-9	2019	RESULTS: Our study showed for the first time that pure HER2 breast cancer cells are more resistant to metformin treatment when compared with the other breast cancer phenotypes.	Metformin	102-111	erb-b2 receptor tyrosine kinase 2	Homo sapiens	55-59
31118051-11	2019	The role of PYK2 in promoting invasion of metformin resistant HER2 breast cancer cells was confirmed through investigating the effect of PYK2 knockdown and metformin on cell invasion and by proteomic analysis of associated cellular pathways.	Metformin	42-51	erb-b2 receptor tyrosine kinase 2	Homo sapiens	62-66
31118051-11	2019	The role of PYK2 in promoting invasion of metformin resistant HER2 breast cancer cells was confirmed through investigating the effect of PYK2 knockdown and metformin on cell invasion and by proteomic analysis of associated cellular pathways.	Metformin	156-165	erb-b2 receptor tyrosine kinase 2	Homo sapiens	62-66
31118051-15	2019	CONCLUSIONS: We provide evidence of a PYK2-driven pro-invasive potential of metformin in pure HER2 cancer therapy and propose that metformin-based therapy should consider the molecular heterogeneity of breast cancer to prevent complications associated with cancer chemoresistance, invasion and recurrence in treated patients.	Metformin	76-85	erb-b2 receptor tyrosine kinase 2	Homo sapiens	94-98
31178745-11	2019	We also show that metformin monotherapy was associated with significantly lower levels of inflammatory molecules, like TNFalpha, sTNFRI, and sTNFRII, when compared to other monotherapies.	Metformin	18-27	tumor necrosis factor	Homo sapiens	119-127
31205455-8	2019	In contrast, metformin reduced apoptosis by inhibiting this signaling pathway and increasing the expression level of Bcl-2.	Metformin	13-22	BCL2, apoptosis regulator	Rattus norvegicus	117-122
30953640-0	2019	Metformin promotes autophagy in ischemia/reperfusion myocardium via cytoplasmic AMPKalpha1 and nuclear AMPKalpha2 pathways.	Metformin	0-9	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	80-90
30953640-0	2019	Metformin promotes autophagy in ischemia/reperfusion myocardium via cytoplasmic AMPKalpha1 and nuclear AMPKalpha2 pathways.	Metformin	0-9	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	103-113
30953640-9	2019	Metformin could activate both the AMPKalpha1- and alpha2- mediated pathways, thus restoring autophagy flux during reperfusion.	Metformin	0-9	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	34-44
30953640-10	2019	Nevertheless, in AMPKalpha2 knockout mice, nuclear alpha2-regulated Skp2-CARM1-TFEB signaling was inhibited, while alpha1-related signaling was comparatively unaffected, which partially impaired metformin-enhanced autophagy.	Metformin	195-204	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	17-27
30953640-11	2019	SIGNIFICANCE: Our study suggests that metformin had the dual effects of promoting both cytoplasmic AMPKalpha1- and nuclear AMPKalpha2-related signaling to improve autophagic flux and restore cardiac function during MI/R.	Metformin	38-47	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	99-109
30953640-11	2019	SIGNIFICANCE: Our study suggests that metformin had the dual effects of promoting both cytoplasmic AMPKalpha1- and nuclear AMPKalpha2-related signaling to improve autophagic flux and restore cardiac function during MI/R.	Metformin	38-47	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	123-133
31083566-9	2019	By further analysis, ATP6V1G1, THY1, PRKCA and NDUFB3 were identified as the most promising candidates potentially mediating reprogramming effects of metformin in a maternal high fat diet.	Metformin	150-159	thymus cell antigen 1, theta	Mus musculus	31-35
31083566-9	2019	By further analysis, ATP6V1G1, THY1, PRKCA and NDUFB3 were identified as the most promising candidates potentially mediating reprogramming effects of metformin in a maternal high fat diet.	Metformin	150-159	protein kinase C, alpha	Mus musculus	37-42
31192264-9	2019	Further multivariable logistic regression analysis demonstrated that metformin was negatively associated with CAC severity (OR [95% CI] = 0.58 [0.34-0.99]; P = 0.048), which was independent of age, BMI, eGFR, gender, cigarette smoking, duration of diabetes, hypertension, statin prescription, and number of nonmetformin antidiabetic agents.	Metformin	69-78	epidermal growth factor receptor	Homo sapiens	203-207
31012989-4	2019	To determine metformin"s effect on HIF1alpha expression and survival in vitro, PC3 cells with high basal HIF1alpha levels were subjected to increasing doses of metformin after H2 O2 -induced oxidative stress.	Metformin	13-22	hypoxia inducible factor 1 subunit alpha	Homo sapiens	35-44
31012989-12	2019	Higher, more toxic doses of metformin may be required to inhibit the mammalian target of rapamycin-HIF1alpha pathway in this patient group.	Metformin	28-37	hypoxia inducible factor 1 subunit alpha	Homo sapiens	99-108
31014173-6	2019	Here we show that while metformin can significantly inhibit cell growth and induce apoptosis of OSCC cultured alone in a dose-dependent manner through activating p-AMPKT172 and modulating Bcl-2, Bax, and cleaved PARP.	Metformin	24-33	BCL2 apoptosis regulator	Homo sapiens	188-193
31014173-6	2019	Here we show that while metformin can significantly inhibit cell growth and induce apoptosis of OSCC cultured alone in a dose-dependent manner through activating p-AMPKT172 and modulating Bcl-2, Bax, and cleaved PARP.	Metformin	24-33	BCL2 associated X, apoptosis regulator	Homo sapiens	195-198
30735969-6	2019	In 21 days, metformin showed high stability in wastewater at 24  C and -20  C. The mean concentrations of metformin in all WWTPs ranged from 2.42 mug L-1 to 53.6 mug L-1.	Metformin	12-21	L1 cell adhesion molecule	Homo sapiens	150-161
30735969-6	2019	In 21 days, metformin showed high stability in wastewater at 24  C and -20  C. The mean concentrations of metformin in all WWTPs ranged from 2.42 mug L-1 to 53.6 mug L-1.	Metformin	106-115	L1 cell adhesion molecule	Homo sapiens	150-161
30754072-0	2019	NF-kappaB as the mediator of metformin"s effect on ageing and ageing-related diseases.	Metformin	29-38	nuclear factor kappa B subunit 1	Homo sapiens	0-9
30753544-3	2019	RESULTS: Metformin added to peripheral blood mononuclear cells from healthy volunteers enhanced in vitro cellular metabolism while inhibiting the mammalian target of rapamycin targets p70S6K and 4EBP1, with decreased cytokine production and cellular proliferation and increased phagocytosis activity.	Metformin	9-18	mechanistic target of rapamycin kinase	Homo sapiens	146-175
30753544-4	2019	Metformin administered to healthy human volunteers led to significant downregulation of genes involved in oxidative phosphorylation, mammalian target of rapamycin signaling, and type I interferon response pathways, particularly following stimulation with M. tuberculosis, and upregulation of genes involved in phagocytosis and reactive oxygen species production was increased.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	133-162
30753544-6	2019	At a functional level, metformin lowered ex vivo production of tumor necrosis factor alpha, interferon gamma, and interleukin 1beta but increased phagocytosis activity and reactive oxygen species production.	Metformin	23-32	tumor necrosis factor	Homo sapiens	63-90
30753544-6	2019	At a functional level, metformin lowered ex vivo production of tumor necrosis factor alpha, interferon gamma, and interleukin 1beta but increased phagocytosis activity and reactive oxygen species production.	Metformin	23-32	interferon gamma	Homo sapiens	92-108
30753544-6	2019	At a functional level, metformin lowered ex vivo production of tumor necrosis factor alpha, interferon gamma, and interleukin 1beta but increased phagocytosis activity and reactive oxygen species production.	Metformin	23-32	interleukin 1 beta	Homo sapiens	114-131
31231590-3	2019	Organic cation transport 1, encoded by SLC22A1 gene, is the main transporter of metformin into hepatocytes, which is considered metformin site of action.	Metformin	80-89	solute carrier family 22 member 1	Homo sapiens	39-46
31231590-3	2019	Organic cation transport 1, encoded by SLC22A1 gene, is the main transporter of metformin into hepatocytes, which is considered metformin site of action.	Metformin	128-137	solute carrier family 22 member 1	Homo sapiens	39-46
31231590-11	2019	Only SLC22A1 rs622342 variant was found to be associated with the response of combination therapy, in which AA alleles carriers were 2.7-times more responsive to metformin than C allele carriers (Recessive model, odds ratio = 2.718, p = 0.025, 95% CI = 1.112-6.385).	Metformin	162-171	solute carrier family 22 member 1	Homo sapiens	5-12
31164166-12	2019	In addition, metformin reduced B cell differentiation into germinal center B cells, decreased the serum immunoglobulin G level, and maintained the balance between IL-10- and IL-17-producing B cells.	Metformin	13-22	interleukin 10	Mus musculus	163-179
31002870-0	2019	Metformin ameliorates endotoxemia-induced endothelial pro-inflammatory responses via AMPK-dependent mediation of HDAC5 and KLF2.	Metformin	0-9	histone deacetylase 5	Mus musculus	113-118
31002870-4	2019	In the present study, the potential roles of histone deacetylase 5 (HDAC5) and kruppel-like factor 2 (KLF2) in the effects of metformin on endothelial pro-inflammatory responses were investigated.	Metformin	126-135	histone deacetylase 5	Mus musculus	68-73
31002870-5	2019	The results showed that metformin pretreatment increased the phosphorylation of HDAC5 at serine 498, leading to the upregulation of KLF2, and eliminated lipopolysaccharide (LPS) and tumor necrosis factor   (TNF )-induced upregulation of vascular cell adhesion molecule 1 (VCAM1).	Metformin	24-33	histone deacetylase 5	Mus musculus	80-85
31002870-5	2019	The results showed that metformin pretreatment increased the phosphorylation of HDAC5 at serine 498, leading to the upregulation of KLF2, and eliminated lipopolysaccharide (LPS) and tumor necrosis factor   (TNF )-induced upregulation of vascular cell adhesion molecule 1 (VCAM1).	Metformin	24-33	tumor necrosis factor	Mus musculus	182-203
31002870-5	2019	The results showed that metformin pretreatment increased the phosphorylation of HDAC5 at serine 498, leading to the upregulation of KLF2, and eliminated lipopolysaccharide (LPS) and tumor necrosis factor   (TNF )-induced upregulation of vascular cell adhesion molecule 1 (VCAM1).	Metformin	24-33	tumor necrosis factor	Mus musculus	207-210
31002870-8	2019	Our findings revealed that AMPK activation-mediated HDAC5 phosphorylation and KLF2 restoration is, at least partially, responsible to the anti-inflammatory effects of metformin in endotoxemia-induced endothelial cells, which has important implications for the future development of interfering therapies of sepsis.	Metformin	167-176	histone deacetylase 5	Mus musculus	52-57
31321352-3	2019	Metformin suppresses the mammalian target of rapamycin (mTOR) and our previous study showed that it also inhibits the activity of extracellular signal-regulated kinase (ERK).	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	25-54
31321352-3	2019	Metformin suppresses the mammalian target of rapamycin (mTOR) and our previous study showed that it also inhibits the activity of extracellular signal-regulated kinase (ERK).	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	56-60
31321352-3	2019	Metformin suppresses the mammalian target of rapamycin (mTOR) and our previous study showed that it also inhibits the activity of extracellular signal-regulated kinase (ERK).	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	130-167
31321352-3	2019	Metformin suppresses the mammalian target of rapamycin (mTOR) and our previous study showed that it also inhibits the activity of extracellular signal-regulated kinase (ERK).	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	169-172
31210334-11	2019	In addition, metformin could remarkably inhibit the NF-kappaB activity and promote the Nrf2 expression.	Metformin	13-22	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	52-61
31210334-11	2019	In addition, metformin could remarkably inhibit the NF-kappaB activity and promote the Nrf2 expression.	Metformin	13-22	nuclear factor, erythroid derived 2, like 2	Mus musculus	87-91
31210335-0	2019	Metformin inhibits LPS-induced inflammatory response in VSMCs by regulating TLR4 and PPAR-gamma.	Metformin	0-9	toll-like receptor 4	Rattus norvegicus	76-80
30894020-0	2019	Metformin treatment improves the spatial memory of aged mice in an APOE genotype-dependent manner.	Metformin	0-9	apolipoprotein E	Mus musculus	67-71
30894020-4	2019	It found that in aged ApoE3-TR mice, metformin treatment, at a molecular level, inhibited AMPK activity, increased insulin signaling, and activated mammalian target of rapamycin signaling, resulting in an enhanced expression of postsynaptic proteins; but the response of the neuronal AMPK activity and insulin signaling to metformin was blunt in aged ApoE4-TR mice.	Metformin	37-46	mechanistic target of rapamycin kinase	Homo sapiens	148-177
30894020-4	2019	It found that in aged ApoE3-TR mice, metformin treatment, at a molecular level, inhibited AMPK activity, increased insulin signaling, and activated mammalian target of rapamycin signaling, resulting in an enhanced expression of postsynaptic proteins; but the response of the neuronal AMPK activity and insulin signaling to metformin was blunt in aged ApoE4-TR mice.	Metformin	37-46	apolipoprotein E	Homo sapiens	351-356
30894020-5	2019	Meanwhile, metformin treatment also increased the phosphorylation of tau in both ApoE3-TR and ApoE4-TR mice, implying that metformin may have side effects in human.	Metformin	11-20	apolipoprotein E	Homo sapiens	94-99
30894020-6	2019	These findings suggest that metformin can improve the cognitive performance of aged mice in an APOE genotype-dependent manner, which provides empirical insights into the clinical value of metformin for ApoE4- and age-related AD prevention and treatment.-Zhang, J., Lin, Y., Dai, X., Fang, W., Wu, X., Chen, X.	Metformin	28-37	apolipoprotein E	Mus musculus	95-99
30894020-6	2019	These findings suggest that metformin can improve the cognitive performance of aged mice in an APOE genotype-dependent manner, which provides empirical insights into the clinical value of metformin for ApoE4- and age-related AD prevention and treatment.-Zhang, J., Lin, Y., Dai, X., Fang, W., Wu, X., Chen, X.	Metformin	188-197	apolipoprotein E	Mus musculus	95-99
30894020-6	2019	These findings suggest that metformin can improve the cognitive performance of aged mice in an APOE genotype-dependent manner, which provides empirical insights into the clinical value of metformin for ApoE4- and age-related AD prevention and treatment.-Zhang, J., Lin, Y., Dai, X., Fang, W., Wu, X., Chen, X.	Metformin	188-197	apolipoprotein E	Homo sapiens	202-207
30894020-7	2019	Metformin treatment improves the spatial memory of aged mice in an APOE genotype-dependent manner.	Metformin	0-9	apolipoprotein E	Mus musculus	67-71
30924377-0	2019	Anticancer effect of metformin against 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine-induced rat mammary carcinogenesis is through AMPK pathway and modulation of oxidative stress markers.	Metformin	21-30	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	134-138
30924377-5	2019	KEY FINDINGS: Metformin antitumor effect was mediated by increasing the adenosine monophosphate protein kinase (AMPK) activity, liver kinase B1, and decreasing the aromatase and insulin levels compared with the PhIP-administered group.	Metformin	14-23	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	72-110
30924377-5	2019	KEY FINDINGS: Metformin antitumor effect was mediated by increasing the adenosine monophosphate protein kinase (AMPK) activity, liver kinase B1, and decreasing the aromatase and insulin levels compared with the PhIP-administered group.	Metformin	14-23	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	112-116
30924377-9	2019	CONCLUSIONS: These results showed that metformin antitumor effect was mediated through AMPK pathway, reducing oxidative stress and serum lipid levels.	Metformin	39-48	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	87-91
30334569-0	2019	Metformin inhibits mTOR-HIF-1alpha axis and profibrogenic and inflammatory biomarkers in thioacetamide-induced hepatic tissue alterations.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	19-23
30334569-0	2019	Metformin inhibits mTOR-HIF-1alpha axis and profibrogenic and inflammatory biomarkers in thioacetamide-induced hepatic tissue alterations.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	24-34
30334569-2	2019	Therefore, we tested whether metformin can protect against liver injuries including fibrosis induced by TAA possibly via the downregulation of mTOR-HIF-1alpha axis and profibrogenic and inflammatory biomarkers.	Metformin	29-38	mechanistic target of rapamycin kinase	Homo sapiens	143-147
30334569-2	2019	Therefore, we tested whether metformin can protect against liver injuries including fibrosis induced by TAA possibly via the downregulation of mTOR-HIF-1alpha axis and profibrogenic and inflammatory biomarkers.	Metformin	29-38	hypoxia inducible factor 1 subunit alpha	Homo sapiens	148-158
30334569-5	2019	Metformin also significantly ( p < 0.05) inhibited TAA-induced HIF-1alpha, mTOR, the profibrogenic biomarker alpha-smooth muscle actin, tissue inhibitor of metalloproteinases-1, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase in harvested liver homogenates and blood samples.	Metformin	0-9	TIMP metallopeptidase inhibitor 1	Homo sapiens	136-176
30334569-5	2019	Metformin also significantly ( p < 0.05) inhibited TAA-induced HIF-1alpha, mTOR, the profibrogenic biomarker alpha-smooth muscle actin, tissue inhibitor of metalloproteinases-1, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase in harvested liver homogenates and blood samples.	Metformin	0-9	tumor necrosis factor	Homo sapiens	178-205
30334569-5	2019	Metformin also significantly ( p < 0.05) inhibited TAA-induced HIF-1alpha, mTOR, the profibrogenic biomarker alpha-smooth muscle actin, tissue inhibitor of metalloproteinases-1, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase in harvested liver homogenates and blood samples.	Metformin	0-9	tumor necrosis factor	Homo sapiens	207-216
30334569-5	2019	Metformin also significantly ( p < 0.05) inhibited TAA-induced HIF-1alpha, mTOR, the profibrogenic biomarker alpha-smooth muscle actin, tissue inhibitor of metalloproteinases-1, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase in harvested liver homogenates and blood samples.	Metformin	0-9	interleukin 6	Homo sapiens	219-232
30334569-5	2019	Metformin also significantly ( p < 0.05) inhibited TAA-induced HIF-1alpha, mTOR, the profibrogenic biomarker alpha-smooth muscle actin, tissue inhibitor of metalloproteinases-1, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase in harvested liver homogenates and blood samples.	Metformin	0-9	interleukin 6	Homo sapiens	234-238
31042624-4	2019	This study shows that metformin suppressed CD133 expression mainly by affecting the CD133 P1 promoter via adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling but not the mammalian target of rapamycin (mTOR).	Metformin	22-31	mechanistic target of rapamycin kinase	Homo sapiens	221-225
31042624-6	2019	Further experiments demonstrated that CCAAT/enhancer-binding protein beta (CEBPbeta) was upregulated by metformin and that two isoforms of CEBPbeta reciprocally regulated the expression of CD133.	Metformin	104-113	CCAAT enhancer binding protein alpha	Homo sapiens	75-83
31042624-9	2019	Our results indicated that metformin-AMPK-CEBPbeta signaling plays a crucial role in regulating the gene expression of CD133.	Metformin	27-36	CCAAT enhancer binding protein alpha	Homo sapiens	42-50
30981189-12	2019	The combination of mangiferin with metformin was insulin dependent (Akt pathway) whereas the combination of mangiferin and gliclazide was insulin independent (AMPK pathway).	Metformin	35-44	insulin	Homo sapiens	49-56
30771436-0	2019	Metformin induces human esophageal carcinoma cell pyroptosis by targeting the miR-497/PELP1 axis.	Metformin	0-9	proline, glutamate and leucine rich protein 1	Homo sapiens	86-91
30771436-5	2019	Intriguingly, metformin treatment leads to gasdermin D (GSDMD)-mediated pyroptosis, which is abrogated by forced expression of PELP1.	Metformin	14-23	proline, glutamate and leucine rich protein 1	Homo sapiens	127-132
30771436-6	2019	Mechanistically, metformin induces pyroptosis of ESCC by targeting miR-497/PELP1 axis.	Metformin	17-26	proline, glutamate and leucine rich protein 1	Homo sapiens	75-80
31205703-0	2019	Prevalence of vitamin B12 deficiency among metformin-treated type 2 diabetic patients in a tertiary institution, South-South Nigeria.	Metformin	43-52	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	22-25
31205703-1	2019	Background: The risk of chronic metformin pharmacotherapy to cause vitamin B12 deficiency and its associated medical complications has been of immense concern among diabetic patients.	Metformin	32-41	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	75-78
31205703-2	2019	Some studies have postulated that vitamin B12 deficiency is highly prevalent among chronic metformin-treated adult diabetic patients.	Metformin	91-100	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	42-45
31205703-3	2019	Aim: This study aimed to determine the prevalence of vitamin B12 deficiency among metformin-treated and metformin-naive type 2 diabetes mellitus patients.	Metformin	82-91	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	61-64
31205703-3	2019	Aim: This study aimed to determine the prevalence of vitamin B12 deficiency among metformin-treated and metformin-naive type 2 diabetes mellitus patients.	Metformin	104-113	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	61-64
31205703-8	2019	Results: The prevalence of vitamin B12 deficiency was 41% and 20% among metformin-treated and metformin-naive type 2 diabetes mellitus groups, respectively (p = 0.001).	Metformin	72-81	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	35-38
31205703-8	2019	Results: The prevalence of vitamin B12 deficiency was 41% and 20% among metformin-treated and metformin-naive type 2 diabetes mellitus groups, respectively (p = 0.001).	Metformin	94-103	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	35-38
31205703-9	2019	Borderline vitamin B12 status was present among 59% of metformin-treated group and 80% of metformin-naive group (p = 0.001).	Metformin	55-64	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	19-22
31205703-9	2019	Borderline vitamin B12 status was present among 59% of metformin-treated group and 80% of metformin-naive group (p = 0.001).	Metformin	90-99	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	19-22
31205703-11	2019	Conclusion: The prevalence of vitamin B12 deficiency was significantly high in diabetics, especially the metformin-treated patients.	Metformin	105-114	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	38-41
30935688-0	2019	Metformin alleviates inflammatory response in non-alcoholic steatohepatitis by restraining signal transducer and activator of transcription 3-mediated autophagy inhibition in vitro and in vivo.	Metformin	0-9	signal transducer and activator of transcription 3	Mus musculus	91-141
30935688-6	2019	Furthermore, the effects of metformin on STAT3 expression level and NASH inflammation were investigated.	Metformin	28-37	signal transducer and activator of transcription 3	Mus musculus	41-46
30935688-7	2019	The current results showed that metformin activated autophagy and decreased the mRNA expressions of inflammatory cytokines, IL-1beta, IL-6, and TNF-alpha via inhibition of the STAT3 mRNA and protein expression.	Metformin	32-41	interleukin 1 beta	Mus musculus	124-132
30935688-7	2019	The current results showed that metformin activated autophagy and decreased the mRNA expressions of inflammatory cytokines, IL-1beta, IL-6, and TNF-alpha via inhibition of the STAT3 mRNA and protein expression.	Metformin	32-41	interleukin 6	Mus musculus	134-138
30935688-7	2019	The current results showed that metformin activated autophagy and decreased the mRNA expressions of inflammatory cytokines, IL-1beta, IL-6, and TNF-alpha via inhibition of the STAT3 mRNA and protein expression.	Metformin	32-41	tumor necrosis factor	Mus musculus	144-153
30935688-7	2019	The current results showed that metformin activated autophagy and decreased the mRNA expressions of inflammatory cytokines, IL-1beta, IL-6, and TNF-alpha via inhibition of the STAT3 mRNA and protein expression.	Metformin	32-41	signal transducer and activator of transcription 3	Mus musculus	176-181
30935688-12	2019	In conclusion, this study demonstrated that metformin alleviated the inflammatory response in the liver and the hepatocyte of the NASH model via STAT3-mediated autophagy induction.	Metformin	44-53	signal transducer and activator of transcription 3	Mus musculus	145-150
31205453-1	2019	This paper includes synthesis and characterization of mixed ligand complexes derived from mefenamic acid and metformin using transition metal ions such as Co(II) and Cu(II).	Metformin	109-118	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	155-161
30851273-3	2019	This research aimed to elucidate whether and how metformin affects NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activity in oxidized low-density lipoprotein (ox-LDL) stimulated macrophages.	Metformin	49-58	NLR family pyrin domain containing 3	Homo sapiens	67-103
30615231-7	2019	Metformin attenuated the fall in systolic BP (P < 0.001), increased plasma GLP-1 concentrations (P < 0.05) and slowed gastric emptying (P < 0.05) without significantly affecting diastolic BP or HR.	Metformin	0-9	glucagon	Homo sapiens	75-80
30615231-8	2019	In conclusion, metformin acutely attenuates the hypotensive response to oral glucose, associated with augmented GLP-1 secretion and delayed gastric emptying, effects potentially relevant to its favourable cardiovascular profile.	Metformin	15-24	glucagon	Homo sapiens	112-117
30911997-11	2019	The surface cumulative rank curve revealed that metformin + lifestyle might be the best intervention with respect to the improvement of the homeostasis model of assessment insulin resistance and EE/DRSP + lifestyle appeared to be the best intervention for the reduction of total cholesterol and low-density lipoprotein cholesterol.	Metformin	48-57	insulin	Homo sapiens	172-179
30911997-14	2019	Conventional PCOS treatments, such as metformin, EE/CA, and EE/DRSP, combined with lifestyle control can be particularly effective in improving the homeostasis model assessment of insulin resistance and lipid metabolism.	Metformin	38-47	insulin	Homo sapiens	180-187
30608001-0	2019	Comparison of myo-inositol and metformin on glycemic control, lipid profiles, and gene expression related to insulin and lipid metabolism in women with polycystic ovary syndrome: a randomized controlled clinical trial.	Metformin	31-40	insulin	Homo sapiens	109-116
30816444-0	2019	MUL1 E3 ligase regulates the antitumor effects of metformin in chemoresistant ovarian cancer cells via AKT degradation.	Metformin	50-59	AKT serine/threonine kinase 1	Homo sapiens	103-106
30816444-2	2019	Metformin is used as a first-line drug for the treatment of type 2 diabetes; however, drug repositioning studies have revealed its antitumor effects, mainly mediated through AMP-activated protein kinase (AMPK) activation and AKT/mammalian target of rapamycin (mTOR) pathway inhibition in various types of cancer, including drug-resistant cancer cells.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	225-228
30816444-2	2019	Metformin is used as a first-line drug for the treatment of type 2 diabetes; however, drug repositioning studies have revealed its antitumor effects, mainly mediated through AMP-activated protein kinase (AMPK) activation and AKT/mammalian target of rapamycin (mTOR) pathway inhibition in various types of cancer, including drug-resistant cancer cells.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	229-258
30816444-2	2019	Metformin is used as a first-line drug for the treatment of type 2 diabetes; however, drug repositioning studies have revealed its antitumor effects, mainly mediated through AMP-activated protein kinase (AMPK) activation and AKT/mammalian target of rapamycin (mTOR) pathway inhibition in various types of cancer, including drug-resistant cancer cells.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	260-264
30816444-3	2019	The current study revealed that the novel antitumor mechanism of metformin is mediated by regulation of mitochondrial E3 ubiquitin protein ligase 1 (MUL1) expression that negatively regulates AKT.	Metformin	65-74	AKT serine/threonine kinase 1	Homo sapiens	192-195
30816444-4	2019	The results demonstrated that metformin decreased the expression of AKT protein levels via MUL1 E3 ligase.	Metformin	30-39	AKT serine/threonine kinase 1	Homo sapiens	68-71
30816444-5	2019	In addition, metformin increased both mRNA and protein levels of MUL1 and promoted degradation of AKT in a proteasome-dependent manner.	Metformin	13-22	AKT serine/threonine kinase 1	Homo sapiens	98-101
30816444-6	2019	Silencing MUL1 expression suppressed the metformin-mediated AKT degradation and its downstream effects.	Metformin	41-50	AKT serine/threonine kinase 1	Homo sapiens	60-63
30816444-8	2019	Together, these data indicate that MUL1 regulates metformin-mediated AKT degradation and the antitumor effects of metformin in chemoresistant ovarian cancer cell lines.	Metformin	50-59	AKT serine/threonine kinase 1	Homo sapiens	69-72
30032440-4	2019	Metformin (50 muM) significantly decreased SOST and DKK1 mRNA expression, stimulating alkaline phosphatase activity and proliferation of osteoblast, and increased OPG secretion and the ratio of OPG/RANKL, inhibiting osteoclastogenesis.	Metformin	0-9	dickkopf WNT signaling pathway inhibitor 1	Mus musculus	52-56
30814053-0	2019	mTOR inhibition by metformin impacts monosodium urate crystal-induced inflammation and cell death in gout: a prelude to a new add-on therapy?	Metformin	19-28	mechanistic target of rapamycin kinase	Homo sapiens	0-4
30814053-10	2019	By inhibiting mTOR signalling with metformin or rapamycin, a reduction of cell death and release of inflammatory mediators was observed.	Metformin	35-44	mechanistic target of rapamycin kinase	Homo sapiens	14-18
30814053-11	2019	Consistent with this, we show that patients with gout who are treated with the mTOR inhibitor metformin have a lower frequency of gout attacks.	Metformin	94-103	mechanistic target of rapamycin kinase	Homo sapiens	79-83
30246336-11	2019	Metformin repressed the Twist1 expression, and therefore osteoblastic differentiation was increased.	Metformin	0-9	twist family bHLH transcription factor 1	Homo sapiens	24-30
30246336-15	2019	In addition, we found a connection between the Twist1 expression level and osteoblastic differentiation by using a Twist-inhibitor (metformin).	Metformin	132-141	twist family bHLH transcription factor 1	Homo sapiens	47-53
30316907-5	2019	RESULTS: OCP resulted in a higher reduction in serum luteinizing hormone (LH) and androgens whereas metformin resulted in significant reduction in BMI, waist circumference, and insulin resistance.	Metformin	100-109	insulin	Homo sapiens	177-184
30316907-7	2019	There was a significant negative correlation between changes in LH and testosterone levels with changes in PI and RI in OCP group whereas changes in serum fasting insulin levels negatively correlated with changes in PI and RI values in the Metformin group.	Metformin	240-249	insulin	Homo sapiens	163-170
30629889-1	2019	BACKGROUND: Metformin improves insulin action, but feasibility in treating low milk supply is unknown.	Metformin	12-21	insulin	Homo sapiens	31-38
30629889-2	2019	RESEARCH AIM: To determine the feasibility of a metformin- versus-placebo definitive randomized clinical trial in women with low milk production and signs of insulin resistance.	Metformin	48-57	insulin	Homo sapiens	158-165
30896853-9	2019	Furthermore, serum levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha, and phosphorylation of MAPK1/3, MAPK14 and MAPK8 in the kidneys were decreased in GDM mice following metformin treatment at E18.5, compared with the untreated GDM group.	Metformin	188-197	interleukin 6	Mus musculus	29-47
30896853-9	2019	Furthermore, serum levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha, and phosphorylation of MAPK1/3, MAPK14 and MAPK8 in the kidneys were decreased in GDM mice following metformin treatment at E18.5, compared with the untreated GDM group.	Metformin	188-197	mitogen-activated protein kinase 13	Mus musculus	110-117
30896853-10	2019	The present study suggested that inflammation may be associated with renal dysfunction in GDM mice, and that the MAPK signaling pathway may be involved in the protective effect of metformin on renal dysfunction in GDM mice.	Metformin	180-189	mitogen-activated protein kinase 1	Mus musculus	113-117
30742852-11	2019	Also Metformin could activate CREB (both forms), BDNF and Akt (both forms) proteins" expression and inhibited GSK3 (both forms) protein expression in methamphetamine treated rats.	Metformin	5-14	AKT serine/threonine kinase 1	Rattus norvegicus	58-61
30742852-12	2019	SIGNIFICANCE: According to obtained data, metformin could protect the brain against methamphetamine-induced neurodegeneration probably by mediation of CREB/BDNF or Akt/GSK3 signaling pathways.	Metformin	42-51	AKT serine/threonine kinase 1	Rattus norvegicus	164-167
30742852-13	2019	These data suggested that CREB/BDNF or Akt/GSK3 signaling pathways may have a critical role in methamphetamine induced neurotoxicity and/or neuroprotective effects of metformin.	Metformin	167-176	AKT serine/threonine kinase 1	Rattus norvegicus	39-42
30670777-6	2019	Rapamycin, a lactate transport blocker and metformin were used as modulators of the Akt-mTOR pathway and cell metabolism.	Metformin	43-52	AKT serine/threonine kinase 1	Homo sapiens	84-87
30670777-6	2019	Rapamycin, a lactate transport blocker and metformin were used as modulators of the Akt-mTOR pathway and cell metabolism.	Metformin	43-52	mechanistic target of rapamycin kinase	Homo sapiens	88-92
29848180-7	2019	Using quantitative real-time polymerase chain reaction and Western immunoblotting, metformin significantly decreased estrogen receptor (ER) alpha messenger RNA abundance but did not consistently affect the expression of progesterone receptor.	Metformin	83-92	estrogen receptor 1	Homo sapiens	117-145
29848180-8	2019	Estrogen receptor alpha protein levels significantly decreased across all metformin doses tested, which resulted in a significant decrease in the expression of the ER targets genes Keratin-19 and Wnt-1 inducible signaling pathway 2.	Metformin	74-83	estrogen receptor 1	Homo sapiens	0-23
29848180-9	2019	In addition, metformin increased phosphorylation of AMPK in a dose-dependent manner (10-200 micromol/L) indicating an effect on mammalian target of rapamycin (mTOR) signaling.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	128-157
29848180-9	2019	In addition, metformin increased phosphorylation of AMPK in a dose-dependent manner (10-200 micromol/L) indicating an effect on mammalian target of rapamycin (mTOR) signaling.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	159-163
29848180-10	2019	Our data suggest that metformin therapy represents a potential fertility-sparing option for women with early-stage EC, given its capacity to inhibit EC cell proliferation, ERalpha expression, and the mTOR cell proliferation pathway.	Metformin	22-31	estrogen receptor 1	Homo sapiens	172-179
29848180-10	2019	Our data suggest that metformin therapy represents a potential fertility-sparing option for women with early-stage EC, given its capacity to inhibit EC cell proliferation, ERalpha expression, and the mTOR cell proliferation pathway.	Metformin	22-31	mechanistic target of rapamycin kinase	Homo sapiens	200-204
29976116-9	2019	IPA predicted that fetal liver gene upregulation associated with metformin exposure is a result of metformin inhibition of the common upstream regulator, phosphatase and tensin homolog ( PTEN).	Metformin	65-74	phosphatase and tensin homolog	Mus musculus	187-191
29976116-9	2019	IPA predicted that fetal liver gene upregulation associated with metformin exposure is a result of metformin inhibition of the common upstream regulator, phosphatase and tensin homolog ( PTEN).	Metformin	99-108	phosphatase and tensin homolog	Mus musculus	187-191
30079640-6	2019	Although metformin was originally developed as an insulin sensitizer six decades ago, it has also been shown to improve leptin resistance.	Metformin	9-18	insulin	Homo sapiens	50-57
30032440-2	2019	We found that, in ultra-high-molecular-weight polyethylene particle-induced osteolysis mouse models, metformin had bone protect property and reduced the negative regulator of bone formation sclerostin (SOST) and Dickkopf-related protein 1 (DKK1), and increased osteoprotegerin (OPG) secretion and the ratio of OPG/Receptor Activator for Nuclear Factor-kappaB Ligand (RANKL).	Metformin	101-110	dickkopf WNT signaling pathway inhibitor 1	Mus musculus	212-238
30032440-2	2019	We found that, in ultra-high-molecular-weight polyethylene particle-induced osteolysis mouse models, metformin had bone protect property and reduced the negative regulator of bone formation sclerostin (SOST) and Dickkopf-related protein 1 (DKK1), and increased osteoprotegerin (OPG) secretion and the ratio of OPG/Receptor Activator for Nuclear Factor-kappaB Ligand (RANKL).	Metformin	101-110	dickkopf WNT signaling pathway inhibitor 1	Mus musculus	240-244
30079640-8	2019	Moreover, administration of a combination of metformin and phosphodiesterase 5 inhibitors improves erectile function in patients with ED who have a poor response to sildenafil and are insulin resistant.	Metformin	45-54	insulin	Homo sapiens	184-191
31035702-1	2019	Metformin is an anti-hyperglycemic drug widely used for the treatment of insulin resistance and glucose intolerance and is currently considered for preventing large-for-gestational-age (LGA) offspring in pregnant women affected by obesity or diabetes.	Metformin	0-9	insulin	Homo sapiens	73-80
31091555-9	2019	Both metformin and CO can differentially induce several protein factors, including fibroblast growth factor 21 (FGF21) and sestrin2 (SESN2), which maintain metabolic homeostasis; nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of the antioxidant response; and REDD1, which exhibits an anticancer effect.	Metformin	5-14	fibroblast growth factor 21	Homo sapiens	83-110
31091555-9	2019	Both metformin and CO can differentially induce several protein factors, including fibroblast growth factor 21 (FGF21) and sestrin2 (SESN2), which maintain metabolic homeostasis; nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of the antioxidant response; and REDD1, which exhibits an anticancer effect.	Metformin	5-14	fibroblast growth factor 21	Homo sapiens	112-117
31091555-9	2019	Both metformin and CO can differentially induce several protein factors, including fibroblast growth factor 21 (FGF21) and sestrin2 (SESN2), which maintain metabolic homeostasis; nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of the antioxidant response; and REDD1, which exhibits an anticancer effect.	Metformin	5-14	NFE2 like bZIP transcription factor 2	Homo sapiens	179-222
31091555-9	2019	Both metformin and CO can differentially induce several protein factors, including fibroblast growth factor 21 (FGF21) and sestrin2 (SESN2), which maintain metabolic homeostasis; nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of the antioxidant response; and REDD1, which exhibits an anticancer effect.	Metformin	5-14	NFE2 like bZIP transcription factor 2	Homo sapiens	224-228
31091555-11	2019	Metformin stimulates p53- and AMPK-dependent pathways whereas CO can selectively trigger the PERK-dependent signaling pathway.	Metformin	0-9	tumor protein p53	Homo sapiens	21-24
31080404-0	2019	Rescue of Retinal Degeneration in rd1 Mice by Intravitreally Injected Metformin.	Metformin	70-79	phosphodiesterase 6B, cGMP, rod receptor, beta polypeptide	Mus musculus	34-37
31080404-6	2019	We found that metformin significantly reduced apoptosis in photoreceptors and delayed the degeneration of photoreceptors and rod bipolar cells in rd1 mice, thus markedly improving the visual function of rd1 mice at P14, P18, and P22 when tested with a light/dark transition test and ERG.	Metformin	14-23	phosphodiesterase 6B, cGMP, rod receptor, beta polypeptide	Mus musculus	146-149
31080404-6	2019	We found that metformin significantly reduced apoptosis in photoreceptors and delayed the degeneration of photoreceptors and rod bipolar cells in rd1 mice, thus markedly improving the visual function of rd1 mice at P14, P18, and P22 when tested with a light/dark transition test and ERG.	Metformin	14-23	phosphodiesterase 6B, cGMP, rod receptor, beta polypeptide	Mus musculus	203-206
31080404-6	2019	We found that metformin significantly reduced apoptosis in photoreceptors and delayed the degeneration of photoreceptors and rod bipolar cells in rd1 mice, thus markedly improving the visual function of rd1 mice at P14, P18, and P22 when tested with a light/dark transition test and ERG.	Metformin	14-23	SUB1 homolog, transcriptional regulator	Mus musculus	215-218
31080404-6	2019	We found that metformin significantly reduced apoptosis in photoreceptors and delayed the degeneration of photoreceptors and rod bipolar cells in rd1 mice, thus markedly improving the visual function of rd1 mice at P14, P18, and P22 when tested with a light/dark transition test and ERG.	Metformin	14-23	stathmin 1	Mus musculus	220-223
31080404-6	2019	We found that metformin significantly reduced apoptosis in photoreceptors and delayed the degeneration of photoreceptors and rod bipolar cells in rd1 mice, thus markedly improving the visual function of rd1 mice at P14, P18, and P22 when tested with a light/dark transition test and ERG.	Metformin	14-23	dynein cytoplasmic 1 heavy chain 1	Mus musculus	229-232
31080404-7	2019	Microglial activation in the outer nuclear layer (ONL) of the retina of rd1 mice was significantly suppressed by metformin.	Metformin	113-122	phosphodiesterase 6B, cGMP, rod receptor, beta polypeptide	Mus musculus	72-75
31080404-10	2019	These data suggest that metformin exerts a protective effect in rd1 mice via both immunoregulatory and new neuroprotective mechanisms.	Metformin	24-33	phosphodiesterase 6B, cGMP, rod receptor, beta polypeptide	Mus musculus	64-67
31249600-8	2019	We correlate the metformin-induced delay in satellite cell activation with the inhibition of the ribosome protein RPS6, one of the downstream effectors of the mTOR pathway.	Metformin	17-26	mechanistic target of rapamycin kinase	Homo sapiens	159-163
31006191-0	2019	[Effects of metformin on the expression of estrogen synthetase and ER mRNA in uterine leiomyoma tissues].	Metformin	12-21	cytochrome P450 family 19 subfamily A member 1	Homo sapiens	43-62
31006191-1	2019	Objective: To elucidate whether metformin could regulate the mRNA expression level of estrogen synthetase and ER in human uterine leiomyoma tissues.	Metformin	32-41	cytochrome P450 family 19 subfamily A member 1	Homo sapiens	86-105
31006191-11	2019	(2) After cultured with different concentrations of metformin (10, 50 and 100 mumol/L), the P450arom mRNA levels in the uterine leiomyoma tissues were 9+-4, 8+-5 and 8+-3 respectively in the treatment groups and was 16+-5 in the control group.	Metformin	52-61	cytochrome P450 family 19 subfamily A member 1	Homo sapiens	92-100
31014052-3	2019	Western blot was used to detect the expressions of microtubule-associated protein light chain 3 (LC3), p62 and cysteinyl aspartate specific proteinase 3 (caspase-3) after treatment with aspirin, metformin and 3-Methyladenine (3-MA).	Metformin	195-204	caspase 3	Homo sapiens	111-163
31114366-3	2019	Metformin inhibits mTOR activity by activating ATM (ataxia telangiectasia mutated) and LKB1 (liver kinase B1) and then adenosine monophosphate-activated kinase (AMPK), and thus prevents protein synthesis and cell growth.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	19-23
31114366-4	2019	Metformin can activate p53 by activating AMPK and thereby ultimately stop the cell cycle.	Metformin	0-9	tumor protein p53	Homo sapiens	23-26
30959948-0	2019	Association between Polymorphisms of OCT1 and Metabolic Response to Metformin in Women with Polycystic Ovary Syndrome.	Metformin	68-77	solute carrier family 22 member 1	Homo sapiens	37-41
31005944-9	2019	Treatment of non-diabetic individuals with metformin controls inflammation by improving glucose metabolism and by regulating intracellular immunometabolic checkpoints such as the adenosin 5 monophosphate activated protein kinase and mammalian target of rapamycin, in association with microbiota modification.	Metformin	43-52	mechanistic target of rapamycin kinase	Homo sapiens	233-262
30563932-2	2019	Metformin, an insulin sensitizer, reduces endometrial tumor growth in vitro.	Metformin	0-9	insulin	Homo sapiens	14-21
30563932-7	2019	Secondary outcomes investigated the effect of metformin on markers of the PI3K-Akt-mTOR and insulin signaling pathways and obesity.	Metformin	46-55	AKT serine/threonine kinase 1	Homo sapiens	79-82
31105845-0	2019	Metformin mitigates autoimmune insulitis by inhibiting Th1 and Th17 responses while promoting Treg production.	Metformin	0-9	negative elongation factor complex member C/D, Th1l	Mus musculus	55-58
31105845-7	2019	In this study, we found that AMPK activator metformin suppresses T cell proliferation and inhibits the differentiation of Th1 and Th17 cells while promoting the development of Tregs in vitro in a dose-dependent manner.	Metformin	44-53	negative elongation factor complex member C/D, Th1l	Mus musculus	122-125
30959948-1	2019	Insulin-sensitizer treatment with metformin is widely used in polycystic ovary syndrome (PCOS).	Metformin	34-43	insulin	Homo sapiens	0-7
30959948-3	2019	Organic cation transporter (OCT) 1 and 2 have been reported to mediate metformin transport in the liver and kidney, respectively.	Metformin	71-80	solute carrier family 22 member 1	Homo sapiens	0-40
30959948-4	2019	In this study, we investigated the association between the polymorphisms of OCT1 and OCT2 and the treatment effectiveness of metformin in PCOS patients.	Metformin	125-134	solute carrier family 22 member 1	Homo sapiens	76-80
30959948-8	2019	However, PCOS patients with the G allele of OCT1 rs683369 and/or with the A allele of OCT1 rs628031 had increased insulin sensitivity compared to those with wild-type genotype after receiving metformin treatment.	Metformin	192-201	solute carrier family 22 member 1	Homo sapiens	86-90
30959948-8	2019	However, PCOS patients with the G allele of OCT1 rs683369 and/or with the A allele of OCT1 rs628031 had increased insulin sensitivity compared to those with wild-type genotype after receiving metformin treatment.	Metformin	192-201	insulin	Homo sapiens	114-121
30959948-9	2019	Moreover, the interactions of metformin*SNP were significant in both OCT1 rs683369 (p &lt; 0.001) and rs628031 (p = 0.001) during the treatment period.	Metformin	30-39	solute carrier family 22 member 1	Homo sapiens	69-73
30959948-10	2019	Taken together, genetic polymorphisms of OCT1 contributed to different metformin treatment responses, and further study is needed to establish personalized treatment programs using a pharmacogenomic algorithm approach in PCOS patients.	Metformin	71-80	solute carrier family 22 member 1	Homo sapiens	41-45
30695683-0	2019	Metformin combined with nelfinavir induces SIRT3/mROS-dependent autophagy in human cervical cancer cells and xenograft in nude mice.	Metformin	0-9	sirtuin 3	Homo sapiens	43-48
30695683-10	2019	Therefore, it can be concluded that metformin, in combination with nelfinavir, can induce SIRT3/mROS-dependent autophagy and sensitize NK cell-mediated lysis in human cervical cancer cells and cervical cancer cell xenografts in nude mice.	Metformin	36-45	sirtuin 3	Homo sapiens	90-95
31139382-0	2019	Metformin-induced autophagy and irisin improves INS-1 cell function and survival in high-glucose environment via AMPK/SIRT1/PGC-1alpha signal pathway.	Metformin	0-9	sirtuin 1	Rattus norvegicus	118-123
30971831-6	2019	Metformin treatment modified gene expression related to OS and the IFN-alpha signaling pathway.	Metformin	0-9	interferon alpha 1	Homo sapiens	67-76
30592549-0	2019	Impact of Insulin Tregopil and Its Permeation Enhancer on Pharmacokinetics of Metformin in Healthy Volunteers: Randomized, Open-Label, Placebo-Controlled, Crossover Study.	Metformin	78-87	insulin	Homo sapiens	10-17
31139382-0	2019	Metformin-induced autophagy and irisin improves INS-1 cell function and survival in high-glucose environment via AMPK/SIRT1/PGC-1alpha signal pathway.	Metformin	0-9	PPARG coactivator 1 alpha	Rattus norvegicus	124-134
31139382-4	2019	Meanwhile, autophagy inhibitor CQ and SIRT1 inhibitor Ex527 can block above functions of metformin.	Metformin	89-98	sirtuin 1	Rattus norvegicus	38-43
31139382-5	2019	Therefore, metformin can promote INS-1 cell proliferation, enhance GSIS, and suppress apoptosis by activating AMPK/SIRT1/PGC-1alpha signal pathway, up-regulating irisin expression, and inducing autophagy in INS-1 cells in high-glucose environment.	Metformin	11-20	sirtuin 1	Rattus norvegicus	115-120
31139382-5	2019	Therefore, metformin can promote INS-1 cell proliferation, enhance GSIS, and suppress apoptosis by activating AMPK/SIRT1/PGC-1alpha signal pathway, up-regulating irisin expression, and inducing autophagy in INS-1 cells in high-glucose environment.	Metformin	11-20	PPARG coactivator 1 alpha	Rattus norvegicus	121-131
30689265-0	2019	Glucose starvation induces resistance to metformin through the elevation of mitochondrial multidrug resistance protein 1.	Metformin	41-50	ATP binding cassette subfamily B member 1	Homo sapiens	90-120
31106005-0	2019	Metformin reverses PARP inhibitors-induced epithelial-mesenchymal transition and PD-L1 upregulation in triple-negative breast cancer.	Metformin	0-9	poly(ADP-ribose) polymerase 1	Homo sapiens	19-23
31106005-6	2019	Blocking the p-Akt S473 axis by metformin reversed EMT and PD-L1 expression which sensitized PARPi-resistant cells to cytotoxic T cells.	Metformin	32-41	AKT serine/threonine kinase 1	Homo sapiens	15-18
31106005-7	2019	Thus, a combination of metformin and PARP inhibitors may be a promising therapeutic strategy to increase the efficacy of PARP inhibitors and tumor sensitivity to immunotherapy.	Metformin	23-32	poly(ADP-ribose) polymerase 1	Homo sapiens	121-125
30784939-9	2019	Moreover, genistein alone and/or in combination with metformin also downregulated the inflammatory responses by decreasing the levels of interleuin-6, tumor necrosis factor-alpha and C-reactive protein in serum (P &lt; 0.05) and intestine (P &lt; 0.001) more efficiently as compared to that of metformin-treated experimental animals.	Metformin	53-62	tumor necrosis factor	Rattus norvegicus	137-178
30784939-9	2019	Moreover, genistein alone and/or in combination with metformin also downregulated the inflammatory responses by decreasing the levels of interleuin-6, tumor necrosis factor-alpha and C-reactive protein in serum (P &lt; 0.05) and intestine (P &lt; 0.001) more efficiently as compared to that of metformin-treated experimental animals.	Metformin	53-62	C-reactive protein	Rattus norvegicus	183-201
31205529-9	2019	Metformin inhibited mammalian target of rapamycin (mTOR) by activation of tuberous sclerosis complex 2 (TSC-2) through phosphorylation of adenosine monophosphate-activated protein kinase at threonine-172 (AMPKThr172).	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	20-49
31205529-9	2019	Metformin inhibited mammalian target of rapamycin (mTOR) by activation of tuberous sclerosis complex 2 (TSC-2) through phosphorylation of adenosine monophosphate-activated protein kinase at threonine-172 (AMPKThr172).	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	51-55
30689265-8	2019	Furthermore, apoptosis and autophagy were increased in multidrug resistance protein 1 knockout HMM cells cultured under glucose starvation with metformin treatment.	Metformin	144-153	ATP binding cassette subfamily B member 1	Homo sapiens	55-85
30689265-9	2019	The data suggest that mitochondrial Mdr1 plays a critical role in the chemoresistance to metformin in HMM cells, which could be a potential target for improving its therapeutic efficacy.	Metformin	89-98	ATP binding cassette subfamily B member 1	Homo sapiens	36-40
30995433-1	2019	Objective: Characterize the effectiveness of insulin glargine alone, exenatide alone, or combined in subjects taking stable doses of metformin and evaluate their impact on hemoglobin A1C, hypoglycemia, weight, and glucose variability.	Metformin	133-142	insulin	Homo sapiens	45-52
30552782-7	2019	Suppression of LKB1 or promotion of AMP by metformin also abrogated the hyperproliferative phenotype caused by SIRT4 loss, which further confirmed that the LKB1/AMPKalpha/mTOR axis is required in SIRT4-deficiency-promoted HCC tumorigenesis.	Metformin	43-52	sirtuin 4	Homo sapiens	111-116
30536182-0	2019	Metformin plus chemotherapy versus chemotherapy alone in the first-line treatment of HER2-negative metastatic breast cancer.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	85-89
30229901-2	2019	We aimed to investigate the association between different glucose-lowering treatments, including DPP-4 inhibitors and metformin, both with potential NRF2 modulating effects, and new-onset metastatic cancer among type 2 diabetes patients with comorbid incident cancer.	Metformin	118-127	NFE2 like bZIP transcription factor 2	Homo sapiens	149-153
30720062-0	2019	Metformin triggers the intrinsic apoptotic response in human AGS gastric adenocarcinoma cells by activating AMPK and suppressing mTOR/AKT signaling.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	129-133
30720062-0	2019	Metformin triggers the intrinsic apoptotic response in human AGS gastric adenocarcinoma cells by activating AMPK and suppressing mTOR/AKT signaling.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	134-137
30720062-4	2019	In the current study, metformin exhibited a potent anti-proliferative effect and induced apoptotic characteristics in human AGS gastric adenocarcinoma cells, as demonstrated by MTT assay, morphological observation method, terminal deoxynucleotidyl transferase dUTP nick end labeling and caspase-3/7 assay kits.	Metformin	22-31	caspase 3	Homo sapiens	287-296
30720062-5	2019	Western blot analysis demonstrated that treatment with metformin increased the phosphorylation of AMPK, and decreased the phosphorylation of AKT, mTOR and p70S6k.	Metformin	55-64	AKT serine/threonine kinase 1	Homo sapiens	141-144
30720062-5	2019	Western blot analysis demonstrated that treatment with metformin increased the phosphorylation of AMPK, and decreased the phosphorylation of AKT, mTOR and p70S6k.	Metformin	55-64	mechanistic target of rapamycin kinase	Homo sapiens	146-150
30720062-7	2019	Metformin also reduced the phosphorylation of mitogen-activated protein kinases (ERK, JNK and p38).	Metformin	0-9	mitogen-activated protein kinase 14	Homo sapiens	94-97
30720062-9	2019	Metformin altered apoptosis-associated signaling to downregulate the BAD phosphorylation and Bcl-2, pro-caspase-9, pro-caspase-3 and pro-caspase-7 expression, and to upregulate BAD, cytochrome c, and Apaf-1 proteins levels in AGS cells.	Metformin	0-9	BCL2 apoptosis regulator	Homo sapiens	93-98
30720062-9	2019	Metformin altered apoptosis-associated signaling to downregulate the BAD phosphorylation and Bcl-2, pro-caspase-9, pro-caspase-3 and pro-caspase-7 expression, and to upregulate BAD, cytochrome c, and Apaf-1 proteins levels in AGS cells.	Metformin	0-9	caspase 3	Homo sapiens	115-128
30720062-9	2019	Metformin altered apoptosis-associated signaling to downregulate the BAD phosphorylation and Bcl-2, pro-caspase-9, pro-caspase-3 and pro-caspase-7 expression, and to upregulate BAD, cytochrome c, and Apaf-1 proteins levels in AGS cells.	Metformin	0-9	cytochrome c, somatic	Homo sapiens	182-194
30720062-9	2019	Metformin altered apoptosis-associated signaling to downregulate the BAD phosphorylation and Bcl-2, pro-caspase-9, pro-caspase-3 and pro-caspase-7 expression, and to upregulate BAD, cytochrome c, and Apaf-1 proteins levels in AGS cells.	Metformin	0-9	apoptotic peptidase activating factor 1	Homo sapiens	200-206
30802200-2	2019	The approved fixed-dose combination (FDC) of ertugliflozin and immediate-release metformin is dosed twice daily (BID).	Metformin	81-90	BH3 interacting domain death agonist	Homo sapiens	113-116
30552782-7	2019	Suppression of LKB1 or promotion of AMP by metformin also abrogated the hyperproliferative phenotype caused by SIRT4 loss, which further confirmed that the LKB1/AMPKalpha/mTOR axis is required in SIRT4-deficiency-promoted HCC tumorigenesis.	Metformin	43-52	mechanistic target of rapamycin kinase	Homo sapiens	171-175
30710424-9	2019	The marked reduction in SIRT1 expression by combination of metformin and tenovin-6 increased acetylation of p53 at lysine 382 and enhanced p53 stability in LKB1-deficient A549 cells.	Metformin	59-68	tumor protein p53	Homo sapiens	108-111
30710424-9	2019	The marked reduction in SIRT1 expression by combination of metformin and tenovin-6 increased acetylation of p53 at lysine 382 and enhanced p53 stability in LKB1-deficient A549 cells.	Metformin	59-68	tumor protein p53	Homo sapiens	139-142
30663219-6	2019	The aim of this study was to assess whether treatment with metformin for T2DM is associated with a prolonged overall survival (OS) in patients diagnosed with HCC.	Metformin	59-68	Moloney sarcoma oncogene	Mus musculus	127-129
30610588-0	2019	Efficacy and safety of the combination of metformin, everolimus and exemestane in overweight and obese postmenopausal patients with metastatic, hormone receptor-positive, HER2-negative breast cancer: a phase II study.	Metformin	42-51	nuclear receptor subfamily 4 group A member 1	Homo sapiens	144-160
30610588-2	2019	Thus, we hypothesized that the addition of metformin to everolimus and exemestane, could lead to better outcomes in overweight and obese patients with metastatic, hormone receptor-positive, HER2-negative breast cancer.	Metformin	43-52	nuclear receptor subfamily 4 group A member 1	Homo sapiens	163-179
30610588-2	2019	Thus, we hypothesized that the addition of metformin to everolimus and exemestane, could lead to better outcomes in overweight and obese patients with metastatic, hormone receptor-positive, HER2-negative breast cancer.	Metformin	43-52	erb-b2 receptor tyrosine kinase 2	Homo sapiens	190-194
30610588-3	2019	We conducted a phase II trial to evaluate the efficacy and safety of the combination of metformin, everolimus and exemestane in overweight and obese postmenopausal women with metastatic, hormone receptor-positive, HER2-negative breast cancer.	Metformin	88-97	nuclear receptor subfamily 4 group A member 1	Homo sapiens	187-203
30610588-3	2019	We conducted a phase II trial to evaluate the efficacy and safety of the combination of metformin, everolimus and exemestane in overweight and obese postmenopausal women with metastatic, hormone receptor-positive, HER2-negative breast cancer.	Metformin	88-97	erb-b2 receptor tyrosine kinase 2	Homo sapiens	214-218
30610588-11	2019	Conclusion The combination of metformin, everolimus and exemestane was safe and had moderate clinical benefit in overweight and obese with patients metastatic, hormone receptor-positive, HER2-negative breast cancer.	Metformin	30-39	nuclear receptor subfamily 4 group A member 1	Homo sapiens	160-176
30610588-11	2019	Conclusion The combination of metformin, everolimus and exemestane was safe and had moderate clinical benefit in overweight and obese with patients metastatic, hormone receptor-positive, HER2-negative breast cancer.	Metformin	30-39	erb-b2 receptor tyrosine kinase 2	Homo sapiens	187-191
30655321-9	2019	In support of this, metformin blocked hypoxia-induced SPHK1, which was associated with inhibited nuclear translocation and transcriptional activity of hypoxia-inducible factors (HIF1alpha and HIF2alpha).	Metformin	20-29	hypoxia inducible factor 1 subunit alpha	Homo sapiens	178-187
30663219-9	2019	Patients on metformin had a significantly longer median OS (mOS) compared to diabetic patients not treated with metformin (22 vs 15 months, P = 0.019).	Metformin	12-21	Moloney sarcoma oncogene	Mus musculus	56-58
30663219-9	2019	Patients on metformin had a significantly longer median OS (mOS) compared to diabetic patients not treated with metformin (22 vs 15 months, P = 0.019).	Metformin	12-21	Moloney sarcoma oncogene	Mus musculus	60-63
30663219-12	2019	In the matched cohorts, mOS remained significantly longer in metformin-treated patients (22 vs 16 months, P = 0.021).	Metformin	61-70	Moloney sarcoma oncogene	Mus musculus	24-27
29934960-0	2019	Metformin inhibits TGF-beta 1-induced MCP-1 expression through BAMBI-mediated suppression of MEK/ERK1/2 signalling.	Metformin	0-9	transforming growth factor, beta 1	Rattus norvegicus	19-29
30710234-8	2019	Moreover, EGCG and metformin treated cells showed decreased expression levels of VEGF.	Metformin	19-28	vascular endothelial growth factor A	Homo sapiens	81-85
29934960-13	2019	Pretreatment with metformin suppressed upregulation of MCP-1 and downregulation of BAMBI, as well as phosphorylation of ERK1/2 induced by TGF-beta1.	Metformin	18-27	transforming growth factor, beta 1	Rattus norvegicus	138-147
29934960-4	2019	This study aimed to investigate the effects of metformin on transforming growth factor beta 1 (TGF-beta1)-induced MCP-1 expression and the underlying mechanisms in rat renal tubular epithelial cells.	Metformin	47-56	transforming growth factor, beta 1	Rattus norvegicus	60-93
29934960-17	2019	CONCLUSION: In rat renal tubular epithelial cells, metformin prevents TGF-beta1-induced MCP-1 expression, in which BAMBI-mediated inhibition of MEK/ERK1/2 might be involved.	Metformin	51-60	transforming growth factor, beta 1	Rattus norvegicus	70-79
29934960-4	2019	This study aimed to investigate the effects of metformin on transforming growth factor beta 1 (TGF-beta1)-induced MCP-1 expression and the underlying mechanisms in rat renal tubular epithelial cells.	Metformin	47-56	transforming growth factor, beta 1	Rattus norvegicus	95-104
30575815-6	2019	In vitro, glucose, insulin, VEGFA and hypoxia upregulated endothelial FABP4, which was reversed by metformin through mTOR pathway inhibition.	Metformin	99-108	insulin	Homo sapiens	19-26
30842661-6	2019	Expression of a haem-resistant BACH1 mutant in cells that express a short hairpin RNA for BACH1 rescues the BACH1 phenotype and restores metformin resistance in hemin-treated cells and tumours7.	Metformin	137-146	BTB domain and CNC homolog 1	Homo sapiens	31-36
30842661-6	2019	Expression of a haem-resistant BACH1 mutant in cells that express a short hairpin RNA for BACH1 rescues the BACH1 phenotype and restores metformin resistance in hemin-treated cells and tumours7.	Metformin	137-146	BTB domain and CNC homolog 1	Homo sapiens	90-95
30842661-6	2019	Expression of a haem-resistant BACH1 mutant in cells that express a short hairpin RNA for BACH1 rescues the BACH1 phenotype and restores metformin resistance in hemin-treated cells and tumours7.	Metformin	137-146	BTB domain and CNC homolog 1	Homo sapiens	90-95
30466344-11	2019	Moreover, we determined that the effect of metformin was related to the inhibition of endoplasmic reticulum stress-induced apoptosis via the Phosphatidylinositol 3 kinase (PI3K)/Protein kinase B (AKT) and Extracellular regulated protein kinases1/2 pathways.	Metformin	43-52	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta	Rattus norvegicus	141-170
30466344-11	2019	Moreover, we determined that the effect of metformin was related to the inhibition of endoplasmic reticulum stress-induced apoptosis via the Phosphatidylinositol 3 kinase (PI3K)/Protein kinase B (AKT) and Extracellular regulated protein kinases1/2 pathways.	Metformin	43-52	AKT serine/threonine kinase 1	Rattus norvegicus	196-199
30575815-6	2019	In vitro, glucose, insulin, VEGFA and hypoxia upregulated endothelial FABP4, which was reversed by metformin through mTOR pathway inhibition.	Metformin	99-108	vascular endothelial growth factor A	Homo sapiens	28-33
30575815-6	2019	In vitro, glucose, insulin, VEGFA and hypoxia upregulated endothelial FABP4, which was reversed by metformin through mTOR pathway inhibition.	Metformin	99-108	mechanistic target of rapamycin kinase	Homo sapiens	117-121
30849634-5	2019	As expected, metformin increased the phosphorylation of AMPK and decreased the panobinostat-caused phosphorylation of S6 ribosomal protein, thus inhibiting the panobinostat-activated mTOR pathway.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	183-187
30917505-7	2019	SIRT-3 expression was higher in diabetic than non-diabetic patients, and in metformin-treated than insulin-treated patients.	Metformin	76-85	sirtuin 3	Homo sapiens	0-6
30926854-0	2019	Metformin induces the AP-1 transcription factor network in normal dermal fibroblasts.	Metformin	0-9	JunB proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	22-26
30926854-6	2019	We further identified that different concentrations of metformin induced different transcript profiles; however, significant enrichment in the activator protein 1 (AP-1) transcription factor network was common between the different treatments.	Metformin	55-64	JunB proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	143-162
30926854-6	2019	We further identified that different concentrations of metformin induced different transcript profiles; however, significant enrichment in the activator protein 1 (AP-1) transcription factor network was common between the different treatments.	Metformin	55-64	JunB proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	164-168
30926854-8	2019	Promoter analysis and chromatin immunoprecipitation assays of genes that changed expression in response to metformin revealed enrichment of the transcriptional regulator forkhead box O3a (FOXO3a) in normal human fibroblasts, but not of the predicted serum response factor (SRF).	Metformin	107-116	forkhead box O3	Homo sapiens	170-186
30926854-8	2019	Promoter analysis and chromatin immunoprecipitation assays of genes that changed expression in response to metformin revealed enrichment of the transcriptional regulator forkhead box O3a (FOXO3a) in normal human fibroblasts, but not of the predicted serum response factor (SRF).	Metformin	107-116	forkhead box O3	Homo sapiens	188-194
30917505-8	2019	Interestingly, p-mTOR was higher in patients with metabolic syndrome than those with different etiology, and, similar to SIRT-3, in metformin-treated than insulin-treated patients.	Metformin	132-141	mechanistic target of rapamycin kinase	Homo sapiens	17-21
30905926-0	2019	Neuro-Protective Role of Metformin in Patients with Acute Stroke and Type 2 Diabetes Mellitus via AMPK/Mammalian Target of Rapamycin (mTOR) Signaling Pathway and Oxidative Stress.	Metformin	25-34	mechanistic target of rapamycin kinase	Homo sapiens	103-132
30905926-0	2019	Neuro-Protective Role of Metformin in Patients with Acute Stroke and Type 2 Diabetes Mellitus via AMPK/Mammalian Target of Rapamycin (mTOR) Signaling Pathway and Oxidative Stress.	Metformin	25-34	mechanistic target of rapamycin kinase	Homo sapiens	134-138
30905926-11	2019	CONCLUSIONS Metformin can improve the neurological function and oxidative stress status of acute stroke patients with type 2 diabetes, and its mechanism may be related to the AMPK/mTOR signaling pathway and oxidative stress.	Metformin	12-21	mechanistic target of rapamycin kinase	Homo sapiens	180-184
30934600-0	2019	Metformin Pharmacogenetics: Effects of SLC22A1, SLC22A2, and SLC22A3 Polymorphisms on Glycemic Control and HbA1c Levels.	Metformin	0-9	solute carrier family 22 member 1	Homo sapiens	39-46
30934600-3	2019	The objective of this study was to investigate the relationship between twenty-one single nucleotide polymorphisms (SNPs) in the SLC22A1, SLC22A2, and SLC22A3 genes and their effects on metformin pharmacogenetics in Jordanian patients diagnosed with type 2 diabetes mellitus.	Metformin	186-195	solute carrier family 22 member 1	Homo sapiens	129-136
30909494-6	2019	Our findings demonstrate a differential response between the two ccRCC cell lines studied, with Caki-2 cells being more sensitive to metformin compared to Caki-1 cells, which could be linked to the differential expression of HIF-1 despite both cell lines carrying a wild-type VHL.	Metformin	133-142	hypoxia inducible factor 1 subunit alpha	Homo sapiens	225-230
31011335-4	2019	In this study, we examined the effect of TGF-beta1 on EPCs and the therapeutic outcome of metformin treatment on TGF-beta1-induced EPCs.	Metformin	90-99	transforming growth factor beta 1	Homo sapiens	113-122
31011335-9	2019	Metformin treatment suppressed TGF-beta-induced expression of all above factors, with the effect at 2 mmol/l being significant (p &lt; 0.05).	Metformin	0-9	transforming growth factor beta 1	Homo sapiens	31-39
31011335-11	2019	In conclusion, our study showed that TGF-beta1 induces the expression of fibrosis biomarkers in EPCs, which is attenuated by treatment with metformin.	Metformin	140-149	transforming growth factor beta 1	Homo sapiens	37-46
30866414-7	2019	Moreover, we showed that p53 family member DeltaNp63alpha transcriptionally suppressed integrin beta1 expression and is responsible for metformin-mediated upregulation of integrin beta1.	Metformin	136-145	tumor protein p53	Homo sapiens	25-28
30218617-13	2019	Cystatin C-based eGFR selects more complicated patients, where lower doses of metformin are possibly advisable.	Metformin	78-87	epidermal growth factor receptor	Homo sapiens	17-21
30845774-5	2019	Of note, abdominal fat tissue of obese pre-DM patients treated with metformin therapy presented higher SIRT6 expression and lower NF-kappaB, PPAR-gamma, and SREBP-1 expression levels compared to pre-DM control group.	Metformin	68-77	nuclear factor kappa B subunit 1	Homo sapiens	130-139
30845774-5	2019	Of note, abdominal fat tissue of obese pre-DM patients treated with metformin therapy presented higher SIRT6 expression and lower NF-kappaB, PPAR-gamma, and SREBP-1 expression levels compared to pre-DM control group.	Metformin	68-77	peroxisome proliferator activated receptor gamma	Homo sapiens	141-151
30841429-9	2019	Metformin might improve mitochondrial biogenesis in the BAT (nuclear respiratory factor 1, mitochondrial transcription factor A), lipolysis (perilipin, adipose triglyceride lipase, hormone-sensitive lipase), and fatty acid uptake (lipoprotein lipase, cluster of differentiation 36, adipocyte protein 2).	Metformin	0-9	nuclear respiratory factor 1	Mus musculus	61-89
30915409-9	2019	Conclusions: Allopurinol synergistically increases the protective effect of metformin and vitamin E in treatment of NAFLD, namely via reduction of uric acid synthesis and iNOS expression.	Metformin	76-85	nitric oxide synthase 2	Rattus norvegicus	171-175
30912338-2	2019	On the 1-year anniversary of his death in 2018, we challenge three myths associated with insulin resistance: metformin improves insulin resistance; measurement of waist circumference predicts insulin resistance better than body mass index; and insulin resistance causes weight gain.	Metformin	109-118	insulin	Homo sapiens	89-96
30851950-13	2019	Because metformin targets insulin resistance and inflammation, it is a plausible pharmacologic agent to prevent frailty.	Metformin	8-17	insulin	Homo sapiens	26-33
31014100-4	2019	Among glucose-lowering agents, metformin and thiazolidinediones provide cellular actions that counter some effects of insulin resistance: reduced glucotoxicity and weight-lowering with antidiabetic therapies also improve insulin action, except that endogenously- or exogenously-created hyperinsulinaemia may partially compromise these benefits.	Metformin	31-40	insulin	Homo sapiens	118-125
31014100-4	2019	Among glucose-lowering agents, metformin and thiazolidinediones provide cellular actions that counter some effects of insulin resistance: reduced glucotoxicity and weight-lowering with antidiabetic therapies also improve insulin action, except that endogenously- or exogenously-created hyperinsulinaemia may partially compromise these benefits.	Metformin	31-40	insulin	Homo sapiens	221-228
30912338-2	2019	On the 1-year anniversary of his death in 2018, we challenge three myths associated with insulin resistance: metformin improves insulin resistance; measurement of waist circumference predicts insulin resistance better than body mass index; and insulin resistance causes weight gain.	Metformin	109-118	insulin	Homo sapiens	128-135
30912338-2	2019	On the 1-year anniversary of his death in 2018, we challenge three myths associated with insulin resistance: metformin improves insulin resistance; measurement of waist circumference predicts insulin resistance better than body mass index; and insulin resistance causes weight gain.	Metformin	109-118	insulin	Homo sapiens	128-135
30912338-2	2019	On the 1-year anniversary of his death in 2018, we challenge three myths associated with insulin resistance: metformin improves insulin resistance; measurement of waist circumference predicts insulin resistance better than body mass index; and insulin resistance causes weight gain.	Metformin	109-118	insulin	Homo sapiens	128-135
30913008-9	2019	A pre-emptive insulin dose reduction at discharge should be considered for patients with newly diagnosed diabetes, ketosis-prone diabetes, metformin prescription, and those with HbA1c &lt;10% at presentation.	Metformin	139-148	insulin	Homo sapiens	14-21
30709546-0	2019	Direct toxicity of insulin on the human placenta and protection by metformin.	Metformin	67-76	insulin	Homo sapiens	19-26
30709546-10	2019	Pretreatment of trophoblasts with therapeutic doses of metformin prevented the detrimental effects of insulin.	Metformin	55-64	insulin	Homo sapiens	102-109
30427060-8	2019	Finally, KDM individuals on metformin treatment exhibited significantly lower levels of sCD14, sCD163 and CRP compared with those on non-metformin-containing regimens.	Metformin	28-37	C-reactive protein	Homo sapiens	106-109
30540558-10	2019	Insulin concentration decreased in the metformin+LCD group (P=0.046).	Metformin	39-48	insulin	Homo sapiens	0-7
30145806-10	2019	Our findings indicated that exenatide + metformin and vildagliptin + metformin have better efficacy in T2DM since they can improve insulin sensitivity.	Metformin	40-49	insulin	Homo sapiens	131-138
30983607-2	2019	Metformin and alpha-lipoic acid, two types of insulin-sensitizing agents, have been demonstrated to reduce insulin levels and improve insulin sensitivity.	Metformin	0-9	insulin	Homo sapiens	46-53
30983607-2	2019	Metformin and alpha-lipoic acid, two types of insulin-sensitizing agents, have been demonstrated to reduce insulin levels and improve insulin sensitivity.	Metformin	0-9	insulin	Homo sapiens	107-114
30983607-2	2019	Metformin and alpha-lipoic acid, two types of insulin-sensitizing agents, have been demonstrated to reduce insulin levels and improve insulin sensitivity.	Metformin	0-9	insulin	Homo sapiens	107-114
30983607-4	2019	Aims: This study aimed to compare the effectiveness, safety, and improvement of the insulin resistance profile of Canthex  and metformin in acanthosis nigricans.	Metformin	127-136	insulin	Homo sapiens	84-91
30145806-10	2019	Our findings indicated that exenatide + metformin and vildagliptin + metformin have better efficacy in T2DM since they can improve insulin sensitivity.	Metformin	69-78	insulin	Homo sapiens	131-138
30146703-0	2019	In vitro evaluation of effects of metformin on morphine and methadone tolerance through mammalian target of rapamycin signaling pathway.	Metformin	34-43	mechanistic target of rapamycin kinase	Homo sapiens	88-117
30146703-3	2019	Metformin activates 5" adenosine monophosphate-activated protein kinase (AMPK) which directly suppresses the mTOR complex 1 signaling pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	109-113
30146703-4	2019	On the other hand, metformin can also inhibit mTOR directly and in an AMPK-independent manner.	Metformin	19-28	mechanistic target of rapamycin kinase	Homo sapiens	46-50
30146703-9	2019	Contribution of mTOR signaling pathway in metformin-induced effect was shown by the inhibition of phosphorylation of S6K1 and 4E-BP1, the downstream targets of mTOR.	Metformin	42-51	mechanistic target of rapamycin kinase	Homo sapiens	16-20
30146703-9	2019	Contribution of mTOR signaling pathway in metformin-induced effect was shown by the inhibition of phosphorylation of S6K1 and 4E-BP1, the downstream targets of mTOR.	Metformin	42-51	BP1	Homo sapiens	129-132
30146703-9	2019	Contribution of mTOR signaling pathway in metformin-induced effect was shown by the inhibition of phosphorylation of S6K1 and 4E-BP1, the downstream targets of mTOR.	Metformin	42-51	mechanistic target of rapamycin kinase	Homo sapiens	160-164
30628691-0	2019	Protective effects of metformin on lipopolysaccharide-induced airway epithelial cell injury via NF-kappaB signaling inhibition.	Metformin	22-31	nuclear factor kappa B subunit 1	Homo sapiens	96-105
30936596-3	2019	The AMP-activated protein kinase (AMPK), as a metabolic sensor, could be activated with metformin and it can also launch a p53-dependent metabolic checkpoint and might inhibit cancer cell growth.	Metformin	88-97	tumor protein p53	Homo sapiens	123-126
30936596-8	2019	Real-time PCR revealed that metformin induced apoptosis in TE8 and TE11 cells by activating p53, down-regulating Bcl-2 expression.	Metformin	28-37	tumor protein p53	Homo sapiens	92-95
30936596-8	2019	Real-time PCR revealed that metformin induced apoptosis in TE8 and TE11 cells by activating p53, down-regulating Bcl-2 expression.	Metformin	28-37	BCL2 apoptosis regulator	Homo sapiens	113-118
30936596-9	2019	The induced apoptosis by 2DG raised by metformin and the combination modulated the expression of Bcl-2 protein in all cell lines and it was more effective in TE11 cell line.	Metformin	39-48	BCL2 apoptosis regulator	Homo sapiens	97-102
30936596-10	2019	Conclusion: Metformin induced apoptosis in ESCC by down-regulating Bcl-2 expression, and up-regulating p53 and induced apoptosis increased by 2-deoxy-d-glucose.	Metformin	12-21	BCL2 apoptosis regulator	Homo sapiens	67-72
30936596-10	2019	Conclusion: Metformin induced apoptosis in ESCC by down-regulating Bcl-2 expression, and up-regulating p53 and induced apoptosis increased by 2-deoxy-d-glucose.	Metformin	12-21	tumor protein p53	Homo sapiens	103-106
30692212-9	2019	Antidiabetic metformin prevented CSE-induced HBEC senescence and mitochondrial accumulation via increased DEPTOR expression.	Metformin	13-22	DEP domain containing MTOR-interacting protein	Mus musculus	106-112
30628691-10	2019	Furthermore, it was confirmed that metformin suppressed the LPS-induced secretion of TNF-alpha, IL-6, ICAM-1 and VCAM-1.	Metformin	35-44	tumor necrosis factor	Homo sapiens	85-94
30628691-10	2019	Furthermore, it was confirmed that metformin suppressed the LPS-induced secretion of TNF-alpha, IL-6, ICAM-1 and VCAM-1.	Metformin	35-44	interleukin 6	Homo sapiens	96-100
30628691-10	2019	Furthermore, it was confirmed that metformin suppressed the LPS-induced secretion of TNF-alpha, IL-6, ICAM-1 and VCAM-1.	Metformin	35-44	vascular cell adhesion molecule 1	Homo sapiens	113-119
30628691-12	2019	The results demonstrated that metformin inhibited NF-kappaB mRNA expression and the nuclear translocation of NF-kappaB p65.	Metformin	30-39	nuclear factor kappa B subunit 1	Homo sapiens	50-59
30628691-12	2019	The results demonstrated that metformin inhibited NF-kappaB mRNA expression and the nuclear translocation of NF-kappaB p65.	Metformin	30-39	nuclear factor kappa B subunit 1	Homo sapiens	109-118
30628691-13	2019	To the best of our knowledge, the present study was the first to demonstrate that metformin ameliorated LPS-induced bronchial epithelial cell injury via NF-kappaB signaling suppression.	Metformin	82-91	nuclear factor kappa B subunit 1	Homo sapiens	153-162
30595105-0	2019	Role of Metformin in the Treatment of Patients with Thyroid Nodules and Insulin Resistance: A Systematic Review and Meta-Analysis.	Metformin	8-17	insulin	Homo sapiens	72-79
30664988-4	2019	Metformin therapy reduced the levels of insulin and HOMA-IR, sex hormones and sex hormone-binding globulin, Ki67, caspase-3, p-Akt, obesity, hs-CRP, blood glucose and lipid profile.	Metformin	0-9	insulin	Homo sapiens	40-47
30664988-4	2019	Metformin therapy reduced the levels of insulin and HOMA-IR, sex hormones and sex hormone-binding globulin, Ki67, caspase-3, p-Akt, obesity, hs-CRP, blood glucose and lipid profile.	Metformin	0-9	caspase 3	Homo sapiens	114-123
30890498-9	2019	Our results showed that metformin treatment decreased MAIBD and relapse frequency in the patients, and significantly lowered the clinical inflammatory indexes including CRP and ESR.	Metformin	24-33	C-reactive protein	Homo sapiens	169-172
30890498-10	2019	The results of ELISA and qRT-PCR revealed that metformin treatment obviously increased Foxp3 and TGF-beta expressions at both the protein and mRNA levels and significantly decreased the levels of ROR-gammat, IL-17 and TNF-alpha as well as IL-35 level in these patients.	Metformin	47-56	transforming growth factor beta 1	Homo sapiens	97-105
30890498-10	2019	The results of ELISA and qRT-PCR revealed that metformin treatment obviously increased Foxp3 and TGF-beta expressions at both the protein and mRNA levels and significantly decreased the levels of ROR-gammat, IL-17 and TNF-alpha as well as IL-35 level in these patients.	Metformin	47-56	tumor necrosis factor	Homo sapiens	218-227
30911317-10	2019	In addition, phosphorylated Erk1/2 was decreased while phosphorylated Akt was increased in metformin treatment.	Metformin	91-100	mitogen-activated protein kinase 3	Homo sapiens	28-34
30911317-10	2019	In addition, phosphorylated Erk1/2 was decreased while phosphorylated Akt was increased in metformin treatment.	Metformin	91-100	AKT serine/threonine kinase 1	Homo sapiens	70-73
30911317-11	2019	Taken together, these findings suggest that metformin promotes neuronal differentiation via ROS activation through Cdk5/Sox6 crosstalk, relating to Erk1/2 and Akt signaling.	Metformin	44-53	mitogen-activated protein kinase 3	Homo sapiens	148-154
30911317-11	2019	Taken together, these findings suggest that metformin promotes neuronal differentiation via ROS activation through Cdk5/Sox6 crosstalk, relating to Erk1/2 and Akt signaling.	Metformin	44-53	AKT serine/threonine kinase 1	Homo sapiens	159-162
30779140-10	2019	RESULTS: We found that metformin treatment can robustly ameliorate periodontal infection and tissue destruction and reduce blood glucose and serum IL-1beta levels in mice with diabetic periodontitis.	Metformin	23-32	interleukin 1 beta	Mus musculus	147-155
30779140-11	2019	Moreover, gingival tissue exhibited less macrophage infiltration and decreased expression of Nek7, NLRP3, caspase-1 and mammalian target of rapamycin (mTOR), which were simultaneously observed in RAW 264.7 cell models stimulated with metformin.	Metformin	234-243	mechanistic target of rapamycin kinase	Homo sapiens	120-149
30784061-8	2019	Notably, metformin, an antidiabetic drug, could significantly induce Parkin expression and enhance the interaction between Parkin and HIF-1alpha.	Metformin	9-18	hypoxia inducible factor 1 subunit alpha	Homo sapiens	134-144
30784077-0	2019	Metformin protects PC12 cells and hippocampal neurons from H2 O 2 -induced oxidative damage through activation of AMPK pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	114-118
30784077-7	2019	Western blot analysis further demonstrated that metformin stimulated the phosphorylation and activation of AMP-activated protein kinase (AMPK) in PC12 cells, while application of AMPK inhibitor compound C, or knockdown of the expression of AMPK by specific small interfering RNA or short hairpin RNA blocked the protective effect of metformin.	Metformin	48-57	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	107-135
30784077-7	2019	Western blot analysis further demonstrated that metformin stimulated the phosphorylation and activation of AMP-activated protein kinase (AMPK) in PC12 cells, while application of AMPK inhibitor compound C, or knockdown of the expression of AMPK by specific small interfering RNA or short hairpin RNA blocked the protective effect of metformin.	Metformin	48-57	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	137-141
30784077-7	2019	Western blot analysis further demonstrated that metformin stimulated the phosphorylation and activation of AMP-activated protein kinase (AMPK) in PC12 cells, while application of AMPK inhibitor compound C, or knockdown of the expression of AMPK by specific small interfering RNA or short hairpin RNA blocked the protective effect of metformin.	Metformin	333-342	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	107-135
30784077-7	2019	Western blot analysis further demonstrated that metformin stimulated the phosphorylation and activation of AMP-activated protein kinase (AMPK) in PC12 cells, while application of AMPK inhibitor compound C, or knockdown of the expression of AMPK by specific small interfering RNA or short hairpin RNA blocked the protective effect of metformin.	Metformin	333-342	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	137-141
30784077-9	2019	Taken together, these results indicated that metformin is able to protect neuronal cells from oxidative injury, at least in part, via the activation of AMPK.	Metformin	45-54	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	152-156
30899369-0	2019	Metformin induces the M2 macrophage polarization to accelerate the wound healing via regulating AMPK/mTOR/NLRP3 inflammasome singling pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	101-105
30899369-0	2019	Metformin induces the M2 macrophage polarization to accelerate the wound healing via regulating AMPK/mTOR/NLRP3 inflammasome singling pathway.	Metformin	0-9	NLR family pyrin domain containing 3	Homo sapiens	106-111
30899369-9	2019	We also found that the level of relative proteins of NLRP3 inflammasome was markedly decreased after metformin treatment.	Metformin	101-110	NLR family pyrin domain containing 3	Homo sapiens	53-58
30899369-10	2019	Furthermore, blockage of AMPK or activation of mTOR abolished the effects of metformin treatment on depressing NLRP3 inflammasome activation, M2 polarization and improving wound healing.	Metformin	77-86	mechanistic target of rapamycin kinase	Homo sapiens	47-51
30899369-10	2019	Furthermore, blockage of AMPK or activation of mTOR abolished the effects of metformin treatment on depressing NLRP3 inflammasome activation, M2 polarization and improving wound healing.	Metformin	77-86	NLR family pyrin domain containing 3	Homo sapiens	111-116
30899369-11	2019	It suggested that the treatment effects of metformin on wound healing were through regulating AMPK/mTOR/NLRP3 inflammasome signaling axis.	Metformin	43-52	mechanistic target of rapamycin kinase	Homo sapiens	99-103
30899369-11	2019	It suggested that the treatment effects of metformin on wound healing were through regulating AMPK/mTOR/NLRP3 inflammasome signaling axis.	Metformin	43-52	NLR family pyrin domain containing 3	Homo sapiens	104-109
30899369-12	2019	CONCLUSION: Metformin regulated AMPK/mTOR singling pathway to inhibit NLRP3 inflammasome activation, which boosted M2 macrophage polarization to accelerate the wound healing.	Metformin	12-21	mechanistic target of rapamycin kinase	Homo sapiens	37-41
30899369-12	2019	CONCLUSION: Metformin regulated AMPK/mTOR singling pathway to inhibit NLRP3 inflammasome activation, which boosted M2 macrophage polarization to accelerate the wound healing.	Metformin	12-21	NLR family pyrin domain containing 3	Homo sapiens	70-75
30625338-0	2019	Metformin delays AKT/c-Met-driven hepatocarcinogenesis by regulating signaling pathways for de novo lipogenesis and ATP generation.	Metformin	0-9	thymoma viral proto-oncogene 1	Mus musculus	17-20
30625338-4	2019	Here, we investigate the preventive efficacy of metformin in a rapid AKT/c-Met-triggered HCC mouse model featuring excessive levels of steatosis.	Metformin	48-57	thymoma viral proto-oncogene 1	Mus musculus	69-72
30625338-7	2019	The results show that metformin obstructs the malignant transformation of hepatocytes in AKT/c-Met mice.	Metformin	22-31	thymoma viral proto-oncogene 1	Mus musculus	89-92
30625338-8	2019	Mechanistically, metformin reduces the expression of phospho-ERK (Thr202/Tyr204) and two forms of proto-oncogenes, Cyclin D1 and c-Myc, in AKT/c-Met mice.	Metformin	17-26	thymoma viral proto-oncogene 1	Mus musculus	139-142
30625338-9	2019	Moreover, metformin ameliorates FASN-mediated aberrant lipogenesis and HK2/PKM2-driven ATP generation in vivo.	Metformin	10-19	fatty acid synthase	Mus musculus	32-36
30625338-10	2019	Furthermore, metformin represses the expression of FASN and HK-2 by targeting c-Myc in an AMPK-dependent manner in vitro.	Metformin	13-22	fatty acid synthase	Mus musculus	51-55
30765814-0	2019	Metformin inhibits lithocholic acid-induced interleukin 8 upregulation in colorectal cancer cells by suppressing ROS production and NF-kB activity.	Metformin	0-9	C-X-C motif chemokine ligand 8	Homo sapiens	44-57
30765814-2	2019	In this study, we describe the inhibitory effect of metformin in interleukin 8 (IL-8) upregulation by lithocholic acid (LCA) in HCT116 colorectal cancer (CRC) cells.	Metformin	52-61	C-X-C motif chemokine ligand 8	Homo sapiens	65-78
30765814-2	2019	In this study, we describe the inhibitory effect of metformin in interleukin 8 (IL-8) upregulation by lithocholic acid (LCA) in HCT116 colorectal cancer (CRC) cells.	Metformin	52-61	C-X-C motif chemokine ligand 8	Homo sapiens	80-84
30765814-4	2019	Metformin was demonstrated to block LCA-stimulated ROS production, in turn suppressing NF-kappaB signaling that was critical for IL-8 upregulation.	Metformin	0-9	nuclear factor kappa B subunit 1	Homo sapiens	87-96
30765814-4	2019	Metformin was demonstrated to block LCA-stimulated ROS production, in turn suppressing NF-kappaB signaling that was critical for IL-8 upregulation.	Metformin	0-9	C-X-C motif chemokine ligand 8	Homo sapiens	129-133
30765814-7	2019	In conclusion, metformin inhibited NADPH oxidase, which in turn suppressed ROS production and NF-kappaB activation to prevent IL-8 upregulation stimulated by LCA; this prevention thus obstructed endothelial cell proliferation and tubelike formation.	Metformin	15-24	nuclear factor kappa B subunit 1	Homo sapiens	94-103
30765814-7	2019	In conclusion, metformin inhibited NADPH oxidase, which in turn suppressed ROS production and NF-kappaB activation to prevent IL-8 upregulation stimulated by LCA; this prevention thus obstructed endothelial cell proliferation and tubelike formation.	Metformin	15-24	C-X-C motif chemokine ligand 8	Homo sapiens	126-130
30834005-2	2019	Organic Cation Transporter (OCT) 1 protein encoded by the SLC22A1 gene is primarily responsible for the process of metformin influx to the hepatocytes as the target of antihyperglycemic action as well as metformin elimination through the renal.	Metformin	115-124	solute carrier family 22 member 1	Homo sapiens	0-34
30834005-2	2019	Organic Cation Transporter (OCT) 1 protein encoded by the SLC22A1 gene is primarily responsible for the process of metformin influx to the hepatocytes as the target of antihyperglycemic action as well as metformin elimination through the renal.	Metformin	115-124	solute carrier family 22 member 1	Homo sapiens	58-65
30834005-2	2019	Organic Cation Transporter (OCT) 1 protein encoded by the SLC22A1 gene is primarily responsible for the process of metformin influx to the hepatocytes as the target of antihyperglycemic action as well as metformin elimination through the renal.	Metformin	204-213	solute carrier family 22 member 1	Homo sapiens	0-34
30834005-2	2019	Organic Cation Transporter (OCT) 1 protein encoded by the SLC22A1 gene is primarily responsible for the process of metformin influx to the hepatocytes as the target of antihyperglycemic action as well as metformin elimination through the renal.	Metformin	204-213	solute carrier family 22 member 1	Homo sapiens	58-65
30760281-13	2019	Utilization of a specific pharmacological inhibitor or ASK1-siRNA identified a potential role for ASK1 as an apoptotic protein in the regulation of low glucose and metformin-induced cell apoptosis via ASK1-mediated mitochondrial damage through the ASK1/Noxa pathway and via ER stress through the ROS/ASK1/JNK pathway.	Metformin	164-173	phorbol-12-myristate-13-acetate-induced protein 1	Homo sapiens	253-257
30760281-13	2019	Utilization of a specific pharmacological inhibitor or ASK1-siRNA identified a potential role for ASK1 as an apoptotic protein in the regulation of low glucose and metformin-induced cell apoptosis via ASK1-mediated mitochondrial damage through the ASK1/Noxa pathway and via ER stress through the ROS/ASK1/JNK pathway.	Metformin	164-173	mitogen-activated protein kinase 8	Homo sapiens	305-308
30759121-6	2019	RESULTS: Metformin was the most common non-insulin medication used prior to insulin initiation (N = 53,017, 72.7%), followed by sulfonylureas (N = 25,439, 34.9%) and DPP4 inhibitors (N = 8,540, 11.7%).	Metformin	9-18	insulin	Homo sapiens	76-83
30759121-11	2019	CONCLUSION: While metformin was commonly continued among commercially insured adults starting insulin, rates of continuation of other non-insulin diabetes medications were also high.	Metformin	18-27	insulin	Homo sapiens	94-101
30755615-4	2019	Second, we found that molecular activation of small intestinal mTOR blunts the glucose-lowering effect of the oral anti-diabetic agent metformin, while inhibiting small intestinal mTOR alone lowers plasma glucose levels by inhibiting glucose production in rodents with diabetes as well.	Metformin	135-144	mechanistic target of rapamycin kinase	Homo sapiens	63-67
30754729-3	2019	Using the next-generation sequencing approach, we identified threeupregulated microRNAs (miRNA; miR-192-5p, miR-584-3p, and miR-1246) in melanoma cellstreated with metformin.	Metformin	164-173	microRNA 192	Homo sapiens	96-103
30554148-6	2019	Significantly, metformin prevents oxidation of heme in three protein scaffolds, cytochrome c, myoglobin and hemoglobin, with Kd values &lt; 3 mM suggesting a dual oxidation and reduction role in the regulation of heme redox transition.	Metformin	15-24	cytochrome c, somatic	Homo sapiens	80-92
30733434-4	2019	Thr222 phosphorylation following AMPK activation is required for protein stabilization of Insig-1, inhibition of cleavage and processing of SREBP-1, and lipogenic gene expression in response to metformin or A769662.	Metformin	194-203	insulin induced gene 1	Mus musculus	90-97
30318339-3	2019	Treatment of mice with metformin or exposure of murine or human alveolar macrophages to metformin prevented the particulate matter-induced generation of complex III mitochondrial reactive oxygen species, which were necessary for the opening of calcium release-activated channels (CRAC) and release of IL-6.	Metformin	23-32	interleukin 6	Homo sapiens	301-305
30318339-3	2019	Treatment of mice with metformin or exposure of murine or human alveolar macrophages to metformin prevented the particulate matter-induced generation of complex III mitochondrial reactive oxygen species, which were necessary for the opening of calcium release-activated channels (CRAC) and release of IL-6.	Metformin	88-97	interleukin 6	Homo sapiens	301-305
30548390-1	2019	Metformin and exercise independently improve insulin sensitivity and decrease the risk of diabetes.	Metformin	0-9	insulin	Homo sapiens	45-52
30548390-3	2019	However, recent evidence indicates that adding metformin to exercise antagonizes the exercise-induced improvement in insulin sensitivity and cardiorespiratory fitness.	Metformin	47-56	insulin	Homo sapiens	117-124
30548390-4	2019	The purpose of this study was to test the hypothesis that metformin diminishes the improvement in insulin sensitivity and cardiorespiratory fitness after aerobic exercise training (AET) by inhibiting skeletal muscle mitochondrial respiration and protein synthesis in older adults (62 +- 1 years).	Metformin	58-67	insulin	Homo sapiens	98-105
30548390-7	2019	However, metformin attenuated the increase in whole-body insulin sensitivity and VO2 max after AET.	Metformin	9-18	insulin	Homo sapiens	57-64
30427219-11	2019	When inner medullary tissue was treated with the PKC activator phorbol dibutyrate (PDBu), the AMPK activator metformin, or both, AQP2 phosphorylation at S261 was decreased with PDBu or metformin alone, but there was no additive effect on phosphorylation with PDBu and metformin together.	Metformin	109-118	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	94-98
30427219-11	2019	When inner medullary tissue was treated with the PKC activator phorbol dibutyrate (PDBu), the AMPK activator metformin, or both, AQP2 phosphorylation at S261 was decreased with PDBu or metformin alone, but there was no additive effect on phosphorylation with PDBu and metformin together.	Metformin	185-194	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	94-98
30427219-11	2019	When inner medullary tissue was treated with the PKC activator phorbol dibutyrate (PDBu), the AMPK activator metformin, or both, AQP2 phosphorylation at S261 was decreased with PDBu or metformin alone, but there was no additive effect on phosphorylation with PDBu and metformin together.	Metformin	185-194	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	94-98
30061044-7	2019	The study demonstrates that although there is a relationship between eGFR and metformin levels, there is not a relationship between metformin levels and plasma lactate.	Metformin	78-87	epidermal growth factor receptor	Homo sapiens	69-73
30465181-9	2019	ALP activity of metformin group was 70% higher than that without metformin at 14 days (p &lt; 0.05).	Metformin	16-25	alkaline phosphatase, placental	Homo sapiens	0-3
30840303-0	2019	Metformin inhibits proliferation and migration of endometrial cancer cells through regulating PI3K/AKT/MDM2 pathway.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	99-102
30840303-10	2019	Western blotting results manifested that the activation of PI3K/AKT/MDM2 signaling pathway was inhibited by metformin (p&lt;0.05).	Metformin	108-117	AKT serine/threonine kinase 1	Homo sapiens	64-67
30840303-11	2019	CONCLUSIONS: Metformin can inhibit the proliferation and migration of EC cells by inhibiting the activation of PI3K/AKT/MDM2 signaling pathway.	Metformin	13-22	AKT serine/threonine kinase 1	Homo sapiens	116-119
30321069-5	2019	Metformin inhibits SHIP2 in cultured cells and in skeletal muscle and kidney of db/db mice.	Metformin	0-9	inositol polyphosphate phosphatase-like 1	Mus musculus	19-24
30680029-0	2019	Metformin protects against sevoflurane-induced neuronal apoptosis through the S1P1 and ERK signaling pathways.	Metformin	0-9	mitogen-activated protein kinase 3	Homo sapiens	87-90
30680029-6	2019	The current study revealed that metformin may reduce sevoflurane-induced neuronal apoptosis via activating mitogen-activated protein kinase (ERK)1/2 phosphorylation.	Metformin	32-41	mitogen-activated protein kinase 3	Homo sapiens	141-148
30680029-7	2019	VPC23019 and U0126 eliminated the neuroprotective effects of metformin on neuronal apoptosis, which suggests that metformin is able to protect against sevoflurane-induced neurotoxicity via activation of the S1P1-dependent ERK1/2 signaling pathway.	Metformin	61-70	mitogen-activated protein kinase 3	Homo sapiens	222-226
30680029-7	2019	VPC23019 and U0126 eliminated the neuroprotective effects of metformin on neuronal apoptosis, which suggests that metformin is able to protect against sevoflurane-induced neurotoxicity via activation of the S1P1-dependent ERK1/2 signaling pathway.	Metformin	114-123	mitogen-activated protein kinase 3	Homo sapiens	222-226
30675314-0	2019	Metformin selectively targets 4T1 tumorspheres and enhances the antitumor effects of doxorubicin by downregulating the AKT and STAT3 signaling pathways.	Metformin	0-9	thymoma viral proto-oncogene 1	Mus musculus	119-122
30675314-0	2019	Metformin selectively targets 4T1 tumorspheres and enhances the antitumor effects of doxorubicin by downregulating the AKT and STAT3 signaling pathways.	Metformin	0-9	signal transducer and activator of transcription 3	Mus musculus	127-132
30595105-15	2019	CONCLUSIONS: Metformin induces reductions in thyroid nodule size and TSH and HOMA-IR levels in patients with thyroid nodules and insulin resistance.	Metformin	13-22	insulin	Homo sapiens	129-136
30697423-0	2019	The novel function of tumor protein D54 in regulating pyruvate dehydrogenase and metformin cytotoxicity in breast cancer.	Metformin	81-90	TPD52 like 2	Homo sapiens	22-39
30697423-4	2019	In this study, we revealed the novel function of TPD54 in breast cancer through understanding how TPD54 altered the cancer cell sensitivity to metformin.	Metformin	143-152	TPD52 like 2	Homo sapiens	49-54
30697423-4	2019	In this study, we revealed the novel function of TPD54 in breast cancer through understanding how TPD54 altered the cancer cell sensitivity to metformin.	Metformin	143-152	TPD52 like 2	Homo sapiens	98-103
30697423-5	2019	Methods: The role of TPD54 in altering cellular sensitivity to metformin treatment was carried out by either knockdown or overexpression of TPD54, followed by measuring cell viability and reactive oxygen species (ROS) production in MCF7 breast cancer cell line and breast cancer patient-derived xenografts.	Metformin	63-72	TPD52 like 2	Homo sapiens	21-26
30697423-5	2019	Methods: The role of TPD54 in altering cellular sensitivity to metformin treatment was carried out by either knockdown or overexpression of TPD54, followed by measuring cell viability and reactive oxygen species (ROS) production in MCF7 breast cancer cell line and breast cancer patient-derived xenografts.	Metformin	63-72	TPD52 like 2	Homo sapiens	140-145
30697423-8	2019	Results: TPD54 inhibited colony formation and enhanced cellular sensitivity to metformin treatment in MCF7 cells and breast cancer patient-derived xenografts.	Metformin	79-88	TPD52 like 2	Homo sapiens	9-14
30697423-10	2019	TPD54 knockdown increased PDH E1alpha protein degradation and led to decreased PDH enzyme activity, which reduced mitochondrial oxygen consumption and reactive oxygen species (ROS) production, thus contributing to the resistance of breast cancer cells to metformin treatment.	Metformin	255-264	TPD52 like 2	Homo sapiens	0-5
30697423-10	2019	TPD54 knockdown increased PDH E1alpha protein degradation and led to decreased PDH enzyme activity, which reduced mitochondrial oxygen consumption and reactive oxygen species (ROS) production, thus contributing to the resistance of breast cancer cells to metformin treatment.	Metformin	255-264	pyruvate dehydrogenase phosphatase catalytic subunit 1	Homo sapiens	79-82
30697423-11	2019	Conclusion: We have discovered a novel mechanism by which TPD54 regulates pyruvate dehydrogenase and affects the sensitivity of breast cancer to metformin treatment.	Metformin	145-154	TPD52 like 2	Homo sapiens	58-63
30697423-11	2019	Conclusion: We have discovered a novel mechanism by which TPD54 regulates pyruvate dehydrogenase and affects the sensitivity of breast cancer to metformin treatment.	Metformin	145-154	pyruvate dehydrogenase phosphatase catalytic subunit 1	Homo sapiens	74-96
30697423-12	2019	Our findings highlight the important post-translational regulation of PDK1 on PDH E1alpha and the potential application of TPD54 as a biomarker for selecting tumors that may be sensitive to metformin therapy.	Metformin	190-199	TPD52 like 2	Homo sapiens	123-128
30697423-13	2019	These provide new insights into understanding the regulation of PDH complexes and the resistance mechanisms of cancer cells to metformin treatment.	Metformin	127-136	pyruvate dehydrogenase phosphatase catalytic subunit 1	Homo sapiens	64-67
30745857-5	2019	Using endometrial tissues from PCOS patients with hyperplasia, we found that in response to metformin treatment in vitro, hexokinase 2 (HK2) expression was decreased, whereas phosphofructokinase (PFK), PKM2, and lactate dehydrogenase A (LDHA) expression was increased compared to controls.	Metformin	92-101	lactate dehydrogenase A	Homo sapiens	212-235
30745857-5	2019	Using endometrial tissues from PCOS patients with hyperplasia, we found that in response to metformin treatment in vitro, hexokinase 2 (HK2) expression was decreased, whereas phosphofructokinase (PFK), PKM2, and lactate dehydrogenase A (LDHA) expression was increased compared to controls.	Metformin	92-101	lactate dehydrogenase A	Homo sapiens	237-241
30745857-6	2019	Although there was no change in PDH expression, metformin treatment increased the expression of TFAM and cleaved caspase-3.	Metformin	48-57	transcription factor A, mitochondrial	Homo sapiens	96-100
30745857-8	2019	Our in vitro study showed that treatment with metformin inhibited ERalpha expression without affecting ERbeta expression.	Metformin	46-55	estrogen receptor 1	Homo sapiens	66-73
30584213-0	2019	Protective effects of metformin against osteoarthritis through upregulation of SIRT3-mediated PINK1/Parkin-dependent mitophagy in primary chondrocytes.	Metformin	22-31	sirtuin 3	Homo sapiens	79-84
30584213-2	2019	Metformin, one of the most common prescriptions for patients with type 2 diabetes, can reportedly activate Sirtuin 3 (SIRT3) expression which protects mitochondria from oxidative stress.	Metformin	0-9	sirtuin 3	Homo sapiens	107-116
30584213-2	2019	Metformin, one of the most common prescriptions for patients with type 2 diabetes, can reportedly activate Sirtuin 3 (SIRT3) expression which protects mitochondria from oxidative stress.	Metformin	0-9	sirtuin 3	Homo sapiens	118-123
30584213-3	2019	In this study, we investigated the inhibitory property of metformin on mitochondrial damage by focusing on the interleukin-1 beta (IL-1beta)-stimulated osteoarthritis model by using primary murine chondrocytes.	Metformin	58-67	interleukin 1 beta	Mus musculus	111-129
30584213-3	2019	In this study, we investigated the inhibitory property of metformin on mitochondrial damage by focusing on the interleukin-1 beta (IL-1beta)-stimulated osteoarthritis model by using primary murine chondrocytes.	Metformin	58-67	interleukin 1 beta	Mus musculus	131-139
30584213-5	2019	Metformin treatment upregulated SIRT3 expression and mitigated loss of cell viability and decreased the generation of mitochondria-induced ROS in chondrocytes stimulated with IL-1beta.	Metformin	0-9	sirtuin 3	Homo sapiens	32-37
30584213-5	2019	Metformin treatment upregulated SIRT3 expression and mitigated loss of cell viability and decreased the generation of mitochondria-induced ROS in chondrocytes stimulated with IL-1beta.	Metformin	0-9	interleukin 1 beta	Homo sapiens	175-183
30584213-6	2019	Metformin also attenuated IL-1beta-induced expressions of catabolic genes such as matrix metalloproteinase-3 (MMP3) and MMP13 and enhanced the anabolic indicator Collagen II.	Metformin	0-9	interleukin 1 beta	Homo sapiens	26-34
30584213-6	2019	Metformin also attenuated IL-1beta-induced expressions of catabolic genes such as matrix metalloproteinase-3 (MMP3) and MMP13 and enhanced the anabolic indicator Collagen II.	Metformin	0-9	matrix metallopeptidase 3	Homo sapiens	82-108
30584213-6	2019	Metformin also attenuated IL-1beta-induced expressions of catabolic genes such as matrix metalloproteinase-3 (MMP3) and MMP13 and enhanced the anabolic indicator Collagen II.	Metformin	0-9	matrix metallopeptidase 3	Homo sapiens	110-114
30584213-6	2019	Metformin also attenuated IL-1beta-induced expressions of catabolic genes such as matrix metalloproteinase-3 (MMP3) and MMP13 and enhanced the anabolic indicator Collagen II.	Metformin	0-9	matrix metallopeptidase 13	Homo sapiens	120-125
30584213-9	2019	Overall, our findings provide evidence that metformin suppresses IL-1beta-induced oxidative and osteoarthritis-like inflammatory changes by enhancing the SIRT3/PINK1/Parkin signaling pathway, thereby indicating metformin"s potential in prevention and treatment of osteoarthritic joint disease.	Metformin	44-53	interleukin 1 beta	Homo sapiens	65-73
30584213-9	2019	Overall, our findings provide evidence that metformin suppresses IL-1beta-induced oxidative and osteoarthritis-like inflammatory changes by enhancing the SIRT3/PINK1/Parkin signaling pathway, thereby indicating metformin"s potential in prevention and treatment of osteoarthritic joint disease.	Metformin	44-53	sirtuin 3	Homo sapiens	154-159
30584213-9	2019	Overall, our findings provide evidence that metformin suppresses IL-1beta-induced oxidative and osteoarthritis-like inflammatory changes by enhancing the SIRT3/PINK1/Parkin signaling pathway, thereby indicating metformin"s potential in prevention and treatment of osteoarthritic joint disease.	Metformin	211-220	interleukin 1 beta	Homo sapiens	65-73
30584213-9	2019	Overall, our findings provide evidence that metformin suppresses IL-1beta-induced oxidative and osteoarthritis-like inflammatory changes by enhancing the SIRT3/PINK1/Parkin signaling pathway, thereby indicating metformin"s potential in prevention and treatment of osteoarthritic joint disease.	Metformin	211-220	sirtuin 3	Homo sapiens	154-159
30428337-9	2019	These results suggest that the combination of metformin and berberine induced a pharmacokinetic interaction by cooperatively inhibiting OCT and MATE1-mediated transport.	Metformin	46-55	solute carrier family 47 member 1	Rattus norvegicus	144-149
30666163-0	2019	Metformin induces apoptotic cytotoxicity depending on AMPK/PKA/GSK-3beta-mediated c-FLIPL degradation in non-small cell lung cancer.	Metformin	0-9	CASP8 and FADD like apoptosis regulator	Homo sapiens	82-89
30666163-2	2019	The aim of the present study was to investigate the role of cellular FADD-like IL-1beta-converting enzyme (FLICE)-inhibitory protein large (c-FLIPL) in metformin-induced anticancer activity in non-small cell lung cancer (NSCLC) in vitro.	Metformin	152-161	CASP8 and FADD like apoptosis regulator	Homo sapiens	140-147
30666163-9	2019	Moreover, metformin greatly inhibited c-FLIPL expression and then promoted its degradation.	Metformin	10-19	CASP8 and FADD like apoptosis regulator	Homo sapiens	38-45
30666163-10	2019	Furthermore, metformin significantly activated Adenosine 5"-monophosphate (AMP)-activated protein kinase (AMPK) and its downstream glycogen synthase kinase 3beta (GSK-3beta), block the expression of AMPK, and GSK-3beta with siRNA partially reversed metformin-induced cytotoxicity and restored the expression of c-FLIPL in lung cancer cells.	Metformin	13-22	CASP8 and FADD like apoptosis regulator	Homo sapiens	311-318
30666163-11	2019	Metformin also suppressed the activity of AMPK downstream protein kinase A (PKA), PKA activators, both 8-Br-cAMP and forskolin, greatly increased c-FLIPL expression in NSCLC cells.	Metformin	0-9	CASP8 and FADD like apoptosis regulator	Homo sapiens	146-153
30666163-12	2019	Conclusion: This study provided evidence that metformin killed NSCLC cells through AMPK/PKA/GSK-3beta axis-mediated c-FLIPL degradation.	Metformin	46-55	CASP8 and FADD like apoptosis regulator	Homo sapiens	116-123
30635619-6	2019	Inhibiting autophagy with wortmannin or ATG7 silencing, the effect of metformin decreased, indicating an autophagy-related cytotoxic activity under stress conditions.	Metformin	70-79	autophagy related 7	Mus musculus	40-44
30625181-6	2019	Similarly, metformin treatment suppressed expressions of anti-apoptotic genes BCL2 and Bcl-xL, and mesenchymal genes vimentin, N-cadherin, Zeb1 and Zeb2 with simultaneous enhancement of apoptotic caspase 3 and Bax, and epithelial genes E-cadherin and keratin 19 expressions, confirming an inhibitory effect of metformin in tumorigenesis.	Metformin	11-20	BCL2 apoptosis regulator	Homo sapiens	78-82
30625181-6	2019	Similarly, metformin treatment suppressed expressions of anti-apoptotic genes BCL2 and Bcl-xL, and mesenchymal genes vimentin, N-cadherin, Zeb1 and Zeb2 with simultaneous enhancement of apoptotic caspase 3 and Bax, and epithelial genes E-cadherin and keratin 19 expressions, confirming an inhibitory effect of metformin in tumorigenesis.	Metformin	11-20	BCL2 like 1	Homo sapiens	87-93
30625181-6	2019	Similarly, metformin treatment suppressed expressions of anti-apoptotic genes BCL2 and Bcl-xL, and mesenchymal genes vimentin, N-cadherin, Zeb1 and Zeb2 with simultaneous enhancement of apoptotic caspase 3 and Bax, and epithelial genes E-cadherin and keratin 19 expressions, confirming an inhibitory effect of metformin in tumorigenesis.	Metformin	11-20	caspase 3	Homo sapiens	196-205
30625181-6	2019	Similarly, metformin treatment suppressed expressions of anti-apoptotic genes BCL2 and Bcl-xL, and mesenchymal genes vimentin, N-cadherin, Zeb1 and Zeb2 with simultaneous enhancement of apoptotic caspase 3 and Bax, and epithelial genes E-cadherin and keratin 19 expressions, confirming an inhibitory effect of metformin in tumorigenesis.	Metformin	11-20	BCL2 associated X, apoptosis regulator	Homo sapiens	210-213
30625181-6	2019	Similarly, metformin treatment suppressed expressions of anti-apoptotic genes BCL2 and Bcl-xL, and mesenchymal genes vimentin, N-cadherin, Zeb1 and Zeb2 with simultaneous enhancement of apoptotic caspase 3 and Bax, and epithelial genes E-cadherin and keratin 19 expressions, confirming an inhibitory effect of metformin in tumorigenesis.	Metformin	11-20	cadherin 1	Homo sapiens	236-246
30625181-9	2019	Similarly, cholesterol treatment inverted metformin-reduced several gene expressions (e.g., Bcl-xL, BCL2, Zeb1, vimentin, and BMI-1).	Metformin	42-51	BCL2 like 1	Homo sapiens	92-98
30625181-9	2019	Similarly, cholesterol treatment inverted metformin-reduced several gene expressions (e.g., Bcl-xL, BCL2, Zeb1, vimentin, and BMI-1).	Metformin	42-51	BCL2 apoptosis regulator	Homo sapiens	100-104
30728892-8	2019	We propose that the protumorigenic role of HIF1alpha in VHL cancers may be blunted through drugs inhibiting mitochondrial respiratory complexes, such as metformin.	Metformin	153-162	hypoxia inducible factor 1 subunit alpha	Homo sapiens	43-52
30729133-0	2019	High Glucose with Insulin Induces Cell Cycle Progression and Activation of Oncogenic Signaling of Bladder Epithelial Cells Cotreated with Metformin and Pioglitazone.	Metformin	138-147	insulin	Homo sapiens	18-25
30729133-6	2019	Metformin or pioglitazone suppressed cell viability concentration and time dependently, which was reversed by exposure to high glucose with or without insulin.	Metformin	0-9	insulin	Homo sapiens	151-158
30729133-7	2019	Prolonged exposure to high glucose and insulin enhanced cyclin D, cyclin-dependent kinase 4 (Cdk4), and Cdk2 expression and suppressed cyclin-dependent kinase inhibitors p21 and p15/16 in HBlEpC cotreated with pioglitazone and metformin.	Metformin	227-236	insulin	Homo sapiens	39-46
30293774-4	2019	Metformin counteracts VDAC1 induction.	Metformin	0-9	voltage-dependent anion channel 1	Mus musculus	22-27
30293774-7	2019	Through direct inhibition of VDAC1 conductance, metformin, like specific VDAC1 inhibitors and antibodies, restores the impaired generation of ATP and glucose-stimulated insulin secretion in T2D islets.	Metformin	48-57	voltage-dependent anion channel 1	Mus musculus	29-34
30626087-10	2019	Furthermore, metformin (2 mM) inhibited the mTOR pathway and its downstream components under zero glucose/glucose-starved conditions indicating that using metformin in combination with agents that inhibit the glycolytic pathway should be more beneficial for the treatment of triple-negative breast cancers in diabetic individuals.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	44-48
30626087-10	2019	Furthermore, metformin (2 mM) inhibited the mTOR pathway and its downstream components under zero glucose/glucose-starved conditions indicating that using metformin in combination with agents that inhibit the glycolytic pathway should be more beneficial for the treatment of triple-negative breast cancers in diabetic individuals.	Metformin	155-164	mechanistic target of rapamycin kinase	Homo sapiens	44-48
30567709-0	2019	Metformin improves diastolic function in an HFpEF-like mouse model by increasing titin compliance.	Metformin	0-9	titin	Mus musculus	81-86
30567709-9	2019	Extraction experiments on skinned ventricular muscle strips show that the metformin-induced reduction of passive stiffness in TAC/DOCA mice is due to an increase in titin compliance.	Metformin	74-83	titin	Mus musculus	165-170
30567709-11	2019	Metformin-treated mice have unaltered PEVK phosphorylation but increased phosphorylation of PKA sites in the N2B element, a change which has previously been shown to lower titin"s stiffness.	Metformin	0-9	titin	Mus musculus	172-177
30567709-13	2019	We conclude that metformin offers therapeutic benefit during HFpEF by lowering titin-based passive stiffness.	Metformin	17-26	titin	Mus musculus	79-84
30170182-0	2019	Restoring mitochondrial biogenesis with metformin attenuates beta-GP-induced phenotypic transformation of VSMCs into an osteogenic phenotype via inhibition of PDK4/oxidative stress-mediated apoptosis.	Metformin	40-49	pyruvate dehydrogenase kinase 4	Homo sapiens	159-163
30170182-10	2019	In summary, we uncovered a novel mechanism by which metformin attenuates the phenotypic transformation of VSMCs into an osteogenic phenotype via inhibition of the PDK4/oxidative stress-mediated apoptosis pathway, and mitochondrial homeostasis is involved in this process.	Metformin	52-61	pyruvate dehydrogenase kinase 4	Homo sapiens	163-167
30612112-0	2019	Acupuncture or metformin to improve insulin resistance in women with polycystic ovary syndrome: study protocol of a combined multinational cross sectional case-control study and a randomised controlled trial.	Metformin	15-24	insulin	Homo sapiens	36-43
30612112-3	2019	Therefore, we here aim to investigate if acupuncture treatment or metformin together with lifestyle or lifestyle management alone improves insulin sensitivity and related symptoms in overweight/obese women with PCOS.	Metformin	66-75	insulin	Homo sapiens	139-146
31281219-0	2019	Metformin poisoning treated with high dose insulin dextrose therapy: a case series.	Metformin	0-9	insulin	Homo sapiens	43-50
31281219-1	2019	Purpose: We describe the compassionate use of high dose insulin dextrose (HID) for life threatening metformin associated lactic acidosis (MALA) in four patients admitted to intensive care.	Metformin	100-109	insulin	Homo sapiens	56-63
32160445-2	2019	mTOR protein kinase is an perspective therapeutic target for the treatment of multiple cancers, both with the mTOR inhibitors themselves (rapamycin and its derivatives) and in combination with inhibitors of other pathways (for example, metformin).	Metformin	236-245	mechanistic target of rapamycin kinase	Homo sapiens	0-4
30153063-2	2019	Metformin is commonly used to treat insulin resistance-glucose intolerance, and flutamide, an androgen receptor (AR) antagonist, is used to target hyperandrogenemia and dyslipidemia.	Metformin	0-9	insulin	Homo sapiens	36-43
30153063-6	2019	Metformin was shown to improve fasting insulin and HOMA-IR, whereas flutamide and combination treatment were shown to reduce plasma triglycerides, ApoB48, and ApoB100, and this was associated with decreased intestinal secretion of ApoB48/triglyceride.	Metformin	0-9	insulin	Homo sapiens	39-46
30153063-9	2019	Metformin-flutamide treatment upregulated hepatic and intestinal insulin signaling, including insulin receptor, MAPK1, and AKT2.	Metformin	0-9	insulin	Homo sapiens	65-72
30153063-9	2019	Metformin-flutamide treatment upregulated hepatic and intestinal insulin signaling, including insulin receptor, MAPK1, and AKT2.	Metformin	0-9	insulin	Homo sapiens	94-101
30153063-9	2019	Metformin-flutamide treatment upregulated hepatic and intestinal insulin signaling, including insulin receptor, MAPK1, and AKT2.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	112-117
30488476-2	2019	Metformin is excreted into urine through active secretion mediated by rOCTs and rMATE1.The aim of this study was to identify the effects of high uric acid on the disposition and its mechanism.	Metformin	0-9	solute carrier family 47 member 1	Rattus norvegicus	80-86
30551411-12	2019	Metformin alleviated EP-triggered p38 MAPK inactivation and PGR (PGRA and PGRB) expression.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	34-37
30551411-14	2019	CONCLUSION: Metformin alleviated EP-induced decidualization of endometrial stromal cells by modulating secretion of multiple cytokines, inhibiting expression of MMP-2 and MMP-9, activating p38-MAPK signaling and reducing PGR expression, providing a deep insight into the molecular basis of metfromin therapy for PCOS patients.	Metformin	12-21	mitogen-activated protein kinase 1	Homo sapiens	189-192
30551471-10	2019	Inhibition of JAK/STAT pathway and activation of Nrf2/HO-1 pathway seems to be among the mechanisms mediating the effects of curcumin and metformin.	Metformin	138-147	NFE2 like bZIP transcription factor 2	Rattus norvegicus	49-53
30551515-0	2019	Metformin increases antitumor activity of MEK inhibitor binimetinib in 2D and 3D models of human metastatic melanoma cells.	Metformin	0-9	mitogen-activated protein kinase kinase 7	Homo sapiens	42-45
30551515-7	2019	The mechanism of metformin and binimetinib synergy in melanoma cells was associated with increased activation of p-AMPKalpha and decreased p-ERK, but not with alterations in p-mTOR.	Metformin	17-26	mitogen-activated protein kinase 1	Homo sapiens	141-144
30290005-0	2019	The journey of metformin from glycaemic control to mTOR inhibition and the suppression of tumour growth.	Metformin	15-24	mechanistic target of rapamycin kinase	Homo sapiens	51-55
30290005-7	2019	Because of its effect on the mTOR pathway, there may be a role for metformin in slowing or reversing growth of life-threatening hamartomas in tuberous sclerosis complex.	Metformin	67-76	mechanistic target of rapamycin kinase	Homo sapiens	29-33
30318707-12	2019	AMP-activated protein kinase (AMPK) activated by metformin-induced stimulation of forkhead box O3a (FoxO3a) transcriptional activity, followed by increased expression of GABAA receptor-associated protein (GABARAP) and its binding to GABAA receptors finally resulted in the membrane insertion of GABAA receptors.	Metformin	49-58	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	0-28
30318707-12	2019	AMP-activated protein kinase (AMPK) activated by metformin-induced stimulation of forkhead box O3a (FoxO3a) transcriptional activity, followed by increased expression of GABAA receptor-associated protein (GABARAP) and its binding to GABAA receptors finally resulted in the membrane insertion of GABAA receptors.	Metformin	49-58	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	30-34
30318707-13	2019	CONCLUSIONS AND IMPLICATIONS: Metformin increased mIPSCs by up-regulating the membrane insertion of GABAA receptors, via a pathway involving AMPK, FoxO3a, and the GABAA receptor-associated protein.	Metformin	30-39	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	141-145
30359174-9	2019	In addition, metformin increased the level of NDUFA9, a Q-module subunit required for complex I assembly, in colorectal epithelial cells.	Metformin	13-22	NADH:ubiquinone oxidoreductase subunit A9	Mus musculus	46-52
30359174-10	2019	These observations of metformin in the inhibition of colitis and CAC might associate with its activity of activating the LKB1/AMPK pathway in colorectal epithelial cells.	Metformin	22-31	serine/threonine kinase 11	Mus musculus	121-125
30520054-3	2019	In the present study, we examined the role of metformin in nuclear factor kappa B (NF-kappaB)-mediated inflammatory responses in HaCaT cells, a cell line for the keratinocyte.	Metformin	46-55	nuclear factor kappa B subunit 1	Homo sapiens	59-81
30520054-3	2019	In the present study, we examined the role of metformin in nuclear factor kappa B (NF-kappaB)-mediated inflammatory responses in HaCaT cells, a cell line for the keratinocyte.	Metformin	46-55	nuclear factor kappa B subunit 1	Homo sapiens	83-92
30520054-4	2019	Our results demonstrated that metformin significantly decreased the mRNA and protein levels of tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-6, IL-8, and IL-1beta induced by TNFalpha.	Metformin	30-39	tumor necrosis factor	Homo sapiens	125-133
30520054-4	2019	Our results demonstrated that metformin significantly decreased the mRNA and protein levels of tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-6, IL-8, and IL-1beta induced by TNFalpha.	Metformin	30-39	interleukin 6	Homo sapiens	136-154
30520054-4	2019	Our results demonstrated that metformin significantly decreased the mRNA and protein levels of tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-6, IL-8, and IL-1beta induced by TNFalpha.	Metformin	30-39	C-X-C motif chemokine ligand 8	Homo sapiens	156-160
30520054-4	2019	Our results demonstrated that metformin significantly decreased the mRNA and protein levels of tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-6, IL-8, and IL-1beta induced by TNFalpha.	Metformin	30-39	interleukin 1 beta	Homo sapiens	166-174
30520054-4	2019	Our results demonstrated that metformin significantly decreased the mRNA and protein levels of tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-6, IL-8, and IL-1beta induced by TNFalpha.	Metformin	30-39	tumor necrosis factor	Homo sapiens	186-194
30520054-5	2019	Immunofluorescence staining and western blot analysis showed that metformin inhibited the nuclear localization of p65, a subunit of nuclear factor NF-kappaB.	Metformin	66-75	nuclear factor kappa B subunit 1	Homo sapiens	147-156
30520054-6	2019	In addition, metformin suppressed the transcription activity of NF-kappaB by inhibiting the degradation of IkappaBalpha.	Metformin	13-22	nuclear factor kappa B subunit 1	Homo sapiens	64-73
30520054-6	2019	In addition, metformin suppressed the transcription activity of NF-kappaB by inhibiting the degradation of IkappaBalpha.	Metformin	13-22	NFKB inhibitor alpha	Homo sapiens	107-119
30520054-7	2019	The inhibitory effect of metformin on NF-kappaB signalling is comparable with a specific IKKbeta inhibitor BI605906.	Metformin	25-34	nuclear factor kappa B subunit 1	Homo sapiens	38-47
30306875-2	2019	INTRODUCTION: Metformin enhances insulin sensitivity, being used to prevent and treat diabetes, although its mechanism of action remains elusive.	Metformin	14-23	insulin	Homo sapiens	33-40
30693913-6	2019	RESULTS Metformin treatment significantly reduced A549 or H1651 cell growth and invasive capacity in vitro as well as Ser184 phosphorylation of Bax, Ser62 phosphorylation of Myc, and Ser473 phosphorylation of Akt, all of which could be partially attenuated by OA treatment, O/E alpha4 or sh-PP2Ac.	Metformin	8-17	AKT serine/threonine kinase 1	Homo sapiens	209-212
30693913-7	2019	Metformin treatment also significantly reduced tumor formation in vivo as well as protein expression of PCNA, Akt, Myc, and serine phosphorylation of the latter 2, which can be partially blocked by O/E alpha4 or sh-PP2Ac.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	110-113
30019648-9	2019	Metformin is AMPK activators that can suppress mTOR, STAT3 and HIF-1 so AMPK activation plays important role in suppressing inflammation and osteoclastogenesis and decreasing cancer.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	47-51
30019648-9	2019	Metformin is AMPK activators that can suppress mTOR, STAT3 and HIF-1 so AMPK activation plays important role in suppressing inflammation and osteoclastogenesis and decreasing cancer.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	53-58
30019648-9	2019	Metformin is AMPK activators that can suppress mTOR, STAT3 and HIF-1 so AMPK activation plays important role in suppressing inflammation and osteoclastogenesis and decreasing cancer.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	63-68
30019648-10	2019	CONCLUSION: Metformin effect on AMPK and mTOR pathways gives the capability to change Treg/Th17 balance and decrease Th17 differentiation and inflammation, osteoclastogenesis and cancers in RA patients.	Metformin	12-21	mechanistic target of rapamycin kinase	Homo sapiens	41-45
31533598-13	2019	Lastly, metformin cannot significantly change SBP and BMI, but can clearly increase DBP.	Metformin	8-17	D-box binding PAR bZIP transcription factor	Homo sapiens	84-87
31533598-16	2019	In addition, metformin can significantly change DBP, but it has no clearly effect on SBP and BMI.	Metformin	13-22	D-box binding PAR bZIP transcription factor	Homo sapiens	48-51
31336483-1	2019	OBJECTIVES: The aim of this study was to study the effects of metformin therapy on serum chemerin levels in some phenotypes of polycystic ovarian syndrome cases, and to correlate chemerin levels with insulin resistance parameters and with hormonal profile.	Metformin	62-71	insulin	Homo sapiens	200-207
31336483-9	2019	After three months of metformin therapy, the serum chemerin, insulin, and HOMA-IR concentrations were significantly decreased in polycystic ovarian syndrome cases as compared with the levels before therapy.	Metformin	22-31	insulin	Homo sapiens	61-68
31336505-4	2019	In contrast, intensive control with metformin (leading to insulin resistance improvement) reduces diabetes complications, including cardiovascular events, suggesting that enhancement of insulin sensitivity rather than plasma glucose level has a major role improving diabetes outcomes.	Metformin	36-45	insulin	Homo sapiens	58-65
31336505-4	2019	In contrast, intensive control with metformin (leading to insulin resistance improvement) reduces diabetes complications, including cardiovascular events, suggesting that enhancement of insulin sensitivity rather than plasma glucose level has a major role improving diabetes outcomes.	Metformin	36-45	insulin	Homo sapiens	186-193
30334082-8	2019	Only the association between adiponectin and diabetes was maintained in the lifestyle (0.69 [0.52, 0.92]) and metformin groups (0.79 [0.66, 0.94]).	Metformin	110-119	adiponectin, C1Q and collagen domain containing	Homo sapiens	29-40
30334082-10	2019	A novel association appeared for change in IL-6 in the metformin group (1.09 [1.021, 1.173]) and for baseline leptin in the lifestyle groups (1.31 [1.06, 1.63]).	Metformin	55-64	interleukin 6	Homo sapiens	43-47
31235122-6	2019	Glycemic control, most treated diabetic patients with metformin mono- and dual therapies showed an ameliorative effect in HbA1c, IFN-gamma, MPV, and PDW values compared to recent diabetic ones.	Metformin	54-63	interferon gamma	Homo sapiens	129-138
29529688-0	2019	Levels of Nitric Oxide Metabolites and Myeloperoxidase in Subjects with Type 2 Diabetes Mellitus on Metformin Therapy .	Metformin	100-109	myeloperoxidase	Homo sapiens	39-54
29529688-9	2019	CONCLUSION: Concertation of MPO and nitric oxide were significantly increased in a T2DM subject even when on metformin therapy.	Metformin	109-118	myeloperoxidase	Homo sapiens	28-31
30182764-0	2019	A pilot trial of metformin for insulin resistance and mood disturbances in adolescent and adult women with polycystic ovary syndrome.	Metformin	17-26	insulin	Homo sapiens	31-38
30182764-1	2019	We examine the effects of metformin on insulin resistance (IR) and mood including in adolescent and adult women with polycystic ovary syndrome (PCOS).	Metformin	26-35	insulin	Homo sapiens	39-46
30797286-9	2019	Metformin enhances the effects of anti-TB and insulin therapy in increasing the smear reversion by increasing autophagy.	Metformin	0-9	insulin	Homo sapiens	46-53
30745824-0	2019	Metformin Promotes the Survival of Random-Pattern Skin Flaps by Inducing Autophagy via the AMPK-mTOR-TFEB signaling pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	96-100
30745824-6	2019	Moreover, metformin also activated the AMPK-mTOR-TFEB signaling pathway in ischemic areas.	Metformin	10-19	mechanistic target of rapamycin kinase	Homo sapiens	44-48
30745824-7	2019	Inhibitions of AMPK via Compound C (CC) or AMPK shRNA adeno-associated virus (AAV) vector resulted in the downregulation of the AMPK-mTOR-TFEB signaling pathway and autophagy level in metformin-treated flaps.	Metformin	184-193	mechanistic target of rapamycin kinase	Homo sapiens	133-137
30880507-0	2019	Metformin inhibits both oleic acid-induced and CB1R receptor agonist-induced lipid accumulation in Hep3B cells: The preliminary report.	Metformin	0-9	cannabinoid receptor 1	Homo sapiens	47-51
30880507-4	2019	Both endocannabinoids and metformin may modulate hepatosteatosis; therefore, it was interesting to examine whether metformin may affect lipid accumulation in hepatocytes by acting on cannabinoid receptors, CB1 and CB2, in in vitro study.	Metformin	115-124	cannabinoid receptor 1	Homo sapiens	206-209
30880507-13	2019	The results indicate that metformin may interact with endocannabinoid system in the liver by inhibiting CB1R agonist-stimulated fat accumulation in hepatocytes.	Metformin	26-35	cannabinoid receptor 1	Homo sapiens	104-108
31409137-0	2019	Metformin Prolongs Survival in Type 2 Diabetes Lung Cancer Patients With EGFR-TKIs.	Metformin	0-9	epidermal growth factor receptor	Homo sapiens	73-77
31409137-6	2019	Conclusions: In conclusion, metformin may potentially enhance the therapeutic effect and increase survival in type 2 DM patients with lung cancer receiving EGFR-TKI therapy.	Metformin	28-37	epidermal growth factor receptor	Homo sapiens	156-160
30909226-0	2019	Metformin Therapy Aggravates Neurodegenerative Processes in ApoE-/- Mice.	Metformin	0-9	apolipoprotein E	Mus musculus	60-64
30909226-8	2019	Metformin-treated mice revealed increased expression of lipogenic genes, i.e., lxralpha and srebp1c.	Metformin	0-9	nuclear receptor subfamily 1, group H, member 3	Mus musculus	79-87
30909226-12	2019	Thus, metformin-associated lipogenesis as well as inflammation aggravated neurodegenerative processes in ApoE- /- mice.	Metformin	6-15	apolipoprotein E	Mus musculus	105-109
31939444-0	2019	Metformin enhances radiosensitivity in hepatocellular carcinoma by inhibition of specificity protein 1 and epithelial-to-mesenchymal transition.	Metformin	0-9	Sp1 transcription factor	Homo sapiens	81-102
31939444-3	2019	This study aims to investigate the effect of metformin on radiosensitivity of HCC cells and the roles of specificity protein 1 (Sp1) as a target of metformin.	Metformin	148-157	Sp1 transcription factor	Homo sapiens	105-126
31939444-10	2019	Metformin attenuated transforming growth factor-beta1 induced decrease of E-cadherin and increase of Vimentin proteins.	Metformin	0-9	cadherin 1	Homo sapiens	74-84
30620715-12	2019	In PHiov, metformin restored the expression of all the mediators, whereas, in PHanov, metformin restored only that of IR and IRS1/2.	Metformin	86-95	insulin receptor substrate 1	Rattus norvegicus	125-131
31804919-4	2019	METHODS: Rosuvastatin, digoxin, and metformin were selected as probe substrates of hepatic transporters OATP1B1, OATP1B3, BCRP, P-gp, and OCT1.	Metformin	36-45	solute carrier organic anion transporter family member 1B3	Homo sapiens	113-120
31804919-4	2019	METHODS: Rosuvastatin, digoxin, and metformin were selected as probe substrates of hepatic transporters OATP1B1, OATP1B3, BCRP, P-gp, and OCT1.	Metformin	36-45	solute carrier family 22 member 1	Homo sapiens	138-142
31085922-0	2019	Metformin Prevents Progression of Experimental Pulmonary Hypertension via Inhibition of Autophagy and Activation of Adenosine Monophosphate-Activated Protein Kinase.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	116-164
30218721-9	2019	Moreover, metformin increased Ox-LDL-impaired IL-10 secretion, an important anti-foam cell cytokine in atherosclerosis.	Metformin	10-19	interleukin 10	Mus musculus	46-51
30414431-0	2019	Metformin alleviates hyperglycemia-induced apoptosis and differentiation suppression in osteoblasts through inhibiting the TLR4 signaling pathway.	Metformin	0-9	toll-like receptor 4	Rattus norvegicus	123-127
30414431-6	2019	KEY FINDINGS: Metformin improved osteoblast differentiation, reduced apoptosis in hyperglycemic osteoblasts, and inhibited TLR4, MyD88 and NF-kappaB expression in a dose-dependent manner.	Metformin	14-23	toll-like receptor 4	Rattus norvegicus	123-127
30414431-7	2019	Down-regulating the expression or inhibiting the activity of TLR4 enhanced these protective effects of metformin on osteoblast differentiation, cell viability and cell apoptosis in hyperglycemic conditions, whereas up-regulating the expression or activating the activity of TLR4 had the opposite effects.	Metformin	103-112	toll-like receptor 4	Rattus norvegicus	61-65
30414431-7	2019	Down-regulating the expression or inhibiting the activity of TLR4 enhanced these protective effects of metformin on osteoblast differentiation, cell viability and cell apoptosis in hyperglycemic conditions, whereas up-regulating the expression or activating the activity of TLR4 had the opposite effects.	Metformin	103-112	toll-like receptor 4	Rattus norvegicus	274-278
30414431-9	2019	Metformin increased ALP and OCN secretion, enhanced BMP-2 expression, improved bone mineral density (BMD), and decreased TLR4, MyD88 and NF-kappaB levels in the femur tissues of diabetic rats.	Metformin	0-9	toll-like receptor 4	Rattus norvegicus	121-125
30414431-10	2019	SIGNIFICANCE: Taken together our experimentation support the hypothesis that metformin may alleviate hyperglycemia-induced apoptosis and differentiation suppression in osteoblasts by inhibiting the TLR4/MyD88/NF-kappaB signaling pathway.	Metformin	77-86	toll-like receptor 4	Rattus norvegicus	198-202
30681616-0	2019	The effects of metformin on insulin resistance in overweight or obese children and adolescents: A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials.	Metformin	15-24	insulin	Homo sapiens	28-35
30681616-2	2019	OBJECTIVES: This study aimed to assess whether metformin could effectively and safely improve homeostasis model assessment insulin resistance index (HOMA-IR) and other related laboratory indicators including fasting glucose, fasting insulin, high-density lipoprotein cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C).	Metformin	47-56	insulin	Homo sapiens	123-130
30681616-2	2019	OBJECTIVES: This study aimed to assess whether metformin could effectively and safely improve homeostasis model assessment insulin resistance index (HOMA-IR) and other related laboratory indicators including fasting glucose, fasting insulin, high-density lipoprotein cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C).	Metformin	47-56	insulin	Homo sapiens	233-240
30306875-10	2019	In addition, metformin reduces plasma insulin concentration in subjects with impaired glucose tolerance and diabetes and decreases the amount of insulin required for metabolic control in patients with diabetes, reflecting improvement of insulin activity.	Metformin	13-22	insulin	Homo sapiens	38-45
30306875-10	2019	In addition, metformin reduces plasma insulin concentration in subjects with impaired glucose tolerance and diabetes and decreases the amount of insulin required for metabolic control in patients with diabetes, reflecting improvement of insulin activity.	Metformin	13-22	insulin	Homo sapiens	145-152
30306875-10	2019	In addition, metformin reduces plasma insulin concentration in subjects with impaired glucose tolerance and diabetes and decreases the amount of insulin required for metabolic control in patients with diabetes, reflecting improvement of insulin activity.	Metformin	13-22	insulin	Homo sapiens	145-152
30888659-6	2019	Resveratrol, rapamycin, metformin and aspirin, showing effectiveness in model organism life- and healthspan extension mainly target the master regulators of aging such as mTOR, FOXO and PGC1alpha, affecting autophagy, inflammation and oxidative stress.	Metformin	24-33	mechanistic target of rapamycin kinase	Homo sapiens	171-175
30888659-6	2019	Resveratrol, rapamycin, metformin and aspirin, showing effectiveness in model organism life- and healthspan extension mainly target the master regulators of aging such as mTOR, FOXO and PGC1alpha, affecting autophagy, inflammation and oxidative stress.	Metformin	24-33	PPARG coactivator 1 alpha	Homo sapiens	186-195
32190786-4	2019	This results in altered methionine cycle metabolite levels mimicking the effects of metformin and lifespan extension that is dependent on the starvation- and hypoxia-induced flavin containing monoxygenase, FMO-2.	Metformin	84-93	Dimethylaniline monooxygenase [N-oxide-forming]	Caenorhabditis elegans	206-211
30290168-0	2019	Metformin attenuates cardiovascular and renal injury in uninephrectomized rats on DOCA-salt: Involvement of AMPK and miRNAs in cardioprotection.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	108-112
30290168-5	2019	Metformin was used to delineate the role of AMPK in mitigating the hypertension-induced CV and renal dysfunction.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	44-48
30803422-0	2019	Metformin diminishes the unfavourable impact of Nrf2 in breast cancer patients with type 2 diabetes.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	48-52
30803422-3	2019	In previous studies, the widely used diabetes drug metformin has appeared to have a critical role in the regulation of Nrf2 function.	Metformin	51-60	NFE2 like bZIP transcription factor 2	Homo sapiens	119-123
30803422-6	2019	We found that high-level cytoplasmic Nrf2 expression predicted dismal overall survival and breast cancer-specific survival, but only in the patients who were not taking metformin at the time of diagnosis.	Metformin	169-178	NFE2 like bZIP transcription factor 2	Homo sapiens	37-41
30803422-7	2019	Similarly, low-level nuclear Keap1 expression had an adverse prognostic value in terms of overall survival and breast cancer-specific survival in patients without metformin.	Metformin	163-172	kelch like ECH associated protein 1	Homo sapiens	29-34
30566007-0	2018	Metformin Improves Insulin Sensitivity and Vascular Health in Youth With Type 1 Diabetes Mellitus.	Metformin	0-9	insulin	Homo sapiens	19-26
30025915-13	2018	Meanwhile, metformin down-regulated the anti-apoptotic protein B cell lymphoma 2 (Bcl-2) but up-regulated the pro-apoptotic protein Bcl2-associated X (BAX), which suggests the involvement of the mitochondrial-mediated apoptosis pathway.	Metformin	11-20	B cell leukemia/lymphoma 2	Mus musculus	63-80
30025915-13	2018	Meanwhile, metformin down-regulated the anti-apoptotic protein B cell lymphoma 2 (Bcl-2) but up-regulated the pro-apoptotic protein Bcl2-associated X (BAX), which suggests the involvement of the mitochondrial-mediated apoptosis pathway.	Metformin	11-20	B cell leukemia/lymphoma 2	Mus musculus	82-87
30025915-14	2018	Furthermore, metformin promoted AMP-activated protein kinase (AMPK) phosphorylation but inhibited insulin-like growth factor-1 receptor (IGF-1R) expression, protein kinase B (PKB/AKT) phosphorylation and mammalian target of rapamycin (mTOR) phosphorylation.	Metformin	13-22	thymoma viral proto-oncogene 1	Mus musculus	179-182
30025915-14	2018	Furthermore, metformin promoted AMP-activated protein kinase (AMPK) phosphorylation but inhibited insulin-like growth factor-1 receptor (IGF-1R) expression, protein kinase B (PKB/AKT) phosphorylation and mammalian target of rapamycin (mTOR) phosphorylation.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	204-233
30025915-14	2018	Furthermore, metformin promoted AMP-activated protein kinase (AMPK) phosphorylation but inhibited insulin-like growth factor-1 receptor (IGF-1R) expression, protein kinase B (PKB/AKT) phosphorylation and mammalian target of rapamycin (mTOR) phosphorylation.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	235-239
30025915-16	2018	We conclude that metformin inhibits cell proliferation and induces apoptosis in AtT20 cells by activating AMPK/mTOR and inhibiting IGF-1R/AKT/mTOR signaling pathways.	Metformin	17-26	insulin-like growth factor I receptor	Mus musculus	131-137
30025915-16	2018	We conclude that metformin inhibits cell proliferation and induces apoptosis in AtT20 cells by activating AMPK/mTOR and inhibiting IGF-1R/AKT/mTOR signaling pathways.	Metformin	17-26	thymoma viral proto-oncogene 1	Mus musculus	138-141
30545309-0	2018	Metformin regulates atrial SK2 and SK3 expression through inhibiting the PKC/ERK signaling pathway in type 2 diabetic rats.	Metformin	0-9	potassium calcium-activated channel subfamily N member 2	Rattus norvegicus	27-30
30545309-0	2018	Metformin regulates atrial SK2 and SK3 expression through inhibiting the PKC/ERK signaling pathway in type 2 diabetic rats.	Metformin	0-9	Eph receptor B1	Rattus norvegicus	77-80
30545309-1	2018	BACKGROUND: Our previous study showed that metformin regulates the mRNA and protein levels of type 2 small conductance calcium-activated potassium channel (SK2) and type 3 small conductance calcium-activated potassium channels (SK3) in atrial tissue as well as the ion current of atrial myocytes in rats with type 2 diabetes mellitus (T2DM), but the underlying signaling mechanism is unknown.	Metformin	43-52	potassium calcium-activated channel subfamily N member 2	Rattus norvegicus	156-159
30545309-2	2018	This study aimed to investigate whether metformin regulates atrial SK2 and SK3 protein expression in T2DM rats though the protein kinase C (PKC)/extracellular signal-regulated kinase (ERK) signaling pathway.	Metformin	40-49	potassium calcium-activated channel subfamily N member 2	Rattus norvegicus	67-70
30545309-2	2018	This study aimed to investigate whether metformin regulates atrial SK2 and SK3 protein expression in T2DM rats though the protein kinase C (PKC)/extracellular signal-regulated kinase (ERK) signaling pathway.	Metformin	40-49	Eph receptor B1	Rattus norvegicus	184-187
30545309-8	2018	Eight weeks of metformin treatment inhibited the PKC activity and pERK and SK3 expression, and elevated SK2 expression compared with the T2DM group.	Metformin	15-24	potassium calcium-activated channel subfamily N member 2	Rattus norvegicus	104-107
30545309-9	2018	Compared with the metformin-treated only group, the injection of rh-EGF increased pERK and SK3 expression, and decreased SK2 expression; the injection of PMA increased PKC activity and SK3 expression, and decreased SK2 expression.	Metformin	18-27	potassium calcium-activated channel subfamily N member 2	Rattus norvegicus	121-124
30545309-9	2018	Compared with the metformin-treated only group, the injection of rh-EGF increased pERK and SK3 expression, and decreased SK2 expression; the injection of PMA increased PKC activity and SK3 expression, and decreased SK2 expression.	Metformin	18-27	potassium calcium-activated channel subfamily N member 2	Rattus norvegicus	215-218
30545309-12	2018	Long-term metformin treatment prevents the SK2 downregulation and the SK3 upregulation through inhibiting the PKC/ERK signaling pathway.	Metformin	10-19	potassium calcium-activated channel subfamily N member 2	Rattus norvegicus	43-46
30545309-12	2018	Long-term metformin treatment prevents the SK2 downregulation and the SK3 upregulation through inhibiting the PKC/ERK signaling pathway.	Metformin	10-19	Eph receptor B1	Rattus norvegicus	114-117
30540938-0	2018	Dual Inhibition of the Lactate Transporters MCT1 and MCT4 Is Synthetic Lethal with Metformin due to NAD+ Depletion in Cancer Cells.	Metformin	83-92	solute carrier family 16 member 1	Homo sapiens	44-48
30544975-1	2018	The organic cation transporter 1 (OCT1, SLC22A1) is strongly expressed in the human liver and facilitates the hepatic uptake of drugs such as morphine, metformin, tropisetron, sumatriptan and fenoterol and of endogenous substances such as thiamine.	Metformin	152-161	solute carrier family 22 member 1	Homo sapiens	4-32
30544975-1	2018	The organic cation transporter 1 (OCT1, SLC22A1) is strongly expressed in the human liver and facilitates the hepatic uptake of drugs such as morphine, metformin, tropisetron, sumatriptan and fenoterol and of endogenous substances such as thiamine.	Metformin	152-161	solute carrier family 22 member 1	Homo sapiens	34-38
30544975-1	2018	The organic cation transporter 1 (OCT1, SLC22A1) is strongly expressed in the human liver and facilitates the hepatic uptake of drugs such as morphine, metformin, tropisetron, sumatriptan and fenoterol and of endogenous substances such as thiamine.	Metformin	152-161	solute carrier family 22 member 1	Homo sapiens	40-47
30651935-7	2018	Chromatin immunoprecipitation (ChIP)-RT PCR analysis indicates that metformin treatment results in an increased H2A.Z occupancy on the androgen receptor (AR) and AR-regulated genes that is more prominent in the androgen dependent AR positive LNCaP cells.	Metformin	68-77	androgen receptor	Homo sapiens	135-152
30651935-7	2018	Chromatin immunoprecipitation (ChIP)-RT PCR analysis indicates that metformin treatment results in an increased H2A.Z occupancy on the androgen receptor (AR) and AR-regulated genes that is more prominent in the androgen dependent AR positive LNCaP cells.	Metformin	68-77	androgen receptor	Homo sapiens	154-156
30651935-7	2018	Chromatin immunoprecipitation (ChIP)-RT PCR analysis indicates that metformin treatment results in an increased H2A.Z occupancy on the androgen receptor (AR) and AR-regulated genes that is more prominent in the androgen dependent AR positive LNCaP cells.	Metformin	68-77	androgen receptor	Homo sapiens	162-164
30651935-7	2018	Chromatin immunoprecipitation (ChIP)-RT PCR analysis indicates that metformin treatment results in an increased H2A.Z occupancy on the androgen receptor (AR) and AR-regulated genes that is more prominent in the androgen dependent AR positive LNCaP cells.	Metformin	68-77	androgen receptor	Homo sapiens	162-164
30651935-9	2018	Based on preliminary data with an EZH2-specific inhibitor, we suggest that the effects of metformin on the early stages of PCa may involve both EZH2 and H2A.Z through the alteration of different molecular pathways.	Metformin	90-99	enhancer of zeste 2 polycomb repressive complex 2 subunit	Homo sapiens	34-38
30651935-9	2018	Based on preliminary data with an EZH2-specific inhibitor, we suggest that the effects of metformin on the early stages of PCa may involve both EZH2 and H2A.Z through the alteration of different molecular pathways.	Metformin	90-99	enhancer of zeste 2 polycomb repressive complex 2 subunit	Homo sapiens	144-148
30292140-0	2018	Metformin Protects against H2O2-Induced Cardiomyocyte Injury by Inhibiting the miR-1a-3p/GRP94 Pathway.	Metformin	0-9	heat shock protein 90 beta family member 1	Rattus norvegicus	89-94
30292140-8	2018	Furthermore, as a direct allosteric AMPK activator, metformin was shown to activate AMPK and significantly reduce C/EBP beta and miR-1a-3p levels compared with those in the control group.	Metformin	52-61	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	36-40
30292140-8	2018	Furthermore, as a direct allosteric AMPK activator, metformin was shown to activate AMPK and significantly reduce C/EBP beta and miR-1a-3p levels compared with those in the control group.	Metformin	52-61	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	84-88
30292140-9	2018	In conclusion, metformin protects cardiomyocytes against H2O2 damage through the AMPK/C/EBP beta/miR-1a-3p/GRP94 pathway, which indicates that metformin may be applied for the treatment of I/R injury.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	81-85
30292140-9	2018	In conclusion, metformin protects cardiomyocytes against H2O2 damage through the AMPK/C/EBP beta/miR-1a-3p/GRP94 pathway, which indicates that metformin may be applied for the treatment of I/R injury.	Metformin	15-24	heat shock protein 90 beta family member 1	Rattus norvegicus	107-112
30292140-9	2018	In conclusion, metformin protects cardiomyocytes against H2O2 damage through the AMPK/C/EBP beta/miR-1a-3p/GRP94 pathway, which indicates that metformin may be applied for the treatment of I/R injury.	Metformin	143-152	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	81-85
30292140-9	2018	In conclusion, metformin protects cardiomyocytes against H2O2 damage through the AMPK/C/EBP beta/miR-1a-3p/GRP94 pathway, which indicates that metformin may be applied for the treatment of I/R injury.	Metformin	143-152	heat shock protein 90 beta family member 1	Rattus norvegicus	107-112
30518693-1	2018	BACKGROUND: Metformin reduces plasma glucose and has been shown to increase glucagon-like peptide 1 (GLP-1) secretion.	Metformin	12-21	glucagon	Homo sapiens	76-99
30518693-1	2018	BACKGROUND: Metformin reduces plasma glucose and has been shown to increase glucagon-like peptide 1 (GLP-1) secretion.	Metformin	12-21	glucagon	Homo sapiens	101-106
30518693-3	2018	The current study investigated metformin-induced GLP-1 secretion and its contribution to the overall glucose-lowering effect of metformin and underlying mechanisms in patients with type 2 diabetes.	Metformin	31-40	glucagon	Homo sapiens	49-54
30518693-3	2018	The current study investigated metformin-induced GLP-1 secretion and its contribution to the overall glucose-lowering effect of metformin and underlying mechanisms in patients with type 2 diabetes.	Metformin	128-137	glucagon	Homo sapiens	49-54
30518693-8	2018	The direct effect of metformin on GLP-1 secretion was tested ex vivo in human ileal and colonic tissue with and without dorsomorphin-induced inhibiting of the AMPK activity.	Metformin	21-30	glucagon	Homo sapiens	34-39
30518693-9	2018	RESULTS: Metformin increased postprandial GLP-1 secretion compared with placebo (P = 0.014), and the postprandial glucose excursions were significantly smaller after metformin + saline compared with metformin + Ex9-39 (P = 0.004).	Metformin	9-18	glucagon	Homo sapiens	42-47
30518693-10	2018	Ex vivo metformin acutely increased GLP-1 secretion (colonic tissue, P &lt; 0.01; ileal tissue, P &lt; 0.05), but the effect was abolished by inhibition of AMPK activity.	Metformin	8-17	glucagon	Homo sapiens	36-41
30518693-11	2018	CONCLUSIONS: Metformin has a direct and AMPK-dependent effect on GLP-1-secreting L cells and increases postprandial GLP-1 secretion, which seems to contribute to metformin"s glucose-lowering effect and mode of action.	Metformin	13-22	glucagon	Homo sapiens	65-70
30518693-11	2018	CONCLUSIONS: Metformin has a direct and AMPK-dependent effect on GLP-1-secreting L cells and increases postprandial GLP-1 secretion, which seems to contribute to metformin"s glucose-lowering effect and mode of action.	Metformin	13-22	glucagon	Homo sapiens	116-121
30518693-11	2018	CONCLUSIONS: Metformin has a direct and AMPK-dependent effect on GLP-1-secreting L cells and increases postprandial GLP-1 secretion, which seems to contribute to metformin"s glucose-lowering effect and mode of action.	Metformin	162-171	glucagon	Homo sapiens	116-121
30584280-0	2018	SREBP-2, a new target of metformin?	Metformin	25-34	sterol regulatory element binding transcription factor 2	Homo sapiens	0-7
30584280-7	2018	Metformin reduced the sterol regulatory element-binding protein-2 (SREBP-2) and its downstream target proteins and increased low-density lipoprotein receptor (LDLR) levels.	Metformin	0-9	sterol regulatory element binding transcription factor 2	Homo sapiens	22-65
30584280-7	2018	Metformin reduced the sterol regulatory element-binding protein-2 (SREBP-2) and its downstream target proteins and increased low-density lipoprotein receptor (LDLR) levels.	Metformin	0-9	sterol regulatory element binding transcription factor 2	Homo sapiens	67-74
30584280-8	2018	Conclusion: Our preliminary results demonstrate that metformin as a first-line and initial medication suppresses the synthesis of SREBP-2 and upregulates LDLR, and consequently decreases cholesterol production via activation of AMPK, at least partly.	Metformin	53-62	sterol regulatory element binding transcription factor 2	Homo sapiens	130-137
30372835-12	2018	The protein level of VE-cadherin decreased in cells received Metformin.	Metformin	61-70	cadherin 5	Homo sapiens	21-32
30372835-13	2018	Compared to the control, Metformin blunted the expression of VEGF subtypes and directed cells to energy status by induction of PRKAA1, PRKAB2, and PRKAG1 genes (p &lt; 0.05).	Metformin	25-34	vascular endothelial growth factor A	Homo sapiens	61-65
30372835-13	2018	Compared to the control, Metformin blunted the expression of VEGF subtypes and directed cells to energy status by induction of PRKAA1, PRKAB2, and PRKAG1 genes (p &lt; 0.05).	Metformin	25-34	protein kinase AMP-activated non-catalytic subunit beta 2	Homo sapiens	135-141
30088260-0	2018	Metformin inhibits human breast cancer cell growth by promoting apoptosis via a ROS-independent pathway involving mitochondrial dysfunction: pivotal role of superoxide dismutase (SOD).	Metformin	0-9	superoxide dismutase 1	Homo sapiens	157-177
30088260-0	2018	Metformin inhibits human breast cancer cell growth by promoting apoptosis via a ROS-independent pathway involving mitochondrial dysfunction: pivotal role of superoxide dismutase (SOD).	Metformin	0-9	superoxide dismutase 1	Homo sapiens	179-182
30088260-11	2018	CONCLUSIONS: Our data indicate that metformin may play a pivotal role in modulating the anti-oxidant system, including the SOD machinery, in breast cancer-derived cells.	Metformin	36-45	superoxide dismutase 1	Homo sapiens	123-126
30088260-12	2018	Our observations were validated by in silico analyses, indicating a close interaction between SOD and metformin.	Metformin	102-111	superoxide dismutase 1	Homo sapiens	94-97
30088260-14	2018	Finally, we found that metformin may modulate the pro-apoptotic Bax, anti-apoptotic Bcl-2, MMP-2, MMP-9, miR-21 and miR-155 expression levels.	Metformin	23-32	BCL2 associated X, apoptosis regulator	Homo sapiens	64-67
30088260-14	2018	Finally, we found that metformin may modulate the pro-apoptotic Bax, anti-apoptotic Bcl-2, MMP-2, MMP-9, miR-21 and miR-155 expression levels.	Metformin	23-32	BCL2 apoptosis regulator	Homo sapiens	84-89
29656591-8	2018	The inhibitor of AMPK, compound C, could block the EPO-induced autophagy and beneficial action on SCI, whereas the activator of AMPK, metformin, could mimic the effects of EPO.	Metformin	134-143	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	128-132
30307719-0	2018	Metformin synergistically enhances the antitumor activity of the third-generation EGFR-TKI CO-1686 in lung cancer cells through suppressing NF-kappaB signaling.	Metformin	0-9	epidermal growth factor receptor	Homo sapiens	82-86
30307719-12	2018	Metformin combined with CO-1686 synergistically inhibited the p-IKBalpha, p-IKKalpha/beta, p50, and p65.	Metformin	0-9	NFKB inhibitor alpha	Homo sapiens	64-72
30307719-12	2018	Metformin combined with CO-1686 synergistically inhibited the p-IKBalpha, p-IKKalpha/beta, p50, and p65.	Metformin	0-9	nuclear factor kappa B subunit 1	Homo sapiens	91-94
30242671-0	2018	Effects of metformin on the PI3K/AKT/FOXO1 pathway in anaplastic thyroid Cancer cell lines.	Metformin	11-20	AKT serine/threonine kinase 1	Homo sapiens	33-36
30242671-0	2018	Effects of metformin on the PI3K/AKT/FOXO1 pathway in anaplastic thyroid Cancer cell lines.	Metformin	11-20	forkhead box O1	Homo sapiens	37-42
30242671-6	2018	RT-qPCR results showed that expression levels of PI3K, AKT and FOXO1 was inhibited by metformin (P &lt; 0.05).	Metformin	86-95	AKT serine/threonine kinase 1	Homo sapiens	55-58
30242671-6	2018	RT-qPCR results showed that expression levels of PI3K, AKT and FOXO1 was inhibited by metformin (P &lt; 0.05).	Metformin	86-95	forkhead box O1	Homo sapiens	63-68
30242671-9	2018	CONCLUSUION: The downregulation of FOXO1 was intensified by metformin, but no increase in cell viability was observed following FOXO1 downregulation by metformin.	Metformin	60-69	forkhead box O1	Homo sapiens	35-40
30242671-10	2018	However, the exact molecular mechanism of metformin on inhibition of the PI3K/AKT pathway and subsequent decrease in cell viability remains unclear and further studies are required for its clarification.	Metformin	42-51	AKT serine/threonine kinase 1	Homo sapiens	78-81
30511324-3	2018	OBJECTIVE: We conducted a systematic review to provide an overview of the efficacy of &gt;= 6 months of metformin treatment in children and adults with respect to weight, insulin resistance, and progression toward type 2 diabetes mellitus (T2DM).	Metformin	104-113	insulin	Homo sapiens	171-178
30511324-12	2018	Three studies showed a significant improvement in insulin sensitivity in the metformin versus the control group.	Metformin	77-86	insulin	Homo sapiens	50-57
30097812-0	2018	Anti-inflammatory Action of Metformin with Respect to CX3CL1/CX3CR1 Signaling in Human Placental Circulation in Normal-Glucose Versus High-Glucose Environments.	Metformin	28-37	C-X3-C motif chemokine ligand 1	Homo sapiens	54-60
30242842-3	2018	Metformin at relatively low doses was shown to suppress FcepsilonR1-mediated degranulation, IL-13, TNF-alpha and sphingosine-1-phosphate (S1P) secretion in murine bone marrow-derived mast cells (BMMCs).	Metformin	0-9	interleukin 13	Mus musculus	92-97
30242842-3	2018	Metformin at relatively low doses was shown to suppress FcepsilonR1-mediated degranulation, IL-13, TNF-alpha and sphingosine-1-phosphate (S1P) secretion in murine bone marrow-derived mast cells (BMMCs).	Metformin	0-9	tumor necrosis factor	Mus musculus	99-108
30097812-3	2018	By preventing the activation of NF-kappaB, metformin exhibits anti-inflammatory properties.	Metformin	43-52	nuclear factor kappa B subunit 1	Homo sapiens	32-41
30097812-4	2018	We examined the influence of hyperglycemia (25 mmol/L glucose; HG group; N = 36) on metformin-mediated effects on CX3CL1 and TNF-alpha production by placental lobules perfused extracorporeally.	Metformin	84-93	C-X3-C motif chemokine ligand 1	Homo sapiens	114-120
30097812-4	2018	We examined the influence of hyperglycemia (25 mmol/L glucose; HG group; N = 36) on metformin-mediated effects on CX3CL1 and TNF-alpha production by placental lobules perfused extracorporeally.	Metformin	84-93	tumor necrosis factor	Homo sapiens	125-134
30097812-7	2018	Metformin (2.5 and 5.0 mg/L; subgroups B and C) lowered the production of CX3CL1 and TNF-alpha in a dose-dependent and time-dependent manner.	Metformin	0-9	C-X3-C motif chemokine ligand 1	Homo sapiens	74-80
30097812-7	2018	Metformin (2.5 and 5.0 mg/L; subgroups B and C) lowered the production of CX3CL1 and TNF-alpha in a dose-dependent and time-dependent manner.	Metformin	0-9	tumor necrosis factor	Homo sapiens	85-94
30097812-9	2018	Moreover, CX3CL1 levels after perfusion with 5.0 mg/L metformin were reduced by 33.28 and 33.83% (at 120 and 150 min, respectively) in the HG-C subgroup versus 24.98 and 23.66% in the NG-C subgroup, which indicated an augmentation of the metformin action over time in hyperglycemia.	Metformin	54-63	C-X3-C motif chemokine ligand 1	Homo sapiens	10-16
30097812-9	2018	Moreover, CX3CL1 levels after perfusion with 5.0 mg/L metformin were reduced by 33.28 and 33.83% (at 120 and 150 min, respectively) in the HG-C subgroup versus 24.98 and 23.66% in the NG-C subgroup, which indicated an augmentation of the metformin action over time in hyperglycemia.	Metformin	238-247	C-X3-C motif chemokine ligand 1	Homo sapiens	10-16
30334324-0	2018	Metformin inhibits growth and prolactin secretion of pituitary prolactinoma cells and xenografts.	Metformin	0-9	prolactin	Homo sapiens	30-39
29931409-10	2018	Mean serum levels of malondialdehyde and neurotensin were significantly lower in metformin arm after the 6th and the 12th cycles.	Metformin	81-90	neurotensin	Homo sapiens	41-52
30397356-0	2018	Gut microbiota and intestinal FXR mediate the clinical benefits of metformin.	Metformin	67-76	nuclear receptor subfamily 1, group H, member 4	Mus musculus	30-33
30397356-8	2018	Thus, we conclude that metformin acts in part through a B. fragilis-GUDCA-intestinal FXR axis to improve metabolic dysfunction, including hyperglycemia.	Metformin	23-32	nuclear receptor subfamily 1, group H, member 4	Mus musculus	85-88
30272364-0	2018	Metformin suppresses hypoxia-induced migration via the HIF-1alpha/VEGF pathway in gallbladder cancer in vitro and in vivo.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	55-65
30054562-6	2018	LKB1-AMPK activation in GC cell lines was tumor suppressive, as metformin (an AMPK activator) inhibited GC cell growth in the CAB39L-silenced cells.	Metformin	64-73	calcium binding protein 39 like	Homo sapiens	126-132
30272364-0	2018	Metformin suppresses hypoxia-induced migration via the HIF-1alpha/VEGF pathway in gallbladder cancer in vitro and in vivo.	Metformin	0-9	vascular endothelial growth factor A	Homo sapiens	66-70
30272364-10	2018	Further experiments demonstrated that metformin inhibited hypoxia-induced migration via HIF-1alpha/VEGF in vitro.	Metformin	38-47	vascular endothelial growth factor A	Homo sapiens	99-103
30115526-7	2018	Patients with 9-years duration of diabetes or with combination therapy of insulin-metformin-sulfonylureas differed in mean BMI for adequate or inadequate glycaemic control (29.5 versus 31.2kg/m2; P&lt;0.001 and 29.8 versus 33.2; P&lt;0.01, respectively).	Metformin	82-91	insulin	Homo sapiens	74-81
30272364-11	2018	In addition, metformin suppressed GBC growth and downregulated the expression of HIF-1alpha and VEGF in a GBC-SD cell xenograft model.	Metformin	13-22	hypoxia inducible factor 1 subunit alpha	Homo sapiens	81-91
30272364-11	2018	In addition, metformin suppressed GBC growth and downregulated the expression of HIF-1alpha and VEGF in a GBC-SD cell xenograft model.	Metformin	13-22	vascular endothelial growth factor A	Homo sapiens	96-100
30272364-12	2018	Taken together, these results suggest that HIF-1alpha may contribute to tumor migration via the overexpression of VEGF in GBC, while metformin is able to inhibit tumor migration by targeting the HIF-1alpha/VEGF pathway.	Metformin	133-142	hypoxia inducible factor 1 subunit alpha	Homo sapiens	195-205
30272364-12	2018	Taken together, these results suggest that HIF-1alpha may contribute to tumor migration via the overexpression of VEGF in GBC, while metformin is able to inhibit tumor migration by targeting the HIF-1alpha/VEGF pathway.	Metformin	133-142	vascular endothelial growth factor A	Homo sapiens	206-210
30056057-3	2018	Current evidence suggests that the anti-diabetic drug metformin improves insulin resistance and protects against endothelial dysfunction in the vasculature.	Metformin	54-63	insulin	Homo sapiens	73-80
30598667-9	2018	Our data further revealed that the novel CPC-chitosan-metformin composite enhanced the odontogenic differentiation of DPCs, as evidenced by higher ALP activity, elevated expression of odontoblastic markers, and strong mineral deposition.	Metformin	54-63	alkaline phosphatase, placental	Homo sapiens	147-150
30542300-3	2018	In this study, we pooled the data from two clinical trials, which were originally examining the efficacy of betahistine and the efficacy of metformin in treating antipsychotic-induced weight gain and insulin resistance.	Metformin	140-149	insulin	Homo sapiens	200-207
30542300-6	2018	After treatment, metformin group had a mean decrease in BMI of 1.46 +- 0.14 (p &lt; 0.001) and insulin resistance index (IRI) of 4.30 +- 2.02 (p &lt; 0.001).	Metformin	17-26	insulin	Homo sapiens	95-102
30542300-9	2018	Between the two treatment groups, metformin significantly decreased weight, BMI, fasting glucose, insulin level, and IRI but not waist circumference when compared with betahistine.	Metformin	34-43	insulin	Homo sapiens	98-105
30542300-10	2018	Moreover, metformin significantly decreased weight, BMI, waist circumference, fasting glucose, insulin level, and IRI when compared with placebo, whereas betahistine significantly decreased body weight, waist circumference, BMI, insulin level, and IRI but not fasting glucose when compared with placebo.	Metformin	10-19	insulin	Homo sapiens	95-102
30542300-11	2018	In this study, we found that both metformin treatment and betahistine treatment were efficacious in improving antipsychotic-induced weight gain and insulin resistance, and metformin was more efficacious in preventing and revising the weight gain induced by antipsychotics.	Metformin	34-43	insulin	Homo sapiens	148-155
30469399-0	2018	Metformin Inhibits Migration and Invasion by Suppressing ROS Production and COX2 Expression in MDA-MB-231 Breast Cancer Cells.	Metformin	0-9	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	76-80
30486321-5	2018	In vitro study showed that metformin that is introduced to the culture medium at concentration equal 500 microM may promote the differentiation of rASCs into bone-forming cells, which express mRNA and secrets proteins that are related to the functional tissue (namely, alkaline phosphatase and osteocalcin).	Metformin	27-36	bone gamma-carboxyglutamate protein	Rattus norvegicus	294-305
30524372-1	2018	Initially produced in Europe in 1958, metformin is still one of the most widely prescribed drugs to treat type II diabetes and other comorbidities associated with insulin resistance.	Metformin	38-47	insulin	Homo sapiens	163-170
30524372-2	2018	Metformin has been shown to improve fertility outcomes in females with insulin resistance associated with polycystic ovary syndrome (PCOS) and in obese males with reduced fertility.	Metformin	0-9	insulin	Homo sapiens	71-78
30519161-6	2018	Our results indicate that metformin overall inhibits microglia activation measured by OX-6 (MHCII marker), IKKbeta (pro-inflammatory marker) and arginase (anti-inflammatory marker) immunoreactivity.	Metformin	26-35	inhibitor of nuclear factor kappa B kinase subunit beta	Rattus norvegicus	107-114
30469399-8	2018	At 100 microM, however, metformin reduced ICAM1 and COX2 expression, as well as reduced PGE2 production and endogenous mitochondrial ROS production while failing to significantly impact cell viability.	Metformin	24-33	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	52-56
30442142-0	2018	Metformin causes cancer cell death through downregulation of p53-dependent differentiated embryo chondrocyte 1.	Metformin	0-9	tumor protein p53	Homo sapiens	61-64
30442142-4	2018	METHODS: We first examined the cytotoxic effects of metformin in the HeLa human cervical carcinoma and ZR-75-1 breast cancer cell lines using assays of cell viability, cleaved poly-ADP-ribose polymerase, and Annexin V-fluorescein isothiocyanate apoptosis, as well as flow cytometric analyses of the cell cycle profile and reactive oxygen species (ROS).	Metformin	52-61	poly(ADP-ribose) polymerase 1	Homo sapiens	176-202
30442142-5	2018	We later clarified the effect of metformin on p53 protein stability using transient transfection and cycloheximide chase analyses.	Metformin	33-42	tumor protein p53	Homo sapiens	46-49
30442142-6	2018	RESULTS: We observed that metformin represses cell cycle progression, thereby inducing subG1 populations, and had induced apoptosis through downregulation of p53 protein and a target gene, differentiated embryo chondrocyte 1 (DEC1).	Metformin	26-35	tumor protein p53	Homo sapiens	158-161
30442142-9	2018	Examination of the mechanisms underlying metformin-induced HeLa cell death revealed that reduced stability of p53 in metformin-treated cells leads to decreases in DEC1 and induction of apoptosis.	Metformin	41-50	tumor protein p53	Homo sapiens	110-113
30442142-9	2018	Examination of the mechanisms underlying metformin-induced HeLa cell death revealed that reduced stability of p53 in metformin-treated cells leads to decreases in DEC1 and induction of apoptosis.	Metformin	117-126	tumor protein p53	Homo sapiens	110-113
30442142-10	2018	CONCLUSION: The involvement of DEC1 provides new insight into the positive or negative functional roles of p53 in the metformin-induced cytotoxicity in tumor cells.	Metformin	118-127	tumor protein p53	Homo sapiens	107-110
30098371-7	2018	In our project we aim to understand the effects of metformin on p53 and DNA-BER system based on the oxidative status in type 2 diabetes patients.	Metformin	51-60	tumor protein p53	Homo sapiens	64-67
30098371-10	2018	Although the increase in DNA pol beta was not significant, XRCC1 and p53 levels were significantly upregulated with metformin treatment in type 2 diabetes patients.	Metformin	116-125	tumor protein p53	Homo sapiens	69-72
30294927-4	2018	The data demonstrated that nuciferine significantly reduced metformin accumulation in MDCK cells stably expressing human OCT1 (MDCK-hOCT1) or hMATE1 (MDCK-hMATE1), and primary cultured mouse hepatocytes.	Metformin	60-69	solute carrier family 22 member 1	Homo sapiens	121-125
30294927-5	2018	Furthermore, the presence of nuciferine in the basal compartment caused a concentration-dependent reduction of intracellular metformin accumulation in MDCK-hOCT1/hMATE1 cell monolayers.	Metformin	125-134	solute carrier family 22 member 1	Homo sapiens	156-161
30172698-2	2018	In a previous study, we found that the addition of metformin to nivolumab, an anti-programmed cell death protein 1 (PD-1) antibody, yielded substantial tumor regression in mouse models.	Metformin	51-60	programmed cell death 1	Mus musculus	83-114
30172698-2	2018	In a previous study, we found that the addition of metformin to nivolumab, an anti-programmed cell death protein 1 (PD-1) antibody, yielded substantial tumor regression in mouse models.	Metformin	51-60	programmed cell death 1	Mus musculus	116-120
29630425-0	2018	Suppressive effects of metformin on T-helper 1-related chemokines expression in the human monocytic leukemia cell line THP-1.	Metformin	23-32	GLI family zinc finger 2	Homo sapiens	119-124
29630425-4	2018	We investigated the anti-inflammatory mechanism of metformin in the human monocytic leukemia cell line THP-1.	Metformin	51-60	GLI family zinc finger 2	Homo sapiens	103-108
29630425-5	2018	MATERIALS AND METHODS: The human monocytic leukemia cell line THP-1 was pretreated with metformin and stimulated with lipopolysaccharide (LPS).	Metformin	88-97	GLI family zinc finger 2	Homo sapiens	62-67
29630425-8	2018	RESULTS: Metformin suppressed LPS-induced IP-10 and MCP-1 production as well as LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38, extracellular signal-regulated kinase (ERK), and nuclear factor-kappa B (NF-kappaB).	Metformin	9-18	mitogen-activated protein kinase 1	Homo sapiens	147-184
29630425-8	2018	RESULTS: Metformin suppressed LPS-induced IP-10 and MCP-1 production as well as LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38, extracellular signal-regulated kinase (ERK), and nuclear factor-kappa B (NF-kappaB).	Metformin	9-18	mitogen-activated protein kinase 1	Homo sapiens	186-189
29630425-8	2018	RESULTS: Metformin suppressed LPS-induced IP-10 and MCP-1 production as well as LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38, extracellular signal-regulated kinase (ERK), and nuclear factor-kappa B (NF-kappaB).	Metformin	9-18	nuclear factor kappa B subunit 1	Homo sapiens	196-218
29630425-8	2018	RESULTS: Metformin suppressed LPS-induced IP-10 and MCP-1 production as well as LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38, extracellular signal-regulated kinase (ERK), and nuclear factor-kappa B (NF-kappaB).	Metformin	9-18	nuclear factor kappa B subunit 1	Homo sapiens	220-229
29630425-10	2018	CONCLUSIONS: Metformin suppressed the production of Th1-related chemokines IP-10 and MCP-1 in THP-1 cells.	Metformin	13-22	negative elongation factor complex member C/D, Th1l	Mus musculus	52-55
29630425-10	2018	CONCLUSIONS: Metformin suppressed the production of Th1-related chemokines IP-10 and MCP-1 in THP-1 cells.	Metformin	13-22	GLI family zinc finger 2	Homo sapiens	94-99
29630425-11	2018	Suppressive effects of metformin on IP-10 production might be attributed at least partially to the JNK, p38, ERK, and NF-kappaB pathways as well as to epigenetic regulation through the acetylation of histones H3 and H4.	Metformin	23-32	mitogen-activated protein kinase 8	Homo sapiens	99-102
29630425-11	2018	Suppressive effects of metformin on IP-10 production might be attributed at least partially to the JNK, p38, ERK, and NF-kappaB pathways as well as to epigenetic regulation through the acetylation of histones H3 and H4.	Metformin	23-32	mitogen-activated protein kinase 1	Homo sapiens	104-107
29630425-11	2018	Suppressive effects of metformin on IP-10 production might be attributed at least partially to the JNK, p38, ERK, and NF-kappaB pathways as well as to epigenetic regulation through the acetylation of histones H3 and H4.	Metformin	23-32	mitogen-activated protein kinase 1	Homo sapiens	109-112
29630425-11	2018	Suppressive effects of metformin on IP-10 production might be attributed at least partially to the JNK, p38, ERK, and NF-kappaB pathways as well as to epigenetic regulation through the acetylation of histones H3 and H4.	Metformin	23-32	nuclear factor kappa B subunit 1	Homo sapiens	118-127
30389502-0	2018	The antineoplastic drug metformin downregulates YAP by interfering with IRF-1 binding to the YAP promoter in NSCLC.	Metformin	24-33	interferon regulatory factor 1	Homo sapiens	72-77
30389502-11	2018	Mechanistically, we found that metformin depressed YAP promoter by competing with the binding of the transcription factor IRF-1 in lung cancer cells.	Metformin	31-40	interferon regulatory factor 1	Homo sapiens	122-127
30389502-13	2018	INTERPRETATION: we concluded that metformin depresses YAP promoter by interfering with the binding of the transcription factor IRF-1.	Metformin	34-43	interferon regulatory factor 1	Homo sapiens	127-132
30536344-5	2018	MATERIALS AND METHODS: Osteoblast-marker genes, including Col-1, OCN, and RUNX2, were measured by RT-PCR in differentiated MSCs treated with Metformin.	Metformin	141-150	bone gamma-carboxyglutamate protein	Homo sapiens	65-68
30536344-5	2018	MATERIALS AND METHODS: Osteoblast-marker genes, including Col-1, OCN, and RUNX2, were measured by RT-PCR in differentiated MSCs treated with Metformin.	Metformin	141-150	RUNX family transcription factor 2	Homo sapiens	74-79
29529690-7	2018	High-dose metformin treatment reduced circulating levels of FSH and tended to reduce serum levels of LH, and these effects correlated with an improvement in insulin sensitivity.	Metformin	10-19	insulin	Homo sapiens	157-164
29529690-10	2018	CONCLUSIONS: Our study shows that the effect of metformin on hypothalamic-pituitary-ovarian axis activity in postmenopausal women depends on its dose and the magnitude of insulin resistance.	Metformin	48-57	insulin	Homo sapiens	171-178
30375241-5	2018	The transporter variants identified to have an important influence on the absorption, distribution, and elimination of metformin, particularly those in organic cation transporter 1 (OCT1, gene SLC22A1), are reviewed.	Metformin	119-128	solute carrier family 22 member 1	Homo sapiens	193-200
30479698-0	2018	A phase 2 trial of neoadjuvant metformin in combination with trastuzumab and chemotherapy in women with early HER2-positive breast cancer: the METTEN study.	Metformin	31-40	erb-b2 receptor tyrosine kinase 2	Homo sapiens	110-114
30375241-5	2018	The transporter variants identified to have an important influence on the absorption, distribution, and elimination of metformin, particularly those in organic cation transporter 1 (OCT1, gene SLC22A1), are reviewed.	Metformin	119-128	solute carrier family 22 member 1	Homo sapiens	152-180
30375241-5	2018	The transporter variants identified to have an important influence on the absorption, distribution, and elimination of metformin, particularly those in organic cation transporter 1 (OCT1, gene SLC22A1), are reviewed.	Metformin	119-128	solute carrier family 22 member 1	Homo sapiens	182-186
30872064-9	2019	CONCLUSIONS: BIAsp 30 administered either TID or BID with metformin was a safe and effective option when intensifying treatment after failure of basal insulin and OADs in patients with T2DM.	Metformin	58-67	BH3 interacting domain death agonist	Homo sapiens	49-52
30188871-0	2018	Metformin Regulates the Expression of SK2 and SK3 in the Atria of Rats With Type 2 Diabetes Mellitus Through the NOX4/p38MAPK Signaling Pathway.	Metformin	0-9	potassium calcium-activated channel subfamily N member 2	Rattus norvegicus	38-41
30188871-1	2018	We previously found that metformin regulates the ion current conducted by the small conductance calcium-activated potassium channels (SK channels) in the atria of rats with type 2 diabetes mellitus (T2DM) as well as the mRNA and protein expression of the SK2 and SK3 subtypes of SK channels.	Metformin	25-34	potassium calcium-activated channel subfamily N member 2	Rattus norvegicus	255-258
30188871-2	2018	In this study, we hypothesized that the nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4)/p38 mitogen-activated protein kinase (p38MAPK) signaling pathway was involved in the metformin-mediated regulation of SK2 and SK3 expression in the atria of rats with T2DM.	Metformin	186-195	potassium calcium-activated channel subfamily N member 2	Rattus norvegicus	219-222
30188871-7	2018	The 8-week treatment with metformin markedly reduced the expression levels of NOX4 mRNA and protein and p-p38MAPK protein, upregulated the SK2 expression, and downregulated the SK3 expression.	Metformin	26-35	potassium calcium-activated channel subfamily N member 2	Rattus norvegicus	139-142
30188871-12	2018	Long-term metformin treatment upregulates SK2 protein expression and downregulates SK3 protein expression by inhibiting the NOX4/p38MAPK signaling pathway.	Metformin	10-19	potassium calcium-activated channel subfamily N member 2	Rattus norvegicus	42-45
29788487-10	2018	Statistically significant group differences (ie, percent change in metformin group minus placebo group) were -7.9% (95% CI = -15.0% to -0.8%) for insulin, -10.0% (95% CI = -18.5% to -1.5%) for estradiol, -9.5% (95% CI = -15.2% to -3.8%) for testosterone, and 7.5% (95% CI = 2.4% to 12.6%) for SHBG.	Metformin	67-76	insulin	Homo sapiens	146-153
30333878-0	2018	Metformin reverses the resistance mechanism of lung adenocarcinoma cells that knocks down the Nrf2 gene.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	94-98
30333878-2	2018	However, it has remained elusive whether metformin affects Nrf2 and regulates Nrf2/ARE in adenocarcinoma.	Metformin	41-50	NFE2 like bZIP transcription factor 2	Homo sapiens	78-82
30333878-4	2018	The results indicated that Nrf2, glutathione S-transferase alpha 1 (GSTA1) and ATP-binding cassette subfamily C member 1 (ABCC1) were dose-dependently reduced by metformin, and that the effect in A549 cells was greater than that in A549/DDP cells.	Metformin	162-171	NFE2 like bZIP transcription factor 2	Homo sapiens	27-31
30333878-4	2018	The results indicated that Nrf2, glutathione S-transferase alpha 1 (GSTA1) and ATP-binding cassette subfamily C member 1 (ABCC1) were dose-dependently reduced by metformin, and that the effect in A549 cells was greater than that in A549/DDP cells.	Metformin	162-171	ATP binding cassette subfamily C member 1	Homo sapiens	79-120
30333878-4	2018	The results indicated that Nrf2, glutathione S-transferase alpha 1 (GSTA1) and ATP-binding cassette subfamily C member 1 (ABCC1) were dose-dependently reduced by metformin, and that the effect in A549 cells was greater than that in A549/DDP cells.	Metformin	162-171	ATP binding cassette subfamily C member 1	Homo sapiens	122-127
30333878-6	2018	After transfection of A549/DDP cells with Nrf2 short hairpin RNA (shRNA), GSTA1 and ABCC1 were markedly decreased, compared with the shRNA-control group of A549/DDP, and low dose-metformin reduced the proliferation and increased apoptosis of A549/DDP cells.	Metformin	179-188	NFE2 like bZIP transcription factor 2	Homo sapiens	42-46
30333878-7	2018	Metformin inhibited the Akt and extracellular signal-regulated kinase (ERK)1/2 pathways in A549 cells and activated the p38 MAPK and c-Jun N-terminal kinase (JNK) pathways.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	24-27
30333878-7	2018	Metformin inhibited the Akt and extracellular signal-regulated kinase (ERK)1/2 pathways in A549 cells and activated the p38 MAPK and c-Jun N-terminal kinase (JNK) pathways.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	32-78
30333878-7	2018	Metformin inhibited the Akt and extracellular signal-regulated kinase (ERK)1/2 pathways in A549 cells and activated the p38 MAPK and c-Jun N-terminal kinase (JNK) pathways.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	120-123
30333878-7	2018	Metformin inhibited the Akt and extracellular signal-regulated kinase (ERK)1/2 pathways in A549 cells and activated the p38 MAPK and c-Jun N-terminal kinase (JNK) pathways.	Metformin	0-9	mitogen-activated protein kinase 8	Homo sapiens	133-156
30333878-7	2018	Metformin inhibited the Akt and extracellular signal-regulated kinase (ERK)1/2 pathways in A549 cells and activated the p38 MAPK and c-Jun N-terminal kinase (JNK) pathways.	Metformin	0-9	mitogen-activated protein kinase 8	Homo sapiens	158-161
30333878-8	2018	Furthermore, in the presence of metformin, inhibitors of the p38 MAPK and JNK signaling pathway at different concentrations did not affect the levels of Nrf2, but inhibitors of the Akt and ERK1/2 pathway at different doses reduced the expression of Nrf2.	Metformin	32-41	mitogen-activated protein kinase 1	Homo sapiens	61-64
30333878-8	2018	Furthermore, in the presence of metformin, inhibitors of the p38 MAPK and JNK signaling pathway at different concentrations did not affect the levels of Nrf2, but inhibitors of the Akt and ERK1/2 pathway at different doses reduced the expression of Nrf2.	Metformin	32-41	mitogen-activated protein kinase 3	Homo sapiens	65-69
30333878-8	2018	Furthermore, in the presence of metformin, inhibitors of the p38 MAPK and JNK signaling pathway at different concentrations did not affect the levels of Nrf2, but inhibitors of the Akt and ERK1/2 pathway at different doses reduced the expression of Nrf2.	Metformin	32-41	mitogen-activated protein kinase 8	Homo sapiens	74-77
30333878-9	2018	In addition, inhibitors of p38 MAPK and JNK did not affect the effect of metformin on Nrf2, while inhibitors of Akt and ERK1/2 dose-dependently enhanced the inhibitory effects of metformin in A549 cells.	Metformin	179-188	mitogen-activated protein kinase 3	Homo sapiens	31-35
30333878-9	2018	In addition, inhibitors of p38 MAPK and JNK did not affect the effect of metformin on Nrf2, while inhibitors of Akt and ERK1/2 dose-dependently enhanced the inhibitory effects of metformin in A549 cells.	Metformin	179-188	AKT serine/threonine kinase 1	Homo sapiens	112-115
30333878-9	2018	In addition, inhibitors of p38 MAPK and JNK did not affect the effect of metformin on Nrf2, while inhibitors of Akt and ERK1/2 dose-dependently enhanced the inhibitory effects of metformin in A549 cells.	Metformin	179-188	mitogen-activated protein kinase 3	Homo sapiens	120-126
30333878-10	2018	In conclusion, metformin inhibits the phosphoinositide-3 kinase/Akt and ERK1/2 signaling pathways in A549 cells to reduce the expression of Nrf2, GSTA1 and ABCC1.	Metformin	15-24	AKT serine/threonine kinase 1	Homo sapiens	64-67
30333878-10	2018	In conclusion, metformin inhibits the phosphoinositide-3 kinase/Akt and ERK1/2 signaling pathways in A549 cells to reduce the expression of Nrf2, GSTA1 and ABCC1.	Metformin	15-24	mitogen-activated protein kinase 3	Homo sapiens	72-78
30333878-10	2018	In conclusion, metformin inhibits the phosphoinositide-3 kinase/Akt and ERK1/2 signaling pathways in A549 cells to reduce the expression of Nrf2, GSTA1 and ABCC1.	Metformin	15-24	NFE2 like bZIP transcription factor 2	Homo sapiens	140-144
30333878-10	2018	In conclusion, metformin inhibits the phosphoinositide-3 kinase/Akt and ERK1/2 signaling pathways in A549 cells to reduce the expression of Nrf2, GSTA1 and ABCC1.	Metformin	15-24	ATP binding cassette subfamily C member 1	Homo sapiens	156-161
30266241-8	2018	Moreover, metformin could elevate DOX-induced apoptosis in DU145 cells in a concentration-dependent manner and DOX-induced caspase-3 activity.	Metformin	10-19	caspase 3	Homo sapiens	123-132
30266241-9	2018	These findings suggest that the combined treatment of metformin with DOX potentiates the anticancer efficacy of DOX in DU145 cells via inhibiting ABCB1 function, cell cycle arrest at G1/S transition and apoptosis induction.	Metformin	54-63	ATP binding cassette subfamily B member 1	Homo sapiens	146-151
29943489-10	2018	CONCLUSION: Among all types of ADT and insulin therapies, metformin is the only agent with a decreased risk of active TB in the T2DM population.	Metformin	58-67	insulin	Homo sapiens	39-46
29959433-15	2018	While metformin led to weight loss, both metformin and minocycline significantly decreased neuroinflammation in the assessment of cord tissue histopathology, and levels of TNF-alpha and interleukin-1beta (p &lt; 0.001).	Metformin	41-50	tumor necrosis factor	Rattus norvegicus	172-181
29959433-15	2018	While metformin led to weight loss, both metformin and minocycline significantly decreased neuroinflammation in the assessment of cord tissue histopathology, and levels of TNF-alpha and interleukin-1beta (p &lt; 0.001).	Metformin	41-50	interleukin 1 beta	Rattus norvegicus	186-203
30378162-11	2018	Western blot analysis showed increased protein levels of pTie-2/Tie2 and Pakt/AKT in cEPCs harvested from T2DM, treated with insulin metformin plus.	Metformin	133-142	AKT serine/threonine kinase 1	Homo sapiens	78-81
30378162-11	2018	Western blot analysis showed increased protein levels of pTie-2/Tie2 and Pakt/AKT in cEPCs harvested from T2DM, treated with insulin metformin plus.	Metformin	133-142	insulin	Homo sapiens	125-132
30800266-2	2019	After the advent of long-acting insulin, the first oral agents, sulfonylureas became available in the mid-1950s, quickly followed (outside of the United States) by metformin.	Metformin	164-173	insulin	Homo sapiens	32-39
30347712-8	2018	Metformin reduced miR-222, miR-195 and miR-21a levels in TG; p = 0.007, p = 0.002 p = 0.0012, respectively.	Metformin	0-9	microRNA 195	Homo sapiens	27-34
30347712-13	2018	Metformin has cardioprotective effects through downregulating miR-222, miR-195 and miR-21a, beyond improving glycemic control.	Metformin	0-9	microRNA 195	Homo sapiens	71-78
30337733-1	2018	OBJECTIVE: To determine the effect of metformin and adiponectin on the proliferation of EC cells and the relationship between metformin and adiponectin.	Metformin	126-135	adiponectin, C1Q and collagen domain containing	Homo sapiens	140-151
30337733-3	2018	qRT-PCR and Western blot were used to detect the effect of different concentrations of metformin on the changes of adiponectin receptors (AdipoR1 and AdipoR2) of the EC cells both in mRNA and protein level and the role of compound C, an adenosine monophosphate-activated protein kinase (AMPK) inhibitor, on the above effects.	Metformin	87-96	adiponectin, C1Q and collagen domain containing	Homo sapiens	115-126
30337733-5	2018	(2)Metformin and adiponectin had synergy anti-proliferative effect on EC cells and the combination index (CI) value of IK cells was 0.906 34 and of HEC-1B cells was 0.827 65.	Metformin	3-12	NDC80 kinetochore complex component	Homo sapiens	148-153
30337733-11	2018	Besides, metformin can increase adiponectin receptors expressions of EC cells both in mRNA and protein levels and this effect is accomplished by the activation of AMPK signaling pathway.	Metformin	9-18	adiponectin, C1Q and collagen domain containing	Homo sapiens	32-43
30326091-0	2018	Metformin use was linked to hospitalization for acidosis at 6 y only in patients with eGFR &lt; 30 mL/min/1.73 m2.	Metformin	0-9	epidermal growth factor receptor	Homo sapiens	86-90
30326091-0	2018	Metformin use was linked to hospitalization for acidosis at 6 y only in patients with eGFR &lt; 30 mL/min/1.73 m2.	Metformin	0-9	CD59 molecule (CD59 blood group)	Homo sapiens	102-107
30416652-10	2018	The Western blotting results revealed that metformin and cisplatin co-treatment inhibited TGFbeta1 expression and Smad2 and Smad3 phosphorylation.	Metformin	43-52	transforming growth factor beta 1	Homo sapiens	90-98
30321183-0	2018	The association of metformin use with vitamin B12 deficiency and peripheral neuropathy in Saudi individuals with type 2 diabetes mellitus.	Metformin	19-28	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	46-49
30321183-8	2018	RESULTS: The prevalence of B12 deficiency was 7.8% overall, but 9.4% and 2.2% in metformin users and non-metformin users, respectively.	Metformin	105-114	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	27-30
30321183-9	2018	The odds ratio for serum vitamin B12 deficiency in metformin users was 4.72 (95% CI, 1.11-20.15, P = 0.036).	Metformin	51-60	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	33-36
30321183-11	2018	Low levels of vitamin B12 occurred when metformin was taken at a dose of more than 2,000 mg/day (AOR, 21.67; 95% CI, 2.87-163.47) or for more than 4 years (AOR, 6.35; 95% CI, 1.47-24.47).	Metformin	40-49	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	22-25
30321183-12	2018	CONCLUSION: Individuals with T2DM treated with metformin, particularly those who use metformin at large dosages (&gt; 2,000 mg/day) and for a longer duration (&gt; 4 years), should be regularly screened for vitamin B12 deficiency and metformin is associated with B12 deficiency, but this is not associated with peripheral neuropathy.	Metformin	47-56	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	215-218
30321183-12	2018	CONCLUSION: Individuals with T2DM treated with metformin, particularly those who use metformin at large dosages (&gt; 2,000 mg/day) and for a longer duration (&gt; 4 years), should be regularly screened for vitamin B12 deficiency and metformin is associated with B12 deficiency, but this is not associated with peripheral neuropathy.	Metformin	47-56	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	263-266
30321183-12	2018	CONCLUSION: Individuals with T2DM treated with metformin, particularly those who use metformin at large dosages (&gt; 2,000 mg/day) and for a longer duration (&gt; 4 years), should be regularly screened for vitamin B12 deficiency and metformin is associated with B12 deficiency, but this is not associated with peripheral neuropathy.	Metformin	85-94	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	215-218
30321183-12	2018	CONCLUSION: Individuals with T2DM treated with metformin, particularly those who use metformin at large dosages (&gt; 2,000 mg/day) and for a longer duration (&gt; 4 years), should be regularly screened for vitamin B12 deficiency and metformin is associated with B12 deficiency, but this is not associated with peripheral neuropathy.	Metformin	85-94	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	263-266
30321183-12	2018	CONCLUSION: Individuals with T2DM treated with metformin, particularly those who use metformin at large dosages (&gt; 2,000 mg/day) and for a longer duration (&gt; 4 years), should be regularly screened for vitamin B12 deficiency and metformin is associated with B12 deficiency, but this is not associated with peripheral neuropathy.	Metformin	85-94	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	215-218
30321183-12	2018	CONCLUSION: Individuals with T2DM treated with metformin, particularly those who use metformin at large dosages (&gt; 2,000 mg/day) and for a longer duration (&gt; 4 years), should be regularly screened for vitamin B12 deficiency and metformin is associated with B12 deficiency, but this is not associated with peripheral neuropathy.	Metformin	85-94	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	263-266
30308035-0	2018	Anti-metastatic effect of metformin via repression of interleukin 6-induced epithelial-mesenchymal transition in human colon cancer cells.	Metformin	26-35	interleukin 6	Homo sapiens	54-67
30308035-2	2018	Although inhibition of the mTOR pathway is known to be the most important mechanism for the antitumor effects of metformin, other mechanisms remain unclear.	Metformin	113-122	mechanistic target of rapamycin kinase	Homo sapiens	27-31
30308035-7	2018	Furthermore, pathway analysis revealed that the metformin-predicted group was characterized by decreased interleukin (IL)-6 pathway signaling, epithelial-mesenchymal transition, and colon cancer metastatic signaling.	Metformin	48-57	interleukin 6	Homo sapiens	105-123
30308035-10	2018	These findings suggest that blockade of IL-6-induced epithelial-mesenchymal transition is an antitumor mechanism of metformin.	Metformin	116-125	interleukin 6	Homo sapiens	40-44
30533337-5	2018	Metformin effects on prostate cancer, notably its therapeutic targets shared with antiandrogens and/or PI3K/Akt inhibitors, are reviewed in this article.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	108-111
30533337-6	2018	From that, the hypothesis of PI3K/Akt-antiandrogens dual blockade optimization by metformin addition in CRPC will be deduced.	Metformin	82-91	AKT serine/threonine kinase 1	Homo sapiens	34-37
30275441-0	2018	Metformin Increases Cardiac Rupture After Myocardial Infarction via the AMPK-MTOR/PGC-1alpha Signaling Pathway in Rats with Acute Myocardial Infarction.	Metformin	0-9	PPARG coactivator 1 alpha	Rattus norvegicus	82-92
29726717-4	2018	Concomitant administration of metformin and Zn produced a significant decrease in serum levels of glucose and insulin and testicular levels of malondialdehyde and tumor necrosis factor alpha.	Metformin	30-39	tumor necrosis factor	Rattus norvegicus	163-190
29726717-6	2018	Moreover, co-administration of Zn and metformin significantly improved testicular histopathology, with a significant reduction in percent area of collagen fibers and nuclear factor kappa B (p65) immunoreactivity and a significant increase in seminiferous tubule diameter and connexin 43 immunoreactivity as compared with the diabetic and metformin-treated diabetic groups.	Metformin	38-47	synaptotagmin 1	Rattus norvegicus	190-193
29726717-6	2018	Moreover, co-administration of Zn and metformin significantly improved testicular histopathology, with a significant reduction in percent area of collagen fibers and nuclear factor kappa B (p65) immunoreactivity and a significant increase in seminiferous tubule diameter and connexin 43 immunoreactivity as compared with the diabetic and metformin-treated diabetic groups.	Metformin	38-47	gap junction protein, alpha 1	Rattus norvegicus	275-286
30138624-2	2018	The substrates and inhibitors of hOCT1 are structurally and physiochemically diverse and include some widely prescribed drugs (metformin and imatinib), vitamins (thiamine), and neurotransmitters (serotonin).	Metformin	127-136	solute carrier family 22 member 1	Homo sapiens	33-38
30222970-0	2018	Metformin downregulates the mitochondrial carrier SLC25A10 in a glucose dependent manner.	Metformin	0-9	solute carrier family 25 member 10	Homo sapiens	50-58
30222970-3	2018	In this study we addressed the role of a mitochondrial transporter commonly upregulated in cancer cells, SLC25A10, for cell survival and metabolism in the presence of metformin.	Metformin	167-176	solute carrier family 25 member 10	Homo sapiens	105-113
30222970-5	2018	We show that metformin treatment results in decreased gene expression of the SLC25A10 carrier both in lung cancer A549 mock cells and A549 SLC25A10 knockdown (siSLC25A10) cells.	Metformin	13-22	solute carrier family 25 member 10	Homo sapiens	77-85
30222970-5	2018	We show that metformin treatment results in decreased gene expression of the SLC25A10 carrier both in lung cancer A549 mock cells and A549 SLC25A10 knockdown (siSLC25A10) cells.	Metformin	13-22	solute carrier family 25 member 10	Homo sapiens	139-147
30222970-9	2018	In addition, the gene expression of the cyclin-dependent kinase inhibitor 1A was markedly increased in the siSLC25A10 compared to control A549 cells, and with even larger increases in the presence of metformin and at low glucose concentration.	Metformin	200-209	cyclin dependent kinase inhibitor 1A	Homo sapiens	40-76
30222970-10	2018	Our data show that in siSLC25A10 cell lines, metformin significantly alters the SLC25A10 carrier at both mRNA and protein levels and can thereby affect the supply of nutrients and the metabolic state of cancer cells.	Metformin	45-54	solute carrier family 25 member 10	Homo sapiens	24-32
30119191-2	2018	Metformin is a first-line antihyperglycemic agent that works mainly by regulating hepatic glucose production and peripheral insulin sensitivity.	Metformin	0-9	insulin	Homo sapiens	124-131
29334602-7	2018	The combination of TMZ and metformin enhanced AMPK phosphorylation and inhibited mammalian target of rapamycin phosphorylation, AKT phosphorylation, and p53 expression.	Metformin	27-36	AKT serine/threonine kinase 1	Homo sapiens	128-131
29334602-7	2018	The combination of TMZ and metformin enhanced AMPK phosphorylation and inhibited mammalian target of rapamycin phosphorylation, AKT phosphorylation, and p53 expression.	Metformin	27-36	tumor protein p53	Homo sapiens	153-156
30132243-0	2018	Metformin Plus Caloric Restriction Show Anti-epileptic Effects Mediated by mTOR Pathway Inhibition.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	75-79
30058059-13	2018	CONCLUSION: DPP-4 inhibitors, followed by metformin, were the most frequently prescribed OADGs in combination with insulin in a real-world setting in Japan.	Metformin	42-51	insulin	Homo sapiens	115-122
30058059-14	2018	The diabetologists considered more drug characteristics for DPP-4 inhibitor or metformin-insulin combinations.	Metformin	79-88	insulin	Homo sapiens	89-96
30209797-3	2018	Current data suggest that adding metformin to insulin therapy in T1DM temporarily lowers HbA1c and reduces weight and insulin requirements, but this treatment fails to show a longer-term glycaemic benefit.	Metformin	33-42	insulin	Homo sapiens	118-125
30259865-3	2018	In breast cancer cell lines, metformin has been shown to induce phosphorylation at specific serine sites in insulin regulated substrate of mTOR pathway that results in apoptosis over cell proliferation.	Metformin	29-38	insulin	Homo sapiens	108-115
30259865-3	2018	In breast cancer cell lines, metformin has been shown to induce phosphorylation at specific serine sites in insulin regulated substrate of mTOR pathway that results in apoptosis over cell proliferation.	Metformin	29-38	mechanistic target of rapamycin kinase	Homo sapiens	139-143
30259865-4	2018	The author models and performs bifurcation analysis to simulate cell proliferation and apoptosis in mTOR signalling pathway to capture the dynamics both in the presence and absence of metformin in cancer cells.	Metformin	184-193	mechanistic target of rapamycin kinase	Homo sapiens	100-104
30259865-5	2018	Metformin is shown to negatively regulate PI3K through AMPK induced IRS1 phosphorylation and this brings about a reversal of AKT bistablity in codimension-1 bifurcation diagram from S-shaped, related to cell proliferation in the absence of drug metformin, to Z-shaped, related to apoptosis in the presence of drug metformin.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	125-128
30259865-5	2018	Metformin is shown to negatively regulate PI3K through AMPK induced IRS1 phosphorylation and this brings about a reversal of AKT bistablity in codimension-1 bifurcation diagram from S-shaped, related to cell proliferation in the absence of drug metformin, to Z-shaped, related to apoptosis in the presence of drug metformin.	Metformin	245-254	AKT serine/threonine kinase 1	Homo sapiens	125-128
30259865-5	2018	Metformin is shown to negatively regulate PI3K through AMPK induced IRS1 phosphorylation and this brings about a reversal of AKT bistablity in codimension-1 bifurcation diagram from S-shaped, related to cell proliferation in the absence of drug metformin, to Z-shaped, related to apoptosis in the presence of drug metformin.	Metformin	314-323	AKT serine/threonine kinase 1	Homo sapiens	125-128
29392539-9	2018	The effects of metformin and aspirin partly relied on cyclooxygenase-2 (COX-2) upregulation, without the production of lipoxins.	Metformin	15-24	prostaglandin-endoperoxide synthase 2	Homo sapiens	54-70
29392539-9	2018	The effects of metformin and aspirin partly relied on cyclooxygenase-2 (COX-2) upregulation, without the production of lipoxins.	Metformin	15-24	prostaglandin-endoperoxide synthase 2	Homo sapiens	72-77
30787519-15	2018	There was a reduction in AMH in all groups of insulin sensitizers with significant fall in the metformin only group.	Metformin	95-104	insulin	Homo sapiens	46-53
30307162-4	2018	Inclusion of metformin during palmitate exposure normalized insulin secretion both after 2 and 7 days.	Metformin	13-22	insulin	Homo sapiens	60-67
30307162-8	2018	Presence of metformin during 7-day culture with palmitate normalized the level of p-AMPK, p-EIF2alpha, CHOP and cleaved caspase 3 but significantly increased the level of sorcin.	Metformin	12-21	DNA damage inducible transcript 3	Homo sapiens	103-107
30307162-9	2018	Our study demonstrates that metformin prevents early insulin hypersecretion and later decrease in insulin secretion from palmitate-treated human islets by utilizing different mechanisms.	Metformin	28-37	insulin	Homo sapiens	53-60
30224835-4	2018	So various trials have tried to compare metformin (an insulin-sensitizing agent) and orlistat (an anti-obesity drug) aiming to achieve weight loss and hence higher ovulation rate for the group of obese PCOS patients.	Metformin	40-49	insulin	Homo sapiens	54-61
29921847-0	2018	Metformin sensitizes endometrial cancer cells to chemotherapy through IDH1-induced Nrf2 expression via an epigenetic mechanism.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	83-87
29921847-12	2018	Dot blot and HMeDIP assays revealed that metformin blocked IDH1-alpha-KG-TET1-mediated enhancement of Nrf2 hydroxymethylation levels, eliminating chemoresistance.	Metformin	41-50	NFE2 like bZIP transcription factor 2	Homo sapiens	102-106
29921847-14	2018	Our findings highlight a critical role of IDH1-alpha-KG-TET1-Nrf2 signaling in chemoresistance and suggest that rational combination therapy with metformin and chemotherapeutics has the potential to suppress chemoresistance.	Metformin	146-155	NFE2 like bZIP transcription factor 2	Homo sapiens	61-65
30275489-0	2018	Metabolic profiling of metformin treatment for low-level Pb-induced nephrotoxicity in rat urine.	Metformin	23-32	serine peptidase inhibitor, Kunitz type, 2	Rattus norvegicus	57-59
29877750-8	2018	Our results showed that metformin attenuated ROS generation, downregulated pro-apoptotic BAX expression, and upregulated expression of the Bcl-2 protein in the PC12 cells.	Metformin	24-33	BCL2, apoptosis regulator	Rattus norvegicus	139-144
30178023-9	2018	Recommendation 2: Introduce human insulin treatment to patients with type 2 diabetes who do not achieve glycemic control with metformin and/or a sulfonylurea (strong recommendation, very-low-quality evidence).	Metformin	126-135	insulin	Homo sapiens	34-41
30146065-6	2018	Metformin significantly reduced the GDF15 production from treatment-damaged HCC cells by targeting JNK.	Metformin	0-9	mitogen-activated protein kinase 8	Homo sapiens	99-102
30118770-10	2018	The in vitro experimental results showed that both catalpol and metformin enhanced glucose uptake via activation of PI3K/AKT pathway.	Metformin	64-73	thymoma viral proto-oncogene 1	Mus musculus	121-124
30217067-0	2018	Hyperglycemia-Associated Dysregulation of O-GlcNAcylation and HIF1A Reduces Anticancer Action of Metformin in Ovarian Cancer Cells (SKOV-3).	Metformin	97-106	hypoxia inducible factor 1 subunit alpha	Homo sapiens	62-67
30217067-9	2018	Both hyperglycemia and metformin induced changes in the expression of genes involved in the O-GlcNAcylation status and HIF1A pathway.	Metformin	23-32	hypoxia inducible factor 1 subunit alpha	Homo sapiens	119-124
30217067-10	2018	The obtained results suggest that dysregulation of O-GlcNAcylation, and the related HIF1A pathway, via hyperglycemia, is responsible for the decreased cytotoxic efficiency of metformin in human ovarian cancer cells.	Metformin	175-184	hypoxia inducible factor 1 subunit alpha	Homo sapiens	84-89
30206377-7	2018	We were able to show in vivo that reducing phospho-STAT3-miR-21 levels in C57/BL6 mice liver, by long-term treatment with metformin, protected mice from aging-dependent hepatic vesicular steatosis.	Metformin	122-131	signal transducer and activator of transcription 3	Mus musculus	51-56
30017187-3	2018	In human granulosa cells, it was found that metformin treatment suppressed phosphorylation of Smad1/5/9 activated by BMP-15 compared with that induced by other BMP ligands.	Metformin	44-53	bone morphogenetic protein 15	Homo sapiens	117-123
30017187-3	2018	In human granulosa cells, it was found that metformin treatment suppressed phosphorylation of Smad1/5/9 activated by BMP-15 compared with that induced by other BMP ligands.	Metformin	44-53	bone morphogenetic protein 15	Homo sapiens	117-120
30017187-5	2018	Thus, the mechanism by which metformin suppresses BMP-15-induced Smad1/5/9 phosphorylation is likely, at least in part, to be upregulation of inhibitory Smad6 expression in granulosa cells.	Metformin	29-38	bone morphogenetic protein 15	Homo sapiens	50-56
30017187-6	2018	The results suggest the existence of functional interaction between metformin and BMP signaling, in which metformin enhances progesterone production by downregulating endogenous BMP-15 activity in granulosa cells.	Metformin	68-77	bone morphogenetic protein 15	Homo sapiens	178-184
30017187-6	2018	The results suggest the existence of functional interaction between metformin and BMP signaling, in which metformin enhances progesterone production by downregulating endogenous BMP-15 activity in granulosa cells.	Metformin	106-115	bone morphogenetic protein 15	Homo sapiens	82-85
30017187-6	2018	The results suggest the existence of functional interaction between metformin and BMP signaling, in which metformin enhances progesterone production by downregulating endogenous BMP-15 activity in granulosa cells.	Metformin	106-115	bone morphogenetic protein 15	Homo sapiens	178-184
30017190-6	2018	Moreover, alpha-LA lowered the levels of O-linked beta-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells.	Metformin	189-198	thioredoxin interacting protein	Mus musculus	97-128
30017190-6	2018	Moreover, alpha-LA lowered the levels of O-linked beta-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells.	Metformin	189-198	thioredoxin interacting protein	Mus musculus	130-135
30197416-0	2018	Long-term metformin treatment in adolescents with obesity and insulin resistance, results of an open label extension study.	Metformin	10-19	insulin	Homo sapiens	62-69
30197416-3	2018	Therefore, an 18 month open label extension study following an 18 months randomized placebo-controlled trial (RCT) on the efficacy, safety, and tolerability of metformin in adolescents with obesity and insulin resistance was performed.	Metformin	160-169	insulin	Homo sapiens	202-209
30197416-4	2018	SUBJECTS/METHODS: After completion of the RCT, metformin was offered to all participants with a body mass index standard deviation score (BMI-sds) &gt; 2.3 and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) &gt;= 3.4.	Metformin	47-56	insulin	Homo sapiens	193-200
30208162-2	2018	Many antidiabetes treatments, particularly metformin, enhance insulin signaling, but this pathway can be inhibited by specific cancer treatments.	Metformin	43-52	insulin	Homo sapiens	62-69
30191328-3	2018	METHODS: The inhibition by select compounds on the uptake of the probe substrate metformin was assessed in HEK293 cells overexpressing human OCT2, OCT1, MATE1, MATE2-K, and mouse Oct2, Oct1, and Mate1.	Metformin	81-90	solute carrier family 22 member 1	Homo sapiens	147-151
30191328-3	2018	METHODS: The inhibition by select compounds on the uptake of the probe substrate metformin was assessed in HEK293 cells overexpressing human OCT2, OCT1, MATE1, MATE2-K, and mouse Oct2, Oct1, and Mate1.	Metformin	81-90	POU domain, class 2, transcription factor 2	Mus musculus	179-183
30017802-4	2018	For the EMT model, the TGF-beta-induced CRC cell lines SW480 and HCT116 were treated with metformin.	Metformin	90-99	transforming growth factor beta 1	Homo sapiens	23-31
30017802-8	2018	The up-regulation of E-cadherin and the down-regulation of vimentin for both SW480 and HCT116 cells revealed the anti-EMT abilities of metformin.	Metformin	135-144	cadherin 1	Homo sapiens	21-31
30017802-9	2018	For the [SNAIL/miR-34]:[ZEB/miR-200] system, metformin increased miR-200a, miR-200c and miR-429 levels and decreased miR-34a, SNAIL1 and ZEB1 levels in the TGF-beta-induced EMT.	Metformin	45-54	snail family transcriptional repressor 1	Homo sapiens	9-14
30017802-9	2018	For the [SNAIL/miR-34]:[ZEB/miR-200] system, metformin increased miR-200a, miR-200c and miR-429 levels and decreased miR-34a, SNAIL1 and ZEB1 levels in the TGF-beta-induced EMT.	Metformin	45-54	microRNA 200a	Homo sapiens	65-73
30017802-9	2018	For the [SNAIL/miR-34]:[ZEB/miR-200] system, metformin increased miR-200a, miR-200c and miR-429 levels and decreased miR-34a, SNAIL1 and ZEB1 levels in the TGF-beta-induced EMT.	Metformin	45-54	microRNA 429	Homo sapiens	88-95
30017802-9	2018	For the [SNAIL/miR-34]:[ZEB/miR-200] system, metformin increased miR-200a, miR-200c and miR-429 levels and decreased miR-34a, SNAIL1 and ZEB1 levels in the TGF-beta-induced EMT.	Metformin	45-54	snail family transcriptional repressor 1	Homo sapiens	126-132
30017802-9	2018	For the [SNAIL/miR-34]:[ZEB/miR-200] system, metformin increased miR-200a, miR-200c and miR-429 levels and decreased miR-34a, SNAIL1 and ZEB1 levels in the TGF-beta-induced EMT.	Metformin	45-54	transforming growth factor beta 1	Homo sapiens	156-164
30017802-10	2018	From immunofluorescence, we observed increased E-cadherin and ZEB1 co-expression in metformin-treated cells.	Metformin	84-93	cadherin 1	Homo sapiens	47-57
30017802-11	2018	Metformin may perform bidirectional regulations of the [SNAIL/miR-34]:[ZEB/miR-200] system in the EMT process for colorectal cancer.	Metformin	0-9	snail family transcriptional repressor 1	Homo sapiens	56-61
30375241-6	2018	Expert opinion: Candidate gene studies have shown that genetic variations in SLC22A1 and other drug transporters influence the pharmacokinetics, glycemic responses, and gastrointestinal intolerance to metformin, although results are somewhat discordant.	Metformin	201-210	solute carrier family 22 member 1	Homo sapiens	77-84
30286566-7	2018	Metformin is the drug of choice for young T2DM patients; if marked hyperglycemia is present, basal insulin is given with metformin.	Metformin	121-130	insulin	Homo sapiens	99-106
30176891-0	2018	Effect of metformin on the survival of patients with ALL who express high levels of the ABCB1 drug resistance gene.	Metformin	10-19	ATP binding cassette subfamily B member 1	Homo sapiens	88-93
30176891-3	2018	Therefore, the objective of this study was to assess the effect of metformin on the treatment regimen in patients with ALL who exhibited high levels of ABCB1 gene expression and to determine its impact on overall survival.	Metformin	67-76	ATP binding cassette subfamily B member 1	Homo sapiens	152-157
30176891-9	2018	In the individual analysis, we identified a benefit to adding metformin in the group of patients with high ABCB1 gene expression (p = 0.025).	Metformin	62-71	ATP binding cassette subfamily B member 1	Homo sapiens	107-112
30176891-11	2018	CONCLUSION: The combined use of metformin with chemotherapy is effective in patients with elevated levels of ABCB1 gene expression.	Metformin	32-41	ATP binding cassette subfamily B member 1	Homo sapiens	109-114
29803716-11	2018	For CRP, a significant small to medium effect was observed with probiotics (-0.43 mg/L), ARBs (-0.2 mg/L), omega-3 (-0.17 mg/L) and metformin (-0.16 mg/L).	Metformin	132-141	C-reactive protein	Homo sapiens	4-7
30066055-4	2018	Recently, the diabetes drug metformin was found to inhibit CYP AA epoxygenase activity, allowing the design of more potent biguanides to target tumor growth.	Metformin	28-37	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	59-62
29380373-10	2018	Folic acid induced nephropathy was associated with the overexpression of inflammatory markers MCP-1, F4/80, type IV collagen, fibronectin and TGF-beta1 compared to control groups, which were partially attenuated by metformin treatment.	Metformin	215-224	mast cell protease 1	Mus musculus	94-99
29185360-0	2018	Role of metformin on base excision repair pathway in p53 wild-type H2009 and HepG2 cancer cells.	Metformin	8-17	tumor protein p53	Homo sapiens	53-56
29185360-3	2018	The understanding of the participation of oxidative stress in the action mechanism of metformin and its related effects on p53 and on DNA base excision repair (BER) system can help us to get closer to solve metformin puzzle in cancer.	Metformin	86-95	tumor protein p53	Homo sapiens	123-126
29807101-4	2018	A potential anti-tumourigenic effect of metformin may be mediated by its role in activating AMP-kinase, which in turn inhibits mammalian target of rapamycin (mTOR).	Metformin	40-49	mechanistic target of rapamycin kinase	Homo sapiens	127-156
29807101-4	2018	A potential anti-tumourigenic effect of metformin may be mediated by its role in activating AMP-kinase, which in turn inhibits mammalian target of rapamycin (mTOR).	Metformin	40-49	mechanistic target of rapamycin kinase	Homo sapiens	158-162
29380373-11	2018	In vitro studies confirmed that metformin inhibited TGF-beta1 induced inflammatory and fibrotic responses through Smad3, ERK1/2, and P38 pathways in human renal proximal tubular cells.	Metformin	32-41	transforming growth factor beta 1	Homo sapiens	52-61
29380373-11	2018	In vitro studies confirmed that metformin inhibited TGF-beta1 induced inflammatory and fibrotic responses through Smad3, ERK1/2, and P38 pathways in human renal proximal tubular cells.	Metformin	32-41	mitogen-activated protein kinase 3	Homo sapiens	121-127
30230981-0	2018	Metformin Inhibits Chemokine Expression Through the AMPK/NF-kappaB Signaling Pathway.	Metformin	0-9	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	57-66
30230981-7	2018	We observed that metformin prevented the stimulating effect of LPS on these chemokines as well as IL-1 and IL-6.	Metformin	17-26	interleukin 6	Mus musculus	107-111
30230981-9	2018	Finally, we investigated whether the NF-kappaB signaling pathway is regulated by metformin in this setting.	Metformin	81-90	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	37-46
30230981-10	2018	Our results showed that metformin inhibited the phosphorylation of I-kappaBalpha and p65 while it activated AMPK.	Metformin	24-33	nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha	Mus musculus	67-80
30230981-11	2018	Therefore, the results suggest that metformin inhibits LPS-induced chemokine expression through the AMPK and NF-kappaB signaling pathways.	Metformin	36-45	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	109-118
30009823-10	2018	In addition, activation of AMPK by metformin suppressed NF-kappaB-mediated autophagy activation and down-regulation of RND3 and therefore reduced RVSP, RVHI, and %MT in MCT-induced PAH.	Metformin	35-44	nuclear factor kappa B subunit 1	Homo sapiens	56-65
29976587-3	2018	Metformin has a well described antifibrotic effect, and increases phosphorylation of ACC by AMPK, thereby increasing FAO.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	92-96
29956804-6	2018	Furthermore, metformin reduced TGF-beta1 production and Smad2/3 phosphorylation in pancreatic cancer cells.	Metformin	13-22	SMAD family member 2	Mus musculus	56-63
29956804-9	2018	Collectively, our study revealed a new possible mechanism for the antitumor effects of metformin via autocrine TGF-beta1/Smad2/3 signaling in PDAC.	Metformin	87-96	SMAD family member 2	Mus musculus	121-128
29753686-6	2018	Long-term metformin treatment after MIwas associated with (1) a reduction in myocardial fibrosis and Gal-3 levels; (2) an increase in adenosine monophosphate-activated protein kinase (AMPK) alpha1/alpha2 levels; and (3) an inhibition of both mRNA expression and enzymatic activities of mitoNox and PKCalpha.	Metformin	10-19	galectin 3	Rattus norvegicus	101-106
29753686-6	2018	Long-term metformin treatment after MIwas associated with (1) a reduction in myocardial fibrosis and Gal-3 levels; (2) an increase in adenosine monophosphate-activated protein kinase (AMPK) alpha1/alpha2 levels; and (3) an inhibition of both mRNA expression and enzymatic activities of mitoNox and PKCalpha.	Metformin	10-19	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	134-182
29753686-6	2018	Long-term metformin treatment after MIwas associated with (1) a reduction in myocardial fibrosis and Gal-3 levels; (2) an increase in adenosine monophosphate-activated protein kinase (AMPK) alpha1/alpha2 levels; and (3) an inhibition of both mRNA expression and enzymatic activities of mitoNox and PKCalpha.	Metformin	10-19	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	184-188
29753686-7	2018	These findings were replicated in the cellular model, where the silencing of AMPK expression blocked the ability of metformin to protect cardiomyocytes from strain.	Metformin	116-125	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	77-81
29753686-9	2018	In conclusion, a metformin-induced increase in AMPK improves myocardial remodeling post-MI, which is related to the inhibition of the mitoNox/PKCalpha/Gal-3 pathway.	Metformin	17-26	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	47-51
29753686-9	2018	In conclusion, a metformin-induced increase in AMPK improves myocardial remodeling post-MI, which is related to the inhibition of the mitoNox/PKCalpha/Gal-3 pathway.	Metformin	17-26	galectin 3	Rattus norvegicus	151-156
29691295-0	2018	Metformin Targets Mitochondrial Glycerophosphate Dehydrogenase to Control Rate of Oxidative Phosphorylation and Growth of Thyroid Cancer In Vitro and In Vivo.	Metformin	0-9	glycerol-3-phosphate dehydrogenase 2	Homo sapiens	18-62
30142908-7	2018	In the metformin group, fasting plasma glucose and HbA1c levels reached a nadir at 8 months, at which time insulin secretion, glucose and insulin sensitivity were significantly better than at baseline and higher than in the insulin group.	Metformin	7-16	insulin	Homo sapiens	107-114
30142908-7	2018	In the metformin group, fasting plasma glucose and HbA1c levels reached a nadir at 8 months, at which time insulin secretion, glucose and insulin sensitivity were significantly better than at baseline and higher than in the insulin group.	Metformin	7-16	insulin	Homo sapiens	138-145
30154647-0	2018	Combined treatment with metformin and gefitinib overcomes primary resistance to EGFR-TKIs with EGFR mutation via targeting IGF-1R signaling pathway.	Metformin	24-33	epidermal growth factor receptor	Homo sapiens	80-84
30154647-0	2018	Combined treatment with metformin and gefitinib overcomes primary resistance to EGFR-TKIs with EGFR mutation via targeting IGF-1R signaling pathway.	Metformin	24-33	epidermal growth factor receptor	Homo sapiens	95-99
30171812-0	2018	Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway.	Metformin	23-32	AKT serine/threonine kinase 1	Homo sapiens	133-136
30171812-0	2018	Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway.	Metformin	23-32	mechanistic target of rapamycin kinase	Homo sapiens	137-166
30171812-0	2018	Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway.	Metformin	23-32	mechanistic target of rapamycin kinase	Homo sapiens	168-172
30233494-0	2018	Efficacy of Metformin for Benign Thyroid Nodules in Subjects With Insulin Resistance: A Systematic Review and Meta-Analysis.	Metformin	12-21	insulin	Homo sapiens	66-73
30233494-1	2018	Background: To evaluate the effect of metformin therapy on decreasing benign thyroid nodule volume in subjects with insulin resistance (IR).	Metformin	38-47	insulin	Homo sapiens	116-123
30116997-3	2018	RECENT FINDINGS: Metformin and glucagon-like peptide-1 receptor agonists have been associated with weight reduction and decrease in daily insulin requirements without sustainable improvement in glycemic control.	Metformin	17-26	insulin	Homo sapiens	138-145
29691295-1	2018	Purpose: Mitochondrial glycerophosphate dehydrogenase (MGPDH) is the key enzyme connecting oxidative phosphorylation (OXPHOS) and glycolysis as well as a target of the antidiabetic drug metformin in the liver.	Metformin	186-195	glycerol-3-phosphate dehydrogenase 2	Homo sapiens	9-53
29691295-1	2018	Purpose: Mitochondrial glycerophosphate dehydrogenase (MGPDH) is the key enzyme connecting oxidative phosphorylation (OXPHOS) and glycolysis as well as a target of the antidiabetic drug metformin in the liver.	Metformin	186-195	glycerol-3-phosphate dehydrogenase 2	Homo sapiens	55-60
29691295-3	2018	In this study, we evaluated MGPDH as a potential target of metformin in thyroid cancer and investigated its contribution in thyroid cancer metabolism.Experimental Design: We analyzed MGPDH expression in 253 thyroid cancer and normal tissues by immunostaining and examined its expression and localization in thyroid cancer-derived cell lines (FTC133, BCPAP) by confocal microscopy.	Metformin	59-68	glycerol-3-phosphate dehydrogenase 2	Homo sapiens	28-33
30111296-11	2018	This cytotoxic effect was profound upon incorporation of metformin, an indirect mTOR inhibitor, in cisplatin nano-cubosomes.	Metformin	57-66	mechanistic target of rapamycin kinase	Homo sapiens	80-84
29691295-4	2018	The effects of metformin on MGPDH expression were determined by qRT-PCR and Western blot analysis.	Metformin	15-24	glycerol-3-phosphate dehydrogenase 2	Homo sapiens	28-33
29691295-6	2018	We analyzed the effects of metformin on tumor growth and MGPDH expression in metastatic thyroid cancer mouse models.Results: We show for the first time that MGPDH is overexpressed in thyroid cancer compared with normal thyroid.	Metformin	27-36	glycerol-3-phosphate dehydrogenase 2	Homo sapiens	157-162
29691295-7	2018	We demonstrate that MGPDH regulates human thyroid cancer cell growth and OXPHOS rate in vitro Metformin treatment is associated with downregulation of MGPDH expression and inhibition of OXPHOS in thyroid cancer in vitro Cells characterized by high MGPDH expression are more sensitive to OXPHOS-inhibitory effects of metformin in vitro and growth-inhibitory effects of metformin in vitro and in vivoConclusions: Our study established MGPDH as a novel regulator of thyroid cancer growth and metabolism that can be effectively targeted by metformin.	Metformin	94-103	glycerol-3-phosphate dehydrogenase 2	Homo sapiens	20-25
29691295-7	2018	We demonstrate that MGPDH regulates human thyroid cancer cell growth and OXPHOS rate in vitro Metformin treatment is associated with downregulation of MGPDH expression and inhibition of OXPHOS in thyroid cancer in vitro Cells characterized by high MGPDH expression are more sensitive to OXPHOS-inhibitory effects of metformin in vitro and growth-inhibitory effects of metformin in vitro and in vivoConclusions: Our study established MGPDH as a novel regulator of thyroid cancer growth and metabolism that can be effectively targeted by metformin.	Metformin	94-103	glycerol-3-phosphate dehydrogenase 2	Homo sapiens	151-156
29691295-7	2018	We demonstrate that MGPDH regulates human thyroid cancer cell growth and OXPHOS rate in vitro Metformin treatment is associated with downregulation of MGPDH expression and inhibition of OXPHOS in thyroid cancer in vitro Cells characterized by high MGPDH expression are more sensitive to OXPHOS-inhibitory effects of metformin in vitro and growth-inhibitory effects of metformin in vitro and in vivoConclusions: Our study established MGPDH as a novel regulator of thyroid cancer growth and metabolism that can be effectively targeted by metformin.	Metformin	94-103	glycerol-3-phosphate dehydrogenase 2	Homo sapiens	151-156
29691295-7	2018	We demonstrate that MGPDH regulates human thyroid cancer cell growth and OXPHOS rate in vitro Metformin treatment is associated with downregulation of MGPDH expression and inhibition of OXPHOS in thyroid cancer in vitro Cells characterized by high MGPDH expression are more sensitive to OXPHOS-inhibitory effects of metformin in vitro and growth-inhibitory effects of metformin in vitro and in vivoConclusions: Our study established MGPDH as a novel regulator of thyroid cancer growth and metabolism that can be effectively targeted by metformin.	Metformin	94-103	glycerol-3-phosphate dehydrogenase 2	Homo sapiens	151-156
29691295-7	2018	We demonstrate that MGPDH regulates human thyroid cancer cell growth and OXPHOS rate in vitro Metformin treatment is associated with downregulation of MGPDH expression and inhibition of OXPHOS in thyroid cancer in vitro Cells characterized by high MGPDH expression are more sensitive to OXPHOS-inhibitory effects of metformin in vitro and growth-inhibitory effects of metformin in vitro and in vivoConclusions: Our study established MGPDH as a novel regulator of thyroid cancer growth and metabolism that can be effectively targeted by metformin.	Metformin	316-325	glycerol-3-phosphate dehydrogenase 2	Homo sapiens	20-25
29691295-7	2018	We demonstrate that MGPDH regulates human thyroid cancer cell growth and OXPHOS rate in vitro Metformin treatment is associated with downregulation of MGPDH expression and inhibition of OXPHOS in thyroid cancer in vitro Cells characterized by high MGPDH expression are more sensitive to OXPHOS-inhibitory effects of metformin in vitro and growth-inhibitory effects of metformin in vitro and in vivoConclusions: Our study established MGPDH as a novel regulator of thyroid cancer growth and metabolism that can be effectively targeted by metformin.	Metformin	368-377	glycerol-3-phosphate dehydrogenase 2	Homo sapiens	20-25
29691295-7	2018	We demonstrate that MGPDH regulates human thyroid cancer cell growth and OXPHOS rate in vitro Metformin treatment is associated with downregulation of MGPDH expression and inhibition of OXPHOS in thyroid cancer in vitro Cells characterized by high MGPDH expression are more sensitive to OXPHOS-inhibitory effects of metformin in vitro and growth-inhibitory effects of metformin in vitro and in vivoConclusions: Our study established MGPDH as a novel regulator of thyroid cancer growth and metabolism that can be effectively targeted by metformin.	Metformin	368-377	glycerol-3-phosphate dehydrogenase 2	Homo sapiens	20-25
30215039-5	2018	Assays for the mechanisms of action of antitumor effects revealed that alpha-fetoprotein expression was suppressed by both metformin and sorafenib, but no synergistic effect was observed.	Metformin	123-132	alpha fetoprotein	Homo sapiens	71-88
29893190-6	2018	Furthermore, metformin-preconditioned hiPSC-NSCs show increased engraftment 1 week post-transplantation in a rat endothelin-1 focal ischemic stroke model.	Metformin	13-22	endothelin 1	Rattus norvegicus	113-125
29659168-6	2018	We also indicate that metformin increases the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2), which binds to the antioxidant response elements in the GPX7 gene promoter to induce its expression.	Metformin	22-31	NFE2 like bZIP transcription factor 2	Homo sapiens	70-113
29659168-6	2018	We also indicate that metformin increases the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2), which binds to the antioxidant response elements in the GPX7 gene promoter to induce its expression.	Metformin	22-31	NFE2 like bZIP transcription factor 2	Homo sapiens	115-119
29659168-7	2018	Moreover, the metformin-Nrf2-GPx7 pathway delays aging in worms.	Metformin	14-23	NFE2 like bZIP transcription factor 2	Homo sapiens	24-28
29659168-8	2018	Our study provides mechanistic insights into the beneficial effects of metformin on human cellular aging and highlights the importance of the Nrf2-GPx7 pathway in pro-longevity signaling.	Metformin	71-80	NFE2 like bZIP transcription factor 2	Homo sapiens	142-146
29847773-0	2018	Metformin enhances cisplatin induced inhibition of cholangiocarcinoma cells via AMPK-mTOR pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	85-89
30147674-4	2018	In type 2 diabetes patients, metformin reduces hyperglycemia and increases insulin sensitivity by enhancing insulin-stimulated glucose uptake in muscles, liver, and adipose tissue and by reducing glucose output by the liver.	Metformin	29-38	insulin	Homo sapiens	75-82
30147674-5	2018	Lowering insulin and insulin-like growth factor 1 (IGF-1) levels that stimulate cancer growth could be important features of metformin"s mode of action.	Metformin	125-134	insulin	Homo sapiens	9-16
30147674-5	2018	Lowering insulin and insulin-like growth factor 1 (IGF-1) levels that stimulate cancer growth could be important features of metformin"s mode of action.	Metformin	125-134	insulin like growth factor 1	Homo sapiens	21-49
30147674-5	2018	Lowering insulin and insulin-like growth factor 1 (IGF-1) levels that stimulate cancer growth could be important features of metformin"s mode of action.	Metformin	125-134	insulin like growth factor 1	Homo sapiens	51-56
30084684-1	2018	A growing body of data, guideline recommendations, algorithms, and position papers supports the use of glucagon-like peptide-1 (GLP-1) receptor agonists in type 2 diabetes (T2D), given their beneficial effects on glycemic control, weight, lipid parameters, and blood pressure, and low risk for hypoglycemia when used in patients who have not achieved glycemic goals with metformin and lifestyle interventions.	Metformin	371-380	glucagon	Homo sapiens	103-126
29969038-5	2018	We found that metformin improved the expression of intestinal tight junction proteins (ZO1, occludin, and Claudin1) that were reduced by LPS stimulation.	Metformin	14-23	tight junction protein 1	Homo sapiens	87-90
29969038-6	2018	Moreover, metformin alleviated LPS-induced NF-kappaB phosphorylation, promoted Nrf2 nuclear translocation, and increased the expression of the antioxidative genes (HO-1 and NQO-1), leading to reduced intestinal ROS content.	Metformin	10-19	NFE2 like bZIP transcription factor 2	Homo sapiens	79-83
29969038-6	2018	Moreover, metformin alleviated LPS-induced NF-kappaB phosphorylation, promoted Nrf2 nuclear translocation, and increased the expression of the antioxidative genes (HO-1 and NQO-1), leading to reduced intestinal ROS content.	Metformin	10-19	NAD(P)H quinone dehydrogenase 1	Homo sapiens	173-178
29859833-7	2018	In addition, co-administration of the mTOR activator 3BDO but not the sirtuin 1 inhibitor EX-527 abolished the effects of metformin on IL-6 induction and pulmonary lesions.	Metformin	122-131	interleukin 6	Mus musculus	135-139
30178862-16	2018	After NR8383 was treated with metformin and LPS, the expression of SIRT1 was higher than that of LPS treatment alone, but the expression of p-p38, p-ERK, and p-NF-kappaB was significantly decreased.	Metformin	30-39	mitogen-activated protein kinase 1	Mus musculus	149-152
29948021-2	2018	Metformin may potentiate mTOR inhibition by sirolimus while mitigating its adverse effects.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	25-29
29859833-4	2018	The results indicated that treatment with metformin suppressed LPS-induced upregulation of IL-6 and TNF-alpha, alleviated pulmonary histological abnormalities, improved the survival rate of LPS-challenged mice.	Metformin	42-51	interleukin 6	Mus musculus	91-95
29859833-4	2018	The results indicated that treatment with metformin suppressed LPS-induced upregulation of IL-6 and TNF-alpha, alleviated pulmonary histological abnormalities, improved the survival rate of LPS-challenged mice.	Metformin	42-51	tumor necrosis factor	Mus musculus	100-109
29844095-7	2018	Following an oral glucose tolerance test in the presence of metformin, carriers of the p.E508K variant with diabetes had a lower maximum insulin peak and total and incremental insulin AUC value as compared with noncarriers with diabetes (P &lt; 0.05).	Metformin	60-69	insulin	Homo sapiens	137-144
30178862-16	2018	After NR8383 was treated with metformin and LPS, the expression of SIRT1 was higher than that of LPS treatment alone, but the expression of p-p38, p-ERK, and p-NF-kappaB was significantly decreased.	Metformin	30-39	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	160-169
29738369-5	2018	Metformin has further been reported to restore depleted PGC-1alpha levels and improve mitochondrial biogenesis by increasing phosphorylation of eNOSser1177, which produces NO and leads to reduced vascular inflammation and myocardial injury after ischemia.	Metformin	0-9	PPARG coactivator 1 alpha	Homo sapiens	56-66
29922884-0	2018	Comment on "Targeting AMPK, mTOR and beta-Catenin by Combined Metformin and Aspirin Therapy in HCC: An Appraisal in Egyptian HCC Patients".	Metformin	62-71	mechanistic target of rapamycin kinase	Homo sapiens	28-32
29660403-10	2018	In contrast, both metformin and fulvene-5, inhibitors of NOX4, facilitated the reversal of TP53 WT and Mut adaptive responses from pro-survival to radio-sensitization and vice versa, respectively.	Metformin	18-27	tumor protein p53	Homo sapiens	91-95
29660403-13	2018	Under these conditions NOX4 expression was inhibited by about 50%, resulting in a reversal in the expression of the TP53 WT and Mut survivin-associated adaptive responses as was observed following metformin and fulvene-5 treatment.	Metformin	197-206	tumor protein p53	Homo sapiens	116-120
30075530-4	2018	For the effect of metformin, women who used traditional Chinese medicine including Di Huang series have a lower risk of breast cancer HR: 0.35 (95%CI: 0.23-0.51) in women younger than 55 and HR: 0.54 (95%CI: 0.37-0.79) in women older than 55.The protective effect of the Di Huang Wan series may be due to the synergetic effect of reducing blood glucose or increasing insulin sensitivity and delaying the insulin resistance of cells.	Metformin	18-27	insulin	Homo sapiens	367-374
30075530-4	2018	For the effect of metformin, women who used traditional Chinese medicine including Di Huang series have a lower risk of breast cancer HR: 0.35 (95%CI: 0.23-0.51) in women younger than 55 and HR: 0.54 (95%CI: 0.37-0.79) in women older than 55.The protective effect of the Di Huang Wan series may be due to the synergetic effect of reducing blood glucose or increasing insulin sensitivity and delaying the insulin resistance of cells.	Metformin	18-27	insulin	Homo sapiens	404-411
30104887-0	2018	Metformin induces miR-378 to downregulate the CDK1, leading to suppression of cell proliferation in hepatocellular carcinoma.	Metformin	0-9	microRNA 378a	Mus musculus	18-25
30008897-7	2018	It was revealed that degradation of cellular caspase 8 (FLICE)-like inhibitory protein (c-FLIP) and activation of procaspase-8 were associated with metformin-mediated apoptosis.	Metformin	148-157	CASP8 and FADD like apoptosis regulator	Homo sapiens	88-94
30008897-9	2018	Treatment with benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD-fmk, a pan-caspase inhibitor) almost completely blocked metformin-induced apoptosis and degradation of c-FLIPL protein.	Metformin	128-137	CASP8 and FADD like apoptosis regulator	Homo sapiens	175-182
30008897-11	2018	Taken together, the results of the present study demonstrated that metformin-induced apoptosis involved degradation of the c-FLIPL protein and activation of caspase-8 in human renal cell carcinoma A498 cells and suggested that metformin could be potentially used for the treatment of renal cancer.	Metformin	67-76	CASP8 and FADD like apoptosis regulator	Homo sapiens	123-130
30008897-11	2018	Taken together, the results of the present study demonstrated that metformin-induced apoptosis involved degradation of the c-FLIPL protein and activation of caspase-8 in human renal cell carcinoma A498 cells and suggested that metformin could be potentially used for the treatment of renal cancer.	Metformin	227-236	CASP8 and FADD like apoptosis regulator	Homo sapiens	123-130
30104887-9	2018	At the same time, metformin efficiently decreased CDK1 expression and elevated miR-378 level.	Metformin	18-27	microRNA 378a	Mus musculus	79-86
30104887-13	2018	Discussion: Metformin-suppressed HCC cell proliferation was dependent on the inhibitory effect of miR-378 on CDK1 expression.	Metformin	12-21	microRNA 378a	Mus musculus	98-105
30104887-14	2018	Taken together, we concluded that metformin inhibited HCC cell proliferation via modulating miR-378/CDK1 axis.	Metformin	34-43	microRNA 378a	Mus musculus	92-99
30104887-15	2018	Conclusion: Collectively, the current results provide the first evidence, to our knowledge, that miR-378/CDK1 axis is involved in metformin modulating the proliferation of HCC cells, which suggests a novel molecular mechanism underlying the thera peutic effect of metformin on HCC.	Metformin	130-139	microRNA 378a	Mus musculus	97-104
30104887-15	2018	Conclusion: Collectively, the current results provide the first evidence, to our knowledge, that miR-378/CDK1 axis is involved in metformin modulating the proliferation of HCC cells, which suggests a novel molecular mechanism underlying the thera peutic effect of metformin on HCC.	Metformin	264-273	microRNA 378a	Mus musculus	97-104
30187872-3	2018	Women with insulin resistance also received metformin.	Metformin	44-53	insulin	Homo sapiens	11-18
30116349-8	2018	Furthermore, secretion of TNF-alpha, IL-1alpha, M-CSF and TCA-3 into the conditioned media was significantly decreased by metformin (5 and 10 mM; P&lt;0.05).	Metformin	122-131	tumor necrosis factor	Mus musculus	26-35
30187872-9	2018	BMI and WHR decreased in all the patients with insulin resistance aftercombination treatment with metformin (P &lt; 0.05), but increased significantly in patients without insulin resistance (P &lt; 0.05).	Metformin	98-107	insulin	Homo sapiens	47-54
29858905-0	2018	A novel mutation in the proopiomelanocortin (POMC) gene of a Hispanic child: metformin treatment shows a beneficial impact on the body mass index.	Metformin	77-86	proopiomelanocortin	Homo sapiens	24-43
30054579-0	2018	Streptozotocin-induced beta-cell damage, high fat diet, and metformin administration regulate Hes3 expression in the adult mouse brain.	Metformin	60-69	hes family bHLH transcription factor 3	Mus musculus	94-98
30054579-6	2018	Our data show that streptozotocin-induced beta-cell damage, high fat diet, as well as metformin, a common type 2 diabetes medication, regulate Hes3 levels in the brain.	Metformin	86-95	hes family bHLH transcription factor 3	Mus musculus	143-147
29678660-0	2018	Metformin combined with quercetin synergistically repressed prostate cancer cells via inhibition of VEGF/PI3K/Akt signaling pathway.	Metformin	0-9	vascular endothelial growth factor A	Homo sapiens	100-104
29678660-0	2018	Metformin combined with quercetin synergistically repressed prostate cancer cells via inhibition of VEGF/PI3K/Akt signaling pathway.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	110-113
29678660-5	2018	Our data also indicated that co-treatment of metformin and quercetin strongly inhibited the VEGF/Akt/PI3K pathway.	Metformin	45-54	vascular endothelial growth factor A	Homo sapiens	92-96
29678660-5	2018	Our data also indicated that co-treatment of metformin and quercetin strongly inhibited the VEGF/Akt/PI3K pathway.	Metformin	45-54	AKT serine/threonine kinase 1	Homo sapiens	97-100
29678660-7	2018	In conclusion, our findings indicate that the combination therapy of metformin and quercetin exerted synergistic antitumor effects in prostate cancers via inhibition of VEGF/Akt/PI3K pathway.	Metformin	69-78	vascular endothelial growth factor A	Homo sapiens	169-173
29678660-7	2018	In conclusion, our findings indicate that the combination therapy of metformin and quercetin exerted synergistic antitumor effects in prostate cancers via inhibition of VEGF/Akt/PI3K pathway.	Metformin	69-78	AKT serine/threonine kinase 1	Homo sapiens	174-177
30100873-9	2018	We also observed a significant decrease in the level of fasting insulin and insulin resistance (IR) index in the metformin-donepezil group, with a lower CCA-IMT value than that in the acarbose-donepezil group after a year of treatment (P &lt; 0.05).	Metformin	113-122	insulin	Homo sapiens	64-71
30100873-9	2018	We also observed a significant decrease in the level of fasting insulin and insulin resistance (IR) index in the metformin-donepezil group, with a lower CCA-IMT value than that in the acarbose-donepezil group after a year of treatment (P &lt; 0.05).	Metformin	113-122	insulin	Homo sapiens	76-83
30258965-11	2018	Moreover, the signal axis of Rarb/Runx3/Col6a1 is pharmaceutically accessible to a widely used antidiabetic substance, metformin, and Rar modulator.	Metformin	119-128	retinoic acid receptor beta	Homo sapiens	29-33
30041690-0	2018	Genetic polymorphisms of organic cation transporters 1 (OCT1) and responses to metformin therapy in individuals with type 2 diabetes mellitus: a systematic review protocol.	Metformin	79-88	solute carrier family 22 member 1	Homo sapiens	25-54
30041690-0	2018	Genetic polymorphisms of organic cation transporters 1 (OCT1) and responses to metformin therapy in individuals with type 2 diabetes mellitus: a systematic review protocol.	Metformin	79-88	solute carrier family 22 member 1	Homo sapiens	56-60
30041690-3	2018	This systematic review aims to highlight and summarize the overall effects of OCT1 polymorphisms on therapeutic responses to metformin and to evaluate their potential role in terms of interethnic differences with metformin responses.	Metformin	125-134	solute carrier family 22 member 1	Homo sapiens	78-82
30041690-4	2018	METHODS/DESIGN: We will systematically review observational studies reporting on the genetic association between OCT1 polymorphisms and metformin responses in T2DM patients.	Metformin	136-145	solute carrier family 22 member 1	Homo sapiens	113-117
30041690-11	2018	DISCUSSION: This review will summarize the genetic effects of OCT1 polymorphisms associated with variabilities in glycemic responses to metformin.	Metformin	136-145	solute carrier family 22 member 1	Homo sapiens	62-66
29760016-7	2018	When applied to cultured cardiomyocytes, insulin and metformin increased titin phosphorylation at S4010, S4099, and S11878 via enhanced ERK1/2 (extracellular signal regulated kinase 1/2) and PKCalpha (protein kinase Calpha) activity; NRG-1 application enhanced ERK1/2 activity but reduced PKCalpha activity.	Metformin	53-62	mitogen-activated protein kinase 3	Homo sapiens	136-142
29760016-7	2018	When applied to cultured cardiomyocytes, insulin and metformin increased titin phosphorylation at S4010, S4099, and S11878 via enhanced ERK1/2 (extracellular signal regulated kinase 1/2) and PKCalpha (protein kinase Calpha) activity; NRG-1 application enhanced ERK1/2 activity but reduced PKCalpha activity.	Metformin	53-62	mitogen-activated protein kinase 1	Homo sapiens	144-185
29760016-7	2018	When applied to cultured cardiomyocytes, insulin and metformin increased titin phosphorylation at S4010, S4099, and S11878 via enhanced ERK1/2 (extracellular signal regulated kinase 1/2) and PKCalpha (protein kinase Calpha) activity; NRG-1 application enhanced ERK1/2 activity but reduced PKCalpha activity.	Metformin	53-62	protein kinase C alpha	Homo sapiens	191-199
29760016-7	2018	When applied to cultured cardiomyocytes, insulin and metformin increased titin phosphorylation at S4010, S4099, and S11878 via enhanced ERK1/2 (extracellular signal regulated kinase 1/2) and PKCalpha (protein kinase Calpha) activity; NRG-1 application enhanced ERK1/2 activity but reduced PKCalpha activity.	Metformin	53-62	protein kinase C alpha	Homo sapiens	201-222
29760016-7	2018	When applied to cultured cardiomyocytes, insulin and metformin increased titin phosphorylation at S4010, S4099, and S11878 via enhanced ERK1/2 (extracellular signal regulated kinase 1/2) and PKCalpha (protein kinase Calpha) activity; NRG-1 application enhanced ERK1/2 activity but reduced PKCalpha activity.	Metformin	53-62	mitogen-activated protein kinase 3	Homo sapiens	261-267
29760016-7	2018	When applied to cultured cardiomyocytes, insulin and metformin increased titin phosphorylation at S4010, S4099, and S11878 via enhanced ERK1/2 (extracellular signal regulated kinase 1/2) and PKCalpha (protein kinase Calpha) activity; NRG-1 application enhanced ERK1/2 activity but reduced PKCalpha activity.	Metformin	53-62	protein kinase C alpha	Homo sapiens	289-297
29884740-0	2018	Metformin induces FOXO3-dependent fetal hemoglobin production in human primary erythroid cells.	Metformin	0-9	forkhead box O3	Homo sapiens	18-23
29884740-6	2018	Moreover, treatment of primary CD34+ cell-derived erythroid cultures with metformin, an FDA-approved drug known to enhance FOXO3 activity in nonerythroid cells, caused dose-related FOXO3-dependent increases in the percentage of HbF protein and the fraction of HbF-immunostaining cells (F cells).	Metformin	74-83	CD34 molecule	Homo sapiens	31-35
29884740-6	2018	Moreover, treatment of primary CD34+ cell-derived erythroid cultures with metformin, an FDA-approved drug known to enhance FOXO3 activity in nonerythroid cells, caused dose-related FOXO3-dependent increases in the percentage of HbF protein and the fraction of HbF-immunostaining cells (F cells).	Metformin	74-83	forkhead box O3	Homo sapiens	123-128
29884740-6	2018	Moreover, treatment of primary CD34+ cell-derived erythroid cultures with metformin, an FDA-approved drug known to enhance FOXO3 activity in nonerythroid cells, caused dose-related FOXO3-dependent increases in the percentage of HbF protein and the fraction of HbF-immunostaining cells (F cells).	Metformin	74-83	forkhead box O3	Homo sapiens	181-186
29884740-8	2018	HbF induction by metformin in erythroid precursors was dependent on FOXO3 expression and did not alter expression of BCL11A, MYB, or KLF1.	Metformin	17-26	forkhead box O3	Homo sapiens	68-73
29858905-0	2018	A novel mutation in the proopiomelanocortin (POMC) gene of a Hispanic child: metformin treatment shows a beneficial impact on the body mass index.	Metformin	77-86	proopiomelanocortin	Homo sapiens	45-49
29650774-6	2018	Furthermore, rare variants in STAT3 associated with worse metformin response (q &lt;0.1).	Metformin	58-67	signal transducer and activator of transcription 3	Mus musculus	30-35
30250766-4	2018	Considering the fact that androgen excess could be caused by either insulin resistance or hyperprolactinemia, we decided to treat one sister with insulin sensitizer metformin and other with dopamine agonist cabergoline.	Metformin	165-174	insulin	Homo sapiens	146-153
29705631-5	2018	Metformin inhibited tumor cell proliferation and induced apoptosis through activation of AMPK/mTOR pathway and further influencing energy metabolism, phospholipid metabolism and glucose catabolism.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	94-98
29704494-8	2018	During the process of tumor metastasis, miR-142-3p was significantly upregulated, whereas lncRNA MATAL1 and HMGA2 were suppressed by metformin.	Metformin	133-142	high mobility group AT-hook 2	Mus musculus	108-113
29853564-4	2018	This study was undertaken to assess the possibility that metformin induces Abcg5 and Abcg8 expression in liver and to elucidate the underlying mechanisms.	Metformin	57-66	ATP binding cassette subfamily G member 5	Mus musculus	75-80
29853564-5	2018	APPROACH AND RESULTS: Metformin-treated mouse or human primary hepatocytes showed increased expression of Abcg5/8 and the bile salt export pump, Bsep.	Metformin	22-31	ATP binding cassette subfamily G member 5	Homo sapiens	106-113
29853564-6	2018	Administration of metformin to Western-type diet-fed mice showed significant upregulation of Abcg5/8 and Bsep.	Metformin	18-27	ATP binding cassette subfamily G member 5	Mus musculus	93-100
29853564-6	2018	Administration of metformin to Western-type diet-fed mice showed significant upregulation of Abcg5/8 and Bsep.	Metformin	18-27	ATP-binding cassette, sub-family B (MDR/TAP), member 11	Mus musculus	105-109
30123261-0	2018	Low-Dose Spironolactone-Pioglitazone-Metformin Normalizes Circulating Fetuin-A Concentrations in Adolescent Girls with Polycystic Ovary Syndrome.	Metformin	37-46	alpha 2-HS glycoprotein	Homo sapiens	70-78
29988028-7	2018	Pharmacological activation of AMPK by metformin significantly abrogated the loss of RUNX2-S118 phosphorylation and protected from tunicamycin-induced endoplasmic reticulum stress, high glucose-induced in vitro adipogenesis and streptozotocin-induced in vivo bone adiposity and bone phenotype.	Metformin	38-47	RUNX family transcription factor 2	Homo sapiens	84-89
29970197-10	2018	There was a significant difference in the birth weight of babies in the metformin with insulin group of 207 g (p value 0.04) in favour of metformin.	Metformin	72-81	insulin	Homo sapiens	87-94
29581079-1	2018	BACKGROUND: We sought to determine whether insulin-sensitizing therapy (thiazolidinediones or metformin) decreased the risk of developing atrial fibrillation compared with insulin-providing therapy (insulin, sulfonylurea, or a meglitinide).	Metformin	94-103	insulin	Homo sapiens	43-50
29650774-8	2018	Here, we provide novel evidence for associations of common and rare variants in PRPF31, CPA6, and STAT3 with metformin response that may provide insight into mechanisms important for metformin efficacy in T2D.	Metformin	109-118	signal transducer and activator of transcription 3	Mus musculus	98-103
29650774-8	2018	Here, we provide novel evidence for associations of common and rare variants in PRPF31, CPA6, and STAT3 with metformin response that may provide insight into mechanisms important for metformin efficacy in T2D.	Metformin	183-192	signal transducer and activator of transcription 3	Mus musculus	98-103
30008442-2	2018	Although not licensed for use in type 1 diabetes, metformin is included in some clinical guidelines as adjuvant therapy for people with type 1 diabetes who are overweight and wish to improve glycaemic control while minimising the dose of insulin.1,2 The REMOVAL study is the largest trial to date that has investigated the longer-term effects of metformin in people with type 1 diabetes.3 Here, we consider the role of metformin in individuals with type 1 diabetes in light of these results and other study findings.	Metformin	50-59	insulin	Homo sapiens	238-245
29728363-6	2018	Importantly, hepatocyte insulin sensitivity can be restored by PDGF-AA-blocking antibodies, PDGF receptor inhibitors, and by metformin, opening therapeutic avenues.	Metformin	125-134	insulin	Homo sapiens	24-31
30063424-3	2018	Insulin, the only other drug approved for use in youth with T2D, is also used as add-on therapy when patients fail metformin mono-therapy.	Metformin	115-124	insulin	Homo sapiens	0-7
31565651-11	2018	Results showed an upregulation of both DUOX1 and DUOX2 pathways in the presence of metformin, while the level of IL-13 did not show any significant change.	Metformin	83-92	dual oxidase 1	Rattus norvegicus	39-44
29979413-15	2018	CONCLUSION: Genetic effects of OCT1 polymorphisms on metformin responses were population specific.	Metformin	53-62	solute carrier family 22 member 1	Homo sapiens	31-35
29659176-9	2018	A specific AMPK activator metformin increased Wnt3a, beta-catenin, Nrf2 phosphorylation and activation but reduced the levels of IL-6 and IL-8 in NHBE cells and mouse lungs exposed to CSE.	Metformin	26-35	nuclear factor, erythroid derived 2, like 2	Mus musculus	67-71
29659176-9	2018	A specific AMPK activator metformin increased Wnt3a, beta-catenin, Nrf2 phosphorylation and activation but reduced the levels of IL-6 and IL-8 in NHBE cells and mouse lungs exposed to CSE.	Metformin	26-35	interleukin 6	Mus musculus	129-133
29659176-10	2018	Furthermore, Nrf2 deficiency abolished the protection of metformin against CSE-induced increase in IL-6 and IL-8 in NHBE cells.	Metformin	57-66	nuclear factor, erythroid derived 2, like 2	Mus musculus	13-17
29659176-10	2018	Furthermore, Nrf2 deficiency abolished the protection of metformin against CSE-induced increase in IL-6 and IL-8 in NHBE cells.	Metformin	57-66	interleukin 6	Mus musculus	99-103
29979413-0	2018	Genetic polymorphisms of organic cation transporter 1 (OCT1) and responses to metformin therapy in individuals with type 2 diabetes: A systematic review.	Metformin	78-87	solute carrier family 22 member 1	Homo sapiens	25-53
29487223-2	2018	Metformin has been shown to have antitumor effects via a variety of insulin-dependent and insulin-independent mechanisms and to be potentially synergistic with chemotherapy.	Metformin	0-9	insulin	Homo sapiens	68-75
29979413-0	2018	Genetic polymorphisms of organic cation transporter 1 (OCT1) and responses to metformin therapy in individuals with type 2 diabetes: A systematic review.	Metformin	78-87	solute carrier family 22 member 1	Homo sapiens	55-59
29979413-5	2018	AIM: This study aims to highlight and summarize the overall effects of organic cation transporter 1(OCT1) polymorphisms on therapeutic responses to metformin and to evaluate the potential role of such polymorphisms in interethnic differences in metformin therapy.	Metformin	148-157	solute carrier family 22 member 1	Homo sapiens	71-104
29979413-7	2018	We searched for PubMed/MEDLINE, Embase, and CINAHL, relevant studies reporting the effects of OCT1 polymorphisms on metformin therapy in T2DM individuals.	Metformin	116-125	solute carrier family 22 member 1	Homo sapiens	94-98
29516618-6	2018	In cross-sectional analysis, greater prescribing of metformin and analogue insulin were associated with a higher proportion of patients achieving HbA1c &lt;=58 mmol/mol; the use of SGLT2 inhibitors and metformin was associated with a reduced proportion of patients with HbA1c &gt;86 mol/mol; otherwise associations for sulphonylureas, GLP-1 analogues, SGLT2 inhibitors and DPP-4 inhibitors were neutral or negative.	Metformin	52-61	glucagon	Homo sapiens	335-340
29516618-6	2018	In cross-sectional analysis, greater prescribing of metformin and analogue insulin were associated with a higher proportion of patients achieving HbA1c &lt;=58 mmol/mol; the use of SGLT2 inhibitors and metformin was associated with a reduced proportion of patients with HbA1c &gt;86 mol/mol; otherwise associations for sulphonylureas, GLP-1 analogues, SGLT2 inhibitors and DPP-4 inhibitors were neutral or negative.	Metformin	202-211	glucagon	Homo sapiens	335-340
29487223-2	2018	Metformin has been shown to have antitumor effects via a variety of insulin-dependent and insulin-independent mechanisms and to be potentially synergistic with chemotherapy.	Metformin	0-9	insulin	Homo sapiens	90-97
29635803-12	2018	Metformin maintained high activation of AMPK and decreased ERK1/2 levels after HF in both cell lines and only after HI in PNT1A, which was able to decrease the cell proliferation triggered by these treatments.	Metformin	0-9	mitogen-activated protein kinase 3	Homo sapiens	59-65
29542325-9	2018	Metformin use reduced MYC levels in Caco2 and consequently, SLC1A5 and GLS expression, with a greater effect in cells dependent on glutaminolytic metabolism.	Metformin	0-9	solute carrier family 1 member 5	Rattus norvegicus	60-66
29808777-11	2018	Considering the increasing prevalence of obesity and the role of insulin resistance in the development of cancer, metformin might be the preferred treatment for its dual anti-diabetic and antitumor effects.	Metformin	114-123	insulin	Homo sapiens	65-72
29530699-5	2018	Surprisingly, combining the patient"s treatment with metformin decreased prolactin (PRL) levels to 12 ng/mL and significantly decreased the size of the tumor after 1 year of combination therapy.	Metformin	53-62	prolactin	Homo sapiens	84-87
29530699-10	2018	Interestingly, the patient"s PRL level decreased from 208 ng/mL to 150 ng/mL 2 months after using combination treatment with bromocriptine and metformin.	Metformin	143-152	prolactin	Homo sapiens	29-32
29530699-10	2018	Interestingly, the patient"s PRL level decreased from 208 ng/mL to 150 ng/mL 2 months after using combination treatment with bromocriptine and metformin.	Metformin	143-152	skull development traits QTL 2	Mus musculus	74-78
29530699-12	2018	After 3 months of combined treatment with bromocriptine and metformin, the patient"s PRL level decreased to 2.08 ng/mL, testosterone levels increased significantly, and the tumor size decreased.	Metformin	60-69	prolactin	Homo sapiens	85-88
29958542-3	2018	We aim to investigate the potential therapeutic effects of combined therapy of resveratrol and metformin on polycystic ovaries via SIRT1 and AMPK activation.	Metformin	95-104	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	141-145
29958542-16	2018	Resveratrol and metformin increased SIRT1 and AMPK immunreactivity, respectively, compared to the PCOS group.	Metformin	16-25	sirtuin 1	Rattus norvegicus	36-41
29958542-16	2018	Resveratrol and metformin increased SIRT1 and AMPK immunreactivity, respectively, compared to the PCOS group.	Metformin	16-25	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	46-50
29958542-17	2018	CONCLUSIONS: The results suggest that combined therapy of metformin and resveratrol may improve the weight gain, hormone profile and ovarian follicular cell architecture by inducing antioxidant and antiinflammatory systems via SIRT1 and AMPK activation in PCOS.	Metformin	58-67	sirtuin 1	Rattus norvegicus	227-232
29958542-17	2018	CONCLUSIONS: The results suggest that combined therapy of metformin and resveratrol may improve the weight gain, hormone profile and ovarian follicular cell architecture by inducing antioxidant and antiinflammatory systems via SIRT1 and AMPK activation in PCOS.	Metformin	58-67	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	237-241
29958416-0	2018	Caffeic Acid Targets AMPK Signaling and Regulates Tricarboxylic Acid Cycle Anaplerosis while Metformin Downregulates HIF-1alpha-Induced Glycolytic Enzymes in Human Cervical Squamous Cell Carcinoma Lines.	Metformin	93-102	hypoxia inducible factor 1 subunit alpha	Homo sapiens	117-127
30050950-0	2018	Metformin Improves Epithelial-to-Mesenchymal Transition Induced by TGF-beta1 in Renal Tubular Epithelial NRK-52E Cells via Inhibiting Egr-1.	Metformin	0-9	transforming growth factor, beta 1	Rattus norvegicus	67-76
30050950-0	2018	Metformin Improves Epithelial-to-Mesenchymal Transition Induced by TGF-beta1 in Renal Tubular Epithelial NRK-52E Cells via Inhibiting Egr-1.	Metformin	0-9	early growth response 1	Rattus norvegicus	134-139
30050950-3	2018	However, it is unknown whether metformin improves EMT via inhibiting Egr-1.	Metformin	31-40	early growth response 1	Rattus norvegicus	69-74
30050950-6	2018	We observed that TGF-beta1 significantly reduced E-cadherin expression and upregulated the expressions of FN, alpha-SMA, and Egr-1, which can be reversed by metformin.	Metformin	157-166	transforming growth factor, beta 1	Rattus norvegicus	17-26
30050950-6	2018	We observed that TGF-beta1 significantly reduced E-cadherin expression and upregulated the expressions of FN, alpha-SMA, and Egr-1, which can be reversed by metformin.	Metformin	157-166	early growth response 1	Rattus norvegicus	125-130
30050950-7	2018	M61-Egr-1 transfection could exacerbate EMT, which can be reversed by metformin.	Metformin	70-79	early growth response 1	Rattus norvegicus	4-9
30050950-8	2018	Taken together, our data show that Egr-1 plays an important role in TGF-beta1-induced EMT of renal tubular epithelial cells and metformin improves EMT while inhibiting Egr-1, which provides a potential novel target to combat renal fibrosis.	Metformin	128-137	early growth response 1	Rattus norvegicus	168-173
30800563-9	2019	The improvement of blood glucose, fasting insulin and serum lipid levels proved the effectiveness of metformin without increasing body weight.	Metformin	101-110	insulin	Homo sapiens	42-49
30046513-8	2018	Finally, AKT inactivation by downregulation of the phosphorylation level upon metformin treatment was also evidenced.	Metformin	78-87	AKT serine/threonine kinase 1	Homo sapiens	9-12
29946148-0	2018	Metformin add-on continuous subcutaneous insulin infusion on precise insulin doses in patients with type 2 diabetes.	Metformin	0-9	insulin	Homo sapiens	41-48
30062227-3	2018	In both randomized clinical trials and observational studies, antihyperglycemic drugs that act through insulin signaling (i.e., sulfonylureas, thiazolidinediones, and incretins) increase the risk or worsen the clinical course of heart failure, whereas drugs that ameliorate hyperinsulinemia and do not signal through insulin (i.e., metformin and sodium-glucose cotransporter 2 inhibitors) reduce the risk of heart failure.	Metformin	332-341	insulin	Homo sapiens	103-110
29946148-0	2018	Metformin add-on continuous subcutaneous insulin infusion on precise insulin doses in patients with type 2 diabetes.	Metformin	0-9	insulin	Homo sapiens	69-76
29946148-1	2018	To investigate whether metformin add-on to the continuous subcutaneous insulin infusion (Met + CSII) therapy leads to a significant reduction in insulin doses required by type 2 diabetes (T2D) patients to maintain glycemic control, and an improvement in glycemic variation (GV) compared to CSII only therapy.	Metformin	23-32	insulin	Homo sapiens	145-152
29946148-10	2018	Our data suggest that metformin add-on to CSII therapy leads to a significant reduction in insulin doses required by T2D patients to control glycemic variations.	Metformin	22-31	insulin	Homo sapiens	91-98
29915999-7	2018	Fampridine also inhibited OCT2 mediated uptake of Metformin with estimated IC50 of 66.8 muM.	Metformin	50-59	latexin	Homo sapiens	88-91
29580688-0	2018	SIRT3 aggravates metformin-induced energy stress and apoptosis in ovarian cancer cells.	Metformin	17-26	sirtuin 3	Homo sapiens	0-5
29580688-5	2018	Additionally, treatment with metformin increased the activation of sirtuin 3 (SIRT3), a mitochondrial deacetylase.	Metformin	29-38	sirtuin 3	Homo sapiens	67-76
29580688-5	2018	Additionally, treatment with metformin increased the activation of sirtuin 3 (SIRT3), a mitochondrial deacetylase.	Metformin	29-38	sirtuin 3	Homo sapiens	78-83
29580688-6	2018	We demonstrated that SIRT3 overexpression aggravated metformin-induced apoptosis, energy stress and mitochondrial dysfunction.	Metformin	53-62	sirtuin 3	Homo sapiens	21-26
29540537-7	2018	Expression of active form of AMP-activated protein kinase was reduced in inflammatory bowel disease patients and treatment of mucosal cells of such patients with metformin enhanced AMP-activated protein kinase activation and reduced p38 MAP kinase activation, thereby inhibiting interleukin-6 expression.	Metformin	162-171	mitogen-activated protein kinase 14	Homo sapiens	233-236
29540537-7	2018	Expression of active form of AMP-activated protein kinase was reduced in inflammatory bowel disease patients and treatment of mucosal cells of such patients with metformin enhanced AMP-activated protein kinase activation and reduced p38 MAP kinase activation, thereby inhibiting interleukin-6 expression.	Metformin	162-171	interleukin 6	Homo sapiens	279-292
29895585-0	2018	Metformin Improves Neurologic Outcome Via AMP-Activated Protein Kinase-Mediated Autophagy Activation in a Rat Model of Cardiac Arrest and Resuscitation.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	42-70
29895585-6	2018	Moreover, metformin ameliorated CA-induced neuronal degeneration and glial activation in the hippocampal CA1 region, which was accompanied by augmented AMPK phosphorylation and autophagy activation in affected neuronal tissue.	Metformin	10-19	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	152-156
29895585-7	2018	Inhibition of AMPK or autophagy with pharmacological inhibitors abolished metformin-afforded neuroprotection, and augmented autophagy induction by metformin treatment appeared downstream of AMPK activation.	Metformin	74-83	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	14-18
29895585-7	2018	Inhibition of AMPK or autophagy with pharmacological inhibitors abolished metformin-afforded neuroprotection, and augmented autophagy induction by metformin treatment appeared downstream of AMPK activation.	Metformin	147-156	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	190-194
29895585-8	2018	CONCLUSIONS: Taken together, our data demonstrate, for the first time, that metformin confers neuroprotection against ischemic brain injury after CA/cardiopulmonary resuscitation by augmenting AMPK-dependent autophagy activation.	Metformin	76-85	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	193-197
29567539-3	2018	Additionally, Metformin attenuated TGF-beta-induced epithelial-mesenchymal transition in glioma cells.	Metformin	14-23	transforming growth factor beta 1	Homo sapiens	35-43
29698747-10	2018	Moreover, metformin administration inhibited microglial activation and decreased the production of pro-inflammatory cytokines including TNF-alpha, IL-1beta and IL-6.	Metformin	10-19	tumor necrosis factor	Rattus norvegicus	136-145
29698747-10	2018	Moreover, metformin administration inhibited microglial activation and decreased the production of pro-inflammatory cytokines including TNF-alpha, IL-1beta and IL-6.	Metformin	10-19	interleukin 1 alpha	Rattus norvegicus	147-155
29698747-10	2018	Moreover, metformin administration inhibited microglial activation and decreased the production of pro-inflammatory cytokines including TNF-alpha, IL-1beta and IL-6.	Metformin	10-19	interleukin 6	Rattus norvegicus	160-164
29039022-9	2018	Interestingly, persistent enhancement of the mammalian target of rapamycin, dopamine D1 receptor, and extracellular signaling-regulated kinase 1/2 signaling was maintained in the DA-denervated striatum during metformin treatment.	Metformin	209-218	mechanistic target of rapamycin kinase	Homo sapiens	45-74
29039022-9	2018	Interestingly, persistent enhancement of the mammalian target of rapamycin, dopamine D1 receptor, and extracellular signaling-regulated kinase 1/2 signaling was maintained in the DA-denervated striatum during metformin treatment.	Metformin	209-218	dopamine receptor D1	Homo sapiens	76-96
29039022-10	2018	Metformin globally normalized the increased glycogen synthase kinase 3beta activity induced by chronic treatment of L-DOPA in a manner associated with Akt activation in unilaterally 6-OHDA-lesioned mice.	Metformin	0-9	thymoma viral proto-oncogene 1	Mus musculus	151-154
29897998-6	2018	Results showed that combination treatment with liraglutide (100 nmol/L) and metformin (0.75 mmol/L) significantly decreased cell viability and colony formation, caused cell cycle arrest, upregulated the level of pro-apoptotic proteins Bax and cleaved caspase-3, and inhibited cell migration in the cells, although their single treatment did not exhibit such effects.	Metformin	76-85	BCL2 associated X, apoptosis regulator	Homo sapiens	235-238
29884917-6	2018	Potential treatments currently available for CKD-induced insulin resistance include lifestyle modification and metformin.	Metformin	111-120	insulin	Homo sapiens	57-64
29679571-0	2018	Metformin ameliorates TGF-beta1-induced osteoblastic differentiation of human aortic valve interstitial cells by inhibiting beta-catenin signaling.	Metformin	0-9	transforming growth factor beta 1	Homo sapiens	22-31
29679571-4	2018	Our results showed that metformin ameliorated TGF-beta1-induced production of osteogenic proteins Runx2 and osteopontin as well as calcium deposition in the cultured human AVICs.	Metformin	24-33	transforming growth factor beta 1	Homo sapiens	46-55
29679571-5	2018	Experiments using AICAR, Compound C and AMPKalpha siRNA showed that the beneficial effect of metformin on TGF-beta1-induced osteoblastic differentiation of human AVICs was mediated by AMPKalpha.	Metformin	93-102	transforming growth factor beta 1	Homo sapiens	106-115
29679571-6	2018	Moreover, metformin inhibited the TGF-beta1-induced activation of beta-catenin, and beta-catenin siRNA blocked TGF-beta1-induced osteoblastic differentiation of AVICs.	Metformin	10-19	transforming growth factor beta 1	Homo sapiens	34-43
29679571-7	2018	Smad2/3 and JNK were phosphorylated to promote the TGF-beta1-induced activation of beta-catenin and osteoblastic differentiation of AVICs, and metformin also alleviated TGF-beta1-induced activation of Smad2/3 and JNK.	Metformin	143-152	transforming growth factor beta 1	Homo sapiens	51-60
29679571-7	2018	Smad2/3 and JNK were phosphorylated to promote the TGF-beta1-induced activation of beta-catenin and osteoblastic differentiation of AVICs, and metformin also alleviated TGF-beta1-induced activation of Smad2/3 and JNK.	Metformin	143-152	transforming growth factor beta 1	Homo sapiens	169-178
29679571-7	2018	Smad2/3 and JNK were phosphorylated to promote the TGF-beta1-induced activation of beta-catenin and osteoblastic differentiation of AVICs, and metformin also alleviated TGF-beta1-induced activation of Smad2/3 and JNK.	Metformin	143-152	mitogen-activated protein kinase 8	Homo sapiens	213-216
29550639-4	2018	In contrast, long-term (24 h) exposure to metformin (5 muM-1 mM) concentration-dependently increased 3H-DG uptake in both cell lines.	Metformin	42-51	latexin	Homo sapiens	55-58
29550639-6	2018	Long-term exposure of MCF-7 and MDA-MB-231 cells to metformin (5 muM-1 mM) concentration-dependently reduced cell viability and culture mass and slightly increased cell proliferation rates.	Metformin	52-61	latexin	Homo sapiens	65-68
29264933-5	2018	RESULTS: Among the 74,334 individuals aged &gt;=18 years with T2DM who initiated basal insulin from 2006-2015, 30% were taking metformin (MET) and SU when initiating insulin.	Metformin	127-136	insulin	Homo sapiens	166-173
29460218-6	2018	Insulin-treated patients (insulin alone or insulin plus SU/metformin) also reported experiencing more hypoglycemia (all p-values &lt;0.012).	Metformin	59-68	insulin	Homo sapiens	0-7
29169197-0	2018	Sex-Dependent Effect of Metformin on Serum Prolactin Levels In Hyperprolactinemic Patients With Type 2 Diabetes: A Pilot Study.	Metformin	24-33	prolactin	Homo sapiens	43-52
29169197-9	2018	However, only in women metformin decreased elevated prolactin levels and this effect correlated with an improvement insulin sensitivity, as well as with the impact on SPINA-GT.	Metformin	23-32	prolactin	Homo sapiens	52-61
29169197-10	2018	CONCLUSIONS: The results of the study suggest that the effect of metformin on serum prolactin levels is sex-dependent.	Metformin	65-74	prolactin	Homo sapiens	84-93
29549478-0	2018	Metformin Promotes HaCaT Cell Apoptosis through Generation of Reactive Oxygen Species via Raf-1-ERK1/2-Nrf2 Inactivation.	Metformin	0-9	mitogen-activated protein kinase 3	Homo sapiens	96-102
29779196-2	2018	The efficacy of an insulin-to-liraglutide switch in an obese population with concurrent use of sulfonylurea and metformin is unknown.	Metformin	112-121	insulin	Homo sapiens	19-26
30023463-4	2018	We previously reported that metformin inhibits the phosphorylation of ERK and BEZ235, a dual inhibitor of PI3K and mTOR, has anti-tumor activity against HCT15 CRC cells harboring mutations of KRAS and PIK3CA.	Metformin	28-37	mitogen-activated protein kinase 1	Homo sapiens	70-73
30023463-4	2018	We previously reported that metformin inhibits the phosphorylation of ERK and BEZ235, a dual inhibitor of PI3K and mTOR, has anti-tumor activity against HCT15 CRC cells harboring mutations of KRAS and PIK3CA.	Metformin	28-37	mechanistic target of rapamycin kinase	Homo sapiens	115-119
30023463-4	2018	We previously reported that metformin inhibits the phosphorylation of ERK and BEZ235, a dual inhibitor of PI3K and mTOR, has anti-tumor activity against HCT15 CRC cells harboring mutations of KRAS and PIK3CA.	Metformin	28-37	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	201-207
30023463-7	2018	Our study shows that both of the two signaling pathways can be blocked by this combinational strategy: metformin suppressed both pathways by inhibiting the phosphorylation of ERK, 4E-BP1 and S6, and BEZ235 suppressed PI3K/AKT/ mTOR pathway by reducing the phosphorylation of 4E-BP1 and S6.	Metformin	103-112	mitogen-activated protein kinase 1	Homo sapiens	175-178
30023463-7	2018	Our study shows that both of the two signaling pathways can be blocked by this combinational strategy: metformin suppressed both pathways by inhibiting the phosphorylation of ERK, 4E-BP1 and S6, and BEZ235 suppressed PI3K/AKT/ mTOR pathway by reducing the phosphorylation of 4E-BP1 and S6.	Metformin	103-112	AKT serine/threonine kinase 1	Homo sapiens	222-225
30023463-7	2018	Our study shows that both of the two signaling pathways can be blocked by this combinational strategy: metformin suppressed both pathways by inhibiting the phosphorylation of ERK, 4E-BP1 and S6, and BEZ235 suppressed PI3K/AKT/ mTOR pathway by reducing the phosphorylation of 4E-BP1 and S6.	Metformin	103-112	mechanistic target of rapamycin kinase	Homo sapiens	227-231
29655055-3	2018	The levels of the pro-inflammatory cytokines interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha were decreased by GE, metformin and fasudil in diabetic db/db mice.	Metformin	129-138	interleukin 1 beta	Mus musculus	45-67
29655055-3	2018	The levels of the pro-inflammatory cytokines interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha were decreased by GE, metformin and fasudil in diabetic db/db mice.	Metformin	129-138	interleukin 6	Mus musculus	69-106
29512687-13	2018	Ces1C and Cyp7a1 may be considered novel therapeutic target genes in the liver, which are involved in the antidiabetic effects of metformin.	Metformin	130-139	carboxylesterase 1C	Rattus norvegicus	0-5
29512687-13	2018	Ces1C and Cyp7a1 may be considered novel therapeutic target genes in the liver, which are involved in the antidiabetic effects of metformin.	Metformin	130-139	cytochrome P450 family 7 subfamily A member 1	Rattus norvegicus	10-16
29620187-6	2018	Additionally, overexpression of EZH2 to increase H3K27me3 abrogated the effect of metformin on the cell proliferation, migration and apoptosis in SKOV3 and ES2 cells.	Metformin	82-91	enhancer of zeste 2 polycomb repressive complex 2 subunit	Homo sapiens	32-36
29549478-0	2018	Metformin Promotes HaCaT Cell Apoptosis through Generation of Reactive Oxygen Species via Raf-1-ERK1/2-Nrf2 Inactivation.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	103-107
29789508-5	2018	The biphasic effect of different doses of metformin on adipogenesis was accompanied by increasing or decreasing the expression of adipogenic and lipogenic genes including peroxisome proliferator-activated receptor (PPARgamma), CCAAT/enhancer binding protein alpha (C/EBPalpha), and fatty acid synthase (FASN) at both messenger RNA (mRNA) and protein levels.	Metformin	42-51	fatty acid synthase	Mus musculus	282-301
29231260-8	2018	This study indicated that metformin imposed inhibitory effect on the HBV-associated HCC by negatively regulating the HULC/p18/miR-200a/ZEB1 signaling pathway.	Metformin	26-35	H3 histone pseudogene 12	Homo sapiens	122-125
29231260-8	2018	This study indicated that metformin imposed inhibitory effect on the HBV-associated HCC by negatively regulating the HULC/p18/miR-200a/ZEB1 signaling pathway.	Metformin	26-35	microRNA 200a	Homo sapiens	126-134
29526538-10	2018	In contrast, pharmacological activation of AMPK by metformin significantly inhibited mitochondrial permeability transition pore (mPTP) opening and ROS generation.	Metformin	51-60	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	43-47
29653414-7	2018	RESULTS: Metformin or/and alpha-LA attenuated the severity of the DSS-induced colitis through improving the reductions in body weights, the DAI, the colonic oxidative stress markers, TNF-alpha, and NF-kappaB levels, and the morphological mucosal damage scores.	Metformin	9-18	tumor necrosis factor	Rattus norvegicus	183-192
29871814-7	2018	Therefore, the immunocorrective potentials of modified IL-2 and the anti-diabetic drug metformin are thoroughly discussed in the context of tumor immunobiology, mTOR pathways and revised Warburg effect.	Metformin	87-96	mechanistic target of rapamycin kinase	Homo sapiens	161-165
29870029-0	2018	Metformin added to intensive insulin therapy improves metabolic control in patients with type 1 diabetes and excess body fat.	Metformin	0-9	insulin	Homo sapiens	29-36
29870029-10	2018	CONCLUSIONS In patients with type 1 diabetes and excess body fat, treated with intensive functional insulin therapy, the addition of metformin improves metabolic control of diabetes at 6 months.	Metformin	133-142	insulin	Homo sapiens	100-107
29899823-6	2018	Metformin treatment increased the number of lung CD8-effector-memory T and CD4+Foxp3+IL-10+ T cells in B16F10-transplanted mice.	Metformin	0-9	interleukin 10	Mus musculus	85-90
29899823-9	2018	The metformin/sitagliptin combination was effective in a BRAFV600E/PTEN tamoxifen-inducible murine melanoma model.	Metformin	4-13	phosphatase and tensin homolog	Mus musculus	67-71
29795113-0	2018	Inhibition of LCMR1 and ATG12 by demethylation-activated miR-570-3p is involved in the anti-metastasis effects of metformin on human osteosarcoma.	Metformin	114-123	autophagy related 12	Homo sapiens	24-29
29988567-6	2018	Although chronic therapy with metformin fails to achieve recovery from hyperglycemia, a key feature of diabetes in middle-aged diabetic mice, it improves hippocampal-dependent spatial memory functions accompanied by increased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), atypical protein kinase C zeta (aPKC zeta), and insulin receptor substrate 1 (IRS1) at selective serine residues in the hippocampus.	Metformin	30-39	protein kinase C, zeta	Mus musculus	302-332
29988567-6	2018	Although chronic therapy with metformin fails to achieve recovery from hyperglycemia, a key feature of diabetes in middle-aged diabetic mice, it improves hippocampal-dependent spatial memory functions accompanied by increased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), atypical protein kinase C zeta (aPKC zeta), and insulin receptor substrate 1 (IRS1) at selective serine residues in the hippocampus.	Metformin	30-39	protein kinase C, zeta	Mus musculus	334-343
29988567-7	2018	Our findings suggest that signaling networks acting through long-term metformin-stimulated phosphorylation of AMPK, aPKC zeta/lambda, and IRS1 serine sites contribute to neuroprotective effects on hippocampal neurogenesis and cognitive function independent of a hypoglycemic effect.	Metformin	70-79	protein kinase C, zeta	Mus musculus	116-125
29754323-9	2018	The levels of body mass index, glucose, HbA1c, homeostasis model assessment insulin resistance, and homeostasis model assessment beta-cell function were improved significantly by both exenatide and metformin treatment.	Metformin	198-207	insulin	Homo sapiens	76-83
29256045-0	2018	Metformin Promotes 2-Deoxy-2-[18F]Fluoro-D-Glucose Uptake in Hepatocellular Carcinoma Cells Through FoxO1-Mediated Downregulation of Glucose-6-Phosphatase.	Metformin	0-9	forkhead box O1	Homo sapiens	100-105
29256045-9	2018	RESULTS: Treatment of HCC cells with metformin (Met) leads to a dose-dependent reduction in the expression levels of FoxO1 at the protein level, but not at the mRNA level.	Metformin	37-46	forkhead box O1	Homo sapiens	117-122
29397517-3	2018	We aimed to investigate metformin"s effects on proliferation, metastasis, and hormone receptor expressions in breast cancer cell line MCF-7 incubated in two different glucose conditions.	Metformin	24-33	nuclear receptor subfamily 4 group A member 1	Homo sapiens	78-94
29545331-7	2018	For the first time, we found that the tumor stroma of patients with routine metformin administration exhibited lower IL6 expression.	Metformin	76-85	interleukin 6	Homo sapiens	117-120
29545331-9	2018	We found that metformin partly reversed cisplatin-stimulated IL6 secretion in the stromal fibroblasts and attenuated fibroblast-facilitated tumor growth in 3D organotypic cocultures and murine xenograft models.	Metformin	14-23	interleukin 6	Mus musculus	61-64
29545331-10	2018	Mechanistically, we found that metformin inhibited IL6 secretion via suppressing NFkappaB signaling, an upstream controller of stromal inflammation.	Metformin	31-40	interleukin 6	Homo sapiens	51-54
29480578-5	2018	In in vivo rats, treatment with HCT and metformin for 28 days in rats (28MH rats) reduced the rat Oct2-mediated renal excretion of metformin and thereby the increased systemic exposure of metformin compared with only metformin-treated rats for 28 days (28M rats).	Metformin	40-49	POU class 2 homeobox 2	Rattus norvegicus	98-102
29480578-5	2018	In in vivo rats, treatment with HCT and metformin for 28 days in rats (28MH rats) reduced the rat Oct2-mediated renal excretion of metformin and thereby the increased systemic exposure of metformin compared with only metformin-treated rats for 28 days (28M rats).	Metformin	131-140	POU class 2 homeobox 2	Rattus norvegicus	98-102
29480578-5	2018	In in vivo rats, treatment with HCT and metformin for 28 days in rats (28MH rats) reduced the rat Oct2-mediated renal excretion of metformin and thereby the increased systemic exposure of metformin compared with only metformin-treated rats for 28 days (28M rats).	Metformin	131-140	POU class 2 homeobox 2	Rattus norvegicus	98-102
29480578-5	2018	In in vivo rats, treatment with HCT and metformin for 28 days in rats (28MH rats) reduced the rat Oct2-mediated renal excretion of metformin and thereby the increased systemic exposure of metformin compared with only metformin-treated rats for 28 days (28M rats).	Metformin	131-140	POU class 2 homeobox 2	Rattus norvegicus	98-102
29854390-9	2018	The potential advantages of metformin in pregnant women with T2DM are then discussed, including oral dosing and improved acceptability, lower resource utilization and cost, decreased insulin requirements, less maternal weight gain and less risk of maternal and neonatal hypoglycaemia.	Metformin	28-37	insulin	Homo sapiens	183-190
29880175-3	2018	RESULTS: Adiponectin levels changed -28.27%, -20.37% and 35.78% after OC, combination and metformin therapies, respectively.	Metformin	90-99	adiponectin, C1Q and collagen domain containing	Homo sapiens	9-20
29880175-4	2018	High sensitive C-reactive protein levels (hsCRP) changed with OC, combination and metformin therapies by 102.32%, 3.2% and -7.14%, respectively.	Metformin	82-91	C-reactive protein	Homo sapiens	15-33
29795113-8	2018	Our results, for the first time, presents evidence that the miR-570-3p-mediated suppression of LCMR1 and ATG12 is involved in the metformin-induced inhibition of metastasis in osteosarcoma cells.	Metformin	130-139	autophagy related 12	Homo sapiens	105-110
29789508-5	2018	The biphasic effect of different doses of metformin on adipogenesis was accompanied by increasing or decreasing the expression of adipogenic and lipogenic genes including peroxisome proliferator-activated receptor (PPARgamma), CCAAT/enhancer binding protein alpha (C/EBPalpha), and fatty acid synthase (FASN) at both messenger RNA (mRNA) and protein levels.	Metformin	42-51	fatty acid synthase	Mus musculus	303-307
29789508-6	2018	Furthermore, only the higher concentrations of metformin induced the phosphorylation of adenosine 5"-monophosphate (AMP)-activated protein kinase (AMPK), p38, and c-Jun N-terminal kinase (JNK) and reduced the phosphorylation of extracellular regulated protein kinases (ERK) and Akt.	Metformin	47-56	thymoma viral proto-oncogene 1	Mus musculus	278-281
29759071-14	2018	Additionally, the phosphorylation of AMPK after metformin treatment was 2-fold higher, and the expression of sterol regulatory element-binding protein-1c (SREBP-1c) after metformin treatment was about 2-fold lower compared to high glucose and high insulin group in HepG2 cells.	Metformin	171-180	insulin	Homo sapiens	248-255
29772687-6	2018	The results demonstrate that metformin exerts growth inhibitory effects on cultured HT29 cells by increasing both apoptosis and autophagy; moreover, it affects the survival of cultured cells inhibiting the transcriptional activation of Nuclear factor E2-related factor 2 (NRF-2) and nuclear factor-kappa B (NF-kappaB).	Metformin	29-38	NFE2 like bZIP transcription factor 2	Homo sapiens	236-270
29772687-6	2018	The results demonstrate that metformin exerts growth inhibitory effects on cultured HT29 cells by increasing both apoptosis and autophagy; moreover, it affects the survival of cultured cells inhibiting the transcriptional activation of Nuclear factor E2-related factor 2 (NRF-2) and nuclear factor-kappa B (NF-kappaB).	Metformin	29-38	NFE2 like bZIP transcription factor 2	Homo sapiens	272-277
29772687-6	2018	The results demonstrate that metformin exerts growth inhibitory effects on cultured HT29 cells by increasing both apoptosis and autophagy; moreover, it affects the survival of cultured cells inhibiting the transcriptional activation of Nuclear factor E2-related factor 2 (NRF-2) and nuclear factor-kappa B (NF-kappaB).	Metformin	29-38	nuclear factor kappa B subunit 1	Homo sapiens	283-305
29772687-6	2018	The results demonstrate that metformin exerts growth inhibitory effects on cultured HT29 cells by increasing both apoptosis and autophagy; moreover, it affects the survival of cultured cells inhibiting the transcriptional activation of Nuclear factor E2-related factor 2 (NRF-2) and nuclear factor-kappa B (NF-kappaB).	Metformin	29-38	nuclear factor kappa B subunit 1	Homo sapiens	307-316
29576523-13	2018	CONCLUSION: As women with higher fasting glucose levels have higher chance of necessitating insulin in later pregnancies, appropriate addition of insulin at metformin initiation for these women could help better glycaemic control throughout pregnancy.	Metformin	157-166	insulin	Homo sapiens	92-99
29759071-10	2018	RESULTS: Metformin decreased TG accumulation to normal level in HepG2 cells exposed to high glucose and high insulin.	Metformin	9-18	insulin	Homo sapiens	109-116
29524481-7	2018	Metformin continuation was inversely associated with age (fully adjusted (a) OR 0.60 per 10 years [0.42-0.86]), serum creatinine above safety thresholds (aOR 0.09 [0.02-0.36]), lower income (P = 0.025 for trend), taking more medications (aOR 0.92 per medication [0.86-0.98]), and initiating rapid, short, or premixed insulin (aOR 0.59 [0.39-0.89]).	Metformin	0-9	insulin	Homo sapiens	317-324
29474539-9	2018	Metformin, an activator of AMPK, also inhibited hepatic expression of miR-1224-5p.	Metformin	0-9	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	27-31
29635345-3	2018	Metformin and the bis-indole substituted analogs also induced expression of several glycolytic genes and Rab4, which has previously been linked to enhancing cell membrane accumulation of Glut4 and overall glucose uptake in C2C12 cells, and these responses were also observed after treatment with metformin and the NR4A1 ligands.	Metformin	0-9	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	187-192
29635345-3	2018	Metformin and the bis-indole substituted analogs also induced expression of several glycolytic genes and Rab4, which has previously been linked to enhancing cell membrane accumulation of Glut4 and overall glucose uptake in C2C12 cells, and these responses were also observed after treatment with metformin and the NR4A1 ligands.	Metformin	296-305	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	187-192
29579593-5	2018	Activation of AMPK with chemicals A-769662, 2-deoxyglucose (2-DG), and metformin or constitutively active (CA) AMPK markedly decreased necroptosis and cytotoxicity induced by MNNG.	Metformin	71-80	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	14-18
29579593-8	2018	The AMPK agonist metformin ameliorated myocardial ischemia and reperfusion (IR) injury and reduced necroptosis through down-regulating the expression of PGAM5 in the Langendorff-perfused rat hearts.	Metformin	17-26	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	4-8
29579593-10	2018	Metformin may act as a valuable agent for the protection of myocardial ischemia and reperfusion injury by activating AMPK and reducing necroptosis.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	117-121
30134793-7	2018	Treatment with metformin inhibited these variations and promoted the release of cytokine IL-10 with anti-inflammatory capability.	Metformin	15-24	interleukin 10	Mus musculus	89-94
30134793-8	2018	In vivo, metformin reduced the production of pro-inflammatory cytokines, osteoclastogenesis, and osteolysis, increasing IL-10 production.	Metformin	9-18	interleukin 10	Mus musculus	120-125
29137475-6	2018	Metformin treatment significantly reduced reactive dicarbonyls in the myocardium (MG: p&lt;0.05, GL: p&lt;0.05, 3-DG: p&lt;0.01) along with increase of myocardial concentrations of reduced glutathione (p&lt;0.01) and glyoxalase 1 mRNA expression (p&lt;0.05).	Metformin	0-9	glyoxalase 1	Rattus norvegicus	217-229
29724198-0	2018	The synergistic effects of saxagliptin and metformin on CD34+ endothelial progenitor cells in early type 2 diabetes patients: a randomized clinical trial.	Metformin	43-52	CD34 molecule	Homo sapiens	56-60
29482945-8	2018	Furthermore, metformin could increase anti-proliferative effects of mTORC1 and PI3K/mTOR inhibitors as well as natural products such as berberine and the anti-malarial drug chloroquine in certain PDAC lines.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	68-72
29352482-6	2018	Multivariate modelling revealed that metformin AUC0-48h increased with age, food and carriage of rs12208357 in SLC22A1 but was inversely associated with body surface area and individual proportions of African ancestry.	Metformin	37-46	solute carrier family 22 member 1	Homo sapiens	111-118
29352482-7	2018	CONCLUSIONS: A pharmacogenetic marker in OCT1 (SLC22A1 rs12208357), combined with demographic covariates (age, body surface area and individual proportion of African ancestry) and a food effect explained 29.7% of the variability in metformin AUC0-48h .	Metformin	232-241	solute carrier family 22 member 1	Homo sapiens	47-54
29394501-10	2018	Metformin blocked T317-induced fatty liver by inhibiting T317-induced hepatic LXRalpha nuclear translocation and expression of lipogenic genes and by activating AMPKalpha.	Metformin	0-9	nuclear receptor subfamily 1, group H, member 3	Mus musculus	78-86
29394501-11	2018	Moreover, co-treatment with T317 and metformin improved triglyceride metabolism by inducing expression of adipose triglyceride lipase, hormone-sensitive lipase, PPARalpha and carnitine acetyltransferase and by inhibiting acyl-CoA:diacylglycerol acyltransferase 1 expression.	Metformin	37-46	peroxisome proliferator activated receptor alpha	Mus musculus	161-170
29274299-7	2018	Although metformin significantly upregulated the protein levels of the pro-apoptotic markers cleaved-caspase 3 and Bax in Jurkat cells, rosiglitazone did not have such an effect.	Metformin	9-18	BCL2 associated X, apoptosis regulator	Homo sapiens	115-118
29601127-6	2018	Notably, metformin could increase Snail protein ubiquitination via augmenting the location of LKB1 at cytoplasm as well as increasing LKB1 expression.	Metformin	9-18	snail family transcriptional repressor 1	Homo sapiens	34-39
29601127-8	2018	Targeting the LKB1/FBXL14/Snail axis may represent a promising therapeutic strategy and metformin might be beneficial for PC therapy through activating the LKB1-mediated Snail ubiquitination pathway.	Metformin	88-97	snail family transcriptional repressor 1	Homo sapiens	170-175
29193038-3	2018	OCT1 mediates metformin distribution to the liver (key biophase).	Metformin	14-23	solute carrier family 22 member 1	Homo sapiens	0-4
29193038-4	2018	As OCT1 modulation impacts metformin response, but not pharmacokinetics (PK), metformin DDI studies require pharmacodynamic endpoint(s) to inform rational metformin dose adjustment.	Metformin	27-36	solute carrier family 22 member 1	Homo sapiens	3-7
29221717-6	2018	TNFalpha plasma levels were decreased significantly vs. baseline by metformin combined with TLC intervention (-22.90+-46.76%, P=0.01).	Metformin	68-77	tumor necrosis factor	Homo sapiens	0-8
29555409-6	2018	A clinically relevant concentration of metformin led to AMPK activation, enhanced mineralized nodule formation and increased expression of the osteogenic transcription factor Runt-related transcription factor 2 (RUNX2).	Metformin	39-48	RUNX family transcription factor 2	Homo sapiens	175-210
29555409-6	2018	A clinically relevant concentration of metformin led to AMPK activation, enhanced mineralized nodule formation and increased expression of the osteogenic transcription factor Runt-related transcription factor 2 (RUNX2).	Metformin	39-48	RUNX family transcription factor 2	Homo sapiens	212-217
29576523-2	2018	However, almost half of metformin-treated women required additional insulin.	Metformin	24-33	insulin	Homo sapiens	68-75
29576523-9	2018	Of the included 138 metformin-treated women, 77 (55.8%) required supplementary insulin (metformin failure).	Metformin	20-29	insulin	Homo sapiens	79-86
29576523-9	2018	Of the included 138 metformin-treated women, 77 (55.8%) required supplementary insulin (metformin failure).	Metformin	88-97	insulin	Homo sapiens	79-86
29576523-13	2018	CONCLUSION: As women with higher fasting glucose levels have higher chance of necessitating insulin in later pregnancies, appropriate addition of insulin at metformin initiation for these women could help better glycaemic control throughout pregnancy.	Metformin	157-166	insulin	Homo sapiens	146-153
29512924-11	2018	Compared with THP alone (400 mumol L-1 , 50 muL), the combination with metformin (60 mmol L-1 , 50 muL) stopped growth of bladder cancer completely in vivo (combination group VS normal group P = .078).	Metformin	71-80	L1 cell adhesion molecule	Homo sapiens	90-102
29728793-0	2018	Metformin Protects Against Spinal Cord Injury by Regulating Autophagy via the mTOR Signaling Pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	78-82
29172796-0	2018	Effect of orlistat or metformin in overweight and obese polycystic ovary syndrome patients with insulin resistance.	Metformin	22-31	insulin	Homo sapiens	96-103
29502204-8	2018	Administration of metformin enhanced pAP-2alpha level, reduced miR-124 expression, and increased P4Halpha1 and collagens in carotid atherosclerotic plaque in diabetic Apoe-/- mice.	Metformin	18-27	apolipoprotein E	Mus musculus	167-171
29179590-8	2018	The data indicate that metformin reduces estrogen-induced EH in rats, via activation of the caspase-dependent mitochondrial apoptotic pathway, to the same degree as progesterone.	Metformin	23-32	caspase 9	Rattus norvegicus	92-99
29182407-0	2018	Metformin is associated with reduced cell proliferation in human endometrial cancer by inbibiting PI3K/AKT/mTOR signaling.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	103-106
29182407-0	2018	Metformin is associated with reduced cell proliferation in human endometrial cancer by inbibiting PI3K/AKT/mTOR signaling.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	107-111
29182407-7	2018	In parallel, the reduced PI3K, p-AKT, p-S6K1, and p-4EBP1 staining induced by metformin appeared to play an important role for the anti-proliferative effects of metformin in endometrial cancer patients.	Metformin	78-87	AKT serine/threonine kinase 1	Homo sapiens	33-36
29182407-7	2018	In parallel, the reduced PI3K, p-AKT, p-S6K1, and p-4EBP1 staining induced by metformin appeared to play an important role for the anti-proliferative effects of metformin in endometrial cancer patients.	Metformin	161-170	AKT serine/threonine kinase 1	Homo sapiens	33-36
29182407-8	2018	Metformin significantly decreased proliferation in human endometrial cancer may by inhibiting PI3K/AKT/mTOR signaling.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	99-102
29182407-8	2018	Metformin significantly decreased proliferation in human endometrial cancer may by inhibiting PI3K/AKT/mTOR signaling.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	103-107
29728793-8	2018	Western blot and immunofluorescent analysis revealed that mammalian target of rapamycin (mTOR) and P70S6 kinase (P70S6K) decreased, while the expression of autophagy markers increased and apoptosis markers declined in animals treated with metformin following SCI.	Metformin	239-248	mechanistic target of rapamycin kinase	Homo sapiens	58-87
29728793-9	2018	Taken together, these findings suggest that metformin functions as a neuroprotective agent following SCI by promoting autophagy and inhibiting apoptosis by regulating the mTOR/P70S6K signaling pathway.	Metformin	44-53	mechanistic target of rapamycin kinase	Homo sapiens	171-175
29725482-0	2018	Metformin inhibits the proliferation and metastasis of osteosarcoma cells by suppressing the phosphorylation of Akt.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	112-115
29232177-12	2018	Metformin reduced MCT1 staining by 28% ( P = .05) and increased carcinoma cell apoptosis 1.8-fold as marked by TUNEL assay ( P = .005).	Metformin	0-9	modifier of curly tail 1	Mus musculus	18-22
29765528-0	2018	Metabolic changes associated with metformin potentiates Bcl-2 inhibitor, Venetoclax, and CDK9 inhibitor, BAY1143572 and reduces viability of lymphoma cells.	Metformin	34-43	BCL2 apoptosis regulator	Homo sapiens	56-61
30008760-5	2018	Considering the efficacy and safety of combination therapy of insulin with older hypoglycemic agents, in general metformin and pioglitazone have the best and worst profiles, respectively.	Metformin	113-122	insulin	Homo sapiens	62-69
30008760-10	2018	Conclusions: Considering the quality and longevity of evidence, compared to insulin monotherapy, insulin combined with metformin and pioglitazone has the best and worst profiles, respectively.	Metformin	119-128	insulin	Homo sapiens	97-104
29765528-0	2018	Metabolic changes associated with metformin potentiates Bcl-2 inhibitor, Venetoclax, and CDK9 inhibitor, BAY1143572 and reduces viability of lymphoma cells.	Metformin	34-43	cyclin dependent kinase 9	Homo sapiens	89-93
29651002-5	2018	After 3 months, metformin prevented HFCD-induced weight gain, hepatic steatosis, depletion of intact acini, formation of advanced PanIN lesions, and stimulation of ERK and mTORC1 in pancreas.	Metformin	16-25	mitogen-activated protein kinase 1	Mus musculus	164-167
29665787-11	2018	However, the addition of VPA dramatically upregulated histone H3 acetylation, increased the sensibility of AKT and inhibited pSMAD3/SMAD4, letting the combination of VPA and metformin remarkably reappear the anti-tumour effects of metformin in 786-M-R cells.	Metformin	174-183	AKT serine/threonine kinase 1	Homo sapiens	107-110
29651002-8	2018	The obesogenic diet also induced a marked increase in the expression of TAZ in pancreas, an effect abrogated by metformin.	Metformin	112-121	tafazzin, phospholipid-lysophospholipid transacylase	Mus musculus	72-75
29662316-9	2018	Furthermore, our study revealed that metformin activated AMPK and suppressed mTOR and HIF1alpha expression.	Metformin	37-46	mechanistic target of rapamycin kinase	Homo sapiens	77-81
29636010-8	2018	In the atrial myocytes from control, GK and metformin-treated GK rats, the expression of KCa2.2 (SK2 channel) was down-regulated and the expression of KCa2.3 (SK3 channel) was up-regulated in the atrium of GK rats as compared with that of control rats, and metformin reversed diabetes-induced alterations in atrial SK channel expression.	Metformin	44-53	potassium calcium-activated channel subfamily N member 2	Rattus norvegicus	89-95
29636010-8	2018	In the atrial myocytes from control, GK and metformin-treated GK rats, the expression of KCa2.2 (SK2 channel) was down-regulated and the expression of KCa2.3 (SK3 channel) was up-regulated in the atrium of GK rats as compared with that of control rats, and metformin reversed diabetes-induced alterations in atrial SK channel expression.	Metformin	44-53	potassium calcium-activated channel subfamily N member 2	Rattus norvegicus	97-100
29383869-8	2018	While each tissue had a signature reflecting its own function, we identified a cascade of predictive upstream transcriptional regulators, including mTORC1, MYC, TNF, TGFss1, and miRNA-29b that may explain tissue-specific transcriptomic changes in response to metformin treatment.	Metformin	259-268	tumor necrosis factor	Homo sapiens	161-164
30104075-1	2018	BACKGROUND: Insulin sensitizers like metformin and pioglitazone are clinically used since last decades for the treatment of PCOS, but their efficacy and possible role in PCOS patients remains questionable.	Metformin	37-46	insulin	Homo sapiens	12-19
30104075-8	2018	LH receptor and FSH receptor mRNA expression were altered by pioglitazone and metformin treatment.	Metformin	78-87	luteinizing hormone/choriogonadotropin receptor	Rattus norvegicus	0-11
29662316-9	2018	Furthermore, our study revealed that metformin activated AMPK and suppressed mTOR and HIF1alpha expression.	Metformin	37-46	hypoxia inducible factor 1 subunit alpha	Homo sapiens	86-95
29662316-12	2018	Conclusion: Taken together, these results indicated that metformin may play an important role in modulating CD19-CAR T cell biological functions in an AMPK-dependent and mTOR/HIF1alpha-independent manner.	Metformin	57-66	mechanistic target of rapamycin kinase	Homo sapiens	170-174
29662316-12	2018	Conclusion: Taken together, these results indicated that metformin may play an important role in modulating CD19-CAR T cell biological functions in an AMPK-dependent and mTOR/HIF1alpha-independent manner.	Metformin	57-66	hypoxia inducible factor 1 subunit alpha	Homo sapiens	175-184
29576625-8	2018	Metformin and phenformin decreased mTOR activity in chondrosarcoma cells, and metformin decreased LC3B-II levels, which is counteracted by chloroquine.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	35-39
29366775-9	2018	Furthermore, a chronic low dose administration of metformin significantly attenuated vascular aging and inhibited age-associated atherosclerotic plaque formation in ApoE-/- mice.	Metformin	50-59	apolipoprotein E	Mus musculus	165-169
29396886-0	2018	Antitumor effects of metformin are a result of inhibiting nuclear factor kappa B nuclear translocation in esophageal squamous cell carcinoma.	Metformin	21-30	nuclear factor kappa B subunit 1	Homo sapiens	58-80
29396886-7	2018	We found that localization of NF-kappaB in the nucleus was reduced after metformin treatment.	Metformin	73-82	nuclear factor kappa B subunit 1	Homo sapiens	30-39
29396886-8	2018	This suggests that metformin inhibited the activation of NF-kappaB.	Metformin	19-28	nuclear factor kappa B subunit 1	Homo sapiens	57-66
29396886-11	2018	Metformin inhibited cell motility and induced E-cadherin expression.	Metformin	0-9	cadherin 1	Homo sapiens	46-56
29396886-12	2018	In conclusion, metformin showed multiple antitumor effects such as growth suppression, invasion inhibition, and control of EMT by inhibiting NF-kappaB localization on ESCC.	Metformin	15-24	nuclear factor kappa B subunit 1	Homo sapiens	141-150
28230250-0	2018	Metformin attenuates angiotensin II-induced TGFbeta1 expression by targeting hepatocyte nuclear factor-4-alpha.	Metformin	0-9	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	21-35
28230250-1	2018	BACKGROUND AND PURPOSE: Metformin, a small molecule, antihyperglycaemic agent, is a well-known activator of AMP-activated protein kinase (AMPK) and protects against cardiac fibrosis.	Metformin	24-33	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	138-142
28230250-4	2018	Here, we investigated the effects of metformin on TGFbeta1 production induced by angiotensin II (AngII) and the underlying mechanisms.	Metformin	37-46	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	81-95
28230250-4	2018	Here, we investigated the effects of metformin on TGFbeta1 production induced by angiotensin II (AngII) and the underlying mechanisms.	Metformin	37-46	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	97-102
28230250-7	2018	KEY RESULTS: In CFs, metformin inhibited AngII-induced TGFbeta1 expression via AMPK activation.	Metformin	21-30	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	41-46
28230250-7	2018	KEY RESULTS: In CFs, metformin inhibited AngII-induced TGFbeta1 expression via AMPK activation.	Metformin	21-30	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	79-83
28230250-11	2018	Metformin inhibited the AngII-induced increases in HNF4alpha protein expression and binding to the Tgfb1 promoter in CFs.	Metformin	0-9	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	24-29
28230250-12	2018	In vivo, metformin blocked the AngII-induced increase in cardiac HNF4alpha protein levels in wild-type mice but not in AMPKalpha2-/- mice.	Metformin	9-18	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	31-36
28230250-13	2018	Consequently, metformin inhibited AngII-induced TGFbeta1 production and cardiac fibrosis in wild-type mice but not in AMPKalpha2-/- mice.	Metformin	14-23	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	34-39
28230250-15	2018	Metformin inhibits AngII-induced HNF4alpha expression via AMPK activation, thus decreasing TGFbeta1 transcription and cardiac fibrosis.	Metformin	0-9	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	19-24
28230250-15	2018	Metformin inhibits AngII-induced HNF4alpha expression via AMPK activation, thus decreasing TGFbeta1 transcription and cardiac fibrosis.	Metformin	0-9	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	58-62
29508275-16	2018	Metformin combined with insulin is associated with decreased weight gain, lower insulin dose, and less hypoglycemia when compared with insulin alone (C).	Metformin	0-9	insulin	Homo sapiens	80-87
29508275-16	2018	Metformin combined with insulin is associated with decreased weight gain, lower insulin dose, and less hypoglycemia when compared with insulin alone (C).	Metformin	0-9	insulin	Homo sapiens	80-87
29306537-11	2018	The Western blot assay showed that DPCs express functional organic cation transporter 1, a transmembrane protein that mediates the intracellular uptake of metformin.	Metformin	155-164	solute carrier family 22 member 1	Homo sapiens	59-87
29393487-0	2018	Effects of metformin on the expression of AMPK and STAT3 in the spinal dorsal horn of rats with neuropathic pain.	Metformin	11-20	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	42-46
29484415-8	2018	Western blotting showed that metformin decreased the expression of LDHA, which plays a key role in the Warburg effect.	Metformin	29-38	lactate dehydrogenase A	Homo sapiens	67-71
29589999-11	2018	The IL-1beta-induced hyaluronan production and mRNA expression of IL-6, cyclooxygenase-2, and intercellular adhesion molecule-1 were also significantly suppressed after metformin or phenformin co-treatment.	Metformin	169-178	interleukin 1 beta	Homo sapiens	4-12
29589999-11	2018	The IL-1beta-induced hyaluronan production and mRNA expression of IL-6, cyclooxygenase-2, and intercellular adhesion molecule-1 were also significantly suppressed after metformin or phenformin co-treatment.	Metformin	169-178	interleukin 6	Homo sapiens	66-70
29589999-11	2018	The IL-1beta-induced hyaluronan production and mRNA expression of IL-6, cyclooxygenase-2, and intercellular adhesion molecule-1 were also significantly suppressed after metformin or phenformin co-treatment.	Metformin	169-178	prostaglandin-endoperoxide synthase 2	Homo sapiens	72-127
29348175-6	2018	Under high-glucose conditions, pharmacological activation of AMPK in isolated mouse islets or MIN6 cells by metformin or 5-aminoimidazole-4-carboxamide riboside decreased MafA protein levels and mRNA expression of insulin and GSIS-related genes (i.e. glut2 and sur1).	Metformin	108-117	ATP-binding cassette, sub-family C (CFTR/MRP), member 8	Mus musculus	261-265
29157127-5	2018	Metformin treatment decreased the expression of IL-1beta and IL-6 in epididymal fat, which was correlated with the abundance of various bacterial genera.	Metformin	0-9	interleukin 1 beta	Mus musculus	48-56
29157127-5	2018	Metformin treatment decreased the expression of IL-1beta and IL-6 in epididymal fat, which was correlated with the abundance of various bacterial genera.	Metformin	0-9	interleukin 6	Mus musculus	61-65
29499335-7	2018	Metformin-mediated activation of AMPK was able to significantly abrogate cholesterol uptake by inhibiting SREBP2-M. Interestingly, although metformin administration attenuated angiotensin (Ang)-II-impaired lipid homeostasis in both aorta and liver tissues of ApoE-/- mice, the results indicate that SREBP2 through LDLR regulates lipid homeostasis in aorta but not in liver tissue.	Metformin	0-9	apolipoprotein E	Mus musculus	259-263
29499335-7	2018	Metformin-mediated activation of AMPK was able to significantly abrogate cholesterol uptake by inhibiting SREBP2-M. Interestingly, although metformin administration attenuated angiotensin (Ang)-II-impaired lipid homeostasis in both aorta and liver tissues of ApoE-/- mice, the results indicate that SREBP2 through LDLR regulates lipid homeostasis in aorta but not in liver tissue.	Metformin	140-149	apolipoprotein E	Mus musculus	259-263
29552226-0	2018	The co-treatment of metformin with flavone synergistically induces apoptosis through inhibition of PI3K/AKT pathway in breast cancer cells.	Metformin	20-29	AKT serine/threonine kinase 1	Homo sapiens	104-107
29552226-1	2018	Metformin, a widely used antidiabetic drug, exhibits anticancer effects which are mediated by the phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (AKT) signaling pathway.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	160-163
29611351-5	2018	Recent reports suggested that sildenafil, metformin, and simvastatin might improve ADH-independent urine concentration.	Metformin	42-51	arginine vasopressin	Homo sapiens	83-86
29272251-4	2018	The effects of metformin in cancer cells resemble the patterns observed after treatment with drugs that downregulate specificity protein 1 (Sp1), Sp3 and Sp4 or by knockdown of Sp1, Sp3 and Sp4 by RNA interference.	Metformin	15-24	Sp1 transcription factor	Homo sapiens	117-138
29272251-4	2018	The effects of metformin in cancer cells resemble the patterns observed after treatment with drugs that downregulate specificity protein 1 (Sp1), Sp3 and Sp4 or by knockdown of Sp1, Sp3 and Sp4 by RNA interference.	Metformin	15-24	Sp3 transcription factor	Homo sapiens	146-149
29272251-4	2018	The effects of metformin in cancer cells resemble the patterns observed after treatment with drugs that downregulate specificity protein 1 (Sp1), Sp3 and Sp4 or by knockdown of Sp1, Sp3 and Sp4 by RNA interference.	Metformin	15-24	Sp3 transcription factor	Homo sapiens	182-185
29272251-5	2018	Studies in pancreatic cancer cells clearly demonstrate that metformin decreases expression of Sp1, Sp3, Sp4 and pro-oncogenic Sp-regulated genes, demonstrating that one of the underlying mechanisms of action of metformin as an anticancer agent involves targeting of Sp transcription factors.	Metformin	60-69	Sp3 transcription factor	Homo sapiens	99-102
29272251-5	2018	Studies in pancreatic cancer cells clearly demonstrate that metformin decreases expression of Sp1, Sp3, Sp4 and pro-oncogenic Sp-regulated genes, demonstrating that one of the underlying mechanisms of action of metformin as an anticancer agent involves targeting of Sp transcription factors.	Metformin	211-220	Sp3 transcription factor	Homo sapiens	99-102
29559078-0	2018	[Metformin is a possible glucagon-like peptide 1 stimulator].	Metformin	1-10	glucagon	Homo sapiens	25-48
29900050-0	2018	Metformin blocks myeloid-derived suppressor cell accumulation through AMPK-DACH1-CXCL1 axis.	Metformin	0-9	chemokine (C-X-C motif) ligand 1	Mus musculus	81-86
29900050-11	2018	Metformin inhibited CXCL1 secretion in ESCC cells and tumor xenografts by enhancing AMPK phosphorylation and inducing DACH1 expression, leading to NF-kappaB inhibition and reducing MDSC migration.	Metformin	0-9	chemokine (C-X-C motif) ligand 1	Mus musculus	20-25
29900050-13	2018	Conclusions: A novel anti-tumor effect of metformin, which is mediated by reducing PMN-MDSC accumulation in the tumor microenvironment via AMPK/DACH1/CXCL1 axis.	Metformin	42-51	chemokine (C-X-C motif) ligand 1	Mus musculus	150-155
29513760-6	2018	Several inflammatory molecules upregulated by tumor necrosis factor-alpha in human retinal vascular endothelial cells were markedly reduced by metformin, including nuclear factor kappa B p65 (NFkappaB p65), intercellular adhesion molecule-1 (ICAM-1), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8).	Metformin	143-152	tumor necrosis factor	Homo sapiens	46-73
29513760-6	2018	Several inflammatory molecules upregulated by tumor necrosis factor-alpha in human retinal vascular endothelial cells were markedly reduced by metformin, including nuclear factor kappa B p65 (NFkappaB p65), intercellular adhesion molecule-1 (ICAM-1), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8).	Metformin	143-152	C-X-C motif chemokine ligand 8	Homo sapiens	295-308
29513760-6	2018	Several inflammatory molecules upregulated by tumor necrosis factor-alpha in human retinal vascular endothelial cells were markedly reduced by metformin, including nuclear factor kappa B p65 (NFkappaB p65), intercellular adhesion molecule-1 (ICAM-1), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8).	Metformin	143-152	C-X-C motif chemokine ligand 8	Homo sapiens	310-314
29500444-0	2018	Metformin-induced caveolin-1 expression promotes T-DM1 drug efficacy in breast cancer cells.	Metformin	0-9	caveolin 1	Homo sapiens	18-28
29500444-5	2018	In this study, diabetes drug metformin was investigated in terms of induction of caveolin-1 expression for increased efficacy of subsequent T-DM1 application.	Metformin	29-38	caveolin 1	Homo sapiens	81-91
29500444-9	2018	Result showed that in BT-474 cells pretreated with metformin, cellular caveolin-1 overexpression was induced, which then promoted drug efficacy by enhancing T-DM1 internalization.	Metformin	51-60	caveolin 1	Homo sapiens	71-81
29500444-10	2018	As cellular caveolin-1 was suppressed by shRNA, the effect of metformin-enhanced T-DM1 cytotoxicity was decreased.	Metformin	62-71	caveolin 1	Homo sapiens	12-22
29500444-11	2018	This study demonstrated that metformin can be applied prior to T-DM1 treatment to improve the clinical efficacy of T-DM1 by enhancing caveolin-1-mediated endocytosis.	Metformin	29-38	caveolin 1	Homo sapiens	134-144
29670840-2	2018	Metformin and rapamycin may decrease the expression of VEGF protein and subsequently angiogenesis.	Metformin	0-9	vascular endothelial growth factor A	Homo sapiens	55-59
29670844-5	2018	Results: Metformin and CaD, either alone or in combination, caused a significant reduction in HFFr diet-induced high serum aspartate aminotransferase (AST), hepatic steatosis and lipid accumulation without effect on insulin resistance and AMPK phosphorylation.	Metformin	9-18	glutamic-oxaloacetic transaminase 2	Rattus norvegicus	123-149
29670844-5	2018	Results: Metformin and CaD, either alone or in combination, caused a significant reduction in HFFr diet-induced high serum aspartate aminotransferase (AST), hepatic steatosis and lipid accumulation without effect on insulin resistance and AMPK phosphorylation.	Metformin	9-18	glutamic-oxaloacetic transaminase 2	Rattus norvegicus	151-154
29670844-5	2018	Results: Metformin and CaD, either alone or in combination, caused a significant reduction in HFFr diet-induced high serum aspartate aminotransferase (AST), hepatic steatosis and lipid accumulation without effect on insulin resistance and AMPK phosphorylation.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	239-243
29670844-7	2018	Conclusion: Taken together, our results suggest that metformin and CaD could protect against the onset of HFFr diet-induced NAFLD in an insulin and AMPK-independent manner, without any marked additional benefits of their combination.	Metformin	53-62	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	148-152
29393487-5	2018	Metformin is a widely available drug that possesses the ability to activate AMPK.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	76-80
29393487-7	2018	The present study investigated the analgesic effect of metformin on NP induced by chronic constriction injury (CCI), and the influence of metformin on the expression of AMPK and STAT3 in the spinal dorsal horn (SDH).	Metformin	138-147	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	169-173
29393487-9	2018	Administering intraperitoneal injections of metformin (200 mg/kg) for 6 successive days activated AMPK and suppressed the expression of p-STAT3, in addition to reversing hyperalgesia.	Metformin	44-53	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	98-102
28967181-0	2018	Metformin and beta-cell function in insulin-treated patients with type 2 diabetes: A randomized placebo-controlled 4.3-year trial.	Metformin	0-9	insulin	Homo sapiens	36-43
29285837-0	2018	New metformin derivative HL156A prevents oral cancer progression by inhibiting the insulin-like growth factor/AKT/mammalian target of rapamycin pathways.	Metformin	4-13	AKT serine/threonine kinase 1	Homo sapiens	110-113
29285837-0	2018	New metformin derivative HL156A prevents oral cancer progression by inhibiting the insulin-like growth factor/AKT/mammalian target of rapamycin pathways.	Metformin	4-13	mechanistic target of rapamycin kinase	Homo sapiens	114-143
29326107-6	2018	In a subset of participants, the T allele was associated with higher basal glucagon-like peptide 1 (GLP-1) levels at visit 1 (beta = 1.52, P = 0.02 and beta = 0.96, P = 0.002 for total and active GLP-1, respectively), and across all points of the OGTT after metformin administration.	Metformin	258-267	glucagon	Homo sapiens	75-98
29326107-6	2018	In a subset of participants, the T allele was associated with higher basal glucagon-like peptide 1 (GLP-1) levels at visit 1 (beta = 1.52, P = 0.02 and beta = 0.96, P = 0.002 for total and active GLP-1, respectively), and across all points of the OGTT after metformin administration.	Metformin	258-267	glucagon	Homo sapiens	100-105
29456653-6	2018	Furthermore, ox-LDL-induced cytochrome c (cyto-c) release and mitochondrial membrane potential loss were inhibited by metformin.	Metformin	118-127	cytochrome c, somatic	Homo sapiens	28-40
29456653-6	2018	Furthermore, ox-LDL-induced cytochrome c (cyto-c) release and mitochondrial membrane potential loss were inhibited by metformin.	Metformin	118-127	cytochrome c, somatic	Homo sapiens	42-48
29456653-7	2018	As lipid uptake in macrophages contributed to ER stress, cyto-c release and mitochondrial membrane potential loss, the mechanisms involved in metformin-inhibited macrophage lipid uptake were investigated.	Metformin	142-151	cytochrome c, somatic	Homo sapiens	57-63
29293982-20	2018	The MD in homoeostasis model assessment of insulin resistance (HOMA-IR) were also in favour of metformin therapy compared to COC and/or AA.	Metformin	95-104	insulin	Homo sapiens	43-50
29138876-6	2018	RESULTS: Individuals aged &gt;=65 years on metformin + pioglitazone had a significantly lower risk of dementia compared with those on metformin + sulfonylurea (HR 0.56; 95% CI 0.34, 0.93), and a lower, but insignificant, risk of dementia compared with those on other metformin-based dual regimens (i.e. metformin + acarbose, metformin + meglitinide, metformin + insulin or metformin + dipeptidyl peptidase 4 inhibitors).	Metformin	43-52	insulin	Homo sapiens	362-369
29286156-0	2018	Metformin-induced activation of AMPK inhibits the proliferation and migration of human aortic smooth muscle cells through upregulation of p53 and IFI16.	Metformin	0-9	tumor protein p53	Homo sapiens	138-141
29286156-8	2018	In addition, metformin was able to activate p53, IFI16 and AMPK, in order to inhibit proliferation and migration of HASMCs.	Metformin	13-22	tumor protein p53	Homo sapiens	44-47
29286156-9	2018	Furthermore, siRNA-mediated knockdown of p53 and IFI16 attenuated AMPK activation and reversed the suppressive effects of metformin.	Metformin	122-131	tumor protein p53	Homo sapiens	41-44
29286156-11	2018	These results indicated that metformin-induced activation of AMPK suppresses the proliferation and migration of HASMCs by upregulating p53 and IFI16.	Metformin	29-38	tumor protein p53	Homo sapiens	135-138
29117515-0	2018	Metformin and epothilone A treatment up regulate pro-apoptotic PARP-1, Casp-3 and H2AX genes and decrease of AKT kinase level to control cell death of human hepatocellular carcinoma and ovary adenocarcinoma cells.	Metformin	0-9	poly(ADP-ribose) polymerase 1	Homo sapiens	63-69
29117515-6	2018	Compared to either drug alone, combination of epothilone A and metformin was more potent; decreased Akt level; and elevated percentage of apoptotic cells, induced cell cycle arrest at G1 phase and elevated the sub-G1 cell population by increasing the mRNA level of caspase-3, poly (ADP-ribose) polymerase-1 and H2AX.	Metformin	63-72	AKT serine/threonine kinase 1	Homo sapiens	100-103
29117515-6	2018	Compared to either drug alone, combination of epothilone A and metformin was more potent; decreased Akt level; and elevated percentage of apoptotic cells, induced cell cycle arrest at G1 phase and elevated the sub-G1 cell population by increasing the mRNA level of caspase-3, poly (ADP-ribose) polymerase-1 and H2AX.	Metformin	63-72	caspase 3	Homo sapiens	265-306
28106245-3	2018	There is increasing observational and experimental evidence that improving diet and the use of metformin (a calorie-restriction mimetic drug) may modify the risk of developing MetS and ArCD.	Metformin	95-104	apolipoprotein B mRNA editing enzyme catalytic subunit 3G	Homo sapiens	185-189
28142230-9	2018	CK25 and metformin significantly increased the phosphorylation of hepatic adenosine monophosphate-activated protein kinase (AMPK).	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	74-122
28142230-9	2018	CK25 and metformin significantly increased the phosphorylation of hepatic adenosine monophosphate-activated protein kinase (AMPK).	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	124-128
28954218-13	2018	Insulin therapy associated to metformin is able to improve fasting microvascular endothelial function even before complete metabolic control.	Metformin	30-39	insulin	Homo sapiens	0-7
29286158-0	2018	Metformin inhibits HaCaT cell viability via the miR-21/PTEN/Akt signaling pathway.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	60-63
29286158-10	2018	Metformin was, therefore, concluded to inhibit HaCaT cell growth in a time-and dose-dependent manner, and the miR-21/PTEN/Akt signaling pathway may serve a crucial role in the molecular mechanism of metformin"s effect on HaCaT cells.	Metformin	199-208	AKT serine/threonine kinase 1	Homo sapiens	122-125
29435022-5	2018	A Transwell assay and western blot analysis revealed that metformin inhibited the migration and invasion of EC109 cells, nuclear factor-kappaB activation, matrix metallopeptidase 9 and N-cadherin expression in a phosphorylated-AKT dependent manner.	Metformin	58-67	AKT serine/threonine kinase 1	Homo sapiens	227-230
29435022-6	2018	These results suggested that metformin inhibits the migration and invasion of human esophageal carcinoma cells by suppressing AKT phosphorylation and regulating the expression of migration- and invasion-associated genes.	Metformin	29-38	AKT serine/threonine kinase 1	Homo sapiens	126-129
29162538-0	2018	Metformin promotes the proliferation and differentiation of murine preosteoblast by regulating the expression of sirt6 and oct4.	Metformin	0-9	sirtuin 6	Mus musculus	113-118
29162538-4	2018	In our research, we show that metformin can promote proliferation of murine preosteoblast by regulating AMPK-mTORC2 and AKT-mTORC1 signaling axis.	Metformin	30-39	thymoma viral proto-oncogene 1	Mus musculus	120-123
29162538-5	2018	Furthermore, we have observed that metformin can promote SIRT6 expression before and during differentiation of murine preosteoblast.	Metformin	35-44	sirtuin 6	Mus musculus	57-62
28915221-0	2018	Metformin Exerts Beneficial Effects in Hemorrhagic Shock in An AMPKalpha1-Independent Manner.	Metformin	0-9	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	63-73
28915221-11	2018	Beneficial effects of metformin were associated with organ-specific nuclear-cytoplasmic shuttling and activation of liver kinase B1 and AMPKalpha2.	Metformin	22-31	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	136-146
28915221-13	2018	Our data also suggest that metformin affords beneficial effects, at least in part, independently of AMPKalpha1 and secondary to AMPKalpha2 activation, increase of Complex II function and reduction of oxidative stress.	Metformin	27-36	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	128-138
29117515-0	2018	Metformin and epothilone A treatment up regulate pro-apoptotic PARP-1, Casp-3 and H2AX genes and decrease of AKT kinase level to control cell death of human hepatocellular carcinoma and ovary adenocarcinoma cells.	Metformin	0-9	caspase 3	Homo sapiens	71-77
29117515-0	2018	Metformin and epothilone A treatment up regulate pro-apoptotic PARP-1, Casp-3 and H2AX genes and decrease of AKT kinase level to control cell death of human hepatocellular carcinoma and ovary adenocarcinoma cells.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	109-112
29482528-9	2018	Saxagliptin, metformin, and the combination treatment significantly reduced the homeostasis model assessment- insulin resistance index and increased the deposition index (P &lt; 0.01 for all).	Metformin	13-22	insulin	Homo sapiens	110-117
29483552-3	2018	Prior incubation of ASMCs with metformin induced AMPK activation and blocked TGF-beta1-induced cell proliferation.	Metformin	31-40	transforming growth factor beta 1	Homo sapiens	77-86
29520235-10	2018	Our findings challenge the view that metformin causes an inhibition of glucose release from the liver by an acute inhibition of mitochondrial glycerol 3-phosphate dehydrogenase (EC 1.1.5.3).	Metformin	37-46	glycerol-3-phosphate dehydrogenase 1	Rattus norvegicus	142-176
29681936-0	2018	Metformin Regulating miR-34a Pathway to Inhibit Egr1 in Rat Mesangial Cells Cultured with High Glucose.	Metformin	0-9	early growth response 1	Rattus norvegicus	48-52
29681936-11	2018	Metformin attenuates high glucose-stimulated inflammation and fibrosis in MCs by regulating miR-34a-mediated SIRT1/AMPKalpha activity and the downstream Egr1 protein.	Metformin	0-9	sirtuin 1	Rattus norvegicus	109-114
29466360-8	2018	We examined the ability of metformin + esomeprazole to rescue TNF-alpha induced vascular cell adhesion molecule-1 (VCAM-1) and Endothelin-1 (ET-1) expression, leukocyte adhesion (markers of endothelial dysfunction).	Metformin	27-36	tumor necrosis factor	Homo sapiens	62-71
29466360-11	2018	The low-dose combination of metformin + esomeprazole additively reduced TNF-alpha-induced VCAM-1 mRNA, but not VCAM-1 protein expression.	Metformin	28-37	tumor necrosis factor	Homo sapiens	72-81
29466360-11	2018	The low-dose combination of metformin + esomeprazole additively reduced TNF-alpha-induced VCAM-1 mRNA, but not VCAM-1 protein expression.	Metformin	28-37	vascular cell adhesion molecule 1	Homo sapiens	90-96
29466360-13	2018	However, combining metformin and esomeprazole additively reduced ET-1 mRNA expression.	Metformin	19-28	endothelin 1	Homo sapiens	65-69
29467030-2	2018	In patients with cardiovascular disease, kidney disease, and/or diabetes, renin-angiotensin system blockers, non-steroidal anti-inflammatory drugs, diuretics, and metformin can increase the risk of CI-AKI when undergoing contrast imaging.	Metformin	163-172	renin	Homo sapiens	74-79
29472557-6	2018	Metformin reduced cyclin D1 expression and RB, STAT3, STAT5, ERK1/2 and p70S6K phosphorylation.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	47-52
29472557-6	2018	Metformin reduced cyclin D1 expression and RB, STAT3, STAT5, ERK1/2 and p70S6K phosphorylation.	Metformin	0-9	mitogen-activated protein kinase 3	Homo sapiens	61-67
29447230-8	2018	We also found that a predisposition to mitochondrial dysfunction, caused by a genetic mutation or pharmacological suppression of the electron transport chain by biguanides such as metformin and phenformin, promoted propofol-induced caspase activation and cell death induced by clinical relevant concentrations of propofol in not more than 25 muM.	Metformin	180-189	latexin	Homo sapiens	342-345
29681936-11	2018	Metformin attenuates high glucose-stimulated inflammation and fibrosis in MCs by regulating miR-34a-mediated SIRT1/AMPKalpha activity and the downstream Egr1 protein.	Metformin	0-9	early growth response 1	Rattus norvegicus	153-157
29444159-1	2018	OBJECTIVE: Metformin, an antidiabetic drug, inhibits the endometrial cancer cell growth in vivo by improving the insulin resistance; however, its mechanism of action is not completely understood.	Metformin	11-20	insulin	Homo sapiens	113-120
29342230-2	2018	To uncover the anti-cancer mechanisms of metformin, preclinical studies determined that metformin impairs cellular metabolism and suppresses oncogenic signaling pathways, including receptor tyrosine kinase, PI3K/Akt, and mTOR pathways.	Metformin	41-50	mechanistic target of rapamycin kinase	Homo sapiens	221-225
29445193-7	2018	In cancer cells treated with chemotherapeutic agents, accumulation of FoxO3A into the mitochondria promoted survival in a MEK/ERK-dependent manner, while mitochondrial FoxO3A was required for apoptosis induction by metformin.	Metformin	215-224	forkhead box O3	Homo sapiens	70-76
29445193-7	2018	In cancer cells treated with chemotherapeutic agents, accumulation of FoxO3A into the mitochondria promoted survival in a MEK/ERK-dependent manner, while mitochondrial FoxO3A was required for apoptosis induction by metformin.	Metformin	215-224	forkhead box O3	Homo sapiens	168-174
29415987-8	2018	Mechanistically, both HSP60 knockdown and oxidative phosphorylation (OXPHOS) inhibition by metformin decreased Erk1/2 phosphorylation and induced apoptosis and cell cycle arrest, whereas Erk1/2 reactivation with EGF promoted cell proliferation.	Metformin	91-100	mitogen-activated protein kinase 3	Homo sapiens	111-117
29415987-11	2018	Thus, our findings indicate for the first time that HSP60 may serve as a novel diagnostic target of human pancreatic cancer, and that inhibition of mitochondrial function using drugs such as metformin may be a beneficial therapeutic strategy targeting pancreatic cancer cells with aberrant function of the HSP60/OXPHOS/Erk1/2 phosphorylation axis.	Metformin	191-200	mitogen-activated protein kinase 3	Homo sapiens	319-325
29541641-0	2018	Exenatide with Metformin Ameliorated Visceral Adiposity and Insulin Resistance.	Metformin	15-24	insulin	Homo sapiens	60-67
29541641-7	2018	The whole 12-month sequential treatment with exenatide and glargine added to metformin basically improved the insulin sensitivity and glucolipid control though VAT rebounded at the end, however without deteriorating the other parameters.	Metformin	77-86	insulin	Homo sapiens	110-117
29363663-0	2018	Metformin Might Inhibit Virus through Increasing Insulin Sensitivity.	Metformin	0-9	insulin	Homo sapiens	49-56
28935544-10	2018	In vivo, we discovered that metformin not only decreased the serum level of the pro-inflammatory cytokines IL-6 and TNF-alpha but also lowered the expression of the M1 macrophage markers CD11c and MCP-1 in adipose tissue.	Metformin	28-37	interleukin 6	Mus musculus	107-111
28935544-10	2018	In vivo, we discovered that metformin not only decreased the serum level of the pro-inflammatory cytokines IL-6 and TNF-alpha but also lowered the expression of the M1 macrophage markers CD11c and MCP-1 in adipose tissue.	Metformin	28-37	tumor necrosis factor	Mus musculus	116-125
28935544-10	2018	In vivo, we discovered that metformin not only decreased the serum level of the pro-inflammatory cytokines IL-6 and TNF-alpha but also lowered the expression of the M1 macrophage markers CD11c and MCP-1 in adipose tissue.	Metformin	28-37	mast cell protease 1	Mus musculus	197-202
28935544-11	2018	In vitro, metformin reduced the secretion of IL-6 and TNF-alpha in palmitate-stimulated RAW264.7 macrophages, while compound C treatment blocked the effect of metformin.	Metformin	10-19	interleukin 6	Mus musculus	45-49
28935544-11	2018	In vitro, metformin reduced the secretion of IL-6 and TNF-alpha in palmitate-stimulated RAW264.7 macrophages, while compound C treatment blocked the effect of metformin.	Metformin	10-19	tumor necrosis factor	Mus musculus	54-63
29089189-0	2018	Metformin intoxication: Vasopressin"s key role in the management of severe lactic acidosis.	Metformin	0-9	arginine vasopressin	Homo sapiens	24-35
29342230-2	2018	To uncover the anti-cancer mechanisms of metformin, preclinical studies determined that metformin impairs cellular metabolism and suppresses oncogenic signaling pathways, including receptor tyrosine kinase, PI3K/Akt, and mTOR pathways.	Metformin	88-97	AKT serine/threonine kinase 1	Homo sapiens	212-215
29342230-2	2018	To uncover the anti-cancer mechanisms of metformin, preclinical studies determined that metformin impairs cellular metabolism and suppresses oncogenic signaling pathways, including receptor tyrosine kinase, PI3K/Akt, and mTOR pathways.	Metformin	88-97	mechanistic target of rapamycin kinase	Homo sapiens	221-225
29139080-5	2018	Metformin reduces the insulin dose requirement, insulin-induced weight gain, and total and LDL cholesterol, but results in an increased risk of gastrointestinal adverse effects and a minor increase in the risk of hypoglycemia.	Metformin	0-9	insulin	Homo sapiens	22-29
29874752-7	2018	In this study, there was significant induction of CYP19A2 in individual exposures of diltiazem, fluoxetine, gemfibrozil and metformin at concentrations measured in Lake Michigan.	Metformin	124-133	cytochrome P450, family 19, subfamily A, polypeptide 1b	Danio rerio	50-57
29110119-0	2018	Metformin synergistically enhances antitumor activity of cisplatin in gallbladder cancer via the PI3K/AKT/ERK pathway.	Metformin	0-9	thymoma viral proto-oncogene 1	Mus musculus	102-105
29110119-0	2018	Metformin synergistically enhances antitumor activity of cisplatin in gallbladder cancer via the PI3K/AKT/ERK pathway.	Metformin	0-9	mitogen-activated protein kinase 1	Mus musculus	106-109
29139080-5	2018	Metformin reduces the insulin dose requirement, insulin-induced weight gain, and total and LDL cholesterol, but results in an increased risk of gastrointestinal adverse effects and a minor increase in the risk of hypoglycemia.	Metformin	0-9	insulin	Homo sapiens	48-55
29285650-9	2018	CONCLUSIONS: Our results demonstrate that gemigliptin induces cytotoxic activity, and has a synergistic activity with metformin in inducing cytotoxicity via regulation of Akt and AMPK in thyroid carcinoma cells.	Metformin	118-127	AKT serine/threonine kinase 1	Homo sapiens	171-174
29285650-10	2018	Furthermore, gemigliptin augments the inhibitory effect of metformin on proliferation and migration through involvement of matrix metalloproteinase-2, matrix metalloproteinase-9, p53, p21, VCAM-1, and ERK in thyroid carcinoma cells.	Metformin	59-68	tumor protein p53	Homo sapiens	179-182
29285650-10	2018	Furthermore, gemigliptin augments the inhibitory effect of metformin on proliferation and migration through involvement of matrix metalloproteinase-2, matrix metalloproteinase-9, p53, p21, VCAM-1, and ERK in thyroid carcinoma cells.	Metformin	59-68	vascular cell adhesion molecule 1	Homo sapiens	189-195
29285650-10	2018	Furthermore, gemigliptin augments the inhibitory effect of metformin on proliferation and migration through involvement of matrix metalloproteinase-2, matrix metalloproteinase-9, p53, p21, VCAM-1, and ERK in thyroid carcinoma cells.	Metformin	59-68	mitogen-activated protein kinase 1	Homo sapiens	201-204
28494141-5	2018	Immunoblotting and cellular uptake assays showed that iPSC-MSCs express functional organic cation transporter-1 (OCT-1), a transmembrane protein that mediates the intracellular uptake of metformin.	Metformin	187-196	solute carrier family 22 member 1	Homo sapiens	83-111
28494141-5	2018	Immunoblotting and cellular uptake assays showed that iPSC-MSCs express functional organic cation transporter-1 (OCT-1), a transmembrane protein that mediates the intracellular uptake of metformin.	Metformin	187-196	solute carrier family 22 member 1	Homo sapiens	113-118
28494141-6	2018	Although metformin treatment did not impair iPSC-MSC viability, it significantly stimulated alkaline phosphatase activity, enhanced mineralized nodule formation and increased expression of osteogenic markers, including Runt-related transcription factor 2 (RUNX2) and osterix.	Metformin	9-18	RUNX family transcription factor 2	Homo sapiens	219-254
28494141-6	2018	Although metformin treatment did not impair iPSC-MSC viability, it significantly stimulated alkaline phosphatase activity, enhanced mineralized nodule formation and increased expression of osteogenic markers, including Runt-related transcription factor 2 (RUNX2) and osterix.	Metformin	9-18	RUNX family transcription factor 2	Homo sapiens	256-261
28494141-7	2018	Inhibition of LKB1 activity, a common upstream AMPK kinase, markedly reversed metformin-induced AMPK activation, RUNX2 expression and nuclear localization.	Metformin	78-87	RUNX family transcription factor 2	Homo sapiens	113-118
29080083-5	2018	We show that metformin potently reduces the progression of seizures and blocks seizure-induced over-expression of brain-derived neurotropic factor (BDNF) and its receptor, Tropomyosin receptor kinase B (TrkB).	Metformin	13-22	neurotrophic receptor tyrosine kinase 2	Rattus norvegicus	172-201
29080083-5	2018	We show that metformin potently reduces the progression of seizures and blocks seizure-induced over-expression of brain-derived neurotropic factor (BDNF) and its receptor, Tropomyosin receptor kinase B (TrkB).	Metformin	13-22	neurotrophic receptor tyrosine kinase 2	Rattus norvegicus	203-207
29094287-3	2018	OBJECTIVE: The current work aimed to investigate the possibility of targeting AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and beta-catenin proteins through combined metformin/aspirin treatment in the HepG2 cell line, and to explore such molecular targets in Egyptian HCC patients.	Metformin	196-205	mechanistic target of rapamycin kinase	Homo sapiens	115-144
29094287-3	2018	OBJECTIVE: The current work aimed to investigate the possibility of targeting AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and beta-catenin proteins through combined metformin/aspirin treatment in the HepG2 cell line, and to explore such molecular targets in Egyptian HCC patients.	Metformin	196-205	mechanistic target of rapamycin kinase	Homo sapiens	146-150
29094287-7	2018	RESULTS: Metformin/aspirin combined treatment had a synergistic effect on cell cycle arrest at the G2/M phase and apoptosis induction in a caspase-dependent manner via downregulation of pAMPK and mTOR protein expression.	Metformin	9-18	mechanistic target of rapamycin kinase	Homo sapiens	196-200
29094287-10	2018	CONCLUSIONS: Targeting AMPK, mTOR and beta-catenin by combined metformin/aspirin treatment could be a promising therapeutic strategy for Egyptian HCC patients, and possibly other HCC patients.	Metformin	63-72	mechanistic target of rapamycin kinase	Homo sapiens	29-33
29434877-1	2018	Previous studies have suggested that metformin may improve the survival rate of patients with pancreatic cancer (PC) by regulating the adenosine monophosphate-activated protein kinase/mammalian target of rapamycin (mTOR) signaling pathway.	Metformin	37-46	mechanistic target of rapamycin kinase	Homo sapiens	184-213
29434877-1	2018	Previous studies have suggested that metformin may improve the survival rate of patients with pancreatic cancer (PC) by regulating the adenosine monophosphate-activated protein kinase/mammalian target of rapamycin (mTOR) signaling pathway.	Metformin	37-46	mechanistic target of rapamycin kinase	Homo sapiens	215-219
29434877-6	2018	Additionally, metformin (20 mmol/l) + rapamycin (200 ng/ml) significantly suppressed the expression of phosphorylated mTOR compared with metformin or rapamycin alone.	Metformin	14-23	mechanistic target of rapamycin kinase	Homo sapiens	118-122
29434877-6	2018	Additionally, metformin (20 mmol/l) + rapamycin (200 ng/ml) significantly suppressed the expression of phosphorylated mTOR compared with metformin or rapamycin alone.	Metformin	137-146	mechanistic target of rapamycin kinase	Homo sapiens	118-122
29168915-5	2018	Interestingly, "high-risk" T2DM patients characterized by severe chemotaxis impairment reveal significantly higher C-reactive protein levels and poor lipid metabolism characteristics as compared to "low-risk" subjects, and their neutrophil chemotaxis responses can be mitigated after in vitro metformin treatment.	Metformin	293-302	C-reactive protein	Homo sapiens	115-133
29044702-1	2018	AIMS: To perform meta-analyses of studies evaluating the risk of pre-eclampsia in high-risk insulin-resistant women taking metformin prior to, or during pregnancy.	Metformin	123-132	insulin	Homo sapiens	92-99
29044702-7	2018	A meta-analysis of eight randomized controlled trials comparing metformin (n = 838) with insulin (n = 836), however, showed a reduced risk of pre-eclampsia with metformin [RR, 0.68 (95% CI 0.48-0.95); P = 0.02; I2  = 0%].	Metformin	161-170	insulin	Homo sapiens	89-96
29044702-10	2018	The mean weight gain from time of enrolment to delivery was lower in the metformin group (P = 0.05, metformin vs. placebo; P = 0.004, metformin vs. insulin).	Metformin	73-82	insulin	Homo sapiens	148-155
29385156-9	2018	CONCLUSIONS: Patients who have OA and T2DM receiving combination COX-2 inhibitors and metformin therapy associated with lower joint replacement surgery rates than those without and this may be attributable to combination therapy much more decrease pro-inflammatory factors associated than those without metformin therapy.	Metformin	303-312	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	65-70
29385181-0	2018	Simvastatin and metformin inhibit cell growth in hepatitis C virus infected cells via mTOR increasing PTEN and autophagy.	Metformin	16-25	mechanistic target of rapamycin kinase	Homo sapiens	86-90
29385181-7	2018	Simvastatin and metformin co-administered down-regulated mTOR and TCTP, while PTEN was increased.	Metformin	16-25	mechanistic target of rapamycin kinase	Homo sapiens	57-61
29385181-10	2018	In human primary hepatocytes, metformin treatment inhibited mTOR and PTEN, but up-regulated p62, LC3BII and Caspase 3.	Metformin	30-39	mechanistic target of rapamycin kinase	Homo sapiens	60-64
29385181-10	2018	In human primary hepatocytes, metformin treatment inhibited mTOR and PTEN, but up-regulated p62, LC3BII and Caspase 3.	Metformin	30-39	caspase 3	Homo sapiens	97-117
31508193-6	2018	The presence of the R337H TP53 mutation suggests a mechanism for the observed response to metformin.	Metformin	90-99	tumor protein p53	Homo sapiens	26-30
29278707-12	2018	Moreover, metformin and AICAR reduced interleukin-6 and, transforming growth factor-beta1 production in succinate-treated LX-2 cells.	Metformin	10-19	transforming growth factor beta 1	Homo sapiens	38-89
29278707-15	2018	Metformin ameliorated steatohepatitis, liver fibrosis, inflammatory cytokine production and decreased alpha -SMA and GPR91expression in the livers of the MCD diet-fed mice.	Metformin	0-9	actin alpha 2, smooth muscle, aorta	Mus musculus	102-112
29278707-15	2018	Metformin ameliorated steatohepatitis, liver fibrosis, inflammatory cytokine production and decreased alpha -SMA and GPR91expression in the livers of the MCD diet-fed mice.	Metformin	0-9	succinate receptor 1	Mus musculus	117-122
29351188-0	2018	Proangiogenic Effect of Metformin in Endothelial Cells Is via Upregulation of VEGFR1/2 and Their Signaling under Hyperglycemia-Hypoxia.	Metformin	24-33	fms related receptor tyrosine kinase 1	Homo sapiens	78-86
29351188-8	2018	Metformin promoted HUVEC migration and inhibited apoptosis via upregulation of vascular endothelial growth factor (VEGF) receptors (VEGFR1/R2), fatty acid binding protein 4 (FABP4), ERK/mitogen-activated protein kinase signaling, chemokine ligand 8, lymphocyte antigen 96, Rho kinase 1 (ROCK1), matrix metalloproteinase 16 (MMP16) and tissue factor inhibitor-2 under hyperglycemia-chemical hypoxia.	Metformin	0-9	fms related receptor tyrosine kinase 1	Homo sapiens	132-141
29351188-8	2018	Metformin promoted HUVEC migration and inhibited apoptosis via upregulation of vascular endothelial growth factor (VEGF) receptors (VEGFR1/R2), fatty acid binding protein 4 (FABP4), ERK/mitogen-activated protein kinase signaling, chemokine ligand 8, lymphocyte antigen 96, Rho kinase 1 (ROCK1), matrix metalloproteinase 16 (MMP16) and tissue factor inhibitor-2 under hyperglycemia-chemical hypoxia.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	182-185
29351188-9	2018	Therefore, metformin"s dual effect in hyperglycemia-chemical hypoxia is mediated by direct effect on VEGFR1/R2 leading to activation of cell migration through MMP16 and ROCK1 upregulation, and inhibition of apoptosis by increase in phospho-ERK1/2 and FABP4, components of VEGF signaling cascades.	Metformin	11-20	fms related receptor tyrosine kinase 1	Homo sapiens	101-107
29338714-1	2018	BACKGROUND: This retrospective study investigated the effect of adding metformin to pharmacologic insulin dosing in type 1 diabetics on insulin therapy 1 year after treatment compared with patients on insulin therapy alone.	Metformin	71-80	insulin	Homo sapiens	136-143
29303184-8	2018	The transcytosis efficiencies of insulin could be further increased by the addition of metformin or HA2 (3.6-fold or 4.1-fold higher than that of free insulin).	Metformin	87-96	insulin	Homo sapiens	33-40
29337896-0	2018	Caffeic Acid and Metformin Inhibit Invasive Phenotype Induced by TGF-beta1 in C-4I and HTB-35/SiHa Human Cervical Squamous Carcinoma Cells by Acting on Different Molecular Targets.	Metformin	17-26	transforming growth factor beta 1	Homo sapiens	65-74
28689771-8	2018	Therapeutic interventions with tacrolimus or metformin normalized the expression of decidual IFNgamma, PGR and FKBP52, increased co-localization of protein inhibitor of activated STATy (PIASy) to PGR and resulted in the upregulation of uterine IL11and LIF.	Metformin	45-54	interferon gamma	Mus musculus	93-101
29323154-10	2018	In conclusion, the effect of metformin on CSCs varies depending on the AMPK-mTOR and glutamine metabolism.	Metformin	29-38	mechanistic target of rapamycin kinase	Homo sapiens	76-80
29151256-6	2018	Metformin caused a decrease in oxidative stress in the heart, accompanied by a decrease in diene conjugates, the elimination of ROS (stable total antioxidant status), and the activation of catalase and glutathione reductase.	Metformin	0-9	catalase	Rattus norvegicus	189-197
29338714-1	2018	BACKGROUND: This retrospective study investigated the effect of adding metformin to pharmacologic insulin dosing in type 1 diabetics on insulin therapy 1 year after treatment compared with patients on insulin therapy alone.	Metformin	71-80	insulin	Homo sapiens	136-143
29338714-6	2018	Metabolic syndrome was more decreased in the metformin-insulin group than in the insulin alone group after treatment (-8.9 +- 1.3 vs. 2.5 +- 0.6%, p = 0.028).	Metformin	45-54	insulin	Homo sapiens	55-62
29338714-7	2018	Insulin dose requirement was lower in the metformin-insulin group than in the insulin alone group (-0.03 vs. 0.11 IU/kg/d, p = 0.006).	Metformin	42-51	insulin	Homo sapiens	0-7
29338714-7	2018	Insulin dose requirement was lower in the metformin-insulin group than in the insulin alone group (-0.03 vs. 0.11 IU/kg/d, p = 0.006).	Metformin	42-51	insulin	Homo sapiens	52-59
29338714-11	2018	These results were independent of blood lipid improvement or weight loss, although on average weight remained decreased with metformin-insulin therapy, whereas the average weight increased with insulin therapy alone.	Metformin	125-134	insulin	Homo sapiens	135-142
30114554-0	2018	Association of metformin use with vitamin B12 deficiency in the institutionalized elderly.	Metformin	15-24	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	42-45
30114554-3	2018	The present retrospective study evaluated the association of metformin use with vitamin B12 deficiency in the same group of patients.	Metformin	61-70	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	88-91
30114554-5	2018	The prevalence of vitamin B12 deficiency in diabetic patients taking metformin was 53.2% compared with 31% (P &lt; 0.001) of diabetic patients not taking metformin and 33.3% (P &lt; 0.001) of those without diabetes.	Metformin	69-78	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	26-29
30114554-6	2018	Among the vitamin B12 deficient patients, diabetic patients taking metformin had lower serum vitamin B12 concentration (97 pmol/L) than the diabetic patients not taking metformin (113 pmol/L, P &lt; 0.001) and those without diabetes (111 pmol/L, P &lt; 0.001).	Metformin	67-76	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	18-21
30114554-6	2018	Among the vitamin B12 deficient patients, diabetic patients taking metformin had lower serum vitamin B12 concentration (97 pmol/L) than the diabetic patients not taking metformin (113 pmol/L, P &lt; 0.001) and those without diabetes (111 pmol/L, P &lt; 0.001).	Metformin	67-76	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	101-104
30114554-7	2018	Subanalysis of 174 metformin users found that dose and duration of metformin use were significantly associated with vitamin B12 deficiency.	Metformin	19-28	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	124-127
30114554-7	2018	Subanalysis of 174 metformin users found that dose and duration of metformin use were significantly associated with vitamin B12 deficiency.	Metformin	67-76	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	124-127
30114554-10	2018	Prevalence of vitamin B12 deficiency among those taking metformin &gt;=1500 mg/day for &gt;2 years was 75.9% and was more than 2 times that of patients taking metformin &lt;1500 mg/day for &lt;=2 years (35.3%).	Metformin	56-65	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	22-25
30114554-10	2018	Prevalence of vitamin B12 deficiency among those taking metformin &gt;=1500 mg/day for &gt;2 years was 75.9% and was more than 2 times that of patients taking metformin &lt;1500 mg/day for &lt;=2 years (35.3%).	Metformin	159-168	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	22-25
30114554-11	2018	In conclusion, metformin use is associated with increased risk and severity of vitamin B12 deficiency in the institutionalized elderly residents.	Metformin	15-24	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	87-90
29032153-0	2018	Metformin overcomes high glucose-induced insulin resistance of podocytes by pleiotropic effects on SIRT1 and AMPK.	Metformin	0-9	sirtuin 1	Rattus norvegicus	99-104
29032153-0	2018	Metformin overcomes high glucose-induced insulin resistance of podocytes by pleiotropic effects on SIRT1 and AMPK.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	109-113
29032153-4	2018	The present work was undertaken to investigate metformin"s ability to restore the insulin responsiveness of podocytes by regulating SIRT1 and AMPK activities.	Metformin	47-56	sirtuin 1	Rattus norvegicus	132-137
29032153-4	2018	The present work was undertaken to investigate metformin"s ability to restore the insulin responsiveness of podocytes by regulating SIRT1 and AMPK activities.	Metformin	47-56	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	142-146
29032153-9	2018	Our results demonstrated that metformin activated SIRT1 and AMPK, prevented hyperglycemia-induced reduction of SIRT1 protein levels, ameliorated glucose uptake into podocytes, and decreased glomerular filtration barrier permeability.	Metformin	30-39	sirtuin 1	Rattus norvegicus	50-55
29032153-9	2018	Our results demonstrated that metformin activated SIRT1 and AMPK, prevented hyperglycemia-induced reduction of SIRT1 protein levels, ameliorated glucose uptake into podocytes, and decreased glomerular filtration barrier permeability.	Metformin	30-39	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	60-64
29032153-10	2018	Furthermore, metformin activated AMPK in a SIRT1-independent manner, as the increase in AMPK phosphorylation after metformin treatment was not affected by SIRT1 downregulation.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	33-37
29032153-10	2018	Furthermore, metformin activated AMPK in a SIRT1-independent manner, as the increase in AMPK phosphorylation after metformin treatment was not affected by SIRT1 downregulation.	Metformin	13-22	sirtuin 1	Rattus norvegicus	43-48
29032153-10	2018	Furthermore, metformin activated AMPK in a SIRT1-independent manner, as the increase in AMPK phosphorylation after metformin treatment was not affected by SIRT1 downregulation.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	88-92
29032153-10	2018	Furthermore, metformin activated AMPK in a SIRT1-independent manner, as the increase in AMPK phosphorylation after metformin treatment was not affected by SIRT1 downregulation.	Metformin	115-124	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	88-92
29032153-11	2018	Therefore, the potentiating effect of metformin on insulin-resistant podocytes seemed to be dependent on AMPK, as well as SIRT1 activity, establishing multilateral effects of metformin action.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	105-109
29032153-11	2018	Therefore, the potentiating effect of metformin on insulin-resistant podocytes seemed to be dependent on AMPK, as well as SIRT1 activity, establishing multilateral effects of metformin action.	Metformin	38-47	sirtuin 1	Rattus norvegicus	122-127
29032153-11	2018	Therefore, the potentiating effect of metformin on insulin-resistant podocytes seemed to be dependent on AMPK, as well as SIRT1 activity, establishing multilateral effects of metformin action.	Metformin	175-184	sirtuin 1	Rattus norvegicus	122-127
29793317-11	2018	This protective effect may be attributed to activation of AMPK by metformin, with consequent reduction in oxidative stress and TGF-beta.	Metformin	66-75	transforming growth factor, beta 1	Rattus norvegicus	127-135
29793317-13	2018	CONCLUSION: These data suggest that metformin protects against bleomycin-induced pulmonary fibrosis through activation of AMPK and amelioration of TGF-beta signaling pathways.	Metformin	36-45	transforming growth factor, beta 1	Rattus norvegicus	147-155
29086064-11	2018	Metformin effects on mitochondria led to the activation and phosphorylation of the energetic sensor AMPK along with an upregulation of the pro-survival AKT pathway in both cell populations.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	152-155
29779024-1	2018	BACKGROUND: Metformin inhibits cyclic AMP generation and activates AMP-activated protein kinase (AMPK), which inhibits the cystic fibrosis transmembrane conductance regulator and Mammalian Target of Rapamycin pathways.	Metformin	12-21	CF transmembrane conductance regulator	Homo sapiens	123-174
29779024-1	2018	BACKGROUND: Metformin inhibits cyclic AMP generation and activates AMP-activated protein kinase (AMPK), which inhibits the cystic fibrosis transmembrane conductance regulator and Mammalian Target of Rapamycin pathways.	Metformin	12-21	mechanistic target of rapamycin kinase	Homo sapiens	179-208
30067448-9	2018	However, tissue TMA analyses by IHC showed decreased mTOR activation, as indicated by phospho-mTOR in cancer tissue of patients with metformin and also with insulin use compared to the control group.	Metformin	133-142	mechanistic target of rapamycin kinase	Homo sapiens	53-57
30067448-9	2018	However, tissue TMA analyses by IHC showed decreased mTOR activation, as indicated by phospho-mTOR in cancer tissue of patients with metformin and also with insulin use compared to the control group.	Metformin	133-142	mechanistic target of rapamycin kinase	Homo sapiens	94-98
30067448-10	2018	In addition, we were able to show that the androgen receptor and the epithelial-cell contact marker E-cadherin decreased upon metformin use compared to the control group.	Metformin	126-135	androgen receptor	Homo sapiens	43-60
30067448-10	2018	In addition, we were able to show that the androgen receptor and the epithelial-cell contact marker E-cadherin decreased upon metformin use compared to the control group.	Metformin	126-135	cadherin 1	Homo sapiens	100-110
29991051-11	2018	Activation of AMPK by AICAR and metformin significantly improved sperm motility, membrane integrity and acrosome reaction, largely maintained sperm mitochondrial membrane potentials, lactate content and ATP content, and enhanced the activity of AMPK, PK and LDH, whereas inhibition by Compound C triggered the converse effects.	Metformin	32-41	pyruvate kinase PKLR	Capra hircus	16-18
30032136-12	2018	Increased levels of apoptosis, activation of caspase-3 and cleavage of PARP were detected after cotreatment with metformin and FTY720.	Metformin	113-122	caspase 3	Homo sapiens	45-54
30032136-14	2018	The metformin/FTY720 regimen markedly induced ROS generation; moreover, apoptosis, ER stress and inhibition of PI3K/AKT/ mTOR were attenuated by the ROS scavenger NAC.	Metformin	4-13	AKT serine/threonine kinase 1	Homo sapiens	116-119
30032136-14	2018	The metformin/FTY720 regimen markedly induced ROS generation; moreover, apoptosis, ER stress and inhibition of PI3K/AKT/ mTOR were attenuated by the ROS scavenger NAC.	Metformin	4-13	mechanistic target of rapamycin kinase	Homo sapiens	121-125
30481793-7	2018	RESULTS: We found that metformin significantly inhibited proliferation and induced apoptosis of both ESCC cell lines in a dose- and time-dependent manner, and the expression of Bcl-2 was down-regulated and Bax and Caspase-3 were up-regulated.	Metformin	23-32	BCL2 associated X, apoptosis regulator	Homo sapiens	206-209
30481793-7	2018	RESULTS: We found that metformin significantly inhibited proliferation and induced apoptosis of both ESCC cell lines in a dose- and time-dependent manner, and the expression of Bcl-2 was down-regulated and Bax and Caspase-3 were up-regulated.	Metformin	23-32	caspase 3	Homo sapiens	214-223
29554661-6	2018	RESULTS: The contents of pro-inflammatory cytokines interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha were inhibited by ALK, metformin or fasudil in diabetic db/db mice.	Metformin	143-152	interleukin 1 beta	Mus musculus	52-74
30205369-7	2018	RESULTS: Metformin/phenformin inhibited basal, but not GHRH/ghrelin-stimulated GH/ACTH/ FSH-secretion and GH/POMC-expression, without altering secretion or expression of other pituitary hormones (PRL/LH/TSH), FSH-expression or cell viability in both primate models.	Metformin	9-18	proopiomelanocortin	Homo sapiens	109-113
29949790-0	2018	OCT1-Mediated Metformin Uptake Regulates Pancreatic Stellate Cell Activity.	Metformin	14-23	solute carrier family 22 member 1	Homo sapiens	0-4
29949790-10	2018	Adenosine monophosphate-activated protein kinase (AMPK), an important regulatory molecule responsible for metformin action, and the organic cation transporter member 1 (OCT1), which is believed to be the most important transporter for the pharmacological action of metformin, were investigated for their possible involvements in metformin-induced proliferation and ECM production.	Metformin	265-274	solute carrier family 22 member 1	Homo sapiens	132-167
29949790-10	2018	Adenosine monophosphate-activated protein kinase (AMPK), an important regulatory molecule responsible for metformin action, and the organic cation transporter member 1 (OCT1), which is believed to be the most important transporter for the pharmacological action of metformin, were investigated for their possible involvements in metformin-induced proliferation and ECM production.	Metformin	265-274	solute carrier family 22 member 1	Homo sapiens	169-173
29949790-10	2018	Adenosine monophosphate-activated protein kinase (AMPK), an important regulatory molecule responsible for metformin action, and the organic cation transporter member 1 (OCT1), which is believed to be the most important transporter for the pharmacological action of metformin, were investigated for their possible involvements in metformin-induced proliferation and ECM production.	Metformin	265-274	solute carrier family 22 member 1	Homo sapiens	132-167
29949790-10	2018	Adenosine monophosphate-activated protein kinase (AMPK), an important regulatory molecule responsible for metformin action, and the organic cation transporter member 1 (OCT1), which is believed to be the most important transporter for the pharmacological action of metformin, were investigated for their possible involvements in metformin-induced proliferation and ECM production.	Metformin	265-274	solute carrier family 22 member 1	Homo sapiens	169-173
29949790-12	2018	Silencing of OCT1 expression resulted in a reduction in the effects of metformin on PSCs activity.	Metformin	71-80	solute carrier family 22 member 1	Homo sapiens	13-17
29949790-13	2018	CONCLUSIONS: Collectively, the data indicate that OCT1 may contribute to uptake metformin and regulate PSCs activity.	Metformin	80-89	solute carrier family 22 member 1	Homo sapiens	50-54
29949790-14	2018	OCT1 is a target of metformin in regulating PSCs activity.	Metformin	20-29	solute carrier family 22 member 1	Homo sapiens	0-4
29554661-6	2018	RESULTS: The contents of pro-inflammatory cytokines interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha were inhibited by ALK, metformin or fasudil in diabetic db/db mice.	Metformin	143-152	interleukin 6	Mus musculus	76-80
29554661-6	2018	RESULTS: The contents of pro-inflammatory cytokines interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha were inhibited by ALK, metformin or fasudil in diabetic db/db mice.	Metformin	143-152	tumor necrosis factor	Mus musculus	85-119
33385166-4	2018	Metformin has been shown to inhibit the effects of tumor necrosis factor (TNF)-alpha.	Metformin	0-9	tumor necrosis factor	Homo sapiens	51-84
29399562-5	2018	In addition, mRNA expression of pro-apoptotic genes, p21 and Bax, was decreased and of anti-apoptotic genes, Bcl-2 and Bcl-xl, was increased with metformin treatment compared to QUIN-induced cells.	Metformin	146-155	BCL2 associated X, apoptosis regulator	Homo sapiens	61-64
29399562-5	2018	In addition, mRNA expression of pro-apoptotic genes, p21 and Bax, was decreased and of anti-apoptotic genes, Bcl-2 and Bcl-xl, was increased with metformin treatment compared to QUIN-induced cells.	Metformin	146-155	BCL2 apoptosis regulator	Homo sapiens	109-114
29399562-5	2018	In addition, mRNA expression of pro-apoptotic genes, p21 and Bax, was decreased and of anti-apoptotic genes, Bcl-2 and Bcl-xl, was increased with metformin treatment compared to QUIN-induced cells.	Metformin	146-155	BCL2 like 1	Homo sapiens	119-125
29399562-6	2018	The immunoreactivity of phosphorylated ERK1/2 was elevated in cells treated with metformin, indicating the ERK1/2 signaling pathway in the neuroprotective effects of metformin in QUIN-induced cell death.	Metformin	81-90	mitogen-activated protein kinase 3	Homo sapiens	39-45
29399562-6	2018	The immunoreactivity of phosphorylated ERK1/2 was elevated in cells treated with metformin, indicating the ERK1/2 signaling pathway in the neuroprotective effects of metformin in QUIN-induced cell death.	Metformin	81-90	mitogen-activated protein kinase 3	Homo sapiens	107-113
29399562-6	2018	The immunoreactivity of phosphorylated ERK1/2 was elevated in cells treated with metformin, indicating the ERK1/2 signaling pathway in the neuroprotective effects of metformin in QUIN-induced cell death.	Metformin	166-175	mitogen-activated protein kinase 3	Homo sapiens	39-45
29399562-6	2018	The immunoreactivity of phosphorylated ERK1/2 was elevated in cells treated with metformin, indicating the ERK1/2 signaling pathway in the neuroprotective effects of metformin in QUIN-induced cell death.	Metformin	166-175	mitogen-activated protein kinase 3	Homo sapiens	107-113
29399562-7	2018	Collectively, our data demonstrates that metformin exerts its neuroprotective effects by inhibiting intracellular calcium increases, allowing it to regulate ERK1/2 signaling and modulate cell survival and death genes.	Metformin	41-50	mitogen-activated protein kinase 3	Homo sapiens	157-163
28081696-0	2018	Effect of Metformin Therapy on Serum Fetuin Levels in Insulin Resistant Type 1 Diabetics.	Metformin	10-19	insulin	Homo sapiens	54-61
28081696-12	2018	After Metformin therapy, FBS, PPB and HbA1c%, Hs- CRP and fetuin decreased (rho&lt;=0.001) while eGDR and insulin dose in units/kg increased (rho &lt;0.001).	Metformin	6-15	C-reactive protein	Homo sapiens	50-53
28081696-15	2018	Levels of fetuin-A and HsCRP decreased after Metformin therapy.	Metformin	45-54	alpha 2-HS glycoprotein	Homo sapiens	10-18
33385166-6	2018	In addition, metformin reduces cellular proliferation by decreasing the amount of available insulin or by directly affecting the mammalian target of rapamycin complex involved with regulating protein synthesis.	Metformin	13-22	insulin	Homo sapiens	92-99
33385166-6	2018	In addition, metformin reduces cellular proliferation by decreasing the amount of available insulin or by directly affecting the mammalian target of rapamycin complex involved with regulating protein synthesis.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	129-158
30173657-0	2018	The Role of SAPK/JNK Pathway in the Synergistic Effects of Metformin and Dacarbazine on Apoptosis in Raji and Ramos Lymphoma Cells.	Metformin	59-68	mitogen-activated protein kinase 8	Homo sapiens	17-20
29110599-0	2018	Effect of Metformin on Plasma Fibrinogen Concentrations: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.	Metformin	10-19	fibrinogen beta chain	Homo sapiens	30-40
29110599-2	2018	Because metformin has shown a potential protective effect on different atherothrombotic risk factors, we assessed in this meta-analysis its effect on plasma fibrinogen concentrations.	Metformin	8-17	fibrinogen beta chain	Homo sapiens	157-167
29110599-3	2018	METHODS: A systematic review and meta-analysis was carried out to identify randomized placebo-controlled trials evaluating the effect of metformin administration on fibrinogen levels.	Metformin	137-146	fibrinogen beta chain	Homo sapiens	165-175
28681986-0	2018	Metformin-associated prevention of weight gain in insulin-treated type 2 diabetic patients cannot be explained by decreased energy intake: A post hoc analysis of a randomized placebo-controlled 4.3-year trial.	Metformin	0-9	insulin	Homo sapiens	50-57
29089306-9	2018	Importantly, OCT1-mediated uptake of a typical OCT1 substrate metformin was inhibited by pazopanib with an IC50 value of 0.253 microM, indicating that pazopanib has the potential for clinically relevant inhibition of human OCT1.	Metformin	62-71	solute carrier family 22 member 1	Homo sapiens	13-17
29089306-9	2018	Importantly, OCT1-mediated uptake of a typical OCT1 substrate metformin was inhibited by pazopanib with an IC50 value of 0.253 microM, indicating that pazopanib has the potential for clinically relevant inhibition of human OCT1.	Metformin	62-71	solute carrier family 22 member 1	Homo sapiens	47-51
29089306-9	2018	Importantly, OCT1-mediated uptake of a typical OCT1 substrate metformin was inhibited by pazopanib with an IC50 value of 0.253 microM, indicating that pazopanib has the potential for clinically relevant inhibition of human OCT1.	Metformin	62-71	solute carrier family 22 member 1	Homo sapiens	47-51
29952416-1	2018	Introduction:To observe the effects of metformin on urinary excretion of MIF, CD74 and podocalyxin in type 2 diabetics and to explore its possible renoprotective mechanisms.	Metformin	39-48	podocalyxin like	Homo sapiens	87-98
29189162-11	2018	Drugs that inhibit TnT-formation such as metformin and everolimus can be targeted towards TnTs in the management of cancer growth, proliferation, tumor invasion and metastasis.	Metformin	41-50	chromosome 16 open reading frame 82	Homo sapiens	19-22
29461234-7	2018	It was established that metformin therapy among patients with acute myocardial infarction and diabetes mellitus type 2 leads to the faster decreasing of sCD40-ligand in comparison with insulin therapy, which can contribute to the improvemenet of the prognosis in this cohort.	Metformin	24-33	insulin	Homo sapiens	185-192
28696014-10	2018	Thus, metformin exerts potent effect on suppression of ossification and inflammation in AS fibroblasts via the activation of Pi3k/Akt and AMPK pathways, which may be developed as a potential agent for treatment of AS.	Metformin	6-15	AKT serine/threonine kinase 1	Homo sapiens	130-133
29043702-2	2018	The aim of this study was to investigate the effects of metformin (MET), N-acetylcysteine (NAC) and their combination on the hormonal levels and expression profile of GDF-9, BMP-15 and c-kit, as hallmarks of oocyte quality, in PCOS patients.	Metformin	56-65	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	185-190
29148173-0	2018	Metformin protects against intestinal barrier dysfunction via AMPKalpha1-dependent inhibition of JNK signalling activation.	Metformin	0-9	mitogen-activated protein kinase 8	Homo sapiens	97-100
29148173-4	2018	We showed that metformin alleviated dextran sodium sulphate (DSS)-induced decreases in transepithelial electrical resistance, FITC-dextran hyperpermeability, loss of the tight junction (TJ) proteins occludin and ZO-1 and bacterial translocation in Caco-2 cell monolayers or in colitis mice models.	Metformin	15-24	tight junction protein 1	Homo sapiens	212-216
29148173-6	2018	We found that metformin ameliorated the induction of colitis and reduced the levels of pro-inflammatory cytokines IL-6, TNF-a and IL-1beta.	Metformin	14-23	interleukin 6	Homo sapiens	114-118
29148173-6	2018	We found that metformin ameliorated the induction of colitis and reduced the levels of pro-inflammatory cytokines IL-6, TNF-a and IL-1beta.	Metformin	14-23	tumor necrosis factor	Homo sapiens	120-125
29148173-6	2018	We found that metformin ameliorated the induction of colitis and reduced the levels of pro-inflammatory cytokines IL-6, TNF-a and IL-1beta.	Metformin	14-23	interleukin 1 beta	Homo sapiens	130-138
29148173-7	2018	In addition, metformin suppressed DSS-induced JNK activation, an effect dependent on AMP-activated protein kinase alpha1 (AMPKalpha1) activation.	Metformin	13-22	mitogen-activated protein kinase 8	Homo sapiens	46-49
29094444-0	2018	Metformin as a prophylactic treatment of gestational diabetes in pregnant patients with pregestational insulin resistance: A randomized study.	Metformin	0-9	insulin	Homo sapiens	103-110
29094444-1	2018	AIM: We aimed to assess the use of metformin (MTF) in the prevention of gestational diabetes mellitus (GDM) in patients with pregestational insulin resistance (PIR).	Metformin	35-44	insulin	Homo sapiens	140-147
29094444-1	2018	AIM: We aimed to assess the use of metformin (MTF) in the prevention of gestational diabetes mellitus (GDM) in patients with pregestational insulin resistance (PIR).	Metformin	46-49	insulin	Homo sapiens	140-147
29422962-5	2018	Studies have demonstrated that reducing insulin and insulin-like growth factor levels in the peripheral blood circulation may lead to the inhibition of phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin (mTOR) signaling or activation of AMP-activated protein kinase, which inhibits mTOR signaling, a process that may be associated with the antitumor effect of metformin.	Metformin	371-380	AKT serine/threonine kinase 1	Homo sapiens	178-181
29786570-2	2018	The aim: The purpose of the paper is to determine the dynamics of the insulin resistance indices in patients with type 2 diabetes mellitus concomitant with coronary heart disease in the combination therapy with metformin and pioglitazone during 3 and 6 months.	Metformin	211-220	insulin	Homo sapiens	70-77
29786570-5	2018	RESULTS: Results: The resulting data proved the statistically significant lowering of the markers and level of the insulin resistance under the effect of combination treatment with metformin and pioglitazone.	Metformin	181-190	insulin	Homo sapiens	115-122
29422962-5	2018	Studies have demonstrated that reducing insulin and insulin-like growth factor levels in the peripheral blood circulation may lead to the inhibition of phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin (mTOR) signaling or activation of AMP-activated protein kinase, which inhibits mTOR signaling, a process that may be associated with the antitumor effect of metformin.	Metformin	371-380	mechanistic target of rapamycin kinase	Homo sapiens	215-219
29317579-0	2017	[Metformin reduces plasma triglycerides in ob/ob obese mice via inhibiting the hepatic apoA5 expression].	Metformin	1-10	apolipoprotein A-V	Mus musculus	87-92
29317579-1	2017	OBJECTIVE: To investigate the role of apolipoprotein A5 (apoA5) in the pathogenesis of obesity-related hypertriglyceridemia and the related therapeutic effects of metformin.	Metformin	163-172	apolipoprotein A-V	Mus musculus	38-55
29317579-6	2017	Metformin could dose-dependently decrease the plasma and hepatic levels of apoA5 and TG in ob/ob mice.	Metformin	0-9	apolipoprotein A-V	Mus musculus	75-80
29317579-7	2017	Metformin could also dose-dependently reduce cellular TG contents and apoA5 expression, these effects were attenuated by knockdown of apoA5.	Metformin	0-9	apolipoprotein A-V	Mus musculus	70-75
29317579-7	2017	Metformin could also dose-dependently reduce cellular TG contents and apoA5 expression, these effects were attenuated by knockdown of apoA5.	Metformin	0-9	apolipoprotein A-V	Mus musculus	134-139
29317579-9	2017	Metformin could inhibit hepatic apoA5 expression, leading to the reduction of the plasma level of TG.	Metformin	0-9	apolipoprotein A-V	Mus musculus	32-37
29435189-2	2018	The aim of this study was to evaluate the effect of continuous metformin treatment in patients with type 2 diabetes mellitus (DM) and moderate chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) 30-0 ml/min/1.73 m2) on renal function.	Metformin	63-72	CD59 molecule (CD59 blood group)	Homo sapiens	225-230
29467947-0	2018	Metformin inhibits TGF-beta1-induced epithelial-to-mesenchymal transition-like process and stem-like properties in GBM via AKT/mTOR/ZEB1 pathway.	Metformin	0-9	transforming growth factor beta 1	Homo sapiens	19-28
30815546-12	2018	Discussion: To our knowledge, this is the first report of GLP-1 agonist-associated changes in the human microbiome and its differentiating effects to metformin.	Metformin	150-159	glucagon	Homo sapiens	58-63
29241458-9	2017	IGF1, IGF1R, AKT p-IGF1, p-IGF1R, and p-Akt protein expression was enhanced dose-dependently with metformin, and was also significantly changed by treatment of CP70 cells with 0 mM metformin +10 mM LY294002.	Metformin	98-107	insulin like growth factor 1	Homo sapiens	0-4
29241458-9	2017	IGF1, IGF1R, AKT p-IGF1, p-IGF1R, and p-Akt protein expression was enhanced dose-dependently with metformin, and was also significantly changed by treatment of CP70 cells with 0 mM metformin +10 mM LY294002.	Metformin	98-107	AKT serine/threonine kinase 1	Homo sapiens	13-16
29241458-9	2017	IGF1, IGF1R, AKT p-IGF1, p-IGF1R, and p-Akt protein expression was enhanced dose-dependently with metformin, and was also significantly changed by treatment of CP70 cells with 0 mM metformin +10 mM LY294002.	Metformin	98-107	insulin like growth factor 1	Homo sapiens	6-10
29241458-9	2017	IGF1, IGF1R, AKT p-IGF1, p-IGF1R, and p-Akt protein expression was enhanced dose-dependently with metformin, and was also significantly changed by treatment of CP70 cells with 0 mM metformin +10 mM LY294002.	Metformin	98-107	AKT serine/threonine kinase 1	Homo sapiens	40-43
29241458-9	2017	IGF1, IGF1R, AKT p-IGF1, p-IGF1R, and p-Akt protein expression was enhanced dose-dependently with metformin, and was also significantly changed by treatment of CP70 cells with 0 mM metformin +10 mM LY294002.	Metformin	181-190	insulin like growth factor 1	Homo sapiens	0-4
29241458-9	2017	IGF1, IGF1R, AKT p-IGF1, p-IGF1R, and p-Akt protein expression was enhanced dose-dependently with metformin, and was also significantly changed by treatment of CP70 cells with 0 mM metformin +10 mM LY294002.	Metformin	181-190	AKT serine/threonine kinase 1	Homo sapiens	13-16
29241458-10	2017	Moreover, changes in the expression of MRP2, IGF1, IGF1R, and AKT was metformin-concentration dependent, and was significantly different from that in the untreated control group (P &lt; 0.05).	Metformin	70-79	insulin like growth factor 1	Homo sapiens	45-49
29241458-10	2017	Moreover, changes in the expression of MRP2, IGF1, IGF1R, and AKT was metformin-concentration dependent, and was significantly different from that in the untreated control group (P &lt; 0.05).	Metformin	70-79	AKT serine/threonine kinase 1	Homo sapiens	62-65
29241458-12	2017	CONCLUSION: Metformin can improve the sensitivity of ovarian cancer CP70 cells to cisplatin in a concentration-dependent manner by activating the AKT signaling pathway, inhibiting the IGF1R signaling pathway, and reducing MRP2 expression.	Metformin	12-21	AKT serine/threonine kinase 1	Homo sapiens	146-149
29236753-14	2017	Ranitidine inhibited the OCT1-mediated uptake of metformin and morphine at clinically relevant concentrations.	Metformin	49-58	solute carrier family 22 member 1	Homo sapiens	25-29
28467723-6	2017	Our findings raise the question of whether metformin could modulate the appearance of atherosclerosis in T2D patients and reduce vascular events by decreasing leukocyte oxidative stress through an increase in gpx1 and sirt3 expression, and undermining adhesion molecule levels and leukocyte-endothelium interactions.	Metformin	43-52	sirtuin 3	Homo sapiens	218-223
29215608-0	2017	H19 lncRNA alters methylation and expression of Hnf4alpha in the liver of metformin-exposed fetuses.	Metformin	74-83	hepatocyte nuclear factor 4 alpha	Homo sapiens	48-57
29215608-8	2017	Our results suggest that metformin from the mother can directly act upon the fetal liver to modify Hnf4alpha expression, a key factor for both liver development and function, and that perturbation of this H19/Hnf4alpha-mediated pathway may contribute to the fetal origin of adult metabolic abnormalities.	Metformin	25-34	hepatocyte nuclear factor 4 alpha	Homo sapiens	99-108
29215608-8	2017	Our results suggest that metformin from the mother can directly act upon the fetal liver to modify Hnf4alpha expression, a key factor for both liver development and function, and that perturbation of this H19/Hnf4alpha-mediated pathway may contribute to the fetal origin of adult metabolic abnormalities.	Metformin	25-34	hepatocyte nuclear factor 4 alpha	Homo sapiens	209-218
29467947-0	2018	Metformin inhibits TGF-beta1-induced epithelial-to-mesenchymal transition-like process and stem-like properties in GBM via AKT/mTOR/ZEB1 pathway.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	123-126
29467947-0	2018	Metformin inhibits TGF-beta1-induced epithelial-to-mesenchymal transition-like process and stem-like properties in GBM via AKT/mTOR/ZEB1 pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	127-131
29467947-6	2018	In this study, we confirmed that metformin inhibited TGF-beta1-induced EMT-like process and EMT-associated migration and invasion in LN18 and U87 GBM cells.	Metformin	33-42	transforming growth factor beta 1	Homo sapiens	53-62
29467947-8	2018	We further clarified that metformin specifically inhibited TGF-beta1 activated AKT, the downstream molecular mTOR and the leading transcription factor ZEB1.	Metformin	26-35	transforming growth factor beta 1	Homo sapiens	59-68
29467947-8	2018	We further clarified that metformin specifically inhibited TGF-beta1 activated AKT, the downstream molecular mTOR and the leading transcription factor ZEB1.	Metformin	26-35	AKT serine/threonine kinase 1	Homo sapiens	79-82
29467947-8	2018	We further clarified that metformin specifically inhibited TGF-beta1 activated AKT, the downstream molecular mTOR and the leading transcription factor ZEB1.	Metformin	26-35	mechanistic target of rapamycin kinase	Homo sapiens	109-113
29467947-9	2018	Taken together, our data demonstrate that metformin inhibits TGF-beta1-induced EMT-like process and cancer stem-like properties in GBM cells via AKT/mTOR/ZEB1 pathway and provide evidence of metformin for further clinical investigation targeted GBM.	Metformin	42-51	transforming growth factor beta 1	Homo sapiens	61-70
29467947-9	2018	Taken together, our data demonstrate that metformin inhibits TGF-beta1-induced EMT-like process and cancer stem-like properties in GBM cells via AKT/mTOR/ZEB1 pathway and provide evidence of metformin for further clinical investigation targeted GBM.	Metformin	42-51	AKT serine/threonine kinase 1	Homo sapiens	145-148
29467947-9	2018	Taken together, our data demonstrate that metformin inhibits TGF-beta1-induced EMT-like process and cancer stem-like properties in GBM cells via AKT/mTOR/ZEB1 pathway and provide evidence of metformin for further clinical investigation targeted GBM.	Metformin	42-51	mechanistic target of rapamycin kinase	Homo sapiens	149-153
29467947-9	2018	Taken together, our data demonstrate that metformin inhibits TGF-beta1-induced EMT-like process and cancer stem-like properties in GBM cells via AKT/mTOR/ZEB1 pathway and provide evidence of metformin for further clinical investigation targeted GBM.	Metformin	191-200	transforming growth factor beta 1	Homo sapiens	61-70
29256528-0	2017	Comparison of metformin and pioglitazone in achieving sustained virological response in chronic hepatitis C patients with insulin resistance: A quasi-experimental study.	Metformin	14-23	insulin	Homo sapiens	122-129
29416762-0	2018	Metformin synergistically suppress tumor growth with doxorubicin and reverse drug resistance by inhibiting the expression and function of P-glycoprotein in MCF7/ADR cells and xenograft models.	Metformin	0-9	ATP binding cassette subfamily B member 1	Homo sapiens	138-152
29416762-6	2018	Metformin increased nuclear doxorubicin accumulation and overcame drug resistance by down-regulating drug-resistant genes such as P-glycoprotein (Pgp).	Metformin	0-9	ATP binding cassette subfamily B member 1	Homo sapiens	130-144
29416762-6	2018	Metformin increased nuclear doxorubicin accumulation and overcame drug resistance by down-regulating drug-resistant genes such as P-glycoprotein (Pgp).	Metformin	0-9	ATP binding cassette subfamily B member 1	Homo sapiens	146-149
29416762-8	2018	In addition, metformin suppressed Pgp expression in vivo.	Metformin	13-22	ATP binding cassette subfamily B member 1	Homo sapiens	34-37
29423021-0	2018	Association of p53 and mitochondrial gene with chemosensitization by metformin in ovarian cancer.	Metformin	69-78	tumor protein p53	Homo sapiens	15-18
29423021-1	2018	Objective: This study aims to investigate the association of p53 and D-loop gene with drug resistance and sensitization induced by metformin in ovarian cancer.	Metformin	131-140	tumor protein p53	Homo sapiens	61-64
28899858-11	2017	Validation by RT-PCR confirmed that the exercise-mediated changes in genes related to exercise capacity, muscle protein metabolism, neuromuscular junction remodeling, and Metformin action were negated in REDD1-null mice.	Metformin	171-180	DNA-damage-inducible transcript 4	Mus musculus	204-209
28847510-6	2017	In contrast, knockdown of Smad6 or Smurf1 prevented metformin-induced reduction of ALK2.	Metformin	52-61	SMAD specific E3 ubiquitin protein ligase 1	Homo sapiens	35-41
28643448-10	2017	Metformin synchronized the apoptotic proteins such as FasL and antiapoptotic proteins such as Bcl2, Bcl-xL and p21 which can be attributed as the major mechanism of cardioprotection.	Metformin	0-9	BCL2, apoptosis regulator	Rattus norvegicus	94-98
28964970-3	2017	The cytotoxic effect of metformin correlated with intracellular reactive oxygen species reduction, activation of AMPK, the inhibition of pro-survival pathways such as mTOR and STAT3 and the down-regulation of v-FLIP, a latent viral antigen that also plays a pivotal role in PEL cell survival.	Metformin	24-33	mechanistic target of rapamycin kinase	Homo sapiens	167-171
28964970-3	2017	The cytotoxic effect of metformin correlated with intracellular reactive oxygen species reduction, activation of AMPK, the inhibition of pro-survival pathways such as mTOR and STAT3 and the down-regulation of v-FLIP, a latent viral antigen that also plays a pivotal role in PEL cell survival.	Metformin	24-33	signal transducer and activator of transcription 3	Homo sapiens	176-181
28964970-5	2017	Mechanistically, metformin altered UPR activated by bortezomib, leading to a reduced expression of BiP, up-regulation of CHOP and down-regulation of Bcl-2.	Metformin	17-26	growth differentiation factor 10	Homo sapiens	99-102
28964970-5	2017	Mechanistically, metformin altered UPR activated by bortezomib, leading to a reduced expression of BiP, up-regulation of CHOP and down-regulation of Bcl-2.	Metformin	17-26	DNA damage inducible transcript 3	Homo sapiens	121-125
28964970-5	2017	Mechanistically, metformin altered UPR activated by bortezomib, leading to a reduced expression of BiP, up-regulation of CHOP and down-regulation of Bcl-2.	Metformin	17-26	BCL2 apoptosis regulator	Homo sapiens	149-154
28943269-2	2017	Case presentation A 45 year old male patient with T2DM for 5 years, current A1c of 8.3% and other co-morbidities is currently treated with metformin 500mg BID and glimepiride 2mg.	Metformin	139-148	BH3 interacting domain death agonist	Homo sapiens	155-158
29276231-12	2017	The insulin requirements of patients with GDM differed significantly depending on their metformin intake.	Metformin	88-97	insulin	Homo sapiens	4-11
29276231-13	2017	24.6% of GDM patients receiving metformin treatment developed GDM requiring insulin treatment compared to 53.8% who did not receive metformin medication.	Metformin	32-41	insulin	Homo sapiens	76-83
28158902-2	2017	The objectives of this study are to investigate the effects of activation of the energy-sensing molecule AMP-activated kinase (AMPK) in renal cells using metformin on endoplasmic reticulum (ER) stress, AKT, mTOR, epithelial-to-mesenchymal transition (EMT), autophagy, and apoptosis that are thought to mediate renal cell injury during proteinuria, and to dissect the AMPK- and non-AMPK mediated effects of metformin using an in vitro model of albumin-induced renal cell injury.	Metformin	154-163	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	105-125
28158902-2	2017	The objectives of this study are to investigate the effects of activation of the energy-sensing molecule AMP-activated kinase (AMPK) in renal cells using metformin on endoplasmic reticulum (ER) stress, AKT, mTOR, epithelial-to-mesenchymal transition (EMT), autophagy, and apoptosis that are thought to mediate renal cell injury during proteinuria, and to dissect the AMPK- and non-AMPK mediated effects of metformin using an in vitro model of albumin-induced renal cell injury.	Metformin	154-163	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	127-131
28158902-2	2017	The objectives of this study are to investigate the effects of activation of the energy-sensing molecule AMP-activated kinase (AMPK) in renal cells using metformin on endoplasmic reticulum (ER) stress, AKT, mTOR, epithelial-to-mesenchymal transition (EMT), autophagy, and apoptosis that are thought to mediate renal cell injury during proteinuria, and to dissect the AMPK- and non-AMPK mediated effects of metformin using an in vitro model of albumin-induced renal cell injury.	Metformin	406-415	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	105-125
28158902-2	2017	The objectives of this study are to investigate the effects of activation of the energy-sensing molecule AMP-activated kinase (AMPK) in renal cells using metformin on endoplasmic reticulum (ER) stress, AKT, mTOR, epithelial-to-mesenchymal transition (EMT), autophagy, and apoptosis that are thought to mediate renal cell injury during proteinuria, and to dissect the AMPK- and non-AMPK mediated effects of metformin using an in vitro model of albumin-induced renal cell injury.	Metformin	406-415	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	127-131
28158902-4	2017	Metformin treatment restored AMPK phosphorylation and augmented autophagy in renal cells exposed to albumin.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	29-33
28158902-5	2017	In addition, metformin treatment attenuated the albumin-induced phosphorylation of AKT and the downstream targets of mTOR, and prevented albumin-mediated inductions of EMT marker (alpha-SMA), pro-apoptotic ER stress marker CHOP, and apoptotic caspases -12 and -3 in renal cells.	Metformin	13-22	AKT serine/threonine kinase 1	Rattus norvegicus	83-86
28158902-6	2017	Blockade of metformin-induced AMPK activation with compound C blunted the ER defense response and autophagy but had no effect on the markers of EMT and apoptosis in our model.	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	30-34
28158902-7	2017	Our studies suggest that metformin protects renal cells against proteinuric cytotoxicity via suppression of AKT and mTOR activation, inhibition of EMT and apoptosis, and augmentation of autophagy and ER defense response through AMPK-independent and AMPK-dependent mechanisms, respectively.	Metformin	25-34	AKT serine/threonine kinase 1	Rattus norvegicus	108-111
28158902-7	2017	Our studies suggest that metformin protects renal cells against proteinuric cytotoxicity via suppression of AKT and mTOR activation, inhibition of EMT and apoptosis, and augmentation of autophagy and ER defense response through AMPK-independent and AMPK-dependent mechanisms, respectively.	Metformin	25-34	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	228-232
28158902-7	2017	Our studies suggest that metformin protects renal cells against proteinuric cytotoxicity via suppression of AKT and mTOR activation, inhibition of EMT and apoptosis, and augmentation of autophagy and ER defense response through AMPK-independent and AMPK-dependent mechanisms, respectively.	Metformin	25-34	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	249-253
28699677-8	2017	Also, our in vitro study showed that metformin inhibited TNF-alpha-induced MMP-9 up-regulation in neutrophils, which might be mediated via an AMPK-dependent pathway.	Metformin	37-46	tumor necrosis factor	Homo sapiens	57-66
28802253-0	2017	The Combination of Metformin and Valproic Acid Induces Synergistic Apoptosis in the Presence of p53 and Androgen Signaling in Prostate Cancer.	Metformin	19-28	tumor protein p53	Homo sapiens	96-99
28990055-4	2017	The objective of the present study was to investigate the effects of DMBG on the expression of the insulin signaling pathway in the ovaries of rats with PCOS, and to identify the potential underlying molecular mechanisms of these effects in PCOS.	Metformin	69-73	insulin	Homo sapiens	99-106
28990055-10	2017	In conclusion, the results of the present study indicate that the reduced expression of proteins involved in insulin signaling may contribute to the development of the clinical features of PCOS, and DMBG reverses reduced expression of insulin signaling components, by a mechanism that is yet to be determined, to attenuate certain symptoms of PCOS, such as obesity.	Metformin	199-203	insulin	Homo sapiens	235-242
29225676-0	2017	Association between insulin resistance and preeclampsia in obese non-diabetic women receiving metformin.	Metformin	94-103	insulin	Homo sapiens	20-27
29225676-1	2017	Objectives: To examine whether the reduced incidence of preeclampsia in non-diabetic obese pregnant women treated with metformin is mediated by changes in insulin resistance.	Metformin	119-128	insulin	Homo sapiens	155-162
29344202-0	2017	Metformin in combination with cisplatin inhibits cell viability and induces apoptosis of human ovarian cancer cells by inactivating ERK 1/2.	Metformin	0-9	mitogen-activated protein kinase 3	Homo sapiens	132-139
29344202-1	2017	Metformin protects against insulin resistance by restoring insulin sensitivity and may also possess anticancer activity.	Metformin	0-9	insulin	Homo sapiens	27-34
29344202-1	2017	Metformin protects against insulin resistance by restoring insulin sensitivity and may also possess anticancer activity.	Metformin	0-9	insulin	Homo sapiens	59-66
29344202-8	2017	The present study demonstrated that expression of p-ERK1/2, VEGF, VEGFR2 and Bcl-2 was downregulated by treatment with increasing concentrations of metformin, whereas expression of Bax and caspase-3 was evidently upregulated.	Metformin	148-157	mitogen-activated protein kinase 3	Homo sapiens	52-58
29344202-8	2017	The present study demonstrated that expression of p-ERK1/2, VEGF, VEGFR2 and Bcl-2 was downregulated by treatment with increasing concentrations of metformin, whereas expression of Bax and caspase-3 was evidently upregulated.	Metformin	148-157	vascular endothelial growth factor A	Homo sapiens	60-64
29344202-8	2017	The present study demonstrated that expression of p-ERK1/2, VEGF, VEGFR2 and Bcl-2 was downregulated by treatment with increasing concentrations of metformin, whereas expression of Bax and caspase-3 was evidently upregulated.	Metformin	148-157	BCL2 apoptosis regulator	Homo sapiens	77-82
29344202-8	2017	The present study demonstrated that expression of p-ERK1/2, VEGF, VEGFR2 and Bcl-2 was downregulated by treatment with increasing concentrations of metformin, whereas expression of Bax and caspase-3 was evidently upregulated.	Metformin	148-157	caspase 3	Homo sapiens	189-198
28142314-0	2017	Metformin attenuates hepatic insulin resistance in type-2 diabetic rats through PI3K/Akt/GLUT-4 signalling independent to bicuculline-sensitive GABAA receptor stimulation.	Metformin	0-9	AKT serine/threonine kinase 1	Rattus norvegicus	85-88
28142314-1	2017	CONTEXT: Metformin attenuates type-2 diabetes mellitus (T2DM)-induced hepatic dysfunction and altered PI3K/Akt/GLUT-4 signalling in experimental studies.	Metformin	9-18	AKT serine/threonine kinase 1	Rattus norvegicus	107-110
28142314-14	2017	Further, metformin mitigated T2DM-induced decrease in hepatic phosphorylated Akt and GLUT-4 translocation in the animals.	Metformin	9-18	AKT serine/threonine kinase 1	Rattus norvegicus	77-80
28142314-16	2017	DISCUSSION AND CONCLUSION: These results suggest that metformin ameliorated T2DM-induced hepatic insulin resistance through bicuculline-sensitive GABAA receptor-independent PI3K/Akt/GLUT-4 signalling pathway in animals.	Metformin	54-63	AKT serine/threonine kinase 1	Rattus norvegicus	178-181
28589443-7	2017	Metformin was also found to markedly decease Beta-secretase 1 (BACE1) protein expression and activity in cell culture models and in vivo, thereby reducing BACE1 cleavage products and the production of Abeta (beta-amyloid).	Metformin	0-9	beta-secretase 1	Homo sapiens	45-61
28589443-7	2017	Metformin was also found to markedly decease Beta-secretase 1 (BACE1) protein expression and activity in cell culture models and in vivo, thereby reducing BACE1 cleavage products and the production of Abeta (beta-amyloid).	Metformin	0-9	beta-secretase 1	Homo sapiens	63-68
28589443-7	2017	Metformin was also found to markedly decease Beta-secretase 1 (BACE1) protein expression and activity in cell culture models and in vivo, thereby reducing BACE1 cleavage products and the production of Abeta (beta-amyloid).	Metformin	0-9	beta-secretase 1	Homo sapiens	155-160
28589443-7	2017	Metformin was also found to markedly decease Beta-secretase 1 (BACE1) protein expression and activity in cell culture models and in vivo, thereby reducing BACE1 cleavage products and the production of Abeta (beta-amyloid).	Metformin	0-9	amyloid beta precursor protein	Homo sapiens	201-206
28589443-8	2017	Furthermore, there is also some evidence that metformin decreases the activity of acetylcholinesterase (AChE), which is responsible for the degradation of acetylcholine (Ach), a neurotransmitter involved in the process of learning and memory.	Metformin	46-55	acetylcholinesterase (Cartwright blood group)	Homo sapiens	82-102
28589443-8	2017	Furthermore, there is also some evidence that metformin decreases the activity of acetylcholinesterase (AChE), which is responsible for the degradation of acetylcholine (Ach), a neurotransmitter involved in the process of learning and memory.	Metformin	46-55	acetylcholinesterase (Cartwright blood group)	Homo sapiens	104-108
29292625-2	2017	Metformin an insulin sensitizer has been widely used in adult PCOS with benefits but the studies in adolescents are few.	Metformin	0-9	insulin	Homo sapiens	13-20
28966224-9	2017	Adiponectin and metformin stimulate osteocalcin expression and the differentiation of osteoblasts via AMPK activation.	Metformin	16-25	bone gamma-carboxyglutamate protein	Homo sapiens	36-47
29183107-0	2017	Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility.	Metformin	27-36	insulin	Homo sapiens	0-7
29183107-3	2017	Insulin-sensitising agents such as metformin may be effective in treating PCOS-related anovulation.	Metformin	35-44	insulin	Homo sapiens	0-7
29230104-0	2017	Metformin Sensitizes Non-small Cell Lung Cancer Cells to an Epigallocatechin-3-Gallate (EGCG) Treatment by Suppressing the Nrf2/HO-1 Signaling Pathway.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	123-127
29230104-7	2017	Metformin also enhanced ROS (reactive oxygen species) generation induced by EGCG (100 muM), subsequently resulting in apoptosis.	Metformin	0-9	latexin	Homo sapiens	86-89
29230104-9	2017	Mechanistically, metformin modulated the EGCG-activated Nrf2/HO-1 pathway through Sirtuin 1 (SIRT1)-dependent deacetylation of Nrf2.	Metformin	17-26	NFE2 like bZIP transcription factor 2	Homo sapiens	56-60
29230104-9	2017	Mechanistically, metformin modulated the EGCG-activated Nrf2/HO-1 pathway through Sirtuin 1 (SIRT1)-dependent deacetylation of Nrf2.	Metformin	17-26	NFE2 like bZIP transcription factor 2	Homo sapiens	127-131
29230104-12	2017	Based on our findings, metformin sensitized NSCLC cells to the EGCG treatment by suppressing the Nrf2/HO-1 signaling pathway.	Metformin	23-32	NFE2 like bZIP transcription factor 2	Homo sapiens	97-101
29180640-6	2017	YOD patients who received metformin combined with CSII therapy required significantly lower insulin doses to maintain euglycemic control compared to patients with LOD.	Metformin	26-35	insulin	Homo sapiens	92-99
29040598-15	2017	Conclusions: Metformin improved vascular smooth muscle function and HbA1c, and lowered insulin dose in type 1 diabetes children.	Metformin	13-22	insulin	Homo sapiens	87-94
28967197-7	2017	Furthermore, inactivation of mitochondria and activation of p53 protein are observed during MGNP treatment, which provides evidence for metformin-induced cell apoptosis pathways.	Metformin	136-145	tumor protein p53	Homo sapiens	60-63
28947430-6	2017	Metformin (200 mg/kg/d) was used to treat wild-type and Sirt2 knockout mice infused with Ang II.	Metformin	0-9	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	89-95
28947430-14	2017	Remarkably, the loss of SIRT2 blunted the response of AMPK to metformin treatment in mice infused with Ang II and repressed the metformin-mediated reduction of cardiac hypertrophy and protection of cardiac function.	Metformin	62-71	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	103-109
29312591-4	2017	In this study, we found that metformin (Met), which is widely used for the treatment of type 2 diabetes (T2D), sensitized lung cancer cells bearing wild-type EGFR to Erlo treatment by enriching cancer cells expressing higher levels of EGFR with persistent phosphorylation.	Metformin	29-38	epidermal growth factor receptor	Homo sapiens	158-162
29312591-4	2017	In this study, we found that metformin (Met), which is widely used for the treatment of type 2 diabetes (T2D), sensitized lung cancer cells bearing wild-type EGFR to Erlo treatment by enriching cancer cells expressing higher levels of EGFR with persistent phosphorylation.	Metformin	29-38	epidermal growth factor receptor	Homo sapiens	235-239
28985579-8	2017	We also observed that SIRT-3 protein expression was significantly higher in patients treated with metformin than in those not taking this medication (65% versus 25%, respectively) (P = .013).	Metformin	98-107	sirtuin 3	Homo sapiens	22-28
29167573-3	2017	We studied the anti-cancer activity of metformin on colorectal cancer (CRC) by using the drug to treat HT29, HCT116 and HCT116 p53-/- CRC cells.	Metformin	39-48	tumor protein p53	Homo sapiens	127-130
29167573-6	2017	The anti-proliferative action of metformin was mediated by two different mechanisms: AMPK activation and increase in the production of reactive oxygen species, which suppressed the mTOR pathway and its downstream targets S6 and 4EBP1.	Metformin	33-42	mechanistic target of rapamycin kinase	Homo sapiens	181-185
29165314-2	2017	Metformin and rapamycin are two FDA-approved mTOR inhibitors proposed for this purpose, exhibiting significant anti-cancer and anti-aging properties beyond their current clinical applications.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	45-49
29188065-8	2017	Conclusion: Non-obese Asian Indian patients with T2DM and on metformin therapy have significantly higher circulating plasma DPP4 levels as compared to non-obese non-diabetic controls, and these levels correlate with fasting insulin and LDL-C levels, upper limb subcutaneous adipose tissue, intra-abdominal adiposity and presence of diabetes.	Metformin	61-70	insulin	Homo sapiens	224-231
29188065-8	2017	Conclusion: Non-obese Asian Indian patients with T2DM and on metformin therapy have significantly higher circulating plasma DPP4 levels as compared to non-obese non-diabetic controls, and these levels correlate with fasting insulin and LDL-C levels, upper limb subcutaneous adipose tissue, intra-abdominal adiposity and presence of diabetes.	Metformin	61-70	component of oligomeric golgi complex 2	Homo sapiens	236-241
28802803-1	2017	This systematic review investigated whether the insulin sensitiser metformin has a geroprotective effect in humans.	Metformin	67-76	insulin	Homo sapiens	48-55
28802803-6	2017	Metformin users also had reduced cancer compared to non-diabetics (rate ratio=0.94, 95%CI 0.92-0.97) and cardiovascular disease (CVD) compared to diabetics receiving non-metformin therapies (HR=0.76, 95%CI 0.66-0.87) or insulin (HR=0.78, 95%CI 0.73-0.83).	Metformin	0-9	insulin	Homo sapiens	220-227
28380657-0	2017	Genetic Polymorphisms in Organic Cation Transporter 1 Attenuates Hepatic Metformin Exposure in Humans.	Metformin	73-82	solute carrier family 22 member 1	Homo sapiens	25-53
28380657-3	2017	The aim of this study was to examine if common polymorphisms in SLC22A1, encoding the transporter protein OCT1, affect the hepatic distribution of metformin in humans.	Metformin	147-156	solute carrier family 22 member 1	Homo sapiens	64-71
28380657-3	2017	The aim of this study was to examine if common polymorphisms in SLC22A1, encoding the transporter protein OCT1, affect the hepatic distribution of metformin in humans.	Metformin	147-156	solute carrier family 22 member 1	Homo sapiens	106-110
28380657-5	2017	Hepatic distribution of metformin was significantly reduced after oral intake in carriers of M420del and R61C variants in SLC22A1 without being associated with changes in circulating levels of metformin.	Metformin	24-33	solute carrier family 22 member 1	Homo sapiens	122-129
28903978-11	2017	Patients were more likely to be given an additional second-line antihyperglycemic medication or insulin if they were given their initial second-line medication without evidence of recommended use of metformin (P &lt; 0.001).	Metformin	199-208	insulin	Homo sapiens	96-103
29066174-0	2017	Attenuation of CD4+CD25+ Regulatory T Cells in the Tumor Microenvironment by Metformin, a Type 2 Diabetes Drug.	Metformin	77-86	CD4 molecule	Homo sapiens	15-18
28985579-2	2017	The aim of the present study was to validate the prognostic significance of metformin in HCC patients treated with sorafenib, providing a biological rationale for the mechanism of resistance to sorafenib in patients on chronic metformin therapy, and to clarify the role of sirtuin-3 (SIRT-3), a protein involved in metabolic diseases and acknowledged as a tumour suppressor in HCC, in this resistance.	Metformin	76-85	sirtuin 3	Homo sapiens	273-282
28985579-2	2017	The aim of the present study was to validate the prognostic significance of metformin in HCC patients treated with sorafenib, providing a biological rationale for the mechanism of resistance to sorafenib in patients on chronic metformin therapy, and to clarify the role of sirtuin-3 (SIRT-3), a protein involved in metabolic diseases and acknowledged as a tumour suppressor in HCC, in this resistance.	Metformin	76-85	sirtuin 3	Homo sapiens	284-290
29228440-0	2017	Metformin regulates tight junction of intestinal epithelial cells via MLCK-MLC signaling pathway.	Metformin	0-9	modulator of VRAC current 1	Homo sapiens	70-73
29228440-7	2017	RESULTS: Metformin attenuates the effects of TNF-alpha on Caco-2 cell TEER and paracellular permeability, prevents TNF-alpha-induced morphological disruption of tight junctions, ameliorates the inhibiting effect of TNF-alpha on epithelial tight junction-related protein expression and suppresses the TNF-alpha-induced increase in MLCK production.	Metformin	9-18	tumor necrosis factor	Homo sapiens	45-54
29228440-7	2017	RESULTS: Metformin attenuates the effects of TNF-alpha on Caco-2 cell TEER and paracellular permeability, prevents TNF-alpha-induced morphological disruption of tight junctions, ameliorates the inhibiting effect of TNF-alpha on epithelial tight junction-related protein expression and suppresses the TNF-alpha-induced increase in MLCK production.	Metformin	9-18	tumor necrosis factor	Homo sapiens	115-124
29228440-7	2017	RESULTS: Metformin attenuates the effects of TNF-alpha on Caco-2 cell TEER and paracellular permeability, prevents TNF-alpha-induced morphological disruption of tight junctions, ameliorates the inhibiting effect of TNF-alpha on epithelial tight junction-related protein expression and suppresses the TNF-alpha-induced increase in MLCK production.	Metformin	9-18	tumor necrosis factor	Homo sapiens	115-124
29228440-7	2017	RESULTS: Metformin attenuates the effects of TNF-alpha on Caco-2 cell TEER and paracellular permeability, prevents TNF-alpha-induced morphological disruption of tight junctions, ameliorates the inhibiting effect of TNF-alpha on epithelial tight junction-related protein expression and suppresses the TNF-alpha-induced increase in MLCK production.	Metformin	9-18	tumor necrosis factor	Homo sapiens	115-124
29228440-8	2017	CONCLUSIONS: Metformin can stabilize and up-regulate tight junction protein by inhibiting MLCK-MLC signaling pathway, thus ameliorating the tight junction of intestinal epithelial cells.	Metformin	13-22	modulator of VRAC current 1	Homo sapiens	90-93
28938439-0	2017	Single-Dose Metformin Enhances Bile Acid-Induced Glucagon-Like Peptide-1 Secretion in Patients With Type 2 Diabetes.	Metformin	12-21	glucagon	Homo sapiens	49-72
28938439-9	2017	Results: Single-dose metformin further enhanced bile acid-mediated induction of GLP-1 secretion (P = 0.02), whereas metformin alone did not increase plasma GLP-1 concentrations compared with placebo (P = 0.17).	Metformin	21-30	glucagon	Homo sapiens	80-85
28938439-12	2017	Conclusions: Metformin elicited an enhancement of the GLP-1 response to cholecystokinin-induced gallbladder emptying in patients with type 2 diabetes, whereas no derived effects on insulin or glucagon secretion were evident in this acute setting.	Metformin	13-22	glucagon	Homo sapiens	54-59
28618116-1	2017	Mutations in the tumor suppressor p53 are highly prevalent in cancers and are known to influence the sensitivity of cells to various chemotherapeutics including the anti-cancer candidates 1,25-dihydrovitamin D3 [1,25D3] and metformin.	Metformin	224-233	tumor protein p53	Homo sapiens	34-37
28921708-4	2017	Both scopoletin and metformin lowered blood glucose and HbA1c , serum ALT, TNF-alpha and IL-6 levels, glucose intolerance, and hepatic lipid accumulation compared with the diabetic control group.	Metformin	20-29	tumor necrosis factor	Mus musculus	75-84
28921708-4	2017	Both scopoletin and metformin lowered blood glucose and HbA1c , serum ALT, TNF-alpha and IL-6 levels, glucose intolerance, and hepatic lipid accumulation compared with the diabetic control group.	Metformin	20-29	interleukin 6	Mus musculus	89-93
28921708-5	2017	Scopoletin or metformin down-regulated hepatic gene expression of triglyceride (Pparg, Plpp2, and Dgat2) and cholesterol (Hmgcr) synthesis as well as inflammation (Tlr4, Myd88, Nfkb1, Tnfa, and Il6), while it up-regulated Cyp7a1 gene.	Metformin	14-23	diacylglycerol O-acyltransferase 2	Mus musculus	98-103
28921708-5	2017	Scopoletin or metformin down-regulated hepatic gene expression of triglyceride (Pparg, Plpp2, and Dgat2) and cholesterol (Hmgcr) synthesis as well as inflammation (Tlr4, Myd88, Nfkb1, Tnfa, and Il6), while it up-regulated Cyp7a1 gene.	Metformin	14-23	toll-like receptor 4	Mus musculus	164-168
28921708-5	2017	Scopoletin or metformin down-regulated hepatic gene expression of triglyceride (Pparg, Plpp2, and Dgat2) and cholesterol (Hmgcr) synthesis as well as inflammation (Tlr4, Myd88, Nfkb1, Tnfa, and Il6), while it up-regulated Cyp7a1 gene.	Metformin	14-23	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	177-182
28921708-5	2017	Scopoletin or metformin down-regulated hepatic gene expression of triglyceride (Pparg, Plpp2, and Dgat2) and cholesterol (Hmgcr) synthesis as well as inflammation (Tlr4, Myd88, Nfkb1, Tnfa, and Il6), while it up-regulated Cyp7a1 gene.	Metformin	14-23	tumor necrosis factor	Mus musculus	184-188
28921708-5	2017	Scopoletin or metformin down-regulated hepatic gene expression of triglyceride (Pparg, Plpp2, and Dgat2) and cholesterol (Hmgcr) synthesis as well as inflammation (Tlr4, Myd88, Nfkb1, Tnfa, and Il6), while it up-regulated Cyp7a1 gene.	Metformin	14-23	interleukin 6	Mus musculus	194-197
28921708-5	2017	Scopoletin or metformin down-regulated hepatic gene expression of triglyceride (Pparg, Plpp2, and Dgat2) and cholesterol (Hmgcr) synthesis as well as inflammation (Tlr4, Myd88, Nfkb1, Tnfa, and Il6), while it up-regulated Cyp7a1 gene.	Metformin	14-23	cytochrome P450, family 7, subfamily a, polypeptide 1	Mus musculus	222-228
28921708-6	2017	Hepatic PPARgamma and DGAT2 protein levels were also down-regulated in scopoletin or metformin group compared with the control group.	Metformin	85-94	diacylglycerol O-acyltransferase 2	Mus musculus	22-27
27817253-0	2017	Multidrug and toxin extrusion protein 1-mediated interaction of metformin and Scutellariae radix in rats.	Metformin	64-73	solute carrier family 47 member 1	Rattus norvegicus	0-39
29262637-0	2017	Metformin reverses bFGF-induced epithelial-mesenchymal transition in HCC cells.	Metformin	0-9	fibroblast growth factor 2	Homo sapiens	19-23
29262637-3	2017	By quantitative proteomics analysis technique, we found metformin could suppress FGF signalling significantly.	Metformin	56-65	fibroblast growth factor 2	Homo sapiens	81-84
29262637-6	2017	However, when treating with metformin and bFGF together, EMT and metastasis induced by bFGF could be inhibited in these cells.	Metformin	28-37	fibroblast growth factor 2	Homo sapiens	87-91
29262637-8	2017	While metformin could repress the bFGF-mediated activation in AKT/GSK-3beta signalling, inhibition on interaction between GSK-3beta and Twist1, enhancement of Twist1 stability.	Metformin	6-15	fibroblast growth factor 2	Homo sapiens	34-38
29262637-8	2017	While metformin could repress the bFGF-mediated activation in AKT/GSK-3beta signalling, inhibition on interaction between GSK-3beta and Twist1, enhancement of Twist1 stability.	Metformin	6-15	AKT serine/threonine kinase 1	Homo sapiens	62-65
29262637-8	2017	While metformin could repress the bFGF-mediated activation in AKT/GSK-3beta signalling, inhibition on interaction between GSK-3beta and Twist1, enhancement of Twist1 stability.	Metformin	6-15	twist family bHLH transcription factor 1	Homo sapiens	136-142
29262637-8	2017	While metformin could repress the bFGF-mediated activation in AKT/GSK-3beta signalling, inhibition on interaction between GSK-3beta and Twist1, enhancement of Twist1 stability.	Metformin	6-15	twist family bHLH transcription factor 1	Homo sapiens	159-165
29262637-9	2017	Taken together, our findings suggested that metformin had prominent negative effects on bFGF-induced EMT and metastasis in HCC cells.	Metformin	44-53	fibroblast growth factor 2	Homo sapiens	88-92
29268066-3	2017	Metformin is the first-line pharmacological treatment for most patients with type 2 diabetes mellitus; however, it has been associated with vitamin B12 deficiency in up to 30% of treated patients.	Metformin	0-9	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	148-151
29268066-12	2017	Vitamin B12 deficiency was also more frequent in patients treated with metformin (24.7% vs 15.8%; p = 0.017), antiplatelet agents (25.4% vs 16.2%, p &lt; 0.001), and calcium channel blockers (26.8% vs 18.2%; p = 0.001).	Metformin	71-80	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	8-11
29268066-13	2017	After adjustment for possible confounders, the variables associated with B12 deficiency were: metformin, hypothyroidism, age and type 2 diabetes mellitus duration.	Metformin	94-103	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	73-76
29268066-15	2017	This study also demonstrates that the B12 deficiency risk is higher in older people, with longer diabetes mellitus duration, hypothyroidism and treated with metformin.	Metformin	157-166	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	38-41
29312569-0	2017	Metformin improves nonalcoholic fatty liver disease in obese mice via down-regulation of apolipoprotein A5 as part of the AMPK/LXRalpha signaling pathway.	Metformin	0-9	apolipoprotein A-V	Mus musculus	89-106
29312569-0	2017	Metformin improves nonalcoholic fatty liver disease in obese mice via down-regulation of apolipoprotein A5 as part of the AMPK/LXRalpha signaling pathway.	Metformin	0-9	nuclear receptor subfamily 1, group H, member 3	Mus musculus	127-135
29312569-2	2017	Recent evidence demonstrated that liver X receptor alpha (LXRalpha), a transcription factor involved in down-regulation of APOA5 mRNA, is activated by AMP-activated protein kinase (AMPK) that contributes to metformin-related antihyperglycemic effects.	Metformin	207-216	nuclear receptor subfamily 1, group H, member 3	Mus musculus	34-56
29312569-2	2017	Recent evidence demonstrated that liver X receptor alpha (LXRalpha), a transcription factor involved in down-regulation of APOA5 mRNA, is activated by AMP-activated protein kinase (AMPK) that contributes to metformin-related antihyperglycemic effects.	Metformin	207-216	nuclear receptor subfamily 1, group H, member 3	Mus musculus	58-66
29312569-2	2017	Recent evidence demonstrated that liver X receptor alpha (LXRalpha), a transcription factor involved in down-regulation of APOA5 mRNA, is activated by AMP-activated protein kinase (AMPK) that contributes to metformin-related antihyperglycemic effects.	Metformin	207-216	apolipoprotein A-V	Mus musculus	123-128
29312569-3	2017	In this study we investigated the role of apoA5 and AMPK/LXRalpha signaling pathway in metformin-related improvement of NAFLD.	Metformin	87-96	apolipoprotein A-V	Mus musculus	42-47
29312569-3	2017	In this study we investigated the role of apoA5 and AMPK/LXRalpha signaling pathway in metformin-related improvement of NAFLD.	Metformin	87-96	nuclear receptor subfamily 1, group H, member 3	Mus musculus	57-65
29312569-6	2017	We found that metformin dose-dependently ameliorated hepatosteatosis and liver dysfunction in ob/ob mice, with a significant reduction in hepatic apoA5 expression and TG level.	Metformin	14-23	apolipoprotein A-V	Mus musculus	146-151
29312569-7	2017	Metformin also dose-dependently increased phosphorylation of hepatic AMPK and LXRalpha in ob/ob mice.	Metformin	0-9	nuclear receptor subfamily 1, group H, member 3	Mus musculus	78-86
29312569-8	2017	Similarly, metformin decreased apoA5 expression and TG level in mouse hepatocytes, with increased phosphorylation of cellular AMPK and LXRalpha.	Metformin	11-20	apolipoprotein A-V	Mus musculus	31-36
29312569-8	2017	Similarly, metformin decreased apoA5 expression and TG level in mouse hepatocytes, with increased phosphorylation of cellular AMPK and LXRalpha.	Metformin	11-20	nuclear receptor subfamily 1, group H, member 3	Mus musculus	135-143
29312569-9	2017	Addition of AMPK inhibitor or siRNA knockdown of LXRalpha significantly attenuated metformin-induced down-regulation of cellular apoA5 expression and TG level.	Metformin	83-92	nuclear receptor subfamily 1, group H, member 3	Mus musculus	49-57
29312569-9	2017	Addition of AMPK inhibitor or siRNA knockdown of LXRalpha significantly attenuated metformin-induced down-regulation of cellular apoA5 expression and TG level.	Metformin	83-92	apolipoprotein A-V	Mus musculus	129-134
29312569-10	2017	AMPK inhibitor also significantly inhibited metformin-induced LXRalpha phosphorylation in these hepatocytes.	Metformin	44-53	nuclear receptor subfamily 1, group H, member 3	Mus musculus	62-70
29312569-11	2017	Therefore, our findings indicate that metformin improves obesity-related NAFLD via inhibition of hepatic apoA5 synthesis as part of the AMPK/LXRalpha signaling pathway.	Metformin	38-47	apolipoprotein A-V	Mus musculus	105-110
29312569-11	2017	Therefore, our findings indicate that metformin improves obesity-related NAFLD via inhibition of hepatic apoA5 synthesis as part of the AMPK/LXRalpha signaling pathway.	Metformin	38-47	nuclear receptor subfamily 1, group H, member 3	Mus musculus	141-149
29142469-7	2017	Metformin increased the expression of AMPK and eNOS protein levels, and promoted the extracellular release of nitric oxide through activation of the AMPK-eNOS mediated pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	38-42
27817253-7	2017	However, 28-day metformin treatment with SB decreased the mRNA level of hepatic MATE1 in rats, resulting in reduced biliary excretion of metformin and thereby higher concentration of metformin in the liver.	Metformin	16-25	solute carrier family 47 member 1	Rattus norvegicus	80-85
27817253-7	2017	However, 28-day metformin treatment with SB decreased the mRNA level of hepatic MATE1 in rats, resulting in reduced biliary excretion of metformin and thereby higher concentration of metformin in the liver.	Metformin	137-146	solute carrier family 47 member 1	Rattus norvegicus	80-85
27817253-7	2017	However, 28-day metformin treatment with SB decreased the mRNA level of hepatic MATE1 in rats, resulting in reduced biliary excretion of metformin and thereby higher concentration of metformin in the liver.	Metformin	137-146	solute carrier family 47 member 1	Rattus norvegicus	80-85
29637133-12	2017	Metformin was initiated for treatment of polycystic ovarian syndrome (70%), insulin resistance (25%) and impaired glucose control (9%).	Metformin	0-9	insulin	Homo sapiens	76-83
28843855-8	2017	Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-kappaB; and reduced interaction between OGT and ChREBP or NF-kappaB.	Metformin	9-18	MLX interacting protein-like	Mus musculus	129-135
28843855-8	2017	Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-kappaB; and reduced interaction between OGT and ChREBP or NF-kappaB.	Metformin	9-18	thioredoxin interacting protein	Mus musculus	137-142
28843855-8	2017	Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-kappaB; and reduced interaction between OGT and ChREBP or NF-kappaB.	Metformin	9-18	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	147-156
28843855-8	2017	Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-kappaB; and reduced interaction between OGT and ChREBP or NF-kappaB.	Metformin	9-18	MLX interacting protein-like	Mus musculus	198-204
28843855-8	2017	Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-kappaB; and reduced interaction between OGT and ChREBP or NF-kappaB.	Metformin	9-18	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	208-217
28919040-4	2017	The diabetes drug metformin inhibited CYP3A4-mediated EET biosynthesis and depleted cancer cell-intrinsic EETs.	Metformin	18-27	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	38-44
28919040-5	2017	Metformin bound to the active-site heme of CYP3A4 in a co-crystal structure, establishing CYP3A4 as a biguanide target.	Metformin	0-9	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	43-49
28919040-5	2017	Metformin bound to the active-site heme of CYP3A4 in a co-crystal structure, establishing CYP3A4 as a biguanide target.	Metformin	0-9	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	90-96
29142469-7	2017	Metformin increased the expression of AMPK and eNOS protein levels, and promoted the extracellular release of nitric oxide through activation of the AMPK-eNOS mediated pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	149-153
29228555-13	2017	Metformin or rosiglitazone led to a reduction of betatrophin expression in insulin-stimulated hepatocytes.	Metformin	0-9	insulin	Homo sapiens	75-82
29085821-7	2017	Additionally, metformin increased the expression levels of p53, Bax, Bad while it reduced expression levels of Akt, Bcl-2, and Mdm2.	Metformin	14-23	tumor protein p53	Homo sapiens	59-62
29085821-7	2017	Additionally, metformin increased the expression levels of p53, Bax, Bad while it reduced expression levels of Akt, Bcl-2, and Mdm2.	Metformin	14-23	BCL2 associated X, apoptosis regulator	Homo sapiens	64-67
29085821-7	2017	Additionally, metformin increased the expression levels of p53, Bax, Bad while it reduced expression levels of Akt, Bcl-2, and Mdm2.	Metformin	14-23	AKT serine/threonine kinase 1	Homo sapiens	111-114
29085821-7	2017	Additionally, metformin increased the expression levels of p53, Bax, Bad while it reduced expression levels of Akt, Bcl-2, and Mdm2.	Metformin	14-23	BCL2 apoptosis regulator	Homo sapiens	116-121
28821394-7	2017	In addition, compared to AGE-treated hNSCs, metformin co-treatment significantly reversed the activity and mRNA transcript level changes of SOD1/2 and Gpx.	Metformin	44-53	superoxide dismutase 1	Homo sapiens	140-146
28821394-8	2017	Furthermore, hNSCs exposed to AGEs had significantly lower mRNA levels among other components of normal cellular oxidative defenses (GSH, Catalase and HO-1), which were all rescued by co-treatment with metformin.	Metformin	202-211	catalase	Homo sapiens	138-146
29254204-7	2017	Peritendinous tissue from metformin-treated rats also showed decreased expression of fibrotic genes including col1a1, col3a1, and alpha-smooth muscle actin (alpha-SMA), and inhibition of transforming growth factor (TGF)-beta1 signaling.	Metformin	26-35	collagen type I alpha 1 chain	Rattus norvegicus	110-116
29254204-7	2017	Peritendinous tissue from metformin-treated rats also showed decreased expression of fibrotic genes including col1a1, col3a1, and alpha-smooth muscle actin (alpha-SMA), and inhibition of transforming growth factor (TGF)-beta1 signaling.	Metformin	26-35	transforming growth factor, beta 1	Rattus norvegicus	187-225
29228555-16	2017	Serum from metformin-treated women with IR decreased betatrophin expression and reinforced insulin signals.	Metformin	11-20	insulin	Homo sapiens	91-98
28791487-0	2017	Metformin attenuates the TLR4 inflammatory pathway in skeletal muscle of diabetic rats.	Metformin	0-9	toll-like receptor 4	Rattus norvegicus	25-29
28791487-2	2017	Our hypothesis was that metformin treatment attenuates the TLR signaling pathways triggered by inflammation in skeletal muscle of hypoinsulinemic/hyperglycemic STZ-induced rats.	Metformin	24-33	toll-like receptor 2	Rattus norvegicus	59-62
28791487-3	2017	Thus, we examined TLR signaling under hypoinsulinemia and hyperglycemia conditions and its correlation with insulin resistance in muscle of diabetic rats treated with metformin.	Metformin	167-176	toll-like receptor 2	Rattus norvegicus	18-21
28884449-3	2017	The discussion focuses upon the potential clinical use of metformin in managing young patients with obesity and insulin resistance.	Metformin	58-67	insulin	Homo sapiens	112-119
28821163-7	2017	The restorative effect of metformin on colonic mucosa was accompanied by a marked reduction in the tissue levels of pro-inflammatory mediators and immunoreactivity of COX-2, iNOS and NFkappaB(p65).	Metformin	26-35	nitric oxide synthase 2	Rattus norvegicus	174-178
28821163-7	2017	The restorative effect of metformin on colonic mucosa was accompanied by a marked reduction in the tissue levels of pro-inflammatory mediators and immunoreactivity of COX-2, iNOS and NFkappaB(p65).	Metformin	26-35	synaptotagmin 1	Rattus norvegicus	192-195
28821163-9	2017	This study shows that metformin targets oxidative stress and down regulates transcription factor NFkappaB(p65) mediated pro-inflammatory signaling and has a therapeutic potential in treating inflammatory conditions of the colon.	Metformin	22-31	synaptotagmin 1	Rattus norvegicus	97-109
28318105-6	2017	In the first years of metformin therapy, small but non-significant decreases were seen in BMI and insulin dose in patients in the MET cohort, while after 10 years no persistent effect on HbA1c, insulin dose or BMI was seen.	Metformin	22-31	insulin	Homo sapiens	98-105
29190959-11	2017	Administration of metformin also activated AMPK signal pathway and retarded AAA progression in Ang II infusion model.	Metformin	18-27	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	95-101
28318105-0	2017	Metformin as add-on to intensive insulin therapy in type 1 diabetes mellitus.	Metformin	0-9	insulin	Homo sapiens	33-40
28318105-7	2017	In conclusion, although metformin may have short-term effects on BMI and insulin dose when used as adjunct therapy in patients with T1DM, no long-term beneficial effects were observed when patients were followed for 10 years.	Metformin	24-33	insulin	Homo sapiens	73-80
28192606-6	2017	Interestingly, metformin reduced the number of phosphorylated histone variant H2AX-positive DNA damage foci and suppressed progerin protein expression, compared to the control.	Metformin	15-24	H2A.X variant histone	Mus musculus	78-82
28729113-8	2017	Importantly, intrathecal injection of metformin, a known scavenger of methylglyoxal, significantly attenuated the upregulation of methylglyoxal and RAGE in dorsal horn, central sensitization and mechanical allodynia induced by bortezomib treatment, and blockage of RAGE also prevented the upregulation of p-STAT3, central sensitization and mechanical allodynia induced by bortezomib treatment.	Metformin	38-47	advanced glycosylation end product-specific receptor	Rattus norvegicus	148-152
28729113-8	2017	Importantly, intrathecal injection of metformin, a known scavenger of methylglyoxal, significantly attenuated the upregulation of methylglyoxal and RAGE in dorsal horn, central sensitization and mechanical allodynia induced by bortezomib treatment, and blockage of RAGE also prevented the upregulation of p-STAT3, central sensitization and mechanical allodynia induced by bortezomib treatment.	Metformin	38-47	advanced glycosylation end product-specific receptor	Rattus norvegicus	265-269
29085506-0	2017	Role of metformin in inhibiting estrogen-induced proliferation and regulating ERalpha and ERbeta expression in human endometrial cancer cells.	Metformin	8-17	estrogen receptor 1	Homo sapiens	78-85
29131265-0	2017	Metformin reduces SATB2-mediated osteosarcoma stem cell-like phenotype and tumor growth via inhibition of N-cadherin/NF-kB signaling.	Metformin	0-9	SATB homeobox 2	Homo sapiens	18-23
29085506-6	2017	Metformin significantly decreased E2-stimulated cell proliferation; an effect that was rescued in the presence of compound C. Metformin treatment markedly increased the phosphorylation of AMPK while decreasing p70S6K phosphorylation, indicating that metformin exerts its effects through stimulation of AMPK and subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	340-369
29085506-6	2017	Metformin significantly decreased E2-stimulated cell proliferation; an effect that was rescued in the presence of compound C. Metformin treatment markedly increased the phosphorylation of AMPK while decreasing p70S6K phosphorylation, indicating that metformin exerts its effects through stimulation of AMPK and subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	371-375
29085506-6	2017	Metformin significantly decreased E2-stimulated cell proliferation; an effect that was rescued in the presence of compound C. Metformin treatment markedly increased the phosphorylation of AMPK while decreasing p70S6K phosphorylation, indicating that metformin exerts its effects through stimulation of AMPK and subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway.	Metformin	126-135	mechanistic target of rapamycin kinase	Homo sapiens	340-369
29085506-6	2017	Metformin significantly decreased E2-stimulated cell proliferation; an effect that was rescued in the presence of compound C. Metformin treatment markedly increased the phosphorylation of AMPK while decreasing p70S6K phosphorylation, indicating that metformin exerts its effects through stimulation of AMPK and subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway.	Metformin	126-135	mechanistic target of rapamycin kinase	Homo sapiens	371-375
29085506-7	2017	In addition, metformin significantly inhibited ERalpha expression while increasing ERbeta expression, whereas treatment with compound C reversed these effects.	Metformin	13-22	estrogen receptor 1	Homo sapiens	47-54
29085506-8	2017	Reverse transcription-quantitative polymerase chain reaction analysis demonstrated that c-fos and c-myc expression were attenuated by metformin, an effect that was rescued in the presence of compound C. Therefore, metformin regulates the expression of ERs, and inhibits estrogen-mediated proliferation of human EC cells through the activation of AMPK and subsequent inhibition of the mTOR signaling pathway.	Metformin	134-143	mechanistic target of rapamycin kinase	Homo sapiens	384-388
29085506-8	2017	Reverse transcription-quantitative polymerase chain reaction analysis demonstrated that c-fos and c-myc expression were attenuated by metformin, an effect that was rescued in the presence of compound C. Therefore, metformin regulates the expression of ERs, and inhibits estrogen-mediated proliferation of human EC cells through the activation of AMPK and subsequent inhibition of the mTOR signaling pathway.	Metformin	214-223	mechanistic target of rapamycin kinase	Homo sapiens	384-388
28319830-1	2017	Metformin is an oral hypoglycemic drug that has been shown to inhibit cancer cell proliferation via up-regulation of AMPK (AMP-activated protein kinase), and possibly inhibition of mTOR (mammalian target of rapamycin).	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	181-185
28664399-12	2017	Furthermore, metformin downregulated the levels of apoptotic factors (p-JNK3, p-c-Jun and cleaved caspase-3) as well as pro-inflammatory cytokines (IL-1beta, IL-4 and IL-6 and TNF-alpha).	Metformin	13-22	interleukin 1 beta	Rattus norvegicus	148-156
28664399-12	2017	Furthermore, metformin downregulated the levels of apoptotic factors (p-JNK3, p-c-Jun and cleaved caspase-3) as well as pro-inflammatory cytokines (IL-1beta, IL-4 and IL-6 and TNF-alpha).	Metformin	13-22	interleukin 6	Rattus norvegicus	167-171
28664399-12	2017	Furthermore, metformin downregulated the levels of apoptotic factors (p-JNK3, p-c-Jun and cleaved caspase-3) as well as pro-inflammatory cytokines (IL-1beta, IL-4 and IL-6 and TNF-alpha).	Metformin	13-22	tumor necrosis factor	Rattus norvegicus	176-185
28319830-1	2017	Metformin is an oral hypoglycemic drug that has been shown to inhibit cancer cell proliferation via up-regulation of AMPK (AMP-activated protein kinase), and possibly inhibition of mTOR (mammalian target of rapamycin).	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	187-216
29212192-0	2017	Vorinostat and metformin sensitize EGFR-TKI resistant NSCLC cells via BIM-dependent apoptosis induction.	Metformin	15-24	epidermal growth factor receptor	Homo sapiens	35-39
29212192-3	2017	Vorinostat in combination with metformin - a compound that can inhibit anti-apoptotic proteins expression, might cooperate to activate apoptotic signaling and overcome EGFR-TKI resistance.	Metformin	31-44	epidermal growth factor receptor	Homo sapiens	168-172
29212192-5	2017	The results showed that vorinostat combined with gefitinib augmented BIM expression and increased the sensitivity of EGFR-TKI resistant NSCLC cells to gefitinib, adding metformin simultaneously could obviously inhibit the expression of anti-apoptotic proteins, and further increased expression levels of BIM and BAX, and as a result, further improved the sensitivity of gefitinib both on the NSCLC cells with intrinsic and acquired resistance to EGFR-TKI.	Metformin	169-178	BCL2 associated X, apoptosis regulator	Homo sapiens	312-315
29212192-5	2017	The results showed that vorinostat combined with gefitinib augmented BIM expression and increased the sensitivity of EGFR-TKI resistant NSCLC cells to gefitinib, adding metformin simultaneously could obviously inhibit the expression of anti-apoptotic proteins, and further increased expression levels of BIM and BAX, and as a result, further improved the sensitivity of gefitinib both on the NSCLC cells with intrinsic and acquired resistance to EGFR-TKI.	Metformin	169-178	epidermal growth factor receptor	Homo sapiens	446-450
29212192-7	2017	These results suggested that the combination of vorinostat and metformin might represent a novel strategy to overcome EGFR-TKI resistance associated with BIM-dependent apoptosis in larger heterogeneous populations.	Metformin	63-72	epidermal growth factor receptor	Homo sapiens	118-122
28947922-6	2017	Lower average and promoter DNA methylation of SLC22A1, SLC22A3, and SLC47A1 was found in diabetic subjects receiving just metformin, compared to those who took insulin plus metformin or no diabetes medication.	Metformin	122-131	solute carrier family 22 member 1	Homo sapiens	46-53
28947922-6	2017	Lower average and promoter DNA methylation of SLC22A1, SLC22A3, and SLC47A1 was found in diabetic subjects receiving just metformin, compared to those who took insulin plus metformin or no diabetes medication.	Metformin	173-182	solute carrier family 22 member 1	Homo sapiens	46-53
28947922-9	2017	Importantly, metformin treatment did also directly decrease DNA methylation of SLC22A1 in hepatocytes cultured in vitro.	Metformin	13-22	solute carrier family 22 member 1	Homo sapiens	79-86
28926637-7	2017	Under glucose-depleted conditions, metformin specifically killed fancc and fancl cells that were deficient in FANCC and FANCL proteins, respectively, which are involved in DNA interstrand cross-link repair.	Metformin	35-44	Fanconi anemia complementation group C	Gallus gallus	65-70
28319830-6	2017	To evaluate the role of mTOR inhibition in metformin-induced cell death, Western blot was performed.	Metformin	43-52	mechanistic target of rapamycin kinase	Homo sapiens	24-28
28979682-6	2017	PPD and metformin significantly decreased the expression of estrogen receptor alpha (ERalpha) in Ishikawa and RL95-2 cells.	Metformin	8-17	estrogen receptor 1	Homo sapiens	60-83
28979682-6	2017	PPD and metformin significantly decreased the expression of estrogen receptor alpha (ERalpha) in Ishikawa and RL95-2 cells.	Metformin	8-17	estrogen receptor 1	Homo sapiens	85-92
28766937-3	2017	Motivated by the growing recognition that anti-diabetic biguanides may act directly upon the gut microbiome, we have determined structures of the complexes formed between the anti-diabetic biguanides (phenformin, buformin, and metformin) and Escherichia coli dihydrofolate reductase (ecDHFR) based on nuclear magnetic resonance, crystallographic, and molecular modeling studies.	Metformin	227-236	dihydrofolate reductase	Escherichia coli	284-290
28766937-4	2017	Interligand Overhauser effects indicate that metformin can form ternary complexes with p-aminobenzoyl-l-glutamate (pABG) as well as other ligands that occupy the region of the folate-binding site that interacts with pABG; however, DHFR inhibition is not cooperative.	Metformin	45-54	dihydrofolate reductase	Escherichia coli	231-235
28766937-5	2017	The biguanides competitively inhibit the activity of ecDHFR, with the phenformin inhibition constant being 100-fold lower than that of metformin.	Metformin	135-144	dihydrofolate reductase	Escherichia coli	53-59
29340030-3	2017	Metformin potently inhibited growth in a dose-dependent manner in all four human OC cell lines through AMPK/mTOR pathways.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	108-112
28926637-7	2017	Under glucose-depleted conditions, metformin specifically killed fancc and fancl cells that were deficient in FANCC and FANCL proteins, respectively, which are involved in DNA interstrand cross-link repair.	Metformin	35-44	Fanconi anemia complementation group C	Gallus gallus	110-115
28926637-8	2017	An analysis of chromosomal aberrations in mitotic chromosome spreads revealed that a clinically relevant concentration of metformin induced DNA double-strand breaks (DSBs) in fancc and fancl cells under glucose-depleted conditions.	Metformin	122-131	Fanconi anemia complementation group C	Gallus gallus	175-180
29066482-0	2017	The Effect of Metformin on the Expression of GPR109A, NF-kappaB and IL-1beta in Peripheral Blood Leukocytes from Patients with Type 2 Diabetes Mellitus.	Metformin	14-23	hydroxycarboxylic acid receptor 2	Homo sapiens	45-52
29066482-0	2017	The Effect of Metformin on the Expression of GPR109A, NF-kappaB and IL-1beta in Peripheral Blood Leukocytes from Patients with Type 2 Diabetes Mellitus.	Metformin	14-23	interleukin 1 beta	Homo sapiens	68-76
29066482-5	2017	We aimed to examine whether metformin plays beneficial effects in T2DM by regulating the GPR109A signaling.	Metformin	28-37	hydroxycarboxylic acid receptor 2	Homo sapiens	89-96
28586507-8	2017	The number of pregnancies treated with insulin only increased (from 23.6% to 28.3%; P&lt;0.0001), as did the number treated with metformin, +/- insulin (from 1.4% to 3.2%; P&lt;0.0001).	Metformin	129-138	insulin	Homo sapiens	144-151
28698075-1	2017	OBJECTIVE: To evaluate the effects of short- and long-term treatment with metformin and NAC, in an adjuvant to clomiphene citrate (CC), on the improvement of hormonal profile (SHBG, total testosterone, FBS, and fasting insulin) and fertility status in CC-resistant women with PCOS.	Metformin	74-83	sex hormone binding globulin	Homo sapiens	176-180
28776086-5	2017	Metformin has been shown to act via both AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms; by inhibition of mitochondrial respiration but also perhaps by inhibition of mitochondrial glycerophosphate dehydrogenase, and a mechanism involving the lysosome.	Metformin	0-9	glycerol-3-phosphate dehydrogenase 2	Homo sapiens	197-241
28962190-0	2017	Metformin in combination with rosiglitazone contribute to the increased serum adiponectin levels in people with type 2 diabetes mellitus.	Metformin	0-9	adiponectin, C1Q and collagen domain containing	Homo sapiens	78-89
28962190-1	2017	To evaluate how metformin plus rosiglitazone affect serum adiponectin levels in people suffering from type 2 diabetes mellitus (T2DM), 240 patients having T2DM were selected in this cohort study.	Metformin	16-25	adiponectin, C1Q and collagen domain containing	Homo sapiens	58-69
28962190-6	2017	Further subgroup analyses indicated that combination therapy of metformin and rosiglitazone may increase the amount of serum adiponectin in T2DM sufferers among the majority subgroups (all P&lt;0.05).	Metformin	64-73	adiponectin, C1Q and collagen domain containing	Homo sapiens	125-136
28962190-7	2017	The combination of metformin and rosiglitazone treatment increased serum adiponectin levels, suggesting that metformin plus rosiglitazone therapy is a suitable choice to treat T2DM.	Metformin	19-28	adiponectin, C1Q and collagen domain containing	Homo sapiens	73-84
28962190-7	2017	The combination of metformin and rosiglitazone treatment increased serum adiponectin levels, suggesting that metformin plus rosiglitazone therapy is a suitable choice to treat T2DM.	Metformin	109-118	adiponectin, C1Q and collagen domain containing	Homo sapiens	73-84
28989873-0	2017	Effect of Metformin-sustained Release Therapy on Low-density Lipoprotein Size and Adiponectin in the South Indian Women with Polycystic Ovary Syndrome.	Metformin	10-19	adiponectin, C1Q and collagen domain containing	Homo sapiens	82-93
28698075-6	2017	The BMI- and insulin-lowering effects of metformin were significantly higher than NAC after long-term treatment.	Metformin	41-50	insulin	Homo sapiens	13-20
28752417-2	2017	Metformin, the most commonly prescribed anti-diabetic drug, exerts its effects through 5"-adenosine monophosphate-activated protein kinase (AMPK) activation.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	87-138
28589542-25	2017	Insulin is an important part of our armamentarium for T2D, and is certainly needed for many patients, but with current therapeutic approaches including metformin, incretin-based treatments, SGLT2 inhibitors, and, possibly, thiazolidinediones, we can reconsider its use in many instances.	Metformin	152-161	insulin	Homo sapiens	0-7
28927780-7	2017	Metformin inhibited ERK1/2, JNK, and PI3K/Akt, but activated p38 pathway in these two cells.	Metformin	0-9	mitogen-activated protein kinase 3	Homo sapiens	20-26
28927780-7	2017	Metformin inhibited ERK1/2, JNK, and PI3K/Akt, but activated p38 pathway in these two cells.	Metformin	0-9	mitogen-activated protein kinase 8	Homo sapiens	28-31
28927780-7	2017	Metformin inhibited ERK1/2, JNK, and PI3K/Akt, but activated p38 pathway in these two cells.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	42-45
28927780-7	2017	Metformin inhibited ERK1/2, JNK, and PI3K/Akt, but activated p38 pathway in these two cells.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	61-64
28927780-9	2017	The combination of specific inhibitors of ERK1/2, JNK or PI3K/Akt pathway and metformin further promoted cell apoptosis and the up-regulation of p21, Bax, Bad, cleaved caspase-3 and -9 as well as the down-regulation of Bcl-2 mediated by metformin alone, but inhibition of p38 pathway exhibited the opposite results.	Metformin	78-87	BCL2 associated X, apoptosis regulator	Homo sapiens	150-153
28927780-9	2017	The combination of specific inhibitors of ERK1/2, JNK or PI3K/Akt pathway and metformin further promoted cell apoptosis and the up-regulation of p21, Bax, Bad, cleaved caspase-3 and -9 as well as the down-regulation of Bcl-2 mediated by metformin alone, but inhibition of p38 pathway exhibited the opposite results.	Metformin	78-87	BCL2 apoptosis regulator	Homo sapiens	219-224
28927780-9	2017	The combination of specific inhibitors of ERK1/2, JNK or PI3K/Akt pathway and metformin further promoted cell apoptosis and the up-regulation of p21, Bax, Bad, cleaved caspase-3 and -9 as well as the down-regulation of Bcl-2 mediated by metformin alone, but inhibition of p38 pathway exhibited the opposite results.	Metformin	78-87	mitogen-activated protein kinase 1	Homo sapiens	272-275
28927780-9	2017	The combination of specific inhibitors of ERK1/2, JNK or PI3K/Akt pathway and metformin further promoted cell apoptosis and the up-regulation of p21, Bax, Bad, cleaved caspase-3 and -9 as well as the down-regulation of Bcl-2 mediated by metformin alone, but inhibition of p38 pathway exhibited the opposite results.	Metformin	237-246	mitogen-activated protein kinase 3	Homo sapiens	42-48
28927780-9	2017	The combination of specific inhibitors of ERK1/2, JNK or PI3K/Akt pathway and metformin further promoted cell apoptosis and the up-regulation of p21, Bax, Bad, cleaved caspase-3 and -9 as well as the down-regulation of Bcl-2 mediated by metformin alone, but inhibition of p38 pathway exhibited the opposite results.	Metformin	237-246	mitogen-activated protein kinase 8	Homo sapiens	50-53
28927780-9	2017	The combination of specific inhibitors of ERK1/2, JNK or PI3K/Akt pathway and metformin further promoted cell apoptosis and the up-regulation of p21, Bax, Bad, cleaved caspase-3 and -9 as well as the down-regulation of Bcl-2 mediated by metformin alone, but inhibition of p38 pathway exhibited the opposite results.	Metformin	237-246	AKT serine/threonine kinase 1	Homo sapiens	62-65
28915960-0	2017	Pleiotropic effects of metformin to rescue statin-induced muscle injury and insulin resistance: A proposed mechanism and potential clinical implications.	Metformin	23-32	insulin	Homo sapiens	76-83
28915960-5	2017	Metformin has outstanding utility in reducing insulin resistance and preventing type-2-diabetes mellitus, but has not been studied for statin-associated muscle symptom rescue or prevention.	Metformin	0-9	insulin	Homo sapiens	46-53
28752417-2	2017	Metformin, the most commonly prescribed anti-diabetic drug, exerts its effects through 5"-adenosine monophosphate-activated protein kinase (AMPK) activation.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	140-144
28752417-7	2017	Metformin protected the hippocampus as evidenced by abolishing down-regulation of the AMPK pathway and up-regulating expression of oxidative stress-related genes.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	86-90
28930827-8	2017	The results of the NAM showed that regarding the incidence of macrosomia and LGA, metformin had lower incidence than glyburide (OR, 0.5411 and 0.4177).	Metformin	82-91	SH3 and cysteine rich domain 3	Homo sapiens	19-22
28930827-8	2017	The results of the NAM showed that regarding the incidence of macrosomia and LGA, metformin had lower incidence than glyburide (OR, 0.5411 and 0.4177).	Metformin	82-91	glutaminase 2	Homo sapiens	77-80
28930827-14	2017	Ranking results showed that glyburide might be the optimum treatment regarding average glucose control, and metformin is the fastest in glucose control for GDM patients; glyburide have the highest incidence of macrosomia, preeclampsia, hyperbilirubinemia, neonatal hypoglycemia, shortest gestational age at delivery, and lowest mean birth weight; metformin (plus insulin when required) have the lowest incidence of macrosomia, PIH, LGA, RDS, low gestational age at delivery, and low birth weight.	Metformin	108-117	insulin	Homo sapiens	363-370
28930827-14	2017	Ranking results showed that glyburide might be the optimum treatment regarding average glucose control, and metformin is the fastest in glucose control for GDM patients; glyburide have the highest incidence of macrosomia, preeclampsia, hyperbilirubinemia, neonatal hypoglycemia, shortest gestational age at delivery, and lowest mean birth weight; metformin (plus insulin when required) have the lowest incidence of macrosomia, PIH, LGA, RDS, low gestational age at delivery, and low birth weight.	Metformin	108-117	glutaminase 2	Homo sapiens	432-435
28953677-0	2017	Effects of metformin treatment on serum levels of C-reactive protein and interleukin-6 in women with polycystic ovary syndrome: a meta-analysis: A PRISMA-compliant article.	Metformin	11-20	C-reactive protein	Homo sapiens	50-68
28953677-0	2017	Effects of metformin treatment on serum levels of C-reactive protein and interleukin-6 in women with polycystic ovary syndrome: a meta-analysis: A PRISMA-compliant article.	Metformin	11-20	interleukin 6	Homo sapiens	73-86
28953677-1	2017	BACKGROUND: Metformin is effective for the treatment of polycystic ovary syndrome (PCOS), but conflicting results regarding its impact on serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6) in women with PCOS have been reported.	Metformin	12-21	C-reactive protein	Homo sapiens	154-172
28953677-1	2017	BACKGROUND: Metformin is effective for the treatment of polycystic ovary syndrome (PCOS), but conflicting results regarding its impact on serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6) in women with PCOS have been reported.	Metformin	12-21	C-reactive protein	Homo sapiens	174-177
28953677-1	2017	BACKGROUND: Metformin is effective for the treatment of polycystic ovary syndrome (PCOS), but conflicting results regarding its impact on serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6) in women with PCOS have been reported.	Metformin	12-21	interleukin 6	Homo sapiens	183-196
28953677-1	2017	BACKGROUND: Metformin is effective for the treatment of polycystic ovary syndrome (PCOS), but conflicting results regarding its impact on serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6) in women with PCOS have been reported.	Metformin	12-21	interleukin 6	Homo sapiens	198-202
28953677-2	2017	To provide high-quality evidence about the effect of treatment with metformin on CRP and IL-6 in PCOS, relevant studies that assessed the serum levels of CRP and IL-6 in women with PCOS receiving metformin treatment were reviewed and analyzed.	Metformin	68-77	C-reactive protein	Homo sapiens	81-84
28953677-7	2017	Data suggest that serum levels of CRP were decreased after metformin treatment in PCOS patients with an SMD (95% CI) of -0.86 [-1.24 to -0.48] and P = .000 (random-effects).	Metformin	59-68	C-reactive protein	Homo sapiens	34-37
28953677-13	2017	In addition, we noticed that metformin treatment could decrease BMI in the CRP and IL-6 related studies (SMD = -0.45, 95% CI: -0.68 to -0.23; SMD = -0.44, 95% CI: -0.73 to -0.16).	Metformin	29-38	C-reactive protein	Homo sapiens	75-78
28953677-13	2017	In addition, we noticed that metformin treatment could decrease BMI in the CRP and IL-6 related studies (SMD = -0.45, 95% CI: -0.68 to -0.23; SMD = -0.44, 95% CI: -0.73 to -0.16).	Metformin	29-38	interleukin 6	Homo sapiens	83-87
28533436-0	2017	Metformin Synergizes with BCL-XL/BCL-2 Inhibitor ABT-263 to Induce Apoptosis Specifically in p53-Defective Cancer Cells.	Metformin	0-9	B cell leukemia/lymphoma 2	Mus musculus	33-38
28827839-10	2017	In comparison to patients of the other weight groups they are treated with insulin more often and considerably less with metformin.	Metformin	121-130	insulin	Homo sapiens	75-82
28858080-6	2017	Insulin consumption was higher in the metformin group in terms of total daily amount and units/kg body weight.	Metformin	38-47	insulin	Homo sapiens	0-7
28927103-3	2017	Metformin decreases the levels of insulin-like growth factor 1 and secondarily inhibits the mammalian target of rapamycin pathway to exhibit anticancer effects.	Metformin	0-9	insulin like growth factor 1	Homo sapiens	34-62
28499942-0	2017	Metformin ameliorates hypoxia/reoxygenation-induced cardiomyocyte apoptosis based on the SIRT3 signaling pathway.	Metformin	0-9	sirtuin 3	Homo sapiens	89-94
28499942-7	2017	Surprisingly, metformin downregulated the levels of relative reactive oxygen species (ROS) and upregulated the levels of relative SOD following H/R injury.	Metformin	14-23	superoxide dismutase 1	Homo sapiens	130-133
28499942-8	2017	Furthermore, metformin-treated cells exhibited reduced cell death, which was demonstrated to be associated with increased SIRT3 expression compared to that in the control group, as evidenced by blocking of the protective effects of metformin on cell apoptosis by the SIRT3 inhibitor Nicotinamide (NAM).	Metformin	13-22	sirtuin 3	Homo sapiens	122-127
28499942-8	2017	Furthermore, metformin-treated cells exhibited reduced cell death, which was demonstrated to be associated with increased SIRT3 expression compared to that in the control group, as evidenced by blocking of the protective effects of metformin on cell apoptosis by the SIRT3 inhibitor Nicotinamide (NAM).	Metformin	13-22	sirtuin 3	Homo sapiens	267-272
28499942-8	2017	Furthermore, metformin-treated cells exhibited reduced cell death, which was demonstrated to be associated with increased SIRT3 expression compared to that in the control group, as evidenced by blocking of the protective effects of metformin on cell apoptosis by the SIRT3 inhibitor Nicotinamide (NAM).	Metformin	232-241	sirtuin 3	Homo sapiens	122-127
28499942-8	2017	Furthermore, metformin-treated cells exhibited reduced cell death, which was demonstrated to be associated with increased SIRT3 expression compared to that in the control group, as evidenced by blocking of the protective effects of metformin on cell apoptosis by the SIRT3 inhibitor Nicotinamide (NAM).	Metformin	232-241	sirtuin 3	Homo sapiens	267-272
28499942-9	2017	Therefore, our results demonstrate that metformin improves cells viability following H/R, and this cardioprotective effect is partly mediated by the SIRT3 signaling pathway.	Metformin	40-49	sirtuin 3	Homo sapiens	149-154
28837141-0	2017	Metformin reverses prostate cancer resistance to enzalutamide by targeting TGF-beta1/STAT3 axis-regulated EMT.	Metformin	0-9	transforming growth factor beta 1	Homo sapiens	75-84
28837141-0	2017	Metformin reverses prostate cancer resistance to enzalutamide by targeting TGF-beta1/STAT3 axis-regulated EMT.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	85-90
28837141-6	2017	Furthermore, based on the effect of metformin on the activation of STAT3 and expression of TGF-beta1, we propose that metformin exerts its effects by targeting the TGF-beta1/STAT3 axis.	Metformin	36-45	signal transducer and activator of transcription 3	Homo sapiens	67-72
28837141-6	2017	Furthermore, based on the effect of metformin on the activation of STAT3 and expression of TGF-beta1, we propose that metformin exerts its effects by targeting the TGF-beta1/STAT3 axis.	Metformin	36-45	transforming growth factor beta 1	Homo sapiens	164-173
28837141-6	2017	Furthermore, based on the effect of metformin on the activation of STAT3 and expression of TGF-beta1, we propose that metformin exerts its effects by targeting the TGF-beta1/STAT3 axis.	Metformin	36-45	signal transducer and activator of transcription 3	Homo sapiens	174-179
28837141-6	2017	Furthermore, based on the effect of metformin on the activation of STAT3 and expression of TGF-beta1, we propose that metformin exerts its effects by targeting the TGF-beta1/STAT3 axis.	Metformin	118-127	signal transducer and activator of transcription 3	Homo sapiens	67-72
28837141-6	2017	Furthermore, based on the effect of metformin on the activation of STAT3 and expression of TGF-beta1, we propose that metformin exerts its effects by targeting the TGF-beta1/STAT3 axis.	Metformin	118-127	transforming growth factor beta 1	Homo sapiens	91-100
28837141-6	2017	Furthermore, based on the effect of metformin on the activation of STAT3 and expression of TGF-beta1, we propose that metformin exerts its effects by targeting the TGF-beta1/STAT3 axis.	Metformin	118-127	transforming growth factor beta 1	Homo sapiens	164-173
28837141-6	2017	Furthermore, based on the effect of metformin on the activation of STAT3 and expression of TGF-beta1, we propose that metformin exerts its effects by targeting the TGF-beta1/STAT3 axis.	Metformin	118-127	signal transducer and activator of transcription 3	Homo sapiens	174-179
29137418-2	2017	Metformin has been shown to inhibit mTOR pathway, with more favorable safety profile, leading to this hypothesis-generating trial to assess whether metformin enhances the efficacy of aromatase inhibitors.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	36-40
29228671-3	2017	However, it remained elusive whether metformin improved skeletal muscle insulin resistance (IRSM) by regulating miR-21 and its target signal TGF-beta1/smads expression.	Metformin	37-46	transforming growth factor, beta 1	Rattus norvegicus	141-150
28827783-4	2017	The CCDC3 expression is markedly reduced in TAp63-null mouse embryonic fibroblasts and brown adipose tissues and by tumor necrosis factor alpha that reduces p63 transcriptional activity, but induced by metformin, an anti-diabetic drug that activates p63.	Metformin	202-211	tumor necrosis factor	Mus musculus	116-143
28767685-6	2017	Treatment with metformin enhanced expression TRIC and LSR via AMPK during cell differentiation.	Metformin	15-24	lipolysis stimulated lipoprotein receptor	Mus musculus	54-57
29088816-0	2017	Metformin inhibits esophageal squamous cell carcinoma-induced angiogenesis by suppressing JAK/STAT3 signaling pathway.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	94-99
29088816-6	2017	More importantly, we investigated the anti-angiogenic effect of metformin, and found that metformin abrogated the ESCC microenvironment-induced transition of NECs toward TECs by inhibiting JAK/STAT3/c-MYC signaling pathway.	Metformin	90-99	signal transducer and activator of transcription 3	Homo sapiens	193-198
27702625-3	2017	As an insulin sensitizer, metformin takes pleiotropic actions and exerts protective effects on multiple organs mainly in insulin-targeted tissues such as liver, muscle, and adipose tissues.	Metformin	26-35	insulin	Homo sapiens	6-13
27702625-3	2017	As an insulin sensitizer, metformin takes pleiotropic actions and exerts protective effects on multiple organs mainly in insulin-targeted tissues such as liver, muscle, and adipose tissues.	Metformin	26-35	insulin	Homo sapiens	121-128
27702625-5	2017	Metformin not only protects T2DM patients from cardiovascular diseases and heart failure, but also restores insulin secretion activities and protects pancreatic beta cells from lipotoxicity or glucotoxicity.	Metformin	0-9	insulin	Homo sapiens	108-115
28206714-9	2017	Metformin counteracted the effect of high glucose on the elevated G6P and fructose 2,6-bisphosphate and on Gck repression, recruitment of Mlx-ChREBP to the G6pc and Pklr promoters and induction of these genes.	Metformin	0-9	MLX interacting protein like	Homo sapiens	142-148
28646699-9	2017	Metformin is the primary insulin-sensitising drug to be used as an adjuvant therapy to lifestyle modification in patients with insulin resistance and impaired glucose tolerance, as well as in those referred to infertility treatment.	Metformin	0-9	insulin	Homo sapiens	25-32
28646699-9	2017	Metformin is the primary insulin-sensitising drug to be used as an adjuvant therapy to lifestyle modification in patients with insulin resistance and impaired glucose tolerance, as well as in those referred to infertility treatment.	Metformin	0-9	insulin	Homo sapiens	127-134
28206714-9	2017	Metformin counteracted the effect of high glucose on the elevated G6P and fructose 2,6-bisphosphate and on Gck repression, recruitment of Mlx-ChREBP to the G6pc and Pklr promoters and induction of these genes.	Metformin	0-9	pyruvate kinase L/R	Homo sapiens	165-169
28676445-12	2017	Furthermore, metformin reduced the protein expressions of COX-2 and PI3K in liver and COX-1 in lung.	Metformin	13-22	cytochrome c oxidase I, mitochondrial	Rattus norvegicus	86-91
28453780-9	2017	Results: After 1 year, the minor allele of rs3212185 (HNF4A) was associated with improved beta-cell function in the metformin and lifestyle groups but not the placebo group; the minor allele of rs6719578 (NEUROD1) was associated with an increase in insulin secretion in the metformin group but not in the placebo and lifestyle groups.	Metformin	116-125	hepatocyte nuclear factor 4 alpha	Homo sapiens	54-59
28453780-9	2017	Results: After 1 year, the minor allele of rs3212185 (HNF4A) was associated with improved beta-cell function in the metformin and lifestyle groups but not the placebo group; the minor allele of rs6719578 (NEUROD1) was associated with an increase in insulin secretion in the metformin group but not in the placebo and lifestyle groups.	Metformin	274-283	hepatocyte nuclear factor 4 alpha	Homo sapiens	54-59
27717194-0	2017	Associations between changes in glucagon-like peptide-1 and bodyweight reduction in patients receiving acarbose or metformin treatment.	Metformin	115-124	glucagon	Homo sapiens	32-55
28829492-0	2017	Metformin increases norepinephrine transporter expression in placenta of patients with polycystic ovary syndrome.	Metformin	0-9	solute carrier family 6 member 2	Homo sapiens	20-46
28829492-1	2017	OBJECTIVE: To evaluate the norepinephrine (NE) and placental NE transporter (NET) in women with polycystic ovary syndrome (PCOS) non-treated and treated with metformin during pregnancy.	Metformin	158-167	solute carrier family 6 member 2	Homo sapiens	77-80
28829492-10	2017	Metformin treatment normalized NE plasma levels at week 24 of gestation and NET expression in the maternal side of the placenta.	Metformin	0-9	solute carrier family 6 member 2	Homo sapiens	76-79
28829492-13	2017	Remarkably, metformin administration during pregnancy decreases circulating norepinephrine levels and increases NET expression in the maternal side of placentas from PCOS women.	Metformin	12-21	solute carrier family 6 member 2	Homo sapiens	112-115
28615149-1	2017	BACKGROUND: Metformin might reduce insulin requirement and improve glycaemia in patients with type 1 diabetes, but whether it has cardiovascular benefits is unknown.	Metformin	12-21	insulin	Homo sapiens	35-42
28146143-12	2017	Combined treatment with Metformin and Insulin reduced blood sugar (control, blood sugar &gt;7.8 mmol/L (22/24), AAA size (P&lt;0.001); metformin, blood sugar &gt;7.8 mmol/L (14/24), AAA size (P&lt;0.0001); insulin, blood sugar &gt;7.8 mmol/L (11/24), AAA size (P&lt;0.0001).	Metformin	24-33	insulin	Homo sapiens	206-213
28146143-12	2017	Combined treatment with Metformin and Insulin reduced blood sugar (control, blood sugar &gt;7.8 mmol/L (22/24), AAA size (P&lt;0.001); metformin, blood sugar &gt;7.8 mmol/L (14/24), AAA size (P&lt;0.0001); insulin, blood sugar &gt;7.8 mmol/L (11/24), AAA size (P&lt;0.0001).	Metformin	135-144	insulin	Homo sapiens	38-45
28611284-0	2017	Activation of the ATF2/CREB-PGC-1alpha pathway by metformin leads to dopaminergic neuroprotection.	Metformin	50-59	PPARG coactivator 1 alpha	Homo sapiens	28-38
27549367-5	2017	Maternal weight gain since enrollment to gestational week 36-37 was also lower in metformin group, making metformin worth using even when metformin is insufficient and supplementary insulin is needed.	Metformin	82-91	insulin	Homo sapiens	182-189
27549367-6	2017	Data also showed that metformin significantly reduced the gestational hypertension complications in GDM patients, probably by reducing the endothelial activation and maternal inflammatory response of insulin resistance.	Metformin	22-31	insulin	Homo sapiens	200-207
28334683-8	2017	Within the T2DM group, preadipocytes from combined metformin and insulin treated subset showed better in vitro adipogenesis compared to metformin alone, which was associated with less presence of macrophages and 4-HNE in the adipose tissues.	Metformin	136-145	insulin	Homo sapiens	65-72
29189867-4	2017	We report a 56 years old non-insulin-requiring type 2 diabetic female who developed a severe metabolic acidosis associated with metformin in relation to an acute renal failure secondary to infectious diarrhea.	Metformin	128-137	insulin	Homo sapiens	29-36
28823275-5	2017	CONCLUSION: Metformin can inhibit the proliferation and induce apoptosis of RPMI8226 and U266 cell lines, which may be related to down-regulation of STAT3 signal transduction pathway.	Metformin	12-21	signal transducer and activator of transcription 3	Homo sapiens	149-154
28933769-7	2017	Interestingly, RA-3 displayed a slightly more enhanced effect than metformin in reducing elevated IL-6 levels and in improving beta cell ultrastructure.	Metformin	67-76	interleukin 6	Rattus norvegicus	98-102
28732480-5	2017	In addition, metformin is a potent activator of activated protein kinase (AMPK) which in turn inhibits the mammalian target of rapamycin (mTOR) and other signal transduction mechanisms.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	107-136
28732480-5	2017	In addition, metformin is a potent activator of activated protein kinase (AMPK) which in turn inhibits the mammalian target of rapamycin (mTOR) and other signal transduction mechanisms.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	138-142
28611284-5	2017	As a potential upstream regulator of mitochondria gene transcription by metformin, PGC-1alpha promoter activity was stimulated by metformin via CREB and ATF2 pathways.	Metformin	72-81	PPARG coactivator 1 alpha	Homo sapiens	83-93
28611284-5	2017	As a potential upstream regulator of mitochondria gene transcription by metformin, PGC-1alpha promoter activity was stimulated by metformin via CREB and ATF2 pathways.	Metformin	130-139	PPARG coactivator 1 alpha	Homo sapiens	83-93
28611284-6	2017	PGC-1alpha and phosphorylation of ATF2 and CREB by metformin were selectively increased in the SN and the striatum, but not the cortex.	Metformin	51-60	PPARG coactivator 1 alpha	Homo sapiens	0-10
28611284-8	2017	Together these results suggest that the metformin-ATF2/CREB-PGC-1alpha pathway might be promising therapeutic target for PD.	Metformin	40-49	PPARG coactivator 1 alpha	Homo sapiens	60-70
28720775-4	2017	TGF-beta1-induced EMT in HPMC was ameliorated by metformin.	Metformin	49-58	transforming growth factor beta 1	Homo sapiens	0-9
28720775-5	2017	Metformin alleviated NAPDH oxidase- and mitochondria-mediated ROS production with an increase in superoxide dismutase (SOD) activity and SOD2 expression.	Metformin	0-9	superoxide dismutase 1	Homo sapiens	97-117
28720775-5	2017	Metformin alleviated NAPDH oxidase- and mitochondria-mediated ROS production with an increase in superoxide dismutase (SOD) activity and SOD2 expression.	Metformin	0-9	superoxide dismutase 1	Homo sapiens	119-122
28720775-6	2017	Metformin inhibited the activation of Smad2/3 and MAPK, GSK-3beta phosphorylation, nuclear translocalization of beta-catenin and Snail in HPMCs.	Metformin	0-9	snail family transcriptional repressor 1	Homo sapiens	129-134
28720775-7	2017	Effect of metformin on TGF-beta1-induced EMT was ameliorated by either AMPK inhibitor or AMPK gene silencing.	Metformin	10-19	transforming growth factor beta 1	Homo sapiens	23-32
28720775-9	2017	In animal model of PD, intraperitoneal metformin decreased the peritoneal thickness and EMT with an increase in ratio of reduced to oxidized glutathione and the expression of SOD whereas it decreased the expression of nitrotyrosine and 8-hydroxy-2"-deoxyguanosine.	Metformin	39-48	superoxide dismutase 1	Homo sapiens	175-178
28717133-7	2017	Consistently, the treatment of insulin in mice dose-dependently upregulated betatrophin levels, and the administration of metformin in IR mice also stimulated betatrophin production since published study showed metformin improved PI3K/Akt pathway and IR.	Metformin	122-131	thymoma viral proto-oncogene 1	Mus musculus	235-238
28717133-7	2017	Consistently, the treatment of insulin in mice dose-dependently upregulated betatrophin levels, and the administration of metformin in IR mice also stimulated betatrophin production since published study showed metformin improved PI3K/Akt pathway and IR.	Metformin	211-220	insulin	Homo sapiens	31-38
28717133-7	2017	Consistently, the treatment of insulin in mice dose-dependently upregulated betatrophin levels, and the administration of metformin in IR mice also stimulated betatrophin production since published study showed metformin improved PI3K/Akt pathway and IR.	Metformin	211-220	thymoma viral proto-oncogene 1	Mus musculus	235-238
28525374-0	2017	The effect of rapamycin, NVP-BEZ235, aspirin, and metformin on PI3K/AKT/mTOR signaling pathway of PIK3CA-related overgrowth spectrum (PROS).	Metformin	50-59	AKT serine/threonine kinase 1	Homo sapiens	68-71
28525374-0	2017	The effect of rapamycin, NVP-BEZ235, aspirin, and metformin on PI3K/AKT/mTOR signaling pathway of PIK3CA-related overgrowth spectrum (PROS).	Metformin	50-59	mechanistic target of rapamycin kinase	Homo sapiens	72-76
28525374-0	2017	The effect of rapamycin, NVP-BEZ235, aspirin, and metformin on PI3K/AKT/mTOR signaling pathway of PIK3CA-related overgrowth spectrum (PROS).	Metformin	50-59	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	98-104
28525374-6	2017	We assessed the therapeutic effects of four compounds (rapamycin, NVP-BEZ235, aspirin, and metformin) on PI3K/AKT/mTOR signaling pathway and cell growth.	Metformin	91-100	AKT serine/threonine kinase 1	Homo sapiens	110-113
28525374-6	2017	We assessed the therapeutic effects of four compounds (rapamycin, NVP-BEZ235, aspirin, and metformin) on PI3K/AKT/mTOR signaling pathway and cell growth.	Metformin	91-100	mechanistic target of rapamycin kinase	Homo sapiens	114-118
28698800-0	2017	Metformin-induced ablation of microRNA 21-5p releases Sestrin-1 and CAB39L antitumoral activities.	Metformin	0-9	calcium binding protein 39 like	Homo sapiens	68-74
31149195-0	2017	PATIENTS TREATED WITH INSULIN AND SULPHONYLUREA ARE AT INCREASED MORTALITY RISK AS COMPARED WITH THOSE TREATED WITH INSULIN PLUS METFORMIN.	Metformin	129-138	insulin	Homo sapiens	116-123
28337819-8	2017	Moreover, insulin-sensitizing drugs (metformin, pioglitazone, and rosiglitazone) suppress LPS-induced TGF-beta and TNF-alpha mRNA expression in PFMC.	Metformin	37-46	insulin	Homo sapiens	10-17
28611274-11	2017	Insulin resistance also improves with both TZDs and metformin.	Metformin	52-61	insulin	Homo sapiens	0-7
28337819-8	2017	Moreover, insulin-sensitizing drugs (metformin, pioglitazone, and rosiglitazone) suppress LPS-induced TGF-beta and TNF-alpha mRNA expression in PFMC.	Metformin	37-46	transforming growth factor beta 1	Homo sapiens	102-110
28337819-8	2017	Moreover, insulin-sensitizing drugs (metformin, pioglitazone, and rosiglitazone) suppress LPS-induced TGF-beta and TNF-alpha mRNA expression in PFMC.	Metformin	37-46	tumor necrosis factor	Homo sapiens	115-124
28447237-0	2017	Effects of metformin versus placebo on vitamin B12 metabolism in non-diabetic breast cancer patients in CCTG MA.32.	Metformin	11-20	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	47-50
28436023-0	2017	Activation of AMP-activated protein kinase by metformin ablates angiotensin II-induced endoplasmic reticulum stress and hypertension in mice in vivo.	Metformin	46-55	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	64-78
28436023-3	2017	The aim of the present study was to determine the effects of metformin on angiotensin II (Ang II) infusion-induced hypertension in vivo.	Metformin	61-70	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	74-88
28436023-3	2017	The aim of the present study was to determine the effects of metformin on angiotensin II (Ang II) infusion-induced hypertension in vivo.	Metformin	61-70	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	90-96
28436023-5	2017	Also, the effect of metformin on Ang II-induced endoplasmic reticulum (ER) stress was explored in cultured human vascular smooth muscle cells (hVSMCs).	Metformin	20-29	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	33-39
28436023-6	2017	KEY RESULTS: Metformin markedly reduced BP in Ang II-infused WT mice but not in AMPKalpha2-deficient mice.	Metformin	13-22	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	46-52
28436023-8	2017	Moreover, AMPK activation by metformin ablated Ang II-induced ER stress in hVSMCs.	Metformin	29-38	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	10-14
28436023-8	2017	Moreover, AMPK activation by metformin ablated Ang II-induced ER stress in hVSMCs.	Metformin	29-38	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	47-53
28436023-10	2017	CONCLUSION AND IMPLICATIONS: Metformin alleviates Ang II-triggered hypertension in mice by activating AMPKalpha2, which mediates phospholamban phosphorylation and inhibits Ang II-induced ER stress in vascular smooth muscle cells.	Metformin	29-38	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	50-56
28436023-10	2017	CONCLUSION AND IMPLICATIONS: Metformin alleviates Ang II-triggered hypertension in mice by activating AMPKalpha2, which mediates phospholamban phosphorylation and inhibits Ang II-induced ER stress in vascular smooth muscle cells.	Metformin	29-38	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	102-112
28436023-10	2017	CONCLUSION AND IMPLICATIONS: Metformin alleviates Ang II-triggered hypertension in mice by activating AMPKalpha2, which mediates phospholamban phosphorylation and inhibits Ang II-induced ER stress in vascular smooth muscle cells.	Metformin	29-38	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	172-178
27857021-9	2017	Further study revealed that metformin could suppress the expression of insulin-like growth factor 1 receptor and its downstream proteins, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT/PKB), phosphorylation of AKT (pAKT), mammalian target of rapamycin (mTOR), p70S6K, and PKM2.	Metformin	28-37	AKT serine/threonine kinase 1	Homo sapiens	190-197
27857021-9	2017	Further study revealed that metformin could suppress the expression of insulin-like growth factor 1 receptor and its downstream proteins, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT/PKB), phosphorylation of AKT (pAKT), mammalian target of rapamycin (mTOR), p70S6K, and PKM2.	Metformin	28-37	AKT serine/threonine kinase 1	Homo sapiens	190-193
27857021-9	2017	Further study revealed that metformin could suppress the expression of insulin-like growth factor 1 receptor and its downstream proteins, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT/PKB), phosphorylation of AKT (pAKT), mammalian target of rapamycin (mTOR), p70S6K, and PKM2.	Metformin	28-37	mechanistic target of rapamycin kinase	Homo sapiens	231-260
27857021-9	2017	Further study revealed that metformin could suppress the expression of insulin-like growth factor 1 receptor and its downstream proteins, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT/PKB), phosphorylation of AKT (pAKT), mammalian target of rapamycin (mTOR), p70S6K, and PKM2.	Metformin	28-37	mechanistic target of rapamycin kinase	Homo sapiens	262-266
27857021-14	2017	CONCLUSION: Metformin restrained esophageal cancer cell proliferation partly by suppressing the PI3K/AKT/mTOR pathway.	Metformin	12-21	AKT serine/threonine kinase 1	Homo sapiens	101-104
27857021-14	2017	CONCLUSION: Metformin restrained esophageal cancer cell proliferation partly by suppressing the PI3K/AKT/mTOR pathway.	Metformin	12-21	mechanistic target of rapamycin kinase	Homo sapiens	105-109
28321905-6	2017	CONCLUSIONS: Our findings suggest that rs2289669 might help predict the glycaemic response to metformin in Chinese people newly diagnosed with Type 2 diabetes, and that differential increases in basal glucagon-like peptide-1 concentration among rs2289669 genotypes might be associated with inter-individual response to metformin.	Metformin	319-328	glucagon	Homo sapiens	201-224
28330386-9	2017	CONCLUSION: In routine clinical practice, intensification of metformin + sulfonylurea therapy by adding insulin is associated with increased risk of cardiovascular events and death compared with adding a dipeptidylpeptidase-4 inhibitor.	Metformin	61-70	insulin	Homo sapiens	104-111
28672943-10	2017	It was also demonstrated that metformin administration significantly decreased the expression levels of TGF-beta1 and attenuated the morphological changes associated with T2DN in rats.	Metformin	30-39	transforming growth factor, beta 1	Rattus norvegicus	104-113
28281393-3	2017	RESULTS: Both metformin and rotenone protected SA-NH (p &lt; .001) while sensitizing FSa (p &lt; .001) to 4 Gy.	Metformin	14-23	RIKEN cDNA 4932438A13 gene	Mus musculus	85-88
28281393-5	2017	Metformin was also directly toxic to FSa cells (p = .002).	Metformin	0-9	RIKEN cDNA 4932438A13 gene	Mus musculus	37-40
28281393-6	2017	In contrast, in vivo metformin (250 mg/kg) sensitized both SA-NH (9-day growth delay, p &lt; .05) and FSa (4-day growth delay, p &lt; .05) tumors if administered 1 h before irradiation.	Metformin	21-30	RIKEN cDNA 4932438A13 gene	Mus musculus	102-105
28473613-8	2017	In this study, metformin combined with exercise training reduced circulating proinsulin, and both groups taking metformin increased insulin clearance.	Metformin	15-24	insulin	Homo sapiens	77-87
28473613-8	2017	In this study, metformin combined with exercise training reduced circulating proinsulin, and both groups taking metformin increased insulin clearance.	Metformin	15-24	insulin	Homo sapiens	80-87
28473613-11	2017	In this study, however, metformin combined with exercise training, but not exercise alone, lowered proinsulin concentrations and increased insulin clearance in adults with prediabetes.	Metformin	24-33	insulin	Homo sapiens	99-109
28473613-11	2017	In this study, however, metformin combined with exercise training, but not exercise alone, lowered proinsulin concentrations and increased insulin clearance in adults with prediabetes.	Metformin	24-33	insulin	Homo sapiens	102-109
28559290-7	2017	Treatment of adipocytes with metformin decreased the effects of lipopolysaccharide on inducing the phosphorylation states of JNK p46 and on increasing the mRNA levels of IL-1beta and TNFalpha.	Metformin	29-38	interleukin 1 beta	Mus musculus	170-178
28559290-7	2017	Treatment of adipocytes with metformin decreased the effects of lipopolysaccharide on inducing the phosphorylation states of JNK p46 and on increasing the mRNA levels of IL-1beta and TNFalpha.	Metformin	29-38	tumor necrosis factor	Mus musculus	183-191
28539171-2	2017	In this systematic review and meta-analysis we evaluated the effect of metformin on clinical outcomes in patients with EC and insulin resistance or T2DM.	Metformin	71-80	insulin	Homo sapiens	126-133
28447237-1	2017	BACKGROUND: Metformin is associated with low levels of vitamin B12 (VitB12) in patients with diabetes.	Metformin	12-21	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	63-66
28437189-8	2017	In addition, metformin was found to significantly decrease collagen 1a and TGF-beta expression and inhibit p-Smad2 and p-Smad3 expression compared to that of the irradiated group alone.	Metformin	13-22	SMAD family member 2	Mus musculus	109-114
29145540-9	2017	Three-month treatment with metformin and pioglitazone significantly improved insulin sensitivity and increased orexin concentrations by 26% (p = 0.025) and 14% (p = 0.076), respectively.	Metformin	27-36	insulin	Homo sapiens	77-84
29145540-12	2017	Three-month anti-hyperglycemic treatment with proportionate doses of metformin or pioglitazone increased orexin concentrations via amelioration of insulin resistance and improvement of glycemic control.	Metformin	69-78	insulin	Homo sapiens	147-154
28977924-8	2017	The proportion of subjects taking metformin declined progressively across age quartiles along with eGFR values, but remained high in oldest subjects (i.e. 54.5 %).	Metformin	34-43	epidermal growth factor receptor	Homo sapiens	99-103
28977924-10	2017	The percentage of patients with low eGFR (i.e. &lt;30 ml/min/1.73m2) taking either metformin or sulphonilureas/repaglinide was particularly high (i.e. 15.3% and 34.3% respectively).	Metformin	83-92	epidermal growth factor receptor	Homo sapiens	36-40
28647726-9	2017	Network meta-analyses suggest that metformin had the highest probability of being the most effective treatment in reducing the risk of most outcomes compared with insulin or glibenclamide.	Metformin	35-44	insulin	Homo sapiens	163-170
28824303-4	2017	Aim: The aim of this study was to investigate the effect and underlying signaling mechanisms of metformin on apoptosis and Cx43 expression in H9c2 cells presenting with hyperglycemia conditions.	Metformin	96-105	gap junction protein, alpha 1	Rattus norvegicus	123-127
28824303-10	2017	Interestingly, metformin attenuated hyperglycemia-increased apoptosis and restored Cx43 expression.	Metformin	15-24	gap junction protein, alpha 1	Rattus norvegicus	83-87
28824303-13	2017	Conclusion: Administration metformin can protect the H9c2 cells against hyperglycemia-induced apoptosis and Cx43 down-regulation, in part, mediated through the induction of autophagy pathway.	Metformin	27-36	gap junction protein, alpha 1	Rattus norvegicus	108-112
28478038-0	2017	Successful metformin treatment of insulin resistance is associated with down-regulation of the kynurenine pathway.	Metformin	11-20	insulin	Homo sapiens	34-41
28601826-0	2017	Study protocol of a phase IB/II clinical trial of metformin and chloroquine in patients with IDH1-mutated or IDH2-mutated solid tumours.	Metformin	50-59	isocitrate dehydrogenase (NADP(+)) 2	Homo sapiens	109-113
28177944-0	2017	Metformin depresses overactivated Notch1/Hes1 signaling in colorectal cancer patients with type 2 diabetes mellitus.	Metformin	0-9	notch receptor 1	Homo sapiens	34-40
28177944-12	2017	In conclusion, the abnormal cell proliferation and differentiation observed in DM-CRC are correlated with overactivated Notch1/Hes1 signaling, which is potentially relieved by metformin treatment.	Metformin	176-185	notch receptor 1	Homo sapiens	120-126
27837308-10	2017	An anti-diabetic drug, metformin, attenuated insulin resistance in PCB-treated 3T3-L1 adipocytes through the reduced expression of Fsp27 protein and LD size.	Metformin	23-32	cell death-inducing DFFA-like effector c	Mus musculus	131-136
28390311-6	2017	However, treatment with metformin suppressed CCl4-induced expression of transforming growth factor beta 1 (TGF-beta1) and phosphorylation of Smad3, which was accompanied with decreased level of alpha smooth muscle actin (alpha-SMA), a marker for the activated hepatic stellate cells (HSCs).	Metformin	24-33	actin alpha 2, smooth muscle, aorta	Mus musculus	194-219
28390311-6	2017	However, treatment with metformin suppressed CCl4-induced expression of transforming growth factor beta 1 (TGF-beta1) and phosphorylation of Smad3, which was accompanied with decreased level of alpha smooth muscle actin (alpha-SMA), a marker for the activated hepatic stellate cells (HSCs).	Metformin	24-33	actin alpha 2, smooth muscle, aorta	Mus musculus	221-230
28324269-0	2017	Metformin sensitizes triple-negative breast cancer to proapoptotic TRAIL receptor agonists by suppressing XIAP expression.	Metformin	0-9	TNF superfamily member 10	Homo sapiens	67-72
28324269-2	2017	We postulated that the metabolic stress induced by the diabetes drug metformin would sensitize breast cancer cells to TRAIL receptor agonists.	Metformin	69-78	TNF superfamily member 10	Homo sapiens	118-123
28324269-7	2017	RESULTS: Metformin sensitized diverse TNBC cells to TRAIL receptor agonists.	Metformin	9-18	TNF superfamily member 10	Homo sapiens	52-57
28324269-8	2017	Metformin selectively enhanced the sensitivity of transformed breast epithelial cells to TRAIL receptor agonist-induced caspase activation and apoptosis with little effect on untransformed breast epithelial cells.	Metformin	0-9	TNF superfamily member 10	Homo sapiens	89-94
28324269-9	2017	These effects of metformin were accompanied by robust reductions in the protein levels of XIAP, a negative regulator of TRAIL-induced apoptosis.	Metformin	17-26	TNF superfamily member 10	Homo sapiens	120-125
28324269-10	2017	Silencing XIAP in TNBC cells mimicked the TRAIL-sensitizing effects of metformin.	Metformin	71-80	TNF superfamily member 10	Homo sapiens	42-47
28324269-12	2017	CONCLUSIONS: Our findings indicate that metformin enhances the activity of TRAIL receptor agonists, thereby supporting the rationale for additional translational studies combining these agents.	Metformin	40-49	TNF superfamily member 10	Homo sapiens	75-80
28378944-9	2017	We found that metformin can exert growth-suppressive effects on these cell lines via inhibition of p-Akt activity and the Bcl-2 family.	Metformin	14-23	BCL2 apoptosis regulator	Homo sapiens	122-127
28273365-0	2017	Metformin attenuates renal fibrosis in both AMPKalpha2-dependent and independent manners.	Metformin	0-9	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	44-54
27167128-9	2017	Activation of AMPK as well as inhibition of its downstream mTOR signaling were detected under metformin treatment in vivo and in vitro; inhibition of AMPK signaling by compound C suppressed autophagy flux induced by metformin in vitro, indicating that AMPK signaling was involved in the effect of metformin on autophagy flux regulation.	Metformin	94-103	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	14-18
27167128-9	2017	Activation of AMPK as well as inhibition of its downstream mTOR signaling were detected under metformin treatment in vivo and in vitro; inhibition of AMPK signaling by compound C suppressed autophagy flux induced by metformin in vitro, indicating that AMPK signaling was involved in the effect of metformin on autophagy flux regulation.	Metformin	216-225	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	14-18
27167128-9	2017	Activation of AMPK as well as inhibition of its downstream mTOR signaling were detected under metformin treatment in vivo and in vitro; inhibition of AMPK signaling by compound C suppressed autophagy flux induced by metformin in vitro, indicating that AMPK signaling was involved in the effect of metformin on autophagy flux regulation.	Metformin	216-225	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	150-154
27167128-9	2017	Activation of AMPK as well as inhibition of its downstream mTOR signaling were detected under metformin treatment in vivo and in vitro; inhibition of AMPK signaling by compound C suppressed autophagy flux induced by metformin in vitro, indicating that AMPK signaling was involved in the effect of metformin on autophagy flux regulation.	Metformin	216-225	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	150-154
27167128-9	2017	Activation of AMPK as well as inhibition of its downstream mTOR signaling were detected under metformin treatment in vivo and in vitro; inhibition of AMPK signaling by compound C suppressed autophagy flux induced by metformin in vitro, indicating that AMPK signaling was involved in the effect of metformin on autophagy flux regulation.	Metformin	216-225	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	14-18
27167128-9	2017	Activation of AMPK as well as inhibition of its downstream mTOR signaling were detected under metformin treatment in vivo and in vitro; inhibition of AMPK signaling by compound C suppressed autophagy flux induced by metformin in vitro, indicating that AMPK signaling was involved in the effect of metformin on autophagy flux regulation.	Metformin	216-225	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	150-154
27167128-9	2017	Activation of AMPK as well as inhibition of its downstream mTOR signaling were detected under metformin treatment in vivo and in vitro; inhibition of AMPK signaling by compound C suppressed autophagy flux induced by metformin in vitro, indicating that AMPK signaling was involved in the effect of metformin on autophagy flux regulation.	Metformin	216-225	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	150-154
28724173-0	2017	A comparative study between myo-inositol and metformin in the treatment of insulin-resistant women.	Metformin	45-54	insulin	Homo sapiens	75-82
28410530-3	2017	In the present study, we found that treatment with metformin inhibited the cardiac expression of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1beta) and interleukin 6 (IL-6) in endotoxin-challenged mice.	Metformin	51-60	tumor necrosis factor	Mus musculus	134-161
28410530-3	2017	In the present study, we found that treatment with metformin inhibited the cardiac expression of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1beta) and interleukin 6 (IL-6) in endotoxin-challenged mice.	Metformin	51-60	tumor necrosis factor	Mus musculus	163-172
28410530-3	2017	In the present study, we found that treatment with metformin inhibited the cardiac expression of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1beta) and interleukin 6 (IL-6) in endotoxin-challenged mice.	Metformin	51-60	interleukin 1 beta	Mus musculus	175-193
28410530-3	2017	In the present study, we found that treatment with metformin inhibited the cardiac expression of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1beta) and interleukin 6 (IL-6) in endotoxin-challenged mice.	Metformin	51-60	interleukin 1 beta	Mus musculus	195-203
28410530-3	2017	In the present study, we found that treatment with metformin inhibited the cardiac expression of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1beta) and interleukin 6 (IL-6) in endotoxin-challenged mice.	Metformin	51-60	interleukin 6	Mus musculus	209-222
28410530-3	2017	In the present study, we found that treatment with metformin inhibited the cardiac expression of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1beta) and interleukin 6 (IL-6) in endotoxin-challenged mice.	Metformin	51-60	interleukin 6	Mus musculus	224-228
28410530-4	2017	Treatment with metformin also alleviated the histological abnormalities in the heart, suppressed the upregulation of myeloperoxidase (MPO), decreased the elevation of creatinine kinase-myocardial band (CK-MB) and brain natriuretic peptide (BNP).	Metformin	15-24	myeloperoxidase	Homo sapiens	117-132
28410530-4	2017	Treatment with metformin also alleviated the histological abnormalities in the heart, suppressed the upregulation of myeloperoxidase (MPO), decreased the elevation of creatinine kinase-myocardial band (CK-MB) and brain natriuretic peptide (BNP).	Metformin	15-24	myeloperoxidase	Homo sapiens	134-137
28410530-6	2017	Meanwhile, the suppressive effects of metformin on MPO, TNF-alpha, CK-MB and BNP were reversed by the AMPK inhibitor.	Metformin	38-47	myeloperoxidase	Homo sapiens	51-54
28410530-6	2017	Meanwhile, the suppressive effects of metformin on MPO, TNF-alpha, CK-MB and BNP were reversed by the AMPK inhibitor.	Metformin	38-47	tumor necrosis factor	Homo sapiens	56-65
28410530-7	2017	On the contrary, administration of AMPK activator mimicked the effects of metformin on AMPKalpha phosphorylation, MPO upregulation, CK-MB release and BNP elevation.	Metformin	74-83	myeloperoxidase	Homo sapiens	114-117
28440424-8	2017	Additionally, metformin reduced the levels of phosphorylated epidermal growth factor receptor and ROR2 as well as markedly altered miRNA expression in HuTu80 cells.	Metformin	14-23	epidermal growth factor receptor	Homo sapiens	61-93
28504725-3	2017	Here we show that metformin, the most widely used drug for type 2 diabetes, rescues core phenotypes in Fmr1-/y mice and selectively normalizes ERK signaling, eIF4E phosphorylation and the expression of MMP-9.	Metformin	18-27	mitogen-activated protein kinase 1	Mus musculus	143-146
28363500-0	2017	Corrigendum to "Metformin affects macrophages" phenotype and improves the activity of glutathione peroxidase, superoxide dismutase, catalase and decreases malondialdehyde concentration in a partially AMPK-independent manner in LPS-stimulated human monocytes/macrophages" [Pharmacol.	Metformin	16-25	catalase	Homo sapiens	132-140
27897089-10	2017	Metformin supplementation downregulated the d-galactose induced expressions of sirtuin-2, IL-6, and TNF-alpha expression, whereas upregulated the Beclin-1 expression.	Metformin	0-9	interleukin 6	Rattus norvegicus	90-94
27897089-10	2017	Metformin supplementation downregulated the d-galactose induced expressions of sirtuin-2, IL-6, and TNF-alpha expression, whereas upregulated the Beclin-1 expression.	Metformin	0-9	tumor necrosis factor	Rattus norvegicus	100-109
28725599-5	2017	In this review, we summarize the evidence regarding the impact of metformin-an insulin sensitizer-on the three mechanisms of arteriogenic ED.	Metformin	66-75	insulin	Homo sapiens	79-86
28273365-1	2017	Metformin is a well-known AMP-activated protein kinase (AMPK) activator, and it has been shown to inhibit organ fibrosis.	Metformin	0-9	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	56-60
28273365-3	2017	Here, we aimed to investigate the role of the AMPKalpha2 isoform in mediating the inhibitory effect of metformin on renal fibrosis.	Metformin	103-112	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	46-56
28273365-7	2017	In AMPKalpha2-/- mice, metformin also tended to inhibit UUO-induced renal fibrosis.	Metformin	23-32	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	3-13
28273365-9	2017	In contrast, metformin reduced UUO-induced TGFbeta1 downstream Smad3 phosphorylation in both WT and AMPKalpha2-/- mice, suggesting that this regulation occurs in an AMPKalpha2-independent manner.	Metformin	13-22	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	100-110
28273365-10	2017	In conclusion, the underlying mechanisms for the protective effects of metformin against renal fibrosis include AMPKalpha2-dependent targeting of TGFbeta1 production and AMPKalpha2-independent targeting of TGFbeta1 downstream signalling.	Metformin	71-80	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	112-122
28273365-10	2017	In conclusion, the underlying mechanisms for the protective effects of metformin against renal fibrosis include AMPKalpha2-dependent targeting of TGFbeta1 production and AMPKalpha2-independent targeting of TGFbeta1 downstream signalling.	Metformin	71-80	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	170-180
28364040-6	2017	The down-regulation of HNF4alpha was dependent on the activation of AMP-activated protein kinase (AMPK), and the reduction of HNF4alpha protein expression by metformin, an AMPK activator, and hypoxia was inhibited by the overexpression of a kinase-dead (KD) form of AMPKalpha2.	Metformin	158-167	hepatocyte nuclear factor 4 alpha	Homo sapiens	23-32
28364040-6	2017	The down-regulation of HNF4alpha was dependent on the activation of AMP-activated protein kinase (AMPK), and the reduction of HNF4alpha protein expression by metformin, an AMPK activator, and hypoxia was inhibited by the overexpression of a kinase-dead (KD) form of AMPKalpha2.	Metformin	158-167	hepatocyte nuclear factor 4 alpha	Homo sapiens	126-135
28364040-8	2017	Adenovirus-mediated overexpression of KD-AMPKalpha2 improved insulin secretion in metformin-treated islets, hypoxic islets, and ob/ob mouse islets.	Metformin	82-91	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	41-51
28553078-9	2017	Levels of TNF-alpha, hs-CRP, and vaspin were reduced by metformin XR but not by the IR formulation.	Metformin	56-65	tumor necrosis factor	Homo sapiens	10-19
28413172-12	2017	Besides, metformin treatment restores Akt phosphorylation in both tissues.	Metformin	9-18	AKT serine/threonine kinase 1	Rattus norvegicus	38-41
28404960-0	2017	Impact of metformin on C-reactive protein levels in women with polycystic ovary syndrome: a meta-analysis.	Metformin	10-19	C-reactive protein	Homo sapiens	23-41
28404960-1	2017	The impact of the recommended first-line treatment with metformin on C-reactive protein (CRP) levels in patients with polycystic ovary syndrome (PCOS) is still controversial.	Metformin	56-65	C-reactive protein	Homo sapiens	69-87
28404960-1	2017	The impact of the recommended first-line treatment with metformin on C-reactive protein (CRP) levels in patients with polycystic ovary syndrome (PCOS) is still controversial.	Metformin	56-65	C-reactive protein	Homo sapiens	89-92
28404960-2	2017	We conducted a meta-analysis of studies reporting the impact of metformin on serum CRP levels in women with PCOS.	Metformin	64-73	C-reactive protein	Homo sapiens	83-86
28404960-6	2017	CRP levels significantly decreased after metformin treatment (WMD = -1.23mg/L, 95%CI: -1.65 to -0.81, I2 = 93% and P &lt; 0.001 for heterogeneity).	Metformin	41-50	C-reactive protein	Homo sapiens	0-3
28404960-8	2017	Interestingly, the degree of decreased CRP levels was not depended on metformin dosage, but more significantly in patients treated beyond 6 months (WMD&gt;=6months = -1.47mg/L vs. WMD&lt;6months = -0.94 mg/L).	Metformin	70-79	C-reactive protein	Homo sapiens	39-42
28404960-11	2017	Therefore, metformin shows the potential effects on CRP levels in women with PCOS.	Metformin	11-20	C-reactive protein	Homo sapiens	52-55
28404960-12	2017	However, considering the very low quality of evidence for the analysis, the effect of metformin on CRP levels are still very uncertain, and large-scale randomized-controlled study is needed to ascertain the long-term effects of metformin in PCOS.	Metformin	86-95	C-reactive protein	Homo sapiens	99-102
28389241-5	2017	Additionally, metformin down regulated inflammatory markers like TLR2, TLR4, CD80, CD86, NF-kappaB, STAT1 and suppressed adipose tissue inflammation by efficiently polarizing adipose tissue macrophages toward anti-inflammatory state by way of indirect inhibition of SHP-1 mRNA and protein expressions.	Metformin	14-23	toll-like receptor 4	Mus musculus	71-75
28389241-5	2017	Additionally, metformin down regulated inflammatory markers like TLR2, TLR4, CD80, CD86, NF-kappaB, STAT1 and suppressed adipose tissue inflammation by efficiently polarizing adipose tissue macrophages toward anti-inflammatory state by way of indirect inhibition of SHP-1 mRNA and protein expressions.	Metformin	14-23	CD80 antigen	Mus musculus	77-81
28389241-5	2017	Additionally, metformin down regulated inflammatory markers like TLR2, TLR4, CD80, CD86, NF-kappaB, STAT1 and suppressed adipose tissue inflammation by efficiently polarizing adipose tissue macrophages toward anti-inflammatory state by way of indirect inhibition of SHP-1 mRNA and protein expressions.	Metformin	14-23	CD86 antigen	Mus musculus	83-87
28389241-5	2017	Additionally, metformin down regulated inflammatory markers like TLR2, TLR4, CD80, CD86, NF-kappaB, STAT1 and suppressed adipose tissue inflammation by efficiently polarizing adipose tissue macrophages toward anti-inflammatory state by way of indirect inhibition of SHP-1 mRNA and protein expressions.	Metformin	14-23	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	89-98
28526011-12	2017	Among those with incident AKI, being on metformin at admission was associated with a higher rate of survival at 28 days (HR 0.81, 95% CI 0.69, 0.94, p = 0.006) even after adjustment for age, sex, pre-admission eGFR, HbA1c and diabetes duration.	Metformin	40-49	epidermal growth factor receptor	Homo sapiens	210-214
29088755-7	2017	This metformin-induced amelioration of hypoxia was accompanied by a significant reduction in expressions of both HIF-1alpha and angiogenesis-associated factors (AAFs).	Metformin	5-14	hypoxia inducible factor 1 subunit alpha	Homo sapiens	113-123
29088755-10	2017	Taken together, metformin ameliorated tumor hypoxia and restrained HIF-1alpha-induced expressions of AAFs through elevating tumor blood perfusion, thus suppressing the excessive tumor angiogenesis.	Metformin	16-25	hypoxia inducible factor 1 subunit alpha	Homo sapiens	67-77
28274614-7	2017	Treatment with metformin reduced phosphorylation of Akt and mTOR and inhibited downstream targets of mTOR.	Metformin	15-24	thymoma viral proto-oncogene 1	Mus musculus	52-55
28427181-0	2017	Metformin inhibits ALK1-mediated angiogenesis via activation of AMPK.	Metformin	0-9	secretory leukocyte peptidase inhibitor	Homo sapiens	19-23
28427181-4	2017	Thus, we treated human umbilical vein endothelial cells with metformin as well as other pharmacological AMPK activators and showed that activation of AMPK inhibited Smad1/5 phosphorylation and tube formation induced by BMP9.	Metformin	61-70	growth differentiation factor 2	Homo sapiens	219-223
28427181-6	2017	Metformin inhibition of BMP9 signaling is possibly mediated by upregulation of Smurf1, leading to degradation of ALK1.	Metformin	0-9	growth differentiation factor 2	Homo sapiens	24-28
28427181-6	2017	Metformin inhibition of BMP9 signaling is possibly mediated by upregulation of Smurf1, leading to degradation of ALK1.	Metformin	0-9	SMAD specific E3 ubiquitin protein ligase 1	Homo sapiens	79-85
28427181-6	2017	Metformin inhibition of BMP9 signaling is possibly mediated by upregulation of Smurf1, leading to degradation of ALK1.	Metformin	0-9	secretory leukocyte peptidase inhibitor	Homo sapiens	113-117
28427181-9	2017	The data revealed that metformin significantly reduced choroidal neovascularization to a level comparable to LDN212854, an ALK1 specific inhibitor.	Metformin	23-32	secretory leukocyte peptidase inhibitor	Homo sapiens	123-127
28427181-10	2017	In conjunction, metformin diminished expression of ALK1 in endothelium of the lesion area.	Metformin	16-25	secretory leukocyte peptidase inhibitor	Homo sapiens	51-55
28427181-12	2017	This may offer us a new avenue for the treatment of related diseases using clinically used pharmacological AMPK activators like metformin in combination with other strategies to enhance the treatment efficacy or in the case of anti-VEGF resistance.	Metformin	128-137	vascular endothelial growth factor A	Homo sapiens	232-236
28553078-9	2017	Levels of TNF-alpha, hs-CRP, and vaspin were reduced by metformin XR but not by the IR formulation.	Metformin	56-65	serpin family A member 12	Homo sapiens	33-39
28977950-2	2017	We carried out a systematic search of Pubmed and Embase databases for studies published before August 2016, which assessed the associations between anti-diabetic medications (metformin, sulfonylureas, thiazolidinediones and insulin) intake and pancreatic cancer prognosis.	Metformin	175-184	insulin	Homo sapiens	224-231
28761738-1	2017	PURPOSE: Our previous works demonstrated the ability of metformin to revert resistance to gefitinib, a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in non-small-cell lung cancer (NSCLC) EGFR/LKB1 wild-type (WT) cell lines.	Metformin	56-65	epidermal growth factor receptor	Homo sapiens	113-145
28464864-0	2017	Metformin produces growth inhibitory effects in combination with nutlin-3a on malignant mesothelioma through a cross-talk between mTOR and p53 pathways.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	130-134
28464864-0	2017	Metformin produces growth inhibitory effects in combination with nutlin-3a on malignant mesothelioma through a cross-talk between mTOR and p53 pathways.	Metformin	0-9	tumor protein p53	Homo sapiens	139-142
28464864-10	2017	Western blot analyses showed that metformin inhibited downstream pathways of the mammalian target of rapamycin (mTOR) but did not activate the p53 pathways, whereas nutlin-3a phosphorylated p53 and suppressed mTOR pathways.	Metformin	34-43	mechanistic target of rapamycin kinase	Homo sapiens	81-110
28464864-10	2017	Western blot analyses showed that metformin inhibited downstream pathways of the mammalian target of rapamycin (mTOR) but did not activate the p53 pathways, whereas nutlin-3a phosphorylated p53 and suppressed mTOR pathways.	Metformin	34-43	mechanistic target of rapamycin kinase	Homo sapiens	112-116
28761738-1	2017	PURPOSE: Our previous works demonstrated the ability of metformin to revert resistance to gefitinib, a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in non-small-cell lung cancer (NSCLC) EGFR/LKB1 wild-type (WT) cell lines.	Metformin	56-65	epidermal growth factor receptor	Homo sapiens	147-151
28761738-1	2017	PURPOSE: Our previous works demonstrated the ability of metformin to revert resistance to gefitinib, a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in non-small-cell lung cancer (NSCLC) EGFR/LKB1 wild-type (WT) cell lines.	Metformin	56-65	epidermal growth factor receptor	Homo sapiens	218-222
28233033-10	2017	In humans, adipose tissue expression of DHH and serum IHH decrease with obesity and type 2 diabetes, which might be explained by the intake of metformin.	Metformin	143-152	desert hedgehog signaling molecule	Homo sapiens	40-43
28065465-2	2017	The CGMT trial is a multicenter, phase II randomized, double-blinded, and placebo-controlled study, which is designed to evaluate the safety and efficacy of metformin in combination with gefitinib as first-line therapy in patients presenting with stage IIIb-IV non-small-cell lung cancer expressing the epidermal growth factor receptor mutant.	Metformin	157-166	epidermal growth factor receptor	Homo sapiens	303-335
28092404-8	2017	RESULTS: Both metformin and MYO significantly reduced the insulin response to OGTT and improved insulin sensitivity.	Metformin	14-23	insulin	Homo sapiens	58-65
28092404-8	2017	RESULTS: Both metformin and MYO significantly reduced the insulin response to OGTT and improved insulin sensitivity.	Metformin	14-23	insulin	Homo sapiens	96-103
28432082-0	2017	Effect of oral contraceptives and/or metformin on GLP-1 secretion and reactive hypoglycaemia in polycystic ovary syndrome.	Metformin	37-46	glucagon	Homo sapiens	50-55
28432082-2	2017	The possible effects of treatment with oral contraceptives (OCP) and/or metformin on GLP-1 secretion and risk of RH in PCOS is undetermined.	Metformin	72-81	glucagon	Homo sapiens	85-90
28432082-9	2017	RESULTS: Fasting GLP-1 levels increased during metformin + OCP vs OCP treatment, whereas AUC GLP-1 levels were unchanged during medical treatment.	Metformin	47-56	glucagon	Homo sapiens	17-22
28238946-0	2017	Involvement of pregnane X receptor in the suppression of carboxylesterases by metformin in vivo and in vitro, mediated by the activation of AMPK and JNK signaling pathway.	Metformin	78-87	nuclear receptor subfamily 1 group I member 2	Homo sapiens	15-34
28238946-0	2017	Involvement of pregnane X receptor in the suppression of carboxylesterases by metformin in vivo and in vitro, mediated by the activation of AMPK and JNK signaling pathway.	Metformin	78-87	mitogen-activated protein kinase 8	Homo sapiens	149-152
28238946-6	2017	The decreased expression of nuclear receptor PXR and its target gene P-gp indicates the involvements of PXR in the suppressed expression of carboxylesterases by metformin.	Metformin	161-170	nuclear receptor subfamily 1 group I member 2	Homo sapiens	45-48
28238946-6	2017	The decreased expression of nuclear receptor PXR and its target gene P-gp indicates the involvements of PXR in the suppressed expression of carboxylesterases by metformin.	Metformin	161-170	nuclear receptor subfamily 1 group I member 2	Homo sapiens	104-107
28238946-7	2017	Furthermore, metformin significantly suppresses the phosphorylation of AMPK and JNK, and the suppression of carboxylesterases induced by metformin is repeatedly abolished by AMPK inhibitor Compound C and JNK inhibitor SP600125.	Metformin	13-22	mitogen-activated protein kinase 8	Homo sapiens	80-83
28238946-7	2017	Furthermore, metformin significantly suppresses the phosphorylation of AMPK and JNK, and the suppression of carboxylesterases induced by metformin is repeatedly abolished by AMPK inhibitor Compound C and JNK inhibitor SP600125.	Metformin	13-22	mitogen-activated protein kinase 8	Homo sapiens	204-207
28238946-7	2017	Furthermore, metformin significantly suppresses the phosphorylation of AMPK and JNK, and the suppression of carboxylesterases induced by metformin is repeatedly abolished by AMPK inhibitor Compound C and JNK inhibitor SP600125.	Metformin	137-146	mitogen-activated protein kinase 8	Homo sapiens	204-207
28238946-8	2017	It implies that the activation of AMPK and JNK pathways mediates the suppression of carboxylesterases by metformin.	Metformin	105-114	mitogen-activated protein kinase 8	Homo sapiens	43-46
28182265-1	2017	OBJECTIVE: To examine the association between long-term metformin therapy and serum vitamin B12 monitoring.	Metformin	56-65	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	92-95
28075066-9	2017	The study demonstrated that treatment with alogliptin + metformin FDC BID resulted in better glycaemic control than either monotherapy and was well tolerated in Asian patients with type 2 diabetes.	Metformin	56-65	BH3 interacting domain death agonist	Homo sapiens	70-73
28553599-0	2017	Serum Vitamin B12 Levels in Type 2 Diabetes Patients on Metformin Compared to those Never on Metformin: A Cross-sectional Study.	Metformin	56-65	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	14-17
28553599-1	2017	CONTEXT: There are limited data about the effect of metformin use on serum Vitamin B12 levels in type 2 diabetes patients from India.	Metformin	52-61	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	83-86
28553599-2	2017	AIMS: We studied serum Vitamin B12 levels in patients with type 2 diabetes mellitus who were receiving metformin and compared them to those never treated with metformin.	Metformin	103-112	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	31-34
28553599-6	2017	RESULTS: The serum Vitamin B12 levels were 267.7 +- 194.4 pmol/l in metformin group and 275.1 +- 197.2 pmol/l in the no metformin group (P = 0.78).	Metformin	68-77	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	27-30
28553599-7	2017	When adjusted for duration of diabetes, metformin use was associated with a 87.7 +- 37.7 pmol/l (95% confidence interval [CI], -162.1--3.3, P = 0.02) lower serum Vitamin B12 levels.	Metformin	40-49	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	170-173
28553599-10	2017	CONCLUSIONS: Metformin use was associated with a lower serum Vitamin B12 levels when adjusted for duration of diabetes.	Metformin	13-22	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	69-72
28339020-0	2017	Metformin inhibits endothelial progenitor cell migration by decreasing matrix metalloproteinases, MMP-2 and MMP-9, via the AMPK/mTOR/autophagy pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	128-132
28182265-6	2017	We estimated the proportion of participants who received a serum B12 test and used multivariable logistic regression, stratified by age, to evaluate the association between metformin use and serum B12 testing.	Metformin	173-182	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	197-200
28182265-8	2017	The mean B12 concentration was significantly lower in the metformin-exposed group (439.2 pg/dL) compared to those without diabetes (522.4 pg/dL) (P = .0015).	Metformin	58-67	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	9-12
28182265-9	2017	About 7% of persons with diabetes receiving metformin were vitamin B12 deficient (&lt;170 pg/dL) compared to 3% of persons without diabetes or metformin use (P = .0001).	Metformin	44-53	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	67-70
28182265-11	2017	CONCLUSION: Long-term metformin therapy is significantly associated with lower serum vitamin B12 concentration, yet those at risk are often not monitored for B12 deficiency.	Metformin	22-31	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	93-96
28182265-12	2017	Because metformin is first line therapy for type 2 diabetes, clinical decision support should be considered to promote serum B12 monitoring among long-term metformin users for timely identification of the potential need for B12 replacement.	Metformin	156-165	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	125-128
28182265-12	2017	Because metformin is first line therapy for type 2 diabetes, clinical decision support should be considered to promote serum B12 monitoring among long-term metformin users for timely identification of the potential need for B12 replacement.	Metformin	156-165	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	224-227
28375706-0	2017	Impact of Diabetes, Insulin, and Metformin Use on the Outcome of Patients With Human Epidermal Growth Factor Receptor 2-Positive Primary Breast Cancer: Analysis From the ALTTO Phase III Randomized Trial.	Metformin	33-42	erb-b2 receptor tyrosine kinase 2	Homo sapiens	79-119
28375706-9	2017	Whereas insulin treatment was associated with a detrimental effect, metformin had a salutary effect in patients with diabetes who had HER2-positive and hormone receptor-positive breast cancer.	Metformin	68-77	erb-b2 receptor tyrosine kinase 2	Homo sapiens	134-138
28375706-10	2017	Conclusion Metformin may improve the worse prognosis that is associated with diabetes and insulin treatment, mainly in patients with primary HER2-positive and hormone receptor-positive breast cancer.	Metformin	11-20	insulin	Homo sapiens	90-97
28375706-10	2017	Conclusion Metformin may improve the worse prognosis that is associated with diabetes and insulin treatment, mainly in patients with primary HER2-positive and hormone receptor-positive breast cancer.	Metformin	11-20	erb-b2 receptor tyrosine kinase 2	Homo sapiens	141-145
28372526-6	2017	The metformin group had significantly lower serum prolactin level at endpoint (four randomized controlled trials, n=501; weighted mean difference: -6.87 ug/L (95% confidence interval: -13.24 to -0.51), p=0.03; I2=80%) with "moderate quality" based on the grading of recommendations assessment, development, and evaluation system.	Metformin	4-13	prolactin	Homo sapiens	50-59
28372526-9	2017	Adjunctive metformin appears to be effective and safe for reducing antipsychotic-induced hyperprolactinemia and prolactin-related symptoms in schizophrenia patients.	Metformin	11-20	prolactin	Homo sapiens	94-103
28391030-2	2017	In the present study we investigated the influence of the anti-diabetic drug metformin on the cytotoxic effects of EGFR targeted therapy and chemotherapy in 7 non-small cell lung cancer (NSCLC) cell lines and a cohort of lung cancer patients with/without T2D.	Metformin	77-86	epidermal growth factor receptor	Homo sapiens	115-119
28391030-4	2017	EGFR downstream signaling evaluation further demonstrated that metformin, at its IC50 value, modified apoptosis caused in erlotinib or chemotherapeutic agent-treated cells via AKT activation and the inhibition of caspase 3 and PARP cleavages.	Metformin	63-72	epidermal growth factor receptor	Homo sapiens	0-4
28391030-4	2017	EGFR downstream signaling evaluation further demonstrated that metformin, at its IC50 value, modified apoptosis caused in erlotinib or chemotherapeutic agent-treated cells via AKT activation and the inhibition of caspase 3 and PARP cleavages.	Metformin	63-72	caspase 3	Homo sapiens	213-222
28391030-4	2017	EGFR downstream signaling evaluation further demonstrated that metformin, at its IC50 value, modified apoptosis caused in erlotinib or chemotherapeutic agent-treated cells via AKT activation and the inhibition of caspase 3 and PARP cleavages.	Metformin	63-72	poly(ADP-ribose) polymerase 1	Homo sapiens	227-231
28391030-8	2017	Consequently, the application of metformin for T2D NSCLC patients receiving chemo or EGFR targeted therapy should be considered with caution.	Metformin	33-42	epidermal growth factor receptor	Homo sapiens	85-89
28459432-0	2017	Metformin inhibits SUV39H1-mediated migration of prostate cancer cells.	Metformin	0-9	SUV39H1 histone lysine methyltransferase	Homo sapiens	19-26
28459432-5	2017	We found that the level of SUV39H1, a histone methyltransferase of H3 Lys9, was reduced in metformin-treated PCa cells in a time-dependent manner.	Metformin	91-100	SUV39H1 histone lysine methyltransferase	Homo sapiens	27-34
28459432-9	2017	Taken together, metformin reduced SUV39H1 to inhibit migration of PCa cells via disturbing the integrin-FAK signaling.	Metformin	16-25	SUV39H1 histone lysine methyltransferase	Homo sapiens	34-41
28811775-6	2017	RESULTS: The results of this study showed that PTZ-induced neuronal cell death by activation of pro apoptotic proteins caspase-3 and 9 whereas the exposure of metformin showed its protective effect against neuronal loss in HCN-2 cell line.	Metformin	159-168	hyperpolarization activated cyclic nucleotide gated potassium and sodium channel 2	Homo sapiens	223-228
31994074-0	2017	Erratum to "Metformin affects macrophages" phenotype and improves the activity of glutathione peroxidase, superoxide dismutase, catalase and decreases malondialdehyde concentration in a partially AMPK-independent manner in LPS-stimulated human monocytes/macrophages".	Metformin	12-21	catalase	Homo sapiens	128-136
28502303-5	2017	The expressions of P21 and c-caspase-3 increased, meanwhile, the expressions of CDK4, cyclin D1, caspase-3 and Bcl-2 decreased by metformin.	Metformin	130-139	cyclin-dependent kinase 4	Rattus norvegicus	80-84
28502303-5	2017	The expressions of P21 and c-caspase-3 increased, meanwhile, the expressions of CDK4, cyclin D1, caspase-3 and Bcl-2 decreased by metformin.	Metformin	130-139	cyclin D1	Rattus norvegicus	86-95
28502303-5	2017	The expressions of P21 and c-caspase-3 increased, meanwhile, the expressions of CDK4, cyclin D1, caspase-3 and Bcl-2 decreased by metformin.	Metformin	130-139	BCL2, apoptosis regulator	Rattus norvegicus	111-116
28502303-7	2017	Furthermore, the expressions of IGF-1R, p-AKT and p-ERK descended after metformin treatment.	Metformin	72-81	AKT serine/threonine kinase 1	Rattus norvegicus	42-45
28445726-6	2017	In cancer patients, the SIRT1 agonist metformin reduced the frequency of Th17 cells and STAT3 acetylation levels.	Metformin	38-47	signal transducer and activator of transcription 3	Homo sapiens	88-93
28439456-14	2017	ELISA assay revealed decreased levels of inflammatory response marker IL-1beta and TNF-alpha in the pancreatic tissues following metformin treatment.	Metformin	129-138	interleukin 1 beta	Mus musculus	70-78
28439456-14	2017	ELISA assay revealed decreased levels of inflammatory response marker IL-1beta and TNF-alpha in the pancreatic tissues following metformin treatment.	Metformin	129-138	tumor necrosis factor	Mus musculus	83-92
28529619-5	2017	By inhibiting hepatic gluconeogenesis and increasing glucose uptake by muscles, metformin decreases blood glucose and circulating Insulin levels.	Metformin	80-89	insulin	Homo sapiens	130-137
29871302-8	2017	The combination of metformin and 5-fluorouracil produced an antagonism action in Hep-2 cells.Western blot assay showed that metformin, cisplatin, 5-fluorouracil could have caused the increase of expression level of AMPK-alpha, P21 and Cyclin D1 in Hep-2 cells while Paclitaxel could have cause the decrease of expression level of Cyclin D1.	Metformin	19-28	cyclin dependent kinase inhibitor 1A	Homo sapiens	227-230
29871302-8	2017	The combination of metformin and 5-fluorouracil produced an antagonism action in Hep-2 cells.Western blot assay showed that metformin, cisplatin, 5-fluorouracil could have caused the increase of expression level of AMPK-alpha, P21 and Cyclin D1 in Hep-2 cells while Paclitaxel could have cause the decrease of expression level of Cyclin D1.	Metformin	124-133	cyclin dependent kinase inhibitor 1A	Homo sapiens	227-230
29871302-11	2017	Metformin has an antagonism on the anticancer effect to 5-fluorouracil in Hep-2 cells, and this antagonistic effect occurred partially through molecular signal pathways of AMPK-alpha, P21 and Cyclin D1 and it"s significantly related to the cell cycle arrest.	Metformin	0-9	cyclin dependent kinase inhibitor 1A	Homo sapiens	184-187
28039583-1	2017	AIMS: To improve insulin sensitivity, insulin-sensitizing drugs such as metformin are commonly used in overweight and obese T1D patients.	Metformin	72-81	insulin	Homo sapiens	17-24
28039583-1	2017	AIMS: To improve insulin sensitivity, insulin-sensitizing drugs such as metformin are commonly used in overweight and obese T1D patients.	Metformin	72-81	insulin	Homo sapiens	38-45
26914484-1	2017	Low serum B12 level is a common occurrence in patients with type 2 diabetes (T2DM) treated with metformin.	Metformin	96-105	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	10-13
29259467-8	2017	Conclusion: Clomiphene-metformin combination treatment appears to be useful, at least for clomiphene-resistant patients, and a BMI of &gt;30 kg/m2 and a fasting insulin of &gt;=15 muU/mL appear to be predictors of a good result with this treatment.	Metformin	23-32	insulin	Homo sapiens	161-168
26914484-3	2017	Our objective was to examine the current practice and clinical determinants of vitamin B12 testing in metformin treated T2DM patients.	Metformin	102-111	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	87-90
26914484-12	2017	Insulin treatment, hypertension, and chronic diabetic complications in metformin treated T2DM patients are associated with higher rates of vitamin B12 testing.	Metformin	71-80	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	147-150
28168653-12	2017	High-dose metformin significantly reduced the expression of matrix metalloproteinase-2 (MMP-2) and mechanistic Target of Rapamycin (mTor), regardless of the concentration of dexamethasone and testosterone.	Metformin	10-19	mechanistic target of rapamycin kinase	Homo sapiens	99-130
28538088-0	2017	Effects of the Insulin Sensitizer Metformin in Alzheimer Disease: Pilot Data From a Randomized Placebo-controlled Crossover Study.	Metformin	34-43	insulin	Homo sapiens	15-22
28538088-2	2017	Given this association, we hypothesized that the central nervous system-penetrant insulin-sensitizing medication metformin would be beneficial as a disease-modifying and/or symptomatic therapy for AD, and conducted a placebo-controlled crossover study of its effects on cerebrospinal fluid (CSF), neuroimaging, and cognitive biomarkers.	Metformin	113-122	insulin	Homo sapiens	82-89
28168653-12	2017	High-dose metformin significantly reduced the expression of matrix metalloproteinase-2 (MMP-2) and mechanistic Target of Rapamycin (mTor), regardless of the concentration of dexamethasone and testosterone.	Metformin	10-19	mechanistic target of rapamycin kinase	Homo sapiens	132-136
28291580-0	2017	Restored Plasma Anandamide and Endometrial Expression of Fatty Acid Amide Hydrolase in Women With Polycystic Ovary Syndrome by the Combination Use of Diane-35 and Metformin.	Metformin	163-172	fatty acid amide hydrolase	Homo sapiens	57-83
28291580-10	2017	We found that after treatment with Diane-35 and metformin, FAAH expression tended toward a significant increase compared with women before the treatment.	Metformin	48-57	fatty acid amide hydrolase	Homo sapiens	59-63
27935183-3	2017	Adjunct metformin reduces insulin dose requirement and stabilizes weight but there are no data on its cardiovascular effects.	Metformin	8-17	insulin	Homo sapiens	26-33
27750350-1	2017	Background: Metformin decreases serum levels of monomeric prolactin.	Metformin	12-21	prolactin	Homo sapiens	58-67
27935183-7	2017	MATERIALS AND METHODS: After 12 weeks of single-blind placebo-controlled run-in, participants with &gt;= 70% adherence are randomized to metformin or matching placebo for 3 years with insulin titrated towards HbA1c 7.0% (53 mmol/mol).	Metformin	137-146	insulin	Homo sapiens	184-191
28485785-0	2017	Study on the influence of metformin on castration-resistant prostate cancer PC-3 cell line biological behavior by its inhibition on PLCepsilon gene-mediated Notch1/Hes and androgen receptor signaling pathway.	Metformin	26-35	notch receptor 1	Homo sapiens	157-163
28276972-6	2017	Insulin basal therapy (+- metformin) may be optimized by the addition of a SGLT2 inhibitor or a glucagon-like peptide-1 (GLP-1) receptor agonist.	Metformin	23-35	glucagon	Homo sapiens	96-119
28485785-0	2017	Study on the influence of metformin on castration-resistant prostate cancer PC-3 cell line biological behavior by its inhibition on PLCepsilon gene-mediated Notch1/Hes and androgen receptor signaling pathway.	Metformin	26-35	androgen receptor	Homo sapiens	172-189
28485785-1	2017	OBJECTIVE: To study the regulation of metformin on the biological behaviors of the castration-resistant prostate cancer (CRPC) PC-3 cell such as proliferation, invasion, apoptosis through influencing Notch1/Hes and androgen receptor (AR) signaling pathway activity by its inhibition on the expression of PLCepsilon gene.	Metformin	38-47	notch receptor 1	Homo sapiens	200-206
28485785-1	2017	OBJECTIVE: To study the regulation of metformin on the biological behaviors of the castration-resistant prostate cancer (CRPC) PC-3 cell such as proliferation, invasion, apoptosis through influencing Notch1/Hes and androgen receptor (AR) signaling pathway activity by its inhibition on the expression of PLCepsilon gene.	Metformin	38-47	androgen receptor	Homo sapiens	215-232
28485785-1	2017	OBJECTIVE: To study the regulation of metformin on the biological behaviors of the castration-resistant prostate cancer (CRPC) PC-3 cell such as proliferation, invasion, apoptosis through influencing Notch1/Hes and androgen receptor (AR) signaling pathway activity by its inhibition on the expression of PLCepsilon gene.	Metformin	38-47	androgen receptor	Homo sapiens	234-236
28485785-10	2017	CONCLUSIONS: Metformin can regulate the biological behaviors of CRPC PC-3 cell line such as proliferation, invasion, migration and apoptosis through influencing Notch1/Hes and AR signaling pathway activity by its inhibition on the expression of PLCepsilon gene.	Metformin	13-22	notch receptor 1	Homo sapiens	161-167
28485785-10	2017	CONCLUSIONS: Metformin can regulate the biological behaviors of CRPC PC-3 cell line such as proliferation, invasion, migration and apoptosis through influencing Notch1/Hes and AR signaling pathway activity by its inhibition on the expression of PLCepsilon gene.	Metformin	13-22	androgen receptor	Homo sapiens	176-178
28196954-4	2017	Multiple studies in vitro and in vivo have demonstrated that metformin can inhibit the growth of thyroid cells and different types of thyroid cancer cells by affecting the insulin/IGF1 and mTOR pathways.	Metformin	61-70	insulin	Homo sapiens	172-179
28196954-4	2017	Multiple studies in vitro and in vivo have demonstrated that metformin can inhibit the growth of thyroid cells and different types of thyroid cancer cells by affecting the insulin/IGF1 and mTOR pathways.	Metformin	61-70	insulin like growth factor 1	Homo sapiens	180-184
28196954-4	2017	Multiple studies in vitro and in vivo have demonstrated that metformin can inhibit the growth of thyroid cells and different types of thyroid cancer cells by affecting the insulin/IGF1 and mTOR pathways.	Metformin	61-70	mechanistic target of rapamycin kinase	Homo sapiens	189-193
28242651-0	2017	Metformin Suppresses Systemic Autoimmunity in Roquinsan/san Mice through Inhibiting B Cell Differentiation into Plasma Cells via Regulation of AMPK/mTOR/STAT3.	Metformin	0-9	signal transducer and activator of transcription 3	Mus musculus	153-158
28242651-10	2017	These alterations in B and T cell subsets by metformin were associated with enhanced AMPK expression and inhibition of mTOR-STAT3 signaling.	Metformin	45-54	signal transducer and activator of transcription 3	Mus musculus	124-129
28242651-12	2017	Taken together, metformin-induced alterations in AMPK-mTOR-STAT3 signaling may have therapeutic value in SLE by inhibiting B cell differentiation into PCs and GCs.	Metformin	16-25	signal transducer and activator of transcription 3	Mus musculus	59-64
28904497-0	2017	The Effect of Metformin Treatment on the Serum Levels of Homocysteine, Folic Acid, and Vitamin B12 in Patients with Polycystic Ovary Syndrome.	Metformin	14-23	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	95-98
28904497-3	2017	The aim of this study was to investigate the effect of metformin on the levels of serum Hcy, vitamin B12 (vit B12), and folic acid in patients with PCOS.	Metformin	55-64	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	101-104
28904497-3	2017	The aim of this study was to investigate the effect of metformin on the levels of serum Hcy, vitamin B12 (vit B12), and folic acid in patients with PCOS.	Metformin	55-64	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	110-113
28904497-7	2017	RESULTS: The mean vit B12 level showed a significant decrease in patients after 6 months of metformin treatment (P = 0.002).	Metformin	92-101	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	22-25
28260041-8	2017	Metformin also significantly inhibited the gene and protein expression levels of SMO, Gli-2 and Gli-3.	Metformin	0-9	GLI family zinc finger 2	Homo sapiens	86-91
28260041-8	2017	Metformin also significantly inhibited the gene and protein expression levels of SMO, Gli-2 and Gli-3.	Metformin	0-9	GLI family zinc finger 3	Homo sapiens	96-101
28193839-3	2017	In this study, we report that, under glucose deprivation, metformin inhibited expression of DeltaNp63alpha, a p53 family member involved in cell adhesion pathways, resulting in disruption of cell matrix adhesion and subsequent apoptosis in human squamous carcinoma cells.	Metformin	58-67	tumor protein p53	Homo sapiens	110-113
28193839-4	2017	We further show that metformin promoted DeltaNp63alpha protein instability independent of AMP-activated protein kinase and that WWP1, an E3 ligase of DeltaNp63alpha, was involved in metformin-mediated down-regulation of DeltaNp63alpha levels.	Metformin	182-191	WW domain containing E3 ubiquitin protein ligase 1	Homo sapiens	128-132
28356082-9	2017	Everolimus combined with metformin additively inhibited cell survival, clonogenicity, mTOR signaling activity and mitochondrial respiration.	Metformin	25-34	mechanistic target of rapamycin kinase	Homo sapiens	86-90
28356082-12	2017	CONCLUSION: Metformin-induced effects are additive to the anti-proliferative and colony inhibitory properties of everolimus through inhibition of mitochondrial respiration and mTOR signaling.	Metformin	12-21	mechanistic target of rapamycin kinase	Homo sapiens	176-180
28043910-0	2017	Metformin inhibits castration-induced EMT in prostate cancer by repressing COX2/PGE2/STAT3 axis.	Metformin	0-9	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	75-79
28157701-4	2017	Metformin treated cancer cells increased macrophage expression of M1-related cytokines IL-12 and TNF-alpha and attenuated M2-related cytokines IL-8, IL-10, and TGF-beta expression.	Metformin	0-9	tumor necrosis factor	Homo sapiens	97-106
28157701-5	2017	Furthermore, metformin treated cancer cells displayed inhibited secretion of IL-4, IL-10 and IL-13; cytokines important for inducing M2 macrophages.	Metformin	13-22	interleukin 4	Homo sapiens	77-81
28157701-5	2017	Furthermore, metformin treated cancer cells displayed inhibited secretion of IL-4, IL-10 and IL-13; cytokines important for inducing M2 macrophages.	Metformin	13-22	interleukin 13	Homo sapiens	93-98
28043910-0	2017	Metformin inhibits castration-induced EMT in prostate cancer by repressing COX2/PGE2/STAT3 axis.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	85-90
28043910-3	2017	In this study, we demonstrated that metformin is capable of inhibiting prostate cancer cell migration and invasion by repressing EMT evidenced by downregulating the mesenchymal markers N-cadherin, Vimentin, and Twist and upregulating the epithelium E-cadherin.	Metformin	36-45	cadherin 1	Homo sapiens	249-259
28043910-5	2017	In addition, we showed the effects of metformin on the expression of genes involved in EMT through repressing the levels of COX2, PGE2 and phosphorylated STAT3.	Metformin	38-47	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	124-128
28043910-5	2017	In addition, we showed the effects of metformin on the expression of genes involved in EMT through repressing the levels of COX2, PGE2 and phosphorylated STAT3.	Metformin	38-47	signal transducer and activator of transcription 3	Homo sapiens	154-159
28043910-6	2017	Furthermore, inactivating COX2 abolishes metformin"s regulatory effects and exogenously administered PGE2 is capable of enhancing STAT3 phosphorylation and expression of EMT biomarker.	Metformin	41-50	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	26-30
28043910-7	2017	We propose that metformin represses prostate cancer EMT and metastasis through targeting the COX2/PGE2/STAT3 axis.	Metformin	16-25	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	93-97
28043910-7	2017	We propose that metformin represses prostate cancer EMT and metastasis through targeting the COX2/PGE2/STAT3 axis.	Metformin	16-25	signal transducer and activator of transcription 3	Homo sapiens	103-108
28334027-6	2017	The results showed reduction of mesenchymal markers, including vimentin and beta-catenin, and induction of epithelial marker, E-cadherin, by metformin in both glucose concentrations.	Metformin	141-150	cadherin 1	Homo sapiens	126-136
28181916-0	2017	4-Phenylbutyric acid and metformin decrease sensitivity to pentylenetetrazol-induced seizures in a malin knockout model of Lafora disease.	Metformin	25-34	NHL repeat containing 1	Mus musculus	99-104
28181916-4	2017	Malin knockout mice treated with 4-phenylbutyric acid (4-PBA) and metformin showed decreased amounts of Lafora bodies and polyubiquitin protein aggregates in the brain, diminished neurodegeneration, and amelioration of some neurological conditions.	Metformin	66-75	NHL repeat containing 1	Mus musculus	0-5
28335557-0	2017	ROS Production and ERK Activity Are Involved in the Effects of d-beta-Hydroxybutyrate and Metformin in a Glucose Deficient Condition.	Metformin	90-99	mitogen-activated protein kinase 1	Homo sapiens	19-22
28335557-11	2017	We demonstrate that glucose deficiency-induced cytotoxicity is mediated by ERK inhibition through ROS production, which is attenuated by D-BHB and intensified by metformin.	Metformin	162-171	mitogen-activated protein kinase 1	Homo sapiens	75-78
28386373-13	2017	Interestingly, metformin increased the progestin sensitivity by down regulation of Nrf2 and survivin.	Metformin	15-24	NFE2 like bZIP transcription factor 2	Homo sapiens	83-87
28087733-5	2017	Metformin induced both the expression of PGC-1alpha and an augmentation of its activity, as demonstrated by the increased expression of target genes, strongly promoting mitochondrial biogenesis.	Metformin	0-9	PPARG coactivator 1 alpha	Homo sapiens	41-51
28087733-9	2017	We finally demonstrated that the expression of genes of the fission/fusion machinery, namely OPA1 and MFN2, was reduced in trisomic cells and increased by metformin treatment.	Metformin	155-164	OPA1 mitochondrial dynamin like GTPase	Homo sapiens	93-97
28060743-5	2017	Although evidence is limited, insulin use has been associated with increased and metformin with decreased incidence of colorectal cancer.	Metformin	81-90	insulin	Homo sapiens	30-37
28042024-3	2017	Metformin activates adenosine monophosphate-activated protein kinase (AMPK) to regulate insulin signaling and promote the translocation of glucose transporter type 4 (GLUT4), thereby stimulating glucose uptake to maintain energy balance.	Metformin	0-9	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	139-165
28042024-3	2017	Metformin activates adenosine monophosphate-activated protein kinase (AMPK) to regulate insulin signaling and promote the translocation of glucose transporter type 4 (GLUT4), thereby stimulating glucose uptake to maintain energy balance.	Metformin	0-9	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	167-172
28253329-12	2017	Metformin (5mM) abrogated the proliferation of benign prostatic epithelial cells induced by IGF-1.	Metformin	0-9	insulin like growth factor 1	Homo sapiens	92-97
28253329-16	2017	CONCLUSIONS: Our study demonstrates that metformin inhibits the proliferation of benign prostatic epithelial cells by suppressing the expression of IGF-1R and IGF-1 secretion in stromal cells.	Metformin	41-50	insulin like growth factor 1	Homo sapiens	148-153
28154203-6	2017	Two-thirds of existing mammary tumors responded to metformin treatment with decreased tumor volumes (P &lt; 0.05), reduced proliferative index (P &lt; 0.01), and activated AMPK (P &lt; 0.05).	Metformin	51-60	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	172-176
28161619-7	2017	In contrast, suppression of HIF-1, p-gp and MRP1 protein expression is its main mechanism when metformin combines with anti-metabolites.	Metformin	95-104	hypoxia inducible factor 1 subunit alpha	Homo sapiens	28-33
28161619-7	2017	In contrast, suppression of HIF-1, p-gp and MRP1 protein expression is its main mechanism when metformin combines with anti-metabolites.	Metformin	95-104	ATP binding cassette subfamily C member 1	Homo sapiens	44-48
27800648-0	2017	Treatment with a novel agent combining docosahexaenoate and metformin increases protectin DX and IL-6 production in skeletal muscle and reduces insulin resistance in obese diabetic db/db mice.	Metformin	60-69	interleukin 6	Mus musculus	97-101
27981444-7	2017	Metformin has also been reported to reverse resistance to epidermal growth factor receptor (EGFR)-inhibiting tyrosine kinase inhibitors.	Metformin	0-9	epidermal growth factor receptor	Homo sapiens	58-90
27981444-7	2017	Metformin has also been reported to reverse resistance to epidermal growth factor receptor (EGFR)-inhibiting tyrosine kinase inhibitors.	Metformin	0-9	epidermal growth factor receptor	Homo sapiens	92-96
28159472-11	2017	NF-kappaB is a transcription factor with a key role in the expression of a variety of genes involved in inflammatory responses, and metformin did prevent the AGE-mediated increase in NF-kappaB mRNA and protein levels in the hNSCs exposed to AGE.	Metformin	132-141	nuclear factor kappa B subunit 1	Homo sapiens	183-192
28159472-12	2017	Indeed, co-treatment with metformin significantly restored inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) levels in AGE-treated hNSCs.	Metformin	26-35	nitric oxide synthase 2	Homo sapiens	59-90
28159472-12	2017	Indeed, co-treatment with metformin significantly restored inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) levels in AGE-treated hNSCs.	Metformin	26-35	nitric oxide synthase 2	Homo sapiens	92-96
28159472-12	2017	Indeed, co-treatment with metformin significantly restored inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) levels in AGE-treated hNSCs.	Metformin	26-35	prostaglandin-endoperoxide synthase 2	Homo sapiens	102-118
28159472-12	2017	Indeed, co-treatment with metformin significantly restored inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) levels in AGE-treated hNSCs.	Metformin	26-35	prostaglandin-endoperoxide synthase 2	Homo sapiens	120-125
28338172-11	2017	The results showed that metformin significantly inhibited the expression levels of key proteins of PI3K/Akt/mTOR signaling pathway.	Metformin	24-33	AKT serine/threonine kinase 1	Homo sapiens	104-107
28338172-11	2017	The results showed that metformin significantly inhibited the expression levels of key proteins of PI3K/Akt/mTOR signaling pathway.	Metformin	24-33	mechanistic target of rapamycin kinase	Homo sapiens	108-112
28183442-9	2017	Furthermore, metformin activated AMPK in uninjured but not in injured vessels.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	33-37
27862873-0	2017	Sustained influence of metformin therapy on circulating glucagon-like peptide-1 levels in individuals with and without type 2 diabetes.	Metformin	23-32	glucagon	Homo sapiens	56-79
28183442-10	2017	Similarly, 10mmol/L metformin inhibited proliferation and activated AMPK in smooth muscle cells of uninjured but not injured vessels, whereas 2mmol/L metformin did not have any effect.	Metformin	20-29	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	68-72
28104298-9	2017	Metformin, an anti-diabetic agent, was found to increase Klf10 and suppress UVRAG expression to improve radiation cytotoxicity in pancreatic cancer.	Metformin	0-9	UV radiation resistance associated	Homo sapiens	76-81
27761984-6	2017	The increment in plasma GLP-1 after metformin vs placebo was related to the reduction in serum 3-OMG concentrations ( P = .019).	Metformin	36-45	glucagon	Homo sapiens	24-29
28017679-0	2017	Metformin protects the brain against ischemia/reperfusion injury through PI3K/Akt1/JNK3 signaling pathways in rats.	Metformin	0-9	AKT serine/threonine kinase 1	Rattus norvegicus	78-82
28017679-2	2017	Therefore, the aim of this study was to investigate the neuroprotective mechanisms of metformin against ischemic brain damage induced by cerebral I/R and to explore whether the Akt-mediated down-regulation of the phosphorylation of JNK3 signaling pathway contributed to the protection provided by metformin.	Metformin	86-95	AKT serine/threonine kinase 1	Rattus norvegicus	177-180
28017679-2	2017	Therefore, the aim of this study was to investigate the neuroprotective mechanisms of metformin against ischemic brain damage induced by cerebral I/R and to explore whether the Akt-mediated down-regulation of the phosphorylation of JNK3 signaling pathway contributed to the protection provided by metformin.	Metformin	297-306	AKT serine/threonine kinase 1	Rattus norvegicus	177-180
28017679-8	2017	The western blot data showed that metformin could promote the activation of Akt1 and reduce the phosphorylation of JNK3 and c-Jun as well as elevation of cleaved caspase-3 in I/R brains.	Metformin	34-43	AKT serine/threonine kinase 1	Rattus norvegicus	76-80
28017679-9	2017	PI3K inhibitor reversed all the protective effects, further indicating that metformin protect hippocampus from ischemic damage through PI3K/Akt1/JNK3/c-Jun signaling pathway.	Metformin	76-85	AKT serine/threonine kinase 1	Rattus norvegicus	140-144
28241849-0	2017	Metformin potentiates the effect of arsenic trioxide suppressing intrahepatic cholangiocarcinoma: roles of p38 MAPK, ERK3, and mTORC1.	Metformin	0-9	mitogen-activated protein kinase 14	Homo sapiens	107-110
28241849-5	2017	METHODS: ICC cell lines (CCLP-1, RBE, and HCCC-9810) were treated with metformin and/or ATO; the anti-proliferation effect was evaluated by cell viability, cell apoptosis, cell cycle, and intracellular-reactive oxygen species (ROS) assays.	Metformin	71-80	PPFIA binding protein 2	Homo sapiens	25-31
28241849-8	2017	In addition, an antibody array was used screening more than 200 molecules clustered in 12 cancer-related pathways in CCLP-1 cells treated with metformin and/or ATO.	Metformin	143-152	PPFIA binding protein 2	Homo sapiens	117-123
28241849-14	2017	Mechanistically, the antibody array revealed that ERK3 exhibited the highest variation in CCLP-1 cells after treatment with metformin and ATO.	Metformin	124-133	PPFIA binding protein 2	Homo sapiens	90-96
28241849-16	2017	Metformin abrogated the activation of p38 MAPK induced by ATO, and this activity was partially dependent on AMPK activation.	Metformin	0-9	mitogen-activated protein kinase 14	Homo sapiens	38-41
28241849-17	2017	Inactivation of p38 MAPK by SB203580 or specific short interfering RNA (siRNA) promoted the inactivation of mTORC1 in ICC cells treated with metformin and ATO.	Metformin	141-150	mitogen-activated protein kinase 14	Homo sapiens	16-19
28241849-23	2017	CONCLUSIONS: Metformin sensitizes arsenic trioxide to suppress intrahepatic cholangiocarcinoma via the regulation of AMPK/p38 MAPK-ERK3/mTORC1 pathways.	Metformin	13-22	mitogen-activated protein kinase 14	Homo sapiens	122-125
28233769-0	2017	Erratum: Metformin sensitizes the response of oral squamous cell carcinoma to cisplatin treatment through inhibition of NF-kappaB/HIF-1alpha signal axis.	Metformin	9-18	hypoxia inducible factor 1 subunit alpha	Homo sapiens	130-140
28230206-0	2017	MiRNA-21 mediates the antiangiogenic activity of metformin through targeting PTEN and SMAD7 expression and PI3K/AKT pathway.	Metformin	49-58	SMAD family member 7	Homo sapiens	86-91
28230206-0	2017	MiRNA-21 mediates the antiangiogenic activity of metformin through targeting PTEN and SMAD7 expression and PI3K/AKT pathway.	Metformin	49-58	AKT serine/threonine kinase 1	Homo sapiens	112-115
28230206-7	2017	Overexpression of miR-21 abrogated the metformin-mediated inhibition of endothelial cells proliferation, migration, tubule formation and the TGF-beta-induced AKT, SMAD- and ERK-dependent phosphorylations, and conversely, down-regulation of miR-21 aggravated metformin"s action and revealed significant promotion effects.	Metformin	39-48	transforming growth factor beta 1	Homo sapiens	141-149
28230206-7	2017	Overexpression of miR-21 abrogated the metformin-mediated inhibition of endothelial cells proliferation, migration, tubule formation and the TGF-beta-induced AKT, SMAD- and ERK-dependent phosphorylations, and conversely, down-regulation of miR-21 aggravated metformin"s action and revealed significant promotion effects.	Metformin	39-48	mitogen-activated protein kinase 1	Homo sapiens	173-176
28230206-7	2017	Overexpression of miR-21 abrogated the metformin-mediated inhibition of endothelial cells proliferation, migration, tubule formation and the TGF-beta-induced AKT, SMAD- and ERK-dependent phosphorylations, and conversely, down-regulation of miR-21 aggravated metformin"s action and revealed significant promotion effects.	Metformin	258-267	transforming growth factor beta 1	Homo sapiens	141-149
28178338-11	2017	In addition, exogenous adiponectin significantly inhibited starvation- and metformin-induced apoptosis, and up-regulated p-AMPK and Bcl-xL levels.	Metformin	75-84	adiponectin, C1Q and collagen domain containing	Homo sapiens	23-34
28122334-2	2017	The drop in energy charge resulting from the metformin mediated inhibition of mitochondrial activity affects the function of the nuclear pore complex, blocks mTOR signaling and enhances the expression of ACAD10.	Metformin	45-54	mechanistic target of rapamycin kinase	Homo sapiens	158-162
28345832-9	2017	Furthermore, metformin exposure resultedin decreased STAT3 activation and down-regulation of anti-apoptotic protein Bcl-2 and Mcl-1 expression.	Metformin	13-22	signal transducer and activator of transcription 3	Homo sapiens	53-58
28345832-9	2017	Furthermore, metformin exposure resultedin decreased STAT3 activation and down-regulation of anti-apoptotic protein Bcl-2 and Mcl-1 expression.	Metformin	13-22	BCL2 apoptosis regulator	Homo sapiens	116-121
28345832-11	2017	Conclusion:These results demonstrated inhibitory effects of metformin on CCA cell migration and invasion, possibly involvingthe STAT3 pathway and reversal of EMT markers expression.	Metformin	60-69	signal transducer and activator of transcription 3	Homo sapiens	128-133
27919710-6	2017	Anti-diabetic and anti-lipidemic drugs such as atorvastatin, metformin, bile acid sequestrants, docosahexaenoic acid and eicosapentaenoic acid may affect ChREBP transactivity.	Metformin	61-70	MLX interacting protein like	Homo sapiens	154-160
27761984-7	2017	Accordingly, metformin inhibits small intestinal glucose absorption, which may contribute to augmented GLP-1 secretion in type 2 diabetes.	Metformin	13-22	glucagon	Homo sapiens	103-108
27817155-12	2017	Insulin was required in six comparator women vs none in the study group (eight vs two required metformin).	Metformin	95-104	insulin	Homo sapiens	0-7
27856287-4	2017	Spinal local application of AMPK agonist metformin (25mug) prevented the long term potentiation (LTP) induction and the activation of mTOR/p70S6K signal pathway, and significantly attenuated the acute thermal hyperalgesia and mechanical allodynia following single oxaliplatin treatment.	Metformin	41-50	mechanistic target of rapamycin kinase	Homo sapiens	134-138
27856287-8	2017	Local application of metformin significantly decreased the mTOR and p70S6K activation induced by tetanus stimulation or oxaliplatin (i.p.).	Metformin	21-30	mechanistic target of rapamycin kinase	Homo sapiens	59-63
27407018-0	2017	Effects of SLC22A1 Polymorphisms on Metformin-Induced Reductions in Adiposity and Metformin Pharmacokinetics in Obese Children With Insulin Resistance.	Metformin	36-45	solute carrier family 22 member 1	Homo sapiens	11-18
27407018-0	2017	Effects of SLC22A1 Polymorphisms on Metformin-Induced Reductions in Adiposity and Metformin Pharmacokinetics in Obese Children With Insulin Resistance.	Metformin	36-45	insulin	Homo sapiens	132-139
27407018-0	2017	Effects of SLC22A1 Polymorphisms on Metformin-Induced Reductions in Adiposity and Metformin Pharmacokinetics in Obese Children With Insulin Resistance.	Metformin	82-91	solute carrier family 22 member 1	Homo sapiens	11-18
27407018-7	2017	However, SLC22A1 variant carriers had smaller reductions in percentage of total trunk fat after metformin therapy, although the percentage reduction in trunk fat was small.	Metformin	96-105	solute carrier family 22 member 1	Homo sapiens	9-16
27407018-9	2017	Future study is needed to evaluate the effects of SLC22A1 polymorphisms on metformin-mediated weight reduction in obese children.	Metformin	75-84	solute carrier family 22 member 1	Homo sapiens	50-57
27131512-0	2017	Effect of metformin by employing 2-hour postload insulin for measuring insulin resistance in Taiwanese women with polycystic ovary syndrome.	Metformin	10-19	insulin	Homo sapiens	71-78
27761984-1	2017	In rodents, metformin slows intestinal glucose absorption, potentially increasing exposure of the distal gut to glucose to enhance postprandial glucagon-like peptide-1 (GLP-1) secretion.	Metformin	12-21	glucagon	Homo sapiens	144-167
27761984-1	2017	In rodents, metformin slows intestinal glucose absorption, potentially increasing exposure of the distal gut to glucose to enhance postprandial glucagon-like peptide-1 (GLP-1) secretion.	Metformin	12-21	glucagon	Homo sapiens	169-174
27761984-5	2017	Compared with placebo, metformin was associated with lower serum 3-OMG ( P &lt; .001) and higher plasma total GLP-1 ( P = .003) concentrations.	Metformin	23-32	glucagon	Homo sapiens	110-115
27128966-4	2017	Metformin promoted cytotoxic effects only in the cancer cells irrespective of the p53 status and not in the normal primary-cultured cells.	Metformin	0-9	tumor protein p53	Homo sapiens	82-85
27128966-8	2017	The activation of GSK3beta correlated with the inhibitory phosphorylation by Akt as well as p70S6K through AMPK activation in response to metformin.	Metformin	138-147	AKT serine/threonine kinase 1	Homo sapiens	77-80
27642000-9	2017	Patients prescribed insulin second-line after metformin had a mean HbA1c of 10.11% (95%CI 9.83, 10.38) prior to first prescription of insulin and 9.98% (95%CI 9.73, 10.23) at baseline.	Metformin	46-55	insulin	Homo sapiens	20-27
27733575-7	2017	Furthermore, we show that a culture of AECs with either fenoldopam or the AMPK activator metformin effectively diminished IL-1beta-induced release of adverse paracrine signaling, which promotes the macrophage proinflammatory response.	Metformin	89-98	interleukin 1 beta	Mus musculus	122-130
28145471-5	2017	Results showed that in PA-treated HUVECs and HFD-fed ApoE-/- mice, combination of metformin and liraglutide at lower dose significantly improved endothelial dysfunction compared with the single treatment.	Metformin	82-91	apolipoprotein E	Mus musculus	53-57
27699813-9	2017	Inversely, inhibition of MEK or treatment with metformin activated FOXO3a through inactivation of ERK signaling and suppressed the viability of LNCaP and 22Rv1 cells in a dose-dependent manner.	Metformin	47-56	forkhead box O3	Homo sapiens	67-73
27699813-9	2017	Inversely, inhibition of MEK or treatment with metformin activated FOXO3a through inactivation of ERK signaling and suppressed the viability of LNCaP and 22Rv1 cells in a dose-dependent manner.	Metformin	47-56	mitogen-activated protein kinase 1	Homo sapiens	98-101
28052008-0	2017	Targeting P-glycoprotein function, p53 and energy metabolism: Combination of metformin and 2-deoxyglucose reverses the multidrug resistance of MCF-7/Dox cells to doxorubicin.	Metformin	77-86	ATP binding cassette subfamily B member 1	Homo sapiens	10-24
28052008-0	2017	Targeting P-glycoprotein function, p53 and energy metabolism: Combination of metformin and 2-deoxyglucose reverses the multidrug resistance of MCF-7/Dox cells to doxorubicin.	Metformin	77-86	tumor protein p53	Homo sapiens	35-38
28052008-7	2017	Combination of metformin and 2-deoxyglucose initiated a strong metabolic stress in MCF-7/Dox cells via inhibiting glucose uptake, lactate, fatty acid, ATP production and protein kinase B(AKT)/ mammalian target of rapamycin(mTOR) pathway.	Metformin	15-24	AKT serine/threonine kinase 1	Homo sapiens	170-191
28052008-7	2017	Combination of metformin and 2-deoxyglucose initiated a strong metabolic stress in MCF-7/Dox cells via inhibiting glucose uptake, lactate, fatty acid, ATP production and protein kinase B(AKT)/ mammalian target of rapamycin(mTOR) pathway.	Metformin	15-24	mechanistic target of rapamycin kinase	Homo sapiens	193-228
28052008-8	2017	Taken together, combination of metformin and 2-deoxyglucose reverses MDR of MCF-7/Dox cells by recovering p53 function and increasing doxorubicin accumulation.	Metformin	31-40	tumor protein p53	Homo sapiens	106-109
28126011-2	2017	Here, we discuss the potential of metformin in cancer therapeutics, particularly its functions in multiple signaling pathways, including AMP-activated protein kinase, mammalian target of rapamycin, insulin-like growth factor, c-Jun N-terminal kinase/mitogen-activated protein kinase (p38 MAPK), human epidermal growth factor receptor-2, and nuclear factor kappaB pathways.	Metformin	34-43	erb-b2 receptor tyrosine kinase 2	Homo sapiens	301-335
28114390-0	2017	High Glucose-Mediated STAT3 Activation in Endometrial Cancer Is Inhibited by Metformin: Therapeutic Implications for Endometrial Cancer.	Metformin	77-86	signal transducer and activator of transcription 3	Homo sapiens	22-27
28114390-2	2017	We therefore investigated whether glucose concentrations influence STAT3 expression in type 1 endometrial cancer, and whether such STAT3 expression might be inhibited by metformin.	Metformin	170-179	signal transducer and activator of transcription 3	Homo sapiens	131-136
28114390-9	2017	Metformin reduced expression levels of pSTAT3 ser727, total STAT3, and its associated cell survival and anti-apoptotic proteins.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	40-45
28114390-12	2017	In vivo, metformin treatment led to a decrease in tumor weight as well as reductions of STAT3, pSTAT3 ser727, its target proteins.	Metformin	9-18	signal transducer and activator of transcription 3	Homo sapiens	88-93
28114390-13	2017	CONCLUSIONS: These results suggest that STAT3 expression in type 1 endometrial cancer is stimulated by a high glucose environment and inhibited by metformin.	Metformin	147-156	signal transducer and activator of transcription 3	Homo sapiens	40-45
28065882-0	2017	Rescue of mutant rhodopsin traffic by metformin-induced AMPK activation accelerates photoreceptor degeneration.	Metformin	38-47	rhodopsin	Homo sapiens	17-26
28030813-0	2017	Stattic and metformin inhibit brain tumor initiating cells by reducing STAT3-phosphorylation.	Metformin	12-21	signal transducer and activator of transcription 3	Homo sapiens	71-76
28030813-4	2017	Evidence from other tumor models suggests that metformin inhibits STAT3, but there is no specific data on brain tumor initiating cells (BTICs).We explored proliferation and migration of 7 BTICs and their differentiated counterparts (TCs) after treatment with Stattic, metformin or the combination thereof.	Metformin	47-56	signal transducer and activator of transcription 3	Homo sapiens	66-71
28030813-9	2017	Treatment with metformin reduced STAT3-phosphorylation in all investigated BTICs and TCs.	Metformin	15-24	signal transducer and activator of transcription 3	Homo sapiens	33-38
28030813-12	2017	Stable STAT3 knock-in partly attenuated the effects of Stattic and metformin on BTICs.In conclusion, metformin was found to inhibit STAT3-phosphorylation in BTICs and TCs.	Metformin	67-76	signal transducer and activator of transcription 3	Homo sapiens	7-12
28030813-12	2017	Stable STAT3 knock-in partly attenuated the effects of Stattic and metformin on BTICs.In conclusion, metformin was found to inhibit STAT3-phosphorylation in BTICs and TCs.	Metformin	67-76	signal transducer and activator of transcription 3	Homo sapiens	132-137
28030813-12	2017	Stable STAT3 knock-in partly attenuated the effects of Stattic and metformin on BTICs.In conclusion, metformin was found to inhibit STAT3-phosphorylation in BTICs and TCs.	Metformin	101-110	signal transducer and activator of transcription 3	Homo sapiens	7-12
28030813-12	2017	Stable STAT3 knock-in partly attenuated the effects of Stattic and metformin on BTICs.In conclusion, metformin was found to inhibit STAT3-phosphorylation in BTICs and TCs.	Metformin	101-110	signal transducer and activator of transcription 3	Homo sapiens	132-137
27845161-5	2017	Treatment of PCOS patients with metformin (2 g/day for 3 months) significantly increased the endometrial mRNA levels of FOXO1, ATG3, and UV radiation resistance-associated gene.	Metformin	32-41	forkhead box O1	Homo sapiens	120-125
27856330-3	2017	The commonly used anti-diabetic drug, metformin, activates the osteogenic transcription factor Runt-related transcription factor 2 (Runx2), which may suppress adipogenesis, leading to improved bone health.	Metformin	38-47	RUNX family transcription factor 2	Homo sapiens	132-137
27856330-5	2017	The anti-adipogenic actions of metformin were observed in multipotent C3H10T1/2 MSCs, in which metformin exerted reciprocal control over the activities of Runx2 and the adipogenic transcription factor, PPARgamma, leading to suppression of adipogenesis.	Metformin	31-40	RUNX family transcription factor 2	Homo sapiens	155-160
27856330-5	2017	The anti-adipogenic actions of metformin were observed in multipotent C3H10T1/2 MSCs, in which metformin exerted reciprocal control over the activities of Runx2 and the adipogenic transcription factor, PPARgamma, leading to suppression of adipogenesis.	Metformin	31-40	peroxisome proliferator activated receptor gamma	Homo sapiens	202-211
27856330-5	2017	The anti-adipogenic actions of metformin were observed in multipotent C3H10T1/2 MSCs, in which metformin exerted reciprocal control over the activities of Runx2 and the adipogenic transcription factor, PPARgamma, leading to suppression of adipogenesis.	Metformin	95-104	RUNX family transcription factor 2	Homo sapiens	155-160
27856330-5	2017	The anti-adipogenic actions of metformin were observed in multipotent C3H10T1/2 MSCs, in which metformin exerted reciprocal control over the activities of Runx2 and the adipogenic transcription factor, PPARgamma, leading to suppression of adipogenesis.	Metformin	95-104	peroxisome proliferator activated receptor gamma	Homo sapiens	202-211
28098811-8	2017	Daily treatment of mice with ASP at a dose of 130 mg/kg for six weeks was more effective at reversing complications than both a low dose ASP or metformin, eliciting enhanced expression of Nrf2 and its downstream antioxidant genes.	Metformin	144-153	nuclear factor, erythroid derived 2, like 2	Mus musculus	188-192
28065882-2	2017	Here, we tested whether the AMPK activator metformin could affect the P23H rhodopsin synthesis and folding.	Metformin	43-52	rhodopsin	Homo sapiens	75-84
28065882-3	2017	In cell models, metformin treatment improved P23H rhodopsin folding and traffic.	Metformin	16-25	rhodopsin	Homo sapiens	50-59
28065882-5	2017	The metformin-rescued P23H rhodopsin was still intrinsically unstable and led to increased structural instability of the rod outer segments.	Metformin	4-13	rhodopsin	Homo sapiens	27-36
29222856-6	2017	RESULTS: The serum homocysteine levels in patients treated with insulin in monotherapy were significantly higher than what was observed in the metformin treated subjects and in the patients receiving insulin combined with metformin.	Metformin	143-152	insulin	Homo sapiens	64-71
29222856-6	2017	RESULTS: The serum homocysteine levels in patients treated with insulin in monotherapy were significantly higher than what was observed in the metformin treated subjects and in the patients receiving insulin combined with metformin.	Metformin	222-231	insulin	Homo sapiens	64-71
26680745-3	2017	Of importance is that the United Kingdom Prospective Diabetes Study 20-year study of type 2 diabetics, completed in 1998, compared patients treated with insulin, sulfonylureas and metformin and concluded that metformin provided vascular protective actions.	Metformin	209-218	insulin	Homo sapiens	153-160
26680745-5	2017	The vascular protective actions of metformin are thought to be secondary to the antihyperglycaemic effects of metformin that are mediated via activation of AMP kinase and subsequent inhibition of hepatic gluconeogenesis, fatty acid oxidation as well as an insulin sensitizing action in striated muscle and adipose tissue.	Metformin	35-44	insulin	Homo sapiens	256-263
26680745-5	2017	The vascular protective actions of metformin are thought to be secondary to the antihyperglycaemic effects of metformin that are mediated via activation of AMP kinase and subsequent inhibition of hepatic gluconeogenesis, fatty acid oxidation as well as an insulin sensitizing action in striated muscle and adipose tissue.	Metformin	110-119	insulin	Homo sapiens	256-263
28249909-6	2017	Data mining of the National Library of Medicine"s MEDLINE Database and Ingenuity Pathway analysis revealed agents of relatively low toxicity-melatonin, metformin, curcumin and sulforaphane-that are capable of inhibiting directly or pharmacogenomically one or both of the SIRT1 and EZH2 pathways and should, in a combinatorial fashion, remove the block in differentiation and decrease the proliferation of the B-cell ALL lymphoblasts.	Metformin	152-161	enhancer of zeste 2 polycomb repressive complex 2 subunit	Homo sapiens	281-285
28011481-0	2017	Metformin Exerts Antiproliferative and Anti-metastatic Effects Against Cholangiocarcinoma Cells by Targeting STAT3 and NF-kB.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	109-114
28042775-6	2017	RESULTS: There was a lower protein expression of ROCK-1, vimentin, CD44 and CD24 in both cell lines after treatment with metformin and Y27632.	Metformin	121-130	CD24 molecule	Homo sapiens	76-80
29073599-0	2017	Combination of Solamargine and Metformin Strengthens IGFBP1 Gene Expression Through Inactivation of Stat3 and Reciprocal Interaction Between FOXO3a and SP1.	Metformin	31-40	signal transducer and activator of transcription 3	Homo sapiens	100-105
29073599-0	2017	Combination of Solamargine and Metformin Strengthens IGFBP1 Gene Expression Through Inactivation of Stat3 and Reciprocal Interaction Between FOXO3a and SP1.	Metformin	31-40	forkhead box O3	Homo sapiens	141-147
27803295-6	2017	Metformin had a dose-dependent inhibitory effect on cell proliferation and apoptosis in vitro through the deregulation of mTOR/AMPK, AKT and extracellular signal regulated kinase (ERK) signalling pathways.	Metformin	0-9	thymoma viral proto-oncogene 1	Mus musculus	133-136
27803295-6	2017	Metformin had a dose-dependent inhibitory effect on cell proliferation and apoptosis in vitro through the deregulation of mTOR/AMPK, AKT and extracellular signal regulated kinase (ERK) signalling pathways.	Metformin	0-9	mitogen-activated protein kinase 1	Mus musculus	141-178
27803295-6	2017	Metformin had a dose-dependent inhibitory effect on cell proliferation and apoptosis in vitro through the deregulation of mTOR/AMPK, AKT and extracellular signal regulated kinase (ERK) signalling pathways.	Metformin	0-9	mitogen-activated protein kinase 1	Mus musculus	180-183
27803295-9	2017	Metformin significantly decreased subcutaneous tumour growth via cell-cycle block and mammalian target of rapamycin (mTOR) pathway inhibition, and also induced hypoxia and decreased angiogenesis.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	86-115
27803295-9	2017	Metformin significantly decreased subcutaneous tumour growth via cell-cycle block and mammalian target of rapamycin (mTOR) pathway inhibition, and also induced hypoxia and decreased angiogenesis.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	117-121
28116648-8	2017	Metformin is noted for its beneficial effects on lifespan extension and on disorders due to increased insulin resistance.	Metformin	0-9	insulin	Homo sapiens	102-109
27919208-7	2017	Metformin inhibits cancer growth in colon by suppressing the colonic epithelial proliferation by inhibiting the mTOR pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	112-116
27919208-10	2017	Metformin reduces tumour cell growth and metastasis by activating the p53 tumour suppressor gene.	Metformin	0-9	tumor protein p53	Homo sapiens	70-73
27737949-0	2017	Metformin Suppresses Diabetes-Accelerated Atherosclerosis via the Inhibition of Drp1-Mediated Mitochondrial Fission.	Metformin	0-9	dynamin 1-like	Mus musculus	80-84
27737949-4	2017	Metformin treatments markedly reduced mitochondrial fragmentation, mitigated mitochondrial-derived superoxide release, improved endothelial-dependent vasodilation, inhibited vascular inflammation, and suppressed atherosclerotic lesions in streptozotocin (STZ)-induced diabetic ApoE-/- mice.	Metformin	0-9	apolipoprotein E	Mus musculus	277-281
27737949-5	2017	In high glucose-exposed endothelial cells, metformin treatment and adenoviral overexpression of constitutively active AMPK downregulated mitochondrial superoxide, lowered levels of dynamin-related protein (Drp1) and its translocation into mitochondria, and prevented mitochondrial fragmentation.	Metformin	43-52	dynamin 1-like	Mus musculus	206-210
27737949-6	2017	In contrast, AMPK-alpha2 deficiency abolished the effects of metformin on Drp1 expression, oxidative stress, and atherosclerosis in diabetic ApoE-/-/AMPK-alpha2-/- mice, indicating that metformin exerts an antiatherosclerotic action in vivo via the AMPK-mediated blockage of Drp1-mediated mitochondrial fission.	Metformin	61-70	dynamin 1-like	Mus musculus	74-78
27737949-6	2017	In contrast, AMPK-alpha2 deficiency abolished the effects of metformin on Drp1 expression, oxidative stress, and atherosclerosis in diabetic ApoE-/-/AMPK-alpha2-/- mice, indicating that metformin exerts an antiatherosclerotic action in vivo via the AMPK-mediated blockage of Drp1-mediated mitochondrial fission.	Metformin	61-70	apolipoprotein E	Mus musculus	141-145
27737949-6	2017	In contrast, AMPK-alpha2 deficiency abolished the effects of metformin on Drp1 expression, oxidative stress, and atherosclerosis in diabetic ApoE-/-/AMPK-alpha2-/- mice, indicating that metformin exerts an antiatherosclerotic action in vivo via the AMPK-mediated blockage of Drp1-mediated mitochondrial fission.	Metformin	61-70	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	13-24
27737949-6	2017	In contrast, AMPK-alpha2 deficiency abolished the effects of metformin on Drp1 expression, oxidative stress, and atherosclerosis in diabetic ApoE-/-/AMPK-alpha2-/- mice, indicating that metformin exerts an antiatherosclerotic action in vivo via the AMPK-mediated blockage of Drp1-mediated mitochondrial fission.	Metformin	61-70	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	13-17
27737949-6	2017	In contrast, AMPK-alpha2 deficiency abolished the effects of metformin on Drp1 expression, oxidative stress, and atherosclerosis in diabetic ApoE-/-/AMPK-alpha2-/- mice, indicating that metformin exerts an antiatherosclerotic action in vivo via the AMPK-mediated blockage of Drp1-mediated mitochondrial fission.	Metformin	61-70	dynamin 1-like	Mus musculus	275-279
27737949-6	2017	In contrast, AMPK-alpha2 deficiency abolished the effects of metformin on Drp1 expression, oxidative stress, and atherosclerosis in diabetic ApoE-/-/AMPK-alpha2-/- mice, indicating that metformin exerts an antiatherosclerotic action in vivo via the AMPK-mediated blockage of Drp1-mediated mitochondrial fission.	Metformin	186-195	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	13-24
27737949-6	2017	In contrast, AMPK-alpha2 deficiency abolished the effects of metformin on Drp1 expression, oxidative stress, and atherosclerosis in diabetic ApoE-/-/AMPK-alpha2-/- mice, indicating that metformin exerts an antiatherosclerotic action in vivo via the AMPK-mediated blockage of Drp1-mediated mitochondrial fission.	Metformin	186-195	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	13-17
27737949-8	2017	These findings show that metformin attenuated the development of atherosclerosis by reducing Drp1-mediated mitochondrial fission in an AMPK-dependent manner.	Metformin	25-34	dynamin 1-like	Mus musculus	93-97
27737949-8	2017	These findings show that metformin attenuated the development of atherosclerosis by reducing Drp1-mediated mitochondrial fission in an AMPK-dependent manner.	Metformin	25-34	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	135-139
28056431-0	2017	Second line initiation of insulin compared with DPP-4 inhibitors after metformin monotherapy is associated with increased risk of all-cause mortality, cardiovascular events, and severe hypoglycemia.	Metformin	71-80	insulin	Homo sapiens	26-33
28056431-1	2017	AIMS: The objective of this nationwide study was to compare the risk of all-cause mortality, fatal and nonfatal cardiovascular disease (CVD), and severe hypoglycemia in patients with type 2 diabetes (T2D) on metformin monotherapy treatment starting second-line treatment with either insulin or dipeptidyl peptidase-4 inhibitor (DPP-4i).	Metformin	208-217	insulin	Homo sapiens	283-290
27711958-10	2017	Metformin treatment not only normalized sexual desire and sexual satisfaction in both studied groups, but also normalized or improved the remaining domains of FSFI in patients with diabetes, and these effects correlated with an improvement in insulin resistance.	Metformin	0-9	insulin	Homo sapiens	243-250
27711958-11	2017	Conclusions: Metformin treatment provides a beneficial effect on female sexual function and the strength of this effect depends on the degree of insulin resistance.	Metformin	13-22	insulin	Homo sapiens	145-152
27814614-3	2017	Here, we show that metformin induces growth inhibition and apoptosis through activating AMPK-mTOR pathway in human colorectal cancer cells.	Metformin	19-28	mechanistic target of rapamycin kinase	Homo sapiens	93-97
27814614-5	2017	Moreover, ADORA1-mediated growth inhibition and apoptosis induced by metformin is AMPK-mTOR pathway dependent in human colorectal cancer cells.	Metformin	69-78	mechanistic target of rapamycin kinase	Homo sapiens	87-91
28744307-5	2017	In Cox multivariate regression analysis, E-cadherin was identified as a prognostic factor for disease-free survival (DFS) (P = 0.038) and metformin use (P = 0.015P = 0.044) and lymph invasion (P = 0.016P = 0.023) were considered as the prognostic factors for both DFS and overall survival (OS).	Metformin	138-147	cadherin 1	Homo sapiens	41-51
27705028-8	2017	Taking the effect of drugs into consideration, the effect on adiponectin and resistin levels was found to be highly significant in Group 2 before and after treatment (11 +- 5 versus 19.2 +- 4.5 mug/ml) (13.6 +- 2.5 versus 7.3 +- 2.9 pg/ml), while more effect was observed in leptin among Group 1 (metformin)-treated cases (27 +- 15 ng/ml versus 15 +- 15 ng/ml).	Metformin	297-306	adiponectin, C1Q and collagen domain containing	Homo sapiens	61-72
27808588-2	2017	Insulin-sensitizer agents such as metformin and inositols have been shown to improve the endocrine and metabolic aspects of PCOS.	Metformin	34-43	insulin	Homo sapiens	0-7
27808588-12	2017	The two insulin-sensitizers, metformin and myo-inositol, show to be useful in PCOS women in lowering BMI and ameliorating insulin sensitivity, and improving menstrual cycle without significant differences between the two treatments.	Metformin	29-38	insulin	Homo sapiens	8-15
27808588-12	2017	The two insulin-sensitizers, metformin and myo-inositol, show to be useful in PCOS women in lowering BMI and ameliorating insulin sensitivity, and improving menstrual cycle without significant differences between the two treatments.	Metformin	29-38	insulin	Homo sapiens	122-129
27898267-3	2017	Insulin-sensitizing drugs, such as Metformin, are effective in treating hyper-insulinemic PCOS patients.	Metformin	35-44	insulin	Homo sapiens	0-7
27959383-0	2017	Combination of metformin and sorafenib suppresses proliferation and induces autophagy of hepatocellular carcinoma via targeting the mTOR pathway.	Metformin	15-24	mechanistic target of rapamycin kinase	Homo sapiens	132-136
29156452-8	2017	Insulin sensitizers like metformin and oral contraceptive pills provide short-term benefits on PCOS symptoms.	Metformin	25-34	insulin	Homo sapiens	0-7
27778642-0	2017	Effects of Conjugated Linoleic Acid and Metformin on Insulin Sensitivity in Obese Children: Randomized Clinical Trial.	Metformin	40-49	insulin	Homo sapiens	53-60
27778642-3	2017	Objective: This study aimed to evaluate the effects of metformin and conjugated linoleic acid (CLA) on insulin sensitivity, measured via euglycemic-hyperinsulinemic clamp technique and insulin pathway expression molecules in muscle biopsies of children with obesity.	Metformin	55-64	insulin	Homo sapiens	103-110
27638143-4	2017	RESULTS: Serum levels of vitamin B12 were significantly lower in patients treated with metformin and/or proton pump inhibitors (PPIs) compared with patients not treated (p&lt;0.001).	Metformin	87-96	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	33-36
27662780-8	2017	Incubation with metformin restored insulin and Pdx1 mRNA expression with significant improvements in GSIS and decrease in ROS production.	Metformin	16-25	pancreatic and duodenal homeobox 1	Rattus norvegicus	47-51
28409163-8	2017	AICAR or metformin was used as a PGC1alpha activator.	Metformin	9-18	PPARG coactivator 1 alpha	Homo sapiens	33-42
28409163-10	2017	Treatment with the PGC1alpha activators AICAR and metformin improved functional mitochondrial mass in HKC8 cells in high-glucose conditions.	Metformin	50-59	PPARG coactivator 1 alpha	Homo sapiens	19-28
28409163-13	2017	AICAR and metformin treatment effectively mitigated albuminuria and renal histopathology and decreased the expression of TGFbeta1 and alphaSMA in the kidneys of diabetic mice.	Metformin	10-19	actin alpha 2, smooth muscle, aorta	Mus musculus	134-142
27920093-7	2017	MicroPET/CT imaging was performed to detect 18F-FDG uptake in vivo After treatment with metformin at 0, 2.5, 5 and 10 mM for 48 h, the ratio of p-AMPK to total AMPK showed significant rising in a dose-dependent manner in both BCPAP and KTC1, whereas p-AKT and p-mTOR expression level were downregulated.	Metformin	88-97	mechanistic target of rapamycin kinase	Homo sapiens	262-266
27802445-0	2017	Comment on "Metformin Decreases Thyroid Volume and Nodule Size in Subjects with Insulin Resistance: A Preliminary Study".	Metformin	12-21	insulin	Homo sapiens	80-87
29308837-7	2017	Metformin remains the cure for the treatment of insulin resistance.	Metformin	0-9	insulin	Homo sapiens	48-55
29147073-0	2017	Metformin Suppressed CXCL8 Expression and Cell Migration in HEK293/TLR4 Cell Line.	Metformin	0-9	C-X-C motif chemokine ligand 8	Homo sapiens	21-26
29147073-5	2017	This study intended to address the role of metformin in regulation of CXCL8 expression and cell proliferation and migration.	Metformin	43-52	C-X-C motif chemokine ligand 8	Homo sapiens	70-75
29147073-6	2017	Our data indicated that metformin suppressed LPS-induced CXCL8 expression in a dose-dependent manner through inhibiting NF-kappaB, but not AP-1 and C/EBP, activities under the conditions we used.	Metformin	24-33	C-X-C motif chemokine ligand 8	Homo sapiens	57-62
29147073-6	2017	Our data indicated that metformin suppressed LPS-induced CXCL8 expression in a dose-dependent manner through inhibiting NF-kappaB, but not AP-1 and C/EBP, activities under the conditions we used.	Metformin	24-33	nuclear factor kappa B subunit 1	Homo sapiens	120-129
29147073-7	2017	This inhibitory effect of metformin is achieved through dampening LPS-induced NF-kappaB nuclear translocation.	Metformin	26-35	nuclear factor kappa B subunit 1	Homo sapiens	78-87
28161303-9	2017	CONCLUSION: Combined exenatide/metformin reduced intra-abdominal fat content, and enhanced insulin resistance and inflammatory status in patients with obesity and type-2 diabetes, representing a novel treatment regimen.	Metformin	31-40	insulin	Homo sapiens	91-98
28606576-9	2017	The insulin sensitizers, metformin and pioglitazone, improved insulin resistance and the concentration of circulating GLP-1, increased the relative number of intestinal L cells to a certain degree.	Metformin	25-34	insulin	Homo sapiens	4-11
28606576-9	2017	The insulin sensitizers, metformin and pioglitazone, improved insulin resistance and the concentration of circulating GLP-1, increased the relative number of intestinal L cells to a certain degree.	Metformin	25-34	insulin	Homo sapiens	62-69
28770024-4	2017	The aim of this study was to assess in vitro the effects of metformin, phenformin, and metformin sulfenamide prodrugs on the activity of human AChE and butyrylcholinesterase (BuChE) and establish the type of inhibition.	Metformin	60-69	acetylcholinesterase (Cartwright blood group)	Homo sapiens	143-147
28770024-5	2017	Metformin inhibited 50% of the AChE activity at micromolar concentrations (2.35 mumol/mL, mixed type of inhibition) and seemed to be selective towards AChE since it presented low anti-BuChE activity.	Metformin	0-9	acetylcholinesterase (Cartwright blood group)	Homo sapiens	31-35
28770024-5	2017	Metformin inhibited 50% of the AChE activity at micromolar concentrations (2.35 mumol/mL, mixed type of inhibition) and seemed to be selective towards AChE since it presented low anti-BuChE activity.	Metformin	0-9	acetylcholinesterase (Cartwright blood group)	Homo sapiens	151-155
28025449-2	2017	Recent studies have shown that metformin can enhance bone formation through induction of endothelial nitric oxide synthase (eNOS).	Metformin	31-40	nitric oxide synthase 3	Homo sapiens	89-122
28025449-8	2017	Treatment for seven days with metformin increased the expression levels of osteogenic protein mRNAs, including alkaline phosphatase, runt-related transcription factor 2, and osteopontin.	Metformin	30-39	RUNX family transcription factor 2	Homo sapiens	133-168
28025449-11	2017	By contrast, when CV-MSCs were cultured for 14 days in the adipogenic medium, 0.05 mM metformin inhibited the expression of adipogenic protein mRNAs, including proliferators-activated receptor-gamma and CCAAT/enhancer binding protein-alpha.	Metformin	86-95	CCAAT enhancer binding protein alpha	Homo sapiens	160-239
27684440-1	2017	PURPOSE: The study aimed to evaluate the effects of metformin on insulin, C-peptide and body weight in Chinese men undergoing androgen deprivation therapy (ADT).	Metformin	52-61	insulin	Homo sapiens	65-72
28334539-2	2017	Current national and international guidelines list insulin treatment as a possible second choice therapy in patient with unsatisfactory glucose control on monotherapy with metformin.	Metformin	172-181	insulin	Homo sapiens	51-58
28002460-0	2016	Metformin Improves Ileal Epithelial Barrier Function in Interleukin-10 Deficient Mice.	Metformin	0-9	interleukin 10	Mus musculus	56-70
28002460-9	2016	In addition, metformin supplementation in IL10KO mice suppressed macrophage pro-inflammatory activity as indicated by reduced M1 macrophage abundance and decreased pro-inflammatory cytokine IL-1beta, TNF-alpha and IFN-gamma expressions.	Metformin	13-22	interleukin 1 beta	Mus musculus	190-198
28002460-9	2016	In addition, metformin supplementation in IL10KO mice suppressed macrophage pro-inflammatory activity as indicated by reduced M1 macrophage abundance and decreased pro-inflammatory cytokine IL-1beta, TNF-alpha and IFN-gamma expressions.	Metformin	13-22	tumor necrosis factor	Mus musculus	200-209
28002460-9	2016	In addition, metformin supplementation in IL10KO mice suppressed macrophage pro-inflammatory activity as indicated by reduced M1 macrophage abundance and decreased pro-inflammatory cytokine IL-1beta, TNF-alpha and IFN-gamma expressions.	Metformin	13-22	interferon gamma	Mus musculus	214-223
28002460-11	2016	In correlation, the mRNA level of differentiation regulator including bmp4, bmpr2 and math1 were also increased in IL10KO mice supplemented with metformin, which likely explains the enhanced epithelial differentiation in IL10KO mice with metformin.	Metformin	145-154	bone morphogenetic protein 4	Mus musculus	70-74
28002460-11	2016	In correlation, the mRNA level of differentiation regulator including bmp4, bmpr2 and math1 were also increased in IL10KO mice supplemented with metformin, which likely explains the enhanced epithelial differentiation in IL10KO mice with metformin.	Metformin	145-154	interleukin 10	Mus musculus	115-119
28002460-11	2016	In correlation, the mRNA level of differentiation regulator including bmp4, bmpr2 and math1 were also increased in IL10KO mice supplemented with metformin, which likely explains the enhanced epithelial differentiation in IL10KO mice with metformin.	Metformin	238-247	bone morphogenetic protein 4	Mus musculus	70-74
28002460-11	2016	In correlation, the mRNA level of differentiation regulator including bmp4, bmpr2 and math1 were also increased in IL10KO mice supplemented with metformin, which likely explains the enhanced epithelial differentiation in IL10KO mice with metformin.	Metformin	238-247	interleukin 10	Mus musculus	115-119
28002460-12	2016	Consistently, in Caco-2 cells, metformin promoted claudin-3 and E-cadherin assembly and mitigated TNF-alpha-induced fragmentation of tight junction proteins.	Metformin	31-40	cadherin 1	Homo sapiens	64-74
28002460-12	2016	Consistently, in Caco-2 cells, metformin promoted claudin-3 and E-cadherin assembly and mitigated TNF-alpha-induced fragmentation of tight junction proteins.	Metformin	31-40	tumor necrosis factor	Homo sapiens	98-107
28018360-7	2016	Importantly, metformin administration increased the mortality of mice with bacterial sepsis, which was likely because metformin treatment enhanced the systemic inflammasome activation as indicated by elevated serum and hepatic IL-1beta levels.	Metformin	13-22	interleukin 1 beta	Mus musculus	227-235
28018360-7	2016	Importantly, metformin administration increased the mortality of mice with bacterial sepsis, which was likely because metformin treatment enhanced the systemic inflammasome activation as indicated by elevated serum and hepatic IL-1beta levels.	Metformin	118-127	interleukin 1 beta	Mus musculus	227-235
27827311-16	2016	CONCLUSIONS: Among patients who intensified metformin monotherapy, the addition of insulin compared with a sulfonylurea was not associated with a higher rate of kidney outcomes but was associated with a higher rate of the composite outcome that included death.	Metformin	44-53	insulin	Homo sapiens	83-90
27636742-0	2016	Metformin inhibits estrogen-dependent endometrial cancer cell growth by activating the AMPK-FOXO1 signal pathway.	Metformin	0-9	forkhead box O1	Homo sapiens	92-97
27636742-4	2016	Metformin treatment suppressed EC cell growth in a time-dependent manner in vitro; this effect was cancelled by cotreatment with an AMPK inhibitor, compound C. Metformin decreased FOXO1 phosphorylation and increased FOXO1 nuclear localization in Ishikawa and HEC-1B cells, with non-significant increase in FOXO1 mRNA expression.	Metformin	0-9	forkhead box O1	Homo sapiens	180-185
27636742-4	2016	Metformin treatment suppressed EC cell growth in a time-dependent manner in vitro; this effect was cancelled by cotreatment with an AMPK inhibitor, compound C. Metformin decreased FOXO1 phosphorylation and increased FOXO1 nuclear localization in Ishikawa and HEC-1B cells, with non-significant increase in FOXO1 mRNA expression.	Metformin	0-9	forkhead box O1	Homo sapiens	216-221
27636742-4	2016	Metformin treatment suppressed EC cell growth in a time-dependent manner in vitro; this effect was cancelled by cotreatment with an AMPK inhibitor, compound C. Metformin decreased FOXO1 phosphorylation and increased FOXO1 nuclear localization in Ishikawa and HEC-1B cells, with non-significant increase in FOXO1 mRNA expression.	Metformin	0-9	forkhead box O1	Homo sapiens	216-221
27636742-4	2016	Metformin treatment suppressed EC cell growth in a time-dependent manner in vitro; this effect was cancelled by cotreatment with an AMPK inhibitor, compound C. Metformin decreased FOXO1 phosphorylation and increased FOXO1 nuclear localization in Ishikawa and HEC-1B cells, with non-significant increase in FOXO1 mRNA expression.	Metformin	160-169	forkhead box O1	Homo sapiens	180-185
27636742-4	2016	Metformin treatment suppressed EC cell growth in a time-dependent manner in vitro; this effect was cancelled by cotreatment with an AMPK inhibitor, compound C. Metformin decreased FOXO1 phosphorylation and increased FOXO1 nuclear localization in Ishikawa and HEC-1B cells, with non-significant increase in FOXO1 mRNA expression.	Metformin	160-169	forkhead box O1	Homo sapiens	216-221
27636742-4	2016	Metformin treatment suppressed EC cell growth in a time-dependent manner in vitro; this effect was cancelled by cotreatment with an AMPK inhibitor, compound C. Metformin decreased FOXO1 phosphorylation and increased FOXO1 nuclear localization in Ishikawa and HEC-1B cells, with non-significant increase in FOXO1 mRNA expression.	Metformin	160-169	forkhead box O1	Homo sapiens	216-221
27636742-5	2016	Moreover, compound C blocked the metformin-induced changes of FOXO1 and its phosphorylation protein, suggesting that metformin upregulated FOXO1 activity by AMPK activation.	Metformin	33-42	forkhead box O1	Homo sapiens	62-67
27636742-5	2016	Moreover, compound C blocked the metformin-induced changes of FOXO1 and its phosphorylation protein, suggesting that metformin upregulated FOXO1 activity by AMPK activation.	Metformin	33-42	forkhead box O1	Homo sapiens	139-144
27636742-5	2016	Moreover, compound C blocked the metformin-induced changes of FOXO1 and its phosphorylation protein, suggesting that metformin upregulated FOXO1 activity by AMPK activation.	Metformin	117-126	forkhead box O1	Homo sapiens	62-67
27636742-5	2016	Moreover, compound C blocked the metformin-induced changes of FOXO1 and its phosphorylation protein, suggesting that metformin upregulated FOXO1 activity by AMPK activation.	Metformin	117-126	forkhead box O1	Homo sapiens	139-144
27636742-7	2016	In addition, transfection with siRNA for FOXO1 cancelled metformin-inhibited cell growth, indicating that FOXO1 mediated metformin to inhibit EC cell proliferation.	Metformin	57-66	forkhead box O1	Homo sapiens	41-46
27636742-7	2016	In addition, transfection with siRNA for FOXO1 cancelled metformin-inhibited cell growth, indicating that FOXO1 mediated metformin to inhibit EC cell proliferation.	Metformin	57-66	forkhead box O1	Homo sapiens	106-111
27636742-7	2016	In addition, transfection with siRNA for FOXO1 cancelled metformin-inhibited cell growth, indicating that FOXO1 mediated metformin to inhibit EC cell proliferation.	Metformin	121-130	forkhead box O1	Homo sapiens	41-46
27636742-7	2016	In addition, transfection with siRNA for FOXO1 cancelled metformin-inhibited cell growth, indicating that FOXO1 mediated metformin to inhibit EC cell proliferation.	Metformin	121-130	forkhead box O1	Homo sapiens	106-111
27636742-9	2016	Taken together, these data provide a novel mechanism of antineoplastic effect for metformin through the regulation of FOXO1, and suggest that the AMPK-FOXO1 pathway may be a therapeutic target to the development of new antineoplastic drugs.	Metformin	82-91	forkhead box O1	Homo sapiens	118-123
27636742-9	2016	Taken together, these data provide a novel mechanism of antineoplastic effect for metformin through the regulation of FOXO1, and suggest that the AMPK-FOXO1 pathway may be a therapeutic target to the development of new antineoplastic drugs.	Metformin	82-91	forkhead box O1	Homo sapiens	151-156
27695899-8	2016	Furthermore, the glucose-lowering drug, metformin, prevented IR cleavage accompanied by inhibition of calpain 2 release in exosomes, and re-established insulin signalling.	Metformin	40-49	calpain 2	Homo sapiens	102-111
27576133-0	2016	Metformin inhibits JAK2V617F activity in MPN cells by activating AMPK and PP2A complexes containing the B56alpha subunit.	Metformin	0-9	protein phosphatase 2 regulatory subunit B'alpha	Homo sapiens	104-112
27576133-2	2016	It is widely accepted that metformin inhibits the growth of malignant cells primarily by suppressing the mTOR pathway or regulating autophagy.	Metformin	27-36	mechanistic target of rapamycin kinase	Homo sapiens	105-109
27745917-2	2016	In preclinical studies, metformin decreases endometrial cancer (EC) cell growth by activation of AMPK/mTOR inhibition.	Metformin	24-33	mechanistic target of rapamycin kinase	Homo sapiens	102-106
27745917-11	2016	After metformin, there were significant decreases in serum IGF-1 (p=0.046), omentin (p=0.007), insulin (p=0.012), C-peptide (p=0.018), and leptin (p=0.0035).	Metformin	6-15	insulin like growth factor 1	Homo sapiens	59-64
27745917-11	2016	After metformin, there were significant decreases in serum IGF-1 (p=0.046), omentin (p=0.007), insulin (p=0.012), C-peptide (p=0.018), and leptin (p=0.0035).	Metformin	6-15	insulin	Homo sapiens	95-102
28331909-0	2016	Evaluating the effect of insulin sensitizers metformin and pioglitazone alone and in combination on women with polycystic ovary syndrome: An RCT.	Metformin	45-54	insulin	Homo sapiens	25-32
28331909-2	2016	One of the common therapeutic methods is using insulin-sensitizing drugs such as metformin and thiazolidinediones.	Metformin	81-90	insulin	Homo sapiens	47-54
28331909-6	2016	RESULTS: Metformin and pioglitazone and combination therapy induced favorable changes in fasting serum insulin, HOMA-IR index, QUICKI, fasting glucose to insulin ratio in women with PCOS.	Metformin	9-18	insulin	Homo sapiens	103-110
28331909-6	2016	RESULTS: Metformin and pioglitazone and combination therapy induced favorable changes in fasting serum insulin, HOMA-IR index, QUICKI, fasting glucose to insulin ratio in women with PCOS.	Metformin	9-18	insulin	Homo sapiens	154-161
27695899-8	2016	Furthermore, the glucose-lowering drug, metformin, prevented IR cleavage accompanied by inhibition of calpain 2 release in exosomes, and re-established insulin signalling.	Metformin	40-49	insulin	Homo sapiens	152-159
27695899-10	2016	CONCLUSIONS/INTERPRETATION: Sequential cleavage of IR by calpain 2 and gamma-secretase may contribute to insulin signalling in cells and its inhibition may be partly responsible for the glucose-lowering effects of metformin.	Metformin	214-223	calpain 2	Homo sapiens	57-66
27695899-10	2016	CONCLUSIONS/INTERPRETATION: Sequential cleavage of IR by calpain 2 and gamma-secretase may contribute to insulin signalling in cells and its inhibition may be partly responsible for the glucose-lowering effects of metformin.	Metformin	214-223	insulin	Homo sapiens	105-112
28208875-7	2016	Similarly, SHBG levels were significantly higher in sulfonylurea treated patients compared to metformin treated patients p &lt; 0.0001.	Metformin	94-103	sex hormone binding globulin	Homo sapiens	11-15
27405060-10	2016	Metformin treatment improved the metabolic and inflammatory phenotype in Bcl-3Hep mice through modulation of PPARalpha and PGC-1alpha.	Metformin	0-9	B cell leukemia/lymphoma 3	Mus musculus	73-78
28129682-0	2016	Metformin Alleviates Lipopolysaccharide-induced Acute Lung Injury through Suppressing Toll-like Receptor 4 Signaling.	Metformin	0-9	toll-like receptor 4	Rattus norvegicus	86-106
28129682-2	2016	In this study we investigated whether activation of AMPK by metformin could protect the lung from lipopolysaccharide (LPS)-induced acute injury by inhibitingng TLR4 pathway.	Metformin	60-69	toll-like receptor 4	Rattus norvegicus	160-164
28129682-11	2016	We conclude that metformin could protect the lung tissue against LPS-evoked TLR4 activation and the protective effect can be related to the activation of AMPK.	Metformin	17-26	toll-like receptor 4	Rattus norvegicus	76-80
27534967-0	2016	Metformin mediated reversal of epithelial to mesenchymal transition is triggered by epigenetic changes in E-cadherin promoter.	Metformin	0-9	cadherin 1	Homo sapiens	106-116
27534967-6	2016	We demonstrated that metformin attenuates ERK signaling by activating AMPK pathway leading to suppression of Snail and Slug resulting in upregulation of crucial tumor suppressor gene E-cadherin.	Metformin	21-30	snail family transcriptional repressor 1	Homo sapiens	109-114
27534967-6	2016	We demonstrated that metformin attenuates ERK signaling by activating AMPK pathway leading to suppression of Snail and Slug resulting in upregulation of crucial tumor suppressor gene E-cadherin.	Metformin	21-30	cadherin 1	Homo sapiens	183-193
27534967-10	2016	To our knowledge this is the first report representing an inverse relationship of AMPK and ERK signaling axis in promoting mesenchymal to epithelial transition (MET) via re-expression of E-cadherin upon metformin treatment thus rationalizing lower incidence of cancer in metformin-administered patients.	Metformin	203-212	cadherin 1	Homo sapiens	187-197
27534967-10	2016	To our knowledge this is the first report representing an inverse relationship of AMPK and ERK signaling axis in promoting mesenchymal to epithelial transition (MET) via re-expression of E-cadherin upon metformin treatment thus rationalizing lower incidence of cancer in metformin-administered patients.	Metformin	271-280	cadherin 1	Homo sapiens	187-197
27534967-13	2016	Metformin induces hypomethylation of the E-cadherin gene promoter.	Metformin	0-9	cadherin 1	Homo sapiens	41-51
26733332-9	2016	High-glucose reduced AMPK phosphorylation and induced mammalian target of rapamycin (mTOR) activation in podocytes, which was abolished and reversed by pre-treatment with metformin.	Metformin	171-180	mechanistic target of rapamycin kinase	Homo sapiens	54-83
26733332-9	2016	High-glucose reduced AMPK phosphorylation and induced mammalian target of rapamycin (mTOR) activation in podocytes, which was abolished and reversed by pre-treatment with metformin.	Metformin	171-180	mechanistic target of rapamycin kinase	Homo sapiens	85-89
26733332-11	2016	In summary, metformin exhibits an anti-apoptotic impact on podocytes under high-glucose conditions via activation of AMPK and inhibition of mTOR signaling.	Metformin	12-21	mechanistic target of rapamycin kinase	Homo sapiens	140-144
27405060-10	2016	Metformin treatment improved the metabolic and inflammatory phenotype in Bcl-3Hep mice through modulation of PPARalpha and PGC-1alpha.	Metformin	0-9	peroxisome proliferator activated receptor alpha	Mus musculus	109-118
27779715-3	2016	Therefore, the present study aimed to explain this phenomenon in regards to the relationship between microRNAs (miRNAs) and their target genes and to predict how AMPKalpha2 may be a downstream target gene of miR-27a, thus exploring the new mechanism of metformin in the treatment of breast cancer regarding miRNAs.	Metformin	253-262	microRNA 27a	Homo sapiens	208-215
27779693-7	2016	Administration of metformin enhanced the efficacy of gemcitabine and cisplatin to suppress the growth of cholangiocarcinoma tumors established in experimental models by inhibiting cell proliferation and inducing cell apoptosis through their effects on AMPK, cyclin D1 and caspase-3.	Metformin	18-27	caspase 3	Homo sapiens	272-281
27779715-0	2016	miR-27a-mediated antiproliferative effects of metformin on the breast cancer cell line MCF-7.	Metformin	46-55	microRNA 27a	Homo sapiens	0-7
27779715-9	2016	miR-27a was downregulated, and AMPKa2 was upregulated after intervention with metformin, and caspase-3 was activated.	Metformin	78-87	microRNA 27a	Homo sapiens	0-7
27780736-0	2016	Add-on therapy with anagliptin in Japanese patients with type-2 diabetes mellitus treated with metformin and miglitol can maintain higher concentrations of biologically active GLP-1/total GIP and a lower concentration of leptin.	Metformin	95-104	glucagon	Homo sapiens	176-181
27252117-13	2016	The tissue levels of IL-6, TNF-alpha and CRP were markedly decreased by 21-day treatment with metformin (200 mg/kg/d) (p &lt; 0.001).	Metformin	94-103	interleukin 6	Mus musculus	21-25
27252117-13	2016	The tissue levels of IL-6, TNF-alpha and CRP were markedly decreased by 21-day treatment with metformin (200 mg/kg/d) (p &lt; 0.001).	Metformin	94-103	tumor necrosis factor	Mus musculus	27-36
27780736-0	2016	Add-on therapy with anagliptin in Japanese patients with type-2 diabetes mellitus treated with metformin and miglitol can maintain higher concentrations of biologically active GLP-1/total GIP and a lower concentration of leptin.	Metformin	95-104	gastric inhibitory polypeptide	Homo sapiens	188-191
27780736-1	2016	Metformin, alpha-glucosidase inhibitors (alpha-GIs), and dipeptidyl peptidase 4 inhibitors (DPP-4Is) reduce hyperglycemia without excessive insulin secretion, and enhance postprandial plasma concentration of glucagon-like peptide-1 (GLP-1) in type-2 diabetes mellitus (T2DM) patients.	Metformin	0-9	glucagon	Homo sapiens	208-231
27780736-1	2016	Metformin, alpha-glucosidase inhibitors (alpha-GIs), and dipeptidyl peptidase 4 inhibitors (DPP-4Is) reduce hyperglycemia without excessive insulin secretion, and enhance postprandial plasma concentration of glucagon-like peptide-1 (GLP-1) in type-2 diabetes mellitus (T2DM) patients.	Metformin	0-9	glucagon	Homo sapiens	233-238
27588386-6	2016	Metformin treatment reduced plasma glucose and insulin resistance, irrespective of the gender.	Metformin	0-9	insulin	Homo sapiens	47-54
27717596-3	2016	The use of insulin sensitizers (i.e. metformin), reduces such metabolic, and most hormonal, impairments.	Metformin	37-46	insulin	Homo sapiens	11-18
27717596-4	2016	As metformin often induces side effects, new integrative strategies have been proposed to treat insulin resistance, such as the use of inositols.	Metformin	3-12	insulin	Homo sapiens	96-103
27562556-14	2016	Furthermore, the protection was reproduced in JNK activation-absent HepaRG cells treated with 20 mM APAP followed by 0.5 or 1 mM metformin 6 h later, confirming JNK-independent protection mechanisms.	Metformin	129-138	mitogen-activated protein kinase 8	Homo sapiens	46-49
27916907-0	2016	Metformin Inhibits TGF-beta1-Induced Epithelial-to-Mesenchymal Transition via PKM2 Relative-mTOR/p70s6k Signaling Pathway in Cervical Carcinoma Cells.	Metformin	0-9	transforming growth factor beta 1	Homo sapiens	19-28
27916907-0	2016	Metformin Inhibits TGF-beta1-Induced Epithelial-to-Mesenchymal Transition via PKM2 Relative-mTOR/p70s6k Signaling Pathway in Cervical Carcinoma Cells.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	92-96
27916907-3	2016	This study investigated the mechanisms of metformin in TGF-beta1-induced Epithelial-to-mesenchymal transition (EMT) in cervical carcinoma cells.	Metformin	42-51	transforming growth factor beta 1	Homo sapiens	55-64
27916907-7	2016	Moreover, metformin partially abolished TGF-beta1-induced EMT cell proliferation and reversed TGF-beta1-induced EMT.	Metformin	10-19	transforming growth factor beta 1	Homo sapiens	40-49
27916907-7	2016	Moreover, metformin partially abolished TGF-beta1-induced EMT cell proliferation and reversed TGF-beta1-induced EMT.	Metformin	10-19	transforming growth factor beta 1	Homo sapiens	94-103
27916907-8	2016	In addition, the anti-EMT effects of metformin could be partially in accord with rapamycin, a specific mTOR inhibitor.	Metformin	37-46	mechanistic target of rapamycin kinase	Homo sapiens	103-107
27916907-10	2016	CONCLUSION: Metformin abolishes TGF-beta1-induced EMT in cervical carcinoma cells by inhibiting mTOR/p70s6k signaling to down-regulate PKM2 expression.	Metformin	12-21	transforming growth factor beta 1	Homo sapiens	32-41
27916907-10	2016	CONCLUSION: Metformin abolishes TGF-beta1-induced EMT in cervical carcinoma cells by inhibiting mTOR/p70s6k signaling to down-regulate PKM2 expression.	Metformin	12-21	mechanistic target of rapamycin kinase	Homo sapiens	96-100
27893782-0	2016	Beneficial Effects of Metformin and/or Salicylate on Palmitate- or TNFalpha-Induced Neuroinflammatory Marker and Neuropeptide Gene Regulation in Immortalized NPY/AgRP Neurons.	Metformin	22-31	tumor necrosis factor	Homo sapiens	67-75
27893782-8	2016	We determined co-treatment with metformin or sodium salicylate alone was successful in alleviating changes observed in feeding peptide mRNA regulation, whereas a preventative pre-treatment with metformin and sodium salicylate together was able to alleviate palmitate- and TNFalpha-induced induction of NPY and/or AgRP mRNA levels.	Metformin	194-203	tumor necrosis factor	Homo sapiens	272-280
27904436-3	2016	In the present study, we determined the effects of metformin on the levels of pro-inflammatory cytokines (i.e., IL-6, TNF-alpha, and MCP-1) and anti-inflammatory mediator IL-10 in blood and urine of patients with type 2 diabetes.	Metformin	51-60	interleukin 6	Homo sapiens	112-116
27904436-6	2016	RESULTS: We found that metformin reduced the levels of IL-6 in blood and MCP-1 in urine, but increased IL-10 levels in blood of patients with type 2 diabetes.	Metformin	23-32	interleukin 6	Homo sapiens	55-59
27904436-8	2016	Furthermore, compared to individual drug treatment, metformin significantly reduced the levels of serum IL-6 and TNF-alpha, as well as urine MCP-1.	Metformin	52-61	interleukin 6	Homo sapiens	104-108
27904436-8	2016	Furthermore, compared to individual drug treatment, metformin significantly reduced the levels of serum IL-6 and TNF-alpha, as well as urine MCP-1.	Metformin	52-61	tumor necrosis factor	Homo sapiens	113-122
27882107-13	2016	Sitagliptin phosphate combined with metformin effectively and safely improves glycemic excursion and carbohydrate metabolism in NEDM patients by promoting the first phase of insulin and incretin secretion and inhibiting glucagon secretion of.	Metformin	36-45	insulin	Homo sapiens	174-181
27780736-9	2016	Add-on therapy with anagliptin in Japanese T2DM patients treated with metformin and miglitol for 52 weeks improved glycemic control and enhanced postprandial concentrations of active GLP-1/total GIP, and reduce the leptin concentration.	Metformin	70-79	glucagon	Homo sapiens	183-188
27645247-8	2016	Moxifloxacin was the only TB drug identified as a potent inhibitor (DDI index of &gt;0.1) of MATE1- and MATE2K-mediated metformin transport, with IC50s of 12 muM (95% confidence intervals [CI], 5.1 to 29 muM) and 7.6 muM (95% CI, 0.2 to 242 muM), respectively.	Metformin	120-129	latexin	Homo sapiens	158-161
27904682-0	2016	Targeting cancer cell metabolism: The combination of metformin and 2-Deoxyglucose regulates apoptosis in ovarian cancer cells via p38 MAPK/JNK signaling pathway.	Metformin	53-62	mitogen-activated protein kinase 14	Homo sapiens	130-133
27904682-0	2016	Targeting cancer cell metabolism: The combination of metformin and 2-Deoxyglucose regulates apoptosis in ovarian cancer cells via p38 MAPK/JNK signaling pathway.	Metformin	53-62	mitogen-activated protein kinase 8	Homo sapiens	139-142
27904682-5	2016	Moreover, metformin and 2-DG could efficiently induce apoptosis in ovarian cancer cells, which was achieved by activating p38 MAPK and JNK pathways.	Metformin	10-19	mitogen-activated protein kinase 14	Homo sapiens	122-125
27904682-5	2016	Moreover, metformin and 2-DG could efficiently induce apoptosis in ovarian cancer cells, which was achieved by activating p38 MAPK and JNK pathways.	Metformin	10-19	mitogen-activated protein kinase 8	Homo sapiens	135-138
27600020-3	2016	Pre-incubation of cells with metformin, an AMPK activator, blocked PDGF-induced activation of mTOR and its downstream targets changes of Skp2 and p27 without changing Akt phosphorylation and inhibited ASMCs proliferation.	Metformin	29-38	mechanistic target of rapamycin kinase	Homo sapiens	94-98
27600020-4	2016	Transfection of ASMCs with AMPK alpha2-specific small interfering RNA (siRNA) reversed the effect of metformin on mTOR phosphorylation, Skp2 and p27 protein expression and cell proliferation.	Metformin	101-110	mechanistic target of rapamycin kinase	Homo sapiens	114-118
27919027-7	2016	Clinically used AMPK activators metformin and salicylate enhanced the inhibitory phosphorylation of endogenous JAK1 and inhibited STAT3 phosphorylation in primary vascular endothelial cells.	Metformin	32-41	Janus kinase 1	Homo sapiens	111-115
27919027-7	2016	Clinically used AMPK activators metformin and salicylate enhanced the inhibitory phosphorylation of endogenous JAK1 and inhibited STAT3 phosphorylation in primary vascular endothelial cells.	Metformin	32-41	signal transducer and activator of transcription 3	Homo sapiens	130-135
27118251-4	2016	Notably, cellular steroidogenesis models have facilitated the understanding of the mechanistic effects of pharmacotherapies, including insulin sensitizers (e.g., pioglitazone and metformin) used for the treatment of insulin resistance in PCOS, on androgen production.	Metformin	179-188	insulin	Homo sapiens	216-223
27748082-0	2016	Metformin induces degradation of mTOR protein in breast cancer cells.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	33-37
27748082-8	2016	We show that metformin treatment in MCF-7 breast cancer cells induced degradation of mTOR and sequestration of this protein in a perinuclear region.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	85-89
27389807-10	2016	In contrast, the AMPK activator metformin decreased beta-arrestin 1 expression and attenuated cardiac fibrosis in both young and old mice upon ISO exposure.	Metformin	32-41	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	17-21
27389807-13	2016	The AMPK activator metformin is a promising therapeutic agent for treating ageing-related cardiac remodelling upon beta-AR over-activation.	Metformin	19-28	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	4-8
26887663-2	2016	METHODS: In the Carotid Atherosclerosis: Metformin for Insulin Resistance (CAMERA) study (NCT00723307), 173 individuals without Type 2 diabetes, but with coronary disease, were randomized to metformin (n=86) or placebo (n=87) for 18 months.	Metformin	41-50	insulin	Homo sapiens	55-62
27493135-3	2016	Considering recent findings that serotonin reuptake transporter (SERT) might also be involved in metformin intestinal absorption, and the role of serotonin in gastrointestinal physiology, in this study we investigated the association between a common polymorphism in the SERT gene and metformin gastrointestinal intolerance.	Metformin	97-106	solute carrier family 6 member 4	Homo sapiens	65-69
27493135-2	2016	We have previously shown that reduced-function alleles of organic cation transporter 1 (OCT1) are associated with increased intolerance to metformin.	Metformin	139-148	solute carrier family 22 member 1	Homo sapiens	58-86
27493135-2	2016	We have previously shown that reduced-function alleles of organic cation transporter 1 (OCT1) are associated with increased intolerance to metformin.	Metformin	139-148	solute carrier family 22 member 1	Homo sapiens	88-92
27493135-3	2016	Considering recent findings that serotonin reuptake transporter (SERT) might also be involved in metformin intestinal absorption, and the role of serotonin in gastrointestinal physiology, in this study we investigated the association between a common polymorphism in the SERT gene and metformin gastrointestinal intolerance.	Metformin	97-106	solute carrier family 6 member 4	Homo sapiens	33-63
27493135-3	2016	Considering recent findings that serotonin reuptake transporter (SERT) might also be involved in metformin intestinal absorption, and the role of serotonin in gastrointestinal physiology, in this study we investigated the association between a common polymorphism in the SERT gene and metformin gastrointestinal intolerance.	Metformin	285-294	solute carrier family 6 member 4	Homo sapiens	65-69
27493135-5	2016	RESULTS: The number of low-expressing SERT S* alleles increased the odds of metformin intolerance (odds ratio [OR] 1.31 [95% CI 1.02-1.67], P = 0.031).	Metformin	76-85	solute carrier family 6 member 4	Homo sapiens	38-42
27493135-7	2016	In the analyses stratified by SERT genotype, the presence of two deficient OCT1 alleles was associated with more than a ninefold higher odds of metformin intolerance in patients carrying the L*L* genotype (OR 9.25 [95% CI 3.18-27.0], P &lt; 10-4); however, it showed a much smaller effect in L*S* carriers and no effect in S*S* carriers.	Metformin	144-153	solute carrier family 6 member 4	Homo sapiens	30-34
27493135-7	2016	In the analyses stratified by SERT genotype, the presence of two deficient OCT1 alleles was associated with more than a ninefold higher odds of metformin intolerance in patients carrying the L*L* genotype (OR 9.25 [95% CI 3.18-27.0], P &lt; 10-4); however, it showed a much smaller effect in L*S* carriers and no effect in S*S* carriers.	Metformin	144-153	solute carrier family 22 member 1	Homo sapiens	75-79
27493135-8	2016	CONCLUSIONS: Our results indicate that the interaction between OCT1 and SERT genes might play an important role in metformin intolerance.	Metformin	115-124	solute carrier family 22 member 1	Homo sapiens	63-67
27493135-8	2016	CONCLUSIONS: Our results indicate that the interaction between OCT1 and SERT genes might play an important role in metformin intolerance.	Metformin	115-124	solute carrier family 6 member 4	Homo sapiens	72-76
27808040-33	2016	In addition, the observed gut hormone responses following CCK-induced gallbladder emptying and metformin, make suggest that bile acid release into the small intestines with subsequent TGR5 and FXR involvement contributes to stimulation of GLP-1 secretion and, therefore, that metformin"s mode of action encompasses both bile acid-dependent and independent stimulation of gut hormone secretion.	Metformin	276-285	cholecystokinin	Homo sapiens	58-61
28173075-10	2016	Mechanistic studies revealed that the E3 ubiquitin ligase, STUB1, could influence metformin response by facilitating proteasome-mediated degradation of cyclin A.	Metformin	82-91	cyclin A2	Homo sapiens	152-160
27756052-0	2016	AMPK activation by metformin inhibits local innate immune responses in the isolated rat heart by suppression of TLR 4-related pathway.	Metformin	19-28	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	0-4
27756052-0	2016	AMPK activation by metformin inhibits local innate immune responses in the isolated rat heart by suppression of TLR 4-related pathway.	Metformin	19-28	toll-like receptor 4	Rattus norvegicus	112-117
27756052-3	2016	The present study investigated whether AMPK activation by metformin could contribute to the regulation of immune responses in the isolated heart via suppression of TLR4 activity, independent of circulatory immunity.	Metformin	58-67	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	39-43
27756052-10	2016	Metformin clearly augmented the phosphorylation of both AMPKalpha and ACC and in addition to improvement of cardiac performance, markedly suppressed the TLR4 activity.	Metformin	0-9	toll-like receptor 4	Rattus norvegicus	153-157
27756052-11	2016	Antagonizing AMPK by compound C which is a selective inhibitor of AMPK pathway, considerably reversed the protective effects of metformin against the TLR4-related activity.	Metformin	128-137	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	13-17
27756052-11	2016	Antagonizing AMPK by compound C which is a selective inhibitor of AMPK pathway, considerably reversed the protective effects of metformin against the TLR4-related activity.	Metformin	128-137	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	66-70
27756052-11	2016	Antagonizing AMPK by compound C which is a selective inhibitor of AMPK pathway, considerably reversed the protective effects of metformin against the TLR4-related activity.	Metformin	128-137	toll-like receptor 4	Rattus norvegicus	150-154
27654259-0	2016	Insulin-Like Growth Factor 1/Mammalian Target of Rapamycin and AMP-Activated Protein Kinase Signaling Involved in the Effects of Metformin in the Human Endometrial Cancer.	Metformin	129-138	insulin like growth factor 1	Homo sapiens	0-28
27654259-7	2016	RESULTS: We found that high IGF-1 plasma concentrations in women with EC were reversed by conventional antidiabetic doses of metformin in the present work.	Metformin	125-134	insulin like growth factor 1	Homo sapiens	28-33
27654259-8	2016	In parallel, the activation of AMPK and suppression of mTOR seemed to play an important role for the effect of metformin in patients with EC.	Metformin	111-120	mechanistic target of rapamycin kinase	Homo sapiens	55-59
27599468-3	2016	The biguanide metformin is reported to prevent transforming growth factor-beta (TGF-beta)-induced EMT and proliferation of cancer.	Metformin	14-23	transforming growth factor beta 1	Homo sapiens	47-78
27599468-3	2016	The biguanide metformin is reported to prevent transforming growth factor-beta (TGF-beta)-induced EMT and proliferation of cancer.	Metformin	14-23	transforming growth factor beta 1	Homo sapiens	80-88
27599468-12	2016	Although phosphorylation of AMP-activated protein kinase was enhanced by IR and metformin, phosphorylation of mammalian target of rapamycin was enhanced by IR and suppressed by metformin.	Metformin	177-186	mechanistic target of rapamycin kinase	Homo sapiens	110-139
27599468-13	2016	These results indicated that metformin suppressed IR-induced EMT via suppression of the TGF-beta-Smad phosphorylation pathway, and a part of the non-Smad pathway.	Metformin	29-38	transforming growth factor beta 1	Homo sapiens	88-96
27760406-0	2016	Synergistic cell death in FLT3-ITD positive acute myeloid leukemia by combined treatment with metformin and 6-benzylthioinosine.	Metformin	94-103	fms related receptor tyrosine kinase 3	Homo sapiens	26-30
27760406-7	2016	The combination of 6-BT with metformin resulted in significant cytotoxicity (60-70%) in monocytic AML cell lines and was associated with inhibition of FLT3-ITD activated STAT5 and reduced c-Myc and GLUT-1 expression.	Metformin	29-38	fms related receptor tyrosine kinase 3	Homo sapiens	151-155
26809842-6	2016	After metformin treatment, the mean difference in the LDL-C value between metformin treatment and placebo was from 0.16 mmol l-1 at baseline to -0.86 mmol l-1 at the end of week 24, decreased by 1.02 mmol l-1 (P&lt;0.0001); and 25.3% of patients in the metformin group had LDL-C &gt;=3.37 mmol l-1, which is significantly &lt;64.8% in the placebo group (P&lt;0.001) at week 24.	Metformin	6-15	component of oligomeric golgi complex 2	Homo sapiens	54-59
26809842-6	2016	After metformin treatment, the mean difference in the LDL-C value between metformin treatment and placebo was from 0.16 mmol l-1 at baseline to -0.86 mmol l-1 at the end of week 24, decreased by 1.02 mmol l-1 (P&lt;0.0001); and 25.3% of patients in the metformin group had LDL-C &gt;=3.37 mmol l-1, which is significantly &lt;64.8% in the placebo group (P&lt;0.001) at week 24.	Metformin	6-15	component of oligomeric golgi complex 2	Homo sapiens	273-278
26809842-6	2016	After metformin treatment, the mean difference in the LDL-C value between metformin treatment and placebo was from 0.16 mmol l-1 at baseline to -0.86 mmol l-1 at the end of week 24, decreased by 1.02 mmol l-1 (P&lt;0.0001); and 25.3% of patients in the metformin group had LDL-C &gt;=3.37 mmol l-1, which is significantly &lt;64.8% in the placebo group (P&lt;0.001) at week 24.	Metformin	74-83	component of oligomeric golgi complex 2	Homo sapiens	54-59
26809842-6	2016	After metformin treatment, the mean difference in the LDL-C value between metformin treatment and placebo was from 0.16 mmol l-1 at baseline to -0.86 mmol l-1 at the end of week 24, decreased by 1.02 mmol l-1 (P&lt;0.0001); and 25.3% of patients in the metformin group had LDL-C &gt;=3.37 mmol l-1, which is significantly &lt;64.8% in the placebo group (P&lt;0.001) at week 24.	Metformin	74-83	component of oligomeric golgi complex 2	Homo sapiens	273-278
26809842-6	2016	After metformin treatment, the mean difference in the LDL-C value between metformin treatment and placebo was from 0.16 mmol l-1 at baseline to -0.86 mmol l-1 at the end of week 24, decreased by 1.02 mmol l-1 (P&lt;0.0001); and 25.3% of patients in the metformin group had LDL-C &gt;=3.37 mmol l-1, which is significantly &lt;64.8% in the placebo group (P&lt;0.001) at week 24.	Metformin	74-83	component of oligomeric golgi complex 2	Homo sapiens	54-59
26809842-6	2016	After metformin treatment, the mean difference in the LDL-C value between metformin treatment and placebo was from 0.16 mmol l-1 at baseline to -0.86 mmol l-1 at the end of week 24, decreased by 1.02 mmol l-1 (P&lt;0.0001); and 25.3% of patients in the metformin group had LDL-C &gt;=3.37 mmol l-1, which is significantly &lt;64.8% in the placebo group (P&lt;0.001) at week 24.	Metformin	74-83	component of oligomeric golgi complex 2	Homo sapiens	273-278
26809842-7	2016	Compared with the placebo, metformin treatment also have a significant effect on reducing weight, body mass index, insulin, insulin resistance index, total cholesterol and triglyceride, and increasing high-density lipoprotein cholesterol.	Metformin	27-36	insulin	Homo sapiens	115-122
26809842-7	2016	Compared with the placebo, metformin treatment also have a significant effect on reducing weight, body mass index, insulin, insulin resistance index, total cholesterol and triglyceride, and increasing high-density lipoprotein cholesterol.	Metformin	27-36	insulin	Homo sapiens	124-131
26809842-9	2016	We found that metformin treatment was effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effects improving antipsychotic-induced insulin resistance appeared earlier than the reducing dyslipidemia.	Metformin	14-23	insulin	Homo sapiens	100-107
27900046-4	2016	Metformin at a low dose potently inhibited the insulin action, decreasing the ability of the endometrial cancer (EC) cell line to migrate and invade in a high and normal glucose environment, and decreasing the migration ability of the primary eEPs.	Metformin	0-9	insulin	Homo sapiens	47-54
27900046-5	2016	In the EC cell line, the insulin treatment increased the proliferation, without any subsequent reduction of proliferation by the addition of 0.1 mM metformin; however, relative cell proliferation sensitivity to metformin was observed in the range between 1 and 5 mM regardless of the glucose concentration present.	Metformin	211-220	insulin	Homo sapiens	25-32
27900046-7	2016	However, at this concentration, metformin can inhibit the insulin action in endometrial epithelial cancer cells, demonstrating an anti-metastatic effect in high and normal glucose environments.	Metformin	32-41	insulin	Homo sapiens	58-65
28167482-6	2016	Metformin caused a significant reduction in blood pressure with p &lt; 0.05 (i.e. SBP 9.9% &amp; DBP 6.4%) while sitagliptin caused a highly significant p &lt;0.01 reduction in blood pressure (i.e. SBP 15.8% &amp; DBP 12.2%).	Metformin	0-9	D-box binding PAR bZIP transcription factor	Homo sapiens	97-100
28167482-6	2016	Metformin caused a significant reduction in blood pressure with p &lt; 0.05 (i.e. SBP 9.9% &amp; DBP 6.4%) while sitagliptin caused a highly significant p &lt;0.01 reduction in blood pressure (i.e. SBP 15.8% &amp; DBP 12.2%).	Metformin	0-9	D-box binding PAR bZIP transcription factor	Homo sapiens	214-217
27787519-8	2016	In addition, metformin was shown to promote the expression of anabolic genes such as Col2a1 and Acan expression while inhibiting the expression of catabolic genes such as Mmp3 and Adamts5 in nucleus pulposus cells.	Metformin	13-22	ADAM metallopeptidase with thrombospondin type 1 motif, 5	Rattus norvegicus	180-187
28076676-4	2016	Long-term metformin use is associated with decreased vitamin B12 levels, and even with biochemical B12 deficiency; this complication can detected early by annual assessments of serum B12 levels and prevented by annual intramuscular B12 administration.	Metformin	10-19	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	61-64
28076676-4	2016	Long-term metformin use is associated with decreased vitamin B12 levels, and even with biochemical B12 deficiency; this complication can detected early by annual assessments of serum B12 levels and prevented by annual intramuscular B12 administration.	Metformin	10-19	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	99-102
28076676-4	2016	Long-term metformin use is associated with decreased vitamin B12 levels, and even with biochemical B12 deficiency; this complication can detected early by annual assessments of serum B12 levels and prevented by annual intramuscular B12 administration.	Metformin	10-19	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	99-102
28076676-4	2016	Long-term metformin use is associated with decreased vitamin B12 levels, and even with biochemical B12 deficiency; this complication can detected early by annual assessments of serum B12 levels and prevented by annual intramuscular B12 administration.	Metformin	10-19	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	99-102
27397427-7	2016	Treatments with either celecoxib or in combination with metformin resulted in a reduction in AT macrophage infiltration and decreases in levels of adipose tissue TNF-alpha, MCP-1, and leptin levels in high-fat (HF) fed rats.	Metformin	56-65	tumor necrosis factor	Rattus norvegicus	162-171
27639960-10	2016	On the other hand, treatment of neurons with metformin resulted in a significant increase in seladin-1.	Metformin	45-54	24-dehydrocholesterol reductase	Rattus norvegicus	93-102
27397427-7	2016	Treatments with either celecoxib or in combination with metformin resulted in a reduction in AT macrophage infiltration and decreases in levels of adipose tissue TNF-alpha, MCP-1, and leptin levels in high-fat (HF) fed rats.	Metformin	56-65	mast cell protease 1-like 1	Rattus norvegicus	173-178
27018756-15	2016	Metformin significantly (P &lt; .05) reduced insulin, BP, CRP, and PAI-1 levels.	Metformin	0-9	insulin	Homo sapiens	45-52
27762347-0	2016	Metformin sensitizes the response of oral squamous cell carcinoma to cisplatin treatment through inhibition of NF-kappaB/HIF-1alpha signal axis.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	121-131
27551045-12	2016	In kidney, metformin increased the activation of AMP-activated protein kinase (AMPK) and decreased inflammatory markers (COX-2 and IL-1beta) and apoptotic markers (poly(ADP-ribose) polymerase (PARP) and caspase 3).	Metformin	11-20	interleukin 1 beta	Rattus norvegicus	131-139
27551045-13	2016	Metformin was effective in lowering elevated basal blood pressure and acute change in mean arterial pressure in response to angiotensin II (Ang II).	Metformin	0-9	angiotensinogen	Rattus norvegicus	124-138
27551045-13	2016	Metformin was effective in lowering elevated basal blood pressure and acute change in mean arterial pressure in response to angiotensin II (Ang II).	Metformin	0-9	angiotensinogen	Rattus norvegicus	140-146
27724912-9	2016	HbA1c (hemoglobin A1c) level &gt;=8.5 %, obesity and insulin treatment in dose-dependent and time-varying manner demonstrated significant association with increased risk of malignancy, while metformin use was associated with a lower risk of cancer.	Metformin	191-200	insulin	Homo sapiens	53-60
27716110-8	2016	Metformin compared to placebo resulted in significant reduction in BMI [-1.13 kg/m2 (95 % CI -1.61 to -0.66)] and insulin resistance index [-1.49 (95 % CI -2.40 to -0.59)] but not fasting blood sugar [-2.48 mg/dl (95 % CI -5.54 to 0.57].	Metformin	0-9	insulin	Homo sapiens	114-121
27323792-0	2016	Comparison of 2 Population Health Management Approaches to Increase Vitamin B12 Monitoring in Patients Taking Metformin.	Metformin	110-119	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	76-79
27323792-2	2016	OBJECTIVES: To compare the effectiveness of and time required for 2 pharmacist-driven population health management interventions to improve vitamin B12 monitoring in patients taking metformin.	Metformin	182-191	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	148-151
27265206-0	2016	Involvement of glucagon-like peptide-1 in the glucose-lowering effect of metformin.	Metformin	73-82	glucagon	Homo sapiens	15-38
27265206-3	2016	Interestingly, intravenously administered metformin is ineffective and recently, metformin was shown to increase plasma concentrations of the glucose-lowering gut incretin hormone glucagon-like peptide-1 (GLP-1), which may contribute to metformin"s glucose-lowering effect in patients with type 2 diabetes.	Metformin	42-51	glucagon	Homo sapiens	180-203
27265206-3	2016	Interestingly, intravenously administered metformin is ineffective and recently, metformin was shown to increase plasma concentrations of the glucose-lowering gut incretin hormone glucagon-like peptide-1 (GLP-1), which may contribute to metformin"s glucose-lowering effect in patients with type 2 diabetes.	Metformin	42-51	glucagon	Homo sapiens	205-210
27265206-3	2016	Interestingly, intravenously administered metformin is ineffective and recently, metformin was shown to increase plasma concentrations of the glucose-lowering gut incretin hormone glucagon-like peptide-1 (GLP-1), which may contribute to metformin"s glucose-lowering effect in patients with type 2 diabetes.	Metformin	81-90	glucagon	Homo sapiens	180-203
27265206-3	2016	Interestingly, intravenously administered metformin is ineffective and recently, metformin was shown to increase plasma concentrations of the glucose-lowering gut incretin hormone glucagon-like peptide-1 (GLP-1), which may contribute to metformin"s glucose-lowering effect in patients with type 2 diabetes.	Metformin	81-90	glucagon	Homo sapiens	205-210
27265206-3	2016	Interestingly, intravenously administered metformin is ineffective and recently, metformin was shown to increase plasma concentrations of the glucose-lowering gut incretin hormone glucagon-like peptide-1 (GLP-1), which may contribute to metformin"s glucose-lowering effect in patients with type 2 diabetes.	Metformin	81-90	glucagon	Homo sapiens	180-203
27265206-3	2016	Interestingly, intravenously administered metformin is ineffective and recently, metformin was shown to increase plasma concentrations of the glucose-lowering gut incretin hormone glucagon-like peptide-1 (GLP-1), which may contribute to metformin"s glucose-lowering effect in patients with type 2 diabetes.	Metformin	81-90	glucagon	Homo sapiens	205-210
27265206-4	2016	The mechanisms behind metformin-induced increments in GLP-1 levels remain unknown, but it has been hypothesized that metformin stimulates GLP-1 secretion directly and/or indirectly and that metformin prolongs the half-life of GLP-1.	Metformin	22-31	glucagon	Homo sapiens	54-59
27265206-4	2016	The mechanisms behind metformin-induced increments in GLP-1 levels remain unknown, but it has been hypothesized that metformin stimulates GLP-1 secretion directly and/or indirectly and that metformin prolongs the half-life of GLP-1.	Metformin	22-31	glucagon	Homo sapiens	138-143
27265206-4	2016	The mechanisms behind metformin-induced increments in GLP-1 levels remain unknown, but it has been hypothesized that metformin stimulates GLP-1 secretion directly and/or indirectly and that metformin prolongs the half-life of GLP-1.	Metformin	22-31	glucagon	Homo sapiens	138-143
27265206-4	2016	The mechanisms behind metformin-induced increments in GLP-1 levels remain unknown, but it has been hypothesized that metformin stimulates GLP-1 secretion directly and/or indirectly and that metformin prolongs the half-life of GLP-1.	Metformin	117-126	glucagon	Homo sapiens	138-143
27265206-4	2016	The mechanisms behind metformin-induced increments in GLP-1 levels remain unknown, but it has been hypothesized that metformin stimulates GLP-1 secretion directly and/or indirectly and that metformin prolongs the half-life of GLP-1.	Metformin	117-126	glucagon	Homo sapiens	138-143
27265206-4	2016	The mechanisms behind metformin-induced increments in GLP-1 levels remain unknown, but it has been hypothesized that metformin stimulates GLP-1 secretion directly and/or indirectly and that metformin prolongs the half-life of GLP-1.	Metformin	117-126	glucagon	Homo sapiens	138-143
27265206-4	2016	The mechanisms behind metformin-induced increments in GLP-1 levels remain unknown, but it has been hypothesized that metformin stimulates GLP-1 secretion directly and/or indirectly and that metformin prolongs the half-life of GLP-1.	Metformin	117-126	glucagon	Homo sapiens	138-143
27265206-5	2016	Also, it has been suggested that metformin may potentiate the glucose-lowering effects of GLP-1 by increasing target tissue sensitivity to GLP-1.	Metformin	33-42	glucagon	Homo sapiens	90-95
27265206-5	2016	Also, it has been suggested that metformin may potentiate the glucose-lowering effects of GLP-1 by increasing target tissue sensitivity to GLP-1.	Metformin	33-42	glucagon	Homo sapiens	139-144
27265206-6	2016	The present article critically reviews the possible mechanisms by which metformin may affect GLP-1 levels and sensitivity and discusses whether such alterations may constitute important and clinically relevant glucose-lowering actions of metformin.	Metformin	72-81	glucagon	Homo sapiens	93-98
25876759-1	2016	Organic cation transporter 2 (rOCT2) and multidrug and toxin extrusion protein 1 (rMATE1) are mainly expressed in rat renal proximal tubules and mediate urinary excretion of cationic drugs, such as metformin.	Metformin	198-207	solute carrier family 47 member 1	Rattus norvegicus	82-88
27554603-6	2016	Co-treatment with metformin distinct abolished the Abeta-caused actions in hNSCs.	Metformin	18-27	amyloid beta precursor protein	Homo sapiens	51-56
27554603-8	2016	Importantly, co-treatment with metformin significantly restored fragmented mitochondria to almost normal morphology in the hNSCs with Abeta.	Metformin	31-40	amyloid beta precursor protein	Homo sapiens	134-139
27376570-7	2016	Baseline eGFR was better in patients under metformin therapy.	Metformin	43-52	epidermal growth factor receptor	Homo sapiens	9-13
27600587-11	2016	The adiponectin concentration in the culture media was also decreased in metformin-treated cells.	Metformin	73-82	adiponectin, C1Q and collagen domain containing	Homo sapiens	4-15
27600587-12	2016	The WST-8 assay revealed no effect on proliferation or growth inhibition following metformin treatment, although metformin suppressed the expression of PPARgamma and C/EBPalpha.	Metformin	113-122	peroxisome proliferator activated receptor gamma	Homo sapiens	152-161
27600587-12	2016	The WST-8 assay revealed no effect on proliferation or growth inhibition following metformin treatment, although metformin suppressed the expression of PPARgamma and C/EBPalpha.	Metformin	113-122	CCAAT enhancer binding protein alpha	Homo sapiens	166-176
27619024-8	2016	Pretreatment of metformin dose dependently suppressed the expression of TNF-alpha mRNA induced by LPS (2 mM, p = 0.03).	Metformin	16-25	tumor necrosis factor	Homo sapiens	72-81
27619024-9	2016	The amount of COX-2 protein production was significantly decreased by metformin pretreatment (4 mM, p = 0.01).	Metformin	70-79	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	14-19
27459533-0	2016	Metformin Increases Cortisol Regeneration by 11betaHSD1 in Obese Men With and Without Type 2 Diabetes Mellitus.	Metformin	0-9	hydroxysteroid 11-beta dehydrogenase 1	Homo sapiens	45-55
27459533-3	2016	OBJECTIVE: To determine whether metformin regulates 11betaHSD1 activity in vivo in obese men with and without type 2 diabetes mellitus.	Metformin	32-41	hydroxysteroid 11-beta dehydrogenase 1	Homo sapiens	52-62
27459533-11	2016	MAIN OUTCOME MEASURES: The effect of metformin on whole-body and hepatic 11betaHSD1 activity.	Metformin	37-46	hydroxysteroid 11-beta dehydrogenase 1	Homo sapiens	73-83
27459533-13	2016	Metformin increased whole-body cortisol regeneration by 11betaHSD1 in both groups compared with placebo and gliclazide and tended to increase hepatic 11betaHSD1 activity.	Metformin	0-9	hydroxysteroid 11-beta dehydrogenase 1	Homo sapiens	56-66
27459533-13	2016	Metformin increased whole-body cortisol regeneration by 11betaHSD1 in both groups compared with placebo and gliclazide and tended to increase hepatic 11betaHSD1 activity.	Metformin	0-9	hydroxysteroid 11-beta dehydrogenase 1	Homo sapiens	150-160
27459533-15	2016	CONCLUSIONS: Metformin increases whole-body cortisol generation by 11betaHSD1 probably through an indirect mechanism, potentially offsetting other metabolic benefits of metformin.	Metformin	13-22	hydroxysteroid 11-beta dehydrogenase 1	Homo sapiens	67-77
27459533-16	2016	Co-prescription with metformin should provide a greater target for selective 11betaHSD1 inhibitors.	Metformin	21-30	hydroxysteroid 11-beta dehydrogenase 1	Homo sapiens	77-87
27018756-15	2016	Metformin significantly (P &lt; .05) reduced insulin, BP, CRP, and PAI-1 levels.	Metformin	0-9	C-reactive protein	Homo sapiens	58-61
27692296-8	2016	Metformin (10 and 50muM) pretreatment significantly decreased the frequency of dicentrics (DCs), acentric fragments (AFs), rings (RIs), micronuclei (MN), and nucleoplasmic bridges (NPBs) in irradiated human peripheral blood lymphocytes.	Metformin	0-9	latexin	Homo sapiens	20-23
27692296-9	2016	Also, treatment with metformin (10 and 50muM) without irradiation did not increase the number of MN, NPBs, DCs, AFs, RIs, and did not show a cytostatic effect in the human peripheral blood lymphocytes.	Metformin	21-30	latexin	Homo sapiens	41-44
27424158-0	2016	Exenatide and metformin express their anti-inflammatory effects on human monocytes/macrophages by the attenuation of MAPKs and NFkappaB signaling.	Metformin	14-23	nuclear factor kappa B subunit 1	Homo sapiens	127-135
27424158-9	2016	Experiments on MAPKs showed effective inhibitory potential of exenatide toward p38, JNK, and ERK, whereas metformin inhibited JNK and ERK only.	Metformin	106-115	mitogen-activated protein kinase 8	Homo sapiens	126-129
27424158-9	2016	Experiments on MAPKs showed effective inhibitory potential of exenatide toward p38, JNK, and ERK, whereas metformin inhibited JNK and ERK only.	Metformin	106-115	mitogen-activated protein kinase 1	Homo sapiens	134-137
27424158-12	2016	In conclusion, here, we report that metformin and exenatide inhibit the proinflammatory phenotype of human monocytes/macrophages via influence on MAPK, C/EBP beta, and NFkappaB.	Metformin	36-45	mitogen-activated protein kinase 1	Homo sapiens	146-150
27424158-12	2016	In conclusion, here, we report that metformin and exenatide inhibit the proinflammatory phenotype of human monocytes/macrophages via influence on MAPK, C/EBP beta, and NFkappaB.	Metformin	36-45	nuclear factor kappa B subunit 1	Homo sapiens	168-176
27424158-13	2016	Exenatide was more effective than metformin in reducing MCP-1 expression and JNK activity.	Metformin	34-43	mitogen-activated protein kinase 8	Homo sapiens	77-80
26960058-0	2016	Metformin pretreatment enhanced learning and memory in cerebral forebrain ischaemia: the role of the AMPK/BDNF/P70SK signalling pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	101-105
27379837-8	2016	Increasing AMPK activity after injury using the drugs 5-amino-1-beta-d-ribofuranosyl-imidazole-4-carboxamide or metformin did not affect spatial learning, but significantly improved spatial memory.	Metformin	112-121	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	11-15
26960058-1	2016	Context Metformin induced AMP-activated protein kinase (AMPK) and protected neurons in cerebral ischaemia.	Metformin	8-17	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	26-54
26960058-1	2016	Context Metformin induced AMP-activated protein kinase (AMPK) and protected neurons in cerebral ischaemia.	Metformin	8-17	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	56-60
26960058-12	2016	Conclusion Short-term memory in ischaemic rats treated with metformin increased step-through latency; sensory-motor evaluation was applied and a group of ischaemia rats that were pretreated with metformin showed high levels of BDNF, P70S6K that seemed to be due to increasing AMPK.	Metformin	60-69	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	276-280
26960058-12	2016	Conclusion Short-term memory in ischaemic rats treated with metformin increased step-through latency; sensory-motor evaluation was applied and a group of ischaemia rats that were pretreated with metformin showed high levels of BDNF, P70S6K that seemed to be due to increasing AMPK.	Metformin	195-204	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	276-280
27755516-7	2016	Life style modification with BMI reduction was recommended and metformin, a drug improving sensitivity to insulin, was administered.	Metformin	63-72	insulin	Homo sapiens	106-113
27362768-5	2016	In addition to the indirect mode of action, metformin may exhibit direct inhibitory effect on cancer cells by targeting mammalian target of rapamycin (mTOR) signaling and anabolic processes.	Metformin	44-53	mechanistic target of rapamycin kinase	Homo sapiens	120-149
27362768-5	2016	In addition to the indirect mode of action, metformin may exhibit direct inhibitory effect on cancer cells by targeting mammalian target of rapamycin (mTOR) signaling and anabolic processes.	Metformin	44-53	mechanistic target of rapamycin kinase	Homo sapiens	151-155
27544029-0	2016	Metformin ameliorates obesity-associated hypertriglyceridemia in mice partly through the apolipoprotein A5 pathway.	Metformin	0-9	apolipoprotein A-V	Mus musculus	89-106
27544029-2	2016	This study is to investigate the role of apoA5 in obesity-associated hypertriglyceridemia and metformin-related hypotriglyceridemic actions.	Metformin	94-103	apolipoprotein A-V	Mus musculus	41-46
27544029-4	2016	The effects of low- and high-dose metformin were determined on plasma and hepatic TG and apoA5 of these obese mice.	Metformin	34-43	apolipoprotein A-V	Mus musculus	89-94
27544029-5	2016	Besides, the effects of metformin on TG and apoA5 were also detected in mouse and human hepatocytes in vitro.	Metformin	24-33	apolipoprotein A-V	Mus musculus	44-49
27544029-8	2016	(2) Metformin dose-dependently decreased hepatic and plasma TG and apoA5 in the obese mice.	Metformin	4-13	apolipoprotein A-V	Mus musculus	67-72
27544029-9	2016	Similarly, metformin dose-dependently reduced cellular TG contents and apoA5 expressions in hepatocytes in vitro.	Metformin	11-20	apolipoprotein A-V	Mus musculus	71-76
27544029-11	2016	CONCLUSION: Increased hepatic and plasma apoA5 could be a result of obesity-associated hypertriglyceridemia, and metformin displays hypotriglyceridemic effects on obese mice partly via the apoA5 pathway.	Metformin	113-122	apolipoprotein A-V	Mus musculus	189-194
27569287-0	2016	TRAIL restores DCA/metformin-mediated cell death in hypoxia.	Metformin	19-28	TNF superfamily member 10	Homo sapiens	0-5
27569287-3	2016	In the present study, we found that TRAIL can overcome the effect of hypoxia on the cell death induced by treatment of DCA and metformin in breast cancer cells.	Metformin	127-136	TNF superfamily member 10	Homo sapiens	36-41
27569287-5	2016	Blocking DR5 by siRNA inhibited DCA/metformin/TRAIL-induced cell death, indicating that DR5 upregulation plays an important role in sensitizing cancer cells to TRAIL-induced cell death.	Metformin	36-45	TNF superfamily member 10	Homo sapiens	46-51
27569287-5	2016	Blocking DR5 by siRNA inhibited DCA/metformin/TRAIL-induced cell death, indicating that DR5 upregulation plays an important role in sensitizing cancer cells to TRAIL-induced cell death.	Metformin	36-45	TNF superfamily member 10	Homo sapiens	160-165
27569287-6	2016	Furthermore, we found that activation of JNK and c-Jun is responsible for upregulation of DR5 induced by DCA/metformin.	Metformin	109-118	mitogen-activated protein kinase 8	Homo sapiens	41-44
27409676-7	2016	Older age, longer diabetes duration, male sex, and use of insulin, sulfonylurea, calcium channel blockers, aspirin, ticlopidine, clopidogrel and dipyridamole were significantly associated with a higher risk in sitagliptin users, but dyslipidemia and use of metformin and statin were protective.	Metformin	257-266	insulin	Homo sapiens	58-65
27640062-15	2016	Insulin-metformin CT compared with IM showed a MD in HbA1c of -0.9% (95% CI -1.2 to -0.5); P &lt; 0.01; 698 participants; 9 trials; low-quality evidence.	Metformin	8-17	insulin	Homo sapiens	0-7
27517746-0	2016	Metformin enhances TRAIL-induced apoptosis by Mcl-1 degradation via Mule in colorectal cancer cells.	Metformin	0-9	TNF superfamily member 10	Homo sapiens	19-24
27517746-2	2016	In this study, we show that subtoxic doses of metformin effectively sensitize human colorectal cancer (CRC) cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), which induces apoptosis.	Metformin	46-55	TNF superfamily member 10	Homo sapiens	180-185
27517746-3	2016	Metformin alone did not induce apoptosis, but significantly potentiated TRAIL-induced apoptosis in CRC cells.	Metformin	0-9	TNF superfamily member 10	Homo sapiens	72-77
27517746-5	2016	We attempted to elucidate the underlying mechanism, and found that metformin significantly reduced the protein levels of myeloid cell leukemia 1 (Mcl-1) in CRC cells and, the overexpression of Mcl-1 inhibited cell death induced by metformin and/or TRAIL.	Metformin	67-76	TNF superfamily member 10	Homo sapiens	248-253
27517746-10	2016	Our study is the first report indicating that metformin enhances TRAIL-induced apoptosis through Noxa and favors the interaction between Mcl-1 and Mule, which consequently affects Mcl-1 ubiquitination.	Metformin	46-55	TNF superfamily member 10	Homo sapiens	65-70
26804175-0	2016	Role of Runx2 in IGF-1Rbeta/Akt- and AMPK/Erk-dependent growth, survival and sensitivity towards metformin in breast cancer bone metastasis.	Metformin	97-106	RUNX family transcription factor 2	Homo sapiens	8-13
26804175-8	2016	Importantly, the Runx2 knockdown in bone-derived cells resulted in increased sensitivity to both Erk1/2 inhibition and AMPKalpha activation by PD184161 and metformin, respectively, despite increased IGF-1Rbeta and AMPKalpha levels.	Metformin	156-165	RUNX family transcription factor 2	Homo sapiens	17-22
26804175-8	2016	Importantly, the Runx2 knockdown in bone-derived cells resulted in increased sensitivity to both Erk1/2 inhibition and AMPKalpha activation by PD184161 and metformin, respectively, despite increased IGF-1Rbeta and AMPKalpha levels.	Metformin	156-165	mitogen-activated protein kinase 3	Homo sapiens	97-103
27600499-7	2016	Compared with control (placebo, sitagliptin, glimepiride, dulaglutide, insulin glargine, and NPH), liraglutide in combination with metformin resulted in significant reductions in HbA1c, bodyweight, FPG, and PPG, and similar reductions in SBP, and DBP.	Metformin	131-140	serglycin	Homo sapiens	207-210
27600499-7	2016	Compared with control (placebo, sitagliptin, glimepiride, dulaglutide, insulin glargine, and NPH), liraglutide in combination with metformin resulted in significant reductions in HbA1c, bodyweight, FPG, and PPG, and similar reductions in SBP, and DBP.	Metformin	131-140	D-box binding PAR bZIP transcription factor	Homo sapiens	247-250
27355267-12	2016	Oral glucose tolerance tests at discharge revealed that metformin significantly improved insulin sensitivity, P &lt; 0.05.	Metformin	56-65	insulin	Homo sapiens	89-96
27246734-6	2016	Western blot revealed that the expression of Beclin-1 and LC3B-II was enhanced, and the phosphorylation levels of the mammalian target of rapamycin (mTOR) protein and p70S6K were reduced by metformin after SCI.	Metformin	190-199	mechanistic target of rapamycin kinase	Homo sapiens	118-147
27246734-6	2016	Western blot revealed that the expression of Beclin-1 and LC3B-II was enhanced, and the phosphorylation levels of the mammalian target of rapamycin (mTOR) protein and p70S6K were reduced by metformin after SCI.	Metformin	190-199	mechanistic target of rapamycin kinase	Homo sapiens	149-153
27246734-7	2016	Metformin significantly reduced the expression of NF-kappaB.	Metformin	0-9	nuclear factor kappa B subunit 1	Homo sapiens	50-59
27246734-8	2016	Moreover, Western blot and immunofluorescence results indicated that caspase 3 activation was reduced, whereas bcl-2 level was significantly increased by metformin.	Metformin	154-163	BCL2 apoptosis regulator	Homo sapiens	111-116
27246734-9	2016	Hence, metformin attenuated SCI by inhibiting apoptosis and inflammation and enhancing the autophagy via the mTOR/p70S6K signalling pathway.	Metformin	7-16	mechanistic target of rapamycin kinase	Homo sapiens	109-113
27343375-6	2016	Metformin and resveratrol inhibited lipolysis through prevention of PKA/HSL activation by decreasing the accumulation of cAMP via preserving PDE3B.	Metformin	0-9	phosphodiesterase 3B, cGMP-inhibited	Mus musculus	141-146
27355267-14	2016	CONCLUSIONS: Metformin decreases glucose equally as effective as insulin without causing hypoglycemia, with additional benefits including improved insulin resistance and decreased endogenous insulin synthesis when compared with insulin controls.	Metformin	13-22	insulin	Homo sapiens	147-154
27355267-14	2016	CONCLUSIONS: Metformin decreases glucose equally as effective as insulin without causing hypoglycemia, with additional benefits including improved insulin resistance and decreased endogenous insulin synthesis when compared with insulin controls.	Metformin	13-22	insulin	Homo sapiens	147-154
27355267-14	2016	CONCLUSIONS: Metformin decreases glucose equally as effective as insulin without causing hypoglycemia, with additional benefits including improved insulin resistance and decreased endogenous insulin synthesis when compared with insulin controls.	Metformin	13-22	insulin	Homo sapiens	147-154
27355267-15	2016	These results indicate that metformin is safe in burn patients and further supports the use of metformin in severely burned patients for postburn control of hyperglycemia and insulin resistance.	Metformin	95-104	insulin	Homo sapiens	175-182
27602077-6	2016	Prior treatment of mice with the AMPK agonist metformin significantly suppressed the LPS-induced development of ALI, reduced the elevation of MDA and increased the activity of SOD.	Metformin	46-55	superoxide dismutase 1, soluble	Mus musculus	176-179
27602077-8	2016	This study suggests that activation of AMPK by metformin inhibits oxidative stress by upregulation of PGC1alpha and SOD1, thereby suppressing the development of ALI/ARDS, and has potential value in the clinical treatment of such conditions.	Metformin	47-56	superoxide dismutase 1, soluble	Mus musculus	116-120
27643646-0	2016	Metformin Increases E-cadherin in Tumors of Diabetic Patients With Endometrial Cancer and Suppresses Epithelial-Mesenchymal Transition in Endometrial Cancer Cell Lines.	Metformin	0-9	cadherin 1	Homo sapiens	20-30
27643646-6	2016	RESULTS: Protein expression and messenger RNA of E-cadherin was found to be increased (P = 0.02 and 0.04, respectively) in 30 EC tumor specimens of diabetic patients treated with metformin compared with 20 EC tumor specimens of diabetic patients treated with other antidiabetic agents.	Metformin	179-188	cadherin 1	Homo sapiens	49-59
27643646-8	2016	Metformin reduced EMT in the cell lines and regulated the expression of the EMT-related epithelial markers, E-cadherin and Pan-keratin; the mesenchymal markers, N-cadherin, fibronectin, and vimentin; and the EMT drivers, Twist-1, snail-1, and ZEB-1.	Metformin	0-9	cadherin 1	Homo sapiens	108-118
27643646-8	2016	Metformin reduced EMT in the cell lines and regulated the expression of the EMT-related epithelial markers, E-cadherin and Pan-keratin; the mesenchymal markers, N-cadherin, fibronectin, and vimentin; and the EMT drivers, Twist-1, snail-1, and ZEB-1.	Metformin	0-9	fibronectin 1	Homo sapiens	173-184
27643646-8	2016	Metformin reduced EMT in the cell lines and regulated the expression of the EMT-related epithelial markers, E-cadherin and Pan-keratin; the mesenchymal markers, N-cadherin, fibronectin, and vimentin; and the EMT drivers, Twist-1, snail-1, and ZEB-1.	Metformin	0-9	twist family bHLH transcription factor 1	Homo sapiens	221-228
27643646-8	2016	Metformin reduced EMT in the cell lines and regulated the expression of the EMT-related epithelial markers, E-cadherin and Pan-keratin; the mesenchymal markers, N-cadherin, fibronectin, and vimentin; and the EMT drivers, Twist-1, snail-1, and ZEB-1.	Metformin	0-9	snail family transcriptional repressor 1	Homo sapiens	230-237
27643646-9	2016	CONCLUSIONS: Tumors of patients on metformin have increased E-cadherin expression, and metformin decreases EMT in EC cell lines in vitro, suggesting clinical biological relevance of metformin in women with EC.	Metformin	35-44	cadherin 1	Homo sapiens	60-70
27706018-2	2016	We found that AICAR or metformin acts as a regulator of LPS/NF-kappaB-or hypoxia/NF-kappaB-mediated cyclooxygenase induction by an AMPK-dependent mechanism with interactions between p65-NF-kappaB phosphorylation and acetylation, including in a human bladder cancer cell line (T24).	Metformin	23-32	nuclear factor kappa B subunit 1	Homo sapiens	60-80
27423273-4	2016	At a pharmacologically relevant concentration, metformin restored AMPK activation, and inhibited Aldo-induced Nox4/H2O2-dependent TRAF3IP2 induction, pro-inflammatory cytokine expression, and CF migration and proliferation.	Metformin	47-56	TRAF3 interacting protein 2	Mus musculus	130-138
27423273-6	2016	These results were recapitulated in vivo, where metformin reversed Aldo+salt-induced oxidative stress, suppression of AMPK activation, TRAF3IP2 induction, pro-inflammatory cytokine expression, and cardiac fibrosis, without significantly modulating systolic blood pressure.	Metformin	48-57	TRAF3 interacting protein 2	Mus musculus	135-143
27904616-0	2016	Effect of folic acid and metformin on insulin resistance and inflammatory factors of obese children and adolescents.	Metformin	25-34	insulin	Homo sapiens	38-45
27378194-1	2016	Metformin exerts antitumor effects mainly through AMP-activated protein kinase [AMPK] activation and phosphatidylinositol 3-kinase [PI3K]-Akt-mammalian target of rapamycin [mTOR] inhibition.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	138-141
27378194-1	2016	Metformin exerts antitumor effects mainly through AMP-activated protein kinase [AMPK] activation and phosphatidylinositol 3-kinase [PI3K]-Akt-mammalian target of rapamycin [mTOR] inhibition.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	173-177
27378194-6	2016	Moreover, metformin decreases the production of insulin, insulin-like growth factor, inflammatory cytokines and vascular endothelial growth factor, and therefore it exerts anti-mitotic, anti-inflammatory and anti-angiogenetic effects.	Metformin	10-19	insulin	Homo sapiens	48-83
27378194-6	2016	Moreover, metformin decreases the production of insulin, insulin-like growth factor, inflammatory cytokines and vascular endothelial growth factor, and therefore it exerts anti-mitotic, anti-inflammatory and anti-angiogenetic effects.	Metformin	10-19	vascular endothelial growth factor A	Homo sapiens	112-146
27904616-7	2016	After folic acid and metformin administration, mean of Hcy, HOMA-IR, TNF-alpha, and IL-8 decreased significantly (P &lt; 0.05).	Metformin	21-30	tumor necrosis factor	Homo sapiens	69-78
27904616-7	2016	After folic acid and metformin administration, mean of Hcy, HOMA-IR, TNF-alpha, and IL-8 decreased significantly (P &lt; 0.05).	Metformin	21-30	C-X-C motif chemokine ligand 8	Homo sapiens	84-88
27317943-6	2016	Specifically, OCT1-mediated metformin access to its site of action in the liver is impacted by genetic polymorphisms and chemical inhibition of OCT1.	Metformin	28-37	solute carrier family 22 member 1	Homo sapiens	14-18
27317943-6	2016	Specifically, OCT1-mediated metformin access to its site of action in the liver is impacted by genetic polymorphisms and chemical inhibition of OCT1.	Metformin	28-37	solute carrier family 22 member 1	Homo sapiens	144-148
27576730-4	2016	Therefore, we sought to investigate the inhibitory role of metformin in lung fibrosis development via modulating TGF-beta signaling.	Metformin	59-68	transforming growth factor beta 1	Homo sapiens	113-121
27576730-7	2016	RESULTS: We found that TGF-beta-induced myofibroblast differentiation was clearly inhibited by metformin treatment in LF.	Metformin	95-104	transforming growth factor beta 1	Homo sapiens	23-31
27576730-8	2016	Metformin-mediated activation of AMPK was responsible for inhibiting TGF-beta-induced NOX4 expression.	Metformin	0-9	transforming growth factor beta 1	Homo sapiens	69-77
27576730-12	2016	CONCLUSIONS: These findings suggest that metformin can be a promising anti-fibrotic modality of treatment for IPF affected by TGF-beta.	Metformin	41-50	transforming growth factor beta 1	Homo sapiens	126-134
27571249-0	2016	Long-term treatment with metformin in obese, insulin-resistant adolescents: results of a randomized double-blinded placebo-controlled trial.	Metformin	25-34	insulin	Homo sapiens	45-52
27571249-2	2016	In this study, the long-term efficacy and safety of metformin versus placebo in adolescents with obesity and insulin resistance is studied.	Metformin	52-61	insulin	Homo sapiens	109-116
27571249-12	2016	CONCLUSIONS: Long-term treatment with metformin in adolescents with obesity and insulin resistance results in stabilization of BMI and improved body composition compared with placebo.	Metformin	38-47	insulin	Homo sapiens	80-87
27571249-13	2016	Therefore, metformin may be useful as an additional therapy in combination with lifestyle intervention in adolescents with obesity and insulin resistance.	Metformin	11-20	insulin	Homo sapiens	135-142
27474170-0	2016	Metformin increases PDH and suppresses HIF-1alpha under hypoxic conditions and induces cell death in oral squamous cell carcinoma.	Metformin	0-9	pyruvate dehydrogenase phosphatase catalytic subunit 1	Homo sapiens	20-23
27474170-0	2016	Metformin increases PDH and suppresses HIF-1alpha under hypoxic conditions and induces cell death in oral squamous cell carcinoma.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	39-49
27474170-3	2016	RESULTS: Low PDH levels were observed in OSCC, and Metformin promotes an increase in PDH levels in hypoxic conditions.	Metformin	51-60	pyruvate dehydrogenase phosphatase catalytic subunit 1	Homo sapiens	85-88
27474170-4	2016	Metformin also reduced HIF-1alpha mRNA and protein levels.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	23-33
27474170-5	2016	Metformin demonstrated antiproliferative effects, inhibited migration, increased the number of apoptotic cells and increased the transcription of caspase 3.	Metformin	0-9	caspase 3	Homo sapiens	146-155
27474170-12	2016	CONCLUSIONS: In conclusion, our current findings show that Metformin reduces HIF-1alpha gene expression and increases PDH expression.	Metformin	59-68	hypoxia inducible factor 1 subunit alpha	Homo sapiens	77-87
27474170-12	2016	CONCLUSIONS: In conclusion, our current findings show that Metformin reduces HIF-1alpha gene expression and increases PDH expression.	Metformin	59-68	pyruvate dehydrogenase phosphatase catalytic subunit 1	Homo sapiens	118-121
27474170-14	2016	Additionally, Metformin enhances the number of apoptotic cells and caspase 3 levels.	Metformin	14-23	caspase 3	Homo sapiens	67-76
27418629-3	2016	METHODS AND RESULTS: In primary hepatocytes from healthy animals, metformin and the IKKbeta (inhibitor of kappa B kinase) inhibitor BI605906 both inhibited tumor necrosis factor-alpha-dependent IkappaB degradation and expression of proinflammatory mediators interleukin-6, interleukin-1beta, and CXCL1/2 (C-X-C motif ligand 1/2).	Metformin	66-75	interleukin 6	Homo sapiens	258-271
27418629-3	2016	METHODS AND RESULTS: In primary hepatocytes from healthy animals, metformin and the IKKbeta (inhibitor of kappa B kinase) inhibitor BI605906 both inhibited tumor necrosis factor-alpha-dependent IkappaB degradation and expression of proinflammatory mediators interleukin-6, interleukin-1beta, and CXCL1/2 (C-X-C motif ligand 1/2).	Metformin	66-75	interleukin 1 beta	Homo sapiens	273-290
27418629-9	2016	Following up these findings in a double-blind placebo controlled trial in nondiabetic heart failure (trial registration: NCT00473876), metformin suppressed plasma cytokines including the aging-associated cytokine CCL11 (C-C motif chemokine ligand 11).	Metformin	135-144	C-C motif chemokine ligand 11	Homo sapiens	213-218
27418629-9	2016	Following up these findings in a double-blind placebo controlled trial in nondiabetic heart failure (trial registration: NCT00473876), metformin suppressed plasma cytokines including the aging-associated cytokine CCL11 (C-C motif chemokine ligand 11).	Metformin	135-144	C-C motif chemokine ligand 11	Homo sapiens	220-249
27621764-2	2016	METHODS: Expression of P-glycoprotein (P-gp) and NF-kappaB in human HepG2 or HepG2/adriamycin (ADM) cells treated with pCMV-NF-kappaB-small interference RNA (siRNA) with or without metformin, was analyzed by Western blot or fluorescence quantitative PCR.	Metformin	181-190	ATP binding cassette subfamily B member 1	Homo sapiens	23-37
27621764-2	2016	METHODS: Expression of P-glycoprotein (P-gp) and NF-kappaB in human HepG2 or HepG2/adriamycin (ADM) cells treated with pCMV-NF-kappaB-small interference RNA (siRNA) with or without metformin, was analyzed by Western blot or fluorescence quantitative PCR.	Metformin	181-190	ATP binding cassette subfamily B member 1	Homo sapiens	39-43
27621764-7	2016	After pretreatment with metformin, HepG2/ADM cells were sensitized to doxorubicin and P-gp was decreased through the NF-kappaB signaling pathway.	Metformin	24-33	ATP binding cassette subfamily B member 1	Homo sapiens	86-90
27621764-9	2016	CONCLUSION: Metformin via silencing NF-kappaB signaling could effectively reverse MDR of HCC cells by down-regulating MDR1/P-gp expression.	Metformin	12-21	ATP binding cassette subfamily B member 1	Homo sapiens	118-122
27621764-9	2016	CONCLUSION: Metformin via silencing NF-kappaB signaling could effectively reverse MDR of HCC cells by down-regulating MDR1/P-gp expression.	Metformin	12-21	ATP binding cassette subfamily B member 1	Homo sapiens	123-127
27259235-6	2016	The anti-diabetic biguanide metformin "reversed" the metabolomic signature and anabolic phenotype of BRCA1 one-hit cells by shutting down mitochondria-driven generation of precursors for lipogenic pathways and reducing the BCAA pool for protein synthesis and TCA fueling.	Metformin	28-37	AT-rich interaction domain 4B	Homo sapiens	223-227
27531132-0	2016	Randomized placebo control study of insulin sensitizers (Metformin and Pioglitazone) in psoriasis patients with metabolic syndrome (Topical Treatment Cohort).	Metformin	57-66	insulin	Homo sapiens	36-43
27531132-3	2016	Study objective is to evaluate the efficacy and safety of Insulin sensitizers (metformin and pioglitazone) in psoriasis patients with metabolic syndrome (MS).	Metformin	79-88	insulin	Homo sapiens	58-65
26944436-2	2016	While metformin, oral glucose lowering agent, prevent/restores vascular remodeling and reduce systemic and local ET-1 levels whether this effect was specific to metformin remained unknown.	Metformin	6-15	endothelin 1	Rattus norvegicus	113-117
27517917-10	2016	Metformin treatment reduced breast cancer cell viability, increased miR-26a expression, and led to a reduction in BCL-2, EZH2, and PTEN expression.	Metformin	0-9	BCL2 apoptosis regulator	Homo sapiens	114-119
27513844-7	2016	In line with the role of AMPK in GR expression, AMPK activator metformin reversed glucocorticoid-induced reduction of AMPK phosphorylation and GR expression as well as behavioral alteration of rats.	Metformin	63-72	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	25-29
27513844-7	2016	In line with the role of AMPK in GR expression, AMPK activator metformin reversed glucocorticoid-induced reduction of AMPK phosphorylation and GR expression as well as behavioral alteration of rats.	Metformin	63-72	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	48-52
27513844-7	2016	In line with the role of AMPK in GR expression, AMPK activator metformin reversed glucocorticoid-induced reduction of AMPK phosphorylation and GR expression as well as behavioral alteration of rats.	Metformin	63-72	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	48-52
27555891-7	2016	Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters (SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin.	Metformin	310-319	solute carrier family 22 member 1	Homo sapiens	208-215
27283492-1	2016	Metformin displays antileukemic effects partly due to activation of AMPK and subsequent inhibition of mTOR signaling.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	102-106
27517917-10	2016	Metformin treatment reduced breast cancer cell viability, increased miR-26a expression, and led to a reduction in BCL-2, EZH2, and PTEN expression.	Metformin	0-9	enhancer of zeste 2 polycomb repressive complex 2 subunit	Homo sapiens	121-125
27488947-7	2016	Metformin could target IGF-1R signaling pathway by attenuating PI3K/AKT and MEK/ERK signaling pathways and down-regulating IGF-1R.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	68-71
27488947-7	2016	Metformin could target IGF-1R signaling pathway by attenuating PI3K/AKT and MEK/ERK signaling pathways and down-regulating IGF-1R.	Metformin	0-9	mitogen-activated protein kinase kinase 7	Homo sapiens	76-79
27391065-3	2016	The anti-diabetic drug metformin has been associated with a decreased cancer prevalence and mortality in several solid tumors, prompting its possible use for ACC treatment.This paper evaluates the in vitro and in vivo anti-cancer effects of metformin using the ACC cell model H295R.Metformin treatment significantly reduces cell viability and proliferation in a dose- and time-dependent manner and associates with a significant inhibition of ERK1/2 and mTOR phosphorylation/activation, as well as with stimulation of AMPK activity.	Metformin	23-32	mitogen-activated protein kinase 3	Homo sapiens	442-448
27391065-3	2016	The anti-diabetic drug metformin has been associated with a decreased cancer prevalence and mortality in several solid tumors, prompting its possible use for ACC treatment.This paper evaluates the in vitro and in vivo anti-cancer effects of metformin using the ACC cell model H295R.Metformin treatment significantly reduces cell viability and proliferation in a dose- and time-dependent manner and associates with a significant inhibition of ERK1/2 and mTOR phosphorylation/activation, as well as with stimulation of AMPK activity.	Metformin	23-32	mechanistic target of rapamycin kinase	Homo sapiens	453-457
27391065-4	2016	Metformin also triggers the apoptotic pathway, shown by the decreased expression of Bcl-2 and HSP27, HSP60 and HSP70, and enhanced membrane exposure of annexin V, resulting in activation of caspase-3 apoptotic effector.	Metformin	0-9	BCL2 apoptosis regulator	Homo sapiens	84-89
27391065-4	2016	Metformin also triggers the apoptotic pathway, shown by the decreased expression of Bcl-2 and HSP27, HSP60 and HSP70, and enhanced membrane exposure of annexin V, resulting in activation of caspase-3 apoptotic effector.	Metformin	0-9	caspase 3	Homo sapiens	190-199
27606384-2	2016	We present the results of a trial designed to test the hypothesis that metformin will improve insulin sensitivity in obese pregnant women, thereby reducing the incidence of high-birthweight babies.	Metformin	71-80	insulin	Homo sapiens	94-101
27606384-10	2016	Embedded substudies were included to assess the effect of metformin on insulin sensitivity using the hyperinsulinaemic-euglycaemic clamp; endothelial function; maternal and fetal fat distribution using magnetic resonance imaging; placental expression of 11beta-hydroxysteroid dehydrogenase types 1 and 2 and glucocorticoid receptor; and myometrial contractility and glycogen storage.	Metformin	58-67	insulin	Homo sapiens	71-78
27606384-16	2016	Subjects taking metformin demonstrated increased insulin sensitivity [glucose disposal per unit plasma insulin difference between means during high-dose insulin 0.02 mg/kg, 95% CI 0.001 to 0.03 mg/kg (fat-free mass)/minute/microIU/l; p = 0.04] compared with those taking placebo and enhanced endogenous glucose production [difference between means 0.54 mg/kg, 95% CI 0.08 to 1.00 mg/kg (fat-free mass)/minute; p = 0.02].	Metformin	16-25	insulin	Homo sapiens	49-56
27606384-16	2016	Subjects taking metformin demonstrated increased insulin sensitivity [glucose disposal per unit plasma insulin difference between means during high-dose insulin 0.02 mg/kg, 95% CI 0.001 to 0.03 mg/kg (fat-free mass)/minute/microIU/l; p = 0.04] compared with those taking placebo and enhanced endogenous glucose production [difference between means 0.54 mg/kg, 95% CI 0.08 to 1.00 mg/kg (fat-free mass)/minute; p = 0.02].	Metformin	16-25	insulin	Homo sapiens	103-110
27606384-16	2016	Subjects taking metformin demonstrated increased insulin sensitivity [glucose disposal per unit plasma insulin difference between means during high-dose insulin 0.02 mg/kg, 95% CI 0.001 to 0.03 mg/kg (fat-free mass)/minute/microIU/l; p = 0.04] compared with those taking placebo and enhanced endogenous glucose production [difference between means 0.54 mg/kg, 95% CI 0.08 to 1.00 mg/kg (fat-free mass)/minute; p = 0.02].	Metformin	16-25	insulin	Homo sapiens	103-110
27180982-8	2016	Metformin also increased PKB Ser473 and AMPK T172 phosphorylation, decreased MDA contents and redox-sensitive PTEN protein levels, activated the anti-oxidative Nrf2 system, and increased IkappaBalpha in liver and muscle of the mice.	Metformin	0-9	phosphatase and tensin homolog	Mus musculus	110-114
27180982-8	2016	Metformin also increased PKB Ser473 and AMPK T172 phosphorylation, decreased MDA contents and redox-sensitive PTEN protein levels, activated the anti-oxidative Nrf2 system, and increased IkappaBalpha in liver and muscle of the mice.	Metformin	0-9	nuclear factor, erythroid derived 2, like 2	Mus musculus	160-164
27180982-8	2016	Metformin also increased PKB Ser473 and AMPK T172 phosphorylation, decreased MDA contents and redox-sensitive PTEN protein levels, activated the anti-oxidative Nrf2 system, and increased IkappaBalpha in liver and muscle of the mice.	Metformin	0-9	nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha	Mus musculus	187-199
27509335-5	2016	Moreover, metformin induces mitochondrial dysfunction and cell death by affecting the level and conformation of Translocase of the Outer Membrane 40 (TOM40), voltage-dependent anion-selective channels 1 (VDAC1) and hexokinase I (HKI), proteins involved in mitochondrial transport of molecules, including Abeta.	Metformin	10-19	voltage-dependent anion channel 1	Mus musculus	158-202
27509335-5	2016	Moreover, metformin induces mitochondrial dysfunction and cell death by affecting the level and conformation of Translocase of the Outer Membrane 40 (TOM40), voltage-dependent anion-selective channels 1 (VDAC1) and hexokinase I (HKI), proteins involved in mitochondrial transport of molecules, including Abeta.	Metformin	10-19	voltage-dependent anion channel 1	Mus musculus	204-209
27059816-8	2016	Insulin sensitivity increased more with metformin versus dulaglutide.	Metformin	40-49	insulin	Homo sapiens	0-7
27059816-9	2016	In conclusion, dulaglutide improves postprandial glycaemic control after a standardized test meal by enhancing beta-cell function, while metformin exerts a greater effect on insulin sensitivity.	Metformin	137-146	insulin	Homo sapiens	174-181
27216492-0	2016	Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials.	Metformin	27-36	peptide YY	Homo sapiens	107-110
27296990-8	2016	In human pulmonary arterial smooth muscle cells, metformin decreased proliferation and decreased estrogen synthesis by decreasing aromatase activity through the PII promoter site of Cyp19a1 Thus, we report for the first time that metformin can reverse pulmonary hypertension through inhibition of aromatase and estrogen synthesis in a manner likely to be mediated by AMP-activated protein kinase.	Metformin	49-58	cytochrome P450 family 19 subfamily A member 1	Homo sapiens	182-189
27296990-8	2016	In human pulmonary arterial smooth muscle cells, metformin decreased proliferation and decreased estrogen synthesis by decreasing aromatase activity through the PII promoter site of Cyp19a1 Thus, we report for the first time that metformin can reverse pulmonary hypertension through inhibition of aromatase and estrogen synthesis in a manner likely to be mediated by AMP-activated protein kinase.	Metformin	230-239	cytochrome P450 family 19 subfamily A member 1	Homo sapiens	182-189
27170051-3	2016	Metformin (MET), commonly used antidiabetic drug, has cardio-protective effects via activation of AMP kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	98-108
27170051-3	2016	Metformin (MET), commonly used antidiabetic drug, has cardio-protective effects via activation of AMP kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	110-114
26864078-3	2016	The anticancer mechanisms of metformin involve both indirect or insulin-dependent pathways and direct or insulin-independent pathways.	Metformin	29-38	insulin	Homo sapiens	64-71
26864078-3	2016	The anticancer mechanisms of metformin involve both indirect or insulin-dependent pathways and direct or insulin-independent pathways.	Metformin	29-38	insulin	Homo sapiens	105-112
26939902-0	2016	Metformin and AICAR regulate NANOG expression via the JNK pathway in HepG2 cells independently of AMPK.	Metformin	0-9	mitogen-activated protein kinase 8	Homo sapiens	54-57
26939902-4	2016	Although inhibitory effects of metformin on NANOG in pancreatic cancer cells and of AICAR in mouse embryonic stem cells have been described, the underlying molecular mechanisms remain uncertain in HCC.	Metformin	31-40	Nanog homeobox	Mus musculus	44-49
26939902-6	2016	Moreover, metformin/AICAR inhibited c-Jun N-terminal kinase (JNK) activity, and blockade of either the JNK MAPK pathway or knockdown of JNK1 gene expression reduced NANOG levels.	Metformin	10-19	mitogen-activated protein kinase 8	Homo sapiens	36-59
26939902-6	2016	Moreover, metformin/AICAR inhibited c-Jun N-terminal kinase (JNK) activity, and blockade of either the JNK MAPK pathway or knockdown of JNK1 gene expression reduced NANOG levels.	Metformin	10-19	mitogen-activated protein kinase 8	Homo sapiens	61-64
26939902-7	2016	The upregulation of NANOG and phospho-JNK by basic fibroblast growth factor (bFGF) was abrogated by metformin/AICAR.	Metformin	100-109	mitogen-activated protein kinase 8	Homo sapiens	38-41
26939902-8	2016	Additionally, although transient upregulation of NANOG within 2 h of treatment with metformin/AICAR was concordant with both JNK and AMPK activation, increased NANOG expression with activation of JNK was also observed following AMPK inhibition with compound C. Taken together, our data suggest that metformin/AICAR regulate NANOG expression via the JNK MAPK pathway in HepG2 cells independently of AMPK, and that this JNK/NANOG signaling pathway may offer new therapeutic strategies for the treatment of HCC.	Metformin	84-93	mitogen-activated protein kinase 8	Homo sapiens	125-128
26939902-8	2016	Additionally, although transient upregulation of NANOG within 2 h of treatment with metformin/AICAR was concordant with both JNK and AMPK activation, increased NANOG expression with activation of JNK was also observed following AMPK inhibition with compound C. Taken together, our data suggest that metformin/AICAR regulate NANOG expression via the JNK MAPK pathway in HepG2 cells independently of AMPK, and that this JNK/NANOG signaling pathway may offer new therapeutic strategies for the treatment of HCC.	Metformin	84-93	mitogen-activated protein kinase 8	Homo sapiens	196-199
26939902-8	2016	Additionally, although transient upregulation of NANOG within 2 h of treatment with metformin/AICAR was concordant with both JNK and AMPK activation, increased NANOG expression with activation of JNK was also observed following AMPK inhibition with compound C. Taken together, our data suggest that metformin/AICAR regulate NANOG expression via the JNK MAPK pathway in HepG2 cells independently of AMPK, and that this JNK/NANOG signaling pathway may offer new therapeutic strategies for the treatment of HCC.	Metformin	84-93	mitogen-activated protein kinase 8	Homo sapiens	196-199
26939902-8	2016	Additionally, although transient upregulation of NANOG within 2 h of treatment with metformin/AICAR was concordant with both JNK and AMPK activation, increased NANOG expression with activation of JNK was also observed following AMPK inhibition with compound C. Taken together, our data suggest that metformin/AICAR regulate NANOG expression via the JNK MAPK pathway in HepG2 cells independently of AMPK, and that this JNK/NANOG signaling pathway may offer new therapeutic strategies for the treatment of HCC.	Metformin	84-93	mitogen-activated protein kinase 8	Homo sapiens	196-199
26939902-8	2016	Additionally, although transient upregulation of NANOG within 2 h of treatment with metformin/AICAR was concordant with both JNK and AMPK activation, increased NANOG expression with activation of JNK was also observed following AMPK inhibition with compound C. Taken together, our data suggest that metformin/AICAR regulate NANOG expression via the JNK MAPK pathway in HepG2 cells independently of AMPK, and that this JNK/NANOG signaling pathway may offer new therapeutic strategies for the treatment of HCC.	Metformin	299-308	mitogen-activated protein kinase 8	Homo sapiens	196-199
26939902-8	2016	Additionally, although transient upregulation of NANOG within 2 h of treatment with metformin/AICAR was concordant with both JNK and AMPK activation, increased NANOG expression with activation of JNK was also observed following AMPK inhibition with compound C. Taken together, our data suggest that metformin/AICAR regulate NANOG expression via the JNK MAPK pathway in HepG2 cells independently of AMPK, and that this JNK/NANOG signaling pathway may offer new therapeutic strategies for the treatment of HCC.	Metformin	299-308	mitogen-activated protein kinase 8	Homo sapiens	196-199
26939902-8	2016	Additionally, although transient upregulation of NANOG within 2 h of treatment with metformin/AICAR was concordant with both JNK and AMPK activation, increased NANOG expression with activation of JNK was also observed following AMPK inhibition with compound C. Taken together, our data suggest that metformin/AICAR regulate NANOG expression via the JNK MAPK pathway in HepG2 cells independently of AMPK, and that this JNK/NANOG signaling pathway may offer new therapeutic strategies for the treatment of HCC.	Metformin	299-308	mitogen-activated protein kinase 8	Homo sapiens	196-199
27256105-6	2016	Conversely, chronic administration of metformin, which activated AMPK, markedly reduced atherosclerotic calcification and Runx2 expression in ApoE(-/-) mice but had less effects in ApoE(-/-)/AMPKalpha1(-/-) mice.	Metformin	38-47	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	65-69
27256105-6	2016	Conversely, chronic administration of metformin, which activated AMPK, markedly reduced atherosclerotic calcification and Runx2 expression in ApoE(-/-) mice but had less effects in ApoE(-/-)/AMPKalpha1(-/-) mice.	Metformin	38-47	apolipoprotein E	Mus musculus	142-146
27256105-6	2016	Conversely, chronic administration of metformin, which activated AMPK, markedly reduced atherosclerotic calcification and Runx2 expression in ApoE(-/-) mice but had less effects in ApoE(-/-)/AMPKalpha1(-/-) mice.	Metformin	38-47	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	191-201
27256105-10	2016	Finally, mutation of protein inhibitor of activated STAT-1 at serine 510 suppressed metformin-induced Runx2 SUMOylation and subsequently prevented metformin"s effect on reducing oxidized low-density lipoprotein-triggered Runx2 expression in VSMC.	Metformin	84-93	protein inhibitor of activated STAT 1	Mus musculus	21-58
27256105-10	2016	Finally, mutation of protein inhibitor of activated STAT-1 at serine 510 suppressed metformin-induced Runx2 SUMOylation and subsequently prevented metformin"s effect on reducing oxidized low-density lipoprotein-triggered Runx2 expression in VSMC.	Metformin	147-156	protein inhibitor of activated STAT 1	Mus musculus	21-58
27430256-7	2016	Eligible participants will be randomized to receive metformin 850 mg BID (n = 75) or placebo (n = 75) for 12 months.	Metformin	52-61	BH3 interacting domain death agonist	Homo sapiens	69-72
27435163-3	2016	We hypothesize that metformin use in pregnancy, as an adjunct to insulin, will decrease adverse outcomes by reducing maternal hyperglycemia, maternal insulin doses, maternal weight gain and gestational hypertension/pre-eclampsia.	Metformin	20-29	insulin	Homo sapiens	150-157
27439433-0	2016	Improving treatment and liver fibrosis outcomes with metformin in HCV-HIV co-infected and HCV mono-infected patients with insulin resistance: study protocol for a randomized controlled trial.	Metformin	53-62	insulin	Homo sapiens	122-129
27491324-5	2016	Metformin, a biguanide, reduces insulin resistance and inhibits hepatic gluconeogenesis, and has an excellent safety profile.	Metformin	0-9	insulin	Homo sapiens	32-39
27491324-6	2016	The combination of metformin and sitagliptin, targeting both characteristics of prediabetes (insulin resistance and progressive beta cell degeneration), may potentially slow or halt the progression from prediabetes to type 2 DM.	Metformin	19-28	insulin	Homo sapiens	93-100
27223082-1	2016	In this study, we demonstrated that hypoxic conditions stimulated an increase in tunneling nanotube (TNT) formation in chemoresistant ovarian cancer cells (SKOV3, C200).We found that suppressing the mTOR pathway using either everolimus or metformin led to suppression of TNT formation in vitro, verifying TNTs as a potential target for cancer-directed therapy.	Metformin	239-248	mechanistic target of rapamycin kinase	Homo sapiens	199-203
27118574-3	2016	In this review, we summarized the molecular mechanisms underlying anticancer effects of metformin, which included insulin- and AMPK-dependent effects, selectively targeting cancer stem cells, reversing multidrug resistance, inhibition of the tumor metastasis and described the antineoplastic effects of metformin combined with chemotherapeutic agents in digestive system cancers (colorectal, gastric, hepatic and pancreatic cancer), reproductive system cancers (ovarian and endometrial cancer), prostate cancer, breast cancer, lung cancer, etc.	Metformin	88-97	insulin	Homo sapiens	114-131
26869171-5	2016	The relation of thiazolidinediones- and metformin- induced post-treatment serum levels of fetuin-A and OPG to changes in CV risk requires more investigations.	Metformin	40-49	alpha 2-HS glycoprotein	Homo sapiens	90-98
27330129-6	2016	However, there have been millions of people exposed to metformin for many years, many of them with serum creatinine values at or close to 1.5 mg/dL with estimated glomerular filtration rates (eGFRs) much below 60 mL/min/1.73 m(2) who have not developed lactic acidosis.	Metformin	55-64	CD59 molecule (CD59 blood group)	Homo sapiens	216-221
27210058-4	2016	Metformin was reported to be effective against various cancers as it inhibits cell proliferation by activating AMPK, and inhibiting mTOR and HIF-1alpha.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	132-136
27210058-4	2016	Metformin was reported to be effective against various cancers as it inhibits cell proliferation by activating AMPK, and inhibiting mTOR and HIF-1alpha.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	141-151
27210058-9	2016	Western blot analysis showed marked downregulation of HIF-1alpha and mTOR expression, and upregulation of AMPKalpha in cells treated with metformin and 5-FU combination treatment.	Metformin	138-147	hypoxia inducible factor 1 subunit alpha	Homo sapiens	54-64
27210058-9	2016	Western blot analysis showed marked downregulation of HIF-1alpha and mTOR expression, and upregulation of AMPKalpha in cells treated with metformin and 5-FU combination treatment.	Metformin	138-147	mechanistic target of rapamycin kinase	Homo sapiens	69-73
27439433-4	2016	Metformin, an insulin sensitizer is known to improve HCV treatment response and has been associated with a reduced risk of developing hepatocellular carcinoma (HCC).	Metformin	0-9	insulin	Homo sapiens	14-21
26849413-10	2016	Abcd2 [adrenoleukodystrophy protein-related protein] levels were increased in metformin-treated X-ALD patient-derived fibroblasts and Abcd1-KO mice primary mixed glial cells.	Metformin	78-87	ATP binding cassette subfamily D member 2	Homo sapiens	0-5
26849413-12	2016	In vivo metformin (100 mg/Kg) in drinking water for 60 days induced Abcd2 levels and mitochondrial oxidative phosphorylation protein levels in the brain and spinal cord of Abcd1-KO mice.	Metformin	8-17	ATP-binding cassette, sub-family D (ALD), member 2	Mus musculus	68-73
26849413-16	2016	Metformin induced peroxisomal Abcd2 levels in vitro and in vivo.	Metformin	0-9	ATP binding cassette subfamily D member 2	Homo sapiens	30-35
26849413-18	2016	Metformin-induced Abcd2 levels were dependent on AMPKalpha1, a metabolic and anti-inflammatory gene, recently documented by our laboratory to play a putative role in X-ALD pathology.	Metformin	0-9	ATP binding cassette subfamily D member 2	Homo sapiens	18-23
26990533-3	2016	Read the highlighted article "Metformin-induced mitochondrial function and ABCD2 up regulation in X-linked adrenoleukodystrophy involves AMP activated protein kinase" on page 86.	Metformin	30-39	ATP binding cassette subfamily D member 2	Homo sapiens	75-80
26733176-0	2016	Targeting P-glycoprotein expression and cancer cell energy metabolism: combination of metformin and 2-deoxyglucose reverses the multidrug resistance of K562/Dox cells to doxorubicin.	Metformin	86-95	ATP binding cassette subfamily B member 1	Homo sapiens	10-24
26331290-4	2016	RESULTS: Acarbose and metformin treatment significantly improved T2DM-associated parameters (weight, fasting plasma glucose [FPG], postprandial glucose [PPG], glucagon-like peptide-1 [GLP-1], HOMA-IR, and total cholesterol) across all HbA1c levels.	Metformin	22-31	glucagon	Homo sapiens	159-182
26331290-4	2016	RESULTS: Acarbose and metformin treatment significantly improved T2DM-associated parameters (weight, fasting plasma glucose [FPG], postprandial glucose [PPG], glucagon-like peptide-1 [GLP-1], HOMA-IR, and total cholesterol) across all HbA1c levels.	Metformin	22-31	glucagon	Homo sapiens	184-189
27251371-7	2016	The neuroprotective effect of metformin on MDMA-induced dopaminergic damage was evaluated by dopamine transporter (DAT) and tyrosine hydroxylase (TH) immunohistochemistry in SNc and CPu.	Metformin	30-39	solute carrier family 6 (neurotransmitter transporter, dopamine), member 3	Mus musculus	93-113
27251371-7	2016	The neuroprotective effect of metformin on MDMA-induced dopaminergic damage was evaluated by dopamine transporter (DAT) and tyrosine hydroxylase (TH) immunohistochemistry in SNc and CPu.	Metformin	30-39	solute carrier family 6 (neurotransmitter transporter, dopamine), member 3	Mus musculus	115-118
27251371-8	2016	Metformin prevented the MDMA-induced loss of TH-positive neurons in the SNc and TH- and DAT-positive fibers in CPu, both at 48 h and 7 days after the last MDMA administration.	Metformin	0-9	solute carrier family 6 (neurotransmitter transporter, dopamine), member 3	Mus musculus	88-91
26305116-0	2016	Metformin inhibits proliferation and proinflammatory cytokines of human keratinocytes in vitro via mTOR-signaling pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	99-103
26305116-9	2016	Metformin can exert an anti-inflammatory effect by direct inhibition of IL-6, TNF-alpha, and VEGF.	Metformin	0-9	interleukin 6	Homo sapiens	72-76
26305116-9	2016	Metformin can exert an anti-inflammatory effect by direct inhibition of IL-6, TNF-alpha, and VEGF.	Metformin	0-9	tumor necrosis factor	Homo sapiens	78-87
26305116-9	2016	Metformin can exert an anti-inflammatory effect by direct inhibition of IL-6, TNF-alpha, and VEGF.	Metformin	0-9	vascular endothelial growth factor A	Homo sapiens	93-97
26305116-10	2016	Metformin at 50 mM significantly reduced the phosphorylation of mTOR and p70S6K, by 49.0 and 62.1%, respectively.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	64-68
26305116-11	2016	DISCUSSION AND CONCLUSION: Metformin treatment significantly inhibited proliferation and proinflammatory responses in HaCaT cells by a mechanism associated with inhibition of the mTOR signaling pathway.	Metformin	27-36	mechanistic target of rapamycin kinase	Homo sapiens	179-183
27113224-7	2016	Given the role of total Akt in regulation of abnormal tau accumulation and degradation, our finding that metformin 100 decreased the elevated total Akt while increasing its phosphorylated form explains its beneficial modulatory effect on phosphorylated tau in both tissues, and could further clarify its protection against memory impairment.	Metformin	105-114	AKT serine/threonine kinase 1	Rattus norvegicus	24-27
27113224-7	2016	Given the role of total Akt in regulation of abnormal tau accumulation and degradation, our finding that metformin 100 decreased the elevated total Akt while increasing its phosphorylated form explains its beneficial modulatory effect on phosphorylated tau in both tissues, and could further clarify its protection against memory impairment.	Metformin	105-114	AKT serine/threonine kinase 1	Rattus norvegicus	148-151
27126953-0	2016	Metformin attenuates graft-versus-host disease via restricting mammalian target of rapamycin/signal transducer and activator of transcription 3 and promoting adenosine monophosphate-activated protein kinase-autophagy for the balance between T helper 17 and Tregs.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	93-143
26733176-4	2016	Metformin was not a substrate of P-gp but suppressed the elevated level of P-gp in K562/Dox cells.	Metformin	0-9	ATP binding cassette subfamily B member 1	Homo sapiens	75-79
26733176-9	2016	In conclusion, metformin decreases P-gp expression in K562/Dox cells via blocking phosphorylation of extracellular signal-regulated kinase.	Metformin	15-24	ATP binding cassette subfamily B member 1	Homo sapiens	35-39
26733176-10	2016	P-gp substrate increases K562/Dox cell apoptosis via aggravating ATP depletion induced by combination of metformin and 2-deoxyglucose.	Metformin	105-114	ATP binding cassette subfamily B member 1	Homo sapiens	0-4
27334428-0	2016	Metformin and gefitinib cooperate to inhibit bladder cancer growth via both AMPK and EGFR pathways joining at Akt and Erk.	Metformin	0-9	thymoma viral proto-oncogene 1	Mus musculus	110-113
27126953-7	2016	The enhanced signal transducer and activator of transcription 3 activation noted during the development of aGVHD was reduced by metformin treatment.	Metformin	128-137	signal transducer and activator of transcription 3	Homo sapiens	13-63
27126953-9	2016	The reduction in mortality associated with metformin treatment was associated with inhibition of the mammalian target of rapamycin/signal transducer and activator of transcription 3 pathway.	Metformin	43-52	signal transducer and activator of transcription 3	Homo sapiens	131-181
27004404-2	2016	Preclinical studies have demonstrated several anticancer molecular mechanisms of metformin including mTOR inhibition, cytotoxic effects, and immunomodulation.	Metformin	81-90	mechanistic target of rapamycin kinase	Homo sapiens	101-105
27349853-0	2016	Metformin is a novel suppressor for transforming growth factor (TGF)-beta1.	Metformin	0-9	transforming growth factor beta 1	Homo sapiens	36-74
27349853-3	2016	Here, we report that transforming growth factor-beta1 (TGF-beta1), which is involved in the pathogenesis of numerous diseases, is a novel target of metformin.	Metformin	148-157	transforming growth factor beta 1	Homo sapiens	21-53
27349853-3	2016	Here, we report that transforming growth factor-beta1 (TGF-beta1), which is involved in the pathogenesis of numerous diseases, is a novel target of metformin.	Metformin	148-157	transforming growth factor beta 1	Homo sapiens	55-64
27349853-4	2016	Using a surface plasmon resonance-based assay, we identified the direct binding of metformin to TGF-beta1 and found that metformin inhibits [(125)I]-TGF-beta1 binding to its receptor.	Metformin	83-92	transforming growth factor beta 1	Homo sapiens	96-105
27349853-4	2016	Using a surface plasmon resonance-based assay, we identified the direct binding of metformin to TGF-beta1 and found that metformin inhibits [(125)I]-TGF-beta1 binding to its receptor.	Metformin	83-92	transforming growth factor beta 1	Homo sapiens	149-158
27349853-4	2016	Using a surface plasmon resonance-based assay, we identified the direct binding of metformin to TGF-beta1 and found that metformin inhibits [(125)I]-TGF-beta1 binding to its receptor.	Metformin	121-130	transforming growth factor beta 1	Homo sapiens	149-158
27349853-5	2016	Furthermore, based on molecular docking and molecular dynamics simulations, metformin was predicted to interact with TGF-beta1 at its receptor-binding domain.	Metformin	76-85	transforming growth factor beta 1	Homo sapiens	117-126
27349853-7	2016	Consequently, metformin suppresses type II TGF-beta1 receptor dimerization upon exposure to TGF-beta1, which is essential for downstream signal transduction.	Metformin	14-23	transforming growth factor beta 1	Homo sapiens	43-52
27349853-7	2016	Consequently, metformin suppresses type II TGF-beta1 receptor dimerization upon exposure to TGF-beta1, which is essential for downstream signal transduction.	Metformin	14-23	transforming growth factor beta 1	Homo sapiens	92-101
27349853-8	2016	Thus, our results indicate that metformin is a novel TGF-beta suppressor with therapeutic potential for numerous diseases in which TGF-beta1 hyperfunction is indicated.	Metformin	32-41	transforming growth factor beta 1	Homo sapiens	53-61
27349853-8	2016	Thus, our results indicate that metformin is a novel TGF-beta suppressor with therapeutic potential for numerous diseases in which TGF-beta1 hyperfunction is indicated.	Metformin	32-41	transforming growth factor beta 1	Homo sapiens	131-140
27304904-5	2016	METHODS: Patients with T2DM from the Third Hospital of Hebei Medical University were treated with oral metformin combined with liraglutide (0.6 mg/day, could be increased by 0.6 mg weekly until 1.2 or 1.8 mg) or exenatide (5 mug bid for four weeks, increased to 10 mug bid).	Metformin	103-112	BH3 interacting domain death agonist	Homo sapiens	229-232
27304904-5	2016	METHODS: Patients with T2DM from the Third Hospital of Hebei Medical University were treated with oral metformin combined with liraglutide (0.6 mg/day, could be increased by 0.6 mg weekly until 1.2 or 1.8 mg) or exenatide (5 mug bid for four weeks, increased to 10 mug bid).	Metformin	103-112	BH3 interacting domain death agonist	Homo sapiens	269-272
27019345-4	2016	The models were used to simulate inhibition of the MATE1, MATE2-K, OCT1 and OCT2 mediated transport of metformin by cimetidine.	Metformin	103-112	solute carrier family 22 member 1	Homo sapiens	67-71
27019345-7	2016	An alternative description of metformin renal transport by OCT1 and OCT2, incorporating electrochemical modulation of the rate of metformin uptake together with 8-18-fold decreases in cimetidine Ki"s for OCTs and MATEs, allowed recovery of the extent of the observed effect of cimetidine on metformin AUC.	Metformin	30-39	solute carrier family 22 member 1	Homo sapiens	59-63
27144340-0	2016	Metformin restores crizotinib sensitivity in crizotinib-resistant human lung cancer cells through inhibition of IGF1-R signaling pathway.	Metformin	0-9	insulin like growth factor 1	Homo sapiens	112-116
27144340-6	2016	Furthermore, the addition of IGF-1 to crizotinib-sensitive H2228 cells induced crizotinib resistance, which was overcome by metformin.	Metformin	124-133	insulin like growth factor 1	Homo sapiens	29-34
27145454-11	2016	The impeded cancer progression was due to the inhibitory effect of metformin on STAT3-ERK-vimentin and fibronectin-integrin signaling to decrease tumor cell invasion and de-differentiation.	Metformin	67-76	signal transducer and activator of transcription 3	Mus musculus	80-85
27145454-11	2016	The impeded cancer progression was due to the inhibitory effect of metformin on STAT3-ERK-vimentin and fibronectin-integrin signaling to decrease tumor cell invasion and de-differentiation.	Metformin	67-76	mitogen-activated protein kinase 1	Mus musculus	86-89
27233831-1	2016	Metformin is the basic drug of antihyperglycemic therapy in type 2 diabetes: according to actual therapeutic guidelines, it should be given in the absence of contraindications or intolerance during the whole course of the disease even after the initiation of insulin therapy.	Metformin	0-9	insulin	Homo sapiens	259-266
26990999-10	2016	Metformin lowered p16 and p21 protein levels and the abundance of inflammatory cytokines and oncogenes that are hallmarks of the senescence-associated secretory phenotype (SASP).	Metformin	0-9	cytochrome P450, family 2, subfamily b, polypeptide 10	Mus musculus	18-21
27128732-4	2016	Increased odds ratio of early discontinuation of metformin was only associated with codeine, an inhibitor of organic cation transporter 1 in both cohorts [adjusted odds ratio (OR) in Danish cohort (95% CI): 1.13 (1.02-1.26), adjusted OR in American cohort (95% CI): 1.32 (1.19-1.47)].	Metformin	49-58	solute carrier family 22 member 1	Homo sapiens	109-137
27234585-9	2016	Finally the action of the insulin-sensitizing drugs metformin and the thiazolidinedione rosiglitazone on follicular cells is reviewed.	Metformin	52-61	insulin	Homo sapiens	26-33
27059094-7	2016	The increased gene expressions of TNF-alpha, IL-6, monocyte chemoattractant protein 1 and F4/80 were also down-regulated by metformin and resveratrol.	Metformin	124-133	tumor necrosis factor	Mus musculus	34-43
27328813-0	2016	Metformin promotes cholesterol efflux in macrophages by up-regulating FGF21 expression: a novel anti-atherosclerotic mechanism.	Metformin	0-9	fibroblast growth factor 21	Homo sapiens	70-75
26831122-0	2016	Effects of Metformin and Exercise Training, Alone or in Combination, on Cardiac Function in Individuals with Insulin Resistance.	Metformin	11-20	insulin	Homo sapiens	109-116
26831122-1	2016	INTRODUCTION: In patients affected by insulin resistance (IR), metformin (MET) therapy has been shown to exert its positive effects by improving glucose tolerance and preventing the evolution to diabetes.	Metformin	63-72	insulin	Homo sapiens	38-45
26861811-7	2016	The decision to introduce basal insulin to metformin must, however be individualized based on a risk-benefit analysis.	Metformin	43-52	insulin	Homo sapiens	32-39
26993065-5	2016	Ablation of OCT1 and OCT2 significantly reduced the distribution of metformin in the liver and small intestine.	Metformin	68-77	POU domain, class 2, transcription factor 2	Mus musculus	21-25
27321322-0	2016	Use of metformin earlier in pregnancy predicts supplemental insulin therapy in women with gestational diabetes.	Metformin	7-16	insulin	Homo sapiens	60-67
27321322-2	2016	We found a significant association between earlier gestational age at initiation of metformin therapy and the necessity for supplemental insulin in women treated with metformin during pregnancy.	Metformin	84-93	insulin	Homo sapiens	137-144
27321322-2	2016	We found a significant association between earlier gestational age at initiation of metformin therapy and the necessity for supplemental insulin in women treated with metformin during pregnancy.	Metformin	167-176	insulin	Homo sapiens	137-144
27035653-11	2016	Finally, treatment of INS-1E cells with metformin for 24 h resulted in inhibition of SREBP-1C expression, increased PDX-1 and GLP-1 receptor levels, consequently, enhancement of exendin-4-induced insulin release.	Metformin	40-49	pancreatic and duodenal homeobox 1	Rattus norvegicus	116-121
27228266-12	2016	Orlistat and metformin had similar positive effects on BMI (-0.65%, 95% CI: -2.03 to 0.73), HOMA (-3.60%, 95% CI: -16.99 to 9.78), testosterone (-2.08%, 95% CI: -13.08 to 8.93) and insulin (-5.51%, 95% CI: -22.27 to 11.26).	Metformin	13-22	insulin	Homo sapiens	181-188
27228266-14	2016	In addition, the available evidence indicates that orlistat and metformin have similar effects in reducing BMI, HOMA, testosterone and insulin in overweight/obese PCOS women.	Metformin	64-73	insulin	Homo sapiens	135-142
26992090-0	2016	Identification of metformin poor responders, requiring supplemental insulin, during randomization of metformin versus insulin for the control of gestational diabetes mellitus.	Metformin	18-27	insulin	Homo sapiens	68-75
26992090-0	2016	Identification of metformin poor responders, requiring supplemental insulin, during randomization of metformin versus insulin for the control of gestational diabetes mellitus.	Metformin	18-27	insulin	Homo sapiens	118-125
26992090-5	2016	RESULTS: Women using metformin (23.4% needing supplemental insulin) gained less weight (P &lt; 0.001), and had lower fasting glucose during the first and last 2 weeks of treatment (P = 0.014 and 0.008, respectively) when compared with insulin monotherapy.	Metformin	21-30	insulin	Homo sapiens	59-66
26992090-5	2016	RESULTS: Women using metformin (23.4% needing supplemental insulin) gained less weight (P &lt; 0.001), and had lower fasting glucose during the first and last 2 weeks of treatment (P = 0.014 and 0.008, respectively) when compared with insulin monotherapy.	Metformin	21-30	insulin	Homo sapiens	235-242
26992090-6	2016	Insulin supplementation in the metformin group was related to initial body mass index, HbA1c, oral glucose tolerance test (GTT), and first week mean glucose level.	Metformin	31-40	insulin	Homo sapiens	0-7
26992090-10	2016	Women using metformin (+- supplemental insulin) had similar glycemic control, less weight gain, and similar rates of side-effects as those on insulin monotherapy.	Metformin	12-21	insulin	Homo sapiens	39-46
27262901-2	2016	An anti-diabetic drug, metformin, has been shown to activate AMP-activated protein kinase (AMPK), which leads to inhibition of mTOR.	Metformin	23-32	mechanistic target of rapamycin kinase	Homo sapiens	127-131
27262901-3	2016	LAT1 inhibition in combination with metformin could result in more prominent suppression of mTOR activity.	Metformin	36-45	mechanistic target of rapamycin kinase	Homo sapiens	92-96
27059094-7	2016	The increased gene expressions of TNF-alpha, IL-6, monocyte chemoattractant protein 1 and F4/80 were also down-regulated by metformin and resveratrol.	Metformin	124-133	interleukin 6	Mus musculus	45-49
27082123-6	2016	Consistently, Bax and Bim were upregulated in metformin-treated cells.	Metformin	46-55	BCL2 associated X, apoptosis regulator	Homo sapiens	14-17
27109601-5	2016	We found that metformin inhibited UVC-induced upregulation of p53, as well as downregulated the expression of two DNA damage markers: gammaH2AX and p-chk2.	Metformin	14-23	tumor protein p53	Homo sapiens	62-65
26718214-5	2016	In accordance, type 2 diabetic patients taking metformin displayed a trend of reduction of serum TGF-beta1, as compared with those without metformin.	Metformin	47-56	transforming growth factor beta 1	Homo sapiens	97-106
27371846-6	2016	LP1 promoted the downregulated expression of Bcl-2 and the upregulated expression of Bax induced by metformin, but it didn"t show any impact on the metformin-activated AMPK pathway.	Metformin	100-109	BCL2 associated X, apoptosis regulator	Homo sapiens	85-88
27109601-9	2016	However, resveratrol displayed synergism when combined with metformin as shown by the downregulation of p53/gammaH2AX/p-chk2.	Metformin	60-69	tumor protein p53	Homo sapiens	104-107
27013659-12	2016	Using metformin, an activator of AMPK, we showed that AMPK activation-induced inhibition of hepatic lipid accumulation was accompanied by reduced expression of miR-291b-3p in the liver.	Metformin	6-15	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	33-37
27013659-12	2016	Using metformin, an activator of AMPK, we showed that AMPK activation-induced inhibition of hepatic lipid accumulation was accompanied by reduced expression of miR-291b-3p in the liver.	Metformin	6-15	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	54-58
27158245-10	2016	The effects of high concentrations of WIN on cytokine and MMP-3 production were decreased by the calcium chelating agent BAPTA, the AMPK activator metformin, the TRPA1 antagonist A967079 and the CB2 antagonist COR170.	Metformin	147-156	matrix metallopeptidase 3	Homo sapiens	58-63
26962099-12	2016	We conclude that AMPK activation by metformin mimics many of the mechanisms by which vasopressin increases urine-concentrating ability.	Metformin	36-45	arginine vasopressin	Rattus norvegicus	85-96
27274280-0	2016	Metformin induces apoptosis of human hepatocellular carcinoma HepG2 cells by activating an AMPK/p53/miR-23a/FOXA1 pathway.	Metformin	0-9	tumor protein p53	Homo sapiens	96-99
27274280-5	2016	Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin.	Metformin	115-124	tumor protein p53	Homo sapiens	91-94
27274280-5	2016	Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin.	Metformin	115-124	tumor protein p53	Homo sapiens	158-161
27274280-5	2016	Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin.	Metformin	115-124	tumor protein p53	Homo sapiens	158-161
27274280-5	2016	Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin.	Metformin	200-209	tumor protein p53	Homo sapiens	91-94
27274280-5	2016	Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin.	Metformin	200-209	tumor protein p53	Homo sapiens	158-161
27274280-5	2016	Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin.	Metformin	200-209	tumor protein p53	Homo sapiens	158-161
27274280-5	2016	Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin.	Metformin	200-209	tumor protein p53	Homo sapiens	91-94
27274280-5	2016	Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin.	Metformin	200-209	tumor protein p53	Homo sapiens	158-161
27274280-5	2016	Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin.	Metformin	200-209	tumor protein p53	Homo sapiens	158-161
27274280-6	2016	In summary, we unraveled a novel AMPK/p53/miR-23a/FOXA1 axis in the regulation of apoptosis in HCC, and the application of metformin could, therefore, be effective in the treatment of HCC.	Metformin	123-132	tumor protein p53	Homo sapiens	38-41
27036040-8	2016	In Sawano cells and normal HEEs, a decrease of LSR induced by leptin and an increase of LSR induced by adiponectin and the drugs for type 2 diabetes metformin and berberine were observed via distinct signaling pathways including JAK2/STAT.	Metformin	149-158	adiponectin, C1Q and collagen domain containing	Homo sapiens	103-114
27293994-8	2016	Treating EC with siYAP/TAZ, YAP inhibitor Verteporfin or metformin alone only partially inhibited the function of insulin and IGF1.	Metformin	57-66	insulin	Homo sapiens	114-121
27152598-1	2016	AIMS: To determine if concomitant metformin reduced the risk of death, major adverse cardiac events (MACE), and cancer in people with type 2 diabetes treated with insulin.	Metformin	34-43	insulin	Homo sapiens	163-170
27136447-0	2016	Comparative evaluation of the therapeutic effect of metformin monotherapy with metformin and acupuncture combined therapy on weight loss and insulin sensitivity in diabetic patients.	Metformin	52-61	insulin	Homo sapiens	141-148
27136447-7	2016	CONCLUSIONS: Consequently, Metformin and acupuncture combined therapy is more effective than Metformin only, proving that acupuncture is an insulin sensitizer and is able to improve insulin sensitivity possibly by reducing body weight and inflammation, while improving lipid metabolism and adipokines.	Metformin	27-36	insulin	Homo sapiens	182-189
27293994-8	2016	Treating EC with siYAP/TAZ, YAP inhibitor Verteporfin or metformin alone only partially inhibited the function of insulin and IGF1.	Metformin	57-66	insulin like growth factor 1	Homo sapiens	126-130
27293994-9	2016	However, combination of siYAP/TAZ with metformin could completely inhibit the effects of insulin.	Metformin	39-48	insulin	Homo sapiens	89-96
27014780-2	2016	Metformin inhibits mTOR through different mechanisms and may enhance temsirolimus"s antitumor activity.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	19-23
26858210-0	2016	The effect of metformin on prolactin levels in patients with drug-induced hyperprolactinemia.	Metformin	14-23	prolactin	Homo sapiens	27-36
26858210-1	2016	BACKGROUND: In bromocriptine-treated hyperprolactinemic patients with impaired glucose tolerance, metformin was found to reduce plasma levels of prolactin.	Metformin	98-107	prolactin	Homo sapiens	42-51
26858210-6	2016	RESULTS: Despite reducing plasma glucose, HOMA1-IR, and glycated hemoglobin in all treatment groups, metformin decreased prolactin levels only if given at high doses to patients with elevated prolactin levels.	Metformin	101-110	prolactin	Homo sapiens	121-130
26858210-6	2016	RESULTS: Despite reducing plasma glucose, HOMA1-IR, and glycated hemoglobin in all treatment groups, metformin decreased prolactin levels only if given at high doses to patients with elevated prolactin levels.	Metformin	101-110	prolactin	Homo sapiens	192-201
26858210-8	2016	CONCLUSIONS: The obtained results suggest that the effect of metformin on plasma prolactin depends on its dose and is observed only in patients with elevated levels of this hormone.	Metformin	61-70	prolactin	Homo sapiens	81-90
27168791-8	2016	Moreover, metformin downregulated the expression of the anti-apoptotic proteins B-cell lymphoma 2 (BCL-2) and myeloid cell leukemia-1, and upregulated the expression of the pro-apoptotic BCL-2-associated X protein in MDA-MB-231 cells.	Metformin	10-19	BCL2 apoptosis regulator	Homo sapiens	80-97
26868993-8	2016	After metformin treatment, PDCD4 expression was distinctly down-regulated for the obese women with PCOS with insulin resistance.	Metformin	6-15	insulin	Homo sapiens	109-116
27168791-8	2016	Moreover, metformin downregulated the expression of the anti-apoptotic proteins B-cell lymphoma 2 (BCL-2) and myeloid cell leukemia-1, and upregulated the expression of the pro-apoptotic BCL-2-associated X protein in MDA-MB-231 cells.	Metformin	10-19	BCL2 apoptosis regulator	Homo sapiens	99-104
27168791-8	2016	Moreover, metformin downregulated the expression of the anti-apoptotic proteins B-cell lymphoma 2 (BCL-2) and myeloid cell leukemia-1, and upregulated the expression of the pro-apoptotic BCL-2-associated X protein in MDA-MB-231 cells.	Metformin	10-19	BCL2 apoptosis regulator	Homo sapiens	187-192
27003305-0	2016	Cholecystokinin-Induced Gallbladder Emptying and Metformin Elicit Additive Glucagon-Like Peptide-1 Responses.	Metformin	49-58	glucagon	Homo sapiens	75-98
27003305-2	2016	Metformin, too, has been shown to increase GLP-1 levels.	Metformin	0-9	glucagon	Homo sapiens	43-48
27003305-11	2016	RESULTS: CCK-induced gallbladder emptying and metformin alone (no observed effect on gallbladder emptying) both elicited significant and additive GLP-1 responses.	Metformin	46-55	glucagon	Homo sapiens	146-151
26669511-10	2016	Collectively, these findings establish a clear relationship between cation-selective transporter expression, the AMPK-mTOR-pS6K signaling cascade, and the antiproliferative activity of metformin in breast cancer.	Metformin	185-194	mechanistic target of rapamycin kinase	Homo sapiens	118-122
26941037-0	2016	Metformin improves hepatic IRS2/PI3K/Akt signaling in insulin-resistant rats of NASH and cirrhosis.	Metformin	0-9	insulin receptor substrate 2	Rattus norvegicus	27-31
26941037-0	2016	Metformin improves hepatic IRS2/PI3K/Akt signaling in insulin-resistant rats of NASH and cirrhosis.	Metformin	0-9	AKT serine/threonine kinase 1	Rattus norvegicus	37-40
26941037-10	2016	In conclusion, our study suggests that metformin upregulates IRbeta expression and the downstream IRS2/PI3K/Akt signaling transduction, therefore, to increase hepatic glycogen storage and improve insulin resistance.	Metformin	39-48	insulin receptor substrate 2	Rattus norvegicus	98-102
26941037-10	2016	In conclusion, our study suggests that metformin upregulates IRbeta expression and the downstream IRS2/PI3K/Akt signaling transduction, therefore, to increase hepatic glycogen storage and improve insulin resistance.	Metformin	39-48	AKT serine/threonine kinase 1	Rattus norvegicus	108-111
27003305-13	2016	CCK-induced gallbladder emptying resulted in a short-lasting glucose-dependent insulinotropic polypeptide response independent of metformin.	Metformin	130-139	cholecystokinin	Homo sapiens	0-3
27003305-15	2016	CONCLUSIONS: CCK-induced gallbladder emptying in healthy subjects elicits significant GLP-1 secretion, which can be potentiated by metformin.	Metformin	131-140	cholecystokinin	Homo sapiens	13-16
27003305-15	2016	CONCLUSIONS: CCK-induced gallbladder emptying in healthy subjects elicits significant GLP-1 secretion, which can be potentiated by metformin.	Metformin	131-140	glucagon	Homo sapiens	86-91
27085783-5	2016	RESULTS: After adjusting for BMI, insulin resistance, glycemia, dietary saturated fat, alcohol intake, physical activity and nine different biomarkers, only adiponectin accounted for the effect of intensive lifestyle change on HDL-C via an increase in large HDL-P. By contrast baseline and change in BMI and tissue plasminogen activator levels attenuated the effect of metformin on HDL-C, with adiponectin having no specific effect.	Metformin	369-378	adiponectin, C1Q and collagen domain containing	Homo sapiens	157-168
26993101-5	2016	Metformin did not affect Akt activation but blocked mTOR phosphorylation in response to PDGF; these were accompanied by the reversion of Skp2 up-regulation and p27 reduction.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	52-56
26953870-15	2016	Both metformin and pioglitazone resulted in a significant increase in the number and regulatory functions of CD4+CD25+FoxP3+ regulatory T cells compared with controls (metformin, 6.7 [1.5] vs 2.1 [1.0], P = .001; pioglitazone, 6.9 [0.8] vs 3.0 [0.8], P = .001).	Metformin	5-14	CD4 molecule	Homo sapiens	109-112
26953870-15	2016	Both metformin and pioglitazone resulted in a significant increase in the number and regulatory functions of CD4+CD25+FoxP3+ regulatory T cells compared with controls (metformin, 6.7 [1.5] vs 2.1 [1.0], P = .001; pioglitazone, 6.9 [0.8] vs 3.0 [0.8], P = .001).	Metformin	168-177	CD4 molecule	Homo sapiens	109-112
26986571-0	2016	Anticancer effect of metformin on estrogen receptor-positive and tamoxifen-resistant breast cancer cell lines.	Metformin	21-30	estrogen receptor 1	Homo sapiens	34-51
26986571-4	2016	The objective of the present study was to investigate the anticancer activity of metformin in relation to ERalpha expression and its signaling pathway in ERalpha-positive MCF-7 and MDA-MB-361 breast cancer cells as well as TR MCF-7 breast cancer cells.	Metformin	81-90	estrogen receptor 1	Homo sapiens	106-113
26986571-4	2016	The objective of the present study was to investigate the anticancer activity of metformin in relation to ERalpha expression and its signaling pathway in ERalpha-positive MCF-7 and MDA-MB-361 breast cancer cells as well as TR MCF-7 breast cancer cells.	Metformin	81-90	estrogen receptor 1	Homo sapiens	154-161
26986571-5	2016	Metformin inhibited both protein and mRNA levels of ERalpha in the presence or absence of estrogen (E2) in the MCF-7, TR MCF-7 and MDA-MB-361 cells.	Metformin	0-9	estrogen receptor 1	Homo sapiens	52-59
26986571-6	2016	Metformin repressed E2-inducible estrogen response element (ERE) luciferase activity, protein levels and mRNA levels of E2/ERalpha-regulated genes [including c-Myc, cyclin D1, progesterone receptor (PR) and pS2] to a greater degree than tamoxifen, resulting in inhibition of cell proliferation of MCF-7, TR MCF-7 and MDA-MB-361 cells.	Metformin	0-9	estrogen receptor 1	Homo sapiens	123-130
26986571-6	2016	Metformin repressed E2-inducible estrogen response element (ERE) luciferase activity, protein levels and mRNA levels of E2/ERalpha-regulated genes [including c-Myc, cyclin D1, progesterone receptor (PR) and pS2] to a greater degree than tamoxifen, resulting in inhibition of cell proliferation of MCF-7, TR MCF-7 and MDA-MB-361 cells.	Metformin	0-9	trefoil factor 1	Homo sapiens	207-210
26986571-7	2016	Collectively, our results suggest that one of the anticancer mechanisms of metformin could be attributable to the repression of expression and transcriptional activity of ERalpha.	Metformin	75-84	estrogen receptor 1	Homo sapiens	171-178
26986571-8	2016	Metformin may be a good therapeutic agent for treating ERalpha-positive breast cancer by inhibiting the expression and function of ERalpha.	Metformin	0-9	estrogen receptor 1	Homo sapiens	55-62
26986571-8	2016	Metformin may be a good therapeutic agent for treating ERalpha-positive breast cancer by inhibiting the expression and function of ERalpha.	Metformin	0-9	estrogen receptor 1	Homo sapiens	131-138
26993101-5	2016	Metformin did not affect Akt activation but blocked mTOR phosphorylation in response to PDGF; these were accompanied by the reversion of Skp2 up-regulation and p27 reduction.	Metformin	0-9	dynactin subunit 6	Homo sapiens	160-163
26605869-3	2016	We have recently shown the association between organic cation transporter 1 (OCT1) variants and severe intolerance to metformin in people with Type 2 diabetes.	Metformin	118-127	solute carrier family 22 member 1	Homo sapiens	47-75
27182828-1	2016	IMPORTANCE: Metformin, an oral antihyperglycemic drug, acts as an insulin sensitizer in the treatment of type 2 diabetes mellitus.	Metformin	12-21	insulin	Homo sapiens	66-73
26917452-1	2016	Metformin, an insulin sensitiser from the biguanide family of molecules, is used for the treatment of insulin resistance in type 2 diabetes individuals.	Metformin	0-9	insulin	Gallus gallus	14-21
26917452-1	2016	Metformin, an insulin sensitiser from the biguanide family of molecules, is used for the treatment of insulin resistance in type 2 diabetes individuals.	Metformin	0-9	insulin	Gallus gallus	102-109
27499787-0	2016	Inhibition of P-glycoprotein expression and function by anti-diabetic drugs gliclazide, metformin, and pioglitazone in vitro and in situ.	Metformin	88-97	ATP binding cassette subfamily B member 1	Homo sapiens	14-28
27499787-5	2016	This study investigated the effects of gliclazide, metformin, and pioglitazone on the function and expression of P-gp.	Metformin	51-60	ATP binding cassette subfamily B member 1	Homo sapiens	113-117
27499787-11	2016	P-gp expression was decreased by gliclazide, metformin and pioglitazone.	Metformin	45-54	ATP binding cassette subfamily B member 1	Homo sapiens	0-4
27499787-13	2016	It was found that gliclazide, metformin, and pioglitazone inhibited P-gp efflux activity in situ and down-regulated P-gp expression in vitro.	Metformin	30-39	ATP binding cassette subfamily B member 1	Homo sapiens	68-72
27499787-13	2016	It was found that gliclazide, metformin, and pioglitazone inhibited P-gp efflux activity in situ and down-regulated P-gp expression in vitro.	Metformin	30-39	ATP binding cassette subfamily B member 1	Homo sapiens	116-120
26581908-0	2016	Anti-cancer effect of metformin by suppressing signaling pathway of HER2 and HER3 in tamoxifen-resistant breast cancer cells.	Metformin	22-31	erb-b2 receptor tyrosine kinase 2	Homo sapiens	68-72
26581908-4	2016	Since HER2/HER3 heterodimers are able to induce strong downstream signaling and activate various biological responses such as cellular proliferation and growth, we investigated the anti-cancer effect of metformin by inhibition of signaling pathway via downregulation of HER2 and HER3 using tamoxifen-resistant MCF-7 (TR MCF-7) cells.	Metformin	203-212	erb-b2 receptor tyrosine kinase 2	Homo sapiens	270-274
26581908-6	2016	Metformin inhibited activation of HER2 (Tyr1248)/HER3 (Tyr1289)/Akt (Ser473) as well as cell proliferation and colony formation by estrogenic promotion in MCF-7 and TR MCF-7 cells.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	34-38
26581908-6	2016	Metformin inhibited activation of HER2 (Tyr1248)/HER3 (Tyr1289)/Akt (Ser473) as well as cell proliferation and colony formation by estrogenic promotion in MCF-7 and TR MCF-7 cells.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	64-67
26581908-7	2016	Known as a HER3 ligand, heregulin (HRG)-beta1-induced phosphorylation of HER2, HER3 and Akt, and protein interaction of HER2/HER3 and colony formation were inhibited by metformin in both cells.	Metformin	169-178	erb-b2 receptor tyrosine kinase 2	Homo sapiens	73-77
26581908-7	2016	Known as a HER3 ligand, heregulin (HRG)-beta1-induced phosphorylation of HER2, HER3 and Akt, and protein interaction of HER2/HER3 and colony formation were inhibited by metformin in both cells.	Metformin	169-178	erb-b2 receptor tyrosine kinase 2	Homo sapiens	120-124
26581908-8	2016	Consistent with the results in the two cell lines, we identified that metformin inhibited HER2/HER3/Akt signaling axis activated by HRG-beta1 using the HER2 and HER3-overexpressing breast cancer cell line SK-BR-3.	Metformin	70-79	erb-b2 receptor tyrosine kinase 2	Homo sapiens	90-94
26581908-8	2016	Consistent with the results in the two cell lines, we identified that metformin inhibited HER2/HER3/Akt signaling axis activated by HRG-beta1 using the HER2 and HER3-overexpressing breast cancer cell line SK-BR-3.	Metformin	70-79	AKT serine/threonine kinase 1	Homo sapiens	100-103
26581908-8	2016	Consistent with the results in the two cell lines, we identified that metformin inhibited HER2/HER3/Akt signaling axis activated by HRG-beta1 using the HER2 and HER3-overexpressing breast cancer cell line SK-BR-3.	Metformin	70-79	erb-b2 receptor tyrosine kinase 2	Homo sapiens	152-156
26581908-10	2016	These data suggest that metformin might overcome tamoxifen resistance through the inhibition of expression and signaling of receptor tyrosine kinase HER2 and HER3.	Metformin	24-33	erb-b2 receptor tyrosine kinase 2	Homo sapiens	149-153
27080466-13	2016	However, metformin decreased the viability of AR-expressing PCa cells.	Metformin	9-18	androgen receptor	Homo sapiens	46-48
27080466-15	2016	Moreover, the growth suppressing effects of metformin on PCa may be via the regulation of the AR signaling pathway.	Metformin	44-53	androgen receptor	Homo sapiens	94-96
26992204-0	2016	Activation of autophagy flux by metformin downregulates cellular FLICE-like inhibitory protein and enhances TRAIL- induced apoptosis.	Metformin	32-41	TNF superfamily member 10	Homo sapiens	108-113
26992204-4	2016	In this study, we demonstrated that metformin could induce TRAIL-mediated apoptotic cell death in TRAIL-resistant human lung adenocarcinoma A549 cells.	Metformin	36-45	TNF superfamily member 10	Homo sapiens	59-64
26992204-4	2016	In this study, we demonstrated that metformin could induce TRAIL-mediated apoptotic cell death in TRAIL-resistant human lung adenocarcinoma A549 cells.	Metformin	36-45	TNF superfamily member 10	Homo sapiens	98-103
26992204-7	2016	Inhibition of autophagy flux using a specific inhibitor and genetically modified ATG5 siRNA blocked the metformin-mediated enhancing effect of TRAIL.	Metformin	104-113	autophagy related 5	Homo sapiens	81-85
26992204-7	2016	Inhibition of autophagy flux using a specific inhibitor and genetically modified ATG5 siRNA blocked the metformin-mediated enhancing effect of TRAIL.	Metformin	104-113	TNF superfamily member 10	Homo sapiens	143-148
26992204-8	2016	These data demonstrated that downregulation of c-FLIP by metformin enhanced TRAIL-induced tumor cell death via activating autophagy flux in TRAIL-resistant lung cancer cells and also suggest that metformin may be a successful combination therapeutic strategy with TRAIL in TRAIL-resistant cancer cells including lung adenocarcinoma cells.	Metformin	57-66	CASP8 and FADD like apoptosis regulator	Homo sapiens	47-53
26992204-8	2016	These data demonstrated that downregulation of c-FLIP by metformin enhanced TRAIL-induced tumor cell death via activating autophagy flux in TRAIL-resistant lung cancer cells and also suggest that metformin may be a successful combination therapeutic strategy with TRAIL in TRAIL-resistant cancer cells including lung adenocarcinoma cells.	Metformin	57-66	TNF superfamily member 10	Homo sapiens	76-81
26992204-8	2016	These data demonstrated that downregulation of c-FLIP by metformin enhanced TRAIL-induced tumor cell death via activating autophagy flux in TRAIL-resistant lung cancer cells and also suggest that metformin may be a successful combination therapeutic strategy with TRAIL in TRAIL-resistant cancer cells including lung adenocarcinoma cells.	Metformin	57-66	TNF superfamily member 10	Homo sapiens	140-145
26992204-8	2016	These data demonstrated that downregulation of c-FLIP by metformin enhanced TRAIL-induced tumor cell death via activating autophagy flux in TRAIL-resistant lung cancer cells and also suggest that metformin may be a successful combination therapeutic strategy with TRAIL in TRAIL-resistant cancer cells including lung adenocarcinoma cells.	Metformin	57-66	TNF superfamily member 10	Homo sapiens	140-145
26992204-8	2016	These data demonstrated that downregulation of c-FLIP by metformin enhanced TRAIL-induced tumor cell death via activating autophagy flux in TRAIL-resistant lung cancer cells and also suggest that metformin may be a successful combination therapeutic strategy with TRAIL in TRAIL-resistant cancer cells including lung adenocarcinoma cells.	Metformin	57-66	TNF superfamily member 10	Homo sapiens	140-145
26992204-8	2016	These data demonstrated that downregulation of c-FLIP by metformin enhanced TRAIL-induced tumor cell death via activating autophagy flux in TRAIL-resistant lung cancer cells and also suggest that metformin may be a successful combination therapeutic strategy with TRAIL in TRAIL-resistant cancer cells including lung adenocarcinoma cells.	Metformin	196-205	CASP8 and FADD like apoptosis regulator	Homo sapiens	47-53
26992204-8	2016	These data demonstrated that downregulation of c-FLIP by metformin enhanced TRAIL-induced tumor cell death via activating autophagy flux in TRAIL-resistant lung cancer cells and also suggest that metformin may be a successful combination therapeutic strategy with TRAIL in TRAIL-resistant cancer cells including lung adenocarcinoma cells.	Metformin	196-205	TNF superfamily member 10	Homo sapiens	76-81
26992204-8	2016	These data demonstrated that downregulation of c-FLIP by metformin enhanced TRAIL-induced tumor cell death via activating autophagy flux in TRAIL-resistant lung cancer cells and also suggest that metformin may be a successful combination therapeutic strategy with TRAIL in TRAIL-resistant cancer cells including lung adenocarcinoma cells.	Metformin	196-205	TNF superfamily member 10	Homo sapiens	140-145
26992204-8	2016	These data demonstrated that downregulation of c-FLIP by metformin enhanced TRAIL-induced tumor cell death via activating autophagy flux in TRAIL-resistant lung cancer cells and also suggest that metformin may be a successful combination therapeutic strategy with TRAIL in TRAIL-resistant cancer cells including lung adenocarcinoma cells.	Metformin	196-205	TNF superfamily member 10	Homo sapiens	140-145
26992204-8	2016	These data demonstrated that downregulation of c-FLIP by metformin enhanced TRAIL-induced tumor cell death via activating autophagy flux in TRAIL-resistant lung cancer cells and also suggest that metformin may be a successful combination therapeutic strategy with TRAIL in TRAIL-resistant cancer cells including lung adenocarcinoma cells.	Metformin	196-205	TNF superfamily member 10	Homo sapiens	140-145
26824324-0	2016	Metformin inhibits 17beta-estradiol-induced epithelial-to-mesenchymal transition via betaKlotho-related ERK1/2 signaling and AMPKalpha signaling in endometrial adenocarcinoma cells.	Metformin	0-9	mitogen-activated protein kinase 3	Homo sapiens	104-110
26824324-5	2016	In addition, metformin increased the expression of betaKlotho, a fibroblast growth factors (FGFs) coreceptor, and decreased ERK1/2 phosphorylation in both Ishikawa and KLE cells.	Metformin	13-22	mitogen-activated protein kinase 3	Homo sapiens	124-130
26824324-9	2016	In conclusion, metformin abolishes 17beta-estradiol-induced cell proliferation and EMT in endometrial adenocarcinoma cells by upregulating betaKlotho expression, inhibiting ERK1/2 signaling, and activating AMPKalpha signaling.	Metformin	15-24	mitogen-activated protein kinase 3	Homo sapiens	173-179
26945512-0	2016	Metformin administration induces hepatotoxic effects in paraoxonase-1-deficient mice.	Metformin	0-9	paraoxonase 1	Mus musculus	56-69
26811361-4	2016	Metformin initiators who intensified treatment with insulin or sulfonylurea were followed to either their first or recurrent hypoglycemia event using Cox proportional hazard models.	Metformin	0-9	insulin	Homo sapiens	52-59
26811361-13	2016	INTERPRETATION: Among patients using metformin who could use either insulin or sulfonylurea, the addition of insulin was associated with a higher risk of hypoglycemia than the addition of sulfonylurea.	Metformin	37-46	insulin	Homo sapiens	68-75
26811361-13	2016	INTERPRETATION: Among patients using metformin who could use either insulin or sulfonylurea, the addition of insulin was associated with a higher risk of hypoglycemia than the addition of sulfonylurea.	Metformin	37-46	insulin	Homo sapiens	109-116
26972495-13	2016	Treatment of cultured skeletal muscle cells with rutaecarpine (20-180 mumol/L) or metformin (20 mumol/L) promoted the phosphorylation of AMPK and ACC2, and increased glucose uptake.	Metformin	82-91	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	137-141
26902691-7	2016	Metformin resulted in a significant reduction of IGF-1, IGF-1: IGFBP-3 molar ratio, insulin, FBG and HOMA-IR.	Metformin	0-9	insulin like growth factor 1	Homo sapiens	49-54
26902691-7	2016	Metformin resulted in a significant reduction of IGF-1, IGF-1: IGFBP-3 molar ratio, insulin, FBG and HOMA-IR.	Metformin	0-9	insulin like growth factor 1	Homo sapiens	56-61
26902691-7	2016	Metformin resulted in a significant reduction of IGF-1, IGF-1: IGFBP-3 molar ratio, insulin, FBG and HOMA-IR.	Metformin	0-9	insulin	Homo sapiens	84-91
26605869-3	2016	We have recently shown the association between organic cation transporter 1 (OCT1) variants and severe intolerance to metformin in people with Type 2 diabetes.	Metformin	118-127	solute carrier family 22 member 1	Homo sapiens	77-81
26605869-4	2016	The aim of this study was to explore the association of OCT1 reduced-function polymorphisms with common metformin-induced gastrointestinal side effects in Type 2 diabetes.	Metformin	104-113	solute carrier family 22 member 1	Homo sapiens	56-60
26605869-9	2016	Interestingly, the number of OCT1 reduced-function alleles was significantly associated with over two-fold higher odds of the common metformin-induced gastrointestinal side effects (odds ratio = 2.31, 95% confidence interval 1.07-5.01, P = 0.034).	Metformin	133-142	solute carrier family 22 member 1	Homo sapiens	29-33
26605869-10	2016	CONCLUSIONS: In conclusion, we showed for the first time the association between OCT1 variants and common metformin-induced gastrointestinal side effects.	Metformin	106-115	solute carrier family 22 member 1	Homo sapiens	81-85
26605869-11	2016	These results confirm recent findings related to the role of OCT1 in severe metformin intolerance, and suggest that high inter-individual variability in mild/moderate and severe gastrointestinal intolerance share a common underlying mechanism.	Metformin	76-85	solute carrier family 22 member 1	Homo sapiens	61-65
27358222-0	2016	Delayed auditory conduction in diabetes: is metformin-induced vitamin B12 deficiency responsible?	Metformin	44-53	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	70-73
27358222-2	2016	A further aim is to assess its association with vitamin B12 deficiency induced by metformin.	Metformin	82-91	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	56-59
25994759-3	2016	RESULTS: Both metformin and ionizing radiation inhibited the expression of ME2, but not ME1, in HNSCC.	Metformin	14-23	malic enzyme 2	Homo sapiens	75-78
26892736-3	2016	Anti-tumor metformin action was found to be mediated, at least in part, via activation of adenosine monophosphate-activated protein kinase (AMPK)-intracellular energy sensor, which inhibits the mammalian target of rapamycin (mTOR) and some other signaling pathways.	Metformin	11-20	mechanistic target of rapamycin kinase	Homo sapiens	194-223
27190787-0	2016	Association Between Serum B12 and Serum Homocysteine Levels in Diabetic Patients on Metformin.	Metformin	84-93	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	26-29
27190787-1	2016	INTRODUCTION: Type-2 Diabetes Mellitus (T2DM) and metformin both can lower serum B12 (s.B12).	Metformin	50-59	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	81-84
27190787-1	2016	INTRODUCTION: Type-2 Diabetes Mellitus (T2DM) and metformin both can lower serum B12 (s.B12).	Metformin	50-59	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	88-91
26892736-3	2016	Anti-tumor metformin action was found to be mediated, at least in part, via activation of adenosine monophosphate-activated protein kinase (AMPK)-intracellular energy sensor, which inhibits the mammalian target of rapamycin (mTOR) and some other signaling pathways.	Metformin	11-20	mechanistic target of rapamycin kinase	Homo sapiens	225-229
26892736-11	2016	Importantly, the acquired resistance to both drugs is based on the constitutive activation of Akt/Snail1/E-cadherin signaling that opens new perspectives to overcome the metformin/tamoxifen resistance of breast cancer.	Metformin	170-179	AKT serine/threonine kinase 1	Homo sapiens	94-97
26892736-11	2016	Importantly, the acquired resistance to both drugs is based on the constitutive activation of Akt/Snail1/E-cadherin signaling that opens new perspectives to overcome the metformin/tamoxifen resistance of breast cancer.	Metformin	170-179	snail family transcriptional repressor 1	Homo sapiens	98-104
26892736-11	2016	Importantly, the acquired resistance to both drugs is based on the constitutive activation of Akt/Snail1/E-cadherin signaling that opens new perspectives to overcome the metformin/tamoxifen resistance of breast cancer.	Metformin	170-179	cadherin 1	Homo sapiens	105-115
27051236-8	2016	AMPK activators, metformin and AICAR, restored the suppressed and mal-localized p130Cas significantly, whereas, compound C, an AMPK inhibitor, further aggravated the changes of p130Cas.	Metformin	17-26	breast cancer anti-estrogen resistance 1	Mus musculus	80-87
27226182-9	2016	Longitudinally, there was a small but significant increase in BMI and a significant increase in high-density lipoprotein-cholesterol in the Insulin Group and a significant increase in the atherogenic index of plasma (AIP) and a trend towards higher triglycerides in the Metformin Group.	Metformin	270-279	insulin	Homo sapiens	140-147
25663310-5	2016	Increased PARP cleavage and increased LC3B-II with ATG5-ATG12 complex suggested the induction of apoptosis and autophagy, respectively, in metformin-treated ovarian cancer cells.	Metformin	139-148	autophagy related 5	Homo sapiens	51-55
27073554-7	2016	Metformin (MET), the first-line drug for treating diabetes, it has been proved that it reduces AKT activation and selectively kills cancer stem cells, but whether it can potentiate the cytotoxicity of TMZ for GSCs remains unknown.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	95-98
26922558-6	2016	RESULTS: In all groups of patients, metformin reduced plasma glucose and triglycerides, serum insulin, glycated hemoglobin as well as HOMA1-IR.	Metformin	36-45	insulin	Homo sapiens	94-101
26922558-8	2016	In patients with untreated amiodarone-induced hypothyroidism, but not in the other groups of patients, metformin reduced serum levels of thyrotropin and this effect correlated weakly with its action on insulin sensitivity.	Metformin	103-112	insulin	Homo sapiens	202-209
27073581-0	2016	The impact of metformin and salinomycin on transforming growth factor beta-induced epithelial-to-mesenchymal transition in non-small cell lung cancer cell lines.	Metformin	14-23	transforming growth factor beta 1	Homo sapiens	43-74
27073581-7	2016	Metformin or salinomycin was added simultaneously with TGFbeta to inhibit TGFbeta-induced EMT.	Metformin	0-9	transforming growth factor beta 1	Homo sapiens	74-81
27073581-11	2016	Simultaneous application of TGFbeta and metformin specifically inhibited EMT and increased E-cadherin expression.	Metformin	40-49	cadherin 1	Homo sapiens	91-101
26561471-0	2016	Mechanism of metformin action in MCF-7 and MDA-MB-231 human breast cancer cells involves oxidative stress generation, DNA damage, and transforming growth factor beta1 induction.	Metformin	13-22	transforming growth factor beta 1	Homo sapiens	134-166
26822064-5	2016	Metformin patients had a significant decrease in serum prolactin level with a mean of 54.6mug/l in the three trials.	Metformin	0-9	prolactin	Homo sapiens	55-64
26822064-9	2016	Our systematic review indicated that adjunctive metformin significantly lowered prolactin level and relieved prolactin-related symptoms in patients with antipsychotic-induced hyperprolactinemia.	Metformin	48-57	prolactin	Homo sapiens	80-89
26822064-9	2016	Our systematic review indicated that adjunctive metformin significantly lowered prolactin level and relieved prolactin-related symptoms in patients with antipsychotic-induced hyperprolactinemia.	Metformin	48-57	prolactin	Homo sapiens	109-118
27009398-0	2016	Metformin stimulates IGFBP-2 gene expression through PPARalpha in diabetic states.	Metformin	0-9	peroxisome proliferator activated receptor alpha	Mus musculus	53-62
27009398-3	2016	In this study, we demonstrate that metformin upregulates Igfbp-2 expression through the AMPK-Sirt1-PPARalpha cascade pathway.	Metformin	35-44	peroxisome proliferator activated receptor alpha	Mus musculus	99-108
27009398-6	2016	Notably, activation of IGF-1 receptor (IGF-1R)-dependent signaling by IGF-1 was inhibited by metformin.	Metformin	93-102	insulin-like growth factor I receptor	Mus musculus	23-37
27009398-6	2016	Notably, activation of IGF-1 receptor (IGF-1R)-dependent signaling by IGF-1 was inhibited by metformin.	Metformin	93-102	insulin-like growth factor I receptor	Mus musculus	39-45
27009398-7	2016	Finally, when compared to untreated type 2 diabetes patients, the metformin-treated diabetic patients showed increased IGFBP-2 levels with diminished serum IGF-1 levels.	Metformin	66-75	insulin like growth factor 1	Homo sapiens	156-161
27009398-8	2016	Taken together, these findings indicate that IGFBP-2 might be a new target of metformin action in diabetes and the metformin-AMPK-Sirt1-PPARalpha-IGFBP-2 network may provide a novel pathway that could be applied to ameliorate metabolic syndromes by controlling IGF-1 bioavailability.	Metformin	78-87	peroxisome proliferator activated receptor alpha	Mus musculus	136-145
27009398-8	2016	Taken together, these findings indicate that IGFBP-2 might be a new target of metformin action in diabetes and the metformin-AMPK-Sirt1-PPARalpha-IGFBP-2 network may provide a novel pathway that could be applied to ameliorate metabolic syndromes by controlling IGF-1 bioavailability.	Metformin	115-124	peroxisome proliferator activated receptor alpha	Mus musculus	136-145
26986624-0	2016	Cardiovascular Protective Effect of Metformin and Telmisartan: Reduction of PARP1 Activity via the AMPK-PARP1 Cascade.	Metformin	36-45	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	99-103
26986624-4	2016	The results showed that metformin and telmisartan, but not glipizide and metoprolol, activated AMPK, which phosphorylated PARP1 Ser-177 in cultured ECs and the vascular wall of rodent models.	Metformin	24-33	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	95-99
26698400-0	2016	Prolonged metformin treatment leads to reduced transcription of Nrf2 and neurotrophic factors without cognitive impairment in older C57BL/6J mice.	Metformin	10-19	nuclear factor, erythroid derived 2, like 2	Mus musculus	64-68
26698400-9	2016	Metformin treatment also decreased expression of the antioxidant pathway regulator, Nrf2.	Metformin	0-9	nuclear factor, erythroid derived 2, like 2	Mus musculus	84-88
26698400-10	2016	The decrease in transcription of neurotrophic factors and Nrf2 with chronic metformin intake, cautions of the possibility that extended metformin use may alter brain biochemistry in a manner that creates a vulnerable brain environment and warrants further investigation.	Metformin	76-85	nuclear factor, erythroid derived 2, like 2	Mus musculus	58-62
26681807-6	2016	Similarly, AMPK activation using genetic manipulation and low-dose metformin treatment protects mouse striatal cells expressing full-length mutant Htt (mHtt), counteracting their vulnerability to stress, with reduction of soluble mHtt levels by metformin and compensation of cytotoxicity by AMPKalpha1.	Metformin	67-76	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	291-301
26963096-2	2016	The underlying mechanisms of such phenomenon is related to the effect of metformin on cell proliferation among which, mTOR, AMPK and other targets have been identified.	Metformin	73-82	mechanistic target of rapamycin kinase	Homo sapiens	118-122
26978596-3	2016	Metformin (MET) was administered to activate AMPK.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	45-49
26963617-12	2016	In the SHR-CRP transgenic strain, we found that metformin treatment decreased circulating levels of inflammatory response marker IL-6, TNFalpha and MCP-1 while levels of human CRP remained unchanged.	Metformin	48-57	interleukin 6	Homo sapiens	129-133
26963617-12	2016	In the SHR-CRP transgenic strain, we found that metformin treatment decreased circulating levels of inflammatory response marker IL-6, TNFalpha and MCP-1 while levels of human CRP remained unchanged.	Metformin	48-57	tumor necrosis factor	Homo sapiens	135-143
26721779-18	2016	Placental conditioned media impaired bradykinin-induced vasodilation; this effect was reversed by metformin.	Metformin	98-107	kininogen 1	Homo sapiens	37-47
26998282-5	2016	Furthermore, treatment with resistin decreased phosphorylation of LKB1 and AMPK, whereas pretreatment with metformin increased phosphorylation of LKB1 and AMPK that is reduced by resistin.	Metformin	107-116	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	155-159
26876755-4	2016	Metformin significantly attenuated neuronal apoptosis in glutamate-treated CGN by reducing cytochrome c releasing, caspase-3 activation and phosphorylation of MAP kinases.	Metformin	0-9	cytochrome c, somatic	Homo sapiens	91-103
26876755-4	2016	Metformin significantly attenuated neuronal apoptosis in glutamate-treated CGN by reducing cytochrome c releasing, caspase-3 activation and phosphorylation of MAP kinases.	Metformin	0-9	caspase 3	Homo sapiens	115-124
26830074-2	2016	We demonstrate statistically significant differences regionally in use of metformin at lower eGFR and increasing reliance upon insulin with/without other medications at low eGFR.	Metformin	74-83	epidermal growth factor receptor	Homo sapiens	93-97
26387747-11	2016	Metformin treatment reduces VEGF-B levels and ameliorates insulin resistance.	Metformin	0-9	insulin	Homo sapiens	58-65
26950284-7	2016	The fasting plasma hs-CRP and FGF-21 levels were significantly decreased in the T2DM group after metformin treatment compared with pretreatment (respectively, 2.56 +- 1.75 mg/L vs. 3.28 +- 1.89 mg/L [P &lt; 0.05] and 232.6 pg/mL [range, 154.3-307.8 pg/mL] vs. 313.9 pg/mL [range, 227.7-474.2 pg/mL] [P &lt; 0.01]).	Metformin	97-106	C-reactive protein	Homo sapiens	22-25
26950284-7	2016	The fasting plasma hs-CRP and FGF-21 levels were significantly decreased in the T2DM group after metformin treatment compared with pretreatment (respectively, 2.56 +- 1.75 mg/L vs. 3.28 +- 1.89 mg/L [P &lt; 0.05] and 232.6 pg/mL [range, 154.3-307.8 pg/mL] vs. 313.9 pg/mL [range, 227.7-474.2 pg/mL] [P &lt; 0.01]).	Metformin	97-106	fibroblast growth factor 21	Homo sapiens	30-36
26950284-8	2016	CONCLUSIONS: In patients with T2DM, the plasma FGF-21 levels are increased but are significantly decreased after metformin treatment.	Metformin	113-122	fibroblast growth factor 21	Homo sapiens	47-53
26950284-9	2016	Metformin may play a role in reducing the FGF-21 levels in patients with T2DM, likely through the amelioration of glucose-lipid metabolism and inflammation.	Metformin	0-9	fibroblast growth factor 21	Homo sapiens	42-48
26700958-6	2016	After incubation of the cells with 5 microM metformin, the intracellular concentrations were 26.4 +- 7.8 muM and 268 +- 11.0 muM, respectively, in HEK-EV and HEK-OCT1.	Metformin	44-53	latexin	Homo sapiens	105-108
26700958-6	2016	After incubation of the cells with 5 microM metformin, the intracellular concentrations were 26.4 +- 7.8 muM and 268 +- 11.0 muM, respectively, in HEK-EV and HEK-OCT1.	Metformin	44-53	latexin	Homo sapiens	125-128
26700958-6	2016	After incubation of the cells with 5 microM metformin, the intracellular concentrations were 26.4 +- 7.8 muM and 268 +- 11.0 muM, respectively, in HEK-EV and HEK-OCT1.	Metformin	44-53	EPH receptor A3	Homo sapiens	147-150
26700958-6	2016	After incubation of the cells with 5 microM metformin, the intracellular concentrations were 26.4 +- 7.8 muM and 268 +- 11.0 muM, respectively, in HEK-EV and HEK-OCT1.	Metformin	44-53	EPH receptor A3	Homo sapiens	158-161
26700958-6	2016	After incubation of the cells with 5 microM metformin, the intracellular concentrations were 26.4 +- 7.8 muM and 268 +- 11.0 muM, respectively, in HEK-EV and HEK-OCT1.	Metformin	44-53	solute carrier family 22 member 1	Homo sapiens	162-166
26700958-7	2016	In addition, intracellular metformin concentrations were lower in high K(+) buffer (140 mM KCl) compared with normal K(+) buffer (5.4 mM KCl) in HEK-OCT1 cells (54.8 +- 3.8 muM and 198.1 +- 11.2 muM, respectively; P &lt; 0.05).	Metformin	27-36	EPH receptor A3	Homo sapiens	145-148
26700958-7	2016	In addition, intracellular metformin concentrations were lower in high K(+) buffer (140 mM KCl) compared with normal K(+) buffer (5.4 mM KCl) in HEK-OCT1 cells (54.8 +- 3.8 muM and 198.1 +- 11.2 muM, respectively; P &lt; 0.05).	Metformin	27-36	solute carrier family 22 member 1	Homo sapiens	149-153
26700958-7	2016	In addition, intracellular metformin concentrations were lower in high K(+) buffer (140 mM KCl) compared with normal K(+) buffer (5.4 mM KCl) in HEK-OCT1 cells (54.8 +- 3.8 muM and 198.1 +- 11.2 muM, respectively; P &lt; 0.05).	Metformin	27-36	latexin	Homo sapiens	173-176
26700958-7	2016	In addition, intracellular metformin concentrations were lower in high K(+) buffer (140 mM KCl) compared with normal K(+) buffer (5.4 mM KCl) in HEK-OCT1 cells (54.8 +- 3.8 muM and 198.1 +- 11.2 muM, respectively; P &lt; 0.05).	Metformin	27-36	latexin	Homo sapiens	195-198
28603691-1	2016	AIMS: Recommendations for metformin use are dependent on eGFR category: eGFR &gt;45 ml/min/1.73 m2 - "first-line agent"; eGFR 30-44 - "use with caution"; eGFR&lt;30 - "do not use".	Metformin	26-35	epidermal growth factor receptor	Homo sapiens	57-61
28603691-1	2016	AIMS: Recommendations for metformin use are dependent on eGFR category: eGFR &gt;45 ml/min/1.73 m2 - "first-line agent"; eGFR 30-44 - "use with caution"; eGFR&lt;30 - "do not use".	Metformin	26-35	epidermal growth factor receptor	Homo sapiens	72-76
28603691-1	2016	AIMS: Recommendations for metformin use are dependent on eGFR category: eGFR &gt;45 ml/min/1.73 m2 - "first-line agent"; eGFR 30-44 - "use with caution"; eGFR&lt;30 - "do not use".	Metformin	26-35	epidermal growth factor receptor	Homo sapiens	72-76
28603691-1	2016	AIMS: Recommendations for metformin use are dependent on eGFR category: eGFR &gt;45 ml/min/1.73 m2 - "first-line agent"; eGFR 30-44 - "use with caution"; eGFR&lt;30 - "do not use".	Metformin	26-35	epidermal growth factor receptor	Homo sapiens	72-76
28603691-4	2016	METHODS: In a consecutive cohort of 550 Veterans with diabetes, metformin use and eligibility were assessed by eGFR category, using eGFRcr and eGFRcys.	Metformin	64-73	epidermal growth factor receptor	Homo sapiens	111-115
28603691-8	2016	Metformin use decreased with severity of eGFRcr category, from 63% in eGFRcr &gt;60 to 3% in eGFRcr &lt;30. eGFRcys reclassified 20% of Veterans into different eGFR categories.	Metformin	0-9	epidermal growth factor receptor	Homo sapiens	41-45
26233336-2	2016	Metformin therapy may reduce vitamin B12 plasma levels, thus contributing to DPN.	Metformin	0-9	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	37-40
26233336-5	2016	Metformin-treated subjects (n = 124, 47 %) showed significantly lower levels of vitamin B12 (P &lt; 0.001), but the prevalence of DPN was not different when compared to those not treated with this drug (33 vs. 27 %, P = NS).	Metformin	0-9	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	88-91
26233336-8	2016	Metformin therapy is associated with a mild vitamin B12 level reduction, but not with DPN.	Metformin	0-9	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	52-55
26743209-3	2016	Metformin improves hyperglycemia mainly through the suppression of hepatic gluconeogenesis along with the improvement of insulin signaling.	Metformin	0-9	insulin	Homo sapiens	121-128
26264935-0	2016	Repurposing of metformin in liver injury: The JNK conundrum.	Metformin	15-24	mitogen-activated protein kinase 8	Homo sapiens	46-49
26551514-0	2016	Reply to "Repurposing of metformin in liver injury: The JNK conundrum".	Metformin	25-34	mitogen-activated protein kinase 8	Homo sapiens	56-59
26874027-0	2016	Metformin-induced protection against oxidative stress is associated with AKT/mTOR restoration in PC12 cells.	Metformin	0-9	AKT serine/threonine kinase 1	Rattus norvegicus	73-76
26874027-2	2016	Pile of concrete evidence imply metformin as an Insulin sensitizer may enhance Akt/mTOR activity however the significance of Akt/mTOR recruitment has not yet been revealed in metformin induced neuroprotection against oxidative stress.	Metformin	32-41	AKT serine/threonine kinase 1	Rattus norvegicus	79-82
26874027-4	2016	Metformin pretreated cells were then subjected to immunoblotting as well as real time PCR to find PI3K, Akt, mTOR and S6K concurrent transcriptional and post-transcriptional changes.	Metformin	0-9	AKT serine/threonine kinase 1	Rattus norvegicus	104-107
26874027-5	2016	The proportions of phosphorylated to non-phosphorylated constituents of PI3K/Akt/mTOR/S6K were determined to address their activation upon metformin treatment.	Metformin	139-148	AKT serine/threonine kinase 1	Rattus norvegicus	77-80
26874027-7	2016	Metformin induced protection concurred with elevated PI3K/Akt/mTOR/S6K activity as well as enhanced GSH levels.	Metformin	0-9	AKT serine/threonine kinase 1	Rattus norvegicus	58-61
26874027-9	2016	SIGNIFICANCE: Taken together our experimentation supports the hypothesis that Akt/mTOR/S6K cascade may contribute to metformin alleviating effect.	Metformin	117-126	AKT serine/threonine kinase 1	Rattus norvegicus	78-81
26874027-10	2016	The present work while highlighting metformin anti-oxidant characteristics, concludes that Akt/mTOR signaling might be central to the drug"s alleviating effects.	Metformin	36-45	AKT serine/threonine kinase 1	Rattus norvegicus	91-94
26835874-0	2016	Trigonella foenum-graecum Seed Extract, 4-Hydroxyisoleucine, and Metformin Stimulate Proximal Insulin Signaling and Increase Expression of Glycogenic Enzymes and GLUT2 in HepG2 Cells.	Metformin	65-74	insulin	Homo sapiens	94-101
26835874-12	2016	CONCLUSIONS: Collectively, these findings provide a mechanism by which FSE exerts antihyperglycemic effects similar to metformin and insulin that occurs via enhanced insulin signaling, gene expression, and increasing glucose uptake.	Metformin	119-128	insulin	Homo sapiens	166-173
25627694-9	2016	4-Phenylbutyric acid and metformin also diminish neurodegeneration (measured in terms of neuronal loss and reactive gliosis) and ameliorate neuropsychological tests of Epm2b-/- mice.	Metformin	25-34	NHL repeat containing 1	Mus musculus	168-173
27038867-20	2016	Insulin sensitizers like metformin, thiazolidines have also resulted in improvements in cognitive functions, mainly in animal experiments.	Metformin	25-34	insulin	Homo sapiens	0-7
26708419-9	2016	In addition, metformin reduced the phosphorylation of epidermal growth factor receptor (EGFR), particularly the phosphorylation of EGFR at Tyr845, and insulin-like growth factor 1 receptor (IGF-1R) in vitro and in vivo.	Metformin	13-22	epidermal growth factor receptor	Homo sapiens	54-86
26708419-9	2016	In addition, metformin reduced the phosphorylation of epidermal growth factor receptor (EGFR), particularly the phosphorylation of EGFR at Tyr845, and insulin-like growth factor 1 receptor (IGF-1R) in vitro and in vivo.	Metformin	13-22	epidermal growth factor receptor	Homo sapiens	88-92
26708419-9	2016	In addition, metformin reduced the phosphorylation of epidermal growth factor receptor (EGFR), particularly the phosphorylation of EGFR at Tyr845, and insulin-like growth factor 1 receptor (IGF-1R) in vitro and in vivo.	Metformin	13-22	epidermal growth factor receptor	Homo sapiens	131-135
26824415-9	2016	In addition, brusatol and metformin overcame progestin resistance by down-regulating Nrf2/AKR1C1 expression.	Metformin	26-35	NFE2 like bZIP transcription factor 2	Homo sapiens	85-89
26930651-7	2016	In ex vivo studies, 100 muM of metformin decreased the TLR4 level by 19.9% (II group) or by 35% (III group) as well as IL-1beta and TNFalpha production.	Metformin	31-40	interleukin 1 beta	Homo sapiens	119-127
26930651-7	2016	In ex vivo studies, 100 muM of metformin decreased the TLR4 level by 19.9% (II group) or by 35% (III group) as well as IL-1beta and TNFalpha production.	Metformin	31-40	tumor necrosis factor	Homo sapiens	132-140
27180669-2	2016	This article deals with the combination therapy comprising metformin and dapagliflozin in a single preparation, molecules affecting different pathophysiological mechanisms of type 2 diabetes, particularly insulin resistance and increased glucose reabsorption in the kidney.	Metformin	59-68	insulin	Homo sapiens	205-212
26792047-5	2016	The proposed mechanism of weight lowering effect of metformin includes changes in hypothalamic physiology, including leptin and insulin sensitivity, as well as circadian rhythm changes affecting food intake, regulation of fat oxidation and storage in liver, skeletal muscle, and adipose tissue.	Metformin	52-61	insulin	Homo sapiens	128-135
26916684-0	2016	Metformin versus placebo in combination with insulin analogues in patients with type 2 diabetes mellitus-the randomised, blinded Copenhagen Insulin and Metformin Therapy (CIMT) trial.	Metformin	0-9	insulin	Homo sapiens	140-147
26921394-6	2016	In addition, we observed that bladder cancer cell lines (RT4, UMUC-3, and J82) with homozygous deletion of either TSC1 or PTEN are more sensitive to metformin than those (TEU2, TCCSUP, and HT1376) with wild-type TSC1 and PTEN genes.	Metformin	149-158	phosphatase and tensin homolog	Mus musculus	122-126
26921394-6	2016	In addition, we observed that bladder cancer cell lines (RT4, UMUC-3, and J82) with homozygous deletion of either TSC1 or PTEN are more sensitive to metformin than those (TEU2, TCCSUP, and HT1376) with wild-type TSC1 and PTEN genes.	Metformin	149-158	phosphatase and tensin homolog	Mus musculus	221-225
26813102-0	2016	SIRT3-AMP-Activated Protein Kinase Activation by Nitrite and Metformin Improves Hyperglycemia and Normalizes Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction.	Metformin	61-70	sirtuin 3	Homo sapiens	0-5
26813102-8	2016	Finally, early treatments with nitrite and metformin at the time of SU5416 injection reduced pulmonary pressures and vascular remodeling in the PH-HFpEF model with robust activation of skeletal muscle SIRT3 and AMP-activated protein kinase.	Metformin	43-52	sirtuin 3	Homo sapiens	201-206
26802022-8	2016	The results demonstrated that metformin activated AMPK and decreased phosphorylation of Akt and Erk.	Metformin	30-39	AKT serine/threonine kinase 1	Homo sapiens	88-91
26802022-8	2016	The results demonstrated that metformin activated AMPK and decreased phosphorylation of Akt and Erk.	Metformin	30-39	mitogen-activated protein kinase 1	Homo sapiens	96-99
26802022-9	2016	Furthermore, combinations of metformin with either Akt or Erk inhibitors synergistically diminished cancer proliferation, suggesting the involvement of Akt- and Erk- related pathways.	Metformin	29-38	AKT serine/threonine kinase 1	Homo sapiens	152-155
26802022-9	2016	Furthermore, combinations of metformin with either Akt or Erk inhibitors synergistically diminished cancer proliferation, suggesting the involvement of Akt- and Erk- related pathways.	Metformin	29-38	mitogen-activated protein kinase 1	Homo sapiens	161-164
26894572-2	2016	Metformin is likely beneficial in obese and/or insulin-resistant children/adolescents, but its role in this setting is still unclear.	Metformin	0-9	insulin	Homo sapiens	47-54
26894572-9	2016	Metformin had greater effectiveness over lifestyle intervention alone in reducing fasting insulin levels and homeostasis model assessment for insulin-resistance index (HOMA-IR) at both 12 and 24 months.	Metformin	0-9	insulin	Homo sapiens	90-97
26916684-7	2016	HbA1c was more reduced in the metformin group (between-group difference -0.42% (95% CI -0.62% to -0.23%), p&lt;0.001)), despite the significantly lower insulin dose at end of trial in the metformin group (1.04 IU/kg (95% CI 0.94 to 1.15)) compared with placebo (1.36 IU/kg (95% CI 1.23 to 1.51), p&lt;0.001).	Metformin	30-39	insulin	Homo sapiens	152-159
27019260-0	2016	The importance of ruling out risk factors for vitamin B12 deficiency induced by metformin in older patients	Metformin	80-89	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	54-57
26878387-5	2016	Although lowering of insulin levels with diet or drugs such as metformin and diazoxide seems generally beneficial, some practitioners also utilize strategic elevations of insulin levels in combination with chemotherapeutic drugs.	Metformin	63-72	insulin	Homo sapiens	21-28
26861446-0	2016	Metformin improves the angiogenic potential of human CD34+ cells co-incident with downregulating CXCL10 and TIMP1 gene expression and increasing VEGFA under hyperglycemia and hypoxia within a therapeutic window for myocardial infarction.	Metformin	0-9	CD34 molecule	Homo sapiens	53-57
26894572-9	2016	Metformin had greater effectiveness over lifestyle intervention alone in reducing fasting insulin levels and homeostasis model assessment for insulin-resistance index (HOMA-IR) at both 12 and 24 months.	Metformin	0-9	insulin	Homo sapiens	142-149
26894572-11	2016	CONCLUSION: Metformin for nondiabetic obese/overweight children and adolescents resulted in a noteworthy insulin resistance improvement, without significant BMI advantage when compared to lifestyle intervention.	Metformin	12-21	insulin	Homo sapiens	105-112
26896068-9	2016	Moreover, metformin enhanced the anti-inflammatory effect of 5-ASA by decreasing the gene expression of IL-1beta, IL-6, COX-2 and TNF-alpha and its receptors; TNF-R1 and TNF-R2.	Metformin	10-19	interleukin 1 beta	Homo sapiens	104-112
26896068-9	2016	Moreover, metformin enhanced the anti-inflammatory effect of 5-ASA by decreasing the gene expression of IL-1beta, IL-6, COX-2 and TNF-alpha and its receptors; TNF-R1 and TNF-R2.	Metformin	10-19	interleukin 6	Homo sapiens	114-118
26896068-9	2016	Moreover, metformin enhanced the anti-inflammatory effect of 5-ASA by decreasing the gene expression of IL-1beta, IL-6, COX-2 and TNF-alpha and its receptors; TNF-R1 and TNF-R2.	Metformin	10-19	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	120-125
26896068-9	2016	Moreover, metformin enhanced the anti-inflammatory effect of 5-ASA by decreasing the gene expression of IL-1beta, IL-6, COX-2 and TNF-alpha and its receptors; TNF-R1 and TNF-R2.	Metformin	10-19	tumor necrosis factor	Homo sapiens	130-139
29931872-3	2016	RESULTS: Compared with that in the model group, SOD and GPX activities were significantly increased and levels of BNP cTnI cardiac weight index (CWI) apoptosis index (AI) were decreased in TTM and metformin (Met) group.	Metformin	197-206	natriuretic peptide B	Rattus norvegicus	114-117
26861446-0	2016	Metformin improves the angiogenic potential of human CD34+ cells co-incident with downregulating CXCL10 and TIMP1 gene expression and increasing VEGFA under hyperglycemia and hypoxia within a therapeutic window for myocardial infarction.	Metformin	0-9	TIMP metallopeptidase inhibitor 1	Homo sapiens	108-113
26861446-0	2016	Metformin improves the angiogenic potential of human CD34+ cells co-incident with downregulating CXCL10 and TIMP1 gene expression and increasing VEGFA under hyperglycemia and hypoxia within a therapeutic window for myocardial infarction.	Metformin	0-9	vascular endothelial growth factor A	Homo sapiens	145-150
26861446-5	2016	The aim of this study was to investigate the effect of metformin on the angiogenic properties of CD34(+) cells under conditions mimicking acute myocardial infarction in diabetes.	Metformin	55-64	CD34 molecule	Homo sapiens	97-101
26861446-6	2016	METHODS: CD34(+) cells were cultured in 5.5 or 16.5 mmol/L glucose +- 0.01 mmol/L metformin and then additionally +- 4 % hypoxia.	Metformin	82-91	CD34 molecule	Homo sapiens	9-13
26861446-9	2016	RESULTS: Metformin increased in vitro angiogenesis under hyperglycemia-hypoxia and augmented the expression of VEGFA.	Metformin	9-18	vascular endothelial growth factor A	Homo sapiens	111-116
26861446-12	2016	CONCLUSIONS: Metformin has a dual effect by simultaneously increasing VEGFA and reducing CXCL10 and TIMP1 in CD34(+) cells in a model of the diabetic state combined with hypoxia.	Metformin	13-22	vascular endothelial growth factor A	Homo sapiens	70-75
26861446-12	2016	CONCLUSIONS: Metformin has a dual effect by simultaneously increasing VEGFA and reducing CXCL10 and TIMP1 in CD34(+) cells in a model of the diabetic state combined with hypoxia.	Metformin	13-22	TIMP metallopeptidase inhibitor 1	Homo sapiens	100-105
26861446-12	2016	CONCLUSIONS: Metformin has a dual effect by simultaneously increasing VEGFA and reducing CXCL10 and TIMP1 in CD34(+) cells in a model of the diabetic state combined with hypoxia.	Metformin	13-22	CD34 molecule	Homo sapiens	109-113
26708162-6	2016	In the animals treated with metformin, the preservation of left ventricular function was associated with the reduction of myeloperoxidase activity (31%, P&lt;0.01) in the heart and decrease of TNF-alpha level both in the serum and heart tissue (20%, P&lt;0.01 and 42%, P&lt;0.05, respectively).	Metformin	28-37	tumor necrosis factor	Rattus norvegicus	193-202
26708162-0	2016	Cardioprotective effect of metformin in lipopolysaccharide-induced sepsis via suppression of toll-like receptor 4 (TLR4) in heart.	Metformin	27-36	toll-like receptor 4	Rattus norvegicus	93-113
26708162-0	2016	Cardioprotective effect of metformin in lipopolysaccharide-induced sepsis via suppression of toll-like receptor 4 (TLR4) in heart.	Metformin	27-36	toll-like receptor 4	Rattus norvegicus	115-119
26708162-7	2016	It was found that the level of phosphorylated AMPK in heart was significantly upregulated by 43% (P&lt;0.001) in the metformin group while the content of TLRs adapter protein of MyD88 was reduced by 45% (P&lt;0.05).	Metformin	117-126	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	46-50
26708162-9	2016	Furthermore, in a mice model of sepsis, coadministration of compound C (20mg/kg) as an AMPK inhibitor reversed the suppressive effects of metformin on TLR4 expression and MYD88 protein level.	Metformin	138-147	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	87-91
26708162-9	2016	Furthermore, in a mice model of sepsis, coadministration of compound C (20mg/kg) as an AMPK inhibitor reversed the suppressive effects of metformin on TLR4 expression and MYD88 protein level.	Metformin	138-147	toll-like receptor 4	Mus musculus	151-155
26708162-10	2016	These results suggest that metformin exhibits cardioprotective effects in sepsis by suppression of TLR4 activity, at least in part through pathways involving AMPK activation.	Metformin	27-36	toll-like receptor 4	Rattus norvegicus	99-103
26708162-10	2016	These results suggest that metformin exhibits cardioprotective effects in sepsis by suppression of TLR4 activity, at least in part through pathways involving AMPK activation.	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	158-162
26712380-0	2016	Influence of metformin on mitochondrial subproteome in the brain of apoE knockout mice.	Metformin	13-22	apolipoprotein E	Mus musculus	68-72
26712380-5	2016	The quantitative assessment of the brain mitoproteome in apoE(-/-) revealed the changes in 10 proteins expression as compared to healthy C57BL/6J mice and 25 proteins expression in metformin-treated apoE(-/-) mice.	Metformin	181-190	apolipoprotein E	Mus musculus	199-203
26794276-1	2016	BACKGROUND: Preclinical studies in endometrial cancer (EC) show that metformin reduces cellular proliferation by PI3K-AKT-mTOR inhibition.	Metformin	69-78	mechanistic target of rapamycin kinase	Homo sapiens	122-126
26717043-7	2016	Fourth, metformin increased the abundance of miR-15a, miR-128, miR-192, and miR-194, which was prevented by knockdown of LITAF.	Metformin	8-17	microRNA 192	Homo sapiens	63-70
26717043-7	2016	Fourth, metformin increased the abundance of miR-15a, miR-128, miR-192, and miR-194, which was prevented by knockdown of LITAF.	Metformin	8-17	lipopolysaccharide induced TNF factor	Homo sapiens	121-126
25916213-8	2016	They also showed that, among diabetics, the risk of developing HR+/HER2- tumors decreased with longer metformin use (ORper year 0.89; 95 % CI 0.81-0.99; based on 24 cases and 43 controls).	Metformin	102-111	erb-b2 receptor tyrosine kinase 2	Homo sapiens	67-71
26841718-6	2016	Notably, kinases, particularly SGK1 and EGFR were identified as key molecular targets of metformin.	Metformin	89-98	epidermal growth factor receptor	Homo sapiens	40-44
26956973-3	2016	p53 wild-type and p53 mutant breast cancer cells were treated with metformin, and expression of TTP and c-Myc was analyzed by semi-quantitative RT-PCR, Western blots, and promoter activity assay.	Metformin	67-76	tumor protein p53	Homo sapiens	0-3
26956973-5	2016	Metformin induces the expression of tristetraprolin (TTP) in breast cancer cells in a p53-independent manner.	Metformin	0-9	tumor protein p53	Homo sapiens	86-89
26740120-5	2016	Metformin influences various cellular pathways, including activation of the LKB1/AMPK pathway, inhibition of cell division, promotion of apoptosis and autophagy, down-regulation of circulating insulin, and activation of the immune system.	Metformin	0-9	insulin	Homo sapiens	193-200
26179926-7	2016	The expression of IRS-1 as well as PI3Kp85alpha were significantly decreased in the model group compared with the normal control group at both mRNA (P&lt;0.001) and protein (P&lt;0.01) level, and both high-dose SJD and DMBG can enhance IRS-1 and PI3K expression (P&lt;0.05).	Metformin	219-223	insulin receptor substrate 1	Rattus norvegicus	18-23
26525880-0	2016	Lifestyle and Metformin Ameliorate Insulin Sensitivity Independently of the Genetic Burden of Established Insulin Resistance Variants in Diabetes Prevention Program Participants.	Metformin	14-23	insulin	Homo sapiens	35-42
26636185-0	2016	Metformin Protects Kidney Cells From Insulin-Mediated Genotoxicity In Vitro and in Male Zucker Diabetic Fatty Rats.	Metformin	0-9	insulin	Homo sapiens	37-44
26381272-8	2016	Evidence from RCTs and observational studies suggested that greater hepatic fat content reduction and improved liver histology were seen in thiazolidinediones for 12-72 weeks; glucagon-like peptide-1 receptor agonists had beneficial effects on hepatic fat content after 26-50 weeks intervention, and insulin/metformin combination with 3-7 months improved hepatic fat content.	Metformin	308-317	glucagon	Homo sapiens	176-199
26636185-2	2016	A possible mechanism is induction of oxidative stress and DNA damage by insulin, Here, the effect of a combination of metformin with insulin was investigated in vitro and in vivo.	Metformin	118-127	insulin	Homo sapiens	72-79
26636185-3	2016	The rationales for this were the reported antioxidative properties of metformin and the aim to gain further insights into the mechanisms responsible for protecting the genome from insulin-mediated oxidative stress and damage.	Metformin	70-79	insulin	Homo sapiens	180-187
26636185-9	2016	Metformin did not show intrinsic antioxidant activity in the cell-free assay, but protected cultured cells from insulin-mediated oxidative stress, DNA damage, and mutation.	Metformin	0-9	insulin	Homo sapiens	112-119
26636185-11	2016	Metformin may protect patients from genomic damage induced by elevated insulin levels.	Metformin	0-9	insulin	Homo sapiens	71-78
26808583-0	2016	Relationship of Serum Adiponectin Levels and Metformin Therapy in Patients with Type 2 Diabetes.	Metformin	45-54	adiponectin, C1Q and collagen domain containing	Homo sapiens	22-33
26808583-1	2016	We performed this meta-analysis to investigate and determine the role of metformin on serum adiponectin levels in Type 2 diabetes (T2DM) patients.	Metformin	73-82	adiponectin, C1Q and collagen domain containing	Homo sapiens	92-103
26808583-3	2016	Eligible human studies assessing the association between serum adiponectin levels and metformin in patients were included, and data were extracted and then analyzed with STATA 12.0 statistical software.	Metformin	86-95	adiponectin, C1Q and collagen domain containing	Homo sapiens	63-74
26808583-6	2016	Country-subgroup analysis showed that serum adiponectin levels in T2DM patients increased after the treatment of metformin in Italy (SMD=0.34, 95% CI=0.09-0.59, p=0.008).	Metformin	113-122	adiponectin, C1Q and collagen domain containing	Homo sapiens	44-55
26808583-7	2016	Further detection method and follow-up time subgroup analyses implied a positive association of metformin with serum adiponectin level in T2DM patients by using all ELISA, PETIA, and RIA in both&lt;12 weeks and&gt;=12 weeks subgroups (all p&lt;0.05).	Metformin	96-105	adiponectin, C1Q and collagen domain containing	Homo sapiens	117-128
26808583-8	2016	The present meta-analysis provides compelling evidence that metformin may increase serum adiponectin levels when treating T2DM.	Metformin	60-69	adiponectin, C1Q and collagen domain containing	Homo sapiens	89-100
26588235-2	2016	Metformin is used in type II diabetes to lower circulating insulin levels.	Metformin	0-9	insulin	Homo sapiens	59-66
26373430-6	2016	When AMPK was activated by AICAR, A769662 and metformin, FcepsilonRI-mediated Syk, ERK, JNK and p38 activation, and TNFalpha release were all inhibited.	Metformin	46-55	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	5-9
26373430-10	2016	In vivo, AMPK activation by metformin could readily reduce vascular permeability and ear swelling in a mouse model of passive cutaneous anaphylaxis mediated by IgE.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	9-13
26582729-4	2016	In this study, we investigated the molecular crosstalk between miR-34a, the protein product of SIRT1 (sirtuin1), and the antidiabetic drug, metformin, in hyperglycemia-mediated impaired angiogenesis in mouse microvascular endothelial cells (MMECs).	Metformin	140-149	microRNA 34a	Mus musculus	63-70
26582729-9	2016	In contrast, overexpression of a miR-34a mimic prevents metformin-mediated protection.	Metformin	56-65	microRNA 34a	Mus musculus	33-40
26582729-10	2016	These data indicate that miR-34a, via the regulation of sirtuin1 expression, has an anti-angiogenic action in MMECs, which can be modulated by metformin.	Metformin	143-152	microRNA 34a	Mus musculus	25-32
26582729-11	2016	In summary, miR-34a represents both a target whereby metformin mediates its vasculoprotective actions and also a potential therapeutic target for the prevention/treatment of diabetic vascular disease.	Metformin	53-62	microRNA 34a	Mus musculus	12-19
26983336-1	2016	For several years there is an evidence for a relationship between the polycystic ovary syndrome (PCOS) and of insulin resistance; therefore metformin, an insulin sensitizer, is used for the treatment for more than 10 years.	Metformin	140-149	insulin	Homo sapiens	110-117
26983336-1	2016	For several years there is an evidence for a relationship between the polycystic ovary syndrome (PCOS) and of insulin resistance; therefore metformin, an insulin sensitizer, is used for the treatment for more than 10 years.	Metformin	140-149	insulin	Homo sapiens	154-161
26845410-0	2016	Corrigendum: Metformin activates a duodenal Ampk-dependent pathway to lower hepatic glucose production in rats.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	44-48
26211973-4	2016	Chronic treatment of db/db mice with antidiabetic drugs such as metformin, glibenclamide and insulin glargine significantly decreased Abeta influx across the BBB determined by intra-arterial infusion of (125)I-Abeta(1-40), and expression of the receptor for advanced glycation end products (RAGE) participating in Abeta influx.	Metformin	64-73	advanced glycosylation end product-specific receptor	Mus musculus	245-289
26211973-4	2016	Chronic treatment of db/db mice with antidiabetic drugs such as metformin, glibenclamide and insulin glargine significantly decreased Abeta influx across the BBB determined by intra-arterial infusion of (125)I-Abeta(1-40), and expression of the receptor for advanced glycation end products (RAGE) participating in Abeta influx.	Metformin	64-73	advanced glycosylation end product-specific receptor	Mus musculus	291-295
26893732-3	2016	The anticancer action of metformin involves the enhancement of phosphorylation of liver kinase B1, activation of adenosine monophosphate-activated protein kinase and inhibition of mammalian target of rapamycin, which reduces cell growth.	Metformin	25-34	mechanistic target of rapamycin kinase	Homo sapiens	180-209
26547662-2	2016	Among users of long-acting insulin, we conducted a population-based case-control study to evaluate the incident myocardial infarction (MI) and incident stroke risks associated with the use of sulfonylureas and the use of metformin.	Metformin	221-230	insulin	Homo sapiens	27-34
26547662-12	2016	Metformin may be an important cardiovascular disease prevention therapy for patients on insulin therapy.	Metformin	0-9	insulin	Homo sapiens	88-95
26927374-0	2016	[Metformin inhibits THP-1 macrophage-derived foam cell formation induced by lipopolysaccharide].	Metformin	1-10	GLI family zinc finger 2	Homo sapiens	20-25
26927374-1	2016	OBJECTIVE: To investigate the impact of metformin (Met) on THP-1 macrophage-derived foam cell formation induced by lipopolysaccharide (LPS) and observe the changes of lipid droplets (LDs) and LDs-associated proteins.	Metformin	40-49	GLI family zinc finger 2	Homo sapiens	59-64
26673006-0	2016	Metformin increases antitumor activity of MEK inhibitors through GLI1 downregulation in LKB1 positive human NSCLC cancer cells.	Metformin	0-9	mitogen-activated protein kinase kinase 7	Homo sapiens	42-45
26673006-3	2016	In these models, metformin as single agent induced an activation and phosphorylation of mitogen-activated-protein-kinase (MAPK) through an increased C-RAF/B-RAF heterodimerization.	Metformin	17-26	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	155-160
26673006-4	2016	EXPERIMENTAL DESIGN: Since single agent metformin enhances proliferating signals through the RAS/RAF/MAPK pathway, and several MEK inhibitors (MEK-I) demonstrated clinical efficacy in combination with other agents in NSCLC, we tested the effects of metformin plus MEK-I (selumetinib or pimasertib) on proliferation, invasiveness, migration abilities in vitro and in vivo in LKB1 positive NSCLC models harboring KRAS wild type and mutated gene.	Metformin	249-258	mitogen-activated protein kinase kinase 7	Homo sapiens	127-130
26673006-4	2016	EXPERIMENTAL DESIGN: Since single agent metformin enhances proliferating signals through the RAS/RAF/MAPK pathway, and several MEK inhibitors (MEK-I) demonstrated clinical efficacy in combination with other agents in NSCLC, we tested the effects of metformin plus MEK-I (selumetinib or pimasertib) on proliferation, invasiveness, migration abilities in vitro and in vivo in LKB1 positive NSCLC models harboring KRAS wild type and mutated gene.	Metformin	249-258	mitogen-activated protein kinase kinase 7	Homo sapiens	143-146
26673006-4	2016	EXPERIMENTAL DESIGN: Since single agent metformin enhances proliferating signals through the RAS/RAF/MAPK pathway, and several MEK inhibitors (MEK-I) demonstrated clinical efficacy in combination with other agents in NSCLC, we tested the effects of metformin plus MEK-I (selumetinib or pimasertib) on proliferation, invasiveness, migration abilities in vitro and in vivo in LKB1 positive NSCLC models harboring KRAS wild type and mutated gene.	Metformin	249-258	mitogen-activated protein kinase kinase 7	Homo sapiens	143-146
26673006-8	2016	CONCLUSIONS: Metformin potentiates the antitumor activity of MEK-Is in human LKB1-wild-type NSCLC cell lines, independently from the KRAS mutational status, through GLI1 downregulation and by reducing the NF-jB (p65)-mediated transcription of MMP-2 and MMP-9.	Metformin	13-22	mitogen-activated protein kinase kinase 7	Homo sapiens	61-64
26616058-0	2016	Targeting HIF-1alpha is a prerequisite for cell sensitivity to dichloroacetate (DCA) and metformin.	Metformin	89-98	hypoxia inducible factor 1 subunit alpha	Homo sapiens	10-20
26529121-5	2016	Metformin treatment prompted a delay in delamination of NCC by inhibiting key markers like Sox-1, Sox-9, HNK-1, and p-75.	Metformin	0-9	beta-1,3-glucuronyltransferase 1	Homo sapiens	105-110
26805826-0	2016	Metformin Prevents Renal Fibrosis in Mice with Unilateral Ureteral Obstruction and Inhibits Ang II-Induced ECM Production in Renal Fibroblasts.	Metformin	0-9	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	92-98
26805826-5	2016	The administration of metformin inhibited the activation of ERK signaling and attenuated the production of extracellular matrix (ECM) proteins and collagen deposition in the obstructed kidneys.	Metformin	22-31	mitogen-activated protein kinase 1	Mus musculus	60-63
26805826-7	2016	Pretreatment of the cells with metformin blocked Ang II-induced ERK signaling activation and ECM overproduction.	Metformin	31-40	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	49-55
26805826-7	2016	Pretreatment of the cells with metformin blocked Ang II-induced ERK signaling activation and ECM overproduction.	Metformin	31-40	mitogen-activated protein kinase 1	Mus musculus	64-67
26805826-8	2016	Our results show that metformin prevents renal fibrosis, possibly through the inhibition of ERK signaling, and may be a novel strategy for the treatment of renal fibrosis.	Metformin	22-31	mitogen-activated protein kinase 1	Mus musculus	92-95
26616058-4	2016	Interestingly, HIF-1alpha activation markedly suppressed DCA/metformin-induced cell death and recovered the expressions of glycolytic enzymes that were decreased by two drugs.	Metformin	61-70	hypoxia inducible factor 1 subunit alpha	Homo sapiens	15-25
26621849-0	2016	Metformin suppresses hypoxia-induced stabilization of HIF-1alpha through reprogramming of oxygen metabolism in hepatocellular carcinoma.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	54-64
26621849-4	2016	The aim of this study was to investigate the effects of metformin on the expression of HIF-1alpha and oxygen metabolism in HCC.	Metformin	56-65	hypoxia inducible factor 1 subunit alpha	Homo sapiens	87-97
26728433-5	2016	In both immune-deficient and immune-competent preclinical models, Atenolol increased Metformin activity against angiogenesis, local and metastatic growth of HER2+ and triple negative BC.	Metformin	85-94	erb-b2 receptor tyrosine kinase 2	Homo sapiens	157-161
26728433-6	2016	Aspirin increased the activity of Metformin only in immune-competent HER2+ BC models.	Metformin	34-43	erb-b2 receptor tyrosine kinase 2	Homo sapiens	69-73
26851795-0	2016	Effect of insulin and metformin on methylation and glycolipid metabolism of peroxisome proliferator-activated receptor gamma coactivator-1A of rat offspring with gestational diabetes mellitus.	Metformin	22-31	PPARG coactivator 1 alpha	Rattus norvegicus	76-139
26851795-1	2016	OBJECTIVE: To discuss the effect of insulin and metformin on a methylation and glycolipid metabolism of peroxisome proliferator-activated receptor gamma coactivator-1A (PPARGC1A) of rat offspring with gestational diabetes mellitus (GDM).	Metformin	48-57	PPARG coactivator 1 alpha	Rattus norvegicus	104-167
26851795-1	2016	OBJECTIVE: To discuss the effect of insulin and metformin on a methylation and glycolipid metabolism of peroxisome proliferator-activated receptor gamma coactivator-1A (PPARGC1A) of rat offspring with gestational diabetes mellitus (GDM).	Metformin	48-57	PPARG coactivator 1 alpha	Rattus norvegicus	169-177
26851795-13	2016	The expression of PPARGC1A mRNA in the insulin group and metformin group was significantly higher and the methylation level of PPARGC1A was significantly lower than the one in the control group (P &lt; 0.05); but there was no significant difference between the insulin group and metformin group (P &gt; 0.05).	Metformin	279-288	PPARG coactivator 1 alpha	Rattus norvegicus	18-26
26851795-13	2016	The expression of PPARGC1A mRNA in the insulin group and metformin group was significantly higher and the methylation level of PPARGC1A was significantly lower than the one in the control group (P &lt; 0.05); but there was no significant difference between the insulin group and metformin group (P &gt; 0.05).	Metformin	279-288	PPARG coactivator 1 alpha	Rattus norvegicus	127-135
26851795-16	2016	CONCLUSIONS: GDM can induce the methylation of PPARGC1A of offspring rats to reduce the expression of PPARGC1A mRNA and then cause the disorder of glycolipid metabolism when the offspring rats grow up; the insulin or metformin in the treatment of pregnant rats with GDM can reduce the methylation level of PPARGC1A and thus improve the abnormal glycolipid metabolism of offspring rats.	Metformin	217-226	PPARG coactivator 1 alpha	Rattus norvegicus	47-55
26695692-0	2016	Metformin Restrains Pancreatic Duodenal Homeobox-1 (PDX-1) Function by Inhibiting ERK Signaling in Pancreatic Ductal Adenocarcinoma.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	82-85
26895247-8	2016	It is postulated that an insulin-sensitizing agent, metformin, has cancer-preventing effects on diabetic patients.	Metformin	52-61	insulin	Homo sapiens	25-32
27403417-0	2016	Metformin Alleviated Abeta-Induced Apoptosis via the Suppression of JNK MAPK Signaling Pathway in Cultured Hippocampal Neurons.	Metformin	0-9	amyloid beta precursor protein	Homo sapiens	21-26
27403417-3	2016	The aim of the current study is to investigate the role of metformin in Abeta-induced cytotoxicity and explore the underlying mechanisms.	Metformin	59-68	amyloid beta precursor protein	Homo sapiens	72-77
27403417-4	2016	First, the experimental results show that metformin salvaged the neurons exposed to Abeta in a concentration-dependent manner with MTT and LDH assay.	Metformin	42-51	amyloid beta precursor protein	Homo sapiens	84-89
27403417-7	2016	Metformin decreased hyperphosphorylated JNK induced by Abeta; however, the protection of metformin against Abeta was blocked when anisomycin, the activator of JNK, was added to the medium, indicating that metformin performed its protection against Abeta in a JNK-dependent way.	Metformin	0-9	mitogen-activated protein kinase 8	Homo sapiens	40-43
27403417-7	2016	Metformin decreased hyperphosphorylated JNK induced by Abeta; however, the protection of metformin against Abeta was blocked when anisomycin, the activator of JNK, was added to the medium, indicating that metformin performed its protection against Abeta in a JNK-dependent way.	Metformin	0-9	amyloid beta precursor protein	Homo sapiens	55-60
27403417-7	2016	Metformin decreased hyperphosphorylated JNK induced by Abeta; however, the protection of metformin against Abeta was blocked when anisomycin, the activator of JNK, was added to the medium, indicating that metformin performed its protection against Abeta in a JNK-dependent way.	Metformin	0-9	mitogen-activated protein kinase 8	Homo sapiens	159-162
27403417-7	2016	Metformin decreased hyperphosphorylated JNK induced by Abeta; however, the protection of metformin against Abeta was blocked when anisomycin, the activator of JNK, was added to the medium, indicating that metformin performed its protection against Abeta in a JNK-dependent way.	Metformin	0-9	mitogen-activated protein kinase 8	Homo sapiens	159-162
27403417-7	2016	Metformin decreased hyperphosphorylated JNK induced by Abeta; however, the protection of metformin against Abeta was blocked when anisomycin, the activator of JNK, was added to the medium, indicating that metformin performed its protection against Abeta in a JNK-dependent way.	Metformin	89-98	amyloid beta precursor protein	Homo sapiens	107-112
27403417-7	2016	Metformin decreased hyperphosphorylated JNK induced by Abeta; however, the protection of metformin against Abeta was blocked when anisomycin, the activator of JNK, was added to the medium, indicating that metformin performed its protection against Abeta in a JNK-dependent way.	Metformin	89-98	mitogen-activated protein kinase 8	Homo sapiens	159-162
27403417-7	2016	Metformin decreased hyperphosphorylated JNK induced by Abeta; however, the protection of metformin against Abeta was blocked when anisomycin, the activator of JNK, was added to the medium, indicating that metformin performed its protection against Abeta in a JNK-dependent way.	Metformin	89-98	amyloid beta precursor protein	Homo sapiens	107-112
27403417-7	2016	Metformin decreased hyperphosphorylated JNK induced by Abeta; however, the protection of metformin against Abeta was blocked when anisomycin, the activator of JNK, was added to the medium, indicating that metformin performed its protection against Abeta in a JNK-dependent way.	Metformin	89-98	mitogen-activated protein kinase 8	Homo sapiens	159-162
27403417-7	2016	Metformin decreased hyperphosphorylated JNK induced by Abeta; however, the protection of metformin against Abeta was blocked when anisomycin, the activator of JNK, was added to the medium, indicating that metformin performed its protection against Abeta in a JNK-dependent way.	Metformin	205-214	mitogen-activated protein kinase 8	Homo sapiens	159-162
27403417-7	2016	Metformin decreased hyperphosphorylated JNK induced by Abeta; however, the protection of metformin against Abeta was blocked when anisomycin, the activator of JNK, was added to the medium, indicating that metformin performed its protection against Abeta in a JNK-dependent way.	Metformin	205-214	mitogen-activated protein kinase 8	Homo sapiens	159-162
27403417-9	2016	Taken together, our findings demonstrate that metformin may have a positive effect on Abeta-induced cytotoxicity, which provides a preclinical strategy against AD for elders with diabetes.	Metformin	46-55	amyloid beta precursor protein	Homo sapiens	86-91
26904687-3	2016	The potential mechanisms underlying the synergistic effect of metformin on cisplatin-induced cytotoxicity under glucose-deprivation conditions may include enhancement of metformin-associated cytotoxicity, marked reduction in the cellular ATP levels, deregulation of the AKT and AMPK signaling pathways, and impaired DNA repair function.	Metformin	62-71	AKT serine/threonine kinase 1	Homo sapiens	270-273
25913633-5	2016	In contrast, metformin has a positive effect on osteoblast differentiation due to increased activity of Runx2 via the AMPK/USF-1/SHP regulatory cascade resulting in a neutral or potentially protective effect on bone.	Metformin	13-22	RUNX family transcription factor 2	Homo sapiens	104-109
26900800-5	2016	We found that both Tennovin-1 and BI2536 increased the anti-neoplastic activity of metformin, an inhibitor of oxidative phosphorylation, in a p53 dependent manner.	Metformin	83-92	tumor protein p53	Homo sapiens	142-145
26919310-0	2016	Metformin attenuates transforming growth factor beta (TGF-beta) mediated oncogenesis in mesenchymal stem-like/claudin-low triple negative breast cancer.	Metformin	0-9	transforming growth factor beta 1	Homo sapiens	54-62
26919310-4	2016	Using several MSL/CL breast cancer cell lines, we show that TGF-beta elicits significant increases in cellular proliferation, migration, invasion, and motility, whereas these effects can be abrogated by a specific inhibitor against TGF-beta receptor I and the anti-diabetic agent metformin, alone or in combination.	Metformin	280-289	transforming growth factor beta 1	Homo sapiens	60-68
26919310-4	2016	Using several MSL/CL breast cancer cell lines, we show that TGF-beta elicits significant increases in cellular proliferation, migration, invasion, and motility, whereas these effects can be abrogated by a specific inhibitor against TGF-beta receptor I and the anti-diabetic agent metformin, alone or in combination.	Metformin	280-289	transforming growth factor beta 1	Homo sapiens	232-240
26919310-6	2016	Mechanistically, metformin blocks endogenous activation of Smad2 and Smad3 and dampens TGF-beta-mediated activation of Smad2, Smad3, and ID1 both at the transcriptional and translational level.	Metformin	17-26	transforming growth factor beta 1	Homo sapiens	87-95
26919310-9	2016	Metformin therapy (with or without other agents) may be a heretofore unrecognized approach to reduce the oncogenic activities associated with TGF-beta mediated oncogenesis.	Metformin	0-9	transforming growth factor beta 1	Homo sapiens	142-150
26695692-10	2016	Metformin inhibited EGF-stimulated PDX-1 expression with an accompanied inhibition of ERK kinase activation in PANC- 1 cells.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	86-89
26695692-11	2016	Taken together, our studies show that PDX-1 is a potential novel target for metformin in PDAC cells and that metformin may exert its anticancer action in PDAC by down-regulating PDX-1 via a mechanism involving inhibition of ERK signaling.	Metformin	109-118	mitogen-activated protein kinase 1	Homo sapiens	224-227
27426125-8	2016	However use of metformin is associated with an increase in ghrelin, PYY, GLP-1 and GIP in women with PCOS.	Metformin	15-24	peptide YY	Homo sapiens	68-71
27426125-8	2016	However use of metformin is associated with an increase in ghrelin, PYY, GLP-1 and GIP in women with PCOS.	Metformin	15-24	glucagon	Homo sapiens	73-78
27426125-8	2016	However use of metformin is associated with an increase in ghrelin, PYY, GLP-1 and GIP in women with PCOS.	Metformin	15-24	gastric inhibitory polypeptide	Homo sapiens	83-86
27514712-9	2016	Oral administration of metformin (insulin sensitizer) to PCOS-patients increases GLUT4 endometrial levels, improving fertility of those patients.	Metformin	23-32	insulin	Homo sapiens	34-41
26967226-0	2016	Metformin Facilitates Amyloid-beta Generation by beta- and gamma-Secretases via Autophagy Activation.	Metformin	0-9	amyloid beta precursor protein	Homo sapiens	22-34
27633039-3	2016	Metformin also increases the affinity of the insulin receptor, reduces high insulin levels and improves insulin resistance.	Metformin	0-9	insulin	Homo sapiens	45-52
27633039-3	2016	Metformin also increases the affinity of the insulin receptor, reduces high insulin levels and improves insulin resistance.	Metformin	0-9	insulin	Homo sapiens	76-83
27633039-10	2016	A study in mice deficient in PON1 showed that in this experimental model, metformin administration increased the severity of steatosis, increased CCL2 expression, did not activate AMPK, and increased the expression of the apoptosis marker caspase-9.	Metformin	74-83	paraoxonase 1	Mus musculus	29-33
26765270-1	2016	Polycystic ovary syndrome (PCOS) is common in obese women with insulin resistant type 2 diabetes for which metformin treatment is getting established in addition to clomiphene.	Metformin	107-116	insulin	Homo sapiens	63-70
26824829-6	2016	Drugs that reduce circulating insulin levels, such as metformin, may reduce cancer risk, and drugs that increase circulating insulin levels, including exogenous insulin and insulin secretagogues, may increase cancer risk.	Metformin	54-63	insulin	Homo sapiens	30-37
28017142-5	2016	Switching antidiabetic therapy from gliclazide to acarbose and metformin, the patient"s serum insulin level and IAA decreased gradually.	Metformin	63-72	insulin	Homo sapiens	94-101
26465200-7	2016	Specifically, both DA and metformin reduced cAMP-enhanced recruitment of the orphan nuclear receptor Nur77 to the HSD3B2 promoter, coupled with decreased transcription and protein expression of HSD3B2.	Metformin	26-35	hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2	Homo sapiens	114-120
26465200-7	2016	Specifically, both DA and metformin reduced cAMP-enhanced recruitment of the orphan nuclear receptor Nur77 to the HSD3B2 promoter, coupled with decreased transcription and protein expression of HSD3B2.	Metformin	26-35	hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2	Homo sapiens	194-200
26834850-17	2016	For children and obese adolescents, metformin is used in the case of insulin resistance and hyperinsulinemia.	Metformin	36-45	insulin	Homo sapiens	69-76
25410163-7	2016	Perturbation experiments in GC tumour cell lines and xenograft models further demonstrated that HNF4alpha is downregulated by AMPKalpha signalling and the AMPK agonist metformin; blockade of HNF4alpha activity resulted in cyclin downregulation, cell cycle arrest and tumour growth inhibition.	Metformin	168-177	hepatocyte nuclear factor 4 alpha	Homo sapiens	96-105
26904472-10	2016	In metformin-treated group, there was a lowest prolactin serum level.	Metformin	3-12	prolactin	Homo sapiens	47-56
26566714-9	2016	Patients on concomitant metformin alone had higher insulin doses at Week 24, but achieved greater reductions in A1C, less weight gain and lower hypoglycaemia rates than patients on a concomitant sulfonylurea or metformin plus a sulfonylurea, regardless of whether cut-offs were exceeded.	Metformin	24-33	insulin	Homo sapiens	51-58
26977146-8	2016	After metformin treatment, SLC22A1 rs594709 GG genotype patients showed a higher increase in FINS (p = 0.015) and decrease in HOMA-IS (p = 0.001) and QUICKI (p = 0.002) than A allele carriers.	Metformin	6-15	solute carrier family 22 member 1	Homo sapiens	27-34
26977146-13	2016	Our data suggest that SLC22A1 rs594709 and SLC47A1 rs2289669 polymorphisms may influence metformin efficacy together in Chinese T2DM patients.	Metformin	89-98	solute carrier family 22 member 1	Homo sapiens	22-29
27478438-6	2016	Metformin plus insulin was associated with reduced hemoglobin A1C levels, total daily insulin dosage, body mass index (BMI), and body weight.	Metformin	0-9	insulin	Homo sapiens	86-93
27478438-11	2016	Among adolescents with T1DM, administering adjunctive metformin therapy in addition to insulin was associated with improved HbA1c levels, total daily insulin dosage, BMI, and body weight.	Metformin	54-63	insulin	Homo sapiens	150-157
27648070-10	2016	Patients treated with metformin had more intense ER stain (p = 0.032) and a lower ODX recurrence score (RS) (p = 0.035).	Metformin	22-31	estrogen receptor 1	Homo sapiens	49-51
26967226-2	2016	Contrary to suggestions that anti-diabetes drugs may have potential for treating AD, we demonstrate here that the insulin sensitizing anti-diabetes drug metformin (Glucophage ) increased the generation of amyloid-beta (Abeta), one of the major pathological hallmarks of AD, by promoting beta- and gamma-secretase-mediated cleavage of amyloid-beta protein precursor (AbetaPP) in SH-SY5Y cells.	Metformin	153-162	amyloid beta precursor protein	Homo sapiens	205-217
26967226-2	2016	Contrary to suggestions that anti-diabetes drugs may have potential for treating AD, we demonstrate here that the insulin sensitizing anti-diabetes drug metformin (Glucophage ) increased the generation of amyloid-beta (Abeta), one of the major pathological hallmarks of AD, by promoting beta- and gamma-secretase-mediated cleavage of amyloid-beta protein precursor (AbetaPP) in SH-SY5Y cells.	Metformin	153-162	amyloid beta precursor protein	Homo sapiens	334-346
26967226-2	2016	Contrary to suggestions that anti-diabetes drugs may have potential for treating AD, we demonstrate here that the insulin sensitizing anti-diabetes drug metformin (Glucophage ) increased the generation of amyloid-beta (Abeta), one of the major pathological hallmarks of AD, by promoting beta- and gamma-secretase-mediated cleavage of amyloid-beta protein precursor (AbetaPP) in SH-SY5Y cells.	Metformin	164-174	amyloid beta precursor protein	Homo sapiens	205-217
26967226-2	2016	Contrary to suggestions that anti-diabetes drugs may have potential for treating AD, we demonstrate here that the insulin sensitizing anti-diabetes drug metformin (Glucophage ) increased the generation of amyloid-beta (Abeta), one of the major pathological hallmarks of AD, by promoting beta- and gamma-secretase-mediated cleavage of amyloid-beta protein precursor (AbetaPP) in SH-SY5Y cells.	Metformin	164-174	amyloid beta precursor protein	Homo sapiens	334-346
26967226-6	2016	Additional experiments indicated that metformin increased phosphorylation of AMP-activated protein kinase, which activates autophagy by suppressing mammalian target of rapamycin (mTOR).	Metformin	38-47	mechanistic target of rapamycin kinase	Homo sapiens	148-177
26967226-6	2016	Additional experiments indicated that metformin increased phosphorylation of AMP-activated protein kinase, which activates autophagy by suppressing mammalian target of rapamycin (mTOR).	Metformin	38-47	mechanistic target of rapamycin kinase	Homo sapiens	179-183
25277876-0	2016	Relationship of the Serum CRP Level With the Efficacy of Metformin in the Treatment of Type 2 Diabetes Mellitus: A Meta-Analysis.	Metformin	57-66	C-reactive protein	Homo sapiens	26-29
27386433-0	2016	Impact of ATM and SLC22A1 Polymorphisms on Therapeutic Response to Metformin in Iranian Diabetic Patients.	Metformin	67-76	solute carrier family 22 member 1	Homo sapiens	18-25
27761470-0	2016	Metformin Inhibits Advanced Glycation End Products-Induced Inflammatory Response in Murine Macrophages Partly through AMPK Activation and RAGE/NFkappaB Pathway Suppression.	Metformin	0-9	advanced glycosylation end product-specific receptor	Mus musculus	138-142
27761470-0	2016	Metformin Inhibits Advanced Glycation End Products-Induced Inflammatory Response in Murine Macrophages Partly through AMPK Activation and RAGE/NFkappaB Pathway Suppression.	Metformin	0-9	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	143-151
27761470-4	2016	In conclusion, metformin inhibits AGEs-induced inflammatory response in murine macrophages partly through AMPK activation and RAGE/NFkappaB pathway suppression.	Metformin	15-24	advanced glycosylation end product-specific receptor	Mus musculus	126-130
27761470-4	2016	In conclusion, metformin inhibits AGEs-induced inflammatory response in murine macrophages partly through AMPK activation and RAGE/NFkappaB pathway suppression.	Metformin	15-24	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	131-139
25277876-2	2016	This meta-analysis was conducted to investigate whether CRP was sensitive in predicting the efficacy of metformin in the treatment of T2DM.	Metformin	104-113	C-reactive protein	Homo sapiens	56-59
25277876-7	2016	Pooled SMD of those studies revealed that serum levels of CRP and hs-CRP significantly decreased in patients with T2DM after receiving the metformin treatment.	Metformin	139-148	C-reactive protein	Homo sapiens	58-61
25277876-7	2016	Pooled SMD of those studies revealed that serum levels of CRP and hs-CRP significantly decreased in patients with T2DM after receiving the metformin treatment.	Metformin	139-148	C-reactive protein	Homo sapiens	69-72
25277876-8	2016	Subgroup analysis by country yielded significant different estimates in the serum levels of CRP between the baseline and after metformin treatment in the China, Israel and India subgroups; but only detected only in the China subgroup considering serum levels of hs-CRP.	Metformin	127-136	C-reactive protein	Homo sapiens	92-95
25277876-9	2016	Follow-up time-stratified analyses indicated that serum levels of CRP were markedly reduced in the metformin-treated group in all subgroups.	Metformin	99-108	C-reactive protein	Homo sapiens	66-69
25277876-11	2016	CONCLUSION: Decreased serum levels of CRP and hs-CRP may contribute to a more sensitive prediction in providing a more accurate efficacy reference in the metformin drug in T2DM patients.	Metformin	154-163	C-reactive protein	Homo sapiens	38-41
25277876-11	2016	CONCLUSION: Decreased serum levels of CRP and hs-CRP may contribute to a more sensitive prediction in providing a more accurate efficacy reference in the metformin drug in T2DM patients.	Metformin	154-163	C-reactive protein	Homo sapiens	49-52
26608911-4	2016	Treatments of B6.Sle1Sle2.Sle3 mice with either 2-deoxy-D-glucose or metformin were sufficient to prevent autoimmune activation, whereas their combination was necessary to reverse the process.	Metformin	69-78	systemic lupus erythmatosus susceptibility 3	Mus musculus	26-30
26618447-0	2016	Metformin Decreases Thyroid Volume and Nodule Size in Subjects with Insulin Resistance: A Preliminary Study.	Metformin	0-9	insulin	Homo sapiens	68-75
26618447-10	2016	Insulin resistance also decreased after metformin therapy (4.5 +- 1.9 vs. 2.9 +- 1.7, p &lt; 0.0001).	Metformin	40-49	insulin	Homo sapiens	0-7
26618447-12	2016	CONCLUSION: In subjects with insulin resistance, metformin therapy significantly decreased thyroid volume and nodule size.	Metformin	49-58	insulin	Homo sapiens	29-36
28217402-6	2016	Furthermore, the anti-diabetic drug, metformin, which indirectly inhibits mTOR, has emerged as a potential therapeutic target for PC.	Metformin	37-46	mechanistic target of rapamycin kinase	Homo sapiens	74-78
28217402-7	2016	The objective of this study is to determine the targeted-metabolomics profile in PDAC cell line (HPAF-II) with mTOR inhibition and the interaction between mTOR ATP-competitive inhibitor (Torin 2) and metformin as potential combined therapy in PC.	Metformin	200-209	mechanistic target of rapamycin kinase	Homo sapiens	155-159
28217402-7	2016	The objective of this study is to determine the targeted-metabolomics profile in PDAC cell line (HPAF-II) with mTOR inhibition and the interaction between mTOR ATP-competitive inhibitor (Torin 2) and metformin as potential combined therapy in PC.	Metformin	200-209	peroxiredoxin 2	Homo sapiens	187-192
28217402-14	2016	Targeted metabolomics data indicate that mTOR complexes inhibition by Torin 2 reduced glycolytic intermediates and TCA metabolites in HPAF- II and may synergize with metformin to decrease the electron acceptors NAD+ and FAD which may lead to reduced energy production.	Metformin	166-175	mechanistic target of rapamycin kinase	Homo sapiens	41-45
28217402-14	2016	Targeted metabolomics data indicate that mTOR complexes inhibition by Torin 2 reduced glycolytic intermediates and TCA metabolites in HPAF- II and may synergize with metformin to decrease the electron acceptors NAD+ and FAD which may lead to reduced energy production.	Metformin	166-175	peroxiredoxin 2	Homo sapiens	70-75
26656973-1	2016	The potential reproductive benefits of metformin, a drug endowed with the capacity to ameliorate insulin resistance in polycystic ovary syndrome (PCOS), has garnered much interest over the past 2 decades.	Metformin	39-48	insulin	Homo sapiens	97-104
26496641-1	2016	PURPOSE: Metformin (MF) acts as a tumour-suppressor in renal cell carcinoma (RCC) by inhibiting the AKT/mTOR pathway via AMPK activation.	Metformin	9-18	AKT serine/threonine kinase 1	Homo sapiens	100-103
26496641-1	2016	PURPOSE: Metformin (MF) acts as a tumour-suppressor in renal cell carcinoma (RCC) by inhibiting the AKT/mTOR pathway via AMPK activation.	Metformin	9-18	mechanistic target of rapamycin kinase	Homo sapiens	104-108
26625311-0	2015	Suppression of tumor angiogenesis by metformin treatment via a mechanism linked to targeting of HER2/HIF-1alpha/VEGF secretion axis.	Metformin	37-46	erb-b2 receptor tyrosine kinase 2	Homo sapiens	96-100
26625311-0	2015	Suppression of tumor angiogenesis by metformin treatment via a mechanism linked to targeting of HER2/HIF-1alpha/VEGF secretion axis.	Metformin	37-46	hypoxia inducible factor 1 subunit alpha	Homo sapiens	101-111
26625311-0	2015	Suppression of tumor angiogenesis by metformin treatment via a mechanism linked to targeting of HER2/HIF-1alpha/VEGF secretion axis.	Metformin	37-46	vascular endothelial growth factor A	Homo sapiens	112-116
26625311-5	2015	Metformin pretreatment significantly suppressed tumor paracrine signaling-induced angiogenic promotion even in the presence of heregulin (HRG)-beta1 (a co-activator of HER2) pretreatment of HER2+ tumor cells.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	168-172
26625311-5	2015	Metformin pretreatment significantly suppressed tumor paracrine signaling-induced angiogenic promotion even in the presence of heregulin (HRG)-beta1 (a co-activator of HER2) pretreatment of HER2+ tumor cells.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	190-194
26625311-6	2015	Similar to that of AG825, a specific inhibitor of HER2 phosphorylation, metformin treatment decreased both total and phosphorylation (Tyr 1221/1222) levels of HER2 protein and significantly reduced microvessel density and the amount of Fitc-conjugated Dextran leaking outside the vessel.	Metformin	72-81	erb-b2 receptor tyrosine kinase 2	Homo sapiens	50-54
26625311-6	2015	Similar to that of AG825, a specific inhibitor of HER2 phosphorylation, metformin treatment decreased both total and phosphorylation (Tyr 1221/1222) levels of HER2 protein and significantly reduced microvessel density and the amount of Fitc-conjugated Dextran leaking outside the vessel.	Metformin	72-81	erb-b2 receptor tyrosine kinase 2	Homo sapiens	159-163
26625311-7	2015	Furthermore, our results of VEGF-neutralizing and -rescuing tests showed that metformin markedly abrogated HER2 signaling-induced tumor angiogenesis by inhibiting VEGF secretion.	Metformin	78-87	vascular endothelial growth factor A	Homo sapiens	28-32
26625311-7	2015	Furthermore, our results of VEGF-neutralizing and -rescuing tests showed that metformin markedly abrogated HER2 signaling-induced tumor angiogenesis by inhibiting VEGF secretion.	Metformin	78-87	erb-b2 receptor tyrosine kinase 2	Homo sapiens	107-111
26625311-7	2015	Furthermore, our results of VEGF-neutralizing and -rescuing tests showed that metformin markedly abrogated HER2 signaling-induced tumor angiogenesis by inhibiting VEGF secretion.	Metformin	78-87	vascular endothelial growth factor A	Homo sapiens	163-167
26625311-9	2015	Importantly, metformin treatment decreased the number of HIF-1alpha nucleus positive cells in 4T1 tumors, accompanied by decreased microvessel density.	Metformin	13-22	hypoxia inducible factor 1 subunit alpha	Homo sapiens	57-67
26625311-10	2015	Our data thus provides novel insight into the mechanism underlying the metformin-induced inhibition of tumor angiogenesis and indicates possibilities of HIF-1alpha-VEGF signaling axis in mediating HER2-induced tumor angiogenesis.	Metformin	71-80	hypoxia inducible factor 1 subunit alpha	Homo sapiens	153-163
26625311-10	2015	Our data thus provides novel insight into the mechanism underlying the metformin-induced inhibition of tumor angiogenesis and indicates possibilities of HIF-1alpha-VEGF signaling axis in mediating HER2-induced tumor angiogenesis.	Metformin	71-80	vascular endothelial growth factor A	Homo sapiens	164-168
26625311-10	2015	Our data thus provides novel insight into the mechanism underlying the metformin-induced inhibition of tumor angiogenesis and indicates possibilities of HIF-1alpha-VEGF signaling axis in mediating HER2-induced tumor angiogenesis.	Metformin	71-80	erb-b2 receptor tyrosine kinase 2	Homo sapiens	197-201
26497205-0	2015	Metformin attenuates gefitinib-induced exacerbation of pulmonary fibrosis by inhibition of TGF-beta signaling pathway.	Metformin	0-9	transforming growth factor beta 1	Homo sapiens	91-99
26497205-7	2015	We found that in lung HFL-1 fibroblast cells, TGF-beta or conditioned medium from TKI-treated lung cancer PC-9 cells or conditioned medium from TKI-resistant PC-9GR cells, induced significant fibrosis, as shown by increased expression of Collegen1a1 and alpha-actin, while metformin inhibited expression of fibrosis markers.	Metformin	273-282	transforming growth factor beta 1	Homo sapiens	46-54
26497205-8	2015	Moreover, metformin decreased activation of TGF-beta signaling as shown by decreased expression of pSMAD2 and pSMAD3.	Metformin	10-19	transforming growth factor beta 1	Homo sapiens	44-52
26497205-11	2015	We have shown that metformin attenuates gefitinib-induced exacerbation of TGF-beta or bleomycin-induced pulmonary fibrosis.	Metformin	19-28	transforming growth factor beta 1	Homo sapiens	74-82
26677765-5	2015	Specifically, we show that metformin enhances adult NPC proliferation and self-renewal dependent upon the p53 family member and transcription factor TAp73, while it promotes neuronal differentiation of these cells by activating the AMPK-aPKC-CBP pathway.	Metformin	27-36	tumor protein p53	Homo sapiens	106-109
26677765-5	2015	Specifically, we show that metformin enhances adult NPC proliferation and self-renewal dependent upon the p53 family member and transcription factor TAp73, while it promotes neuronal differentiation of these cells by activating the AMPK-aPKC-CBP pathway.	Metformin	27-36	CREB binding protein	Homo sapiens	242-245
26528626-3	2015	Recently, our laboratory demonstrated that organic cation transporter 1, OCT1, the major hepatic uptake transporter for metformin, was also the primary hepatic uptake transporter for thiamine, vitamin B1.	Metformin	120-129	solute carrier family 22 member 1	Homo sapiens	43-71
26528626-3	2015	Recently, our laboratory demonstrated that organic cation transporter 1, OCT1, the major hepatic uptake transporter for metformin, was also the primary hepatic uptake transporter for thiamine, vitamin B1.	Metformin	120-129	solute carrier family 22 member 1	Homo sapiens	73-77
26641266-11	2015	Furthermore, we found that metformin alleviates tumor inflammation by reducing the expression of inflammatory cytokines including IL-1beta as well as infiltration and M2 polarization of tumor-associated macrophages (TAMs) in vitro and in vivo.	Metformin	27-36	interleukin 1 beta	Homo sapiens	130-138
26641266-12	2015	These effects on macrophages in vitro appear to be associated with a modulation of the AMPK/STAT3 pathway by metformin.	Metformin	109-118	signal transducer and activator of transcription 3	Homo sapiens	92-97
26629991-0	2015	Metformin and Resveratrol Inhibited High Glucose-Induced Metabolic Memory of Endothelial Senescence through SIRT1/p300/p53/p21 Pathway.	Metformin	0-9	tumor protein p53	Homo sapiens	119-122
27162518-0	2015	VITAMIN B12 LEVELS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS ON METFORMIN.	Metformin	64-73	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	8-11
27162518-1	2015	BACKGROUND: Due to the clinical benefits of metformin, its associated side effects such as vitamin B12 deficiency are usually overlooked and rarely investigated.	Metformin	44-53	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	99-102
27162518-2	2015	OBJECTIVE: This study was carried out to determine the serum level of vitamin B12 in Nigerian patients with type 2 diabetes mellitus (T2DM) on metformin.	Metformin	143-152	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	78-81
27162518-3	2015	METHODS: Serum vitamin B12 level was determined using high performance liquid chromatography (HPLC) in 81 T2DM patients who have been on metformin for 5 years or more.	Metformin	137-146	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	23-26
27162518-7	2015	Vitamin B12 level was significantly lower in patients who have been on metformin for &gt;=10 years compared with patients with &lt;10 years history of metformin use.	Metformin	71-80	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	8-11
27162518-7	2015	Vitamin B12 level was significantly lower in patients who have been on metformin for &gt;=10 years compared with patients with &lt;10 years history of metformin use.	Metformin	151-160	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	8-11
27162518-8	2015	Similarly, patients who were on metformin at a dose of &gt;1000 mg/day had significantly lower vitamin B12 level when compared with patients on &lt;=1000 mg/day.	Metformin	32-41	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	103-106
27162518-9	2015	CONCLUSION: Low serum vitamin B12 level is associated with longer duration and higher dose of metformin use.	Metformin	94-103	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	30-33
27162518-10	2015	Therefore, routine determination of vitamin B12 level in patients with T2DM on high dose of metformin and those with prolonged use of metformin might help in identifying patients that would benefit from vitamin B12 supplements.	Metformin	92-101	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	44-47
27162518-10	2015	Therefore, routine determination of vitamin B12 level in patients with T2DM on high dose of metformin and those with prolonged use of metformin might help in identifying patients that would benefit from vitamin B12 supplements.	Metformin	134-143	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	44-47
26245802-17	2015	We assessed the effect of metformin on down-regulating the NET mtDNA-PDC-IFNalpha pathway.	Metformin	26-35	interferon alpha 1	Homo sapiens	73-81
26467186-8	2015	The 3-h exposure of MMECs to metformin significantly (P&lt;0.05) reversed the HG-induced reduction in phosphorylation of both eNOS and Akt; however, no changes were detected for phosphorylation of AMPK or the expression of SIRT1.	Metformin	29-38	thymoma viral proto-oncogene 1	Mus musculus	135-138
26467186-9	2015	Our data indicate that a 3-h exposure to metformin can reverse/reduce the impact of HG on endothelial function, via mechanisms linked to increased phosphorylation of eNOS and Akt.	Metformin	41-50	thymoma viral proto-oncogene 1	Mus musculus	175-178
26575601-9	2015	Among the anti-diabetic medications in diabetes patients, the OR for insulin users was 25.57 (95% CI 11.55-56.60), sulphonylureas 2.22 (95% CI 1.13, 4.40), and metformin users 1.46 (95% CI 0.85-2.52), compared with no use of any anti-diabetic medications.	Metformin	160-169	insulin	Homo sapiens	69-76
26304716-6	2015	Finally, metformin-mediated AMPK/mTOR/p70S6K was identified as a possible upstream pathway controlling translational regulation of Wee1 and Rad51.	Metformin	9-18	mechanistic target of rapamycin kinase	Homo sapiens	33-37
26341687-2	2015	Studies have shown that the antidiabetic drug metformin could effectively increase the sensitivity of TKI-resistant lung cancer cells to EGFR-TKI.	Metformin	46-55	epidermal growth factor receptor	Homo sapiens	137-141
26341687-9	2015	Secondary data analysis showed that metformin use significantly prolonged the median PFS in subgroups using either first-line EGFR-TKI or second-line EGFR-TKI.	Metformin	36-45	epidermal growth factor receptor	Homo sapiens	126-130
26341687-9	2015	Secondary data analysis showed that metformin use significantly prolonged the median PFS in subgroups using either first-line EGFR-TKI or second-line EGFR-TKI.	Metformin	36-45	epidermal growth factor receptor	Homo sapiens	150-154
26341687-10	2015	CONCLUSIONS: Metformin and EGFR-TKI have a synergistic effect in the treatment of DM2 NSCLC patients harboring EGFR-activating mutations.	Metformin	13-22	epidermal growth factor receptor	Homo sapiens	111-115
26341687-11	2015	Metformin use is associated with improved survival and delayed onset of acquired resistance to EGFR-TKI.	Metformin	0-9	epidermal growth factor receptor	Homo sapiens	95-99
26245802-18	2015	Metformin decreased PMA-induced NET formation and CpG-stimulated PDC IFNalpha generation.	Metformin	0-9	interferon alpha 1	Homo sapiens	69-77
26245802-20	2015	CONCLUSION: Our findings establish a link between mtDNA in NETs, anti-mtDNA antibodies, and PDC IFNalpha pathogenesis in SLE, and highlight that specific strategies to down-regulate this pathway, such as treatment with metformin, may be new approaches to treat SLE.	Metformin	219-228	interferon alpha 1	Homo sapiens	96-104
26505133-0	2015	Metformin synergistically sensitizes FLT3-ITD-positive acute myeloid leukemia to sorafenib by promoting mTOR-mediated apoptosis and autophagy.	Metformin	0-9	fms related receptor tyrosine kinase 3	Homo sapiens	37-41
26391700-11	2015	Treatment with cyproterone acetate/ethinyloestradiol with addition of metformin reduced the level of NF-kappaB, TGF-beta1 and HOMA-IR and increased the level of TSP-1.	Metformin	70-79	nuclear factor kappa B subunit 1	Homo sapiens	101-110
26391700-11	2015	Treatment with cyproterone acetate/ethinyloestradiol with addition of metformin reduced the level of NF-kappaB, TGF-beta1 and HOMA-IR and increased the level of TSP-1.	Metformin	70-79	transforming growth factor beta 1	Homo sapiens	112-121
26391700-11	2015	Treatment with cyproterone acetate/ethinyloestradiol with addition of metformin reduced the level of NF-kappaB, TGF-beta1 and HOMA-IR and increased the level of TSP-1.	Metformin	70-79	thrombospondin 1	Homo sapiens	161-166
26995937-8	2015	RESULTS: The presence of transcripts of three types of IGF-1 isoforms was observed in healthy controls and PCOS patients, regardless of metformin treatment.	Metformin	136-145	insulin like growth factor 1	Homo sapiens	55-60
26505133-0	2015	Metformin synergistically sensitizes FLT3-ITD-positive acute myeloid leukemia to sorafenib by promoting mTOR-mediated apoptosis and autophagy.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	104-108
26505133-3	2015	Our current studies have shown that, the antidiabetic drug metformin also exerts anti-leukemic effect by activating p-AMPK and synergistically sensitizes FLT3 mutated AML to sorafenib.	Metformin	59-68	fms related receptor tyrosine kinase 3	Homo sapiens	154-158
26505133-5	2015	Mechanistically, in the presence of metformin, the anticancer potential of sorafenib, accompanying with increased LC3 levels, is found to be synergistically enhanced with the remarkably reduced protein expression of the mTOR/p70S6K/4EBP1 pathway, while not appreciably altering cell cycle.	Metformin	36-45	mechanistic target of rapamycin kinase	Homo sapiens	220-224
26505133-6	2015	Overall, these results show metformin in aid of sorafenib may represent a promising and attractive strategy for the treatment of FLT3-ITD mutated AML.	Metformin	28-37	fms related receptor tyrosine kinase 3	Homo sapiens	129-133
26455399-7	2015	Furthermore, humans with type 1 diabetes respond to lifestyle modifications or metformin by 20%-60% increased whole-body insulin sensitivity, likely through improvement in both glycemic control and oxidative phosphorylation.	Metformin	79-88	insulin	Homo sapiens	121-128
26705203-7	2015	The corresponding tendency of higher anion gap in metformin users with the estimated glomerular filtration rate &gt;60 mL/min/1.73 m was also observed.	Metformin	50-59	CD59 molecule (CD59 blood group)	Homo sapiens	122-127
26350101-11	2015	Basal insulin therapy in combination with oral drugs, most often metformin - is the most convenient initial regimen.	Metformin	65-74	insulin	Homo sapiens	6-13
26424816-3	2015	Our results showed that activation of AMPK by metformin inhibited TGF-beta-induced Smad2/3 phosphorylation in cancer cells in a dose-dependent manner.	Metformin	46-55	transforming growth factor beta 1	Homo sapiens	66-74
26424816-6	2015	As a consequence, expression of genes downstream of Smad2/3, including plasminogen activator inhibitor-1, fibronectin, and connective tissue growth factor, was suppressed by metformin in a LKB1-dependent fashion.	Metformin	174-183	fibronectin 1	Homo sapiens	106-117
26424816-7	2015	In addition, metformin blocked TGF-beta-induced inteleukin-6 expression through both LKB1-dependent and -independent mechanisms.	Metformin	13-22	transforming growth factor beta 1	Homo sapiens	31-39
26320144-0	2015	Effects of metformin on mitochondrial function of leukocytes from polycystic ovary syndrome patients with insulin resistance.	Metformin	11-20	insulin	Homo sapiens	106-113
26624824-14	2015	Of multiple secondary end points, findings favored metformin only for insulin dose and measures of adiposity; conversely, use of metformin resulted in an increased risk for gastrointestinal adverse events.	Metformin	51-60	insulin	Homo sapiens	70-77
26526073-6	2015	A paradigm in the field of drug transporter pharmacogenetics is the impact of hOCT1 gene variability on metformin clinical parameters, affecting area under the concentration-time curve, Cmax and responsiveness.	Metformin	104-113	solute carrier family 22 member 1	Homo sapiens	78-83
26164004-8	2015	In addition, Western blot showed that metformin activated AMPKalpha at Tyr172, followed by a downregulated phosphorylation of mammalian target of rapamycin (mTOR)/S6 and feedback activation of p-AKT Ser(473) in both OS MG63 cells and CSCs.	Metformin	38-47	mechanistic target of rapamycin kinase	Homo sapiens	126-155
26164004-8	2015	In addition, Western blot showed that metformin activated AMPKalpha at Tyr172, followed by a downregulated phosphorylation of mammalian target of rapamycin (mTOR)/S6 and feedback activation of p-AKT Ser(473) in both OS MG63 cells and CSCs.	Metformin	38-47	mechanistic target of rapamycin kinase	Homo sapiens	157-161
26599019-0	2015	Metformin Radiosensitizes p53-Deficient Colorectal Cancer Cells through Induction of G2/M Arrest and Inhibition of DNA Repair Proteins.	Metformin	0-9	tumor protein p53	Homo sapiens	26-29
26599019-1	2015	The present study addressed whether the combination of metformin and ionizing radiation (IR) would show enhanced antitumor effects in radioresistant p53-deficient colorectal cancer cells, focusing on repair pathways for IR-induced DNA damage.	Metformin	55-64	tumor protein p53	Homo sapiens	149-152
26599019-2	2015	Metformin caused a higher reduction in clonogenic survival as well as greater radiosensitization and inhibition of tumor growth of p53-/- than of p53+/+ colorectal cancer cells and xenografts.	Metformin	0-9	tumor protein p53	Homo sapiens	131-134
26599019-2	2015	Metformin caused a higher reduction in clonogenic survival as well as greater radiosensitization and inhibition of tumor growth of p53-/- than of p53+/+ colorectal cancer cells and xenografts.	Metformin	0-9	tumor protein p53	Homo sapiens	146-149
26599019-5	2015	In conclusion, metformin enhanced radiosensitivity by inducing G2/M arrest and reducing the expression of DNA repair proteins even in radioresistant HCT116 p53-/- colorectal cancer cells and tumors.	Metformin	15-24	tumor protein p53	Homo sapiens	156-159
26885449-5	2015	In association with the reduction of MYC onco-protein, metformin significantly restored p53 tumor suppressor gene expression.	Metformin	55-64	tumor protein p53	Homo sapiens	88-91
26885449-6	2015	The distinctive effects of metformin and PP242 on MYC reduction and P53 restoration suggested that metformin inhibited cell growth through a different pathway from PP242 in salivary carcinoma cells.	Metformin	99-108	tumor protein p53	Homo sapiens	68-71
26885449-9	2015	Moreover, metformin inhibitory effects were enhanced by mTOR inhibitor suggesting that metformin and mTOR inhibitor utilize distinctive signaling pathways to suppress salivary tumor growth.	Metformin	10-19	mechanistic target of rapamycin kinase	Homo sapiens	56-60
26885449-9	2015	Moreover, metformin inhibitory effects were enhanced by mTOR inhibitor suggesting that metformin and mTOR inhibitor utilize distinctive signaling pathways to suppress salivary tumor growth.	Metformin	10-19	mechanistic target of rapamycin kinase	Homo sapiens	101-105
26885449-9	2015	Moreover, metformin inhibitory effects were enhanced by mTOR inhibitor suggesting that metformin and mTOR inhibitor utilize distinctive signaling pathways to suppress salivary tumor growth.	Metformin	87-96	mechanistic target of rapamycin kinase	Homo sapiens	56-60
26537234-10	2015	Additional analyses suggested that the breast cancer risk associated with human insulin use might be beneficially modified by concomitant use of metformin, statin and ACEI/ARB.	Metformin	145-154	insulin	Homo sapiens	80-87
26537234-12	2015	The increased risk of breast cancer associated with human insulin use may be modified by medications such as metformin, statin and ACEI/ARB.	Metformin	109-118	insulin	Homo sapiens	58-65
26497364-2	2015	Here we found that metformin significantly suppressed IL-13 induced M2-like polarization of macrophages, as illustrated by reduced expression of CD206, down-regulation of M2 marker mRNAs, and inhibition of M2-like macrophages promoted migration of cancer cells and endothelial cells.	Metformin	19-28	interleukin 13	Homo sapiens	54-59
26497364-3	2015	Metformin triggered AMPKalpha1 activation in macrophage and silencing of AMPKalpha1 partially abrogated the inhibitory effect of metformin in IL-13 induced M2-like polarization.	Metformin	0-9	interleukin 13	Homo sapiens	142-147
26497364-3	2015	Metformin triggered AMPKalpha1 activation in macrophage and silencing of AMPKalpha1 partially abrogated the inhibitory effect of metformin in IL-13 induced M2-like polarization.	Metformin	129-138	interleukin 13	Homo sapiens	142-147
26344902-11	2015	Finally, metformin modestly attenuated palmitate-induced insulin resistance and cytotoxicity, as did oleate.	Metformin	9-18	insulin	Homo sapiens	57-64
25492374-0	2015	Influence of SLC22A1 rs622342 genetic polymorphism on metformin response in South Indian type 2 diabetes mellitus patients.	Metformin	54-63	solute carrier family 22 member 1	Homo sapiens	13-20
25492374-3	2015	It has been hypothesized that genetic variations of SLC22A1 gene will influence inter-individual variation in glucose lowering efficacy of metformin.	Metformin	139-148	solute carrier family 22 member 1	Homo sapiens	52-59
25492374-5	2015	Henceforth, the objective of the study was to evaluate the impact of SLC22A1 rs622342 gene polymorphism on the clinical efficacy of metformin in South Indian T2DM patients.	Metformin	132-141	solute carrier family 22 member 1	Homo sapiens	69-76
26320144-10	2015	In addition, metformin reduced glucose, follicle-stimulating hormone, IL6 and TNFalpha levels and increased dehydroepiandrosterone sulfate levels.	Metformin	13-22	interleukin 6	Homo sapiens	70-73
26320144-10	2015	In addition, metformin reduced glucose, follicle-stimulating hormone, IL6 and TNFalpha levels and increased dehydroepiandrosterone sulfate levels.	Metformin	13-22	tumor necrosis factor	Homo sapiens	78-86
26318958-9	2015	Further stratification of data from diabetic patients by APOE genotypes and anti-hyperglycemic agents revealed a significant (~23%) decrease in 2-hour glucose (p=0.004) and ~7% decrease in systolic BP (p&lt;0.001) among APOE4 carriers compared to non-carriers on metformin and sulphonylurea (SU) combination therapy, and no such differences were seen in patients on other agents.	Metformin	263-272	apolipoprotein E	Homo sapiens	57-61
26108695-0	2015	Pharmacologic screens reveal metformin that suppresses GRP78-dependent autophagy to enhance the anti-myeloma effect of bortezomib.	Metformin	29-38	heat shock protein family A (Hsp70) member 5	Homo sapiens	55-60
26108695-4	2015	Metformin co-treatment with bortezomib suppressed induction of the critical UPR effector glucose-regulated protein 78 (GRP78) to impair autophagosome formation and enhance apoptosis.	Metformin	0-9	heat shock protein family A (Hsp70) member 5	Homo sapiens	89-117
26108695-4	2015	Metformin co-treatment with bortezomib suppressed induction of the critical UPR effector glucose-regulated protein 78 (GRP78) to impair autophagosome formation and enhance apoptosis.	Metformin	0-9	heat shock protein family A (Hsp70) member 5	Homo sapiens	119-124
26108695-8	2015	Taken together, our results suggest that metformin suppresses GRP78, a key driver of bortezomib-induced autophagy, and support the pharmacologic repositioning of metformin to enhance the anti-myeloma benefit of bortezomib.	Metformin	41-50	heat shock protein family A (Hsp70) member 5	Homo sapiens	62-67
26303871-5	2015	The leucine-metformin combinations reduced fat pad mass, normalized liver weight, liver and plasma lipids and inflammatory markers (interleukin 6, interleukin 1 beta, tumor necrosis factor alpha, monocyte chemotactic protein-1, C-reactive protein) comparable to the effects of therapeutic metformin.	Metformin	12-21	interleukin 6	Mus musculus	132-145
26303871-5	2015	The leucine-metformin combinations reduced fat pad mass, normalized liver weight, liver and plasma lipids and inflammatory markers (interleukin 6, interleukin 1 beta, tumor necrosis factor alpha, monocyte chemotactic protein-1, C-reactive protein) comparable to the effects of therapeutic metformin.	Metformin	12-21	interleukin 1 beta	Mus musculus	147-194
26446233-7	2015	Subgroup analysis revealed that metformin improved the overall survival by 65% after adjusting for hormone receptor expression (HR: 0.35; 95% CI: 0.15-0.84).	Metformin	32-41	nuclear receptor subfamily 4 group A member 1	Homo sapiens	99-115
26446233-12	2015	Subgroup analysis revealed that metformin improved the overall survival by 65% after adjusting for hormone receptor expression.	Metformin	32-41	nuclear receptor subfamily 4 group A member 1	Homo sapiens	99-115
25131985-10	2015	In a subgroup of 285 patients followed-up longitudinally (average treatment period 1.42 yr), addition of metformin resulted in a slight reduction of BMI-SDS [-0.01 (-2.01 to +1.40)], but did not improve HbA1c or insulin requirement.	Metformin	105-114	insulin	Homo sapiens	212-219
25492374-16	2015	Further, metformin showed significant beneficial effects on BMI, HbA1c, FPG, PPG, lipid parameters and BP.	Metformin	9-18	serglycin	Homo sapiens	77-80
25492374-17	2015	These data suggest that the allele and genotypes of SLC22A1 rs622342 gene polymorphism were associated with the therapeutic efficacy of metformin in South Indian patients with T2DM.	Metformin	136-145	solute carrier family 22 member 1	Homo sapiens	52-59
26141671-6	2015	In addition, treatment with metformin significantly reduced the expression of IL-6 and TNF-alpha at the messenger RNA level and attenuated nuclear factor kappa B (NF-kappaB) DNA binding activity in MNCs.	Metformin	28-37	interleukin 6	Homo sapiens	78-82
26141671-6	2015	In addition, treatment with metformin significantly reduced the expression of IL-6 and TNF-alpha at the messenger RNA level and attenuated nuclear factor kappa B (NF-kappaB) DNA binding activity in MNCs.	Metformin	28-37	tumor necrosis factor	Homo sapiens	87-96
26141671-6	2015	In addition, treatment with metformin significantly reduced the expression of IL-6 and TNF-alpha at the messenger RNA level and attenuated nuclear factor kappa B (NF-kappaB) DNA binding activity in MNCs.	Metformin	28-37	nuclear factor kappa B subunit 1	Homo sapiens	139-161
26141671-6	2015	In addition, treatment with metformin significantly reduced the expression of IL-6 and TNF-alpha at the messenger RNA level and attenuated nuclear factor kappa B (NF-kappaB) DNA binding activity in MNCs.	Metformin	28-37	nuclear factor kappa B subunit 1	Homo sapiens	163-172
26141671-9	2015	Moreover, we found that metformin treatment dramatically induced SIRT1 expression, blocked p65 acetylation, and inhibited NF-kappaB activity and the expression of inflammatory factors in MNCs in vitro.	Metformin	24-33	nuclear factor kappa B subunit 1	Homo sapiens	122-131
26141671-10	2015	We conclude that metformin has a novel direct protective role to ameliorate the proinflammatory response through SIRT1 induction, p65 acetylation reduction, NF-kappaB inactivation, and inflammatory inhibition in peripheral blood MNCs of patients with carotid artery AS.	Metformin	17-26	nuclear factor kappa B subunit 1	Homo sapiens	157-166
25332100-6	2015	RESULTS: After 24 months, metformin-treated children were leaner, had higher SHBG levels, and less total and abdominal fat than placebo-treated children (all p &lt;= 0.05).	Metformin	26-35	sex hormone binding globulin	Homo sapiens	77-81
25332100-7	2015	Longitudinal analyses showed that metformin had a significant effect on anthropometric (weight, BMI, and waist) and biochemical variables [glucose, homeostasis model assessment-insulin resistance (HOMA-IR), and triglycerides] (all p &lt;= 0.05); and in total and abdominal fat (p = 0.01 and p = 0.02).	Metformin	34-43	insulin	Homo sapiens	177-184
25332100-8	2015	CONCLUSIONS: Prepubertal intervention with metformin reduces central adiposity and improves insulin sensitivity in non-obese catch-up SGA children.	Metformin	43-52	insulin	Homo sapiens	92-99
26514337-13	2015	Her serum insulin-like growth factor-1 level, measured after glycemic control was achieved with metformin and insulin, was elevated, which is characteristic of acromegaly.	Metformin	96-105	insulin like growth factor 1	Homo sapiens	10-38
26514337-13	2015	Her serum insulin-like growth factor-1 level, measured after glycemic control was achieved with metformin and insulin, was elevated, which is characteristic of acromegaly.	Metformin	96-105	insulin	Homo sapiens	10-17
26579078-5	2015	Furthermore, anti-diabetic treatments such as metformin and sulfonylurea have been observed to modulate the gut microbiota or at least their metabolic profiles, thereby potentially affecting insulin resistance through indirect mechanisms still unknown.	Metformin	46-55	insulin	Homo sapiens	191-198
26054810-10	2015	Further studies showed that metformin could activate AMPK and increase the AMPK target genes in sciatic nerves in diabetic rats.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	53-57
26473366-1	2015	BACKGROUND: Metformin is effective for the treatment of polycystic ovary syndrome, but conflicting results regarding its effect on adipocytokine levels (adiponectin, resistin, visfatin, and leptin) in patients with polycystic ovary syndrome receiving metformin treatment have been reported.	Metformin	12-21	adiponectin, C1Q and collagen domain containing	Homo sapiens	153-164
26473366-7	2015	Metformin treatment was associated with significantly elevated serum adiponectin concentrations (standard mean differences [95% confidence interval], -0.43 [-0.75 to -0.11]) and decreased serum leptin concentrations (0.65 [0.26 to 1.04]), whereas no significant difference in resistin level (-0.01 [-0.49 to 0.45]) or visfatin level (-0.04 [-1.55 to 1.46]) was found.	Metformin	0-9	adiponectin, C1Q and collagen domain containing	Homo sapiens	69-80
26473366-8	2015	CONCLUSIONS: Metformin administration was associated with increased serum adiponectin concentrations and decreased serum leptin levels.	Metformin	13-22	adiponectin, C1Q and collagen domain containing	Homo sapiens	74-85
26692929-6	2015	Mouse skeletal muscle myoblasts C2C12 cells were treated with Metformin for 24 h. The molecules PGC-1alpha, FNDC5, AMPK, and ERK mRNA/proteins were quantified by real-time PCR and western blotting in vivo and in vitro.	Metformin	62-71	mitogen-activated protein kinase 1	Mus musculus	125-128
26359363-6	2015	Moreover, we also suggest that TWIST1 is an upstream molecule of N-cadherin/NF-kappaB signaling and manipulation of TWIST1 expression changes the sensitivity of cancer cells to metformin.	Metformin	177-186	twist family bHLH transcription factor 1	Homo sapiens	31-37
26359363-6	2015	Moreover, we also suggest that TWIST1 is an upstream molecule of N-cadherin/NF-kappaB signaling and manipulation of TWIST1 expression changes the sensitivity of cancer cells to metformin.	Metformin	177-186	twist family bHLH transcription factor 1	Homo sapiens	116-122
26054810-10	2015	Further studies showed that metformin could activate AMPK and increase the AMPK target genes in sciatic nerves in diabetic rats.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	75-79
26054810-11	2015	In conclusion, metformin is able to attenuate diabetes-induced hyperalgesia and allodynia, which might be associated its anti-oxidative effect through AMPK pathway.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	151-155
26319555-6	2015	The AMPK inhibitor compound C, Atg5 knocking-down and eNOS inhibitor l-NAME could reverse the effect exerted by metformin.	Metformin	112-121	autophagy related 5	Homo sapiens	31-35
26186064-3	2015	We have also shown that metformin activates the ERK pathway in Ph+ALL cells, SUP-B15, a side effect that can be overcome by U0126 (MEK1/2 inhibitor) or imatinib.	Metformin	24-33	mitogen-activated protein kinase 1	Homo sapiens	48-51
26386799-9	2015	Patients taking versus not taking insulin had 0.83 more episodes of angina and used 1.40 more NTG doses per week, increases evident only in those taking insulin without concomitant metformin (Pinteraction &lt; .05 for both).	Metformin	181-190	insulin	Homo sapiens	34-41
26276754-1	2015	Metformin is associated with lower breast cancer risk in epidemiologic studies and showed decreased proliferation in HER2-positive breast cancer in a presurgical trial.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	117-121
26276754-8	2015	However, posttreatment Ki-67 in HER2-positive DCIS lesions was significantly lower in women randomized to metformin especially when ER was coexpressed: 22% (11-32) versus 35% (30-40) in HER2-positive DCIS (n = 22, P = .06); 12% (7-18) versus 32% (27-42) in ER-positive/HER2-positive DCIS (n = 15, P = .004).	Metformin	106-115	erb-b2 receptor tyrosine kinase 2	Homo sapiens	32-36
26276754-8	2015	However, posttreatment Ki-67 in HER2-positive DCIS lesions was significantly lower in women randomized to metformin especially when ER was coexpressed: 22% (11-32) versus 35% (30-40) in HER2-positive DCIS (n = 22, P = .06); 12% (7-18) versus 32% (27-42) in ER-positive/HER2-positive DCIS (n = 15, P = .004).	Metformin	106-115	erb-b2 receptor tyrosine kinase 2	Homo sapiens	186-190
26276754-8	2015	However, posttreatment Ki-67 in HER2-positive DCIS lesions was significantly lower in women randomized to metformin especially when ER was coexpressed: 22% (11-32) versus 35% (30-40) in HER2-positive DCIS (n = 22, P = .06); 12% (7-18) versus 32% (27-42) in ER-positive/HER2-positive DCIS (n = 15, P = .004).	Metformin	106-115	erb-b2 receptor tyrosine kinase 2	Homo sapiens	186-190
26276754-10	2015	In tissue samples obtained following 4 weeks of study drug, proliferation was lower in HER2-positive DCIS for women randomized to metformin versus placebo.	Metformin	130-139	erb-b2 receptor tyrosine kinase 2	Homo sapiens	87-91
26276754-11	2015	An adjuvant trial incorporating metformin in HER2-positive DCIS is warranted.	Metformin	32-41	erb-b2 receptor tyrosine kinase 2	Homo sapiens	45-49
26266765-9	2015	Metformin induced apoptosis by down-regulating Bcl-2 and Bcl-xL expression, and up-regulating Bax and Cytochrome c expression.	Metformin	0-9	BCL2 apoptosis regulator	Homo sapiens	47-52
25555492-1	2015	OBJECTIVE: To assess the efficiency of the combined therapy with metformin and dapagliflozin, a new oral anti-diabetic drug with an insulin-independent mechanism of action, in the treatment of type-2 diabetes mellitus (T2DM) compared to DPP4 inhibitors, sulphonylureas and thiazolidindiones, also combined with metformin.	Metformin	65-74	insulin	Homo sapiens	132-139
25450818-3	2015	We investigated the effects of pioglitazone and metformin as representative insulin-sensitizing therapies on fetuin-A and OPG levels.	Metformin	48-57	alpha 2-HS glycoprotein	Homo sapiens	109-117
25450818-11	2015	CONCLUSIONS: Metformin and pioglitazone differentially affect fetuin-A and osteoprotegrin levels in diabetic women and men.	Metformin	13-22	alpha 2-HS glycoprotein	Homo sapiens	62-70
26266765-9	2015	Metformin induced apoptosis by down-regulating Bcl-2 and Bcl-xL expression, and up-regulating Bax and Cytochrome c expression.	Metformin	0-9	BCL2 like 1	Homo sapiens	57-63
26266765-9	2015	Metformin induced apoptosis by down-regulating Bcl-2 and Bcl-xL expression, and up-regulating Bax and Cytochrome c expression.	Metformin	0-9	BCL2 associated X, apoptosis regulator	Homo sapiens	94-97
26266765-9	2015	Metformin induced apoptosis by down-regulating Bcl-2 and Bcl-xL expression, and up-regulating Bax and Cytochrome c expression.	Metformin	0-9	cytochrome c, somatic	Homo sapiens	102-114
26251408-12	2015	Variations of these three metabolites were significantly associated with 17 genes (including FADS1 and FADS2) and controlled by AMPK, a metformin target.	Metformin	136-145	fatty acid desaturase 2	Homo sapiens	103-108
25962401-0	2015	Progression to insulin therapy among patients with type 2 diabetes treated with sitagliptin or sulphonylurea plus metformin dual therapy.	Metformin	114-123	insulin	Homo sapiens	15-22
26236947-5	2015	Intriguingly, AICAR or metformin treatment resulted in significant downregulation of MTDH expression via inhibiting c-Myc expression.	Metformin	23-32	metadherin	Homo sapiens	85-89
26383681-7	2015	Interestingly, metformin may enhance radiation response specifically in certain genetic backgrounds, such as in cells with loss of the tumor suppressors p53 and LKB1, giving rise to a therapeutic ratio and potential predictive biomarkers.	Metformin	15-24	tumor protein p53	Homo sapiens	153-156
26263223-7	2015	In the metformin group, TMEM18 minor allele carriers had a greater reduction in insulin levels (P = 0.04).	Metformin	7-16	insulin	Homo sapiens	80-87
26280837-4	2015	Metformin was significantly superior to placebo (standard mean differences, -0.69 to -0.51; P = 0.01-0.0001) in the primary outcome measures (body weight, body mass index, fasting glucose, fasting insulin, triglycerides, and total cholesterol).	Metformin	0-9	insulin	Homo sapiens	197-204
26335661-4	2015	Metformin inhibited histamine and serotonin uptake by OCT1, OCT3 and SERT in a dose-dependent manner, with OCT1-mediated amine uptake being most potently inhibited (IC50 = 1.5 mM).	Metformin	0-9	solute carrier family 22 member 1	Homo sapiens	54-58
26335661-4	2015	Metformin inhibited histamine and serotonin uptake by OCT1, OCT3 and SERT in a dose-dependent manner, with OCT1-mediated amine uptake being most potently inhibited (IC50 = 1.5 mM).	Metformin	0-9	solute carrier family 6 member 4	Homo sapiens	69-73
26335661-4	2015	Metformin inhibited histamine and serotonin uptake by OCT1, OCT3 and SERT in a dose-dependent manner, with OCT1-mediated amine uptake being most potently inhibited (IC50 = 1.5 mM).	Metformin	0-9	solute carrier family 22 member 1	Homo sapiens	107-111
26165398-3	2015	We aimed to establish whether the insulin sensitising drug metformin improves maternal and fetal outcomes in obese pregnant women without diabetes.	Metformin	59-68	insulin	Homo sapiens	34-41
25936719-0	2015	Metformin improves anxiety-like behaviors through AMPK-dependent regulation of autophagy following transient forebrain ischemia.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	50-54
25936719-2	2015	Metformin, an anti-diabetic drug, is an activator of AMP-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	53-81
25936719-2	2015	Metformin, an anti-diabetic drug, is an activator of AMP-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	83-87
25936719-13	2015	These data indicated that the beneficial role of metformin in behavior and autophagy flux mediates via AMPK.	Metformin	49-58	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	103-107
26194691-0	2015	Increased thrombin generation in women with polycystic ovary syndrome: A pilot study on the effect of metformin and oral contraceptives.	Metformin	102-111	coagulation factor II, thrombin	Homo sapiens	10-18
26491824-6	2015	The use of insulin-sensitizing drugs such as metformin often normalises the menstrual cycle, improving hyperandrogenism and, subsequently, the response to ovulation induction therapies.	Metformin	45-54	insulin	Homo sapiens	11-18
26260849-4	2015	The current study demonstrated that treatment with metformin significantly suppressed the upregulation of tissue factor and plasminogen activator inhibitor-1 in LPS/D-Gal-exposed mice.	Metformin	51-60	galanin and GMAP prepropeptide	Mus musculus	167-170
26260849-6	2015	These data indicate that the LPS/D-Gal-induced elevation of the stable protein level of hypoxia inducible factor 1alpha, the mRNA level of erythropoietin, vascular endothelial growth factor and matrix metalloproteinase-3, and the hepatic level of lactic acid were also suppressed by metformin.	Metformin	283-292	galanin and GMAP prepropeptide	Mus musculus	35-38
26260849-7	2015	The current study indicates that the suppressive effects of metformin on inflammation-induced coagulation may be an additional mechanism underlying the hepatoprotective effects of metformin in mice with LPS/D-Gal-induced fulminant hepatitis.	Metformin	180-189	galanin and GMAP prepropeptide	Mus musculus	209-212
26260219-10	2015	VEGF expression was decreased and E-cadherin increased in the metformin-treated group when compared with the control group.	Metformin	62-71	vascular endothelial growth factor A	Homo sapiens	0-4
26260219-10	2015	VEGF expression was decreased and E-cadherin increased in the metformin-treated group when compared with the control group.	Metformin	62-71	cadherin 1	Homo sapiens	34-44
26260219-13	2015	Metformin treatment may be useful for modulating the metastatic capacity by reducing VEGF expression and blocking epithelial-to-mesenchymal transition.	Metformin	0-9	vascular endothelial growth factor A	Homo sapiens	85-89
26276089-7	2015	Adriamycin or metformin alone or in combination induced significant increase in the survival rate, tissue catalase, reduced glutathione and tissue caspase 3 activity with significant decrease in tumor volume, tissue malondialdehyde, tissue sphingosine kinase 1 activity and tumor necrosis factor alpha and alleviated the histopathological changes with significant increase in Trp53 expression and apoptotic index compared to SEC group.	Metformin	14-23	tumor necrosis factor	Mus musculus	274-301
26265045-3	2015	In the present study, the potential modulatory effects of metformin on TNF-alpha-dependent apoptotic liver damage was investigated in mice with TNF-alpha/d-galactosamine (D-Gal)-induced liver injury.	Metformin	58-67	tumor necrosis factor	Mus musculus	71-80
26265045-3	2015	In the present study, the potential modulatory effects of metformin on TNF-alpha-dependent apoptotic liver damage was investigated in mice with TNF-alpha/d-galactosamine (D-Gal)-induced liver injury.	Metformin	58-67	tumor necrosis factor	Mus musculus	144-153
26265045-7	2015	These data indicated that metformin effectively alleviated TNF-alpha/D-Gal-induced apoptotic liver injury and these beneficial effects were at least partially mediated by AMPK.	Metformin	26-35	tumor necrosis factor	Mus musculus	59-68
26391180-0	2015	Metformin Increases Sensitivity of Pancreatic Cancer Cells to Gemcitabine by Reducing CD133+ Cell Populations and Suppressing ERK/P70S6K Signaling.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	126-129
26100439-2	2015	In the following studies, we observed that metformin, one of the most widely used antidiabetic medications, induces mitochondrial stress and induces FGF21 through a PERK-eIF2alpha-ATF4 pathway, which may contribute to the antidiabetic effect of metformin.	Metformin	43-52	fibroblast growth factor 21	Homo sapiens	149-154
26426900-5	2015	OCT1-, OCT2-, MATE1- and MATE2-K-mediated metformin uptake was significantly reduced in the presence of green tea and EGCG (P &lt; 0.05).	Metformin	42-51	solute carrier family 22 member 1	Homo sapiens	0-4
26435693-0	2015	AICAR and Metformin Exert AMPK-dependent Effects on INS-1E Pancreatic beta-cell Apoptosis via Differential Downstream Mechanisms.	Metformin	10-19	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	26-30
26435693-2	2015	In the current study, we observed the effects of two well-known AMPK activators 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and metformin, on apoptosis in rat insulinoma INS-1E cells, and further explored their possible mechanisms.	Metformin	138-147	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	64-68
26435693-6	2015	Our study revealed that AMPK activators AICAR and metformin exhibited different effects on INS-1E cell apoptosis under different culture conditions, which might be largely attributed to different downstream mediators.	Metformin	50-59	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	24-28
26360050-0	2015	Metformin Ameliorates Inflammatory Bowel Disease by Suppression of the STAT3 Signaling Pathway and Regulation of the between Th17/Treg Balance.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	71-76
26360050-2	2015	We sought to determine whether metformin reduces inflammation, by regulating p-signal transducer and activator of transcription 3 (STAT3) expression and T-helper 17 (Th17) cell proliferation, in a mouse model of inflammatory bowel disease (IBD).	Metformin	31-40	signal transducer and activator of transcription 3	Mus musculus	77-129
26360050-2	2015	We sought to determine whether metformin reduces inflammation, by regulating p-signal transducer and activator of transcription 3 (STAT3) expression and T-helper 17 (Th17) cell proliferation, in a mouse model of inflammatory bowel disease (IBD).	Metformin	31-40	signal transducer and activator of transcription 3	Mus musculus	131-136
26360050-9	2015	Treatment with metformin inhibited the expression of interleukin (IL)-17, p-STAT3, and p-mTOR.	Metformin	15-24	signal transducer and activator of transcription 3	Homo sapiens	76-81
26360050-9	2015	Treatment with metformin inhibited the expression of interleukin (IL)-17, p-STAT3, and p-mTOR.	Metformin	15-24	mechanistic target of rapamycin kinase	Homo sapiens	89-93
26360050-12	2015	CONCLUSIONS: Metformin attenuates IBD severity and reduces inflammation through the inhibition of p-STAT3 and IL-17 expression.	Metformin	13-22	signal transducer and activator of transcription 3	Homo sapiens	100-105
26265439-6	2015	Metformin was administered in vitro either to quiescent cells or during CLL cell activation stimuli, provided by classical co-culturing with CD40L-expressing fibroblasts.	Metformin	0-9	CD40 ligand	Homo sapiens	141-146
26265439-7	2015	At doses that were totally ineffective on normal lymphocytes, metformin induced apoptosis of quiescent CLL cells and inhibition of cell cycle entry when CLL were stimulated by CD40-CD40L ligation.	Metformin	62-71	CD40 ligand	Homo sapiens	181-186
26225749-0	2015	p53 is required for metformin-induced growth inhibition, senescence and apoptosis in breast cancer cells.	Metformin	20-29	tumor protein p53	Homo sapiens	0-3
26225749-2	2015	The tumor inhibitory effect of metformin on p53-mutated breast cancer cells remains unclear.	Metformin	31-40	tumor protein p53	Homo sapiens	44-47
26225749-3	2015	Data from the present study demonstrated that p53 knockdown or mutation has a negative effect on metformin or phenformin-induced growth inhibition, senescence and apoptosis in breast cancer cells.	Metformin	97-106	tumor protein p53	Homo sapiens	46-49
26225749-4	2015	We also found that p53 reactivating agent nutlin-3alpha and CP/31398 promoted metformin-induced growth inhibition, senescence and apoptosis in MCF-7 (wt p53) and MDA-MB-231 (mt p53) cells, respectively.	Metformin	78-87	tumor protein p53	Homo sapiens	19-22
26225749-4	2015	We also found that p53 reactivating agent nutlin-3alpha and CP/31398 promoted metformin-induced growth inhibition, senescence and apoptosis in MCF-7 (wt p53) and MDA-MB-231 (mt p53) cells, respectively.	Metformin	78-87	tumor protein p53	Homo sapiens	153-156
26225749-4	2015	We also found that p53 reactivating agent nutlin-3alpha and CP/31398 promoted metformin-induced growth inhibition, senescence and apoptosis in MCF-7 (wt p53) and MDA-MB-231 (mt p53) cells, respectively.	Metformin	78-87	tumor protein p53	Homo sapiens	153-156
26225749-5	2015	Treatment of MCF-7 cells with metformin or phenformin induced increase in p53 protein levels and the transcription of its downstream target genes, Bax and p21, in a dose-dependent manner.	Metformin	30-39	tumor protein p53	Homo sapiens	74-77
26225749-5	2015	Treatment of MCF-7 cells with metformin or phenformin induced increase in p53 protein levels and the transcription of its downstream target genes, Bax and p21, in a dose-dependent manner.	Metformin	30-39	BCL2 associated X, apoptosis regulator	Homo sapiens	147-150
26225749-6	2015	Moreover, we demonstrated that AMPK-mTOR signaling played a role in metformin-induced p53 up-regulation.	Metformin	68-77	mechanistic target of rapamycin kinase	Homo sapiens	36-40
26225749-6	2015	Moreover, we demonstrated that AMPK-mTOR signaling played a role in metformin-induced p53 up-regulation.	Metformin	68-77	tumor protein p53	Homo sapiens	86-89
26225749-7	2015	The present study showed that p53 is required for metformin or phenformin-induced growth inhibition, senescence and apoptosis in breast cancer cells.	Metformin	50-59	tumor protein p53	Homo sapiens	30-33
26225749-8	2015	The combination of metformin with p53 reactivating agents, like nutlin-3alpha and CP/31398, is a promising strategy for improving metformin-mediated anti-cancer therapy, especially for tumors with p53 mutations.	Metformin	19-28	tumor protein p53	Homo sapiens	197-200
26225749-8	2015	The combination of metformin with p53 reactivating agents, like nutlin-3alpha and CP/31398, is a promising strategy for improving metformin-mediated anti-cancer therapy, especially for tumors with p53 mutations.	Metformin	130-139	tumor protein p53	Homo sapiens	34-37
26225749-8	2015	The combination of metformin with p53 reactivating agents, like nutlin-3alpha and CP/31398, is a promising strategy for improving metformin-mediated anti-cancer therapy, especially for tumors with p53 mutations.	Metformin	130-139	tumor protein p53	Homo sapiens	197-200
26338686-8	2015	Prevalence of eGFR &lt;60 mL/min/1.73 m(2) among metformin initiators was 9.0% in Denmark and 25.2% in the UK.	Metformin	49-58	CD59 molecule (CD59 blood group)	Homo sapiens	29-34
26338686-9	2015	In contrast, prevalence of eGFR values &lt;30 mL/min/1.73 m(2) among metformin initiators was 0.3% in Denmark and 0.4% in the UK.	Metformin	69-78	CD59 molecule (CD59 blood group)	Homo sapiens	49-54
26338686-12	2015	The proportion of patients continuing metformin use, even after a first decline brought the eGFR below 30 mL/min/1.73 m(2), was 44% in Denmark and 62% in the UK.	Metformin	38-47	CD59 molecule (CD59 blood group)	Homo sapiens	109-114
26100439-2	2015	In the following studies, we observed that metformin, one of the most widely used antidiabetic medications, induces mitochondrial stress and induces FGF21 through a PERK-eIF2alpha-ATF4 pathway, which may contribute to the antidiabetic effect of metformin.	Metformin	245-254	fibroblast growth factor 21	Homo sapiens	149-154
26212570-3	2015	Subjects in group 1 (n = 20) were administered 40 mg of teneligliptin once daily for 5 days, and 850 mg of metformin BID was added to ongoing teneligliptin for an additional 3 days.	Metformin	107-116	BH3 interacting domain death agonist	Homo sapiens	117-120
26084759-3	2015	Unless contraindicated or not tolerated, metformin can be initiated and continued concurrently with other anti-diabetic agents or insulin.	Metformin	41-50	insulin	Homo sapiens	130-137
26016715-3	2015	Metformin is almost exclusively eliminated through the kidney primarily through active secretion mediated by Oct1, Oct2, and Mate1.	Metformin	0-9	POU domain, class 2, transcription factor 2	Mus musculus	115-119
26138461-8	2015	Metformin caused a significant reduction in liver fibrosis (Sirius red), hepatic stellate cell activation (alpha-smooth muscle actin, platelet-derived growth factor receptor beta polypeptide, transforming growth factor-betaR1, and Rho kinase), hepatic inflammation (CD68 and CD163), superoxide (dihydroethidium staining), and nitric oxide scavenging (protein nitrotyrosination).	Metformin	0-9	CD163 molecule	Rattus norvegicus	275-280
26142890-7	2015	RESULTS: The predictive parameters (sensitivity, specificity, PPV, and NPV) for improvements in HbA1c at week 24 for metformin were 0.83, 0.81, 0.44, and 0.96; for sulfonylurea, 0.79, 0.94, 0.71, and 0.96; and for insulin glargine, 0.67, 0.89, 0.65, and 0.90.	Metformin	117-126	insulin	Homo sapiens	214-221
26117686-7	2015	The pooled estimates of metformin-insulin differences were very small and statistically non-significant in fasting plasma glucose, postprandial plasma glucose and HbA1c, measured at 36-37 weeks of gestation.	Metformin	24-33	insulin	Homo sapiens	34-41
26117686-8	2015	Notably, 14-46% of those receiving metformin required additional insulin.	Metformin	35-44	insulin	Homo sapiens	65-72
26117686-9	2015	Compared with the insulin group, metformin treatment was associated with a lower incidence of neonatal hypoglycemia (relative risk, RR 0.74; 95% CI 0.58-0.93; P=0.01) and of neonatal intensive care admission (RR 0.76; 95% CI 0.59-0.97; P=0.03).	Metformin	33-42	insulin	Homo sapiens	18-25
26216367-7	2015	In male subjects consuming only metformin, a positive association between HOMA-IR and insulin (p&lt;0.05) was seen.	Metformin	32-41	insulin	Homo sapiens	74-93
26216367-9	2015	Interestingly, the female subjects on metformin displayed a positive association between HOMA-IR and insulin (p&lt;0.05) only.	Metformin	38-47	insulin	Homo sapiens	89-108
26216367-10	2015	A positive association of HOMA-IR with glucose (p&lt;0.01) and insulin (p&lt;0.05) was seen in females on metformin in combination with other anti-diabetic drugs.	Metformin	106-115	insulin	Homo sapiens	63-70
25579456-12	2015	The fraction of phosphorylated [(18)F]FDG was increased in metformin-treated cells compared with controls, suggesting that hexokinase efficiency was increased by metformin.	Metformin	59-68	hexokinase 1	Homo sapiens	123-133
25579456-12	2015	The fraction of phosphorylated [(18)F]FDG was increased in metformin-treated cells compared with controls, suggesting that hexokinase efficiency was increased by metformin.	Metformin	162-171	hexokinase 1	Homo sapiens	123-133
25981877-3	2015	Metformin may harbor a pleiotropic action, (a) decreasing inflammation (via anti COX 2 pathway and other mechanism), (b) decreasing COX 2 and VEGF mediated angiogenesis, (c) increasing negative angiogenic regulation pathway by stimulating SMAD 2/3 expression either directly or via the AMPK pathway and preventing from pulmonary hypertension development and (d) diminushin oxidative stress.	Metformin	0-9	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	81-86
25981877-3	2015	Metformin may harbor a pleiotropic action, (a) decreasing inflammation (via anti COX 2 pathway and other mechanism), (b) decreasing COX 2 and VEGF mediated angiogenesis, (c) increasing negative angiogenic regulation pathway by stimulating SMAD 2/3 expression either directly or via the AMPK pathway and preventing from pulmonary hypertension development and (d) diminushin oxidative stress.	Metformin	0-9	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	132-137
25981877-3	2015	Metformin may harbor a pleiotropic action, (a) decreasing inflammation (via anti COX 2 pathway and other mechanism), (b) decreasing COX 2 and VEGF mediated angiogenesis, (c) increasing negative angiogenic regulation pathway by stimulating SMAD 2/3 expression either directly or via the AMPK pathway and preventing from pulmonary hypertension development and (d) diminushin oxidative stress.	Metformin	0-9	vascular endothelial growth factor A	Homo sapiens	142-146
26622674-8	2015	The expression of the B-cell lymphoma (Bcl)-2 and Bcl-extra large proteins was downregulated following metformin treatment, while Bax protein expression was significantly increased.	Metformin	103-112	B cell leukemia/lymphoma 2	Mus musculus	22-45
26622703-0	2015	Metformin upregulates E-cadherin and inhibits B16F10 cell motility, invasion and migration.	Metformin	0-9	cadherin 1	Mus musculus	22-32
26622703-7	2015	The results showed that metformin effectively upregulated the expression of E-cadherin, and inhibited B16F10 cell motility, migration and invasion, in a dose-dependent manner.	Metformin	24-33	cadherin 1	Mus musculus	76-86
26622703-8	2015	This suggested that the inhibition of motility, migration and invasion of B16F10 cells by metformin may be associated with the upregulation of E-cadherin expression, indicating that metformin may have a role in the treatment of melanoma.	Metformin	90-99	cadherin 1	Mus musculus	143-153
26622703-8	2015	This suggested that the inhibition of motility, migration and invasion of B16F10 cells by metformin may be associated with the upregulation of E-cadherin expression, indicating that metformin may have a role in the treatment of melanoma.	Metformin	182-191	cadherin 1	Mus musculus	143-153
26058395-2	2015	Metformin is known to suppress prostaglandin E2 (PGE2)-induced CYP19A1 messenger RNA (mRNA) expression in human endometriotic stromal cells (ESCs).	Metformin	0-9	cytochrome P450 family 19 subfamily A member 1	Homo sapiens	63-70
26366087-11	2015	In addition, there are still uncertainties surrounding the effects of metformin or oral contraceptives in the management of insulin level, although they improved total testosterone and sex hormone-binding globulin levels.	Metformin	70-79	insulin	Homo sapiens	124-131
26675396-13	2015	Metformin could enhance the EGFR signaling pathway inhibitor AG1478 inhibition of endometrial cancer cells, which may inhibit EGFR expression of phosphorylated proteins to inhibit the phosphorylation of ERK1/2 proteins and then inhibit proliferation of endometrial cancer cells.	Metformin	0-9	epidermal growth factor receptor	Homo sapiens	28-32
26058395-9	2015	CONCLUSION: Metformin could inhibit PGE2-induced CYP19A1 mRNA expression and aromatase activity via AMPK activation and inhibition of CREB to CYP19A1 PII in human ESCs.	Metformin	12-21	cytochrome P450 family 19 subfamily A member 1	Homo sapiens	49-56
26058395-9	2015	CONCLUSION: Metformin could inhibit PGE2-induced CYP19A1 mRNA expression and aromatase activity via AMPK activation and inhibition of CREB to CYP19A1 PII in human ESCs.	Metformin	12-21	cytochrome P450 family 19 subfamily A member 1	Homo sapiens	142-149
25993908-9	2015	In insulin-resistant PCOS patients (HOMA-IR&gt; 2) metformin treatment (1.7 g per day for 4 weeks to 6 months) improved insulin sensitivity, restored mitochondrial integrity and function and normalised platelet aggregation.	Metformin	51-60	insulin	Homo sapiens	3-10
25993908-9	2015	In insulin-resistant PCOS patients (HOMA-IR&gt; 2) metformin treatment (1.7 g per day for 4 weeks to 6 months) improved insulin sensitivity, restored mitochondrial integrity and function and normalised platelet aggregation.	Metformin	51-60	insulin	Homo sapiens	120-127
26056043-0	2015	Metformin combined with aspirin significantly inhibit pancreatic cancer cell growth in vitro and in vivo by suppressing anti-apoptotic proteins Mcl-1 and Bcl-2.	Metformin	0-9	BCL2 apoptosis regulator	Homo sapiens	154-159
26056043-6	2015	Metformin combined with aspirin significantly inhibited the phosphorylation of mTOR and STAT3, and induced apoptosis as measured by caspase-3 and PARP cleavage.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	79-83
26056043-6	2015	Metformin combined with aspirin significantly inhibited the phosphorylation of mTOR and STAT3, and induced apoptosis as measured by caspase-3 and PARP cleavage.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	88-93
26056043-6	2015	Metformin combined with aspirin significantly inhibited the phosphorylation of mTOR and STAT3, and induced apoptosis as measured by caspase-3 and PARP cleavage.	Metformin	0-9	caspase 3	Homo sapiens	132-141
26056043-7	2015	Remarkably, metformin combined with aspirin significantly downregulated the anti-apoptotic proteins Mcl-1 and Bcl-2, and upregulated the pro-apoptotic proteins Bim and Puma, as well as interrupted their interactions.	Metformin	12-21	BCL2 apoptosis regulator	Homo sapiens	110-115
26056043-9	2015	In a PANC-1 xenograft mouse model, we demonstrated that the combination of metformin and aspirin significantly inhibited tumor growth and downregulated the protein expression of Mcl-1 and Bcl-2 in tumors.	Metformin	75-84	B cell leukemia/lymphoma 2	Mus musculus	188-193
26056043-10	2015	Taken together, the combination of metformin and aspirin significantly inhibited pancreatic cancer cell growth in vitro and in vivo by regulating the pro- and anti-apoptotic Bcl-2 family members, supporting the continued investigation of this two drug combination as chemopreventive or chemotherapeutic agents for pancreatic cancer.	Metformin	35-44	BCL2 apoptosis regulator	Homo sapiens	174-179
26675396-13	2015	Metformin could enhance the EGFR signaling pathway inhibitor AG1478 inhibition of endometrial cancer cells, which may inhibit EGFR expression of phosphorylated proteins to inhibit the phosphorylation of ERK1/2 proteins and then inhibit proliferation of endometrial cancer cells.	Metformin	0-9	epidermal growth factor receptor	Homo sapiens	126-130
26675396-13	2015	Metformin could enhance the EGFR signaling pathway inhibitor AG1478 inhibition of endometrial cancer cells, which may inhibit EGFR expression of phosphorylated proteins to inhibit the phosphorylation of ERK1/2 proteins and then inhibit proliferation of endometrial cancer cells.	Metformin	0-9	mitogen-activated protein kinase 3	Homo sapiens	203-209
26314870-10	2015	The combined therapy of DRSP-EE plus metformin not only decreases IR, but also improves apelin level.	Metformin	37-46	apelin	Homo sapiens	88-94
26294325-5	2015	Of the top 10 genes (fold-change &gt; 10, P &lt; 10(-10)) regulated by metformin plus aspirin, PCDH18, CCL2, RASL11A, FAM111B and BMP5 were down-regulated &gt;= 20-fold, while NGFR, NPTX1, C7orf57, MRPL23AS1 and UNC5B were up-regulated &gt;= 10-fold.	Metformin	71-80	protocadherin 18	Homo sapiens	95-101
26294325-5	2015	Of the top 10 genes (fold-change &gt; 10, P &lt; 10(-10)) regulated by metformin plus aspirin, PCDH18, CCL2, RASL11A, FAM111B and BMP5 were down-regulated &gt;= 20-fold, while NGFR, NPTX1, C7orf57, MRPL23AS1 and UNC5B were up-regulated &gt;= 10-fold.	Metformin	71-80	neuronal pentraxin 1	Homo sapiens	182-187
26291325-1	2015	INTRODUCTION: Metformin is proposed as adjuvant therapy in cancer treatment because of its ability to limit cancer incidence by negatively modulating the PI3K/AKT/mTOR pathway.	Metformin	14-23	AKT serine/threonine kinase 1	Homo sapiens	159-162
26291325-1	2015	INTRODUCTION: Metformin is proposed as adjuvant therapy in cancer treatment because of its ability to limit cancer incidence by negatively modulating the PI3K/AKT/mTOR pathway.	Metformin	14-23	mechanistic target of rapamycin kinase	Homo sapiens	163-167
26291325-12	2015	Not only glucose levels but also amino acid concentration can influence the observed metformin inhibitory effect on the mTOR pathway as well as its pro-apoptotic effect.	Metformin	85-94	mechanistic target of rapamycin kinase	Homo sapiens	120-124
26152715-0	2015	Metformin Inhibits the Production of Reactive Oxygen Species from NADH:Ubiquinone Oxidoreductase to Limit Induction of Interleukin-1beta (IL-1beta) and Boosts Interleukin-10 (IL-10) in Lipopolysaccharide (LPS)-activated Macrophages.	Metformin	0-9	interleukin 1 beta	Homo sapiens	119-136
26152715-0	2015	Metformin Inhibits the Production of Reactive Oxygen Species from NADH:Ubiquinone Oxidoreductase to Limit Induction of Interleukin-1beta (IL-1beta) and Boosts Interleukin-10 (IL-10) in Lipopolysaccharide (LPS)-activated Macrophages.	Metformin	0-9	interleukin 1 beta	Homo sapiens	138-146
26152715-1	2015	Metformin, a frontline treatment for type II diabetes mellitus, decreases production of the pro-form of the inflammatory cytokine IL-1beta in response to LPS in macrophages.	Metformin	0-9	interleukin 1 beta	Homo sapiens	130-138
26152715-7	2015	Another complex I inhibitor, rotenone, mimicked the effect of metformin on pro-IL-1beta and IL-10.	Metformin	62-71	interleukin 1 beta	Homo sapiens	79-87
26071397-5	2015	Activation of AMPK with 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside, metformin, or overexpression of constitutively active AMPK markedly attenuated TGF-beta1 functions.	Metformin	80-89	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	14-18
25687657-9	2015	Higher concentrations of metformin lead to a significant (p &lt; 0.05) dose-dependent attenuation of the progesterone effect with regard to IGFBP-1, -3, -5, -6, as well as IGF I receptor, while it did not change the expression of IGFBP-2 and -4, IGF I and II and the IGF II receptor.	Metformin	25-34	insulin like growth factor 1	Homo sapiens	246-258
26314870-0	2015	Evaluation of Apelin and Insulin Resistance in Patients with PCOS and Therapeutic Effect of Drospirenone-Ethinylestradiol Plus Metformin.	Metformin	127-136	insulin	Homo sapiens	25-32
25904026-3	2015	METHODS: A literature review was completed aiming to compare the glycaemic control, maternal and fetal out comes of metformin therapy with insulin.	Metformin	116-125	insulin	Homo sapiens	139-146
26087341-7	2015	Insulin resistance may be improved among obese individuals with T1DM by biguanides (metformin) and glucagon-like peptide-1 agonists (exenatide).	Metformin	84-93	insulin	Homo sapiens	0-7
26464716-0	2015	Genetic variants of OCT1 influence glycemic response to metformin in Han Chinese patients with type-2 diabetes mellitus in Shanghai.	Metformin	56-65	solute carrier family 22 member 1	Homo sapiens	20-24
26050920-11	2015	Metformin influences on AMPK/mTOR cell signaling were evaluated by investigating AKT, AMPK and S6 phosphorylation levels.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	29-33
26050920-11	2015	Metformin influences on AMPK/mTOR cell signaling were evaluated by investigating AKT, AMPK and S6 phosphorylation levels.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	81-84
26464716-1	2015	AIMS/HYPOTHESIS: Genetic variation in OCT1 can influence the glycemic response to metformin.	Metformin	82-91	solute carrier family 22 member 1	Homo sapiens	38-42
26464716-2	2015	We evaluated the effects of the OCT1 single-nucleotide polymorphisms (SNPs), rs1867351, rs4709400, rs628031, and rs2297374, on metformin efficacy in type-2 diabetes mellitus (DM) patients.	Metformin	127-136	solute carrier family 22 member 1	Homo sapiens	32-36
26464716-7	2015	Conclusions /interpretation: The rs1867351, rs4709400, rs628031, and rs2297374 SNPs of OCT1 have selective effects on FPG, PPG, and HbA1c in HCS DM patients in response to metformin treatment.	Metformin	172-181	solute carrier family 22 member 1	Homo sapiens	87-91
26066530-7	2015	INTERVENTIONS: Insulin resistance was treated with lifestyle intervention and metformin, and diabetes with the addition of glitazones, glucagon-like peptide 1 agonists, and/or insulin.	Metformin	78-87	insulin	Homo sapiens	15-22
26147751-5	2015	We further show that metformin decreases the high-glucose-stimulated nuclear entry rate of two transcription factors, carbohydrate response element-binding protein (ChREBP) and forkhead box O1 (FOXO1), as well as their recruitment on the TXNIP promoter.	Metformin	21-30	MLX interacting protein like	Homo sapiens	118-163
25871950-9	2015	Metformin inhibited SirT2 expression in WBCs significantly (P&lt;0.05) and did not induce any significant changes in other SirT forms and p53, whereas it induced p16(INK4a) mRNA expression in WBCs (P&lt;0.05) at the basal levels.	Metformin	0-9	cyclin dependent kinase inhibitor 2A	Mus musculus	162-165
25871950-9	2015	Metformin inhibited SirT2 expression in WBCs significantly (P&lt;0.05) and did not induce any significant changes in other SirT forms and p53, whereas it induced p16(INK4a) mRNA expression in WBCs (P&lt;0.05) at the basal levels.	Metformin	0-9	cyclin dependent kinase inhibitor 2A	Mus musculus	166-171
25871950-10	2015	Additionally, metformin treatment significantly inhibited SirT7, SirT1, and p16(INK4a) mRNA expression in WBCs at 1, 2, and 3 hr, whereas p53 was inhibited significantly at 2 hr after LPS injection.	Metformin	14-23	cyclin dependent kinase inhibitor 2A	Mus musculus	76-79
25871950-10	2015	Additionally, metformin treatment significantly inhibited SirT7, SirT1, and p16(INK4a) mRNA expression in WBCs at 1, 2, and 3 hr, whereas p53 was inhibited significantly at 2 hr after LPS injection.	Metformin	14-23	cyclin dependent kinase inhibitor 2A	Mus musculus	80-85
25962562-9	2015	Following treatment with bisperoxopicolinatooxovanadate (BPV) or metformin in the insulin-resistant skeletal muscle cells, there was an increase in the rate of glucose uptake, an increase in GLUT4 expression and its translocation, a reduction in the expression of PTEN and p-PTEN, and a decrease in cell apoptosis compared with untreated insulin-resistant cells.	Metformin	65-74	insulin	Homo sapiens	82-89
25962562-9	2015	Following treatment with bisperoxopicolinatooxovanadate (BPV) or metformin in the insulin-resistant skeletal muscle cells, there was an increase in the rate of glucose uptake, an increase in GLUT4 expression and its translocation, a reduction in the expression of PTEN and p-PTEN, and a decrease in cell apoptosis compared with untreated insulin-resistant cells.	Metformin	65-74	insulin	Homo sapiens	338-345
26147751-0	2015	New Insight Into Metformin Action: Regulation of ChREBP and FOXO1 Activities in Endothelial Cells.	Metformin	17-26	MLX interacting protein like	Homo sapiens	49-55
26147751-0	2015	New Insight Into Metformin Action: Regulation of ChREBP and FOXO1 Activities in Endothelial Cells.	Metformin	17-26	forkhead box O1	Homo sapiens	60-65
26147751-4	2015	Here we report that high glucose-induced endothelial dysfunction is associated with induction of TXNIP expression in primary human aortic endothelial cells exposed to high-glucose conditions, whereas the metformin treatment suppresses high-glucose-induced TXNIP expression at mRNA and protein levels.	Metformin	204-213	thioredoxin interacting protein	Homo sapiens	256-261
26622608-13	2015	Immunohistochemical analysis revealed that downregulation of the expression of specific proteins associated with AMPK promoted xenograft growth and angiogenesis, while western blotting revealed inhibition of the AKT/mTOR signaling pathway in xenografts treated with metformin in combination with cisplatin.	Metformin	266-275	AKT serine/threonine kinase 1	Homo sapiens	212-215
25894097-0	2015	Metformin represses androgen-dependent and androgen-independent prostate cancers by targeting androgen receptor.	Metformin	0-9	androgen receptor	Homo sapiens	94-111
25854169-0	2015	Metformin inhibits thyroid cancer cell growth, migration, and EMT through the mTOR pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	78-82
25854169-2	2015	Recent evidences have demonstrated that the antidiabetic agent metformin, an activator of 5"-AMP-activated protein kinase, can impair the proliferation and migration of cancer cells via inhibition of mTOR.	Metformin	63-72	mechanistic target of rapamycin kinase	Homo sapiens	200-204
25854169-4	2015	In this study, we show that metformin can inhibit mTOR pathway to impair growth and migration of the thyroid cancer cell lines.	Metformin	28-37	mechanistic target of rapamycin kinase	Homo sapiens	50-54
25854169-5	2015	Cyclin D1 and c-Myc are important regulators of cancer cell growth, and we observed that treatment of thyroid cancer cells with metformin reduced c-Myc and cyclin D1 expression through suppression of mTOR and subsequent inhibition of P70S6K1 and 4E-BP1 phosphorylation.	Metformin	128-137	mechanistic target of rapamycin kinase	Homo sapiens	200-204
25854169-7	2015	Moreover, metformin regulated expression of the EMT-related markers E-cadherin, N-cadherin, and Snail.	Metformin	10-19	cadherin 1	Homo sapiens	68-78
25854169-7	2015	Moreover, metformin regulated expression of the EMT-related markers E-cadherin, N-cadherin, and Snail.	Metformin	10-19	snail family transcriptional repressor 1	Homo sapiens	96-101
25854169-8	2015	Additionally, knockdown of TSC2, the upstream regulatory molecule of mTOR pathway, or treatment of rapamycin, the mTOR inhibitor, could abolish the effects of metformin to regulate thyroid cancer cell proliferation, migration, EMT, and mTOR pathway molecules.	Metformin	159-168	mechanistic target of rapamycin kinase	Homo sapiens	69-73
25854169-8	2015	Additionally, knockdown of TSC2, the upstream regulatory molecule of mTOR pathway, or treatment of rapamycin, the mTOR inhibitor, could abolish the effects of metformin to regulate thyroid cancer cell proliferation, migration, EMT, and mTOR pathway molecules.	Metformin	159-168	mechanistic target of rapamycin kinase	Homo sapiens	114-118
25854169-8	2015	Additionally, knockdown of TSC2, the upstream regulatory molecule of mTOR pathway, or treatment of rapamycin, the mTOR inhibitor, could abolish the effects of metformin to regulate thyroid cancer cell proliferation, migration, EMT, and mTOR pathway molecules.	Metformin	159-168	mechanistic target of rapamycin kinase	Homo sapiens	114-118
25854169-9	2015	These results indicate that metformin can suppress the proliferation, migration, and EMT of thyroid cancer cell lines by inhibiting mTOR signaling.	Metformin	28-37	mechanistic target of rapamycin kinase	Homo sapiens	132-136
26196392-5	2015	Moreover, we observed that metformin induced G0/G1 phase arrest accompanied by the up-regulation of p21CIP1 and p27KIP1.	Metformin	27-36	cyclin dependent kinase inhibitor 1A	Homo sapiens	100-107
26196392-7	2015	Most importantly, the up-regulation of AMPK, p53, p21CIP1, p27KIP1 and the down-regulation of cyclinD1 are involved in the anti-tumor action of metformin in vivo.	Metformin	144-153	tumor protein p53	Homo sapiens	45-48
26196392-7	2015	Most importantly, the up-regulation of AMPK, p53, p21CIP1, p27KIP1 and the down-regulation of cyclinD1 are involved in the anti-tumor action of metformin in vivo.	Metformin	144-153	cyclin dependent kinase inhibitor 1A	Homo sapiens	50-57
26196392-9	2015	AMPK, p53, p21CIP1, p27KIP1 and cyclinD1 are involved in the inhibition of tumor growth that is induced by metformin and cell cycle arrest in ESCC.	Metformin	107-116	tumor protein p53	Homo sapiens	6-9
26196392-9	2015	AMPK, p53, p21CIP1, p27KIP1 and cyclinD1 are involved in the inhibition of tumor growth that is induced by metformin and cell cycle arrest in ESCC.	Metformin	107-116	cyclin dependent kinase inhibitor 1A	Homo sapiens	11-18
26045616-4	2015	Metformin treatment prevented acute stress-induced necroinflammatory reaction, reduced alanine aminotransferase and aspartate aminotransferase serum activity, and diminished lipoperoxidation.	Metformin	0-9	glutamic-oxaloacetic transaminase 2	Rattus norvegicus	116-142
26045616-6	2015	The metformin-treated groups exhibited less severe mitochondrial damage (markers: cytochrome c release, citrate synthase activity, mtDNA copy number, mitochondrial respiration) and apoptosis (caspase 9 and caspase 3 activation).	Metformin	4-13	caspase 9	Rattus norvegicus	192-201
26045616-10	2015	Metformin downregulated the I/R-induced expression of proinflammatory (TNF-alpha, TLR4, IL-1beta, Ccr2) and infiltrating monocyte (Ly6c) and macrophage (CD11b) markers.	Metformin	0-9	tumor necrosis factor	Rattus norvegicus	71-80
26045616-10	2015	Metformin downregulated the I/R-induced expression of proinflammatory (TNF-alpha, TLR4, IL-1beta, Ccr2) and infiltrating monocyte (Ly6c) and macrophage (CD11b) markers.	Metformin	0-9	toll-like receptor 4	Rattus norvegicus	82-86
26045616-10	2015	Metformin downregulated the I/R-induced expression of proinflammatory (TNF-alpha, TLR4, IL-1beta, Ccr2) and infiltrating monocyte (Ly6c) and macrophage (CD11b) markers.	Metformin	0-9	interleukin 1 beta	Rattus norvegicus	88-96
26045616-10	2015	Metformin downregulated the I/R-induced expression of proinflammatory (TNF-alpha, TLR4, IL-1beta, Ccr2) and infiltrating monocyte (Ly6c) and macrophage (CD11b) markers.	Metformin	0-9	C-C motif chemokine receptor 2	Rattus norvegicus	98-102
26045616-10	2015	Metformin downregulated the I/R-induced expression of proinflammatory (TNF-alpha, TLR4, IL-1beta, Ccr2) and infiltrating monocyte (Ly6c) and macrophage (CD11b) markers.	Metformin	0-9	Ly6-C antigen	Rattus norvegicus	131-135
26045616-10	2015	Metformin downregulated the I/R-induced expression of proinflammatory (TNF-alpha, TLR4, IL-1beta, Ccr2) and infiltrating monocyte (Ly6c) and macrophage (CD11b) markers.	Metformin	0-9	integrin subunit alpha M	Rattus norvegicus	153-158
26236179-3	2015	One of these detectors is AMPK (5" AMP-activated protein kinase), a protein kinase activated by ATP deficiency but also by several natural substances such as polyphenols or synthetic molecules like metformin, used in the treatment of insulin resistance.	Metformin	198-207	insulin	Homo sapiens	234-241
25547060-7	2015	Regarding neonatal outcomes, when compared with insulin group, metformin presented significantly lower average birth weights (MD = -44.35, 95 % CI -85.79 to -2.90, P = 0.04), incidence of hypoglycemia (RR = 0.69, 95 % CI 0.55-0.87, P = 0.001) and neonatal intensive care unit (NICU) (RR = 0.82, 95 % CI 0.67-0.99, P = 0.04).	Metformin	63-72	insulin	Homo sapiens	48-55
25547060-8	2015	CONCLUSION: Metformin can significantly reduce several adverse maternal and neonatal outcomes including PIH rate, incidence of hypoglycemia and NICU, thus it may be an effective and safe alternative or additional treatment to insulin for GDM women.	Metformin	12-21	insulin	Homo sapiens	226-233
26147751-5	2015	We further show that metformin decreases the high-glucose-stimulated nuclear entry rate of two transcription factors, carbohydrate response element-binding protein (ChREBP) and forkhead box O1 (FOXO1), as well as their recruitment on the TXNIP promoter.	Metformin	21-30	MLX interacting protein like	Homo sapiens	165-171
26147751-5	2015	We further show that metformin decreases the high-glucose-stimulated nuclear entry rate of two transcription factors, carbohydrate response element-binding protein (ChREBP) and forkhead box O1 (FOXO1), as well as their recruitment on the TXNIP promoter.	Metformin	21-30	forkhead box O1	Homo sapiens	177-192
26147751-5	2015	We further show that metformin decreases the high-glucose-stimulated nuclear entry rate of two transcription factors, carbohydrate response element-binding protein (ChREBP) and forkhead box O1 (FOXO1), as well as their recruitment on the TXNIP promoter.	Metformin	21-30	forkhead box O1	Homo sapiens	194-199
26147751-5	2015	We further show that metformin decreases the high-glucose-stimulated nuclear entry rate of two transcription factors, carbohydrate response element-binding protein (ChREBP) and forkhead box O1 (FOXO1), as well as their recruitment on the TXNIP promoter.	Metformin	21-30	thioredoxin interacting protein	Homo sapiens	238-243
26147751-8	2015	Metformin down-regulates high-glucose-induced TXNIP transcription by inactivating ChREBP and FOXO1 in endothelial cells, partially through AMP-activated protein kinase activation.	Metformin	0-9	thioredoxin interacting protein	Homo sapiens	46-51
26147751-8	2015	Metformin down-regulates high-glucose-induced TXNIP transcription by inactivating ChREBP and FOXO1 in endothelial cells, partially through AMP-activated protein kinase activation.	Metformin	0-9	MLX interacting protein like	Homo sapiens	82-88
26147751-8	2015	Metformin down-regulates high-glucose-induced TXNIP transcription by inactivating ChREBP and FOXO1 in endothelial cells, partially through AMP-activated protein kinase activation.	Metformin	0-9	forkhead box O1	Homo sapiens	93-98
25889897-5	2015	Furthermore, the blockade of AMPK by compound C abrogated, while metformin, an activator of AMPK, strengthened the effect of emodin on the inhibition of ILK expression.	Metformin	65-74	integrin linked kinase	Homo sapiens	153-156
25846811-9	2015	We found an inverse correlation between the intensity of ERK activity and the degree of AMPK activation after stimulation with either glucose deprivation or metformin.	Metformin	157-166	mitogen-activated protein kinase 1	Homo sapiens	57-60
25846811-10	2015	We also found that the inhibition of ERK activity by U0126 restored AMPK activation after metformin treatment.	Metformin	90-99	mitogen-activated protein kinase 1	Homo sapiens	37-40
25846811-12	2015	Importantly, metformin induced ERK activation by suppressing the protein levels of dual specificity phosphatase 6, a negative regulator of ERK.	Metformin	13-22	mitogen-activated protein kinase 1	Homo sapiens	31-34
25846811-12	2015	Importantly, metformin induced ERK activation by suppressing the protein levels of dual specificity phosphatase 6, a negative regulator of ERK.	Metformin	13-22	mitogen-activated protein kinase 1	Homo sapiens	139-142
25846811-13	2015	This crosstalk between AMPK and ERK could diminish the antileukemic activity of metformin.	Metformin	80-89	mitogen-activated protein kinase 1	Homo sapiens	32-35
25975389-0	2015	Metformin targets Axl and Tyro3 receptor tyrosine kinases to inhibit cell proliferation and overcome chemoresistance in ovarian cancer cells.	Metformin	0-9	TYRO3 protein tyrosine kinase	Homo sapiens	26-31
26059289-8	2015	Metformin enhances the action of insulin in liver and skeletal muscle, and its efficacy for delaying or preventing the onset of diabetes has been proven in large, well-designed, randomised trials, such as the Diabetes Prevention Program and other studies.	Metformin	0-9	insulin	Homo sapiens	33-40
26116622-6	2015	Finally, we discuss the current understanding of the actions of FGF21 as a crucial regulator mediating beneficial metabolic effects of therapeutic agents such as metformin, glucagon/glucagon-like peptide 1 analogues, thiazolidinedione, sirtuin 1 activators, and lipoic acid.	Metformin	162-171	fibroblast growth factor 21	Homo sapiens	64-69
25975389-4	2015	We next observed the effect of metformin on expression of Axl and Tyro3 receptor tyrosine kinases (RTKs) which belong to the TAM subfamily of RTKs transducing pro-survival and anti-apoptotic signals.	Metformin	31-40	TYRO3 protein tyrosine kinase	Homo sapiens	66-71
25975389-5	2015	Metformin treatment of ovarian cancer cells decreased both mRNA and protein levels of Axl and Tyro3 in a dose-dependent manner.	Metformin	0-9	TYRO3 protein tyrosine kinase	Homo sapiens	94-99
25975389-6	2015	Axl promoter activity was also inhibited by metformin, indicating that metformin suppresses Axl and Tyro3 expression at the transcriptional level.	Metformin	44-53	TYRO3 protein tyrosine kinase	Homo sapiens	100-105
25975389-6	2015	Axl promoter activity was also inhibited by metformin, indicating that metformin suppresses Axl and Tyro3 expression at the transcriptional level.	Metformin	71-80	TYRO3 protein tyrosine kinase	Homo sapiens	100-105
25975389-7	2015	Metformin treatment was also found to augment its anti-proliferative effect in SKOV3 and taxol-resistant SKOV3/TR cells transfected with Axl and Tyro3 specific siRNAs, siAxl and siTyro3, respectively, suggesting that metformin might target Axl and Tyro3 RTKs to restrain cell proliferation.	Metformin	0-9	TYRO3 protein tyrosine kinase	Homo sapiens	145-150
25975389-7	2015	Metformin treatment was also found to augment its anti-proliferative effect in SKOV3 and taxol-resistant SKOV3/TR cells transfected with Axl and Tyro3 specific siRNAs, siAxl and siTyro3, respectively, suggesting that metformin might target Axl and Tyro3 RTKs to restrain cell proliferation.	Metformin	0-9	TYRO3 protein tyrosine kinase	Homo sapiens	180-185
25975389-9	2015	Collectively, our data showed that metformin caused reduction of Axl and Tyro3 RTKs" expression, inactivation of downstream effectors, and decrease of anti-apoptotic protein level, forming a potent therapeutic strategy to facilitate its anticancer activity as well as to overcome chemoresistance in human ovarian cancer cells.	Metformin	35-44	TYRO3 protein tyrosine kinase	Homo sapiens	73-78
25760137-8	2015	When metformin was added to the high glucose medium, the activity of SOD in supernatant fluid was increased significantly, whereas a significant reduction (P&lt;0.05) was observed in the levels of MDA in the supernatant, intracellular p22phox mRNA and protein, p-p38MAPK protein in addition to ROS production in rat glomerular MCs.	Metformin	5-14	cytochrome b-245 alpha chain	Rattus norvegicus	235-242
25921843-9	2015	Compared to baseline, metformin significantly improved metabolic parameters and insulin sensitivity, increased SIRT1 gene/protein expression and SIRT1 promoter chromatin accessibility, elevated mTOR gene expression with concomitant reduction in p70S6K phosphorylation in subjects" PBMCs, and modified the plasma N-glycan profile.	Metformin	22-31	mechanistic target of rapamycin kinase	Homo sapiens	194-198
25921843-10	2015	Compared to placebo, metformin increased SIRT1 protein expression and reduced p70S6K phosphorylation (a proxy of mTOR activity).	Metformin	21-30	mechanistic target of rapamycin kinase	Homo sapiens	113-117
25351941-7	2015	Metformin pretreatment for 24 h of HER2+ MDA-MB-361 cells, which were subsequently treated for 48 h with Herceptin, induced additional decline in cell survival.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	35-39
25351941-8	2015	The analysis of influence of metformin on phenotype of breast cancer cells revealed significantly lower number of diabetic cancer patients treated with metformin with overexpressed HER2+ tumors (p &lt; 0.013), while the number of patients with ER+PR+ tumors was not significantly changed (p &lt; 0.832).	Metformin	29-38	erb-b2 receptor tyrosine kinase 2	Homo sapiens	181-185
25351941-8	2015	The analysis of influence of metformin on phenotype of breast cancer cells revealed significantly lower number of diabetic cancer patients treated with metformin with overexpressed HER2+ tumors (p &lt; 0.013), while the number of patients with ER+PR+ tumors was not significantly changed (p &lt; 0.832).	Metformin	152-161	erb-b2 receptor tyrosine kinase 2	Homo sapiens	181-185
25351941-10	2015	The use of metformin was associated with pronounced decrease in HER2 overexpressing tumors.	Metformin	11-20	erb-b2 receptor tyrosine kinase 2	Homo sapiens	64-68
26013675-4	2015	RESULTS: Increased risks of HCC were found for use of insulin (odds ratio [OR] = 3.73, 95% confidence interval [CI] 2.52-5.51), sulfonylureas (OR = 1.39, 95%CI 0.98-1.99), and repaglinide (OR = 2.12, 95%CI 1.38-3.26), while a reduced risk was found for use of metformin (OR = 0.57, 95%CI 0.41-0.79).	Metformin	260-269	insulin	Homo sapiens	54-61
25908446-0	2015	Metformin increases peroxisome proliferator-activated receptor gamma Co-activator-1alpha and utrophin a expression in dystrophic skeletal muscle.	Metformin	0-9	utrophin	Mus musculus	93-101
26013675-5	2015	The risk of HCC increased with increasing duration of insulin use (OR = 2.52 for &lt;1 year, 5.41 for 1-2 years, and 6.01 for &gt;=2 years; p for trend &lt; 0.001), while no clear pattern with duration was observed for sulfonylureas, repaglinide, and metformin.	Metformin	251-260	insulin	Homo sapiens	54-61
26013675-6	2015	CONCLUSION: Our study supports the evidence that patients with diabetes using metformin, and possibly other antidiabetic drugs that increase insulin sensibility, have a reduced risk of HCC, while those using insulin or drugs that increase circulating insulin, such as insulin secretagogues, have an increased risk.	Metformin	78-87	insulin	Homo sapiens	141-148
26665932-7	2015	CONCLUSIONS: Metformin can effectively inhibit the proliferation and collagen synthesis of the human keloids fibroblasts in vitro, which may be associated with the suppression of phosphorylation of Akt/FoxO1 signaling pathway	Metformin	13-22	AKT serine/threonine kinase 1	Homo sapiens	198-201
26665932-7	2015	CONCLUSIONS: Metformin can effectively inhibit the proliferation and collagen synthesis of the human keloids fibroblasts in vitro, which may be associated with the suppression of phosphorylation of Akt/FoxO1 signaling pathway	Metformin	13-22	forkhead box O1	Homo sapiens	202-207
26140084-6	2015	Metformin has a number of biochemical effects that would suggest a benefit in treating chronic liver diseases, particularly in the context of insulin resistance and inflammation.	Metformin	0-9	insulin	Homo sapiens	142-149
26480664-3	2015	Patients in the GLP-1 group were given GLP-1 analogue and metformin hydrochloride.	Metformin	58-81	glucagon	Homo sapiens	16-21
26111812-3	2015	In a window of opportunity trial of metformin in non-diabetic breast cancer patients, Dowling and colleagues examined both the direct actions of the drug on cancer cells (as mediated by AMP kinase), as well as its indirect actions (as mediated by circulating insulin).	Metformin	36-45	insulin	Homo sapiens	259-266
26111812-4	2015	The data suggest that short-term administration of metformin in this setting has anti-tumor effects significantly involving the indirect, insulin-dependent pathway.	Metformin	51-60	insulin	Homo sapiens	138-145
26111001-0	2015	Basal Autophagy and Feedback Activation of Akt Are Associated with Resistance to Metformin-Induced Inhibition of Hepatic Tumor Cell Growth.	Metformin	81-90	AKT serine/threonine kinase 1	Homo sapiens	43-46
26111001-5	2015	Mechanistically, we found that metformin inhibited mTOR in all these hepatic tumor cells.	Metformin	31-40	mechanistic target of rapamycin kinase	Homo sapiens	51-55
26111001-6	2015	However, SMMC-7721 cells had higher levels of basal autophagy and mTORC2-mediated feedback activation of Akt than HepG2 cells, which may render SMMC-7721 cells to be more resistant to metformin-induced inhibition of cell growth.	Metformin	184-193	AKT serine/threonine kinase 1	Homo sapiens	105-108
26111001-7	2015	Similarly, HCC-97L and HCC-LM3 cells also had higher feedback activation of AKT than HepG2 cells, which may also account for their resistance to metformin-induced inhibition of cell growth.	Metformin	145-154	AKT serine/threonine kinase 1	Homo sapiens	76-79
26111001-8	2015	Therefore, the various basal autophagy and mTOR activity in different cancer cells may contribute to the controversial findings on the use of metformin in inhibition of cancers in humans.	Metformin	142-151	mechanistic target of rapamycin kinase	Homo sapiens	43-47
26083494-10	2015	The follow-up network analyses and literature mining revealed that seven genes (CDKN1A, ESR1, MAX, MYC, PPARGC1A, SP1, and STK11) and one novel MYC-centered pathway with CDKN1A, SP1, and STK11 might play important roles in metformin"s antidiabetic and anticancer effects.	Metformin	223-232	cyclin dependent kinase inhibitor 1A	Homo sapiens	170-176
25817233-11	2015	Co-treatment with metformin or AICAR decreased the TNF-alpha-induced intracellular TG, accompanied by significantly enhanced AMPK and ACC phosphorylation, suppressed mTOR and p70S6K phosphorylation, and reduced SREBP-1 and FAS expressions.	Metformin	18-27	tumor necrosis factor	Homo sapiens	51-60
25817233-11	2015	Co-treatment with metformin or AICAR decreased the TNF-alpha-induced intracellular TG, accompanied by significantly enhanced AMPK and ACC phosphorylation, suppressed mTOR and p70S6K phosphorylation, and reduced SREBP-1 and FAS expressions.	Metformin	18-27	mechanistic target of rapamycin kinase	Homo sapiens	166-170
26075749-5	2015	Meanwhile, the unfolded protein response regulator CHOP, p-eIF2alpha, calreticulin, GRP78 and ATP2A1, all of which are also considered as ER stress markers, are upregulated by metformin and miR-708-5p.	Metformin	176-185	DNA damage inducible transcript 3	Homo sapiens	51-55
26075749-5	2015	Meanwhile, the unfolded protein response regulator CHOP, p-eIF2alpha, calreticulin, GRP78 and ATP2A1, all of which are also considered as ER stress markers, are upregulated by metformin and miR-708-5p.	Metformin	176-185	calreticulin	Homo sapiens	70-82
26075749-5	2015	Meanwhile, the unfolded protein response regulator CHOP, p-eIF2alpha, calreticulin, GRP78 and ATP2A1, all of which are also considered as ER stress markers, are upregulated by metformin and miR-708-5p.	Metformin	176-185	heat shock protein family A (Hsp70) member 5	Homo sapiens	84-89
26075749-5	2015	Meanwhile, the unfolded protein response regulator CHOP, p-eIF2alpha, calreticulin, GRP78 and ATP2A1, all of which are also considered as ER stress markers, are upregulated by metformin and miR-708-5p.	Metformin	176-185	ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1	Homo sapiens	94-100
26065921-2	2015	Here, we identified microRNA-27b (miR-27b) as a key regulator for the generation of a side-population in breast cancer cells that showed CSC properties, and also found that the anti-type II diabetes (T2D) drug metformin reduced this side-population via miR-27b-mediated repression of ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1), which is involved in T2D development.	Metformin	210-219	ectonucleotide pyrophosphatase/phosphodiesterase 1	Homo sapiens	284-348
26065921-2	2015	Here, we identified microRNA-27b (miR-27b) as a key regulator for the generation of a side-population in breast cancer cells that showed CSC properties, and also found that the anti-type II diabetes (T2D) drug metformin reduced this side-population via miR-27b-mediated repression of ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1), which is involved in T2D development.	Metformin	210-219	ectonucleotide pyrophosphatase/phosphodiesterase 1	Homo sapiens	350-355
26040000-3	2015	Inhibiting lysosomal and autophagic activities promoted endogenous PLN accumulation, whereas accelerating autophagy with metformin enhanced PLN degradation in CMNCs.	Metformin	121-130	phospholamban	Mus musculus	140-143
26040000-4	2015	This reduction in PLN levels was functionally correlated with an increased rate of SERCA2a activity, accounting for an inotropic effect of metformin.	Metformin	139-148	phospholamban	Mus musculus	18-21
26040000-5	2015	Metabolic labeling reaffirmed that metformin promoted wild-type and R9C PLN degradation.	Metformin	35-44	phospholamban	Mus musculus	72-75
25903858-0	2015	Vitamin D3 potentiates the growth inhibitory effects of metformin in DU145 human prostate cancer cells mediated by AMPK/mTOR signalling pathway.	Metformin	56-65	mechanistic target of rapamycin kinase	Homo sapiens	120-124
25472847-11	2015	CONCLUSION: Adding metformin to the conventional insulin regimen effectively achieved tight glycaemic control with a lower dose of insulin.	Metformin	19-28	insulin	Homo sapiens	49-56
25472847-11	2015	CONCLUSION: Adding metformin to the conventional insulin regimen effectively achieved tight glycaemic control with a lower dose of insulin.	Metformin	19-28	insulin	Homo sapiens	131-138
25552600-0	2015	Metformin inhibits monocyte-to-macrophage differentiation via AMPK-mediated inhibition of STAT3 activation: potential role in atherosclerosis.	Metformin	0-9	signal transducer and activator of transcription 3	Mus musculus	90-95
25552600-2	2015	In this study, we investigated the molecular mechanisms responsible for monocyte-to-macrophage differentiation and, subsequently, the effect of metformin in regressing angiotensin II (Ang-II)-mediated atheromatous plaque formation in ApoE(-/-) mice.	Metformin	144-153	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	168-182
25552600-2	2015	In this study, we investigated the molecular mechanisms responsible for monocyte-to-macrophage differentiation and, subsequently, the effect of metformin in regressing angiotensin II (Ang-II)-mediated atheromatous plaque formation in ApoE(-/-) mice.	Metformin	144-153	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	184-190
25552600-2	2015	In this study, we investigated the molecular mechanisms responsible for monocyte-to-macrophage differentiation and, subsequently, the effect of metformin in regressing angiotensin II (Ang-II)-mediated atheromatous plaque formation in ApoE(-/-) mice.	Metformin	144-153	apolipoprotein E	Mus musculus	234-238
25552600-9	2015	Metformin attenuated Ang-II-induced atheromatous plaque formation and aortic aneurysm in ApoE(-/-) mice partly by reducing monocyte infiltration.	Metformin	0-9	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	Mus musculus	21-27
25552600-9	2015	Metformin attenuated Ang-II-induced atheromatous plaque formation and aortic aneurysm in ApoE(-/-) mice partly by reducing monocyte infiltration.	Metformin	0-9	apolipoprotein E	Mus musculus	89-93
25794703-4	2015	Most studies have used metformin, an AMP-activated protein kinase (AMPK) activator, and thiazolidinediones (TZDs), which act as peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists.	Metformin	23-32	peroxisome proliferator activated receptor gamma	Homo sapiens	128-176
25794703-4	2015	Most studies have used metformin, an AMP-activated protein kinase (AMPK) activator, and thiazolidinediones (TZDs), which act as peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists.	Metformin	23-32	peroxisome proliferator activated receptor gamma	Homo sapiens	178-187
25796513-4	2015	In addition, some clinically available pharmacologic agents such as fenofibrates and metformin may modulate energy and macronutrients metabolism by acting through FGF21.	Metformin	85-94	fibroblast growth factor 21	Homo sapiens	163-168
25939711-1	2015	PURPOSE: The aim of the study was to determine the steady-state pharmacokinetics of metformin in healthy volunteers with different numbers of reduced-function alleles in the organic cation transporter 1 gene (OCT1).	Metformin	84-93	solute carrier family 22 member 1	Homo sapiens	174-202
25939711-1	2015	PURPOSE: The aim of the study was to determine the steady-state pharmacokinetics of metformin in healthy volunteers with different numbers of reduced-function alleles in the organic cation transporter 1 gene (OCT1).	Metformin	84-93	solute carrier family 22 member 1	Homo sapiens	209-213
25676019-5	2015	While generating beneficial effects on hyperglycemia, metformin also improves insulin resistance and corrects dyslipidemia in patients with T2D.	Metformin	54-63	insulin	Homo sapiens	78-85
25370454-4	2015	Meanwhile, IL-22-induced STAT3 phosphorylation and upregulation of downstream genes Bcl-2 and cyclin D1 were inhibited by metformin.	Metformin	122-131	signal transducer and activator of transcription 3	Mus musculus	25-30
25370454-4	2015	Meanwhile, IL-22-induced STAT3 phosphorylation and upregulation of downstream genes Bcl-2 and cyclin D1 were inhibited by metformin.	Metformin	122-131	B cell leukemia/lymphoma 2	Mus musculus	84-89
25370454-5	2015	At the cellular level, metformin attenuated Th1- and Th17-derived IL-22 production.	Metformin	23-32	negative elongation factor complex member C/D, Th1l	Mus musculus	44-47
25370454-6	2015	Furthermore, metformin inhibited de novo generation of Th1 and Th17 cells from naive CD4(+) cells.	Metformin	13-22	negative elongation factor complex member C/D, Th1l	Mus musculus	55-58
25370454-7	2015	These observations were further supported by the fact that metformin treatment inhibited CD3/CD28-induced IFN-gamma and IL-17A expression along with the transcription factors that drive their expression (T-bet [Th1] and ROR-gammat [Th17], respectively).	Metformin	59-68	interferon gamma	Mus musculus	106-115
25370454-7	2015	These observations were further supported by the fact that metformin treatment inhibited CD3/CD28-induced IFN-gamma and IL-17A expression along with the transcription factors that drive their expression (T-bet [Th1] and ROR-gammat [Th17], respectively).	Metformin	59-68	negative elongation factor complex member C/D, Th1l	Mus musculus	211-214
25370454-8	2015	The effects of metformin on T cell differentiation were mediated by downregulated STAT3 and STAT4 phosphorylation via the AMP-activated kinase-mammalian target of rapamycin complex 1 pathway.	Metformin	15-24	signal transducer and activator of transcription 3	Homo sapiens	82-87
25891779-0	2015	Metformin attenuates palmitic acid-induced insulin resistance in L6 cells through the AMP-activated protein kinase/sterol regulatory element-binding protein-1c pathway.	Metformin	0-9	insulin	Homo sapiens	43-50
26261558-9	2015	Metformin is also capable of maintaining the biological activities of SCs after hypoxia injury, such as increasing the expression and secretion of BDNF, NGF, GDNF, and N-CAM.	Metformin	0-9	glial cell derived neurotrophic factor	Homo sapiens	158-162
25891779-2	2015	We recently reported that metformin improved insulin receptor substrate-1 (IRS-1)-associated insulin signaling by downregulating sterol regulatory element-binding protein-1c (SREBP-1c) expression.	Metformin	26-35	insulin	Homo sapiens	45-52
25407884-6	2015	Metformin inhibited TNF-alpha production with similar potency to rolipram and azithromycin (IC50 3.35 mum) but showed significantly lower efficacy (45.93%; P &lt; 0.05), and had no inhibitory effect on IL-1beta.	Metformin	0-9	tumor necrosis factor	Equus caballus	20-29
25891779-3	2015	In this study, we investigated whether AMPK activation and SREBP-1c inhibition contribute to the beneficial effects of metformin on IRS-1-associated insulin signaling in L6 myotubes.	Metformin	119-128	insulin	Homo sapiens	149-156
25891779-7	2015	In the PA-treated L6 cells, metformin treatment enhanced AMPK phosphorylation, reduced SREBP-1c expression and increased IRS-1 and Akt protein expression, whereas treatment with compound C blocked the effects of metformin on SREBP-1c expression and the IRS-1 and Akt levels.	Metformin	28-37	AKT serine/threonine kinase 1	Homo sapiens	131-134
25891779-7	2015	In the PA-treated L6 cells, metformin treatment enhanced AMPK phosphorylation, reduced SREBP-1c expression and increased IRS-1 and Akt protein expression, whereas treatment with compound C blocked the effects of metformin on SREBP-1c expression and the IRS-1 and Akt levels.	Metformin	28-37	AKT serine/threonine kinase 1	Homo sapiens	263-266
25891779-9	2015	The results from this study demonstrate that metformin ameliorates PA-induced insulin resistance through the activation of AMPK and the suppression of SREBP-1c in skeletal muscle cells.	Metformin	45-54	insulin	Homo sapiens	78-85
26111693-6	2015	The expressions of caspase-3 and Bax protein were significantly increased (P&lt;0.05) and Bcl-2 protein expression was decreased (P&lt;0.05) with a lowered Bcl-2/Bax ratio in AGEs-treated fibroblasts (P&lt;0.05), and such changes were significantly reversed by metformin treatment (P&lt;0.05).	Metformin	261-270	BCL2 apoptosis regulator	Homo sapiens	156-161
26111693-6	2015	The expressions of caspase-3 and Bax protein were significantly increased (P&lt;0.05) and Bcl-2 protein expression was decreased (P&lt;0.05) with a lowered Bcl-2/Bax ratio in AGEs-treated fibroblasts (P&lt;0.05), and such changes were significantly reversed by metformin treatment (P&lt;0.05).	Metformin	261-270	BCL2 associated X, apoptosis regulator	Homo sapiens	162-165
26111693-7	2015	CONCLUSION: Metformin can antagonize AGEs-induced apoptosis in human dermal fibroblasts by regulating the expressions of caspase-3, Bax and Bcl-2.	Metformin	12-21	caspase 3	Homo sapiens	121-130
26111693-7	2015	CONCLUSION: Metformin can antagonize AGEs-induced apoptosis in human dermal fibroblasts by regulating the expressions of caspase-3, Bax and Bcl-2.	Metformin	12-21	BCL2 associated X, apoptosis regulator	Homo sapiens	132-135
26111693-7	2015	CONCLUSION: Metformin can antagonize AGEs-induced apoptosis in human dermal fibroblasts by regulating the expressions of caspase-3, Bax and Bcl-2.	Metformin	12-21	BCL2 apoptosis regulator	Homo sapiens	140-145
25753371-0	2015	Multidrug and toxin extrusion 1 and human organic cation transporter 1 polymorphisms in patients with castration-resistant prostate cancer receiving metformin (SAKK 08/09).	Metformin	149-158	solute carrier family 22 member 1	Homo sapiens	42-70
25753371-1	2015	BACKGROUND: This study was initiated to explore the impact of organic cation transporter 1 (OCT1) and multidrug and toxin extrusion transporter 1 (MATE1) genetic polymorphisms on toxicity, and clinical activity of metformin in patients with castration-resistant prostate cancer (CRPC).	Metformin	214-223	solute carrier family 22 member 1	Homo sapiens	62-90
25753371-11	2015	CONCLUSIONS: The polymorphic OCT1 C-allele has been shown to be associated with less metformin-related toxicity and a higher risk of tumor progression in patients with CRPC receiving metformin as an anticancer treatment.	Metformin	85-94	solute carrier family 22 member 1	Homo sapiens	29-33
25753371-11	2015	CONCLUSIONS: The polymorphic OCT1 C-allele has been shown to be associated with less metformin-related toxicity and a higher risk of tumor progression in patients with CRPC receiving metformin as an anticancer treatment.	Metformin	183-192	solute carrier family 22 member 1	Homo sapiens	29-33
26117007-0	2015	[Effect of Metformin on Proliferation, Differentiation and Apoptosis of THP-1 Cells].	Metformin	11-20	GLI family zinc finger 2	Homo sapiens	72-77
26117007-1	2015	OBJECTIVE: To investigate the effect of metformin on proliferation, differentiation and apoptosis of THP-1 cells and explore its possible mechanism.	Metformin	40-49	GLI family zinc finger 2	Homo sapiens	101-106
26117007-2	2015	MEHODS: THP-1 cells were cultured with different concentrations of metformin for 24 h and 48 h. The cell proliferation was evaluated by CCK-8, the cell apoptosis was analyzed by Annexin V/7-AAD double labeling, the expression of CD14 and CD11b (surface differentiation antigens on THP-1 cells) was evaluated by flow cytometry, the BCL-XL, BAX, BIM and caspase-3 mRNA expressions of THP-1 cells were detected by real time quantitative PCR.	Metformin	67-76	GLI family zinc finger 2	Homo sapiens	8-13
26117007-3	2015	RESULTS: Metformin could significantly inhibit the growth of THP-1 cells in a time- and dose- dependent manner.	Metformin	9-18	GLI family zinc finger 2	Homo sapiens	61-66
26117007-4	2015	After treated with 20 mmol/L metformin for 24 h, the expressions of CD14 and CD11b in THP-1 cells didn"t change much (P&gt;0.05), the early apoptosis rates in exprimental and control groups were (2.02+-0.85)% and (4.46+-1.33)% respectively, the late apoptosis rates in experimental and control groups were (1.43+-0.83)% and (3.31+-0.59)% respectively.	Metformin	29-38	GLI family zinc finger 2	Homo sapiens	86-91
26117007-5	2015	In process of inducing effect of 20 mmol/L metformin on THP-1 cells, the expressions of BCL-XL and BIM did not significantly changed, while the expressions of BAX and caspase-3 significantly increased (P&lt;0.01).	Metformin	43-52	GLI family zinc finger 2	Homo sapiens	56-61
26117007-5	2015	In process of inducing effect of 20 mmol/L metformin on THP-1 cells, the expressions of BCL-XL and BIM did not significantly changed, while the expressions of BAX and caspase-3 significantly increased (P&lt;0.01).	Metformin	43-52	BCL2 like 1	Homo sapiens	88-94
26117007-5	2015	In process of inducing effect of 20 mmol/L metformin on THP-1 cells, the expressions of BCL-XL and BIM did not significantly changed, while the expressions of BAX and caspase-3 significantly increased (P&lt;0.01).	Metformin	43-52	BCL2 associated X, apoptosis regulator	Homo sapiens	159-162
26117007-5	2015	In process of inducing effect of 20 mmol/L metformin on THP-1 cells, the expressions of BCL-XL and BIM did not significantly changed, while the expressions of BAX and caspase-3 significantly increased (P&lt;0.01).	Metformin	43-52	caspase 3	Homo sapiens	167-176
26117007-6	2015	CONCLUSION: Metformin can effectively inhibit proliferation and induce apoptosis of THP-1 cells.	Metformin	12-21	GLI family zinc finger 2	Homo sapiens	84-89
25899745-0	2015	Metformin reduces the endotoxin-induced down-regulation of apolipoprotein E gene expression in macrophages.	Metformin	0-9	apolipoprotein E	Homo sapiens	59-75
25899745-4	2015	In this study, we questioned whether metformin could have an effect on apoE expression in macrophages in normal conditions or under lipopolysaccharide (LPS)-induced stress.	Metformin	37-46	apolipoprotein E	Homo sapiens	71-75
25899745-5	2015	The results showed that metformin slightly increases the apoE expression only at high doses (5-10 mM).	Metformin	24-33	apolipoprotein E	Homo sapiens	57-61
25899745-6	2015	Low doses of metformin (1-3 mM) significantly reduce the LPS down-regulatory effect on apoE expression in macrophages.	Metformin	13-22	apolipoprotein E	Homo sapiens	87-91
25899745-9	2015	In addition, data revealed that metformin impairs NF-kappaB nuclear translocation, and thus, improves the apoE levels in macrophages under inflammatory stress.	Metformin	32-41	apolipoprotein E	Homo sapiens	106-110
25862373-3	2015	The anti-tumor mechanisms of metformin include activation of the AMP-activated protein kinase/mTOR pathway and direct inhibition of insulin/insulin-like growth factor (IGF)-mediated cellular proliferation.	Metformin	29-38	mechanistic target of rapamycin kinase	Homo sapiens	94-98
25413451-0	2015	Pre-treatment with metformin activates Nrf2 antioxidant pathways and inhibits inflammatory responses through induction of AMPK after transient global cerebral ischemia.	Metformin	19-28	NFE2 like bZIP transcription factor 2	Rattus norvegicus	39-43
25413451-0	2015	Pre-treatment with metformin activates Nrf2 antioxidant pathways and inhibits inflammatory responses through induction of AMPK after transient global cerebral ischemia.	Metformin	19-28	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	122-126
25413451-4	2015	One of the main functions of metformin is proposed to be conducted via AMP-activated protein kinase (AMPK)-dependent pathway in the experimental cerebral ischemia model.	Metformin	29-38	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	71-99
25413451-4	2015	One of the main functions of metformin is proposed to be conducted via AMP-activated protein kinase (AMPK)-dependent pathway in the experimental cerebral ischemia model.	Metformin	29-38	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	101-105
25413451-5	2015	It is also established that metformin can suppress inflammation and activate Nuclear factor erythroid 2-related factor (Nrf2) pathways in neurons.	Metformin	28-37	NFE2 like bZIP transcription factor 2	Rattus norvegicus	77-118
25413451-5	2015	It is also established that metformin can suppress inflammation and activate Nuclear factor erythroid 2-related factor (Nrf2) pathways in neurons.	Metformin	28-37	NFE2 like bZIP transcription factor 2	Rattus norvegicus	120-124
25413451-7	2015	Our results indicated that pretreatment of rats by metformin attenuated cellular levels of nuclear factor-kappaB, Tumor Necrosis Factor alpha and Cyclooxygenase-2 which are considered as three important proteins involved in the inflammation pathway.	Metformin	51-60	tumor necrosis factor	Rattus norvegicus	114-141
25413451-8	2015	Pretreatment by metformin increased the level of Nrf2 and heme oxygenase-1 in the hippocampus of ischemic rats compared with untreated ischemic group.	Metformin	16-25	NFE2 like bZIP transcription factor 2	Rattus norvegicus	49-53
25413451-10	2015	Such protective changes detected by metformin pretreatment were reversed by injecting compound c, an AMPK inhibitor.	Metformin	36-45	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	101-105
25413451-11	2015	These findings suggested that metformin might protect cells through modulating inflammatory and antioxidant pathways via induction of AMPK.	Metformin	30-39	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	134-138
25909163-4	2015	In addition to activation of AMPK and suppression of the mTOR pathway, a series of increased and decreased genes expression were induced by metformin, including PTEN, MMP7, and FN1.	Metformin	140-149	phosphatase and tensin homolog	Mus musculus	161-165
26052399-6	2015	Metformin (through 5"-adenosine monophosphate-activated protein kinase pathway activation) and statins (through 3-hydroxy-3-methylglutaryl coenzyme A inhibition) show anti-tumoral properties modifying several steps of RAS/RAF/MEK/ERK, PI3K/AKT/mTOR and Wnt/beta-catenin signaling cascades.	Metformin	0-9	mitogen-activated protein kinase kinase 7	Homo sapiens	226-229
26052399-6	2015	Metformin (through 5"-adenosine monophosphate-activated protein kinase pathway activation) and statins (through 3-hydroxy-3-methylglutaryl coenzyme A inhibition) show anti-tumoral properties modifying several steps of RAS/RAF/MEK/ERK, PI3K/AKT/mTOR and Wnt/beta-catenin signaling cascades.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	230-233
26052399-6	2015	Metformin (through 5"-adenosine monophosphate-activated protein kinase pathway activation) and statins (through 3-hydroxy-3-methylglutaryl coenzyme A inhibition) show anti-tumoral properties modifying several steps of RAS/RAF/MEK/ERK, PI3K/AKT/mTOR and Wnt/beta-catenin signaling cascades.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	240-243
26052399-6	2015	Metformin (through 5"-adenosine monophosphate-activated protein kinase pathway activation) and statins (through 3-hydroxy-3-methylglutaryl coenzyme A inhibition) show anti-tumoral properties modifying several steps of RAS/RAF/MEK/ERK, PI3K/AKT/mTOR and Wnt/beta-catenin signaling cascades.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	244-248
25742316-0	2015	Metformin and salicylate synergistically activate liver AMPK, inhibit lipogenesis and improve insulin sensitivity.	Metformin	0-9	insulin	Homo sapiens	94-101
25742316-4	2015	We find doses of metformin and salicylate used clinically synergistically activate AMPK in vitro and in vivo, resulting in reduced liver lipogenesis, lower liver lipid levels and improved insulin sensitivity in mice.	Metformin	17-26	insulin	Homo sapiens	188-195
25742316-6	2015	These effects are also observed in primary human hepatocytes and patients with dysglycaemia exhibit additional improvements in a marker of insulin resistance (proinsulin) when treated with ASA and metformin compared with either drug alone.	Metformin	197-206	insulin	Homo sapiens	139-146
25843797-0	2015	DEPTOR-related mTOR suppression is involved in metformin"s anti-cancer action in human liver cancer cells.	Metformin	47-56	mechanistic target of rapamycin kinase	Homo sapiens	15-19
25843797-2	2015	It is thought that the suppression of mTOR signaling is involved in metformin"s anti-cancer action.	Metformin	68-77	mechanistic target of rapamycin kinase	Homo sapiens	38-42
25843797-4	2015	In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells.	Metformin	74-83	mechanistic target of rapamycin kinase	Homo sapiens	87-91
25843797-5	2015	Metformin suppressed phosphorylation of p70-S6 kinase, and ribosome protein S6, downstream targets of mTOR, and suppressed cell proliferation.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	102-106
25843797-6	2015	We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells.	Metformin	108-117	mechanistic target of rapamycin kinase	Homo sapiens	49-53
25843797-6	2015	We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells.	Metformin	108-117	mechanistic target of rapamycin kinase	Homo sapiens	121-125
25843797-7	2015	Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	73-77
25843797-7	2015	Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	114-118
25843797-8	2015	This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner.	Metformin	123-132	mechanistic target of rapamycin kinase	Homo sapiens	136-140
25843797-9	2015	Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	90-94
25843797-10	2015	We conclude that DEPTOR-related mTOR suppression is involved in metformin"s anti-cancer action in liver, and could be a novel target for anti-cancer therapy.	Metformin	64-73	mechanistic target of rapamycin kinase	Homo sapiens	32-36
25895126-5	2015	Metformin treatment in RD and HED mice resulted in a significant reduction in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by decreased levels of growth factors (IGF-1, insulin and leptin), inflammatory cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet mice.	Metformin	0-9	mast cell protease 1	Mus musculus	245-250
25895126-5	2015	Metformin treatment in RD and HED mice resulted in a significant reduction in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by decreased levels of growth factors (IGF-1, insulin and leptin), inflammatory cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet mice.	Metformin	0-9	interleukin 6	Mus musculus	252-256
25955843-0	2015	Metformin Causes G1-Phase Arrest via Down-Regulation of MiR-221 and Enhances TRAIL Sensitivity through DR5 Up-Regulation in Pancreatic Cancer Cells.	Metformin	0-9	TNF superfamily member 10	Homo sapiens	77-82
25955843-8	2015	While recent studies showed that treatment with only TRAIL was not effective against pancreatic cancer cells, the present data showed that metformin sensitized p53-mutated pancreatic cancer cells to TRAIL.	Metformin	139-148	tumor protein p53	Homo sapiens	160-163
25955843-8	2015	While recent studies showed that treatment with only TRAIL was not effective against pancreatic cancer cells, the present data showed that metformin sensitized p53-mutated pancreatic cancer cells to TRAIL.	Metformin	139-148	TNF superfamily member 10	Homo sapiens	199-204
25955843-9	2015	Metformin induced the expressions of death receptor 5 (DR5), a receptor for TRAIL, and Bim with a pro-apoptotic function in the downstream of TRAIL-DR5 pathway.	Metformin	0-9	TNF superfamily member 10	Homo sapiens	76-81
25955843-9	2015	Metformin induced the expressions of death receptor 5 (DR5), a receptor for TRAIL, and Bim with a pro-apoptotic function in the downstream of TRAIL-DR5 pathway.	Metformin	0-9	TNF superfamily member 10	Homo sapiens	142-147
25862373-10	2015	IGF-1 activated both ERK1/2 and Akt, but these effects were attenuated by metformin treatment.	Metformin	74-83	insulin like growth factor 1	Homo sapiens	0-5
25862373-10	2015	IGF-1 activated both ERK1/2 and Akt, but these effects were attenuated by metformin treatment.	Metformin	74-83	mitogen-activated protein kinase 3	Homo sapiens	21-27
25862373-10	2015	IGF-1 activated both ERK1/2 and Akt, but these effects were attenuated by metformin treatment.	Metformin	74-83	AKT serine/threonine kinase 1	Homo sapiens	32-35
25862373-12	2015	Our results suggest that metformin is a potent inhibitor of the IGF-1/IGF-1R system and may be beneficial in prostate cancer treatment.	Metformin	25-34	insulin like growth factor 1	Homo sapiens	64-69
25935404-0	2015	Metformin increases survival in hormone receptor-positive, HER2-positive breast cancer patients with diabetes.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	59-63
25304269-1	2015	OBJECTIVE: To compare the therapeutic effects of metformin (Met) and laparoscopic ovarian drilling (LOD) in clomiphene and insulin-resistant patients with polycystic ovary syndrome (CIRPCOS).	Metformin	49-58	insulin	Homo sapiens	123-130
25607338-3	2015	In this study, the authors aimed to compare the anti-inflammatory properties of pioglitazone and metformin, with respect to their effect on serum concentrations of highly sensitive C-reactive protein (hsCRP), osteoprotegerin (OPG), intercellular adhesion molecule-1 (ICAM-1) and adiponectin.	Metformin	97-106	C-reactive protein	Homo sapiens	181-199
25945500-5	2015	Insulin was added if targets could not be reached on metformin alone at maximum doses.	Metformin	53-62	insulin	Homo sapiens	0-7
25595658-6	2015	Metformin prevented AGEs induced cytochrome c release from mitochondria into cytosol in the hNSCs.	Metformin	0-9	cytochrome c, somatic	Homo sapiens	33-45
25595658-9	2015	Furthermore, co-treatment of hNSCs with metformin significantly blocked AGE-mediated reductions in the expression levels of several neuroprotective genes (PPARgamma, Bcl-2 and CREB).	Metformin	40-49	peroxisome proliferator activated receptor gamma	Homo sapiens	155-164
25595658-9	2015	Furthermore, co-treatment of hNSCs with metformin significantly blocked AGE-mediated reductions in the expression levels of several neuroprotective genes (PPARgamma, Bcl-2 and CREB).	Metformin	40-49	BCL2 apoptosis regulator	Homo sapiens	166-171
25667085-0	2015	Metformin increases APP expression and processing via oxidative stress, mitochondrial dysfunction and NF-kappaB activation: Use of insulin to attenuate metformin"s effect.	Metformin	152-161	insulin	Homo sapiens	131-138
25667085-2	2015	This study demonstrates the effect of metformin, a therapeutic biguanide administered for T2DM therapy, on beta-amyloid precursor protein (APP) metabolism in in vitro, ex vivo and in vivo models.	Metformin	38-47	amyloid beta precursor protein	Homo sapiens	107-137
25667085-3	2015	Furthermore, the protective role of insulin against metformin is also demonstrated.	Metformin	52-61	insulin	Homo sapiens	36-43
25667085-8	2015	These effects of metformin were found to be antagonized by the addition of insulin, which reduced Abeta levels, oxidative stress, mitochondrial dysfunction and cell death.	Metformin	17-26	insulin	Homo sapiens	75-82
25667085-8	2015	These effects of metformin were found to be antagonized by the addition of insulin, which reduced Abeta levels, oxidative stress, mitochondrial dysfunction and cell death.	Metformin	17-26	amyloid beta precursor protein	Homo sapiens	98-103
25497570-8	2015	Treatment with metformin, an activator of AMPK, significantly reduced cartilage matrix formation and inhibited gene expression of sox6, sox9, col2a1 and aggrecan core protein (acp).	Metformin	15-24	collagen type II alpha 1 chain	Homo sapiens	142-148
25808987-4	2015	Although drugs such as metformin that lower insulin resistance can contribute to weight loss, a better understanding of the links between obesity, weight loss and changes in insulin resistance might lead to new approaches to patient management.	Metformin	23-32	insulin	Homo sapiens	44-51
24740684-12	2015	Metformin shows a significantly greater effect on ALT and AST in responders than in non-responders.	Metformin	0-9	solute carrier family 17 member 5	Homo sapiens	58-61
25510240-0	2015	Association of Organic Cation Transporter 1 With Intolerance to Metformin in Type 2 Diabetes: A GoDARTS Study.	Metformin	64-73	solute carrier family 22 member 1	Homo sapiens	15-43
25510240-3	2015	We hypothesized that reduced transport of metformin via organic cation transporter 1 (OCT1) could increase metformin concentration in the intestine, leading to increased risk of severe GI side effects and drug discontinuation.	Metformin	42-51	solute carrier family 22 member 1	Homo sapiens	56-84
25510240-3	2015	We hypothesized that reduced transport of metformin via organic cation transporter 1 (OCT1) could increase metformin concentration in the intestine, leading to increased risk of severe GI side effects and drug discontinuation.	Metformin	42-51	solute carrier family 22 member 1	Homo sapiens	86-90
25510240-3	2015	We hypothesized that reduced transport of metformin via organic cation transporter 1 (OCT1) could increase metformin concentration in the intestine, leading to increased risk of severe GI side effects and drug discontinuation.	Metformin	107-116	solute carrier family 22 member 1	Homo sapiens	56-84
25510240-3	2015	We hypothesized that reduced transport of metformin via organic cation transporter 1 (OCT1) could increase metformin concentration in the intestine, leading to increased risk of severe GI side effects and drug discontinuation.	Metformin	107-116	solute carrier family 22 member 1	Homo sapiens	86-90
25510240-8	2015	Our results suggest that reduced OCT1 transport is an important determinant of metformin intolerance.	Metformin	79-88	solute carrier family 22 member 1	Homo sapiens	33-37
25576058-5	2015	Metformin (but not rapamycin) reduced glucose and insulin levels and expression of miR-34a and its direct targets Notch, Slug, and Snail.	Metformin	0-9	microRNA 34a	Mus musculus	83-90
25576058-5	2015	Metformin (but not rapamycin) reduced glucose and insulin levels and expression of miR-34a and its direct targets Notch, Slug, and Snail.	Metformin	0-9	snail family zinc finger 2	Mus musculus	121-125
25771309-1	2015	OBJECTIVE: The objective of this study was to: (i) evaluate the potentially inappropriate prescribing (PIP; defined as the use of metformin in the presence of contraindications and/or use in excessive dosage based on the renal function) of metformin in people receiving medication reviews in Australia and (ii) identify the predictors for PIP of metformin.	Metformin	130-139	prolactin induced protein	Homo sapiens	103-106
25771309-1	2015	OBJECTIVE: The objective of this study was to: (i) evaluate the potentially inappropriate prescribing (PIP; defined as the use of metformin in the presence of contraindications and/or use in excessive dosage based on the renal function) of metformin in people receiving medication reviews in Australia and (ii) identify the predictors for PIP of metformin.	Metformin	240-249	prolactin induced protein	Homo sapiens	103-106
25771309-1	2015	OBJECTIVE: The objective of this study was to: (i) evaluate the potentially inappropriate prescribing (PIP; defined as the use of metformin in the presence of contraindications and/or use in excessive dosage based on the renal function) of metformin in people receiving medication reviews in Australia and (ii) identify the predictors for PIP of metformin.	Metformin	240-249	prolactin induced protein	Homo sapiens	103-106
25771309-4	2015	Multivariate logistic regression analysis was used to detect risk factors for PIP of metformin.	Metformin	85-94	prolactin induced protein	Homo sapiens	78-81
25771309-6	2015	Overall, there were 12.9% (n=685) of patients in the HMR group and 17.4% (n=184) of patients in the RMMR group who had PIP of metformin.	Metformin	126-135	prolactin induced protein	Homo sapiens	119-122
25771309-7	2015	Multivariate logistic regression showed age, gender and type of medication review service as the significant (p&lt;0.05) independent risk factors for PIP of metformin.	Metformin	157-166	prolactin induced protein	Homo sapiens	150-153
25239203-0	2015	The effect of short-term metformin treatment on plasma prolactin levels in bromocriptine-treated patients with hyperprolactinaemia and impaired glucose tolerance: a pilot study.	Metformin	25-34	prolactin	Homo sapiens	55-64
25239203-2	2015	This study was aimed at investigating whether metformin treatment has an impact on plasma prolactin levels in bromocriptine-treated patients with hyperprolactinaemia and impaired glucose tolerance.	Metformin	46-55	prolactin	Homo sapiens	90-99
25239203-7	2015	In patients with hyperprolactinaemia, but not in the other groups of patients, metformin slightly reduced plasma levels of prolactin, and this effect correlated weakly with the metabolic effects of this drug.	Metformin	79-88	prolactin	Homo sapiens	22-31
25239203-8	2015	Our study shows that metformin decreases plasma prolactin levels only in patients with elevated levels of this hormone.	Metformin	21-30	prolactin	Homo sapiens	48-57
26136915-9	2015	In addition, treatment with metformin downregulated the expression levels of fetuin-A and retinol binding protein-4 (RBP-4), while normalizing the expression of perilipin that had been reduced in the T2DM rats.	Metformin	28-37	alpha-2-HS-glycoprotein	Rattus norvegicus	77-85
26136915-12	2015	In summary, metformin treatment ameliorated a number of the harmful effects associated with T2DM via the modulation of the expression levels of fetuin-A, RBP-4, perilipin and various genes associated with lipid metabolism, resulting in regenerative changes in the liver and pancreatic cells.	Metformin	12-21	alpha-2-HS-glycoprotein	Rattus norvegicus	144-152
25053715-12	2015	Among the KLF5/GATA4/GATA6 direct target genes relevant for cancer development, one target gene, HNF4alpha, was also required for GC proliferation and could be targeted by the antidiabetic drug metformin, revealing a therapeutic opportunity for KLF5/GATA4/GATA6 amplified GCs.	Metformin	194-203	GATA binding protein 4	Mus musculus	15-20
25053715-12	2015	Among the KLF5/GATA4/GATA6 direct target genes relevant for cancer development, one target gene, HNF4alpha, was also required for GC proliferation and could be targeted by the antidiabetic drug metformin, revealing a therapeutic opportunity for KLF5/GATA4/GATA6 amplified GCs.	Metformin	194-203	GATA binding protein 4	Mus musculus	250-255
25791462-2	2015	Metformin has beneficial effects on insulin resistance and endothelial functions.	Metformin	0-9	insulin	Homo sapiens	36-43
25468829-5	2015	Weight loss, aerobic exercise, metformin and pioglitazone have each been shown to be effective for reducing FetA level.	Metformin	31-40	alpha 2-HS glycoprotein	Homo sapiens	108-112
25709052-6	2015	In addition, metformin reduced the phosphorylation of epidermal growth factor receptor and insulin-like growth factor and insulin-like growth factor-1 receptor, as well as angiogenesis-related proteins, such as vascular endothelial growth factor, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2.	Metformin	13-22	TIMP metallopeptidase inhibitor 1	Homo sapiens	247-294
25849133-0	2015	Metformin activates a duodenal Ampk-dependent pathway to lower hepatic glucose production in rats.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	31-35
25849133-2	2015	Metformin lowers blood glucose levels by inhibiting hepatic glucose production (HGP), an effect originally postulated to be due to a hepatic AMP-activated protein kinase (AMPK)-dependent mechanism.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	141-169
25849133-2	2015	Metformin lowers blood glucose levels by inhibiting hepatic glucose production (HGP), an effect originally postulated to be due to a hepatic AMP-activated protein kinase (AMPK)-dependent mechanism.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	171-175
25849133-5	2015	Here we show that intraduodenal infusion of metformin for 50 min activated duodenal mucosal Ampk and lowered HGP in a rat 3 d high fat diet (HFD)-induced model of insulin resistance.	Metformin	44-53	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	92-96
25849133-6	2015	Inhibition of duodenal Ampk negated the HGP-lowering effect of intraduodenal metformin, and both duodenal glucagon-like peptide-1 receptor (Glp-1r)-protein kinase A (Pka) signaling and a neuronal-mediated gut-brain-liver pathway were required for metformin to lower HGP.	Metformin	77-86	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	23-27
25849133-8	2015	In an unclamped setting, inhibition of duodenal Ampk reduced the glucose-lowering effects of a bolus metformin treatment in rat models of diabetes.	Metformin	101-110	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	48-52
25849133-9	2015	These findings show that, in rat models of both obesity and diabetes, metformin activates a previously unappreciated duodenal Ampk-dependent pathway to lower HGP and plasma glucose levels.	Metformin	70-79	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	126-130
24698216-2	2015	Metformin, typically used in type 2 diabetes mellitus (T2DM), is a possible adjunct therapy in T1DM to help improve glycemic control and insulin sensitivity.	Metformin	0-9	insulin	Homo sapiens	137-144
24698216-7	2015	RESULTS: Total daily insulin dose, BMI z-score and waist circumference significantly decreased at 3 and 6 months compared to baseline within the metformin group, even among normal-weight participants.	Metformin	145-154	insulin	Homo sapiens	21-28
24698216-10	2015	CONCLUSIONS: Low-dose metformin likely improves BMI as well as insulin sensitivity in T1DM adolescents, as indicated by a decrease in total daily insulin dose.	Metformin	22-31	insulin	Homo sapiens	63-70
24698216-10	2015	CONCLUSIONS: Low-dose metformin likely improves BMI as well as insulin sensitivity in T1DM adolescents, as indicated by a decrease in total daily insulin dose.	Metformin	22-31	insulin	Homo sapiens	146-153
25875801-0	2015	Metformin suppresses pancreatic tumor growth with inhibition of NFkappaB/STAT3 inflammatory signaling.	Metformin	0-9	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	64-72
25875801-0	2015	Metformin suppresses pancreatic tumor growth with inhibition of NFkappaB/STAT3 inflammatory signaling.	Metformin	0-9	signal transducer and activator of transcription 3	Mus musculus	73-78
25875801-8	2015	Furthermore, metformin treatment decreased the phosphorylation of nuclear factor kappaB and signal transducer and activator of transcription 3 as well as the expression of specificity protein 1 transcription factor and several nuclear factor kappaB-regulated genes.	Metformin	13-22	signal transducer and activator of transcription 3	Mus musculus	92-142
26081514-0	2015	[Effects of metformin on the polarization and Notch 1 expression of RAW264.7 macrophages].	Metformin	12-21	notch receptor 1	Homo sapiens	46-53
26081514-1	2015	OBJECTIVE: To explore the possible effects of metformin on regulating the Notch1 expression and the polarization of RAW264.7 macrophages.	Metformin	46-55	notch receptor 1	Homo sapiens	74-80
26081514-7	2015	RESULTS: At the concentrations of 0-10 mmol/L for 0-48 h, metformin in concentration and time-dependent ways promoted the expression of IL-10 mRNA and inhibited the mRNA expression of IL-1beta in RAW264.7 macrophages (both P &lt; 0.05).	Metformin	58-67	interleukin 1 beta	Homo sapiens	184-192
26081514-8	2015	In metformin-treated cells, the expressions of Arg1 (P = 0.009), IL-10 (P = 0.015) and IL-4 (P = 0.001) mRNA increased while the expressions of IL-1beta (P = 0.001) and IL-6 (P = 0.032) mRNA decreased.	Metformin	3-12	interleukin 4	Homo sapiens	87-91
26081514-8	2015	In metformin-treated cells, the expressions of Arg1 (P = 0.009), IL-10 (P = 0.015) and IL-4 (P = 0.001) mRNA increased while the expressions of IL-1beta (P = 0.001) and IL-6 (P = 0.032) mRNA decreased.	Metformin	3-12	interleukin 1 beta	Homo sapiens	144-152
26081514-8	2015	In metformin-treated cells, the expressions of Arg1 (P = 0.009), IL-10 (P = 0.015) and IL-4 (P = 0.001) mRNA increased while the expressions of IL-1beta (P = 0.001) and IL-6 (P = 0.032) mRNA decreased.	Metformin	3-12	interleukin 6	Homo sapiens	169-173
25879666-7	2015	Metformin also markedly decreased serum levels of insulin and reduced insulin resistance, and inhibited phosphorylation of Akt, mammalian target of rapamycin (mTOR), and p70S6 in the liver.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	123-126
25879666-7	2015	Metformin also markedly decreased serum levels of insulin and reduced insulin resistance, and inhibited phosphorylation of Akt, mammalian target of rapamycin (mTOR), and p70S6 in the liver.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	128-157
25879666-7	2015	Metformin also markedly decreased serum levels of insulin and reduced insulin resistance, and inhibited phosphorylation of Akt, mammalian target of rapamycin (mTOR), and p70S6 in the liver.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	159-163
25879666-9	2015	These findings suggest that metformin prevents liver tumorigenesis by ameliorating insulin sensitivity, inhibiting the activation of Akt/mTOR/p70S6 signaling, and improving adipokine imbalance.	Metformin	28-37	thymoma viral proto-oncogene 1	Mus musculus	133-136
26131086-12	2015	The level of TGF-beta1 in Jiangya Xiaoke prescription group and the metformin group decreased (P &lt; 0.01), and level of TGF-beta1 in Jiangya Xiaoke prescription group was lower significantly than that in metformin group (P &lt; 0.05).	Metformin	206-215	transforming growth factor, beta 1	Rattus norvegicus	122-131
26131086-13	2015	The mRNA expression of TGF-beta1 in Jiangya Xiaoke prescription group and the metformin group was significantly lower than model group (P &lt; 0.01).	Metformin	78-87	transforming growth factor, beta 1	Rattus norvegicus	23-32
25867026-7	2015	We show that metformin induces decreased proliferation, cell cycle arrest, autophagy, apoptosis and cell death in vitro with a concomitant activation of AMPK, Redd1 and inhibition of the mTOR pathway.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	187-191
25889494-3	2015	METHODS: We evaluated the effects of 5-amino-imidazole-4-carboxyamide-1- beta-D-ribofuranoside (AICAR) and metformin on tumor necrosis factor (TNF)-alpha- stimulated chemokine production in human granulosa cells.	Metformin	107-116	tumor necrosis factor	Homo sapiens	120-153
25889494-5	2015	RESULTS: AICAR and metformin markedly reduced the IL-8 and GROalpha production induced by TNF-alpha.	Metformin	19-28	C-X-C motif chemokine ligand 8	Homo sapiens	50-54
25889494-5	2015	RESULTS: AICAR and metformin markedly reduced the IL-8 and GROalpha production induced by TNF-alpha.	Metformin	19-28	tumor necrosis factor	Homo sapiens	90-99
25889494-6	2015	AICAR and metformin also reduced the TNF-alpha-induced phosphorylation of I-kappaB.	Metformin	10-19	tumor necrosis factor	Homo sapiens	37-46
25889494-8	2015	CONCLUSIONS: These results suggest that metformin promotes granulosa cell function by reducing a TNF-alpha- and chemokine-mediated inflammatory reaction through an AMPK-dependent pathway.	Metformin	40-49	tumor necrosis factor	Homo sapiens	97-106
25849717-9	2015	Treatment with anti-diabetic drugs metformin and glibenclamide also reduced IL-1alpha and IL-1beta secretion in infection and cytokine-primed adipose tissue.	Metformin	35-44	interleukin 1 beta	Homo sapiens	90-98
25315630-1	2015	AIMS: To investigate the associations of vitamin B12 (cobalamin and holotranscobalamin) status with depression, cognition and neuropathy in patients with type 2 diabetes using metformin.	Metformin	176-185	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	49-52
25617357-5	2015	Results showed that AMPK activation by metformin reverted oxidative stress-induced inactivation of AMPK and prevented oxidative stress-induced cell death.	Metformin	39-48	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	20-24
25617357-5	2015	Results showed that AMPK activation by metformin reverted oxidative stress-induced inactivation of AMPK and prevented oxidative stress-induced cell death.	Metformin	39-48	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	99-103
25617357-10	2015	In conclusion, this study demonstrates that the protective effects of metformin-induced AMPK activation against oxidative stress converge on mitochondria and are mediated, at least in part, through the dissociation of PPARalpha-CypD interactions, independent of phosphorylation and acetylation of PPARalpha and CypD.	Metformin	70-79	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	88-92
25662675-0	2015	The variant organic cation transporter 2 (OCT2)-T201M contribute to changes in insulin resistance in patients with type 2 diabetes treated with metformin.	Metformin	144-153	insulin	Homo sapiens	79-86
25662675-11	2015	CONCLUSIONS: Our findings suggest that the loss-of-function variant OCT2-T201M (rs145450955) contribute to changes in insulin resistance and beta cell activity in patients with T2D treated with metformin.	Metformin	194-203	insulin	Homo sapiens	118-125
25658660-6	2015	As expected, metformin reduced plasma glucose, insulin resistance and glycated hemoglobin.	Metformin	13-22	insulin	Homo sapiens	47-54
25780442-0	2015	Metformin inhibits the proliferation of A431 cells by modulating the PI3K/Akt signaling pathway.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	74-77
25780442-12	2015	Western blotting results showed that the protein expression levels of PI3K and p-Akt were inhibited by metformin in a time- and dose-dependent manner (P&lt;0.05).	Metformin	103-112	AKT serine/threonine kinase 1	Homo sapiens	81-84
25780442-13	2015	In conclusion, metformin significantly inhibited the proliferation of A431 cells in the current study, which may be strongly associated with the inhibition of the PI3K/Akt signaling pathway.	Metformin	15-24	AKT serine/threonine kinase 1	Homo sapiens	168-171
25495168-1	2015	The aim of this proof-of-concept study was to determine the effects of three-month Metformin therapy on the expression of tumor-regulatory genes (p53, cyclin D2 and BCL-2) in the endometrium of women with polycystic ovary syndrome (PCOS).	Metformin	83-92	tumor protein p53	Homo sapiens	146-149
25495168-1	2015	The aim of this proof-of-concept study was to determine the effects of three-month Metformin therapy on the expression of tumor-regulatory genes (p53, cyclin D2 and BCL-2) in the endometrium of women with polycystic ovary syndrome (PCOS).	Metformin	83-92	cyclin D2	Homo sapiens	151-160
25495168-1	2015	The aim of this proof-of-concept study was to determine the effects of three-month Metformin therapy on the expression of tumor-regulatory genes (p53, cyclin D2 and BCL-2) in the endometrium of women with polycystic ovary syndrome (PCOS).	Metformin	83-92	BCL2 apoptosis regulator	Homo sapiens	165-170
25495168-8	2015	Tumor suppressor gene (p53) was significantly up-regulated after Metformin (10 out of 14 women), with p value 0.016.	Metformin	65-74	tumor protein p53	Homo sapiens	23-26
25495168-10	2015	In conclusion, Metformin therapy improved clinical and metabolic parameters in women with PCOS and up-regulated p53 tumor suppressor gene significantly.	Metformin	15-24	tumor protein p53	Homo sapiens	112-115
25716282-9	2015	Exposure to low (10-7 M) and high (10-4 M) doses of metformin for 7-10 days significantly reduced the conversion of androstenedione (ANDRO) and testosterone (TESTO) (both requiring aromatase), but not the conversion of oestrone or oestrone sulphate (ES) via 17beta-hydroxysteroid dehydrogenase/sulphatase to E2.	Metformin	52-61	hydroxysteroid 17-beta dehydrogenase 7	Homo sapiens	258-293
26148594-8	2015	CONCLUSIONS: Metformin inhibited the expression of MMP-2, cisplatin and the combined treatment inhibited the expression of survivin, MMP-2, VEGF-C, and VEGFR-3, and the combined treatment of metformin with cisplatin resulted in enhanced anti-tumor efficacy.	Metformin	13-22	vascular endothelial growth factor C	Mus musculus	140-146
25899185-12	2015	Mean fasting insulin levels at beginning of study entry were 17.22 +- 2.3 mIU/L and 16.93 +- 2.28 mIU/L in metformin and no metformin group respectively (p=0.589).	Metformin	107-116	insulin	Homo sapiens	13-20
25866577-2	2015	Metformin is the oldest insulin sensitizer used in the management of type 2 diabetes mellitus.	Metformin	0-9	insulin	Homo sapiens	24-31
25866577-3	2015	In PCOs, metformin decreases the serum lipids, androgen and insulin; induces ovulation and regular menstrual cycle; increases the pregnancy rate.	Metformin	9-18	insulin	Homo sapiens	60-67
26445623-8	2015	RESULTS: Adding sulphonylurea to metformin targeted both insulin resistance and insulin deficiency.	Metformin	33-42	insulin	Homo sapiens	57-64
25492486-0	2015	Metformin sensitizes hepatocellular carcinoma to arsenic trioxide-induced apoptosis by downregulating Bcl2 expression.	Metformin	0-9	BCL2 apoptosis regulator	Homo sapiens	102-106
25492486-4	2015	Metformin is reported to decrease Bcl2 expression, and the purpose of this study was to verify whether metformin could potentiate the anti-HCC efficacy of ATO in vitro.	Metformin	0-9	BCL2 apoptosis regulator	Homo sapiens	34-38
25492486-7	2015	Furthermore, this activity proceeded via a mechanism involving metformin-induced downregulation of Bcl2.	Metformin	63-72	BCL2 apoptosis regulator	Homo sapiens	99-103
25601987-7	2015	Impaired effects of metformin on eNOS phosphorylation and NO production were reversed in cells transfected with constitutively active AMP-activated protein kinase.	Metformin	20-29	nitric oxide synthase 3	Homo sapiens	33-37
25948182-7	2015	RESULTS: The metformin lowered the OD value, and the expression levels of both adipogenic genes C/EBPalpha and FABP4 were lower than those of controls, while the expression level of PPARgamma mRNA was not significantly changed, the apoptosis rate of leukemia cells co-caltured with metformin-treated adipocytes was higher than that of co-cultured cells without metformin treatment.	Metformin	13-22	CCAAT enhancer binding protein alpha	Homo sapiens	96-106
25948182-7	2015	RESULTS: The metformin lowered the OD value, and the expression levels of both adipogenic genes C/EBPalpha and FABP4 were lower than those of controls, while the expression level of PPARgamma mRNA was not significantly changed, the apoptosis rate of leukemia cells co-caltured with metformin-treated adipocytes was higher than that of co-cultured cells without metformin treatment.	Metformin	13-22	peroxisome proliferator activated receptor gamma	Homo sapiens	182-191
25825634-6	2015	In particular, the interferences exerted by metformin on AMP-activated protein kinase pathway (the cellular energy sensor), on insulin levels and on Hexokinase could potentially have repercussion on glucose handling and thus on FDG distribution.	Metformin	44-53	insulin	Homo sapiens	127-134
25825634-6	2015	In particular, the interferences exerted by metformin on AMP-activated protein kinase pathway (the cellular energy sensor), on insulin levels and on Hexokinase could potentially have repercussion on glucose handling and thus on FDG distribution.	Metformin	44-53	hexokinase 1	Homo sapiens	149-159
25812009-10	2015	Following metformin administration, fasting glucose and insulin were reduced.	Metformin	10-19	insulin	Homo sapiens	56-63
25785990-0	2015	Anti-angiogenic effect of metformin in mouse oxygen-induced retinopathy is mediated by reducing levels of the vascular endothelial growth factor receptor Flk-1.	Metformin	26-35	vascular endothelial growth factor A	Homo sapiens	110-144
25834454-9	2015	Self-monitoring is essential to achieve good metabolic control, and endocrinologists should first administer metformin if insulin resistance is evident and then add dipeptidyl peptidase 4 inhibitors/glucagon-like peptide 1 receptor agonists or insulin.	Metformin	109-118	insulin	Homo sapiens	122-129
25785990-2	2015	METHODS: OIR mice were treated with metformin by intraperitoneal injection from postnatal day 12 (P12) to P17 or P21.	Metformin	36-45	family with sequence similarity 72, member A	Mus musculus	106-109
26045896-10	2015	Moreover, we demonstrate that metformin induces GLUT4 expression and inhibits AR expression and blocks insulin receptor/PI3K/Akt/mTOR signaling in the same hyperplasia human tissues.	Metformin	30-39	AKT serine/threonine kinase 1	Homo sapiens	125-128
26045896-10	2015	Moreover, we demonstrate that metformin induces GLUT4 expression and inhibits AR expression and blocks insulin receptor/PI3K/Akt/mTOR signaling in the same hyperplasia human tissues.	Metformin	30-39	mechanistic target of rapamycin kinase	Homo sapiens	129-133
26101707-0	2015	Metformin inhibits gastric cancer via the inhibition of HIF1alpha/PKM2 signaling.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	56-65
26101707-9	2015	Metformin downregulated PI3K, Akt, HIF1alpha, PARP, PKM2 and COX expression.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	30-33
26101707-9	2015	Metformin downregulated PI3K, Akt, HIF1alpha, PARP, PKM2 and COX expression.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	35-44
26101707-11	2015	In summary, metformin has profound antitumor effect for gastric cancer by inducing intrinsic apoptosis via the inhibition of HIF1alpha/PKM2 signaling pathway.	Metformin	12-21	hypoxia inducible factor 1 subunit alpha	Homo sapiens	125-134
30603248-4	2016	On the other hand, MCT showed that administration of metformin reduced plasma glucose levels accompanied by the decrease of plasma insulin levels and the increase of plasma glucagon levels, whereas administration of sitagliptin had little effects on these parameters.	Metformin	53-62	insulin	Homo sapiens	131-138
25740979-1	2015	BACKGROUND: Metformin may improve metabolic factors (insulin, glucose, leptin, highly sensitive C-reactive protein [hs-CRP]) associated with poor breast cancer outcomes.	Metformin	12-21	insulin	Homo sapiens	53-60
25740979-1	2015	BACKGROUND: Metformin may improve metabolic factors (insulin, glucose, leptin, highly sensitive C-reactive protein [hs-CRP]) associated with poor breast cancer outcomes.	Metformin	12-21	C-reactive protein	Homo sapiens	96-114
25740979-10	2015	At six months, decreases in weight and blood variables were statistically significantly greater in the metformin arm (vs placebo) in univariate analyses: weight -3.0%, glucose -3.8%, insulin -11.1%, homeostasis model assessment -17.1%, leptin -20.2%, hs-CRP -6.7%; all P values were less than or equal to .03.	Metformin	103-112	insulin	Homo sapiens	183-190
25740979-12	2015	CONCLUSIONS: Metformin statistically significantly improved weight, insulin, glucose, leptin, and CRP at six months.	Metformin	13-22	insulin	Homo sapiens	68-75
24770553-4	2015	Metformin + Con A-treated mice had elevated serum levels of pro-inflammatory cytokines TNF-alpha and IFN-gamma, accompanied by a massive mononuclear cell infiltration in the liver.	Metformin	0-9	tumor necrosis factor	Mus musculus	87-96
25681087-0	2015	Prevention of tumor growth driven by PIK3CA and HPV oncogenes by targeting mTOR signaling with metformin in oral squamous carcinomas expressing OCT3.	Metformin	95-104	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	37-43
25681087-0	2015	Prevention of tumor growth driven by PIK3CA and HPV oncogenes by targeting mTOR signaling with metformin in oral squamous carcinomas expressing OCT3.	Metformin	95-104	mechanistic target of rapamycin kinase	Homo sapiens	75-79
25681087-2	2015	We have recently shown that metformin, an oral antidiabetic drug that is also used to treat lipodystrophy in HIV-infected (HIV(+)) individuals, diminishes mTOR activity and prevents the progression of chemically induced experimental HNSCC premalignant lesions.	Metformin	28-37	mechanistic target of rapamycin kinase	Homo sapiens	155-159
25681087-3	2015	Here, we explored the preclinical activity of metformin in HNSCCs harboring PIK3CA mutations and HPV oncogenes, both representing frequent HNSCC alterations, aimed at developing effective targeted preventive strategies.	Metformin	46-55	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	76-82
25681087-7	2015	We found that metformin inhibits mTOR signaling and tumor growth in HNSCC cells expressing mutated PIK3CA and HPV oncogenes, and that these activities require the expression of organic cation transporter 3 (OCT3/SLC22A3), a metformin uptake transporter.	Metformin	14-23	mechanistic target of rapamycin kinase	Homo sapiens	33-37
25681087-7	2015	We found that metformin inhibits mTOR signaling and tumor growth in HNSCC cells expressing mutated PIK3CA and HPV oncogenes, and that these activities require the expression of organic cation transporter 3 (OCT3/SLC22A3), a metformin uptake transporter.	Metformin	14-23	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	99-105
25542900-9	2015	Ritonavir and metformin effectively suppressed AKT and mTORC1 phosphorylation and prosurvival BCL-2 family member MCL-1 expression in multiple myeloma cell lines in vitro and in vivo.	Metformin	14-23	AKT serine/threonine kinase 1	Homo sapiens	47-50
25542900-9	2015	Ritonavir and metformin effectively suppressed AKT and mTORC1 phosphorylation and prosurvival BCL-2 family member MCL-1 expression in multiple myeloma cell lines in vitro and in vivo.	Metformin	14-23	BCL2 apoptosis regulator	Homo sapiens	94-99
27128216-3	2015	Co-administration of ranolazine 1000 mg BID with metformin 1000 mg BID resulted in 1.53- and 1.79-fold increases in steady-state metformin Cmax and AUCtau , respectively; co-administration of ranolazine 500 mg BID with metformin 1000 mg BID resulted in 1.22- and 1.37-fold increases in steady-state metformin Cmax and AUCtau , respectively.	Metformin	49-58	BH3 interacting domain death agonist	Homo sapiens	67-70
27128216-3	2015	Co-administration of ranolazine 1000 mg BID with metformin 1000 mg BID resulted in 1.53- and 1.79-fold increases in steady-state metformin Cmax and AUCtau , respectively; co-administration of ranolazine 500 mg BID with metformin 1000 mg BID resulted in 1.22- and 1.37-fold increases in steady-state metformin Cmax and AUCtau , respectively.	Metformin	49-58	BH3 interacting domain death agonist	Homo sapiens	67-70
27128216-3	2015	Co-administration of ranolazine 1000 mg BID with metformin 1000 mg BID resulted in 1.53- and 1.79-fold increases in steady-state metformin Cmax and AUCtau , respectively; co-administration of ranolazine 500 mg BID with metformin 1000 mg BID resulted in 1.22- and 1.37-fold increases in steady-state metformin Cmax and AUCtau , respectively.	Metformin	49-58	BH3 interacting domain death agonist	Homo sapiens	67-70
27128216-3	2015	Co-administration of ranolazine 1000 mg BID with metformin 1000 mg BID resulted in 1.53- and 1.79-fold increases in steady-state metformin Cmax and AUCtau , respectively; co-administration of ranolazine 500 mg BID with metformin 1000 mg BID resulted in 1.22- and 1.37-fold increases in steady-state metformin Cmax and AUCtau , respectively.	Metformin	129-138	BH3 interacting domain death agonist	Homo sapiens	40-43
27128216-3	2015	Co-administration of ranolazine 1000 mg BID with metformin 1000 mg BID resulted in 1.53- and 1.79-fold increases in steady-state metformin Cmax and AUCtau , respectively; co-administration of ranolazine 500 mg BID with metformin 1000 mg BID resulted in 1.22- and 1.37-fold increases in steady-state metformin Cmax and AUCtau , respectively.	Metformin	129-138	BH3 interacting domain death agonist	Homo sapiens	67-70
27128216-3	2015	Co-administration of ranolazine 1000 mg BID with metformin 1000 mg BID resulted in 1.53- and 1.79-fold increases in steady-state metformin Cmax and AUCtau , respectively; co-administration of ranolazine 500 mg BID with metformin 1000 mg BID resulted in 1.22- and 1.37-fold increases in steady-state metformin Cmax and AUCtau , respectively.	Metformin	129-138	BH3 interacting domain death agonist	Homo sapiens	67-70
27128216-3	2015	Co-administration of ranolazine 1000 mg BID with metformin 1000 mg BID resulted in 1.53- and 1.79-fold increases in steady-state metformin Cmax and AUCtau , respectively; co-administration of ranolazine 500 mg BID with metformin 1000 mg BID resulted in 1.22- and 1.37-fold increases in steady-state metformin Cmax and AUCtau , respectively.	Metformin	129-138	BH3 interacting domain death agonist	Homo sapiens	67-70
27128216-3	2015	Co-administration of ranolazine 1000 mg BID with metformin 1000 mg BID resulted in 1.53- and 1.79-fold increases in steady-state metformin Cmax and AUCtau , respectively; co-administration of ranolazine 500 mg BID with metformin 1000 mg BID resulted in 1.22- and 1.37-fold increases in steady-state metformin Cmax and AUCtau , respectively.	Metformin	129-138	BH3 interacting domain death agonist	Homo sapiens	40-43
27128216-3	2015	Co-administration of ranolazine 1000 mg BID with metformin 1000 mg BID resulted in 1.53- and 1.79-fold increases in steady-state metformin Cmax and AUCtau , respectively; co-administration of ranolazine 500 mg BID with metformin 1000 mg BID resulted in 1.22- and 1.37-fold increases in steady-state metformin Cmax and AUCtau , respectively.	Metformin	129-138	BH3 interacting domain death agonist	Homo sapiens	67-70
27128216-3	2015	Co-administration of ranolazine 1000 mg BID with metformin 1000 mg BID resulted in 1.53- and 1.79-fold increases in steady-state metformin Cmax and AUCtau , respectively; co-administration of ranolazine 500 mg BID with metformin 1000 mg BID resulted in 1.22- and 1.37-fold increases in steady-state metformin Cmax and AUCtau , respectively.	Metformin	129-138	BH3 interacting domain death agonist	Homo sapiens	67-70
27128216-3	2015	Co-administration of ranolazine 1000 mg BID with metformin 1000 mg BID resulted in 1.53- and 1.79-fold increases in steady-state metformin Cmax and AUCtau , respectively; co-administration of ranolazine 500 mg BID with metformin 1000 mg BID resulted in 1.22- and 1.37-fold increases in steady-state metformin Cmax and AUCtau , respectively.	Metformin	129-138	BH3 interacting domain death agonist	Homo sapiens	67-70
27128216-3	2015	Co-administration of ranolazine 1000 mg BID with metformin 1000 mg BID resulted in 1.53- and 1.79-fold increases in steady-state metformin Cmax and AUCtau , respectively; co-administration of ranolazine 500 mg BID with metformin 1000 mg BID resulted in 1.22- and 1.37-fold increases in steady-state metformin Cmax and AUCtau , respectively.	Metformin	129-138	BH3 interacting domain death agonist	Homo sapiens	40-43
27128216-3	2015	Co-administration of ranolazine 1000 mg BID with metformin 1000 mg BID resulted in 1.53- and 1.79-fold increases in steady-state metformin Cmax and AUCtau , respectively; co-administration of ranolazine 500 mg BID with metformin 1000 mg BID resulted in 1.22- and 1.37-fold increases in steady-state metformin Cmax and AUCtau , respectively.	Metformin	129-138	BH3 interacting domain death agonist	Homo sapiens	67-70
27128216-3	2015	Co-administration of ranolazine 1000 mg BID with metformin 1000 mg BID resulted in 1.53- and 1.79-fold increases in steady-state metformin Cmax and AUCtau , respectively; co-administration of ranolazine 500 mg BID with metformin 1000 mg BID resulted in 1.22- and 1.37-fold increases in steady-state metformin Cmax and AUCtau , respectively.	Metformin	129-138	BH3 interacting domain death agonist	Homo sapiens	67-70
27128216-3	2015	Co-administration of ranolazine 1000 mg BID with metformin 1000 mg BID resulted in 1.53- and 1.79-fold increases in steady-state metformin Cmax and AUCtau , respectively; co-administration of ranolazine 500 mg BID with metformin 1000 mg BID resulted in 1.22- and 1.37-fold increases in steady-state metformin Cmax and AUCtau , respectively.	Metformin	129-138	BH3 interacting domain death agonist	Homo sapiens	67-70
24770553-4	2015	Metformin + Con A-treated mice had elevated serum levels of pro-inflammatory cytokines TNF-alpha and IFN-gamma, accompanied by a massive mononuclear cell infiltration in the liver.	Metformin	0-9	interferon gamma	Mus musculus	101-110
24770553-7	2015	Metformin stimulated inducible nitric oxide synthase (iNOS) expression in the liver and spleen, and genetic deletion of iNOS attenuated the hepatotoxicity of metformin.	Metformin	0-9	nitric oxide synthase 2, inducible	Mus musculus	21-52
24770553-7	2015	Metformin stimulated inducible nitric oxide synthase (iNOS) expression in the liver and spleen, and genetic deletion of iNOS attenuated the hepatotoxicity of metformin.	Metformin	0-9	nitric oxide synthase 2, inducible	Mus musculus	54-58
24770553-7	2015	Metformin stimulated inducible nitric oxide synthase (iNOS) expression in the liver and spleen, and genetic deletion of iNOS attenuated the hepatotoxicity of metformin.	Metformin	158-167	nitric oxide synthase 2, inducible	Mus musculus	120-124
24770553-10	2015	Therefore, metformin aggravates immune-mediated hepatitis by promoting autophagy and activation of immune cells, affecting effector, as well as liver-specific regulatory T cells and iNOS expression.	Metformin	11-20	nitric oxide synthase 2, inducible	Mus musculus	182-186
25425451-7	2015	CONCLUSION: The results of this exploratory study show that combination therapy with metformin/pioglitazone/exenatide in patients with newly diagnosed T2DM is more effective and results in fewer hypoglycaemic events than sequential add-on therapy with metformin, sulfonylurea and then basal insulin.	Metformin	85-94	insulin	Homo sapiens	291-298
24913417-1	2015	Metformin is an old insulin sensitizer that has been widely used in women with polycystic ovary syndrome (PCOS) to treat metabolic comorbidities and may also improve ovarian dysfunction in women with PCOS.	Metformin	0-9	insulin	Homo sapiens	20-27
25216510-11	2015	CONCLUSIONS: Dual inhibition of SGLT1/SGLT2 with LX4211 produced significant dose-ranging improvements in glucose control without dose-increasing glucosuria and was associated with reductions in weight and systolic BP in metformin-treated patients with type 2 diabetes.	Metformin	221-230	solute carrier family 5 member 1	Homo sapiens	32-37
24913417-2	2015	In fact, metformin may improve insulin resistance, a common finding of PCOS, and reduce insulin blood levels.	Metformin	9-18	insulin	Homo sapiens	31-38
24913417-2	2015	In fact, metformin may improve insulin resistance, a common finding of PCOS, and reduce insulin blood levels.	Metformin	9-18	insulin	Homo sapiens	88-95
25729685-8	2015	Metformin is effective insulin sensitizing agent and an established first line drug in type 2 diabetes currently.	Metformin	0-9	insulin	Homo sapiens	23-30
25178647-1	2015	Metformin has a potential role for insulin resistance in polycystic ovary syndrome(PCOS) and has demonstrated efficacy in diabetes.	Metformin	0-9	insulin	Homo sapiens	35-42
25634039-5	2015	Indications for metformin use in IVF cycles included polycystic ovary syndrome (PCOS) patients who were habitual abortions (67%), had prior poor egg quality (61%), had high serum insulin levels (56%).	Metformin	16-25	insulin	Homo sapiens	179-186
25590211-0	2015	Metformin reverts the secretion of CXCL8 induced by TNF-alpha in primary cultures of human thyroid cells: an additional indirect anti-tumor effect of the drug.	Metformin	0-9	C-X-C motif chemokine ligand 8	Homo sapiens	35-40
25590211-0	2015	Metformin reverts the secretion of CXCL8 induced by TNF-alpha in primary cultures of human thyroid cells: an additional indirect anti-tumor effect of the drug.	Metformin	0-9	tumor necrosis factor	Homo sapiens	52-61
25590211-4	2015	OBJECTIVE: This study aimed to evaluate whether metformin inhibits the secretion of CXCL8 induced by Tumor-Necrosis-Factor-alpha (TNF-alpha) in primary cultures of normal and tumor human thyroid cells as well as in thyroid cancer cell lines.	Metformin	48-57	C-X-C motif chemokine ligand 8	Homo sapiens	84-89
25590211-4	2015	OBJECTIVE: This study aimed to evaluate whether metformin inhibits the secretion of CXCL8 induced by Tumor-Necrosis-Factor-alpha (TNF-alpha) in primary cultures of normal and tumor human thyroid cells as well as in thyroid cancer cell lines.	Metformin	48-57	tumor necrosis factor	Homo sapiens	101-128
25590211-4	2015	OBJECTIVE: This study aimed to evaluate whether metformin inhibits the secretion of CXCL8 induced by Tumor-Necrosis-Factor-alpha (TNF-alpha) in primary cultures of normal and tumor human thyroid cells as well as in thyroid cancer cell lines.	Metformin	48-57	tumor necrosis factor	Homo sapiens	130-139
25590211-7	2015	RESULTS: Metformin significantly and dose-dependently inhibited the TNF-alpha-induced CXCL8 secretion in both normal thyrocytes (ANOVA: F = 42.04; P &lt; .0001) and papillary thyroid cancer cells (ANOVA: F = 21.691; P &lt; .0001) but not in TPC-1 and BCPAP cell lines.	Metformin	9-18	tumor necrosis factor	Homo sapiens	68-77
25590211-7	2015	RESULTS: Metformin significantly and dose-dependently inhibited the TNF-alpha-induced CXCL8 secretion in both normal thyrocytes (ANOVA: F = 42.04; P &lt; .0001) and papillary thyroid cancer cells (ANOVA: F = 21.691; P &lt; .0001) but not in TPC-1 and BCPAP cell lines.	Metformin	9-18	C-X-C motif chemokine ligand 8	Homo sapiens	86-91
25590211-7	2015	RESULTS: Metformin significantly and dose-dependently inhibited the TNF-alpha-induced CXCL8 secretion in both normal thyrocytes (ANOVA: F = 42.04; P &lt; .0001) and papillary thyroid cancer cells (ANOVA: F = 21.691; P &lt; .0001) but not in TPC-1 and BCPAP cell lines.	Metformin	9-18	two pore segment channel 1	Homo sapiens	241-246
25590211-8	2015	CONCLUSION: Metformin inhibits the TNF-alpha-induced CXCL8 secretion in primary cultures of normal thyroid cells and differentiated thyroid cancer cells at least of the most frequent poorly aggressive phenotype.	Metformin	12-21	tumor necrosis factor	Homo sapiens	35-44
25590211-8	2015	CONCLUSION: Metformin inhibits the TNF-alpha-induced CXCL8 secretion in primary cultures of normal thyroid cells and differentiated thyroid cancer cells at least of the most frequent poorly aggressive phenotype.	Metformin	12-21	C-X-C motif chemokine ligand 8	Homo sapiens	53-58
25590211-10	2015	Thus, the here-reported inhibiting effect of metformin on TNF-alpha-induced CXCL8 secretion could be considered as a further indirect anticancer property of the drug.	Metformin	45-54	tumor necrosis factor	Homo sapiens	58-67
25590211-10	2015	Thus, the here-reported inhibiting effect of metformin on TNF-alpha-induced CXCL8 secretion could be considered as a further indirect anticancer property of the drug.	Metformin	45-54	C-X-C motif chemokine ligand 8	Homo sapiens	76-81
25598321-6	2015	Interestingly, metformin not only reversed the effect of beta-elemene on phosphorylation of Akt but also strengthened the beta-elemene-reduced DNMT1.	Metformin	15-24	AKT serine/threonine kinase 1	Homo sapiens	92-95
25598321-10	2015	Metformin augments the effect of beta-elemene by blockade of Akt signalling and additively inhibition of DNMT1 protein expression.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	61-64
25663871-0	2015	Effect of metformin on insulin-resistant endothelial cell function.	Metformin	10-19	insulin	Homo sapiens	23-30
25663871-1	2015	The aim of the present study was to investigate the effect of metformin on the function of insulin-resistant (IR) endothelial cells.	Metformin	62-71	insulin	Homo sapiens	91-98
25663871-5	2015	Thus, the present study identified that metformin improves the function of IR endothelial cells, possibly through promoting eNOS protein expression and increasing the NO content.	Metformin	40-49	nitric oxide synthase 3	Homo sapiens	124-128
26038701-8	2015	We demonstrate that (1) Metformin inhibits menadione-induced caspase-9,-6,-3 activation and PARP-cleavage in a concentration-dependent manner.	Metformin	24-33	caspase 9	Rattus norvegicus	61-70
26120598-6	2015	Further investigation into the effects of metformin suggest that the drug directly activates AMPK and dose-dependently suppressed the release of TNF-alpha, IL-6, and MCP-1 by macrophages while enhancing the release of IL-10 in vitro.	Metformin	42-51	tumor necrosis factor	Homo sapiens	145-154
26120598-6	2015	Further investigation into the effects of metformin suggest that the drug directly activates AMPK and dose-dependently suppressed the release of TNF-alpha, IL-6, and MCP-1 by macrophages while enhancing the release of IL-10 in vitro.	Metformin	42-51	interleukin 6	Homo sapiens	156-160
26312913-2	2015	Results from preclinical studies in endometrial cancer show that metformin reduces cellular proliferation by inhibition of the PI3K-AKT-mTOR pathway.	Metformin	65-74	AKT serine/threonine kinase 1	Homo sapiens	132-135
26312913-2	2015	Results from preclinical studies in endometrial cancer show that metformin reduces cellular proliferation by inhibition of the PI3K-AKT-mTOR pathway.	Metformin	65-74	mechanistic target of rapamycin kinase	Homo sapiens	136-140
26312913-18	2015	We are now exploring the hypothesis that metformin reduces Ki-67 expression by inducing phosphorylation of AMP-activated kinase and subsequent mTOR proproliferative inhibition, independent of insulin and insulin-like growth factor receptor activation.	Metformin	41-50	mechanistic target of rapamycin kinase	Homo sapiens	143-147
25605012-6	2015	Co-treatment with the anti-diabetic agent metformin suppressed GRP78 and enhanced the anti-proliferative effect of bortezomib.	Metformin	42-51	heat shock protein family A (Hsp70) member 5	Homo sapiens	63-68
25661368-7	2015	Furthermore, the mechanisms how metformin sensitized ECa109 cells to IR may be targeting the ATM and AMPK/mTOR/HIF-1alpha pathways.	Metformin	32-41	mechanistic target of rapamycin kinase	Homo sapiens	106-110
25486332-0	2015	Inhibitory effect of atenolol on urinary excretion of metformin via down-regulating multidrug and toxin extrusion protein 1 (rMate1) expression in the kidney of rats.	Metformin	54-63	solute carrier family 47 member 1	Rattus norvegicus	125-131
25486332-3	2015	Many patients with type 2 diabetes mellitus (T2DM) receiving metformin may together be given selective beta1 blockers (e.g., atenolol).	Metformin	61-70	potassium calcium-activated channel subfamily M regulatory beta subunit 1	Homo sapiens	103-108
25486332-11	2015	These results indicated that atenolol can inhibit urinary excretion of metformin via decreasing renal rMate1 expression, and long-term atenolol and metformin co-administration may induce potential lactic acidosis.	Metformin	71-80	solute carrier family 47 member 1	Rattus norvegicus	102-108
25486332-12	2015	Our results, for the first time, provided an important experimental evidence that rMate1 is the target of transporter-mediated drug interactions concerning metformin and atenolol.	Metformin	156-165	solute carrier family 47 member 1	Rattus norvegicus	82-88
25673763-5	2015	In vitro, both the mitochondrial metabolism inhibitor metformin and the glucose metabolism inhibitor 2-deoxy-d-glucose (2DG) reduced interferon-gamma (IFN-gamma) production, although at different stages of activation.	Metformin	54-63	interferon gamma	Mus musculus	133-149
25673763-5	2015	In vitro, both the mitochondrial metabolism inhibitor metformin and the glucose metabolism inhibitor 2-deoxy-d-glucose (2DG) reduced interferon-gamma (IFN-gamma) production, although at different stages of activation.	Metformin	54-63	interferon gamma	Mus musculus	151-160
25673763-8	2015	Further, CD4(+) T cells from SLE patients also exhibited enhanced glycolysis and mitochondrial metabolism that correlated with their activation status, and their excessive IFN-gamma production was significantly reduced by metformin in vitro.	Metformin	222-231	CD4 molecule	Homo sapiens	9-12
25673763-8	2015	Further, CD4(+) T cells from SLE patients also exhibited enhanced glycolysis and mitochondrial metabolism that correlated with their activation status, and their excessive IFN-gamma production was significantly reduced by metformin in vitro.	Metformin	222-231	interferon gamma	Homo sapiens	172-181
25658116-13	2015	Metformin upregulated insulin gene expression and suppressed DNA methylation and ectopic triacylglycerol accumulation.	Metformin	0-9	insulin	Homo sapiens	22-29
25428127-6	2015	Metformin (the best known clinical activator of AMPK) suppressed TM- or TG-induced ER stress, as shown by the inhibition of TM- or TG-induced upregulation of glucose-related protein (GRP)78 and phosphorylated eukaryotic initiation factor-2alpha through induction of heme oxygenase-1.	Metformin	0-9	heat shock protein 5	Mus musculus	158-189
25428127-6	2015	Metformin (the best known clinical activator of AMPK) suppressed TM- or TG-induced ER stress, as shown by the inhibition of TM- or TG-induced upregulation of glucose-related protein (GRP)78 and phosphorylated eukaryotic initiation factor-2alpha through induction of heme oxygenase-1.	Metformin	0-9	heme oxygenase 1	Mus musculus	266-282
25428127-10	2015	Consistent with the results of cell culture experiments, metformin reduced renal cortical GRP78 expression and increased heme oxygenase-1 expression in a mouse model of ER stress-induced acute kidney injury by TM.	Metformin	57-66	heat shock protein 5	Mus musculus	90-95
25428127-10	2015	Consistent with the results of cell culture experiments, metformin reduced renal cortical GRP78 expression and increased heme oxygenase-1 expression in a mouse model of ER stress-induced acute kidney injury by TM.	Metformin	57-66	heme oxygenase 1	Mus musculus	121-137
25428127-12	2015	Furthermore, metformin reduced GRP78 expression and renal fibrosis in a mouse model of unilateral ureteral obstruction.	Metformin	13-22	heat shock protein 5	Mus musculus	31-36
25229693-6	2015	Interestingly, administration of AMPK activator metformin (200mg/kg/d, in drinking H2O for 4weeks) rescued against PTEN deletion-induced geometric and functional defects as well as interrupted autophagy and autophagic flux in the heart.	Metformin	48-57	phosphatase and tensin homolog	Mus musculus	115-119
25229693-7	2015	Moreover, metformin administration partially although significantly attenuated PTEN deletion-induced accumulation of superoxide.	Metformin	10-19	phosphatase and tensin homolog	Mus musculus	79-83
25229693-9	2015	Further scrutiny revealed that activation of AMPK and autophagy using metformin and rapamycin, respectively, rescued against PTEN deletion-induced mechanical anomalies with little additive effect.	Metformin	70-79	phosphatase and tensin homolog	Mus musculus	125-129
25661368-7	2015	Furthermore, the mechanisms how metformin sensitized ECa109 cells to IR may be targeting the ATM and AMPK/mTOR/HIF-1alpha pathways.	Metformin	32-41	hypoxia inducible factor 1 subunit alpha	Homo sapiens	111-121
25199921-2	2015	A recent in vitro study found that proton pump inhibitors (PPIs) inhibit OCT1, OCT2 and OCT3, suggesting that PPIs might reduce metformin"s effectiveness.	Metformin	128-137	solute carrier family 22 member 1	Homo sapiens	73-77
25534988-9	2015	In turn, major mechanism of metformin action involved increased expression of proteins implicated in mitochondrial biogenesis and metabolism (PGC-1alpha, PPARalpha, COX IV, cytochrome c, HADHSC).	Metformin	28-37	PPARG coactivator 1 alpha	Homo sapiens	142-152
25534988-9	2015	In turn, major mechanism of metformin action involved increased expression of proteins implicated in mitochondrial biogenesis and metabolism (PGC-1alpha, PPARalpha, COX IV, cytochrome c, HADHSC).	Metformin	28-37	cytochrome c, somatic	Homo sapiens	173-185
25534988-9	2015	In turn, major mechanism of metformin action involved increased expression of proteins implicated in mitochondrial biogenesis and metabolism (PGC-1alpha, PPARalpha, COX IV, cytochrome c, HADHSC).	Metformin	28-37	hydroxyacyl-CoA dehydrogenase	Homo sapiens	187-193
25416412-7	2015	In addition, enhancement of vitamin D3"s chemopreventive effects by metformin was associated with inhibition of the protein expressions of c-Myc and Cyclin D1, via the vitamin D receptor/beta-catenin pathway.	Metformin	68-77	cyclin D1	Rattus norvegicus	149-158
25417601-7	2015	Metformin decreased expression of phosphorylated (p)-AMPK (P = 0.00001), p-Akt (P = 0.0002), p-S6 (51.2%, P = 0.0002), p-4E-BP-1 (P = 0.001), and ER (P = 0.0002) but not PR expression.	Metformin	0-9	estrogen receptor 1	Homo sapiens	146-148
25417601-9	2015	In conclusion, metformin reduced tumor proliferation in a pre-operative window study in obese EC patients, with dramatic effects on inhibition of the mTOR pathway.	Metformin	15-24	mechanistic target of rapamycin kinase	Homo sapiens	150-154
25545400-6	2015	The MET-REMODEL trial is a single-center, phase IV, double blind, randomized, placebo-controlled trial to investigate the efficacy of Metformin in regression of the independent cardiac risk factor of LVH in patients with CAD who are insulin resistant.	Metformin	134-143	insulin	Homo sapiens	233-240
25682077-10	2015	These biomarker data suggest mechanisms for metformin action in vivo in breast cancer patients via up-regulation of tumor pAMPK, down-regulation of pAkt, and suppression of insulin responses reflecting cytostatic rather than cytotoxic mechanisms.	Metformin	44-53	insulin	Homo sapiens	173-180
24534012-2	2015	This study aimed to explore the association between the estimated insulin demand of the diet, as measured by glycemic and insulin load, weight loss, percentage body fat and insulin sensitivity index (ISI) in obese adolescents with clinical features of insulin resistance and/or prediabetes after a 3 month lifestyle and metformin intervention.	Metformin	320-329	insulin	Homo sapiens	66-73
25369141-3	2015	Studies have shown that metformin may benefit those insulin-resistant individuals with T1DM.	Metformin	24-33	insulin	Homo sapiens	52-59
25369141-9	2015	Metformin was associated with a reduction in daily insulin dosage, body weight, total cholesterol level, low-density lipoprotein level, and high-density lipoprotein level but an increase in risk of gastrointestinal AEs compared with placebo treatment in T1DM patients.	Metformin	0-9	insulin	Homo sapiens	51-58
25369141-12	2015	CONCLUSIONS: Metformin may decrease the daily insulin dosage, body weight, and lipid levels in T1DM.	Metformin	13-22	insulin	Homo sapiens	46-53
25377599-0	2015	The impact of metformin treatment on adiponectin and resistin levels in women with polycystic ovary syndrome: a prospective clinical study.	Metformin	14-23	adiponectin, C1Q and collagen domain containing	Homo sapiens	37-48
25377599-7	2015	Adiponectin plasma levels were reduced after metformin treatment, but resistin levels were not significantly affected.	Metformin	45-54	adiponectin, C1Q and collagen domain containing	Homo sapiens	0-11
25905051-7	2015	Metformin lowers circulating insulin and it may be important for treatment of hyperinsulinemia-associated cancers, such as colon and breast cancer.	Metformin	0-9	insulin	Homo sapiens	29-36
25467617-8	2015	RESULTS: Less maternal weight gain was found in the metformin treated groups (9.8 +- 1.5 kg [metformin alone] vs. 9.8 +- 1.4 kg [metformin plus insulin] vs. 12.5 +- 1.1 kg [insulin alone] P &lt; 0.000).	Metformin	52-61	insulin	Homo sapiens	144-151
25467617-8	2015	RESULTS: Less maternal weight gain was found in the metformin treated groups (9.8 +- 1.5 kg [metformin alone] vs. 9.8 +- 1.4 kg [metformin plus insulin] vs. 12.5 +- 1.1 kg [insulin alone] P &lt; 0.000).	Metformin	52-61	insulin	Homo sapiens	173-180
25467617-13	2015	42.7% of patients required supplemental insulin (mean dose of 13.6 +- 2 units) in the metformin group.	Metformin	86-95	insulin	Homo sapiens	40-47
25467617-15	2015	CONCLUSION: Metformin is an effective and cheap treatment option for women with gestational diabetes with or without supplemental insulin.	Metformin	12-21	insulin	Homo sapiens	130-137
25433920-2	2015	We investigated whether metformin (MET) acts directly on skeletal muscle, is transported into skeletal muscle via organic cation transporters (OCTs), and activates AMPK.	Metformin	24-33	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	164-168
25560571-6	2015	A metformin combination therapy significantly decreased such inflamation parameters as hs-CRP, ox-LDL, TNF-alpha and IL-1beta levels relative to monotherapies.	Metformin	2-11	tumor necrosis factor	Homo sapiens	103-112
25560571-6	2015	A metformin combination therapy significantly decreased such inflamation parameters as hs-CRP, ox-LDL, TNF-alpha and IL-1beta levels relative to monotherapies.	Metformin	2-11	interleukin 1 beta	Homo sapiens	117-125
25997252-0	2015	Synergistic antitumor activity of vitamin D3 combined with metformin in human breast carcinoma MDA-MB-231 cells involves m-TOR related signaling pathways.	Metformin	59-68	RAR related orphan receptor C	Homo sapiens	123-126
25678952-5	2015	All four GLP-1 RAs have demonstrated reductions in hemoglobin A1c, fasting blood glucose, and body weight both as monotherapy and in combination with first- and second-line diabetes agents including metformin, sulfonylureas, thiazolidinediones, and insulin.	Metformin	199-208	glucagon	Homo sapiens	9-14
23870192-3	2015	The objective of this study was to investigate the effects of addition of low concentrations of metformin (1 nM to 10 muM) on the percentage of cultured cumulus-oocyte complexes (COC) giving rise to cleavage-stage embryos and AMPK-mediated TSC2 activation.	Metformin	96-105	TSC complex subunit 2	Bos taurus	240-244
23870192-11	2015	Metformin (10 muM) either throughout IVP or during IVF only, increased AMPK-induced PhosphoS1387-TSC2 immunoreactivity (P &lt; 0.01) and this increase corresponded to the total TSC2 protein levels expressed in cells.	Metformin	0-9	TSC complex subunit 2	Bos taurus	97-101
23870192-11	2015	Metformin (10 muM) either throughout IVP or during IVF only, increased AMPK-induced PhosphoS1387-TSC2 immunoreactivity (P &lt; 0.01) and this increase corresponded to the total TSC2 protein levels expressed in cells.	Metformin	0-9	TSC complex subunit 2	Bos taurus	177-181
23870192-12	2015	Our results suggest that there is a dose-dependent negative effect of metformin on the ability of oocytes to cleave following insemination, possibly mediated through an AMPK-induced activation of TSC2.	Metformin	70-79	TSC complex subunit 2	Bos taurus	196-200
25830091-2	2015	The tumour suppressor LKB1 (STK11) and the downstream kinase AMP-activated protein kinase (AMPK), modulate cellular metabolism and growth, and AMPK is an important target of the anti-hyperglycaemic agent metformin.	Metformin	204-213	serine/threonine kinase 11	Mus musculus	22-26
25634597-0	2015	Antihyperglycemic mechanism of metformin occurs via the AMPK/LXRalpha/POMC pathway.	Metformin	31-40	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	56-60
25634597-0	2015	Antihyperglycemic mechanism of metformin occurs via the AMPK/LXRalpha/POMC pathway.	Metformin	31-40	nuclear receptor subfamily 1, group H, member 3	Rattus norvegicus	61-69
25634597-2	2015	Although metformin is known to phosphorylate AMP-activated protein kinase (AMPK), it is unclear how the glucose-lowering effect of metformin is related to AMPK activation.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	45-73
25634597-2	2015	Although metformin is known to phosphorylate AMP-activated protein kinase (AMPK), it is unclear how the glucose-lowering effect of metformin is related to AMPK activation.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	75-79
25634597-8	2015	Actually we found that metformin induced AMPK/liver X receptor alpha (LXRalpha) phosphorylation, followed by pro-opiomelanocortin (POMC) suppression in rat pituitary cells.	Metformin	23-32	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	41-45
25634597-8	2015	Actually we found that metformin induced AMPK/liver X receptor alpha (LXRalpha) phosphorylation, followed by pro-opiomelanocortin (POMC) suppression in rat pituitary cells.	Metformin	23-32	nuclear receptor subfamily 1, group H, member 3	Rattus norvegicus	70-78
25634597-10	2015	Given that cortisol stimulates gluconeogenesis, we propose the anti-hyperglycemic effect of metformin is attributed to reduced POMC/adrenocorticotropic hormone (ACTH)/cortisol levels following AMPK/LXRalpha phosphorylation in the pituitaries.	Metformin	92-101	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	193-197
25634597-10	2015	Given that cortisol stimulates gluconeogenesis, we propose the anti-hyperglycemic effect of metformin is attributed to reduced POMC/adrenocorticotropic hormone (ACTH)/cortisol levels following AMPK/LXRalpha phosphorylation in the pituitaries.	Metformin	92-101	nuclear receptor subfamily 1, group H, member 3	Rattus norvegicus	198-206
25830091-2	2015	The tumour suppressor LKB1 (STK11) and the downstream kinase AMP-activated protein kinase (AMPK), modulate cellular metabolism and growth, and AMPK is an important target of the anti-hyperglycaemic agent metformin.	Metformin	204-213	serine/threonine kinase 11	Mus musculus	28-33
25505174-3	2015	Furthermore, we also provide evidence that Plk1 inhibition makes PCa cells carrying WT p53 much more sensitive to low-dose metformin treatment.	Metformin	123-132	tumor protein p53	Homo sapiens	87-90
25505174-4	2015	Mechanistically, we found that co-treatment with BI2536 and metformin induced p53-dependent apoptosis and further activated the p53/Redd-1 pathway.	Metformin	60-69	tumor protein p53	Homo sapiens	78-81
25505174-4	2015	Mechanistically, we found that co-treatment with BI2536 and metformin induced p53-dependent apoptosis and further activated the p53/Redd-1 pathway.	Metformin	60-69	tumor protein p53	Homo sapiens	128-131
25609400-10	2015	Four secondary outcomes were better for metformin in metformin v insulin, and one was worse for metformin in metformin v glibenclamide.	Metformin	40-49	insulin	Homo sapiens	65-72
25504439-4	2015	We show that both of the main downstream cascades of NRAS can be blocked by this combination: metformin indirectly inhibits the PI3K/AKT/mTOR pathway and trametinib directly impedes the MAPK pathway.	Metformin	94-103	AKT serine/threonine kinase 1	Rattus norvegicus	133-136
25588785-5	2015	We present a protocol for a study to test the hypothesis that metformin will improve insulin sensitivity in obese pregnant women, thereby reducing the incidence of high birthweight babies and other pregnancy complications.	Metformin	62-71	insulin	Homo sapiens	85-92
25179820-0	2015	The anti-diabetic drug metformin inhibits vascular endothelial growth factor expression via the mammalian target of rapamycin complex 1/hypoxia-inducible factor-1alpha signaling pathway in ELT-3 cells.	Metformin	23-32	vascular endothelial growth factor A	Homo sapiens	42-76
25462562-0	2015	Metformin enhances the anti-adipogenic effects of atorvastatin via modulation of STAT3 and TGF-beta/Smad3 signaling.	Metformin	0-9	signal transducer and activator of transcription 3	Homo sapiens	81-86
25305450-6	2015	Western blot showed that metformin activated caspase 3, caspase 9, PARP-1, Bak, and p21 and inactivated Mcl-1, HIAP-1, cyclin D1, CDK4, and CDK6.	Metformin	25-34	caspase 3	Homo sapiens	45-54
25305450-6	2015	Western blot showed that metformin activated caspase 3, caspase 9, PARP-1, Bak, and p21 and inactivated Mcl-1, HIAP-1, cyclin D1, CDK4, and CDK6.	Metformin	25-34	poly(ADP-ribose) polymerase 1	Homo sapiens	67-73
25305450-6	2015	Western blot showed that metformin activated caspase 3, caspase 9, PARP-1, Bak, and p21 and inactivated Mcl-1, HIAP-1, cyclin D1, CDK4, and CDK6.	Metformin	25-34	cyclin dependent kinase 6	Homo sapiens	140-144
25305450-7	2015	Metformin inhibited the expression of insulin growth factor-I receptor (IGF-IR), and phosphatidyl inositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and the downstream mammalian target of rapamycin (mTOR).	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	170-199
25305450-7	2015	Metformin inhibited the expression of insulin growth factor-I receptor (IGF-IR), and phosphatidyl inositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and the downstream mammalian target of rapamycin (mTOR).	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	201-205
25305450-8	2015	IGF-I blocked metformin-induced MM cell apoptosis and reactivation of the PI3K/AKT/mTOR signaling pathway.	Metformin	14-23	insulin like growth factor 1	Homo sapiens	0-5
25305450-8	2015	IGF-I blocked metformin-induced MM cell apoptosis and reactivation of the PI3K/AKT/mTOR signaling pathway.	Metformin	14-23	AKT serine/threonine kinase 1	Homo sapiens	79-82
25305450-8	2015	IGF-I blocked metformin-induced MM cell apoptosis and reactivation of the PI3K/AKT/mTOR signaling pathway.	Metformin	14-23	mechanistic target of rapamycin kinase	Homo sapiens	83-87
25305450-10	2015	We conclude that metformin inhibits MM cell proliferation through the IGF-1R/PI3K/AKT/mTOR signaling pathway.	Metformin	17-26	AKT serine/threonine kinase 1	Homo sapiens	82-85
25305450-10	2015	We conclude that metformin inhibits MM cell proliferation through the IGF-1R/PI3K/AKT/mTOR signaling pathway.	Metformin	17-26	mechanistic target of rapamycin kinase	Homo sapiens	86-90
25359200-4	2015	To investigate whether this inhibitory effect of berberine on OCT1 and OCT2 could change the pharmacokinetics of metformin in vivo, we measured the effect of berberine co-administration on the pharmacokinetics of metformin at a single intravenous dose of 2 mg/kg metformin and 10 mg/kg berberine.	Metformin	113-122	solute carrier family 22 member 1	Homo sapiens	62-66
25359200-5	2015	In HEK293 cells, berberine inhibited OCT1- and OCT2-mediated metformin uptake in a concentration dependent manner and IC50 values for OCT1 and OCT2 were 7.28 and 11.3 muM, respectively.	Metformin	61-70	solute carrier family 22 member 1	Homo sapiens	37-41
26514477-12	2015	CONCLUSIONS: Metformin was able to induce apoptosis in primary ovarian cancer cells by modulating the expression of Bcl-2 family proteins.	Metformin	13-22	BCL2 apoptosis regulator	Homo sapiens	116-121
25462562-0	2015	Metformin enhances the anti-adipogenic effects of atorvastatin via modulation of STAT3 and TGF-beta/Smad3 signaling.	Metformin	0-9	transforming growth factor beta 1	Homo sapiens	91-99
25640355-0	2015	Metformin down-regulates endometrial carcinoma cell secretion of IGF-1 and expression of IGF-1R.	Metformin	0-9	insulin like growth factor 1	Homo sapiens	65-70
25484077-9	2015	Interestingly, metformin treatment upregulated SIRT1 expression and activated PRKA even after siRNA-mediated knockdown of PRKAA1/2 and SIRT1, respectively.	Metformin	15-24	protein kinase, AMP-activated, alpha 1 catalytic subunit	Mus musculus	122-130
26380295-8	2015	Both PPARA and PPARGC1A regulate transcription of genes commonly regulated by glycolysis, by the antidiabetic agent metformin and by NOX, suggesting their major interplay in the control of HCC progression.	Metformin	116-125	PPARG coactivator 1 alpha	Homo sapiens	15-23
25456211-0	2015	AMPK/mTOR-mediated inhibition of survivin partly contributes to metformin-induced apoptosis in human gastric cancer cell.	Metformin	64-73	mechanistic target of rapamycin kinase	Homo sapiens	5-9
25456211-5	2015	We found that metformin treatment selectively induces apoptosis in the 3 cancer cell lines, but not the noncancerous one, as confirmed by flow cytometry, Caspase-Glo assay and western blotting against PARP and cleaved caspase 3.	Metformin	14-23	poly(ADP-ribose) polymerase 1	Homo sapiens	201-205
25456211-10	2015	Similarly, forced overexpression of mTOR downstream effector p70S6K1 relieves metformin-induced inhibition of survivin and partly attenuates metformin-induced apoptosis.	Metformin	78-87	mechanistic target of rapamycin kinase	Homo sapiens	36-40
25456211-10	2015	Similarly, forced overexpression of mTOR downstream effector p70S6K1 relieves metformin-induced inhibition of survivin and partly attenuates metformin-induced apoptosis.	Metformin	141-150	mechanistic target of rapamycin kinase	Homo sapiens	36-40
25456211-13	2015	Taken together, these evidences suggest that AMPK/mTOR-mediated inhibition of survivin may partly contribute to metformin-induced apoptosis of gastric cancer cell.	Metformin	112-121	mechanistic target of rapamycin kinase	Homo sapiens	50-54
25640355-3	2015	However, the IGF-1 level in the medium of cultured cells after treatment with metformin was decreased (p&lt;0.05).	Metformin	78-87	insulin like growth factor 1	Homo sapiens	13-18
25701261-8	2015	Finally, we found that anti-diabetic drug metformin and AMPK ligand AICAR, but not thiazolidinediones (TZDs), specifically suppress the estradiol-induced cellular growth in the insulin-primed cells.	Metformin	42-51	insulin	Homo sapiens	177-184
25701261-9	2015	These findings suggest that estrogen receptor (ER) activation under chronic hyperinsulinemic condition increases breast cancer growth through the modulation of cell cycle and apoptotic factors and nutrient metabolism, and further provide a mechanistic evidence for the clinical benefit of metformin use for ER-positive breast cancer patients with diabetes.	Metformin	289-298	estrogen receptor 1	Homo sapiens	28-45
25701261-9	2015	These findings suggest that estrogen receptor (ER) activation under chronic hyperinsulinemic condition increases breast cancer growth through the modulation of cell cycle and apoptotic factors and nutrient metabolism, and further provide a mechanistic evidence for the clinical benefit of metformin use for ER-positive breast cancer patients with diabetes.	Metformin	289-298	estrogen receptor 1	Homo sapiens	47-49
25701261-9	2015	These findings suggest that estrogen receptor (ER) activation under chronic hyperinsulinemic condition increases breast cancer growth through the modulation of cell cycle and apoptotic factors and nutrient metabolism, and further provide a mechanistic evidence for the clinical benefit of metformin use for ER-positive breast cancer patients with diabetes.	Metformin	289-298	estrogen receptor 1	Homo sapiens	307-309
25640355-4	2015	IGF-1R was highly expressed in human endometrial carcinoma paraffin sections, but IGF-1R and phosphor-protein kinase B/protein kinase B (p-Akt/ Akt) expression was down-regulated after metformin treatment (p&lt;0.05).	Metformin	185-194	AKT serine/threonine kinase 1	Homo sapiens	139-142
25640355-4	2015	IGF-1R was highly expressed in human endometrial carcinoma paraffin sections, but IGF-1R and phosphor-protein kinase B/protein kinase B (p-Akt/ Akt) expression was down-regulated after metformin treatment (p&lt;0.05).	Metformin	185-194	AKT serine/threonine kinase 1	Homo sapiens	144-147
25640355-5	2015	In summary, metformin can reduce the secretion of IGF-1 by Ishikawa and JEC EC cell lines and their expression of IGF-1R to deactivate downstream signaling involving the PI-3K/Akt pathway to inhibit endometrial carcinoma cell growth.	Metformin	12-21	insulin like growth factor 1	Homo sapiens	50-55
25640355-5	2015	In summary, metformin can reduce the secretion of IGF-1 by Ishikawa and JEC EC cell lines and their expression of IGF-1R to deactivate downstream signaling involving the PI-3K/Akt pathway to inhibit endometrial carcinoma cell growth.	Metformin	12-21	AKT serine/threonine kinase 1	Homo sapiens	176-179
25790097-5	2015	This effect was associated to a reduction of pyruvate kinase enzymatic activity and was reversed using metformin, which decreases Akt phosphorylation.	Metformin	103-112	AKT serine/threonine kinase 1	Homo sapiens	130-133
25790097-7	2015	Metformin inhibited HK2, GLUT1, HIF-1alpha expression and glucose consumption.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	32-42
26496168-6	2015	Metformin, an inhibitor of mitochondrial respiratory chain was able to reconvert oxidative metabolism and abrogate TGFbeta expression in LpH-MSC.	Metformin	0-9	transforming growth factor beta 1	Homo sapiens	115-122
26642701-8	2015	After 24 weeks of metformin treatment, the levels of WHR, AST, ALT, TG, chemerin and HOMA-IR were significantly reduced (p &lt; 0.05) and other indexes were not changed significantly.	Metformin	18-27	solute carrier family 17 member 5	Homo sapiens	58-61
25808533-3	2015	The reduction of gluconeogenesis evoked by metformin may be a result of an energy deficit evoked through the inhibition of mitochondrial respiratory chain complex I and/or increased cytosolic redox state and decreased mitochondrial redox state elicited by the inhibition of mitochondrial glycerophosphate dehydrogenase (mGPD).	Metformin	43-52	glycerol-3-phosphate dehydrogenase 2	Homo sapiens	274-318
25808533-3	2015	The reduction of gluconeogenesis evoked by metformin may be a result of an energy deficit evoked through the inhibition of mitochondrial respiratory chain complex I and/or increased cytosolic redox state and decreased mitochondrial redox state elicited by the inhibition of mitochondrial glycerophosphate dehydrogenase (mGPD).	Metformin	43-52	atypical chemokine receptor 1 (Duffy blood group)	Mus musculus	320-324
25808533-5	2015	Recently, it was reported that inhibition of mGPD by metformin decreases the level of dihydroxyacetone phosphate and reduces the conversion of lactate to pyruvate, that in consequence diminishes the utilization of glycerol and lactate for gluconeogenesis.	Metformin	53-62	atypical chemokine receptor 1 (Duffy blood group)	Mus musculus	45-49
25205223-9	2015	In adjusted analyses, SU + insulin was associated with increased all-cause mortality (RR 1.81 [1.63, 2.01]), cardiovascular death (RR 1.35 [1.14, 1.60]) and the composite endpoint (RR 1.25 [1.09, 1.42]) compared with metformin + insulin.	Metformin	217-226	insulin	Homo sapiens	27-34
25328079-11	2015	Our data indicate that sitagliptin and metformin exert different effects on islet hormone secretion in Japanese type 2 diabetic patients on insulin monotherapy.	Metformin	39-48	insulin	Homo sapiens	140-147
25328079-0	2015	Addition of sitagliptin or metformin to insulin monotherapy improves blood glucose control via different effects on insulin and glucagon secretion in hyperglycemic Japanese patients with type 2 diabetes.	Metformin	27-36	insulin	Homo sapiens	116-123
25328079-1	2015	This study aimed to explore the effects of the dipeptidyl peptidase-4 inhibitor sitagliptin and the biguanide metformin on the secretion of insulin and glucagon, as well as incretin levels, in Japanese subjects with type 2 diabetes mellitus poorly controlled with insulin monotherapy.	Metformin	110-119	insulin	Homo sapiens	140-147
25388747-5	2015	The absorption of folic acid and vitamin B12 is importantly decreased by the prolongued use of metformin, which is the first choice drug in uncomplicated diabetes, thus these two nutrients have been found deficient in the disease and most probably need to be supplemented regularly.	Metformin	95-104	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	41-44
25343273-1	2015	Galectin-3, a beta-galactoside-binding lectin, is elevated in obesity and type 2 diabetes mellitus, and metformin treatment reduces these galectin-3 levels.	Metformin	104-113	lectin, galactose binding, soluble 3	Mus musculus	138-148
25388747-9	2015	After reviewing the evidence, no real recommendation on the use of vitamin supplements in type 2 diabetes mellitus can be issued, however patients using metformin during prolongued periods may need folic acid and vitamin B12.	Metformin	153-162	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	221-224
24720899-0	2015	Binding site identification of metformin to human serum albumin and glycated human serum albumin by spectroscopic and molecular modeling techniques: a comparison study.	Metformin	31-40	albumin	Homo sapiens	50-63
25772174-4	2015	Recent preclinical and clinical studies have suggested that metformin not only improves chronic inflammation through the improvement of metabolic parameters such as hyperglycemia, insulin resistance and atherogenic dyslipidemia, but also has a direct anti-inflammatory action.	Metformin	60-69	insulin	Homo sapiens	180-187
25772174-5	2015	Studies have suggested that metformin suppresses inflammatory response by inhibition of nuclear factor kappaB (NFkappaB) via AMP-activated protein kinase (AMPK)-dependent and independent pathways.	Metformin	28-37	nuclear factor kappa B subunit 1	Homo sapiens	88-109
25772174-5	2015	Studies have suggested that metformin suppresses inflammatory response by inhibition of nuclear factor kappaB (NFkappaB) via AMP-activated protein kinase (AMPK)-dependent and independent pathways.	Metformin	28-37	nuclear factor kappa B subunit 1	Homo sapiens	111-119
25162967-5	2015	In the high-dose metformin group, BMI, waist circumference, fasting plasma glucose, homeostatic model assessment of insulin resistance index, and 2-h plasma glucose were significantly decreased.	Metformin	17-26	insulin	Homo sapiens	116-123
25162967-8	2015	Metformin suppressed ACF formation in IGT patients in a dose-dependent manner, possibly through direct and indirect (attenuating insulin resistance) mechanisms.	Metformin	0-9	insulin	Homo sapiens	129-136
25327507-0	2015	A pharmacogenetic association between a variation in calpain 10 (CAPN10) gene and the response to metformin treatment in patients with type 2 diabetes.	Metformin	98-107	calpain 10	Homo sapiens	53-63
25327507-0	2015	A pharmacogenetic association between a variation in calpain 10 (CAPN10) gene and the response to metformin treatment in patients with type 2 diabetes.	Metformin	98-107	calpain 10	Homo sapiens	65-71
25327507-10	2015	CONCLUSIONS: The present study provides the first observation of an association between a variant in CAPN10 gene and the response to metformin therapy in patients with type 2 diabetes.	Metformin	133-142	calpain 10	Homo sapiens	101-107
25552403-10	2015	RESULTS: Trimethoprim inhibited metformin transport with K i values of 27.2, 6.3, and 28.9 muM and NMN transport with IC50 values of 133.9, 29.1, and 0.61 muM for OCT2, MATE1, and MATE2-K, respectively.	Metformin	32-41	latexin	Homo sapiens	91-94
25237893-0	2015	Effects of metformin on endocrine, metabolic milieus and endometrial expression of androgen receptor in patients with polycystic ovary syndrome.	Metformin	11-20	androgen receptor	Homo sapiens	83-100
25237893-11	2015	CONCLUSION: Metformin was effective in decreasing HOMA-IR, LH, free testosterone and the relative expression levels of AR.	Metformin	12-21	androgen receptor	Homo sapiens	119-121
24720899-0	2015	Binding site identification of metformin to human serum albumin and glycated human serum albumin by spectroscopic and molecular modeling techniques: a comparison study.	Metformin	31-40	albumin	Homo sapiens	83-96
24720899-1	2015	The interaction between metformin and human serum albumin (HSA), as well as its glycated form (gHSA) was investigated by multiple spectroscopic techniques, zeta potential, and molecular modeling under physiological conditions.	Metformin	24-33	albumin	Homo sapiens	44-57
26106623-4	2015	Treatment with insulin sensitizing medications such as thiazolidinediones and metformin was more effective in improving glycemic control, particularly in the more insulin resistant patient, when compared to the insulin provision strategy using insulin and or sulfonylureas.	Metformin	78-87	insulin	Homo sapiens	15-22
25053577-7	2015	RESULTS: Among all Vanderbilt cancer patients, metformin was associated with a 22% decrease in overall mortality compared to other oral hypoglycemic medications (HR 0.78; 95% CI 0.69 to 0.88) and with a 39% decrease compared to type 2 diabetes patients on insulin only (HR 0.61; 95% CI 0.50 to 0.73).	Metformin	47-56	insulin	Homo sapiens	256-263
26106623-4	2015	Treatment with insulin sensitizing medications such as thiazolidinediones and metformin was more effective in improving glycemic control, particularly in the more insulin resistant patient, when compared to the insulin provision strategy using insulin and or sulfonylureas.	Metformin	78-87	insulin	Homo sapiens	163-170
26106623-4	2015	Treatment with insulin sensitizing medications such as thiazolidinediones and metformin was more effective in improving glycemic control, particularly in the more insulin resistant patient, when compared to the insulin provision strategy using insulin and or sulfonylureas.	Metformin	78-87	insulin	Homo sapiens	163-170
26106623-4	2015	Treatment with insulin sensitizing medications such as thiazolidinediones and metformin was more effective in improving glycemic control, particularly in the more insulin resistant patient, when compared to the insulin provision strategy using insulin and or sulfonylureas.	Metformin	78-87	insulin	Homo sapiens	163-170
25131770-11	2015	Metformin, an AMPK activator, more strongly suppressed cell growth in p53-mutant cell lines with inactive SIRT1 than in p53-mutant cell lines with active SIRT1.	Metformin	0-9	tumor protein p53	Homo sapiens	70-73
25131770-11	2015	Metformin, an AMPK activator, more strongly suppressed cell growth in p53-mutant cell lines with inactive SIRT1 than in p53-mutant cell lines with active SIRT1.	Metformin	0-9	tumor protein p53	Homo sapiens	120-123
25131770-13	2015	Metformin could be a therapeutic drug for HCC in patients with mutated p53, inactivated SIRT1, and AMPK expression.	Metformin	0-9	tumor protein p53	Homo sapiens	71-74
26880912-6	2015	Results of our study revealed that pretreatment with metformin or sitagliptin produced significant (P &lt; 0.05) cardiac protection manifested by a significant decrease in serum levels of LDH and CK-MB enzymes and cardiac MDA and total nitrites and nitrates levels, a significant increase in cardiac SOD activity, and remarkable improvement in the histopathological features as well as a significant reduction in the immunohistochemical expression of COX-2, iNOS, and caspase-3 enzymes as compared to DOX group.	Metformin	53-62	nitric oxide synthase 2	Rattus norvegicus	458-462
26688757-3	2015	In metformin-sensitive cells, autophagy was not induced but rather it blocked proliferation by means of arresting cells in the S and G2/M phases which was associated with the downregulation of cyclin A, cyclin B1, and cdc2, but not that of cyclin E. In 10E1-CEM cells that overexpress Bcl-2 and are drug-resistant, the effect of metformin on proliferation was more pronounced, also inducing the activation of the caspases 3/7 and hence apoptosis.	Metformin	3-12	cyclin A2	Homo sapiens	193-201
26688757-3	2015	In metformin-sensitive cells, autophagy was not induced but rather it blocked proliferation by means of arresting cells in the S and G2/M phases which was associated with the downregulation of cyclin A, cyclin B1, and cdc2, but not that of cyclin E. In 10E1-CEM cells that overexpress Bcl-2 and are drug-resistant, the effect of metformin on proliferation was more pronounced, also inducing the activation of the caspases 3/7 and hence apoptosis.	Metformin	3-12	BCL2 apoptosis regulator	Homo sapiens	285-290
25709223-8	2015	Metformin also increased t-Bid expression and the subsequent release of cytochrome C into the cytosol.	Metformin	0-9	BH3 interacting domain death agonist	Homo sapiens	27-30
25709223-8	2015	Metformin also increased t-Bid expression and the subsequent release of cytochrome C into the cytosol.	Metformin	0-9	cytochrome c, somatic	Homo sapiens	72-84
26401715-0	2015	IL-1B rs1143623 and EEF1A1P11-RPL7P9 rs10783050 polymorphisms affect the glucose-lowing efficacy of metformin in Chinese overweight or obese Type 2 diabetes mellitus patients.	Metformin	100-109	interleukin 1 beta	Homo sapiens	0-5
26401715-0	2015	IL-1B rs1143623 and EEF1A1P11-RPL7P9 rs10783050 polymorphisms affect the glucose-lowing efficacy of metformin in Chinese overweight or obese Type 2 diabetes mellitus patients.	Metformin	100-109	eukaryotic translation elongation factor 1 alpha 1 pseudogene 11	Homo sapiens	20-29
26401715-7	2015	CONCLUSION: IL1B rs1143623 and EEF1A1P11-RPL7P9 rs10783050 polymorphisms may contribute to metformin"s glucose-lowing efficacy in overweight or obese Chinese T2DM patients.	Metformin	91-100	interleukin 1 beta	Homo sapiens	12-16
26401715-7	2015	CONCLUSION: IL1B rs1143623 and EEF1A1P11-RPL7P9 rs10783050 polymorphisms may contribute to metformin"s glucose-lowing efficacy in overweight or obese Chinese T2DM patients.	Metformin	91-100	eukaryotic translation elongation factor 1 alpha 1 pseudogene 11	Homo sapiens	31-40
25510597-1	2014	BACKGROUND: Metformin, an insulin-sensitizer, may correct several physiologic abnormalities owing to insulin resistance in patients with type 2 diabetes mellitus (DM).	Metformin	12-21	insulin	Homo sapiens	26-33
25874236-7	2015	84.9% patients in metformin group required add-on insulin therapy at mean gestational age of 26.58 +- 3.85 weeks.	Metformin	18-27	insulin	Homo sapiens	50-57
25493642-0	2014	Dose-Dependent AMPK-Dependent and Independent Mechanisms of Berberine and Metformin Inhibition of mTORC1, ERK, DNA Synthesis and Proliferation in Pancreatic Cancer Cells.	Metformin	74-83	mitogen-activated protein kinase 1	Homo sapiens	106-109
25491250-11	2014	Preliminary analysis of total AKT and ERK1/2 levels in plasma EVs from patients with NSCLC before and after sorafenib/metformin treatment (n=12) shows a significant decrease in AKT levels among patients with a favourable treatment response (p&lt;0.005).	Metformin	118-127	AKT serine/threonine kinase 1	Homo sapiens	30-33
25491250-11	2014	Preliminary analysis of total AKT and ERK1/2 levels in plasma EVs from patients with NSCLC before and after sorafenib/metformin treatment (n=12) shows a significant decrease in AKT levels among patients with a favourable treatment response (p&lt;0.005).	Metformin	118-127	mitogen-activated protein kinase 3	Homo sapiens	38-44
25491250-11	2014	Preliminary analysis of total AKT and ERK1/2 levels in plasma EVs from patients with NSCLC before and after sorafenib/metformin treatment (n=12) shows a significant decrease in AKT levels among patients with a favourable treatment response (p&lt;0.005).	Metformin	118-127	AKT serine/threonine kinase 1	Homo sapiens	177-180
25503637-8	2014	Agonist induction of AMPK activity with AICAR or metformin increased macroautophagy protein LC3 and normalized p62/SQSTM1 expression and mTOR activity.	Metformin	49-58	mechanistic target of rapamycin kinase	Homo sapiens	137-141
25510597-1	2014	BACKGROUND: Metformin, an insulin-sensitizer, may correct several physiologic abnormalities owing to insulin resistance in patients with type 2 diabetes mellitus (DM).	Metformin	12-21	insulin	Homo sapiens	101-108
25462874-14	2014	LPS-, AICAR- and metformin-,but not A-769662-, induced neuronal losses were inhibited by presence of compound C. LPS, AICAR or metformin exposure increased the relative number of VIP-IR neurons; co-treatment with (5Z)-7-Oxozeaenol or compound C reversed the relative increase in VIP-IR neurons induced by LPS.	Metformin	17-26	vasoactive intestinal peptide	Rattus norvegicus	179-182
25462874-9	2014	AMPK-induced neuronal loss was verified treating cultures with three different AMPK activators, AICAR (10-4-3x10-3 M), metformin (0.2-20 microg/mL) and A-769662 (10-5-3x10-4 M) with or without the presence of compound C (10-5 M).	Metformin	119-128	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	0-4
25462874-14	2014	LPS-, AICAR- and metformin-,but not A-769662-, induced neuronal losses were inhibited by presence of compound C. LPS, AICAR or metformin exposure increased the relative number of VIP-IR neurons; co-treatment with (5Z)-7-Oxozeaenol or compound C reversed the relative increase in VIP-IR neurons induced by LPS.	Metformin	17-26	vasoactive intestinal peptide	Rattus norvegicus	279-282
25462874-14	2014	LPS-, AICAR- and metformin-,but not A-769662-, induced neuronal losses were inhibited by presence of compound C. LPS, AICAR or metformin exposure increased the relative number of VIP-IR neurons; co-treatment with (5Z)-7-Oxozeaenol or compound C reversed the relative increase in VIP-IR neurons induced by LPS.	Metformin	127-136	vasoactive intestinal peptide	Rattus norvegicus	179-182
25462874-14	2014	LPS-, AICAR- and metformin-,but not A-769662-, induced neuronal losses were inhibited by presence of compound C. LPS, AICAR or metformin exposure increased the relative number of VIP-IR neurons; co-treatment with (5Z)-7-Oxozeaenol or compound C reversed the relative increase in VIP-IR neurons induced by LPS.	Metformin	127-136	vasoactive intestinal peptide	Rattus norvegicus	279-282
25245054-9	2014	In conclusion, metformin inhibits the migration and invasion of HCC cells by suppressing the ERK/JNK-mediated NF-kappaB-dependent pathway, and thereby reducing uPA and MMP-9 expression.	Metformin	15-24	proline rich acidic protein 1	Homo sapiens	160-163
25245054-0	2014	Metformin inhibits the invasion of human hepatocellular carcinoma cells and enhances the chemosensitivity to sorafenib through a downregulation of the ERK/JNK-mediated NF-kappaB-dependent pathway that reduces uPA and MMP-9 expression.	Metformin	0-9	mitogen-activated protein kinase 1	Homo sapiens	151-154
25245054-0	2014	Metformin inhibits the invasion of human hepatocellular carcinoma cells and enhances the chemosensitivity to sorafenib through a downregulation of the ERK/JNK-mediated NF-kappaB-dependent pathway that reduces uPA and MMP-9 expression.	Metformin	0-9	mitogen-activated protein kinase 8	Homo sapiens	155-158
25245054-0	2014	Metformin inhibits the invasion of human hepatocellular carcinoma cells and enhances the chemosensitivity to sorafenib through a downregulation of the ERK/JNK-mediated NF-kappaB-dependent pathway that reduces uPA and MMP-9 expression.	Metformin	0-9	proline rich acidic protein 1	Homo sapiens	209-212
25245054-5	2014	Metformin was also found to significantly inhibit the expression and secretion of MMP-9 and uPA in HCC cells, and suppress the phosphorylation of ERK1/2 and JNK1/2.	Metformin	0-9	proline rich acidic protein 1	Homo sapiens	92-95
25245054-5	2014	Metformin was also found to significantly inhibit the expression and secretion of MMP-9 and uPA in HCC cells, and suppress the phosphorylation of ERK1/2 and JNK1/2.	Metformin	0-9	mitogen-activated protein kinase 3	Homo sapiens	146-152
25245054-5	2014	Metformin was also found to significantly inhibit the expression and secretion of MMP-9 and uPA in HCC cells, and suppress the phosphorylation of ERK1/2 and JNK1/2.	Metformin	0-9	mitogen-activated protein kinase 8	Homo sapiens	157-163
25245054-6	2014	Treatment with an ERK1/2 inhibitor (PD98059) or JNK1/2 inhibitor (SP600125) enhanced the inhibitory effects of metformin on the migration and invasion of HCC cells.	Metformin	111-120	mitogen-activated protein kinase 3	Homo sapiens	18-24
25245054-6	2014	Treatment with an ERK1/2 inhibitor (PD98059) or JNK1/2 inhibitor (SP600125) enhanced the inhibitory effects of metformin on the migration and invasion of HCC cells.	Metformin	111-120	mitogen-activated protein kinase 8	Homo sapiens	48-54
25245054-7	2014	Moreover, metformin-induced inhibition of MMP-9 and uPA promoter activity also blocked the nuclear translocation of NF-kappaB and its binding to the MMP-9 and uPA promoters, and these suppressive effects were further enhanced by PD98059 or SP600125.	Metformin	10-19	proline rich acidic protein 1	Homo sapiens	52-55
25245054-7	2014	Moreover, metformin-induced inhibition of MMP-9 and uPA promoter activity also blocked the nuclear translocation of NF-kappaB and its binding to the MMP-9 and uPA promoters, and these suppressive effects were further enhanced by PD98059 or SP600125.	Metformin	10-19	proline rich acidic protein 1	Homo sapiens	159-162
25245054-9	2014	In conclusion, metformin inhibits the migration and invasion of HCC cells by suppressing the ERK/JNK-mediated NF-kappaB-dependent pathway, and thereby reducing uPA and MMP-9 expression.	Metformin	15-24	mitogen-activated protein kinase 1	Homo sapiens	93-96
25245054-9	2014	In conclusion, metformin inhibits the migration and invasion of HCC cells by suppressing the ERK/JNK-mediated NF-kappaB-dependent pathway, and thereby reducing uPA and MMP-9 expression.	Metformin	15-24	mitogen-activated protein kinase 8	Homo sapiens	97-100
25060604-1	2014	AIM: The organic cation transporter 1 (OCT1) plays a key role in the cellular transport of metformin and its subsequent glucose-lowering effect.	Metformin	91-100	solute carrier family 22 member 1	Homo sapiens	9-37
25060604-1	2014	AIM: The organic cation transporter 1 (OCT1) plays a key role in the cellular transport of metformin and its subsequent glucose-lowering effect.	Metformin	91-100	solute carrier family 22 member 1	Homo sapiens	39-43
25060604-2	2014	A recent non-clinical study reported that metformin uptake into hepatocytes is regulated via OCT1, and that uptake was strongly inhibited by verapamil.	Metformin	42-51	solute carrier family 22 member 1	Homo sapiens	93-97
25060604-7	2014	CONCLUSIONS: Our results suggest that verapamil remarkably decreases the glucose-lowering effect of metformin, possibly by acting as a competitive inhibitor of OCT1.	Metformin	100-109	solute carrier family 22 member 1	Homo sapiens	160-164
25293340-7	2014	Metformin can be used in conjunction with a lifestyle intervention program in obese adolescents with clinical insulin resistance to achieve weight loss and to improve insulin sensitivity.	Metformin	0-9	insulin	Homo sapiens	110-117
25293340-7	2014	Metformin can be used in conjunction with a lifestyle intervention program in obese adolescents with clinical insulin resistance to achieve weight loss and to improve insulin sensitivity.	Metformin	0-9	insulin	Homo sapiens	167-174
24903160-0	2014	Metformin prevents LYRM1-induced insulin resistance in 3T3-L1 adipocytes via a mitochondrial-dependent mechanism.	Metformin	0-9	insulin	Homo sapiens	33-40
25213800-10	2014	CONCLUSION: Assuming a WTP of SEK 500,000 per QALY, treatment strategy with GLP-1 agonists is a cost-effective strategy in comparison to DPP-4 inhibitors and NPH insulin among T2DM patients inadequately controlled with metformin alone in a Swedish setting.	Metformin	219-228	glucagon	Homo sapiens	76-81
24903160-5	2014	Metformin may ameliorate LYRM1-induced insulin resistance and mitochondrial dysfunction in part via a direct antioxidant effect and in part by activating the adenosine monophosphate-activated protein kinase (AMPK)-PGC1/NRFs pathway.	Metformin	0-9	insulin	Homo sapiens	39-46
24903160-4	2014	Metformin enhanced basal and insulin-stimulated glucose uptake and GLUT4 translocation, reduced IRS-1 and Akt phosphorylation and ROS levels, and affected the expression of regulators of mitochondrial biogenesis in LYRM1-over-expressing adipocytes.	Metformin	0-9	insulin	Homo sapiens	29-36
24903160-5	2014	Metformin may ameliorate LYRM1-induced insulin resistance and mitochondrial dysfunction in part via a direct antioxidant effect and in part by activating the adenosine monophosphate-activated protein kinase (AMPK)-PGC1/NRFs pathway.	Metformin	0-9	PPARG coactivator 1 alpha	Homo sapiens	214-218
24903160-4	2014	Metformin enhanced basal and insulin-stimulated glucose uptake and GLUT4 translocation, reduced IRS-1 and Akt phosphorylation and ROS levels, and affected the expression of regulators of mitochondrial biogenesis in LYRM1-over-expressing adipocytes.	Metformin	0-9	AKT serine/threonine kinase 1	Homo sapiens	106-109
24824502-6	2014	AMPK-activating drugs reverse many of the metabolic defects associated with insulin resistance, and recent findings suggest that the insulin-sensitizing effects of the widely used antidiabetic drug metformin are mediated by AMPK.	Metformin	198-207	insulin	Homo sapiens	76-83
25674239-19	2014	Agents that may be considered based on existing data include: bortezomib to inhibit NF-kappaB pathway activation; metformin to inhibit both NF-kappaB and mTORC2 and histone deacteylase inhibitors to inhibit mTORC2 pathway signaling.	Metformin	114-123	nuclear factor kappa B subunit 1	Homo sapiens	140-149
25527624-4	2014	METHODS AND RESULTS: Using ApoE-/- C57BL/6J mice, we found that metformin attenuates atherosclerosis and vascular senescence in mice fed a high-fat diet and prevents the upregulation of angiotensin II type 1 receptor by a high-fat diet in the aortas of mice.	Metformin	64-73	apolipoprotein E	Mus musculus	27-31
24824502-6	2014	AMPK-activating drugs reverse many of the metabolic defects associated with insulin resistance, and recent findings suggest that the insulin-sensitizing effects of the widely used antidiabetic drug metformin are mediated by AMPK.	Metformin	198-207	insulin	Homo sapiens	133-140
25347323-9	2014	In unadjusted analyses, use of medications other than metformin was significantly associated with an increased risk of adding a second oral agent only, insulin only, and a second agent or insulin (P &lt; .001 for all).	Metformin	54-63	insulin	Homo sapiens	152-159
25256878-6	2014	RESULTS: Metformin administration resulted in significant decrease in the body weight, body mass index, hirsutism score, fasting and postprandial blood glucose, fasting serum insulin, HOMA index, sleep disturbances scale, and Epworth sleepiness scale compared to the untreated PCOS group.	Metformin	9-18	insulin	Homo sapiens	175-182
25347323-9	2014	In unadjusted analyses, use of medications other than metformin was significantly associated with an increased risk of adding a second oral agent only, insulin only, and a second agent or insulin (P &lt; .001 for all).	Metformin	54-63	insulin	Homo sapiens	188-195
25310259-7	2014	Metformin targeted the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, suppressed the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and transcriptionally downregulated the expression of multidrug resistance protein 1/P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1).	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	59-88
25310259-7	2014	Metformin targeted the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, suppressed the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and transcriptionally downregulated the expression of multidrug resistance protein 1/P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1).	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	90-94
25310259-7	2014	Metformin targeted the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, suppressed the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and transcriptionally downregulated the expression of multidrug resistance protein 1/P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1).	Metformin	0-9	ATP binding cassette subfamily C member 1	Homo sapiens	290-331
25310259-7	2014	Metformin targeted the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, suppressed the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and transcriptionally downregulated the expression of multidrug resistance protein 1/P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1).	Metformin	0-9	ATP binding cassette subfamily C member 1	Homo sapiens	333-337
25310259-7	2014	Metformin targeted the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, suppressed the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and transcriptionally downregulated the expression of multidrug resistance protein 1/P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1).	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	134-165
25310259-8	2014	Collectively, these findings suggested that metformin may target the AMPK/mTOR/HIF-1alpha/P-gp and MRP1 pathways to reverse MDR in hepatocellular carcinoma.	Metformin	44-53	mechanistic target of rapamycin kinase	Homo sapiens	74-78
25310259-8	2014	Collectively, these findings suggested that metformin may target the AMPK/mTOR/HIF-1alpha/P-gp and MRP1 pathways to reverse MDR in hepatocellular carcinoma.	Metformin	44-53	hypoxia inducible factor 1 subunit alpha	Homo sapiens	79-89
25310259-7	2014	Metformin targeted the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, suppressed the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and transcriptionally downregulated the expression of multidrug resistance protein 1/P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1).	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Homo sapiens	167-177
25310259-8	2014	Collectively, these findings suggested that metformin may target the AMPK/mTOR/HIF-1alpha/P-gp and MRP1 pathways to reverse MDR in hepatocellular carcinoma.	Metformin	44-53	ATP binding cassette subfamily C member 1	Homo sapiens	99-103
25310259-7	2014	Metformin targeted the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, suppressed the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and transcriptionally downregulated the expression of multidrug resistance protein 1/P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1).	Metformin	0-9	ATP binding cassette subfamily B member 1	Homo sapiens	233-263
25310259-7	2014	Metformin targeted the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, suppressed the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and transcriptionally downregulated the expression of multidrug resistance protein 1/P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1).	Metformin	0-9	ATP binding cassette subfamily B member 1	Homo sapiens	264-278
25236366-11	2014	CONCLUSIONS: Altogether, these results show that metformin modifies satiation by activating brainstem circuitry and suggest that NUCB2/nesfatin-1 could be involved in this metformin effect.	Metformin	172-181	nucleobindin 2	Mus musculus	129-134
25236366-11	2014	CONCLUSIONS: Altogether, these results show that metformin modifies satiation by activating brainstem circuitry and suggest that NUCB2/nesfatin-1 could be involved in this metformin effect.	Metformin	172-181	nucleobindin 2	Mus musculus	135-145
25951664-8	2014	Metformin improved metabolic disorders, upregulated activity of renal AMPK, diminished the expression of renal SREBP-1c, TNF-alpha, NOX4 mRNA, decreased accumulation of renal lipids, and prevened renal injury.	Metformin	0-9	tumor necrosis factor	Mus musculus	121-130
25333332-11	2014	In addition, metformin plus radiation significantly upregulated the expression of p-ATM, p-ATR, gamma-H2AX and downregulated the expression of ATM, ATR, p95/NBS1, Rad50, DNA-PK, Ku70 and Ku80.	Metformin	13-22	ATR serine/threonine kinase	Homo sapiens	91-94
25333332-11	2014	In addition, metformin plus radiation significantly upregulated the expression of p-ATM, p-ATR, gamma-H2AX and downregulated the expression of ATM, ATR, p95/NBS1, Rad50, DNA-PK, Ku70 and Ku80.	Metformin	13-22	ATR serine/threonine kinase	Homo sapiens	148-151
25333332-11	2014	In addition, metformin plus radiation significantly upregulated the expression of p-ATM, p-ATR, gamma-H2AX and downregulated the expression of ATM, ATR, p95/NBS1, Rad50, DNA-PK, Ku70 and Ku80.	Metformin	13-22	protein kinase, DNA-activated, catalytic subunit	Homo sapiens	170-176
25472042-13	2014	Culturing TallyHO morulae with the AMPK activator metformin led to a reversal of all the abnormal findings, including increased AMPK phosphorylation, improved insulin-stimulated glucose uptake and normalisation of lipid accumulation.	Metformin	50-59	insulin	Homo sapiens	159-166
25472042-17	2014	Expanding on this we determine that activation of AMPK via metformin reduces lipid droplet accumulation, presumably by eliminating the inhibitory effects of TNF-alpha, resulting in normalisation of fatty acid oxidation and HADH2 (hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit) activity.	Metformin	59-68	tumor necrosis factor	Mus musculus	157-166
25199764-4	2014	Interestingly, metformin upregulated the protein level of small heterodimer partner-interacting leucine zipper (SMILE), a coregulator of nuclear receptors, and knockdown of SMILE expression with shRNA abolished the inhibitory effect of metformin on AR function.	Metformin	15-24	CREB/ATF bZIP transcription factor	Homo sapiens	58-110
25472042-17	2014	Expanding on this we determine that activation of AMPK via metformin reduces lipid droplet accumulation, presumably by eliminating the inhibitory effects of TNF-alpha, resulting in normalisation of fatty acid oxidation and HADH2 (hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit) activity.	Metformin	59-68	hydroxysteroid (17-beta) dehydrogenase 10	Mus musculus	223-228
25315294-1	2014	Oral hypoglycemic agents such as glyburide (second-generation sulfonylurea) and metformin (biguanide) are attractive alternatives to insulin due to lower cost, ease of administration, and better patient adherence.	Metformin	80-89	insulin	Homo sapiens	133-140
25199764-0	2014	SMILE upregulated by metformin inhibits the function of androgen receptor in prostate cancer cells.	Metformin	21-30	CREB/ATF bZIP transcription factor	Homo sapiens	0-5
25199764-4	2014	Interestingly, metformin upregulated the protein level of small heterodimer partner-interacting leucine zipper (SMILE), a coregulator of nuclear receptors, and knockdown of SMILE expression with shRNA abolished the inhibitory effect of metformin on AR function.	Metformin	15-24	CREB/ATF bZIP transcription factor	Homo sapiens	112-117
25199764-0	2014	SMILE upregulated by metformin inhibits the function of androgen receptor in prostate cancer cells.	Metformin	21-30	androgen receptor	Homo sapiens	56-73
25199764-2	2014	In this study, we investigated the effect and action mechanism of metformin on the function of androgen receptor (AR), a key molecule in the proliferation of prostate cancer cells.	Metformin	66-75	androgen receptor	Homo sapiens	95-112
25199764-2	2014	In this study, we investigated the effect and action mechanism of metformin on the function of androgen receptor (AR), a key molecule in the proliferation of prostate cancer cells.	Metformin	66-75	androgen receptor	Homo sapiens	114-116
25199764-3	2014	Metformin was found to reduce androgen-dependent cell growth and the expression of AR target genes by inhibiting AR function in prostate cancer cells such as LNCaP and C4-2 cells.	Metformin	0-9	androgen receptor	Homo sapiens	83-85
25199764-3	2014	Metformin was found to reduce androgen-dependent cell growth and the expression of AR target genes by inhibiting AR function in prostate cancer cells such as LNCaP and C4-2 cells.	Metformin	0-9	androgen receptor	Homo sapiens	113-115
25199764-4	2014	Interestingly, metformin upregulated the protein level of small heterodimer partner-interacting leucine zipper (SMILE), a coregulator of nuclear receptors, and knockdown of SMILE expression with shRNA abolished the inhibitory effect of metformin on AR function.	Metformin	15-24	CREB/ATF bZIP transcription factor	Homo sapiens	173-178
25199764-4	2014	Interestingly, metformin upregulated the protein level of small heterodimer partner-interacting leucine zipper (SMILE), a coregulator of nuclear receptors, and knockdown of SMILE expression with shRNA abolished the inhibitory effect of metformin on AR function.	Metformin	15-24	androgen receptor	Homo sapiens	249-251
25199764-4	2014	Interestingly, metformin upregulated the protein level of small heterodimer partner-interacting leucine zipper (SMILE), a coregulator of nuclear receptors, and knockdown of SMILE expression with shRNA abolished the inhibitory effect of metformin on AR function.	Metformin	236-245	CREB/ATF bZIP transcription factor	Homo sapiens	58-110
25199764-4	2014	Interestingly, metformin upregulated the protein level of small heterodimer partner-interacting leucine zipper (SMILE), a coregulator of nuclear receptors, and knockdown of SMILE expression with shRNA abolished the inhibitory effect of metformin on AR function.	Metformin	236-245	CREB/ATF bZIP transcription factor	Homo sapiens	112-117
25199764-4	2014	Interestingly, metformin upregulated the protein level of small heterodimer partner-interacting leucine zipper (SMILE), a coregulator of nuclear receptors, and knockdown of SMILE expression with shRNA abolished the inhibitory effect of metformin on AR function.	Metformin	236-245	CREB/ATF bZIP transcription factor	Homo sapiens	173-178
25199764-4	2014	Interestingly, metformin upregulated the protein level of small heterodimer partner-interacting leucine zipper (SMILE), a coregulator of nuclear receptors, and knockdown of SMILE expression with shRNA abolished the inhibitory effect of metformin on AR function.	Metformin	236-245	androgen receptor	Homo sapiens	249-251
25199764-8	2014	Taken together, these results suggest that SMILE, which is induced by metformin, functions as a novel AR corepressor and may mediate the inhibitory effect of metformin on androgen-dependent growth of prostate cancer cells.	Metformin	70-79	CREB/ATF bZIP transcription factor	Homo sapiens	43-48
25199764-8	2014	Taken together, these results suggest that SMILE, which is induced by metformin, functions as a novel AR corepressor and may mediate the inhibitory effect of metformin on androgen-dependent growth of prostate cancer cells.	Metformin	70-79	androgen receptor	Homo sapiens	102-104
25199764-8	2014	Taken together, these results suggest that SMILE, which is induced by metformin, functions as a novel AR corepressor and may mediate the inhibitory effect of metformin on androgen-dependent growth of prostate cancer cells.	Metformin	158-167	CREB/ATF bZIP transcription factor	Homo sapiens	43-48
25199764-8	2014	Taken together, these results suggest that SMILE, which is induced by metformin, functions as a novel AR corepressor and may mediate the inhibitory effect of metformin on androgen-dependent growth of prostate cancer cells.	Metformin	158-167	androgen receptor	Homo sapiens	102-104
25406011-1	2014	BACKGROUND: The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation (IVF) cycles has been widely studied.	Metformin	59-68	insulin	Homo sapiens	23-30
25179145-0	2014	Metformin exaggerates phenylephrine-induced AMPK phosphorylation independent of CaMKKbeta and attenuates contractile response in endothelium-denuded rat aorta.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	44-48
25361177-6	2014	Combined metformin and erlotinib led to partial regression of PTEN-null and EGFR-amplified xenografted MDA-MB-468 BBC tumors with evidence of significant apoptosis, reduction of EGFR and AKT signaling, and lack of altered plasma insulin levels.	Metformin	9-18	epidermal growth factor receptor	Homo sapiens	76-80
25179145-3	2014	To date, metformin regulation of AMPK has not been fully studied in intact arterial smooth muscle, especially during contraction evoked by G protein-coupled receptor (GPCR) agonists.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	33-37
25179145-7	2014	Importantly, in metformin-treated aortic rings, phenylephrine challenge showed an exaggerated increase in AMPK phosphorylation by ~ 9.7-fold, which was associated with an increase in AMP/ATP ratio.	Metformin	16-25	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	106-110
25179145-8	2014	Pretreatment with compound C (AMPK inhibitor) prevented AMPK phosphorylation induced by phenylephrine alone and also that induced by phenylephrine after metformin treatment.	Metformin	153-162	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	30-34
25179145-10	2014	Furthermore, attenuation of phenylephrine-induced contraction (observed after metformin treatment) was prevented by AMPK inhibition but not by CaMKKbeta inhibition.	Metformin	78-87	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	116-120
25179145-11	2014	Together, these findings suggest that, upon endothelial damage in the vessel wall, metformin uptake by the underlying vascular smooth muscle would accentuate AMPK phosphorylation by GPCR agonists independent of CaMKKbeta to promote vasorelaxation.	Metformin	83-92	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	158-162
25361177-6	2014	Combined metformin and erlotinib led to partial regression of PTEN-null and EGFR-amplified xenografted MDA-MB-468 BBC tumors with evidence of significant apoptosis, reduction of EGFR and AKT signaling, and lack of altered plasma insulin levels.	Metformin	9-18	epidermal growth factor receptor	Homo sapiens	178-182
25361177-6	2014	Combined metformin and erlotinib led to partial regression of PTEN-null and EGFR-amplified xenografted MDA-MB-468 BBC tumors with evidence of significant apoptosis, reduction of EGFR and AKT signaling, and lack of altered plasma insulin levels.	Metformin	9-18	AKT serine/threonine kinase 1	Homo sapiens	187-190
25361177-6	2014	Combined metformin and erlotinib led to partial regression of PTEN-null and EGFR-amplified xenografted MDA-MB-468 BBC tumors with evidence of significant apoptosis, reduction of EGFR and AKT signaling, and lack of altered plasma insulin levels.	Metformin	9-18	insulin	Homo sapiens	229-236
24828020-0	2014	Safety, efficacy and weight effect of two 11beta-HSD1 inhibitors in metformin-treated patients with type 2 diabetes.	Metformin	68-77	hydroxysteroid 11-beta dehydrogenase 1	Homo sapiens	42-53
25426078-5	2014	Metformin appears to reduce risk for pancreatic cancer and improve survival in diabetics with pancreatic cancer primarily by decreasing insulin/IGF signaling, disrupting mitochondrial respiration, and inhibiting the mammalian target of rapamycin (mTOR) pathway.	Metformin	0-9	insulin	Homo sapiens	136-143
25426078-5	2014	Metformin appears to reduce risk for pancreatic cancer and improve survival in diabetics with pancreatic cancer primarily by decreasing insulin/IGF signaling, disrupting mitochondrial respiration, and inhibiting the mammalian target of rapamycin (mTOR) pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	216-245
25426078-5	2014	Metformin appears to reduce risk for pancreatic cancer and improve survival in diabetics with pancreatic cancer primarily by decreasing insulin/IGF signaling, disrupting mitochondrial respiration, and inhibiting the mammalian target of rapamycin (mTOR) pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	247-251
24840107-7	2014	In contrast, there were lower PON1 (not statistically significant) and ARE (statistically significant) levels in untreated PCOS patients than the control group and they significantly increased after metformin and Diane-35 treatments.	Metformin	199-208	paraoxonase 1	Homo sapiens	30-34
24840107-10	2014	The treatment of PCOS with metformin or Diane-35 had positive effects on lipid profile, increased PON1 level, which is a protector from atherosclerosis and decreased the proatherogenic PAF-AH and ox-LDL levels.	Metformin	27-36	paraoxonase 1	Homo sapiens	98-102
25253174-2	2014	In a recent presurgical trial, we found a heterogeneous effect of metformin on breast cancer proliferation (ki-67) depending upon insulin resistance (HOMA index).	Metformin	66-75	insulin	Homo sapiens	130-137
25253174-3	2014	Here, we determined the associations of additional serum biomarkers of insulin resistance, tumor subtype, and drug concentration with ki-67 response to metformin.	Metformin	152-161	insulin	Homo sapiens	71-78
25253174-5	2014	The ki-67 response to metformin was assessed comparing data obtained from baseline biopsy (ki-67 and tumor subtype) and serum markers (HOMA index, C-peptide, IGF-I, IGFBP-1, IGFBP-3, free IGF-I, hs-CRP, adiponectin) with the same measurements at definitive surgery.	Metformin	22-31	insulin	Homo sapiens	147-156
25253174-5	2014	The ki-67 response to metformin was assessed comparing data obtained from baseline biopsy (ki-67 and tumor subtype) and serum markers (HOMA index, C-peptide, IGF-I, IGFBP-1, IGFBP-3, free IGF-I, hs-CRP, adiponectin) with the same measurements at definitive surgery.	Metformin	22-31	insulin like growth factor 1	Homo sapiens	158-163
25253174-5	2014	The ki-67 response to metformin was assessed comparing data obtained from baseline biopsy (ki-67 and tumor subtype) and serum markers (HOMA index, C-peptide, IGF-I, IGFBP-1, IGFBP-3, free IGF-I, hs-CRP, adiponectin) with the same measurements at definitive surgery.	Metformin	22-31	insulin like growth factor 1	Homo sapiens	188-193
25253174-5	2014	The ki-67 response to metformin was assessed comparing data obtained from baseline biopsy (ki-67 and tumor subtype) and serum markers (HOMA index, C-peptide, IGF-I, IGFBP-1, IGFBP-3, free IGF-I, hs-CRP, adiponectin) with the same measurements at definitive surgery.	Metformin	22-31	adiponectin, C1Q and collagen domain containing	Homo sapiens	203-214
25253174-7	2014	Compared with placebo, metformin significantly decreased ki-67 in women with HOMA &gt; 2.8, those in the lowest IGFBP-1 quintile, those in the highest IGFBP-3 quartile, those with low free IGF-I, those in the top hs-CRP tertile, and those with HER2-positive tumors.	Metformin	23-32	insulin like growth factor 1	Homo sapiens	189-194
24828020-1	2014	AIMS: We assessed safety and efficacy of two selective 11beta-HSD1 inhibitors (RO5093151/RO-151 and RO5027383/RO-838) in this randomized, controlled study in metformin-treated patients with type 2 diabetes.	Metformin	158-167	hydroxysteroid 11-beta dehydrogenase 1	Homo sapiens	55-66
25263501-1	2014	AIMS: We aimed to investigate the pharmacological efficiency of metformin on asymmetric dimethylarginine (ADMA) metabolism in inflammation caused by the lipopolysaccharide (LPS)/D-galactosamine (D-GalN) treatment.	Metformin	64-73	galanin and GMAP prepropeptide	Rattus norvegicus	197-201
25263501-9	2014	Metformin pretreatment alleviated the activity of serum enzymes, and attenuated histopathological lesions caused by LPS/D-GalN injections.	Metformin	0-9	galanin and GMAP prepropeptide	Rattus norvegicus	122-126
25263501-12	2014	CONCLUSION: Our findings showed that metformin administration for one week has a potency to protect liver through regulating ADMA metabolism in LPS/D-GalN-induced injury.	Metformin	37-46	galanin and GMAP prepropeptide	Rattus norvegicus	150-154
24936555-12	2014	CONCLUSIONS: U-500 regular insulin + metformin is effective for the treatment of T2DM patients with severe insulin resistance.	Metformin	37-46	insulin	Homo sapiens	107-114
25106415-6	2014	In contrast, uptake of the positive controls, atorvastatin for OATPs and metformin for OCT1, was significantly enhanced by relevant transporter expression, and uptake into both these HEK293 cells and human hepatocytes was significantly impaired by prototypical inhibitors.	Metformin	73-82	solute carrier family 22 member 1	Homo sapiens	87-91
25219351-13	2014	CONCLUSIONS: A modest increase in metformin exposure and decrease in topiramate exposure was observed at steady state following coadministration of metformin 500 mg BID and topiramate 100mg BID.	Metformin	34-43	BH3 interacting domain death agonist	Homo sapiens	165-168
25219351-13	2014	CONCLUSIONS: A modest increase in metformin exposure and decrease in topiramate exposure was observed at steady state following coadministration of metformin 500 mg BID and topiramate 100mg BID.	Metformin	34-43	BH3 interacting domain death agonist	Homo sapiens	190-193
25219351-13	2014	CONCLUSIONS: A modest increase in metformin exposure and decrease in topiramate exposure was observed at steady state following coadministration of metformin 500 mg BID and topiramate 100mg BID.	Metformin	148-157	BH3 interacting domain death agonist	Homo sapiens	165-168
25054311-4	2014	In both groups of patients, metformin reduced fasting plasma glucose, insulin resistance, triglycerides and glycated hemoglobin.	Metformin	28-37	insulin	Homo sapiens	70-77
25013215-7	2014	RESULTS: Metformin is used clinically off-label in the management of hirsutism, acne and insulin resistance in PCOS, although the evidence for anti-androgenic effects is inconsistent.	Metformin	9-18	insulin	Homo sapiens	89-96
25013215-12	2014	One study with a 2-year follow-up demonstrated that babies born to women treated with metformin also developed less visceral fat, making them less prone to insulin resistance in later life.	Metformin	86-95	insulin	Homo sapiens	156-163
25013215-17	2014	Pre-clinical experiments report that metformin has a growth-static effect on several cancers, including endometrial cancer, which may be partly due to the effect of metformin on the PI3K/AKT/mTOR signal transduction pathway.	Metformin	37-46	AKT serine/threonine kinase 1	Homo sapiens	187-190
25013215-17	2014	Pre-clinical experiments report that metformin has a growth-static effect on several cancers, including endometrial cancer, which may be partly due to the effect of metformin on the PI3K/AKT/mTOR signal transduction pathway.	Metformin	37-46	mechanistic target of rapamycin kinase	Homo sapiens	191-195
25013215-17	2014	Pre-clinical experiments report that metformin has a growth-static effect on several cancers, including endometrial cancer, which may be partly due to the effect of metformin on the PI3K/AKT/mTOR signal transduction pathway.	Metformin	165-174	AKT serine/threonine kinase 1	Homo sapiens	187-190
25013215-17	2014	Pre-clinical experiments report that metformin has a growth-static effect on several cancers, including endometrial cancer, which may be partly due to the effect of metformin on the PI3K/AKT/mTOR signal transduction pathway.	Metformin	165-174	mechanistic target of rapamycin kinase	Homo sapiens	191-195
25040426-9	2014	Metformin, an agent known to increase TSP-1 synthesis in other cell types, also reversed the ammonia-induced TSP-1 reduction.	Metformin	0-9	thrombospondin 1	Homo sapiens	38-43
25151573-1	2014	PURPOSE: In the EASIE (Evaluation of Insulin Glargine Versus Sitagliptin in Insulin-Naive Patients) trial, insulin glargine found a significant reduction in glycosylated hemoglobin compared with sitagliptin in patients with type 2 diabetes who are inadequately controlled with metformin.	Metformin	277-286	insulin	Homo sapiens	107-114
25151573-10	2014	IMPLICATIONS: Insulin glargine is a clinically superior and cost-effective alternative to sitagliptin in patients with type 2 diabetes who are inadequately controlled with metformin.	Metformin	172-181	insulin	Homo sapiens	14-21
25538335-10	2014	Moreover, TNF-alpha, MPO activity, TGF-beta, and nitrite content were significantly increased in diabetic rats, while treatment with coenzyme Q10 or metformin or their combination ameliorate STZ-nicotinamide induced renal damage due to improvement in renal function, oxidative stress, suppression of TNF-alpha, MPO activity, TGF-beta and nitrite content along with histopathological changes.	Metformin	149-158	tumor necrosis factor	Rattus norvegicus	10-19
25538335-10	2014	Moreover, TNF-alpha, MPO activity, TGF-beta, and nitrite content were significantly increased in diabetic rats, while treatment with coenzyme Q10 or metformin or their combination ameliorate STZ-nicotinamide induced renal damage due to improvement in renal function, oxidative stress, suppression of TNF-alpha, MPO activity, TGF-beta and nitrite content along with histopathological changes.	Metformin	149-158	tumor necrosis factor	Rattus norvegicus	300-309
25040426-9	2014	Metformin, an agent known to increase TSP-1 synthesis in other cell types, also reversed the ammonia-induced TSP-1 reduction.	Metformin	0-9	thrombospondin 1	Homo sapiens	109-114
24969550-7	2014	RESULTS: In the chronically ischemic myocardium, metformin significantly upregulates prosurvival proteins: extracellular signal-regulated kinases, nuclear factor kappaB, phosphorylated endothelial nitric oxide synthase, and P38.	Metformin	49-58	mitogen-activated protein kinase 14	Homo sapiens	224-227
24969550-12	2014	Metformin also upregulates mitogen-activated kinase proteins p38 and extracellular signal-regulated protein kinases 1 and 2, which are considered cardioprotective during ischemic preconditioning.	Metformin	0-9	mitogen-activated protein kinase 14	Homo sapiens	61-64
24969550-8	2014	Metformin also significantly inhibits or downregulates proapoptosis proteins: FOXO3 and caspase 3.	Metformin	0-9	forkhead box O3	Homo sapiens	78-83
24969550-8	2014	Metformin also significantly inhibits or downregulates proapoptosis proteins: FOXO3 and caspase 3.	Metformin	0-9	caspase 3	Homo sapiens	88-97
24969550-11	2014	CONCLUSIONS: Metformin selectively alters the apoptosis pathway by inhibiting FOXO3 and decreasing the active form of caspase 3, cleaved caspase 3.	Metformin	13-22	forkhead box O3	Homo sapiens	78-83
24969550-11	2014	CONCLUSIONS: Metformin selectively alters the apoptosis pathway by inhibiting FOXO3 and decreasing the active form of caspase 3, cleaved caspase 3.	Metformin	13-22	caspase 3	Homo sapiens	118-127
24969550-11	2014	CONCLUSIONS: Metformin selectively alters the apoptosis pathway by inhibiting FOXO3 and decreasing the active form of caspase 3, cleaved caspase 3.	Metformin	13-22	caspase 3	Homo sapiens	137-146
25108154-3	2014	Thus, in this study, we focused on the regulation of AMPK and SIRT1 activities implicated in adipocytokine expression and endothelial homeostasis under inflammatory conditions by using salicylate, metformin, AICA riboside (AICAR) and resveratrol as AMPK activating agents.	Metformin	197-206	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	53-57
25123289-8	2014	In cultured human umbilical vein endothelial cells (HUVECs), 1 muM metformin reversed AGE-induced increase of ROS and attenuated AGE- and H2O2- induced downregulation of IKCa and SKCa after long-term incubation (&gt;24 hours).	Metformin	67-76	latexin	Homo sapiens	63-66
25123289-9	2014	Short-term treatment (3 hours) with 1 muM metformin reversed the decrease of IKCa and SKCa currents induced by AGE incubation for 3 hours without changing the channel expression or the AMPK activation in HUVECs.	Metformin	42-51	latexin	Homo sapiens	38-41
25289085-0	2014	Regulation of insulin-like growth factor signaling by metformin in endometrial cancer cells.	Metformin	54-63	insulin	Homo sapiens	14-21
25954799-7	2014	In the Ukpds trial, involving about 1700 overweight diabetic patients, metformin monotherapy for about 10 years was more effective in reducing mortality than glycaemic control based mainly on dietary measures, and also more effective than treatment with a sulphonylurea such as chlorpropamide or glibenclamide, or with insulin.	Metformin	71-80	insulin	Homo sapiens	319-326
24636967-13	2014	Furthermore, metformin and rosiglitazone improved insulin resistance, while aripiprazole, metformin, and sibutramine decreased blood lipids.	Metformin	13-22	insulin	Homo sapiens	50-57
25688512-4	2014	Metformin has recently shown some anti-cancer activity in both in vitro and in vivo studies by its indirect properties to decrease insulin and insulin-like growth factor-1 (IGF-1) levels and by its antitumour effect to promote AMPK activation and consequently inhibition to TSC1-2/mTOR complex.	Metformin	0-9	insulin like growth factor 1	Homo sapiens	143-171
25688512-4	2014	Metformin has recently shown some anti-cancer activity in both in vitro and in vivo studies by its indirect properties to decrease insulin and insulin-like growth factor-1 (IGF-1) levels and by its antitumour effect to promote AMPK activation and consequently inhibition to TSC1-2/mTOR complex.	Metformin	0-9	insulin like growth factor 1	Homo sapiens	173-178
25688512-4	2014	Metformin has recently shown some anti-cancer activity in both in vitro and in vivo studies by its indirect properties to decrease insulin and insulin-like growth factor-1 (IGF-1) levels and by its antitumour effect to promote AMPK activation and consequently inhibition to TSC1-2/mTOR complex.	Metformin	0-9	TSC complex subunit 1	Homo sapiens	274-280
25688512-4	2014	Metformin has recently shown some anti-cancer activity in both in vitro and in vivo studies by its indirect properties to decrease insulin and insulin-like growth factor-1 (IGF-1) levels and by its antitumour effect to promote AMPK activation and consequently inhibition to TSC1-2/mTOR complex.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	281-285
27200644-0	2014	Economic Assessment of Delaying Insulin Treatment Through The Use of Newer Anti-Diabetic Agents, Dapagliflozin (Forxiga ) And Exenatide (Bydureon ), Both As Add-On To Metformin; A Cost-Effectiveness Analysis From A Uk Nhs Perspective.	Metformin	167-176	insulin	Homo sapiens	32-39
25349635-9	2014	Compared with treatment with only diet or metformin, the hazard ratio [HR] for non-response was 5.3 (95% confidence interval [CI]: 1.16-24.6, P = 0.03) for insulin therapy and 5.0 (95% CI: 1.13-22.16, P = 0.03) for sulfonylurea therapy.	Metformin	42-51	insulin	Homo sapiens	156-163
25331307-0	2014	The prevalence of low vitamin B12 status in people with type 2 diabetes receiving metformin therapy in New Zealand--a clinical audit.	Metformin	82-91	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	30-33
25331307-1	2014	AIM: Metformin, the most common hypoglycaemic agent used in type 2 diabetes, is associated with reduced serum vitamin B12 concentrations.	Metformin	5-14	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	118-121
25331307-2	2014	This cross sectional observational study determines the prevalence of low vitamin B12 status in people with type 2 diabetes on metformin therapy in both primary and secondary care in New Zealand.	Metformin	127-136	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	82-85
25331307-8	2014	CONCLUSION: Low serum B12 concentration is a common occurrence in people with type 2 Diabetes treated with Metformin.	Metformin	107-116	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	22-25
25315906-11	2014	In addition, metformin activated AMPK phosphorylation, inhibited NF-kappaB activation, down-regulated cytokine (IL-1beta, IL-6, TNF-alpha) and ICAM-1 expression following tMCAO (P &lt; 0.05).	Metformin	13-22	interleukin 1 beta	Mus musculus	112-120
25315906-11	2014	In addition, metformin activated AMPK phosphorylation, inhibited NF-kappaB activation, down-regulated cytokine (IL-1beta, IL-6, TNF-alpha) and ICAM-1 expression following tMCAO (P &lt; 0.05).	Metformin	13-22	interleukin 6	Mus musculus	122-126
25315906-11	2014	In addition, metformin activated AMPK phosphorylation, inhibited NF-kappaB activation, down-regulated cytokine (IL-1beta, IL-6, TNF-alpha) and ICAM-1 expression following tMCAO (P &lt; 0.05).	Metformin	13-22	tumor necrosis factor	Mus musculus	128-137
25550773-10	2014	Interestingly, the AMPK activator metformin mimicked the effects of HPC in part.	Metformin	34-43	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	19-23
25299054-0	2014	Higher prevalence of metformin-induced vitamin B12 deficiency in sulfonylurea combination compared with insulin combination in patients with type 2 diabetes: a cross-sectional study.	Metformin	21-30	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	47-50
25419360-6	2014	As a result, protein abundance of Bcl-2 and cyclin D1 was decreased and PTEN was increased in cells exposed to metformin.	Metformin	111-120	BCL2 apoptosis regulator	Homo sapiens	34-39
25299054-1	2014	Long-term and high-dose treatment with metformin is known to be associated with vitamin B12 deficiency in patients with type 2 diabetes.	Metformin	39-48	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	88-91
25299054-2	2014	We investigated whether the prevalence of B12 deficiency was different in patients treated with different combination of hypoglycemic agents with metformin during the same time period.	Metformin	146-155	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	42-45
25299054-9	2014	The prevalence of vitamin B12 deficiency in the metformin-treated patients was significantly higher in the S+M group compared with the I+M group (17.4% vs. 4.2%, P = 0.001).	Metformin	48-57	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	26-29
25303400-9	2014	The protective effect of metformin on thyroid cancer incidence was also supported by sensitivity analyses, disregarding age (&lt; 50 or &gt;= 50 years) and sex; and was not affected by excluding users of insulin, sulfonylurea, and insulin and/or sulfonylurea respectively, by previous diagnosis of other cancers or by potential detection examinations that might lead to differential diagnosis of thyroid cancer.	Metformin	25-34	insulin	Homo sapiens	231-238
25299054-11	2014	In conclusion, our study demonstrated that patients with type 2 diabetes who were treated with metformin combined with sulfonylurea require clinical attention for vitamin B12 deficiency and regular monitoring of their vitamin B12 levels.	Metformin	95-104	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	171-174
25299054-11	2014	In conclusion, our study demonstrated that patients with type 2 diabetes who were treated with metformin combined with sulfonylurea require clinical attention for vitamin B12 deficiency and regular monitoring of their vitamin B12 levels.	Metformin	95-104	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	226-229
24682492-1	2014	Combining metformin and exercise is recommended for the treatment of insulin resistance.	Metformin	10-19	insulin	Homo sapiens	69-76
25143389-0	2014	Mechanism of metformin-dependent inhibition of mammalian target of rapamycin (mTOR) and Ras activity in pancreatic cancer: role of specificity protein (Sp) transcription factors.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	47-76
25143389-0	2014	Mechanism of metformin-dependent inhibition of mammalian target of rapamycin (mTOR) and Ras activity in pancreatic cancer: role of specificity protein (Sp) transcription factors.	Metformin	13-22	mechanistic target of rapamycin kinase	Homo sapiens	78-82
25143389-2	2014	A recent study showed that metformin down-regulated specificity protein (Sp) transcription factors (TFs) Sp1, Sp3, and Sp4 in pancreatic cancer cells and tumors, and this was accompanied by down-regulation of several pro-oncogenic Sp-regulated genes.	Metformin	27-36	Sp3 transcription factor	Homo sapiens	110-113
25143389-3	2014	Treatment with metformin or down-regulation of Sp TFs by RNAi also inhibits two major pro-oncogenic pathways in pancreatic cancer cells, namely mammalian target of rapamycin (mTOR) signaling and epidermal growth factor (EGFR)-dependent activation of Ras.	Metformin	15-24	mechanistic target of rapamycin kinase	Homo sapiens	144-173
25143389-3	2014	Treatment with metformin or down-regulation of Sp TFs by RNAi also inhibits two major pro-oncogenic pathways in pancreatic cancer cells, namely mammalian target of rapamycin (mTOR) signaling and epidermal growth factor (EGFR)-dependent activation of Ras.	Metformin	15-24	mechanistic target of rapamycin kinase	Homo sapiens	175-179
25143389-4	2014	Metformin and Sp knockdown by RNAi decreased expression of the insulin-like growth factor-1 receptor (IGF-1R), resulting in inhibition of mTOR signaling.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	138-142
25143389-6	2014	Thus, the antineoplastic activities of metformin in pancreatic cancer are due, in part, to down-regulation of Sp TFs and Sp-regulated IGF-1R and EGFR, which in turn results in inhibition of mTOR and Ras signaling, respectively.	Metformin	39-48	mechanistic target of rapamycin kinase	Homo sapiens	190-194
24682492-2	2014	However, it has been suggested that metformin blunts the insulin-sensitizing effects of exercise.	Metformin	36-45	insulin	Homo sapiens	57-64
24682492-3	2014	We evaluated in a group of insulin-resistant patients the interactions between exercise and their daily dose of metformin.	Metformin	112-121	insulin	Homo sapiens	27-34
24917306-10	2014	Preoperative metformin use caused significant decreases in circulating factors, including insulin, glucose, insulin-like growth factor 1, and leptin.	Metformin	13-22	insulin	Homo sapiens	90-97
24917306-10	2014	Preoperative metformin use caused significant decreases in circulating factors, including insulin, glucose, insulin-like growth factor 1, and leptin.	Metformin	13-22	insulin	Homo sapiens	108-115
24947355-5	2014	Disruption of MAM integrity by genetic or pharmacological inhibition of the mitochondrial MAM protein, cyclophilin D (CypD), altered insulin signaling in mouse and human primary hepatocytes and treatment of CypD knockout mice with metformin improved both insulin sensitivity and MAM integrity.	Metformin	231-240	activating transcription factor 7 interacting protein	Mus musculus	14-17
24827939-1	2014	AIM: Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists are widely used in combinations with metformin in the treatment of type 2 diabetes; however, data on long-term safety compared with conventional combination therapies are limited.	Metformin	129-138	glucagon	Homo sapiens	76-81
25555182-7	2014	CRP was decreased with metformin (P&lt;0.001), but was increased with OCPs (P&lt;0.001).	Metformin	23-32	C-reactive protein	Homo sapiens	0-3
24827939-1	2014	AIM: Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists are widely used in combinations with metformin in the treatment of type 2 diabetes; however, data on long-term safety compared with conventional combination therapies are limited.	Metformin	129-138	glucagon	Homo sapiens	51-74
24793923-9	2014	Ten out of 32 metformin patients required additional insulin.	Metformin	14-23	insulin	Homo sapiens	53-60
25402373-11	2014	Inhibition of cell proliferation by metformin was associated with apoptosis induction only in midgut GOT1, evidenced by increased subG0/1 fraction and PARP cleavage.	Metformin	36-45	poly(ADP-ribose) polymerase 1	Homo sapiens	151-155
25555182-9	2014	OCPs and metformin appear to have differential effects on atherogenic molecules in lean PCOS patients, but metformin was superior in reducing serum AGEs and CRP.	Metformin	107-116	C-reactive protein	Homo sapiens	157-160
25473629-10	2014	In addition, the fasting insulin was significantly greater in metformin group and flutamide group in comparison to metformin+flutamide and placebo groups after treatment (p&lt;0.05).	Metformin	62-71	insulin	Homo sapiens	25-32
25473629-11	2014	Within groups, insulin level showed significant changes (before and after treatment) in metformin+flutamide group and LDL reduction was significant in flutamide group before and after treatment.	Metformin	88-97	insulin	Homo sapiens	15-22
25122066-6	2014	Combination of simvastatin and metformin decreased Akt Ser-473 and Thr-308 phosphorylation and AMPKalpha Ser-485/491 phosphorylation; increased Thr-172 phosphorylation and AMPKalpha activity, as assessed by increased Ser-79 and Ser-872 phosphorylation of acetyl-CoA carboxylase and HMG-CoAR, respectively; decreased HMG-CoAR activity; and reduced total cellular cholesterol and its synthesis in both cell lines.	Metformin	31-40	AKT serine/threonine kinase 1	Homo sapiens	51-54
25175747-5	2014	Specific uptake of cimetidine, acyclovir, metformin, and terbutaline was observed in human embryonic kidney 293 cells transfected with murine Oct1 or Oct2.	Metformin	42-51	POU domain, class 2, transcription factor 2	Mus musculus	150-154
24844968-2	2014	Insulin, metformin and thiazolidinediones (TDZs) are among the major diabetes therapies that improve glycaemic control by acting via molecular targets including the insulin receptor and insulin-like growth factor pathways, adenosine monophosphate-activated kinase and peroxisome proliferator-activated receptor gamma.	Metformin	9-18	insulin	Homo sapiens	165-172
25580176-12	2014	Women taking metformin may require supplemental insulin more frequently than those taking glyburide.	Metformin	13-22	insulin	Homo sapiens	48-55
25580176-13	2014	CONCLUSION: Glyburide and metformin appear to be safe and effective to manage blood glucose in patients with gestational diabetes who prefer to not utilize insulin or who cannot afford insulin therapy.	Metformin	26-35	insulin	Homo sapiens	185-192
24844968-2	2014	Insulin, metformin and thiazolidinediones (TDZs) are among the major diabetes therapies that improve glycaemic control by acting via molecular targets including the insulin receptor and insulin-like growth factor pathways, adenosine monophosphate-activated kinase and peroxisome proliferator-activated receptor gamma.	Metformin	9-18	insulin	Homo sapiens	186-193
25518129-1	2014	Type 2 diabetes is characterised by insulin resistance and deficiencywhich explains the multitude of molecules developed for its treatment.The beneficial effects of metformin and sulfamides have been demonstrated.	Metformin	165-174	insulin	Homo sapiens	36-43
25283155-1	2014	BACKGROUND: Metformin, a standard therapy in type 2 diabetes, reduces vitamin B12 levels.	Metformin	12-21	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	78-81
25110054-8	2014	Finally, metformin inhibits TDO expression through a down-regulation of Sp1 and glucocorticoid receptor (GR) protein levels.	Metformin	9-18	nuclear receptor subfamily 3 group C member 1	Homo sapiens	80-103
25110054-8	2014	Finally, metformin inhibits TDO expression through a down-regulation of Sp1 and glucocorticoid receptor (GR) protein levels.	Metformin	9-18	nuclear receptor subfamily 3 group C member 1	Homo sapiens	105-107
25201727-7	2014	Metformin could inhibit TGF-beta-induced EMT in Vcap cells, as manifested by inhibition of the increase of N-cadherin (p=0.013), Vimentin (p=0.002) and the decrease of E-cadherin (p=0.0023) and beta-catenin (p=0.034) at mRNA and protein levels.	Metformin	0-9	cadherin 1	Homo sapiens	168-178
25283155-7	2014	RESULTS: The prevalence rates of vitamin B12 deficiency (&lt;191 ng/L) were 27% and 12% in Europeans and Indians, respectively and higher in metformin treated type 2 diabetes patients.	Metformin	141-150	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	41-44
25283155-11	2014	Type 2 diabetes management guidelines should include the recommendation for regular testing for B12 levels, especially for those on metformin.	Metformin	132-141	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	96-99
25254953-11	2014	Additionally, under low glucose conditions metformin significantly decreased phosphorylation of AKT and various targets of mTOR, while phospho-AMPK was not significantly altered.	Metformin	43-52	AKT serine/threonine kinase 1	Homo sapiens	96-99
25254953-11	2014	Additionally, under low glucose conditions metformin significantly decreased phosphorylation of AKT and various targets of mTOR, while phospho-AMPK was not significantly altered.	Metformin	43-52	mechanistic target of rapamycin kinase	Homo sapiens	123-127
25295009-7	2014	This article highlights the central role of the mechanistic target of rapamycin (mTOR) in mediating crosstalk between insulin/IGF-1 and GPCR signaling in pancreatic cancer cells and proposes strategies, including the use of metformin, to target this signaling system in PDAC cells.	Metformin	224-233	mechanistic target of rapamycin kinase	Homo sapiens	48-79
25295009-7	2014	This article highlights the central role of the mechanistic target of rapamycin (mTOR) in mediating crosstalk between insulin/IGF-1 and GPCR signaling in pancreatic cancer cells and proposes strategies, including the use of metformin, to target this signaling system in PDAC cells.	Metformin	224-233	mechanistic target of rapamycin kinase	Homo sapiens	81-85
24714080-0	2014	Metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through mTOR/S6K1-mediated downregulation of c-FLIP.	Metformin	0-9	TNF superfamily member 10	Homo sapiens	51-56
24714080-0	2014	Metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through mTOR/S6K1-mediated downregulation of c-FLIP.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	83-87
24714080-0	2014	Metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through mTOR/S6K1-mediated downregulation of c-FLIP.	Metformin	0-9	CASP8 and FADD like apoptosis regulator	Homo sapiens	120-126
24714080-2	2014	In this study, we investigated the effects and molecular mechanisms of metformin in sensitizing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human bladder cancer cells.	Metformin	71-80	TNF superfamily member 10	Homo sapiens	96-151
24714080-2	2014	In this study, we investigated the effects and molecular mechanisms of metformin in sensitizing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human bladder cancer cells.	Metformin	71-80	TNF superfamily member 10	Homo sapiens	153-158
24714080-3	2014	Metformin alone did not induce apoptosis, but markedly potentiated TRAIL-induced apoptosis in 253J and RT4 bladder cancer cells.	Metformin	0-9	TNF superfamily member 10	Homo sapiens	67-72
24714080-6	2014	However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway.	Metformin	9-18	mechanistic target of rapamycin kinase	Homo sapiens	33-37
24714080-6	2014	However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway.	Metformin	9-18	CASP8 and FADD like apoptosis regulator	Homo sapiens	181-188
24714080-6	2014	However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway.	Metformin	9-18	CASP8 and FADD like apoptosis regulator	Homo sapiens	181-187
24714080-6	2014	However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway.	Metformin	9-18	mechanistic target of rapamycin kinase	Homo sapiens	263-267
24714080-6	2014	However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway.	Metformin	206-215	mechanistic target of rapamycin kinase	Homo sapiens	33-37
24714080-6	2014	However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway.	Metformin	206-215	CASP8 and FADD like apoptosis regulator	Homo sapiens	181-188
24853734-5	2014	Five variants in specificity protein 1 (SP1), a transcription factor that modulates the expression of metformin transporters, were associated with changes in treatment HbA1c (P &lt; 0.01) and metformin secretory clearance (P &lt; 0.05).	Metformin	102-111	Sp1 transcription factor	Homo sapiens	17-38
24714080-8	2014	Taken together, our results indicate that metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through downregulation of c-FLIP, which is mediated by the mTOR/S6K1 pathway, but independent of AMPK; furthermore, these findings provide a rationale for the combined application of metformin with TRAIL in the treatment of bladder cancer.	Metformin	42-51	TNF superfamily member 10	Homo sapiens	93-98
24714080-8	2014	Taken together, our results indicate that metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through downregulation of c-FLIP, which is mediated by the mTOR/S6K1 pathway, but independent of AMPK; furthermore, these findings provide a rationale for the combined application of metformin with TRAIL in the treatment of bladder cancer.	Metformin	42-51	CASP8 and FADD like apoptosis regulator	Homo sapiens	143-149
24714080-8	2014	Taken together, our results indicate that metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through downregulation of c-FLIP, which is mediated by the mTOR/S6K1 pathway, but independent of AMPK; furthermore, these findings provide a rationale for the combined application of metformin with TRAIL in the treatment of bladder cancer.	Metformin	42-51	mechanistic target of rapamycin kinase	Homo sapiens	176-180
24714080-8	2014	Taken together, our results indicate that metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through downregulation of c-FLIP, which is mediated by the mTOR/S6K1 pathway, but independent of AMPK; furthermore, these findings provide a rationale for the combined application of metformin with TRAIL in the treatment of bladder cancer.	Metformin	42-51	TNF superfamily member 10	Homo sapiens	315-320
24714080-8	2014	Taken together, our results indicate that metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through downregulation of c-FLIP, which is mediated by the mTOR/S6K1 pathway, but independent of AMPK; furthermore, these findings provide a rationale for the combined application of metformin with TRAIL in the treatment of bladder cancer.	Metformin	300-309	TNF superfamily member 10	Homo sapiens	93-98
24714080-8	2014	Taken together, our results indicate that metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through downregulation of c-FLIP, which is mediated by the mTOR/S6K1 pathway, but independent of AMPK; furthermore, these findings provide a rationale for the combined application of metformin with TRAIL in the treatment of bladder cancer.	Metformin	300-309	CASP8 and FADD like apoptosis regulator	Homo sapiens	143-149
25147257-6	2014	Those about which we know the most-metformin, SUs, insulin, and perhaps now also TZDs-are efficacious in most patients and can be placed into a basic initial algorithm.	Metformin	35-44	insulin	Homo sapiens	51-58
25309796-12	2014	Metformin-mediated Glut4 translocation was also increased by Vav3 knock-down, suggesting that Vav3 is involved in metformin-mediated glucose uptake.	Metformin	0-9	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	19-24
24686086-0	2014	AMPKalpha2 translocates into the nucleus and interacts with hnRNP H: implications in metformin-mediated glucose uptake.	Metformin	85-94	heterogeneous nuclear ribonucleoprotein H1	Rattus norvegicus	60-67
24686086-11	2014	Metformin increased the interaction between AMPKalpha2 and hnRNP H in the nucleus.	Metformin	0-9	heterogeneous nuclear ribonucleoprotein H1	Rattus norvegicus	59-66
24686086-12	2014	Knockdown of hnRNP H blocked metformin-induced glucose uptake.	Metformin	29-38	heterogeneous nuclear ribonucleoprotein H1	Rattus norvegicus	13-20
24686086-13	2014	In summary, these results demonstrate that AMPKalpha2 translocates into the nucleus via phosphorylation, AMPKalpha2 interacts with and phosphorylates hnRNP H in the nucleus, and such a protein-protein interaction modulates metformin-mediated glucose uptake.	Metformin	223-232	heterogeneous nuclear ribonucleoprotein H1	Rattus norvegicus	150-157
25309796-12	2014	Metformin-mediated Glut4 translocation was also increased by Vav3 knock-down, suggesting that Vav3 is involved in metformin-mediated glucose uptake.	Metformin	114-123	solute carrier family 2 (facilitated glucose transporter), member 4	Mus musculus	19-24
24970682-8	2014	Genetic tools demonstrated that the reduction of Sirt1 and Pgc-1alpha by metformin caused Nrf2 downregulation via suppression of PPARgamma transcriptional activity.	Metformin	73-82	peroxisome proliferator activated receptor gamma	Homo sapiens	129-138
24970682-0	2014	Metformin induces microRNA-34a to downregulate the Sirt1/Pgc-1alpha/Nrf2 pathway, leading to increased susceptibility of wild-type p53 cancer cells to oxidative stress and therapeutic agents.	Metformin	0-9	PPARG coactivator 1 alpha	Homo sapiens	57-67
24970682-0	2014	Metformin induces microRNA-34a to downregulate the Sirt1/Pgc-1alpha/Nrf2 pathway, leading to increased susceptibility of wild-type p53 cancer cells to oxidative stress and therapeutic agents.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	68-72
24970682-0	2014	Metformin induces microRNA-34a to downregulate the Sirt1/Pgc-1alpha/Nrf2 pathway, leading to increased susceptibility of wild-type p53 cancer cells to oxidative stress and therapeutic agents.	Metformin	0-9	tumor protein p53	Homo sapiens	131-134
24970682-4	2014	Using human cancer cell lines that exhibit differential expression of p53, we found that metformin reduced Sirt1 protein levels in cancer cells bearing wild-type p53, but did not affect Sirt1 protein levels in cancer cell lines harboring mutant forms of p53.	Metformin	89-98	tumor protein p53	Homo sapiens	70-73
24970682-4	2014	Using human cancer cell lines that exhibit differential expression of p53, we found that metformin reduced Sirt1 protein levels in cancer cells bearing wild-type p53, but did not affect Sirt1 protein levels in cancer cell lines harboring mutant forms of p53.	Metformin	89-98	tumor protein p53	Homo sapiens	162-165
24970682-4	2014	Using human cancer cell lines that exhibit differential expression of p53, we found that metformin reduced Sirt1 protein levels in cancer cells bearing wild-type p53, but did not affect Sirt1 protein levels in cancer cell lines harboring mutant forms of p53.	Metformin	89-98	tumor protein p53	Homo sapiens	162-165
24970682-5	2014	Metformin-induced p53 protein levels in wild-type p53 cancer cells resulted in upregulation of microRNA (miR)-34a.	Metformin	0-9	tumor protein p53	Homo sapiens	18-21
24970682-5	2014	Metformin-induced p53 protein levels in wild-type p53 cancer cells resulted in upregulation of microRNA (miR)-34a.	Metformin	0-9	tumor protein p53	Homo sapiens	50-53
24970682-7	2014	Metformin suppressed peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1alpha (Pgc-1alpha) expression and its downstream target Nrf2 in MCF-7 cells.	Metformin	0-9	PPARG coactivator 1 alpha	Homo sapiens	21-100
24970682-7	2014	Metformin suppressed peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1alpha (Pgc-1alpha) expression and its downstream target Nrf2 in MCF-7 cells.	Metformin	0-9	PPARG coactivator 1 alpha	Homo sapiens	102-112
24970682-7	2014	Metformin suppressed peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1alpha (Pgc-1alpha) expression and its downstream target Nrf2 in MCF-7 cells.	Metformin	0-9	NFE2 like bZIP transcription factor 2	Homo sapiens	151-155
24970682-8	2014	Genetic tools demonstrated that the reduction of Sirt1 and Pgc-1alpha by metformin caused Nrf2 downregulation via suppression of PPARgamma transcriptional activity.	Metformin	73-82	PPARG coactivator 1 alpha	Homo sapiens	59-69
24970682-8	2014	Genetic tools demonstrated that the reduction of Sirt1 and Pgc-1alpha by metformin caused Nrf2 downregulation via suppression of PPARgamma transcriptional activity.	Metformin	73-82	NFE2 like bZIP transcription factor 2	Homo sapiens	90-94
24972190-10	2014	Mean plasma insulin (p=0.0005), IGF-1 (p=0.001), and IGFBP-7 (p=0.0098) were significantly reduced after metformin treatment.	Metformin	105-114	insulin	Homo sapiens	12-19
24972190-10	2014	Mean plasma insulin (p=0.0005), IGF-1 (p=0.001), and IGFBP-7 (p=0.0098) were significantly reduced after metformin treatment.	Metformin	105-114	insulin like growth factor 1	Homo sapiens	32-37
24972190-10	2014	Mean plasma insulin (p=0.0005), IGF-1 (p=0.001), and IGFBP-7 (p=0.0098) were significantly reduced after metformin treatment.	Metformin	105-114	insulin like growth factor binding protein 7	Homo sapiens	53-60
24876433-4	2014	Insulin treatment was started in 394 (4.3%) metformin and in 162 (14.5%) sulfonylurea users within 6 years (P &lt; .001).	Metformin	44-53	insulin	Homo sapiens	0-7
24876433-6	2014	A substantial eGFR decline (category: 15-&lt;30 ml/min/1.73 m(2)) was significantly associated with a higher likelihood to have insulin initiated (adjusted hazard ratio [HR]: 2.39; 95% CI: 1.09-5.23) in metformin but not in sulfonylurea (HR: 0.45; 95% CI: 0.16-1.30) users.	Metformin	203-212	epidermal growth factor receptor	Homo sapiens	14-18
24876433-6	2014	A substantial eGFR decline (category: 15-&lt;30 ml/min/1.73 m(2)) was significantly associated with a higher likelihood to have insulin initiated (adjusted hazard ratio [HR]: 2.39; 95% CI: 1.09-5.23) in metformin but not in sulfonylurea (HR: 0.45; 95% CI: 0.16-1.30) users.	Metformin	203-212	insulin	Homo sapiens	128-135
24970682-11	2014	Furthermore, upregulation of death receptor 5 by metformin-mediated Sirt1 downregulation enhanced the sensitivity of wild-type p53 cancer cells to TRAIL-induced apoptosis.	Metformin	49-58	tumor protein p53	Homo sapiens	127-130
24970682-11	2014	Furthermore, upregulation of death receptor 5 by metformin-mediated Sirt1 downregulation enhanced the sensitivity of wild-type p53 cancer cells to TRAIL-induced apoptosis.	Metformin	49-58	TNF superfamily member 10	Homo sapiens	147-152
24970682-12	2014	Our results demonstrated that metformin induces miR-34a to suppress the Sirt1/Pgc-1alpha/Nrf2 pathway and increases susceptibility of wild-type p53 cancer cells to oxidative stress and TRAIL-induced apoptosis.	Metformin	30-39	PPARG coactivator 1 alpha	Homo sapiens	78-88
24970682-12	2014	Our results demonstrated that metformin induces miR-34a to suppress the Sirt1/Pgc-1alpha/Nrf2 pathway and increases susceptibility of wild-type p53 cancer cells to oxidative stress and TRAIL-induced apoptosis.	Metformin	30-39	NFE2 like bZIP transcription factor 2	Homo sapiens	89-93
24970682-12	2014	Our results demonstrated that metformin induces miR-34a to suppress the Sirt1/Pgc-1alpha/Nrf2 pathway and increases susceptibility of wild-type p53 cancer cells to oxidative stress and TRAIL-induced apoptosis.	Metformin	30-39	tumor protein p53	Homo sapiens	144-147
24970682-12	2014	Our results demonstrated that metformin induces miR-34a to suppress the Sirt1/Pgc-1alpha/Nrf2 pathway and increases susceptibility of wild-type p53 cancer cells to oxidative stress and TRAIL-induced apoptosis.	Metformin	30-39	TNF superfamily member 10	Homo sapiens	185-190
25166296-3	2014	Eventually this progression leads to the use of basal insulin typically with concomitant treatments (e.g., metformin, a GLP-1 RA [glucagon-like peptide-1 receptor agonist], a TZD [thiazolidinedione] or a DPP-4i [dipeptidyl peptidase 4 inhibitor]) and, ultimately, to basal-bolus insulin in some forms.	Metformin	107-116	insulin	Homo sapiens	54-61
25411624-11	2014	Multivariate regression analysis showed that C-peptide values were a significant independent predictor for a reduction in HbA1c levels (beta = 0.865, P = 0.018) with exenatide BID in combination with both sulphonylurea and metformin in obese Korean participants with type 2 diabetes and insulin naivete.	Metformin	223-232	BH3 interacting domain death agonist	Homo sapiens	176-179
25120704-0	2014	Metformin inhibits the proliferation of A549/CDDP cells by activating p38 mitogen-activated protein kinase.	Metformin	0-9	mitogen-activated protein kinase 14	Homo sapiens	70-106
25148570-0	2014	MARCH2: comparative assessment of therapeutic effects of acarbose and metformin in newly diagnosed type 2 diabetes patients.	Metformin	70-79	membrane associated ring-CH-type finger 2	Homo sapiens	0-6
24842192-0	2014	Chronic treatment with metformin suppresses toll-like receptor 4 signaling and attenuates left ventricular dysfunction following myocardial infarction.	Metformin	23-32	toll-like receptor 4	Rattus norvegicus	44-64
24842192-11	2014	Chronic pre-treatment with metformin reduces post-myocardial infarction cardiac dysfunction and suppresses inflammatory responses, possibly through inhibition of TLR4 activities.	Metformin	27-36	toll-like receptor 4	Rattus norvegicus	162-166
24973221-3	2014	Metformin inhibited LPS-induced production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in a concentration-dependent manner and in parallel induction of activating transcription factor-3 (ATF-3), a transcription factor and member of the cAMP-responsive element-binding protein family.	Metformin	0-9	tumor necrosis factor	Mus musculus	46-73
24973221-3	2014	Metformin inhibited LPS-induced production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in a concentration-dependent manner and in parallel induction of activating transcription factor-3 (ATF-3), a transcription factor and member of the cAMP-responsive element-binding protein family.	Metformin	0-9	tumor necrosis factor	Mus musculus	75-84
24973221-3	2014	Metformin inhibited LPS-induced production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in a concentration-dependent manner and in parallel induction of activating transcription factor-3 (ATF-3), a transcription factor and member of the cAMP-responsive element-binding protein family.	Metformin	0-9	interleukin 6	Mus musculus	90-103
24973221-3	2014	Metformin inhibited LPS-induced production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in a concentration-dependent manner and in parallel induction of activating transcription factor-3 (ATF-3), a transcription factor and member of the cAMP-responsive element-binding protein family.	Metformin	0-9	interleukin 6	Mus musculus	105-109
24973221-6	2014	ChIP-PCR analysis revealed that LPS-induced NF-kappaB enrichments on the promoters of IL-6 and TNF-alpha were replaced by ATF-3 upon metformin treatment.	Metformin	133-142	interleukin 6	Mus musculus	86-90
24973221-6	2014	ChIP-PCR analysis revealed that LPS-induced NF-kappaB enrichments on the promoters of IL-6 and TNF-alpha were replaced by ATF-3 upon metformin treatment.	Metformin	133-142	tumor necrosis factor	Mus musculus	95-104
24973221-8	2014	Oral administration of metformin to either mice with LPS-induced endotoxemia or ob/ob mice lowered the plasma and tissue levels of TNF-alpha and IL-6 and increased ATF-3 expression in spleen and lungs.	Metformin	23-32	tumor necrosis factor	Mus musculus	131-140
24973221-8	2014	Oral administration of metformin to either mice with LPS-induced endotoxemia or ob/ob mice lowered the plasma and tissue levels of TNF-alpha and IL-6 and increased ATF-3 expression in spleen and lungs.	Metformin	23-32	interleukin 6	Mus musculus	145-149
24905037-8	2014	Western blot analysis revealed an increase in p-AMPK/AMPK ratio and suppressions of mTOR and Akt expressions in metformin-treated mice compared to the results in mock-treated control mice.	Metformin	112-121	thymoma viral proto-oncogene 1	Mus musculus	93-96
24905037-9	2014	Our results indicate that a physiologic dose of metformin has anti-tumorigenic effects that result from activation of AMPK signaling and inhibition of Akt signaling.	Metformin	48-57	AKT serine/threonine kinase 1	Homo sapiens	151-154
24976178-2	2014	In this study, we demonstrate that acute treatment with AMP-activated protein kinase (AMPK) agonists AICAR and metformin efficiently repressed IL-6-induced hepatic proinflammatory gene expression and activation of STAT3 in a mouse model of diet-induced type 2 diabetes, bringing it back to basal nonstimulated level.	Metformin	111-120	interleukin 6	Mus musculus	143-147
24976178-2	2014	In this study, we demonstrate that acute treatment with AMP-activated protein kinase (AMPK) agonists AICAR and metformin efficiently repressed IL-6-induced hepatic proinflammatory gene expression and activation of STAT3 in a mouse model of diet-induced type 2 diabetes, bringing it back to basal nonstimulated level.	Metformin	111-120	signal transducer and activator of transcription 3	Mus musculus	214-219
25096410-0	2014	Effect of metformin on serum interleukin-6 levels in polycystic ovary syndrome: a systematic review.	Metformin	10-19	interleukin 6	Homo sapiens	29-42
25096410-5	2014	Studies were selected that evaluated the effect of metformin on IL-6 levels in PCOS patients.	Metformin	51-60	interleukin 6	Homo sapiens	64-68
25096410-8	2014	Of these, one study reported a significant decrease in IL-6 levels after metformin treatment in women with PCOS.	Metformin	73-82	interleukin 6	Homo sapiens	55-59
25096410-11	2014	CONCLUSIONS: Serum IL-6 levels of PCOS patients may be influenced by metformin.	Metformin	69-78	interleukin 6	Homo sapiens	19-23
25096410-13	2014	However, further investigations with larger samples are needed to better understand the effects of metformin on IL-6 levels and chronic inflammation in PCOS.	Metformin	99-108	interleukin 6	Homo sapiens	112-116
25089625-1	2014	BACKGROUND: Incretin-based therapies which include glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are recommended by several practice guidelines as second-line agents for add-on therapy to metformin in patients with type 2 diabetes (T2DM) who do not achieve glycemic control with metformin plus lifestyle interventions alone.	Metformin	238-247	glucagon	Homo sapiens	51-74
25247153-1	2014	BACKGROUND: The aim of this study was to measure the body composition in adults with newly diagnosed type 2 diabetes mellitus and to explore the effect of metformin therapy on the various components of body composition, insulin sensitivity, and glucose homeostasis.	Metformin	155-164	insulin	Homo sapiens	220-227
25247153-13	2014	CONCLUSIONS: Metformin therapy results in significant improvement in body composition and insulin sensitivity of adults with newly diagnosed type 2 diabetes.	Metformin	13-22	insulin	Homo sapiens	90-97
24627035-0	2014	Are growth factor receptors modulated by metformin in human endometrial stromal cells after stimulation with androgen and insulin?	Metformin	41-50	insulin	Homo sapiens	122-129
24627035-1	2014	OBJECTIVE: To assess the effect of metformin on gene and protein expression of insulin receptor (IR) and IGF-1 (IGF-1R) receptor in human endometrial stromal cells after stimulation with androgen and insulin.	Metformin	35-44	insulin	Homo sapiens	79-86
24627035-3	2014	RESULTS: IR gene expression was increased after treatment with insulin (2.9-fold change, p = 0.027) and further after metformin treatment (4.7-fold change, p &lt; 0.001), and in IGF-1R, the group treated with insulin (1.83-fold change) and metformin (1.78-fold change) showed more expression, than control group (p &lt; 0.001).	Metformin	240-249	insulin	Homo sapiens	63-70
25088927-8	2014	In recent studies, it has been shown that therapeutic agents including insulin, metformin, angiotensin converting enzyme inhibitors and calcium channel blockers reduce TXNIP expression, although it is uncertain to what extent TXNIP suppression contributes to their clinical efficacy.	Metformin	80-89	thioredoxin interacting protein	Homo sapiens	168-173
24647737-6	2014	In contrast, metformin reduced fasting and glucose-stimulated glycemia, suppressed energy intake, and augmented total and intact GLP-1, total GIP, and glucagon in type 2 diabetic subjects, with no additional glucose lowering when combined with sitagliptin.	Metformin	13-22	glucagon	Homo sapiens	129-134
24647737-6	2014	In contrast, metformin reduced fasting and glucose-stimulated glycemia, suppressed energy intake, and augmented total and intact GLP-1, total GIP, and glucagon in type 2 diabetic subjects, with no additional glucose lowering when combined with sitagliptin.	Metformin	13-22	gastric inhibitory polypeptide	Homo sapiens	142-145
24842984-5	2014	Compared with nonusers, risk of lactic acidosis or elevated lactate concentrations in current metformin users was significantly associated with a renal function &lt;60 mL/min/1.73 m(2) (adjusted HR 6.37 [95% CI 1.48-27.5]).	Metformin	94-103	CD59 molecule (CD59 blood group)	Homo sapiens	171-176
25089625-1	2014	BACKGROUND: Incretin-based therapies which include glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are recommended by several practice guidelines as second-line agents for add-on therapy to metformin in patients with type 2 diabetes (T2DM) who do not achieve glycemic control with metformin plus lifestyle interventions alone.	Metformin	329-338	glucagon	Homo sapiens	51-74
24842984-7	2014	CONCLUSIONS: Our study is consistent with current recommendations that the renal function of metformin users should be adequately monitored and that the dose of metformin should be adjusted, if necessary, if renal function falls below 60 mL/min/1.73 m(2).	Metformin	161-170	CD59 molecule (CD59 blood group)	Homo sapiens	241-246
24921909-9	2014	Among the diabetics, multivariate regression showed that insulin/analogues were associated with increased, but metformin with decreased death with progressive MM.	Metformin	111-120	insulin	Homo sapiens	57-64
25219842-6	2014	RESULTS: Metformin reduced the elevated activites of GSHPx, SOD and catalase as well as MDA levels in cerebrum of rats exposed to ischemia and ischemia/reperfusion injures.	Metformin	9-18	glutathione peroxidase 1	Rattus norvegicus	53-58
25219842-6	2014	RESULTS: Metformin reduced the elevated activites of GSHPx, SOD and catalase as well as MDA levels in cerebrum of rats exposed to ischemia and ischemia/reperfusion injures.	Metformin	9-18	catalase	Rattus norvegicus	68-76
24859412-0	2014	Metformin sensitizes chemotherapy by targeting cancer stem cells and the mTOR pathway in esophageal cancer.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	73-77
24859412-9	2014	Immunoblots and transcriptional analyses further confirm that metformin downregulated these CSC-related genes and the components of the mTOR pathway in a dose-dependent manner.	Metformin	62-71	mechanistic target of rapamycin kinase	Homo sapiens	136-140
24859412-12	2014	Metformin inhibits EC cell growth and sensitizes EC cells to 5-FU cytotoxic effects by targeting CSCs and the components of mTOR.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	124-128
25144611-13	2014	The association between obesity, insulin resistance, as well as increased risk and poor outcomes in endometrial and ovarian cancer patients makes metformin an attractive agent for the prevention and treatment of these diseases.	Metformin	146-155	insulin	Homo sapiens	33-40
24193408-8	2014	Interestingly, combining low concentrations of rapamycin and metformin was more effective for inhibiting mTOR complex 1 activity in TRPP1-deficient cells than either drug alone.	Metformin	61-70	mechanistic target of rapamycin kinase	Homo sapiens	105-109
25076330-6	2014	Metformin is proposed to target metabolic pathways involved in tumorigenesis, specifically the AMPK-mTOR complex.	Metformin	0-9	mechanistic target of rapamycin kinase	Homo sapiens	100-104
24928508-3	2014	In the current study, we find that metformin, via an AMP-activated protein kinase (AMPK)-dependent mechanism, suppresses glucose production and gluconeogenic gene expression in primary hepatocytes at concentrations found in the portal vein of animals (60-80 muM).	Metformin	35-44	latexin	Homo sapiens	258-261
26674650-3	2014	Recently, we have reported that the combined treatment with metformin and progesterone-based oral contraceptives has successfully reversed the early-stage EC into normal endometria in addition to improvement of insulin resistance in women with PCOS.	Metformin	60-69	insulin	Homo sapiens	211-218
25056111-0	2014	Reprogramming ovarian and breast cancer cells into non-cancerous cells by low-dose metformin or SN-38 through FOXO3 activation.	Metformin	83-92	forkhead box O3	Homo sapiens	110-115
25056111-5	2014	Low-dose metformin or SN-38 increases FOXO3 nuclear localization as well as the amount of DNA damage markers and downregulates the expression of a cancer-stemness marker CD44 and other stemness markers, including Nanog, Oct-4, and c-Myc, in these cancer cells.	Metformin	9-18	forkhead box O3	Homo sapiens	38-43
25056111-8	2014	These results suggest that low-dose metformin or SN-38 may reprogram these cancer cells into non-cancerous cells in a FOXO3-dependent manner, and may allow patients to overcome these cancers with minimal side effects.	Metformin	36-45	forkhead box O3	Homo sapiens	118-123
25002509-3	2014	Here, we use LC/MS/MS metabolomics (&gt;200 metabolites) to assess metabolic changes induced by metformin and phenformin in an Src-inducible model of cellular transformation and in mammosphere-derived breast CSCs.	Metformin	96-105	SRC proto-oncogene, non-receptor tyrosine kinase	Homo sapiens	127-130
25028180-12	2014	CONCLUSION: In rats with hyperlipidemia, metformin and atorvastatin therapy is favorable for NO production and CRP reduction, which might be associated with Rho kinase activity decrease.	Metformin	41-50	C-reactive protein	Rattus norvegicus	111-114
25051360-5	2014	The anti-diabetes drug metformin can suppress the growth of breast CICs and herceptin-resistant HER2+ cells.	Metformin	23-32	erb-b2 receptor tyrosine kinase 2	Homo sapiens	96-100
25025689-0	2014	The anti-diabetic drug metformin reduces BACE1 protein level by interfering with the MID1 complex.	Metformin	23-32	beta-secretase 1	Homo sapiens	41-46
25025689-0	2014	The anti-diabetic drug metformin reduces BACE1 protein level by interfering with the MID1 complex.	Metformin	23-32	midline 1	Homo sapiens	85-89
25025689-5	2014	Here, we investigated the effect of metformin on the main amyloidogenic enzyme BACE1 and, thus, on the production of Abeta peptides, the second pathological hallmark of AD.	Metformin	36-45	beta-secretase 1	Homo sapiens	79-84
25025689-7	2014	We show that treatment with metformin decreases BACE1 protein expression by interfering with an mRNA-protein complex that contains the ubiquitin ligase MID1, thereby reducing BACE1 activity.	Metformin	28-37	beta-secretase 1	Homo sapiens	48-53
25025689-7	2014	We show that treatment with metformin decreases BACE1 protein expression by interfering with an mRNA-protein complex that contains the ubiquitin ligase MID1, thereby reducing BACE1 activity.	Metformin	28-37	midline 1	Homo sapiens	152-156
25025689-7	2014	We show that treatment with metformin decreases BACE1 protein expression by interfering with an mRNA-protein complex that contains the ubiquitin ligase MID1, thereby reducing BACE1 activity.	Metformin	28-37	beta-secretase 1	Homo sapiens	175-180
25120382-4	2014	RESULTS: We found that metformin significantly inhibits the proliferation of NB cells, an effect that correlates with the inhibition of Akt, while AMPK activity resulted unchanged.	Metformin	23-32	AKT serine/threonine kinase 1	Homo sapiens	136-139
24874591-6	2014	Fasting plasma insulin increased with glimepiride + metformin, while it did not change with vildagliptin + metformin.	Metformin	52-61	insulin	Homo sapiens	15-22
24988476-8	2014	We found that metformin withdrawal was associated with a reduction of active and total GLP-1 and elevation of serum bile acids, especially cholic acid and its conjugates.	Metformin	14-23	glucagon	Homo sapiens	87-92
24611741-0	2014	Acute metformin preconditioning confers neuroprotection against focal cerebral ischaemia by pre-activation of AMPK-dependent autophagy.	Metformin	6-15	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	110-114
24611741-1	2014	BACKGROUND AND PURPOSE: Recent clinical trials report that metformin, an activator of AMP-activated protein kinase (AMPK) used to treat type 2 diabetes, significantly reduces the risk of stroke by actions that are independent of its glucose-lowering effects.	Metformin	59-68	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	86-114
24611741-1	2014	BACKGROUND AND PURPOSE: Recent clinical trials report that metformin, an activator of AMP-activated protein kinase (AMPK) used to treat type 2 diabetes, significantly reduces the risk of stroke by actions that are independent of its glucose-lowering effects.	Metformin	59-68	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	116-120
24611741-3	2014	Here, we tested the possibility that acute metformin preconditioning confers neuroprotection by pre-activation of AMPK-dependent autophagy in a rat model of permanent middle cerebral artery occlusion (pMCAO).	Metformin	43-52	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	114-118
24611741-7	2014	KEY RESULTS: A single dose of metformin significantly activated AMPK and induced autophagy in the brain.	Metformin	30-39	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	64-68
24611741-11	2014	CONCLUSIONS AND IMPLICATIONS: These results provide the first evidence that acute metformin preconditioning induces autophagy by activation of brain AMPK, which confers neuroprotection against subsequent cerebral ischaemia.	Metformin	82-91	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	149-153
25098218-0	2014	[Metformin increases serum concentration of high molecular weight (HMW-adiponectin) in nondiabetic obese subjects].	Metformin	1-10	adiponectin, C1Q and collagen domain containing	Homo sapiens	71-82
25098218-2	2014	OBJECTIVE: To evaluate the efficacy of two different doses of metformin in comparison with placebo on increased serum levels of high molecular weight (HMW) adiponectin.	Metformin	62-71	adiponectin, C1Q and collagen domain containing	Homo sapiens	156-167
25118505-1	2014	Metformin is an oral insulin-sensitizing anti-diabetic drug.	Metformin	0-9	insulin	Homo sapiens	21-28
25083175-1	2014	BACKGROUND: Studies have demonstrated the efficacy of metformin (MTF ) in reducing insulin resistance and N-acetyl cysteine (NAC) in inhibiting oxidative stress which are involved in the pathogenesis of polycystic ovarian syndrome (PCOS).	Metformin	54-63	insulin	Homo sapiens	83-90
25083175-1	2014	BACKGROUND: Studies have demonstrated the efficacy of metformin (MTF ) in reducing insulin resistance and N-acetyl cysteine (NAC) in inhibiting oxidative stress which are involved in the pathogenesis of polycystic ovarian syndrome (PCOS).	Metformin	65-68	insulin	Homo sapiens	83-90
25083175-12	2014	The serum levels of malonyldialdehyde (MDA), insulin and leptin reduced significantly after treatment in the MTF+NAC group compared to the placebo (p&lt;0.05).	Metformin	109-112	insulin	Homo sapiens	45-52
25642303-5	2014	When MKN-45 cells were treated with metformin/cisplatin, the expression of survivin and mTOR were increased.	Metformin	36-45	mechanistic target of rapamycin kinase	Homo sapiens	88-92
25642303-6	2014	The antagonistic effect of metformin on cisplatin could be through survivin and mTOR signaling pathways.	Metformin	27-36	mechanistic target of rapamycin kinase	Homo sapiens	80-84
25642303-7	2014	Our results also suggest that interfering effect of metformin on cisplatin may be also through upregulation of Akt.	Metformin	52-61	AKT serine/threonine kinase 1	Homo sapiens	111-114
25642303-8	2014	Regarding the pivotal role of Akt in drug resistance, it may be reasonable to conclude that the antagonistic effect of metformin on cisplatin effect may be through this central mediator of drug resistance.	Metformin	119-128	AKT serine/threonine kinase 1	Homo sapiens	30-33
24877601-0	2014	Convergence of IPMK and LKB1-AMPK signaling pathways on metformin action.	Metformin	56-65	serine/threonine kinase 11	Mus musculus	24-28
24877601-3	2014	Although studies have suggested that metformin acts, at least in part, via activation of the liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) pathway, the specific molecular mechanisms underlying metformin"s regulation of glucose and lipid metabolism have not been well delineated.	Metformin	37-46	serine/threonine kinase 11	Mus musculus	93-108
24877601-3	2014	Although studies have suggested that metformin acts, at least in part, via activation of the liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) pathway, the specific molecular mechanisms underlying metformin"s regulation of glucose and lipid metabolism have not been well delineated.	Metformin	37-46	serine/threonine kinase 11	Mus musculus	110-114
24877601-3	2014	Although studies have suggested that metformin acts, at least in part, via activation of the liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) pathway, the specific molecular mechanisms underlying metformin"s regulation of glucose and lipid metabolism have not been well delineated.	Metformin	206-215	serine/threonine kinase 11	Mus musculus	93-108
24877601-3	2014	Although studies have suggested that metformin acts, at least in part, via activation of the liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) pathway, the specific molecular mechanisms underlying metformin"s regulation of glucose and lipid metabolism have not been well delineated.	Metformin	206-215	serine/threonine kinase 11	Mus musculus	110-114
24877601-7	2014	Overexpression of wild-type IPMK was sufficient to restore LKB1-AMPK activation by either metformin or AICAR in IPMK(-/-) murine embryonic fibroblast cells, suggesting that IPMK may act as an upstream regulator of LKB1-AMPK signaling in response to metformin.	Metformin	90-99	serine/threonine kinase 11	Mus musculus	59-63
24877601-8	2014	Moreover, this regulation was mediated by protein-protein interaction between IPMK and LKB1 as a dominant-negative peptide, which abrogates this interaction, attenuated metformin"s ability to activate AMPK.	Metformin	169-178	serine/threonine kinase 11	Mus musculus	87-91
24874591-8	2014	Regarding insulin sensitivity, vildagliptin + metformin increased M value.	Metformin	46-55	insulin	Homo sapiens	10-17
24874591-9	2014	Resistin, RBP-4, vaspin and visfatin were decreased by vildagliptin + metformin, but in group to group comparison, only vaspin reduction resulted statistically significant.	Metformin	70-79	serpin family A member 12	Homo sapiens	17-23
24847880-0	2014	Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase.	Metformin	0-9	glycerol-3-phosphate dehydrogenase 2	Homo sapiens	51-95
24847880-3	2014	Here we show that metformin non-competitively inhibits the redox shuttle enzyme mitochondrial glycerophosphate dehydrogenase, resulting in an altered hepatocellular redox state, reduced conversion of lactate and glycerol to glucose, and decreased hepatic gluconeogenesis.	Metformin	18-27	glycerol-3-phosphate dehydrogenase 2	Homo sapiens	80-124
24847880-5	2014	Antisense oligonucleotide knockdown of hepatic mitochondrial glycerophosphate dehydrogenase in rats resulted in a phenotype akin to chronic metformin treatment, and abrogated metformin-mediated increases in cytosolic redox state, decreases in plasma glucose concentrations, and inhibition of endogenous glucose production.	Metformin	140-149	glycerol-3-phosphate dehydrogenase 2	Homo sapiens	47-91
24847880-5	2014	Antisense oligonucleotide knockdown of hepatic mitochondrial glycerophosphate dehydrogenase in rats resulted in a phenotype akin to chronic metformin treatment, and abrogated metformin-mediated increases in cytosolic redox state, decreases in plasma glucose concentrations, and inhibition of endogenous glucose production.	Metformin	175-184	glycerol-3-phosphate dehydrogenase 2	Homo sapiens	47-91
24966801-10	2014	Inhibition of autophagy, either by Beclin1 knockdown or by 3-methyladenine-mediated inhibition of caspase-3/7, suppressed the anti-proliferative effects of metformin on endometrial cancer cells.	Metformin	156-165	caspase 3	Homo sapiens	98-109
25333030-4	2014	AMPK is present in many tissues making metformin"s effect multi factorial.	Metformin	39-48	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
24843020-6	2014	All of these effects of metformin were reversed when the metformin-resistant Saccharomyces cerevisiae NADH dehydrogenase NDI1 was overexpressed.	Metformin	24-33	NADH-ubiquinone reductase (H(+)-translocating) NDI1	Saccharomyces cerevisiae S288C	121-125
24896641-5	2014	Assessment of palmitate-induced lipoapoptosis by fluorescent microscopy and by detection of caspase-3 showed a significant decrease in metformin treated cells.	Metformin	135-144	caspase 3	Rattus norvegicus	92-101
24843020-6	2014	All of these effects of metformin were reversed when the metformin-resistant Saccharomyces cerevisiae NADH dehydrogenase NDI1 was overexpressed.	Metformin	57-66	NADH-ubiquinone reductase (H(+)-translocating) NDI1	Saccharomyces cerevisiae S288C	121-125
24671882-5	2014	In cultured bovine granulosa cells, INSULIN, IGF1, and two insulin sensitizers-metformin and rosiglitazone-increased rarres2 mRNA expression whereas they decreased cmklr1, gpr1, and cclr2 mRNA expression.	Metformin	79-88	chemerin chemokine-like receptor 2	Bos taurus	172-176
24462823-4	2014	Metformin may have a double-edged sword effect (i) by acting on the organism to decrease hyperglycaemia and hyperinsulinemia in diabetic patients and (ii) at the cellular level, by inhibiting the mTORC1-cancer supporting pathway through AMPK-dependent and independent mechanisms.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	196-202
24480115-0	2014	Metformin modulates PI3K and GLUT4 expression and Akt/PKB phosphorylation in human endometrial stromal cells after stimulation with androgen and insulin.	Metformin	0-9	solute carrier family 2 member 4	Homo sapiens	29-34
24480115-1	2014	OBJECTIVE: To assess the effect of metformin on expression of Akt, ERK, PI3K and GLUT4, proteins associated with the growth factor signaling cascade, in human endometrial stromal cells after stimulation with androgen and insulin.	Metformin	35-44	solute carrier family 2 member 4	Homo sapiens	81-86
24480115-4	2014	RESULTS: PI3K and GLUT4 expression were increased in the insulin-treated group and further attenuated when metformin was added.	Metformin	107-116	solute carrier family 2 member 4	Homo sapiens	18-23
24931021-6	2014	RESULTS: Metformin inhibited the proliferation of Fadu cells in a dose-and time-dependent manner.Flow cytometry showed that cell cycle arrest in G1 phase was induced by metformin in Fadu cells.Immunocytochemistry showed the expressions of both AMPK and P21 in cells treated with metformin were higher than those in cells untreated with metformin.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	244-248
24797033-10	2014	Treatment with metformin attenuated the severity of liver injury, restored AMPK activity and normalized the expression of acetyl-CoA carboxylase and fatty acid synthase.	Metformin	15-24	fatty acid synthase	Rattus norvegicus	149-168
24462945-1	2014	BACKGROUND: Metformin has been shown to have a strong anti-proliferative effect in many breast cancer cell lines, mainly due to the activation of the energy sensing kinase, AMP-activated protein kinase (AMPK).	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	203-207
24462945-9	2014	In addition, we show that metformin-treatment of MDA-MB-231 cells cultured in normoglycemic conditions and not in hyperglycemic conditions caused a striking activation of AMPK, and an AMPK-dependent inhibition of multiple molecular signaling pathways known to control protein synthesis and cell proliferation.	Metformin	26-35	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	171-175
24462945-9	2014	In addition, we show that metformin-treatment of MDA-MB-231 cells cultured in normoglycemic conditions and not in hyperglycemic conditions caused a striking activation of AMPK, and an AMPK-dependent inhibition of multiple molecular signaling pathways known to control protein synthesis and cell proliferation.	Metformin	26-35	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	184-188
24931021-6	2014	RESULTS: Metformin inhibited the proliferation of Fadu cells in a dose-and time-dependent manner.Flow cytometry showed that cell cycle arrest in G1 phase was induced by metformin in Fadu cells.Immunocytochemistry showed the expressions of both AMPK and P21 in cells treated with metformin were higher than those in cells untreated with metformin.	Metformin	169-178	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	244-248
24662793-3	2014	Adenosine-monophosphate-activated protein kinase (AMPK) activation is the most well-known mechanism of metformin action.	Metformin	103-112	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-48
24662793-3	2014	Adenosine-monophosphate-activated protein kinase (AMPK) activation is the most well-known mechanism of metformin action.	Metformin	103-112	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	50-54
24420848-0	2014	Metformin protects against hyperglycemia-induced cardiomyocytes injury by inhibiting the expressions of receptor for advanced glycation end products and high mobility group box 1 protein.	Metformin	0-9	high mobility group box 1	Homo sapiens	153-178
23668534-5	2014	Moreover, recent studies have suggested that metformin enhances the biological effect of GLP-1 by increasing GLP-1 secretion, suppressing activity of DPP-4 and upregulating the expression of GLP-1 receptor in pancreatic beta-cells.	Metformin	45-54	glucagon like peptide 1 receptor	Homo sapiens	191-205
24396411-8	2014	Western blot analysis results showed that the mean level of phosphorylated (p)-AMPK in the HaCaT cells without metformin treatment was 2.856+-0.323.	Metformin	111-120	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	79-83
24396411-9	2014	However, the mean p-AMPK level following metformin treatment for 24 h increased to 5.198+-0.625, indicating a significant difference between these two groups (P&lt;0.05).	Metformin	41-50	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	20-24
24396411-11	2014	In conclusion, metformin treatment upregulated the levels of p-AMPK and p-ERK1/2 in HaCaT cells, and significantly inhibited HaCaT cell proliferation in vitro by a mechanism associated with activation of the mitogen-activated protein kinase signaling pathway.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	63-67
24387947-8	2014	Among others, the anti-diabetic drug, metformin, is a potent activator of AMPK.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	74-78
24474794-4	2014	AMPK activation by two indirect AMPK agonists AICAR and metformin (now in over 50 clinical trials on cancer) has been correlated with reduced cancer cell proliferation and viability.	Metformin	56-65	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
24474794-4	2014	AMPK activation by two indirect AMPK agonists AICAR and metformin (now in over 50 clinical trials on cancer) has been correlated with reduced cancer cell proliferation and viability.	Metformin	56-65	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	32-36
24474794-9	2014	Metformin directly inhibited mTOR by enhancing PRAS40"s association with RAPTOR, whereas AICAR blocked the cell cycle through proteasomal degradation of the G2M phosphatase cdc25c.	Metformin	0-9	regulatory associated protein of MTOR complex 1	Homo sapiens	73-79
24474794-10	2014	Together, our results suggest that although AICAR and metformin are potent AMPK-independent antiproliferative agents, physiological AMPK activation in glioma may be a response mechanism to metabolic stress and anticancer agents.	Metformin	54-63	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	75-79
24233023-10	2014	Our findings indicate that the cooperation between Wnt and its upstream insulin signaling pathways might be a novel and important mechanism underlying the effects of metformin on GLP1 production.	Metformin	166-175	glucagon	Mus musculus	179-183
24196830-9	2014	Combinations of metformin and rapamycin were more effective at blocking epidermal mTORC1 signaling induced by TPA consistent with the greater inhibitory effect on skin tumor promotion.	Metformin	16-25	CREB regulated transcription coactivator 1	Mus musculus	82-88
24196830-10	2014	Collectively, the current data demonstrate that metformin given in the drinking water effectively inhibited skin tumor promotion in both overweight and obese mice and that the mechanism involves activation of epidermal AMPK and attenuated signaling downstream of mTORC1.	Metformin	48-57	CREB regulated transcription coactivator 1	Mus musculus	263-269
25329671-4	2014	Activation of LKB1/AMPK pathway and cancer stem cell destruction along with cell cycle arrest and apoptosis induction are the proposed mechanisms of anticancer potential of metformin.	Metformin	173-182	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	19-23
24550580-10	2014	CONCLUSION: The combination of bromocriptine with metformin significantly decreased FPG, PPPG, and HbA1C compared with metformin alone in type 2 DM patients in a dose-dependent manner.	Metformin	50-59	hemoglobin subunit alpha 1	Homo sapiens	99-103
24173471-3	2014	Research suggests that metformin, a drug long used to treat diabetes, and an alternative remedy in the treatment of obesity, increases the activity of 5-adenosinemonophosphate (AMP)-activated kinase (AMPK).	Metformin	23-32	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	200-204
24462945-10	2014	CONCLUSION: Our data show that normoglycemia sensitizes the triple negative MDA-MB-231 breast cancer cells to the anti-proliferative effect of metformin through an AMPK-dependent mechanism.	Metformin	143-152	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	164-168
24683044-7	2014	Modulation by metformin of 42 of 1281 pulmonary microRNAs in smoke-free mice highlighted a variety of mechanisms, including modulation of AMPK, stress response, inflammation, NFkappaB, Tlr9, Tgf, p53, cell cycle, apoptosis, antioxidant pathways, Ras, Myc, Dicer, angiogenesis, stem cell recruitment, and angiogenesis.	Metformin	14-23	myelocytomatosis oncogene	Mus musculus	251-254
24943970-0	2014	The relationship between anticancer effect of metformin and the transcriptional regulation of certain genes (CHOP, CAV-1, HO-1, SGK-1 and Par-4) on MCF-7 cell line.	Metformin	46-55	Prader Willi/Angelman region RNA 4	Homo sapiens	138-143
24809794-2	2014	ET-1 dose and time-dependently induced PASMCs proliferation, and this effect was suppressed by a selective AMPK activator metformin.	Metformin	122-131	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	107-111
24809794-3	2014	The results of the study further indicated that the proliferation of PASMCs stimulated by ET-1 was associated with the increase of Skp2 and decrease of p27, and metformin reversed ET-1-induced Skp2 elevation and raised p27 protein level.	Metformin	161-170	S-phase kinase associated protein 2	Homo sapiens	193-197
24788596-4	2014	Metformin targeted the AMPK/mTORC1 pathway in ICC cells.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	28-34
24905518-11	2014	All the aforementioned results resulted from AMPK activation, but a residual activity of metformin after AMPK blockade was still noticeable even after inhibition of AMPK by compound C. CONCLUSIONS: Authors believe that metformin-based therapy, a cornerstone in diabetes therapy, not only improves the prognosis of diabetics by reducing blood glucose but also by reducing oxidative stress, inflammatory cytokine production and the shift toward alternative activation of macrophages.	Metformin	89-98	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	105-109
24905518-11	2014	All the aforementioned results resulted from AMPK activation, but a residual activity of metformin after AMPK blockade was still noticeable even after inhibition of AMPK by compound C. CONCLUSIONS: Authors believe that metformin-based therapy, a cornerstone in diabetes therapy, not only improves the prognosis of diabetics by reducing blood glucose but also by reducing oxidative stress, inflammatory cytokine production and the shift toward alternative activation of macrophages.	Metformin	89-98	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	105-109
24905518-11	2014	All the aforementioned results resulted from AMPK activation, but a residual activity of metformin after AMPK blockade was still noticeable even after inhibition of AMPK by compound C. CONCLUSIONS: Authors believe that metformin-based therapy, a cornerstone in diabetes therapy, not only improves the prognosis of diabetics by reducing blood glucose but also by reducing oxidative stress, inflammatory cytokine production and the shift toward alternative activation of macrophages.	Metformin	219-228	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	45-49
24905518-11	2014	All the aforementioned results resulted from AMPK activation, but a residual activity of metformin after AMPK blockade was still noticeable even after inhibition of AMPK by compound C. CONCLUSIONS: Authors believe that metformin-based therapy, a cornerstone in diabetes therapy, not only improves the prognosis of diabetics by reducing blood glucose but also by reducing oxidative stress, inflammatory cytokine production and the shift toward alternative activation of macrophages.	Metformin	219-228	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	105-109
24905518-11	2014	All the aforementioned results resulted from AMPK activation, but a residual activity of metformin after AMPK blockade was still noticeable even after inhibition of AMPK by compound C. CONCLUSIONS: Authors believe that metformin-based therapy, a cornerstone in diabetes therapy, not only improves the prognosis of diabetics by reducing blood glucose but also by reducing oxidative stress, inflammatory cytokine production and the shift toward alternative activation of macrophages.	Metformin	219-228	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	105-109
24844651-0	2014	Metformin sensitizes prostate cancer cells to radiation through EGFR/p-DNA-PKCS in vitro and in vivo.	Metformin	0-9	protein kinase, DNA activated, catalytic polypeptide	Mus musculus	71-79
24844651-8	2014	In addition, the reduced phosphorylation of DNA-PKcs caused by EGFR/PI3K/Akt down-regulation is essential for metformin to induce radiosensitivity in prostate cancer cells.	Metformin	110-119	protein kinase, DNA activated, catalytic polypeptide	Mus musculus	44-52
24858012-0	2014	Metformin induces apoptosis and cell cycle arrest mediated by oxidative stress, AMPK and FOXO3a in MCF-7 breast cancer cells.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	80-84
24858012-8	2014	In MCF-7 cells metformin decreased the activation of IRbeta, Akt and ERK1/2, increased p-AMPK, FOXO3a, p27, Bax and cleaved caspase-3, and decreased phosphorylation of p70S6K and Bcl-2 protein expression.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	89-93
24858012-11	2014	Treatment with metformin resulted in an increase in p-p38 MAPK, catalase, MnSOD and Cu/Zn SOD protein expression.	Metformin	15-24	superoxide dismutase 2	Homo sapiens	74-79
24858012-12	2014	These results show that metformin has an antiproliferative effect associated with cell cycle arrest and apoptosis, which is mediated by oxidative stress, as well as AMPK and FOXO3a activation.	Metformin	24-33	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	165-169
24428821-0	2014	Metformin induces PGC-1alpha expression and selectively affects hepatic PGC-1alpha functions.	Metformin	0-9	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	18-28
24428821-0	2014	Metformin induces PGC-1alpha expression and selectively affects hepatic PGC-1alpha functions.	Metformin	0-9	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	72-82
24428821-1	2014	BACKGROUND AND PURPOSE: The objective of this study was to determine how the AMPK activating antidiabetic drug metformin affects the major activator of hepatic gluconeogenesis, PPARgamma coactivator 1alpha (PGC-1alpha) and liver functions regulated by PGC-1alpha.	Metformin	111-120	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	77-81
24428821-1	2014	BACKGROUND AND PURPOSE: The objective of this study was to determine how the AMPK activating antidiabetic drug metformin affects the major activator of hepatic gluconeogenesis, PPARgamma coactivator 1alpha (PGC-1alpha) and liver functions regulated by PGC-1alpha.	Metformin	111-120	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	177-205
24428821-1	2014	BACKGROUND AND PURPOSE: The objective of this study was to determine how the AMPK activating antidiabetic drug metformin affects the major activator of hepatic gluconeogenesis, PPARgamma coactivator 1alpha (PGC-1alpha) and liver functions regulated by PGC-1alpha.	Metformin	111-120	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	207-217
24428821-1	2014	BACKGROUND AND PURPOSE: The objective of this study was to determine how the AMPK activating antidiabetic drug metformin affects the major activator of hepatic gluconeogenesis, PPARgamma coactivator 1alpha (PGC-1alpha) and liver functions regulated by PGC-1alpha.	Metformin	111-120	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	252-262
24428821-4	2014	KEY RESULTS: Metformin increased PGC-1alpha mRNA and protein expression in mouse primary hepatocytes.	Metformin	13-22	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	33-43
24918793-1	2014	The incretin class of anti-hyperglycemic agents, including glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-inhibitors, is an important addition to the therapeutic armamentarium for the management of appropriate patients with type 2 diabetes mellitus as an adjunct to diet and exercise and/or with the agents metformin, sulfonylureas, thiazolidinediones, or any combination thereof.	Metformin	327-336	glucagon like peptide 1 receptor	Homo sapiens	59-91
24248330-3	2014	Several drugs and nutraceuticals which slightly and safely impede the efficiency of mitochondrial ATP generation-most notably metformin and berberine-can be employed as clinical AMPK activators and, hence, may have potential as calorie restriction mimetics for extending healthspan.	Metformin	126-135	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	178-182
24248330-5	2014	While metformin and berberine appear to have the greatest utility as clinical AMPK activators-as reflected by their efficacy in diabetes management-regular ingestion of vinegar, as well as moderate alcohol consumption, may also achieve a modest degree of health-protective AMPK activation.	Metformin	6-15	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	78-82
24444314-5	2014	Metformin attenuated AngII-induced activation (cleavage) of caspase 3, Bcl-2 down-regulation and p53 up-regulation.	Metformin	0-9	caspase 3	Rattus norvegicus	60-69
24444314-8	2014	The AMPK inhibitor, compound C, prevented AT1R down-regulation, indicating that metformin mediated its effects via AMPK activation.	Metformin	80-89	angiotensin II receptor, type 1a	Rattus norvegicus	42-46
24444314-10	2014	Thus, this study demonstrates that the anti-hypertrophic effects of metformin are associated with AMPK-induced AT1R down-regulation and prevention of mitochondrial dysfunction through the SIRT1/eNOS/p53 pathway.	Metformin	68-77	angiotensin II receptor, type 1a	Rattus norvegicus	111-115
24106875-1	2014	BACKGROUND: Insulin and incretin agents (dipeptidyl peptidase-4 inhibitors [DPP4is] and glucagon-like peptide-1 receptor agonists [GLP1 RAs]) are second-line treatment options in patients with type 2 diabetes (T2D) not achieving glycemic targets with metformin.	Metformin	251-260	glucagon like peptide 1 receptor	Homo sapiens	131-135
24531544-0	2014	Metformin interferes with bile acid homeostasis through AMPK-FXR crosstalk.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	56-60
24531544-7	2014	Furthermore, treatment with AMPK activators, including the antidiabetic biguanide metformin, inhibited FXR agonist induction of FXR target genes in mouse liver and intestine.	Metformin	82-91	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	28-32
24269733-4	2014	Restoration of AMPK activity by metformin or AICAR reduced the in vitro neurotoxicity of ASYN overexpression, acting independently of the prosurvival kinase Akt or the induction of autophagic response.	Metformin	32-41	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	15-19
24569407-1	2014	AIM: Anti-Mullerian hormone (AMG) reduction in women with hyperinsulinemia in therapy with metformin suggests that metformin affects the level of AMH and ovulatory dysfunction through insulin-mediated mechanisms.	Metformin	91-100	amelogenin X-linked	Homo sapiens	29-32
24569407-1	2014	AIM: Anti-Mullerian hormone (AMG) reduction in women with hyperinsulinemia in therapy with metformin suggests that metformin affects the level of AMH and ovulatory dysfunction through insulin-mediated mechanisms.	Metformin	115-124	amelogenin X-linked	Homo sapiens	29-32
24302004-7	2014	Activation of AMPK by metformin inhibited mTORC1-STAT3 signaling, thereby preventing excess amino acid-impaired insulin signaling.	Metformin	22-31	CREB regulated transcription coactivator 1	Mus musculus	42-48
24302004-9	2014	Chronic administration of either metformin or rapamycin inhibited the HPD-activated mTORC1/STAT3/Notch1 signaling pathway and prevented hepatic insulin resistance.	Metformin	33-42	CREB regulated transcription coactivator 1	Mus musculus	84-90
24457597-0	2014	Metformin sensitizes anticancer effect of dasatinib in head and neck squamous cell carcinoma cells through AMPK-dependent ER stress.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	107-111
24457597-7	2014	Furthermore, activation of AMPK by metformin sensitized dasatinib-induced in vitro and in vivo anti-cancer effect.	Metformin	35-44	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	27-31
24457597-9	2014	Our results disclose that AMPK-dependent ER stress plays a crucial role in the anti-cancer effect of dasatinib in HNSCC and further activation of AMPK by metformin might enhance dasatinib efficacy.	Metformin	154-163	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	26-30
24457597-9	2014	Our results disclose that AMPK-dependent ER stress plays a crucial role in the anti-cancer effect of dasatinib in HNSCC and further activation of AMPK by metformin might enhance dasatinib efficacy.	Metformin	154-163	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	146-150
24028077-8	2014	HTR-8/SVneo and HPT-8 cells transfected with a gC1qR vector showed upregulation of cellular apoptosis and mitochondrial dysfunction, interestingly, which were abrogated by the addition of metformin.	Metformin	188-197	complement C1q binding protein	Homo sapiens	47-52
24850385-5	2014	AMPK is activated by two widely used clinical drugs, metformin and aspirin, and also by many natural products of plants that are either derived from traditional medicines or are promoted as "nutraceuticals."	Metformin	53-62	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
23819433-5	2014	Activation of AMPK by metformin resulted in a strong reduction of iodide uptake (up to sixfold with 5 mM metformin after 96 h) and NIS protein levels in vitro, whereas AMPK inhibition by compound C not only stimulated iodide uptake but also enhanced NIS protein levels both in vitro (up to sevenfold with 1 muM compound C after 96 h) and in vivo (1.5-fold after daily injections with 20 mg/kg for 4 days).	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	14-18
23819433-5	2014	Activation of AMPK by metformin resulted in a strong reduction of iodide uptake (up to sixfold with 5 mM metformin after 96 h) and NIS protein levels in vitro, whereas AMPK inhibition by compound C not only stimulated iodide uptake but also enhanced NIS protein levels both in vitro (up to sevenfold with 1 muM compound C after 96 h) and in vivo (1.5-fold after daily injections with 20 mg/kg for 4 days).	Metformin	105-114	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	14-18
23819433-12	2014	CONCLUSION: NIS expression and iodine uptake in thyrocytes can be modulated by metformin and compound C. These compounds exert their effect by modulation of AMPK, which, in turn, regulates the activation of the CRE element in the NIS promoter.	Metformin	79-88	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	157-161
24351837-4	2013	Metformin significantly inhibited the proliferation and colony formation of 5637 and T24 cells in vitro; specifically, metformin induced an apparent cell cycle arrest in G0/G1 phases, accompanied by a strong decrease of cyclin D1, cyclin-dependent kinase 4 (CDK4), E2F1 and an increase of p21waf-1.	Metformin	0-9	cyclin dependent kinase 4	Homo sapiens	258-262
24351837-4	2013	Metformin significantly inhibited the proliferation and colony formation of 5637 and T24 cells in vitro; specifically, metformin induced an apparent cell cycle arrest in G0/G1 phases, accompanied by a strong decrease of cyclin D1, cyclin-dependent kinase 4 (CDK4), E2F1 and an increase of p21waf-1.	Metformin	119-128	cyclin D1	Homo sapiens	220-229
24351837-4	2013	Metformin significantly inhibited the proliferation and colony formation of 5637 and T24 cells in vitro; specifically, metformin induced an apparent cell cycle arrest in G0/G1 phases, accompanied by a strong decrease of cyclin D1, cyclin-dependent kinase 4 (CDK4), E2F1 and an increase of p21waf-1.	Metformin	119-128	cyclin dependent kinase 4	Homo sapiens	231-256
24351837-4	2013	Metformin significantly inhibited the proliferation and colony formation of 5637 and T24 cells in vitro; specifically, metformin induced an apparent cell cycle arrest in G0/G1 phases, accompanied by a strong decrease of cyclin D1, cyclin-dependent kinase 4 (CDK4), E2F1 and an increase of p21waf-1.	Metformin	119-128	cyclin dependent kinase 4	Homo sapiens	258-262
24351837-6	2013	Moreover, daily treatment of metformin led to a substantial inhibition of tumor growth in a xenograft model with concomitant decrease in the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and p-mTOR.	Metformin	29-38	cyclin D1	Homo sapiens	198-207
24308813-8	2013	A decrease in ER expression was noted in women with EC and DM2 receiving metformin as compared to women treated with insulin (p = 0.004).	Metformin	73-82	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	59-62
24097562-0	2013	Metformin-stimulated AMPK-alpha1 promotes microvascular repair in acute lung injury.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Rattus norvegicus	21-32
24130167-0	2013	Metformin targets c-MYC oncogene to prevent prostate cancer.	Metformin	0-9	myelocytomatosis oncogene	Mus musculus	20-23
24130167-6	2013	The purpose of this study is to investigate the effect of metformin on c-myc expression and PCa progression.	Metformin	58-67	myelocytomatosis oncogene	Mus musculus	73-76
24130167-7	2013	Our results demonstrated that (i) in Hi-Myc mice that display murine prostate neoplasia and highly resemble the progression of human prostate tumors, metformin attenuated the development of prostate intraepithelial neoplasia (PIN, the precancerous lesion of prostate) and PCa lesions.	Metformin	150-159	myelocytomatosis oncogene	Mus musculus	40-43
24130167-8	2013	(ii) Metformin reduced c-myc protein levels in vivo and in vitro.	Metformin	5-14	myelocytomatosis oncogene	Mus musculus	25-28
24130167-9	2013	In Myc-CaP mouse PCa cells, metformin decreased c-myc protein levels by at least 50%.	Metformin	28-37	myelocytomatosis oncogene	Mus musculus	3-6
24130167-9	2013	In Myc-CaP mouse PCa cells, metformin decreased c-myc protein levels by at least 50%.	Metformin	28-37	myelocytomatosis oncogene	Mus musculus	50-53
24130167-11	2013	(iv) Reduced PIN formation by metformin was associated with reduced levels of androgen receptor and proliferation marker Ki-67 in Hi-Myc mouse prostate glands.	Metformin	30-39	myelocytomatosis oncogene	Mus musculus	133-136
24130167-12	2013	Our novel findings suggest that by downregulating c-myc, metformin can act as a chemopreventive agent to restrict prostatic neoplasia initiation and transformation.	Metformin	57-66	myelocytomatosis oncogene	Mus musculus	52-55
24130167-13	2013	SUMMARY: Metformin, an old antidiabetes drug, may inhibit prostate intraepithelial neoplasia transforming to cancer lesion via reducing c-MYC, an "old" overexpressed oncogene.	Metformin	9-18	myelocytomatosis oncogene	Mus musculus	138-141
24321717-9	2013	GLP-1 was higher in the pre-lunch (p=0.016) and post-lunch (p=0.018) periods of the metformin conditions compared with the placebo.	Metformin	84-93	glucagon like peptide 1 receptor	Homo sapiens	0-5
24321717-12	2013	Metformin, independent of exercise, significantly increased total plasma GLP-1 and GIP concentrations in these patients.	Metformin	0-9	glucagon like peptide 1 receptor	Homo sapiens	73-78
23971789-9	2013	Available data from clinical trials support second-line use of GLP-1 RAs among patients who fail on metformin, as well as first-line use of these agents in a subset of T2D patients.	Metformin	100-109	glucagon like peptide 1 receptor	Homo sapiens	63-68
24026623-3	2013	However, vandetanib was an even more potent inhibitor of MATE1- and MATE2K-mediated uptake of MPP(+) (IC(50) of 1.23 +- 0.05 and 1.26 +- 0.06 microM, respectively) and metformin (IC(50) of 0.16 +- 0.05 and 0.30 +- 0.09 microM, respectively).	Metformin	168-177	solute carrier family 47 member 2	Homo sapiens	68-74
24096736-0	2014	Metformin reverses multidrug resistance and epithelial-mesenchymal transition (EMT) via activating AMP-activated protein kinase (AMPK) in human breast cancer cells.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	99-127
24096736-0	2014	Metformin reverses multidrug resistance and epithelial-mesenchymal transition (EMT) via activating AMP-activated protein kinase (AMPK) in human breast cancer cells.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	129-133
24096736-7	2014	Moreover, we found metformin treatment activated AMPK signal pathway in MCF7/5-FU and MDA-MB-231 cells and compound C, the AMPK inhibitor, could partly abolish the resensitization and EMT reversal effect of metformin.	Metformin	19-28	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	49-53
24096736-7	2014	Moreover, we found metformin treatment activated AMPK signal pathway in MCF7/5-FU and MDA-MB-231 cells and compound C, the AMPK inhibitor, could partly abolish the resensitization and EMT reversal effect of metformin.	Metformin	19-28	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	123-127
24096736-7	2014	Moreover, we found metformin treatment activated AMPK signal pathway in MCF7/5-FU and MDA-MB-231 cells and compound C, the AMPK inhibitor, could partly abolish the resensitization and EMT reversal effect of metformin.	Metformin	207-216	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	49-53
24096736-7	2014	Moreover, we found metformin treatment activated AMPK signal pathway in MCF7/5-FU and MDA-MB-231 cells and compound C, the AMPK inhibitor, could partly abolish the resensitization and EMT reversal effect of metformin.	Metformin	207-216	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	123-127
24096736-8	2014	To the best of our knowledge, we are the first to report that metformin can resensitize multidrug-resistant breast cancer cells due to activating AMPK signal pathway.	Metformin	62-71	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	146-150
24140245-5	2014	Cox regression models addressed the association of diabetes mellitus (DM) and metformin use with disease recurrence, cancer-specific mortality, and any-cause mortality.	Metformin	78-87	cytochrome c oxidase subunit 8A	Homo sapiens	0-3
24138903-0	2013	Inhibition of p38 MAPK-dependent MutS homologue-2 (MSH2) expression by metformin enhances gefitinib-induced cytotoxicity in human squamous lung cancer cells.	Metformin	71-80	mutS homolog 2	Homo sapiens	33-49
24138903-0	2013	Inhibition of p38 MAPK-dependent MutS homologue-2 (MSH2) expression by metformin enhances gefitinib-induced cytotoxicity in human squamous lung cancer cells.	Metformin	71-80	mutS homolog 2	Homo sapiens	51-55
24138903-13	2013	In human lung squamous cancer cells, metformin decreased gefitinib-induced MSH2 expression and augmented the cytotoxic effect and growth inhibition by gefitinib.	Metformin	37-46	mutS homolog 2	Homo sapiens	75-79
24466367-9	2013	These results suggest that biologic effects of metformin are mediated through decreased CSC markers cluster of differentiation 44 (CD44 and CD133), aldehyde dehydrogenase isoform 1 (ALDH1), and epithelial cell adhesion molecule (EPCAM) and modulation of the mTOR signaling pathway.	Metformin	47-56	aldehyde dehydrogenase family 1, subfamily A1	Mus musculus	148-180
24466367-9	2013	These results suggest that biologic effects of metformin are mediated through decreased CSC markers cluster of differentiation 44 (CD44 and CD133), aldehyde dehydrogenase isoform 1 (ALDH1), and epithelial cell adhesion molecule (EPCAM) and modulation of the mTOR signaling pathway.	Metformin	47-56	aldehyde dehydrogenase family 1, subfamily A1	Mus musculus	182-187
23933835-2	2013	Metformin improves hepatic gluconeogenesis by activating 5"-AMP-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	90-94
23933835-3	2013	However, metformin also activates aPKC in certain tissues; in the liver, this activation could amplify diabetic aberrations and offset the positive effects of AMPK.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	159-163
23933835-5	2013	METHODS: We compared protein kinase activities and alterations in lipogenic and gluconeogenic enzyme levels during activity of the AMPK activators metformin and AICAR, relative to those of an aPKC-iota inhibitor, in hepatocytes from non-diabetic and type 2 diabetic human organ donors.	Metformin	147-156	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	131-135
23933835-10	2013	CONCLUSIONS/INTERPRETATION: Metformin and AICAR activate aPKC together with AMPK in human hepatocytes.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	76-80
23600690-1	2013	REASONS FOR PERFORMING STUDY: Metformin is a potential therapeutic agent for the treatment of insulin resistance (IR).	Metformin	30-39	INS	Equus caballus	94-101
23600690-3	2013	OBJECTIVES: To determine whether pretreatment with metformin reduces plasma glucose concentration and insulin responses following consumption of dextrose in horses.	Metformin	51-60	INS	Equus caballus	102-109
23600690-9	2013	RESULTS: In healthy horses, the administration of metformin resulted in a statistically significant reduction in peak glucose concentration (P = 0.002), area under the glucose curve (P&lt;0.001) and insulin concentration 120 min after dextrose administration (P = 0.011).	Metformin	50-59	INS	Equus caballus	199-206
23600690-10	2013	Following the induction of IR, administration of metformin was associated with significant differences in peak glucose concentration (P&lt;0.001), the percentage increase in glucose concentration (P = 0.010), the area under the glucose curve (P&lt;0.001) and insulin concentration at 120 min (P = 0.034) and 150 min after dextrose administration (P = 0.014).	Metformin	49-58	INS	Equus caballus	259-266
23937224-4	2013	EXPERT OPINION: Future perspective studies are required in nonsmall-cell lung cancer (NSCLC) patients to better investigate the effect of metformin action on the RAS/RAF/MAPK pathway and the best context in which to use metformin in combination with molecularly targeted agents.	Metformin	138-147	zinc fingers and homeoboxes 2	Homo sapiens	166-169
24278407-0	2013	Effects of metformin on CD133+ colorectal cancer cells in diabetic patients.	Metformin	11-20	prominin 1	Homo sapiens	24-29
24278407-7	2013	The results show that metformin treatment had reverse correlations with the proportion of patients with poorly differentiated adenocarcinoma, the proportion of CD133+ cscs in CRC patients with type 2 DM.	Metformin	22-31	prominin 1	Homo sapiens	160-165
24278407-8	2013	Metformin enhanced the antiproliferative effects of 5-FU on CD133+ cscs in SW620 cells.	Metformin	0-9	prominin 1	Homo sapiens	60-65
24278407-10	2013	Inhibition of the proliferation of CD133+ cscs may be a potential mechanism responsible for the association of metformin use with improved CRC outcomes in CRC patients with type 2 diabetes.	Metformin	111-120	prominin 1	Homo sapiens	35-40
23955995-8	2013	Increased GLP-1 responses during meal tolerance test and decreased fasting glucagon level were observed after metformin treatment.	Metformin	110-119	glucagon like peptide 1 receptor	Homo sapiens	10-15
23982736-4	2013	We show that low doses of metformin induced hepatoma cell senescence characterized by accumulation of senescence-associated beta-galactosidase activity (SA-beta-gal) and the senescence marker Dec1, whereas the higher doses initiated apoptotic cell death.	Metformin	26-35	deleted in esophageal cancer 1	Homo sapiens	192-196
24008375-0	2013	Metformin suppresses hepatocellular carcinoma cell growth through induction of cell cycle G1/G0 phase arrest and p21CIP and p27KIP expression and downregulation of cyclin D1 in vitro and in vivo.	Metformin	0-9	cyclin D1	Homo sapiens	164-173
24008375-13	2013	Treatment with metformin upregulated the expression of p21CIP and p27KIP, but downregulated cyclin D1 levels, both in vitro and in vivo.	Metformin	15-24	cyclin D1	Homo sapiens	92-101
24136225-0	2013	FoxO1 controls lysosomal acid lipase in adipocytes: implication of lipophagy during nutrient restriction and metformin treatment.	Metformin	109-118	lipase A, lysosomal acid type	Homo sapiens	15-36
24025223-3	2013	In female rat aortic smooth muscle cells (RASMCs), we observed that metformin significantly alleviated beta-glycerophosphate-induced Ca deposition and alkaline phosphatase activity, corresponding with reduced expression of some specific genes in osteoblast-like cells, including Runx2 and bone morphogenetic protein-2, and positive effects on alpha-actin expression, a specific marker of smooth muscle cells.	Metformin	68-77	bone morphogenetic protein 2	Rattus norvegicus	289-317
24378094-10	2013	Western blotting results revealed that the expression of CD133, phosphorylated Akt and the Bcl-2/Bax ratio were downregulated, and PTEN was upregulated in the Huh-7 cells after treated with 25 mmol/L metformin for 48 hrs.	Metformin	200-209	prominin 1	Homo sapiens	57-62
23835523-5	2013	The notion that 5" AMP-activated protein kinase (AMPK) mediates the anti-hyperglycaemic action of metformin has recently been challenged by genetic loss-of-function studies, thrusting the AMPK-independent effects of the drug into the spotlight for the first time in more than a decade.	Metformin	98-107	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	19-47
23835523-5	2013	The notion that 5" AMP-activated protein kinase (AMPK) mediates the anti-hyperglycaemic action of metformin has recently been challenged by genetic loss-of-function studies, thrusting the AMPK-independent effects of the drug into the spotlight for the first time in more than a decade.	Metformin	98-107	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	49-53
23835523-6	2013	Key AMPK-independent effects of the drug include the mitochondrial actions that have been known for many years and which are still thought to be the primary site of action of metformin.	Metformin	175-184	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	4-8
23831441-0	2013	Eight weeks of treatment with long-acting GLP-1 analog taspoglutide improves postprandial insulin secretion and sensitivity in metformin-treated patients with type 2 diabetes.	Metformin	127-136	glucagon like peptide 1 receptor	Homo sapiens	42-47
23891087-0	2013	Contributions of AMPK and p53 dependent signaling to radiation response in the presence of metformin.	Metformin	91-100	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	17-21
23891087-2	2013	Metformin activates AMPK that in turn can launch a p53-dependent metabolic checkpoint.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	20-24
23891087-4	2013	Since radiation-induced signaling also involves AMPK and p53, we investigated their importance in mediating responses to metformin and radiation.	Metformin	121-130	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	48-52
23891087-8	2013	Loss of AMPK sensitized cells to the anti-proliferative effects of metformin, while loss of p53 promoted both the growth inhibitory and toxic effects of metformin.	Metformin	67-76	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	8-12
24180199-6	2013	Metformin may exert its anti-cancer activity by a direct effect (insulin) and an indirect effect (AMPK and mTOR).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	98-102
23707609-0	2013	Metformin inhibits heme oxygenase-1 expression in cancer cells through inactivation of Raf-ERK-Nrf2 signaling and AMPK-independent pathways.	Metformin	0-9	zinc fingers and homeoboxes 2	Homo sapiens	87-90
23707609-0	2013	Metformin inhibits heme oxygenase-1 expression in cancer cells through inactivation of Raf-ERK-Nrf2 signaling and AMPK-independent pathways.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	114-118
23707609-7	2013	We also found that metformin regulation of Nrf2 expression is mediated by a Keap1-independent mechanism and that metformin significantly attenuated Raf-ERK signaling to suppress Nrf2 expression in cancer cells.	Metformin	113-122	zinc fingers and homeoboxes 2	Homo sapiens	148-151
23707609-9	2013	The inactivation of AMPK by siRNA, DN-AMPK or the pharmacological AMPK inhibitor compound C, revealed that metformin reduced HO-1 expression in an AMPK-independent manner.	Metformin	107-116	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	20-24
23904524-10	2013	Metformin increased AMPK activation levels (p-AMPK/AMPK) by 2.0+-0.3-fold in A-ESCs, 2.3-fold in A-ESCs from the secretory phase, and 1.6-fold in the proliferation phase.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	20-24
23904524-10	2013	Metformin increased AMPK activation levels (p-AMPK/AMPK) by 2.0+-0.3-fold in A-ESCs, 2.3-fold in A-ESCs from the secretory phase, and 1.6-fold in the proliferation phase.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	46-50
23904524-10	2013	Metformin increased AMPK activation levels (p-AMPK/AMPK) by 2.0+-0.3-fold in A-ESCs, 2.3-fold in A-ESCs from the secretory phase, and 1.6-fold in the proliferation phase.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	46-50
23904524-13	2013	Compound C, a selective AMPK inhibitor, abolished the effects of metformin on cell growth and PI3K/AKT signaling.	Metformin	65-74	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	24-28
23904524-14	2013	Metformin inhibits cell growth via AMPK activation and subsequent inhibition of PI3K/AKT signaling in A-ESCs, particularly during the secretory phase, suggesting a greater effect of metformin on A-ESCs from secretory phase.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	35-39
23983487-3	2013	We report on a case of metformin-induced mixed hepatocellular and cholestatic liver injury in an elderly patient with DM-2 as well as review and summarize case reports of metformin hepatotoxicity available in English on the PubMed database.	Metformin	23-32	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	118-122
23983487-8	2013	CONCLUSION: Metformin is an important drug for the treatment of DM-2, which is also used for treatment of patients with fatty liver.	Metformin	12-21	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	64-68
23695170-5	2013	Treatment with metformin as single agent, however, induced an activation and phosphorylation of mitogen-activated protein kinase (MAPK) through an increased C-RAF/B-RAF heterodimerization.	Metformin	15-24	Raf-1 proto-oncogene, serine/threonine kinase	Homo sapiens	157-162
23695170-8	2013	However, further studies are required to investigate better the effect of metformin action on the RAS/RAF/MAPK pathway and the best context in which to use metformin in combination with molecular targeted agents.	Metformin	74-83	zinc fingers and homeoboxes 2	Homo sapiens	102-105
23808738-4	2013	In the case of pharmacotherapy there was confirmed efficiency of metformin, which could be used in states with high risk of DM2 conversion and some antihypertensive drugs, mainly sartans.	Metformin	65-74	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	124-127
23667692-0	2013	Low concentrations of metformin selectively inhibit CD133+ cell proliferation in pancreatic cancer and have anticancer action.	Metformin	22-31	prominin 1	Homo sapiens	52-57
23667692-6	2013	We examined the effect of low concentrations of metformin on different subpopulations of pancreatic cancer cells and found that these selectively inhibited the proliferation of CD133+ but not CD24+CD44+ESA+ cells.	Metformin	48-57	prominin 1	Homo sapiens	177-182
23557965-8	2013	RESULTS: Metformin attenuated both arthritis scores and bone destruction in CAIA mice, decreased the serum levels of the pro-inflammatory cytokines, TNF-alpha and IL-1, and reduced the number of RORgammat+CD4+ T cells in the ALNs.	Metformin	9-18	interleukin 1 complex	Mus musculus	163-167
23568147-6	2013	While metformin induces early and transient activation of AMPK, inhibition of AMPKalpha1/2 does not abrogate anti-proliferative or pro-apoptotic effects of metformin.	Metformin	6-15	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	58-62
24041694-3	2013	We found that metformin increased the expression and release of FGF21 in a diverse set of cell types, including rat hepatoma FaO, primary mouse hepatocytes, and mouse embryonic fibroblasts (MEFs).	Metformin	14-23	fibroblast growth factor 21	Rattus norvegicus	64-69
24041694-7	2013	We showed that metformin activated ATF4 and increased FGF21 expression in the livers of mice, which led to increased serum levels of FGF21.	Metformin	15-24	fibroblast growth factor 21	Mus musculus	54-59
24041694-7	2013	We showed that metformin activated ATF4 and increased FGF21 expression in the livers of mice, which led to increased serum levels of FGF21.	Metformin	15-24	fibroblast growth factor 21	Mus musculus	133-138
23942093-6	2013	To define the mechanisms of anticancer effects of metformin, we examined its influence on AMPK activation and NF-kappaB pathway.	Metformin	50-59	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	90-94
23942093-8	2013	Activation of AMPK by metformin not only inhibited HCC cells growth in vitro and in vivo, but also augmented cisplatin-induced growth inhibition in HCC cells.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	14-18
23942093-9	2013	Knockdown of AMPKalpha expression can greatly decrease the inhibitory effect of metformin, indicating that AMPK activation is required for the anticancer action of metformin.	Metformin	80-89	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	13-17
23942093-9	2013	Knockdown of AMPKalpha expression can greatly decrease the inhibitory effect of metformin, indicating that AMPK activation is required for the anticancer action of metformin.	Metformin	164-173	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	13-17
23942093-10	2013	Mechanistically, metformin/AMPK activation inhibited NF-kappaB signaling through upregulation of IkappaBalpha.	Metformin	17-26	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	27-31
23942093-11	2013	Activation of NF-kappaB signaling by ectopic expression of P65 or overexpression of an undegradable mutant form of IkappaBalpha attenuated the anticancer effects of metformin.	Metformin	165-174	RELA proto-oncogene, NF-kB subunit	Homo sapiens	59-62
23891087-10	2013	CONCLUSIONS: The anti-proliferative activity of metformin may confer benefit in combination with radiotherapy, and this benefit is intensified upon loss of AMPK or p53 signaling.	Metformin	48-57	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	156-160
23707609-9	2013	The inactivation of AMPK by siRNA, DN-AMPK or the pharmacological AMPK inhibitor compound C, revealed that metformin reduced HO-1 expression in an AMPK-independent manner.	Metformin	107-116	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	38-42
23707609-9	2013	The inactivation of AMPK by siRNA, DN-AMPK or the pharmacological AMPK inhibitor compound C, revealed that metformin reduced HO-1 expression in an AMPK-independent manner.	Metformin	107-116	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	38-42
23707609-9	2013	The inactivation of AMPK by siRNA, DN-AMPK or the pharmacological AMPK inhibitor compound C, revealed that metformin reduced HO-1 expression in an AMPK-independent manner.	Metformin	107-116	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	38-42
23707609-10	2013	These results highlight the Raf-ERK-Nrf2 axis as a new molecular target in anticancer therapy in response to metformin treatment.	Metformin	109-118	zinc fingers and homeoboxes 2	Homo sapiens	28-31
23759513-5	2013	Likewise, metformin attenuated inflammatory response and enhanced expressions of neurotrophic factors, thereby protecting OLs via AMPK activation in mixed glial cultures stimulated with lipopolysaccharide/interferon gamma in vitro, as evidenced by analysis of the expression of signatory genes of O1(+)/MBP(+) OLs and their cellular populations.	Metformin	10-19	myelin basic protein	Mus musculus	303-306
21864098-0	2013	Preparation and characterization of metformin hydrochloride loaded-Eudragit RSPO and Eudragit RSPO/PLGA nanoparticles.	Metformin	36-59	R-spondin 1	Homo sapiens	76-80
23238567-5	2013	Sesn2 is upregulated in response to an energetic stress such as 2-DG and metformin, and mediates the inhibition of mammalian target of rapamycin (mTOR), the major cellular regulator of energy metabolism.	Metformin	73-82	sestrin 2	Homo sapiens	0-5
23414799-4	2013	AMPK activators, such as metformin, that are used for diabetes treatment are also effective anticancer agents.	Metformin	25-34	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
23414799-6	2013	For example, metformin activates AMPK at millimolar levels.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	33-37
23066988-0	2013	Metformin directly inhibits ghrelin secretion through AMP-activated protein kinase in rat primary gastric cells.	Metformin	0-9	ghrelin and obestatin prepropeptide	Rattus norvegicus	28-35
23066988-2	2013	Metformin treatment is also associated with lower circulating levels of the orexigenic hormone ghrelin.	Metformin	0-9	ghrelin and obestatin prepropeptide	Rattus norvegicus	95-102
23066988-4	2013	Metformin significantly reduced ghrelin secretion and proghrelin mRNA production and both these effects were blocked by co-incubation with the AMPK inhibitor compound C. Furthermore, the AMPK activator 5-amino-1-beta-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) significantly inhibited ghrelin secretion.	Metformin	0-9	ghrelin and obestatin prepropeptide	Rattus norvegicus	32-39
23066988-4	2013	Metformin significantly reduced ghrelin secretion and proghrelin mRNA production and both these effects were blocked by co-incubation with the AMPK inhibitor compound C. Furthermore, the AMPK activator 5-amino-1-beta-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) significantly inhibited ghrelin secretion.	Metformin	0-9	ghrelin and obestatin prepropeptide	Rattus norvegicus	57-64
23066988-7	2013	Our results show that Metformin directly inhibits stomach ghrelin production and secretion through AMPK.	Metformin	22-31	ghrelin and obestatin prepropeptide	Rattus norvegicus	58-65
23066988-8	2013	This reduction in ghrelin secretion may be one of the key components in Metformin"s mechanism of weight loss.	Metformin	72-81	ghrelin and obestatin prepropeptide	Rattus norvegicus	18-25
22850868-0	2013	Metformin protects against lipoapoptosis and enhances GLP-1 secretion from GLP-1-producing cells.	Metformin	0-9	glucagon	Mus musculus	54-59
22850868-0	2013	Metformin protects against lipoapoptosis and enhances GLP-1 secretion from GLP-1-producing cells.	Metformin	0-9	glucagon	Mus musculus	75-80
22850868-3	2013	In addition, diabetic patients on metformin therapy have elevated levels of the insulinotropic hormone glucagon-like peptide-1 (GLP-1) and metformin has been shown to regulate the expression of the GLP-1R in the pancreas.	Metformin	34-43	glucagon like peptide 1 receptor	Homo sapiens	128-133
22850868-3	2013	In addition, diabetic patients on metformin therapy have elevated levels of the insulinotropic hormone glucagon-like peptide-1 (GLP-1) and metformin has been shown to regulate the expression of the GLP-1R in the pancreas.	Metformin	34-43	glucagon like peptide 1 receptor	Homo sapiens	198-204
22850868-3	2013	In addition, diabetic patients on metformin therapy have elevated levels of the insulinotropic hormone glucagon-like peptide-1 (GLP-1) and metformin has been shown to regulate the expression of the GLP-1R in the pancreas.	Metformin	139-148	glucagon like peptide 1 receptor	Homo sapiens	198-204
22850868-10	2013	In addition, long-term metformin treatment stimulated GLP-1 secretion.	Metformin	23-32	glucagon	Mus musculus	54-59
22850868-11	2013	CONCLUSION: This study demonstrates that metformin protects against lipoapoptosis (possibly by blocking JNK2 activation), and enhances GLP-1 secretion from GLP-1-producing cells in vitro.	Metformin	41-50	glucagon	Mus musculus	135-140
22850868-11	2013	CONCLUSION: This study demonstrates that metformin protects against lipoapoptosis (possibly by blocking JNK2 activation), and enhances GLP-1 secretion from GLP-1-producing cells in vitro.	Metformin	41-50	glucagon	Mus musculus	156-161
22850868-12	2013	These direct effects of the drug might explain the elevated plasma GLP-1 levels seen in diabetic patients on chronic metformin therapy.	Metformin	117-126	glucagon like peptide 1 receptor	Homo sapiens	67-72
23293026-12	2013	Expression of WWP1 blocked metformin-induced glucose uptake.	Metformin	27-36	WW domain containing E3 ubiquitin protein ligase 1	Mus musculus	14-18
23169238-7	2013	Metformin, a PRKAA agonist, inhibited HCV replication not only by activating PRKAA as previously reported, but also by activating AKT independently of the autophagy pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	13-18
23169238-7	2013	Metformin, a PRKAA agonist, inhibited HCV replication not only by activating PRKAA as previously reported, but also by activating AKT independently of the autophagy pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	77-82
23267855-4	2013	The renal and secretory clearances of metformin were higher (22% and 26%, respectively) in carriers of variant MATE2 who were also MATE1 reference (P &lt; 0.05).	Metformin	38-47	solute carrier family 47 member 2	Homo sapiens	111-116
23267855-5	2013	Both MATE genotypes were associated with altered post-metformin glucose tolerance, with variant carriers of MATE1 and MATE2 having an enhanced (P &lt; 0.01) and reduced (P &lt; 0.05) response, respectively.	Metformin	54-63	solute carrier family 47 member 2	Homo sapiens	118-123
23267855-7	2013	These findings suggest that promoter variants of MATE1 and MATE2 are important determinants of metformin disposition and response in healthy volunteers and diabetic patients.	Metformin	95-104	solute carrier family 47 member 2	Homo sapiens	59-64
24009856-5	2013	Metformin decreased both MHC class I and class II-restricted presentation of OVA and suppressed the expression of both MHC molecules and co-stimulatory factors such as CD54, CD80, and CD86 in DCs, but did not affect the phagocytic activity toward exogenous OVA.	Metformin	0-9	intercellular adhesion molecule 1	Mus musculus	168-172
23255107-6	2013	Interestingly, analyzing by FACS the antiproliferative effects of metformin on CD133-expressing subpopulation, a component of glioblastoma cancer stem cells, a higher reduction of proliferation was observed as compared with CD133-negative cells, suggesting a certain degree of cancer stem cell selectivity in its effects.	Metformin	66-75	prominin 1	Homo sapiens	79-84
23255107-6	2013	Interestingly, analyzing by FACS the antiproliferative effects of metformin on CD133-expressing subpopulation, a component of glioblastoma cancer stem cells, a higher reduction of proliferation was observed as compared with CD133-negative cells, suggesting a certain degree of cancer stem cell selectivity in its effects.	Metformin	66-75	prominin 1	Homo sapiens	224-229
23083540-0	2013	Metformin alters the insulin signaling pathway in ischemic cardiac tissue in a swine model of metabolic syndrome.	Metformin	0-9	insulin	Sus scrofa	21-28
23083540-1	2013	OBJECTIVE: The purpose of this study is to evaluate the effect of metformin on insulin signaling in ischemic cardiac tissue in a swine model of metabolic syndrome.	Metformin	66-75	insulin	Sus scrofa	79-86
23083540-11	2013	CONCLUSIONS: Metformin treatment in the context of metabolic syndrome and myocardial ischemia dramatically upregulates the insulin signaling pathway in chronically ischemic myocardium, which is at the crossroads of known metabolic and survival benefits of metformin.	Metformin	13-22	insulin	Sus scrofa	123-130
23083540-11	2013	CONCLUSIONS: Metformin treatment in the context of metabolic syndrome and myocardial ischemia dramatically upregulates the insulin signaling pathway in chronically ischemic myocardium, which is at the crossroads of known metabolic and survival benefits of metformin.	Metformin	256-265	insulin	Sus scrofa	123-130
23879009-13	2013	Metformin has antiproliferative properties; reduces the VEGF levels, causing a reduction in tumor vasculature; causes an increase in progesterone receptor, which increases the response to hormonal therapy; inhibits the expression of glyoxalase I, mediating resistance to chemotherapy; decreases in the concentration of human telomerase; reduces the activity of Akt and Erk kinases, key regulators of metabolism and progression of tumors and also inhibits the formation of metastases.	Metformin	0-9	progesterone receptor	Homo sapiens	133-154
23135276-7	2012	Long term treatment with metformin stimulated phosphorylation of c-Jun N-terminal kinase (JNK) and its downstream molecule c-Jun, which is a critical molecule for CAP transcription.	Metformin	25-34	jun proto-oncogene	Mus musculus	65-70
23151022-11	2012	Metformin treatment led to a remarkable decrease of cyclin D1, cyclin-dependent kinase (CDK) 4 and CDK6 protein levels and phosphorylation of retinoblastoma protein, but did not affect p21 or p27 protein expression in OSCC cells.	Metformin	0-9	cyclin D1	Homo sapiens	52-61
23151022-11	2012	Metformin treatment led to a remarkable decrease of cyclin D1, cyclin-dependent kinase (CDK) 4 and CDK6 protein levels and phosphorylation of retinoblastoma protein, but did not affect p21 or p27 protein expression in OSCC cells.	Metformin	0-9	cyclin dependent kinase 4	Homo sapiens	63-94
23151022-13	2012	Metformin also markedly reduced the expression of cyclin D1 and increased the numbers of apoptotic cells in vivo, thus inhibiting the growth of OSCC xenografts.	Metformin	0-9	cyclin D1	Homo sapiens	50-59
22982676-12	2012	Pre-incubation of palmitate with metformin further increased palmitate induced ROS production, while significantly reducing the expression of p38.	Metformin	33-42	mitogen-activated protein kinase 14	Mus musculus	142-145
22982676-15	2012	However, metformin significantly decreases the expression of p38, indicating that metformin mediated lipoprotection involves reduced activity of the p38 signaling pathway.	Metformin	9-18	mitogen-activated protein kinase 14	Mus musculus	61-64
22982676-15	2012	However, metformin significantly decreases the expression of p38, indicating that metformin mediated lipoprotection involves reduced activity of the p38 signaling pathway.	Metformin	9-18	mitogen-activated protein kinase 14	Mus musculus	149-152
22982676-15	2012	However, metformin significantly decreases the expression of p38, indicating that metformin mediated lipoprotection involves reduced activity of the p38 signaling pathway.	Metformin	82-91	mitogen-activated protein kinase 14	Mus musculus	61-64
22982676-15	2012	However, metformin significantly decreases the expression of p38, indicating that metformin mediated lipoprotection involves reduced activity of the p38 signaling pathway.	Metformin	82-91	mitogen-activated protein kinase 14	Mus musculus	149-152
23960811-6	2012	The elevated levels of serum SGOT, SGPT, ALP, AFP, TC and TG were restored by administration of Metformin in reduced dose (125 mg/kg) daily for 16 weeks p.o.	Metformin	96-105	alpha-fetoprotein	Rattus norvegicus	46-49
23747347-4	2013	Pharmacological activation of AMPK by metformin or other compounds holds a considerable potential to reverse the metabolic abnormalities associated with type 2 diabetes.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	30-34
23753040-5	2013	Multivariate Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for associations between prediagnostic metformin exposure (versus nonmetformin antidiabetic drugs) and colorectal cancer-specific mortality.	Metformin	142-151	cytochrome c oxidase subunit 8A	Homo sapiens	13-16
23771523-0	2013	Inhibition of lung tumorigenesis by metformin is associated with decreased plasma IGF-I and diminished receptor tyrosine kinase signaling.	Metformin	36-45	insulin-like growth factor 1	Mus musculus	82-87
22564403-10	2012	Metformin increased the gene expression of raptor, a component of mTORC1 and known to control protein synthesis, and such increase was also eliminated by compound C. Taken together, metformin preconditioning activates multiple signaling pathways involved in gene expression and protein synthesis.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	66-72
22564403-10	2012	Metformin increased the gene expression of raptor, a component of mTORC1 and known to control protein synthesis, and such increase was also eliminated by compound C. Taken together, metformin preconditioning activates multiple signaling pathways involved in gene expression and protein synthesis.	Metformin	182-191	CREB regulated transcription coactivator 1	Mus musculus	66-72
22561086-7	2012	Moreover, we show that the effect of metformin on Txnip gene transcription is due to the inhibition of mitochondrial complex I and increased glycolysis, and is partially mediated by the AMP activated kinase (AMPK).	Metformin	37-46	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	186-206
22561086-7	2012	Moreover, we show that the effect of metformin on Txnip gene transcription is due to the inhibition of mitochondrial complex I and increased glycolysis, and is partially mediated by the AMP activated kinase (AMPK).	Metformin	37-46	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	208-212
22329512-9	2012	The mRNA expressions of Bcl-2 and PDX-1 in pancreas were up-regulated, but Bax, iNOS and Casp-3 down-regulated in Gl- PS and metformin groups compared to diabetic control group.	Metformin	125-134	caspase 3	Rattus norvegicus	89-95
23771523-2	2013	Previously, we showed that metformin prevented tobacco carcinogen (NNK)-induced lung tumorigenesis in a non-diabetic mouse model, which was associated with decreased IGF-I/insulin receptor signaling but not activation of AMPK in lung tissues, as well as decreased circulating levels of IGF-I and insulin.	Metformin	27-36	insulin-like growth factor 1	Mus musculus	166-171
23771523-2	2013	Previously, we showed that metformin prevented tobacco carcinogen (NNK)-induced lung tumorigenesis in a non-diabetic mouse model, which was associated with decreased IGF-I/insulin receptor signaling but not activation of AMPK in lung tissues, as well as decreased circulating levels of IGF-I and insulin.	Metformin	27-36	insulin-like growth factor 1	Mus musculus	286-291
23771523-5	2013	Metformin further decreased lung tumorigenesis in LID mice without affecting IGF-I levels, suggesting that metformin can act through IGF-I-independent mechanisms.	Metformin	107-116	insulin-like growth factor 1	Mus musculus	133-138
23819460-5	2013	METHODS: Effect of the activation of AMPK on FOXM1 expression was examined by hypoxia and glucose deprivation, as well as pharmacological AMPK activators such as A23187, AICAR and metformin.	Metformin	180-189	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	37-41
23819460-7	2013	RESULTS: Consistent with our previous findings, the activation of AMPK by either AMPK activators such as AICAR, A23187, metformin, glucose deprivation or hypoxia significantly inhibited the cervical cancer cell growth.	Metformin	120-129	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	66-70
23819460-7	2013	RESULTS: Consistent with our previous findings, the activation of AMPK by either AMPK activators such as AICAR, A23187, metformin, glucose deprivation or hypoxia significantly inhibited the cervical cancer cell growth.	Metformin	120-129	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	81-85
23500454-9	2013	Treatment with the insulin-sensitizing drug metformin attenuated estrogen-dependent proliferative expression of c-myc and c-fos in the obese rat endometrium compared to untreated controls and was accompanied by inhibition of phosphorylation of the insulin and IGF1 receptors (IRbeta/IGF1R) and ERK1/2.	Metformin	44-53	MYC proto-oncogene, bHLH transcription factor	Rattus norvegicus	112-117
23500454-9	2013	Treatment with the insulin-sensitizing drug metformin attenuated estrogen-dependent proliferative expression of c-myc and c-fos in the obese rat endometrium compared to untreated controls and was accompanied by inhibition of phosphorylation of the insulin and IGF1 receptors (IRbeta/IGF1R) and ERK1/2.	Metformin	44-53	insulin-like growth factor 1 receptor	Rattus norvegicus	283-288
23500454-9	2013	Treatment with the insulin-sensitizing drug metformin attenuated estrogen-dependent proliferative expression of c-myc and c-fos in the obese rat endometrium compared to untreated controls and was accompanied by inhibition of phosphorylation of the insulin and IGF1 receptors (IRbeta/IGF1R) and ERK1/2.	Metformin	44-53	mitogen activated protein kinase 3	Rattus norvegicus	294-300
23652408-0	2013	Functional characterization of MATE2-K genetic variants and their effects on metformin pharmacokinetics.	Metformin	77-86	solute carrier family 47 member 2	Homo sapiens	31-38
23652408-1	2013	OBJECTIVE: Human multidrug and toxin extrusion member 2 (MATE2-K, SLC47A2) plays an important role in the renal elimination of various clinical drugs including the antidiabetic drug metformin.	Metformin	182-191	solute carrier family 47 member 2	Homo sapiens	57-64
23652408-1	2013	OBJECTIVE: Human multidrug and toxin extrusion member 2 (MATE2-K, SLC47A2) plays an important role in the renal elimination of various clinical drugs including the antidiabetic drug metformin.	Metformin	182-191	solute carrier family 47 member 2	Homo sapiens	66-73
23652408-2	2013	The goal of this study was to characterize genetic variants of MATE2-K and determine their association with the pharmacokinetics of metformin.	Metformin	132-141	solute carrier family 47 member 2	Homo sapiens	63-70
23652408-4	2013	Then, the metformin pharmacokinetic study was carried out to determine the association between MATE2-K promoter haplotypes and metformin pharmacokinetics.	Metformin	127-136	solute carrier family 47 member 2	Homo sapiens	95-102
23652408-8	2013	CONCLUSION: Our study suggests that common promoter haplotypes of MATE2-K are associated with the pharmacokinetics of metformin.	Metformin	118-127	solute carrier family 47 member 2	Homo sapiens	66-73
23620395-6	2013	In addition, we treated Ins2(+/Akita) mice with metformin, which activates AMP-activated protein kinase (AMPK) and thereby slows the degradation of GTPCH I; despite blood glucose levels that were similar to untreated mice, those treated with metformin had significantly less albuminuria.	Metformin	48-57	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	105-109
22694351-3	2012	Because metformin, an AMPK activator that is a favored first-line therapeutic option for type 2 diabetes, may confer benefits in chronic inflammatory diseases and cancers independent of its ability to normalize blood glucose, there is now considerable interest in identifying and exploiting AMPK"s anti-inflammatory effects.	Metformin	8-17	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	22-26
22608319-9	2012	Treatment with metformin inhibited insulin-induced activation of Erk1/2 and S6K1.	Metformin	15-24	mitogen activated protein kinase 3	Rattus norvegicus	65-71
22686561-6	2012	Moreover, metformin effectively inhibited mammalian target of rapamycin complex 1 (mTORC1)-controlled oncogenetic protein translation, which does not occur with allosteric mTORC1 inhibitors, such as rapamycin and its derivatives.	Metformin	10-19	CREB regulated transcription coactivator 1	Mus musculus	83-89
22913889-7	2012	With metformin plus colesevelam versus metformin plus placebo, more patients achieved an HbA1c of &lt; 7.0% (75% vs 56%) and LDL-C of &lt; 100 mg/dL (49% vs 14%; both P &lt; 0.05).	Metformin	5-14	hemoglobin subunit alpha 1	Homo sapiens	89-93
22913889-7	2012	With metformin plus colesevelam versus metformin plus placebo, more patients achieved an HbA1c of &lt; 7.0% (75% vs 56%) and LDL-C of &lt; 100 mg/dL (49% vs 14%; both P &lt; 0.05).	Metformin	39-48	hemoglobin subunit alpha 1	Homo sapiens	89-93
22562515-9	2012	Metformin also prevented the expression of Cox-2 and phosphorylation of p65, and increased the activation of AMPK in the ciliary bodies and retinal tissues.	Metformin	0-9	cytochrome c oxidase II, mitochondrial	Rattus norvegicus	43-48
22562515-10	2012	Moreover, metformin prevented the expression of Cox-2, iNOS, and activation of NF-kB in the HNPECs and decreased the levels of NO and PGE2 in cell culture media.	Metformin	10-19	cytochrome c oxidase II, mitochondrial	Rattus norvegicus	48-53
23620395-6	2013	In addition, we treated Ins2(+/Akita) mice with metformin, which activates AMP-activated protein kinase (AMPK) and thereby slows the degradation of GTPCH I; despite blood glucose levels that were similar to untreated mice, those treated with metformin had significantly less albuminuria.	Metformin	242-251	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	105-109
23632475-0	2013	Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	112-116
23632475-4	2013	Metformin (i) activated the ataxia telengiectasia-mutated (ATM)-AMPK-p53/p21(cip1) and inhibited the Akt-mammalian target of rapamycin (mTOR)-eIF4E-binding protein 1 (4EBP1) pathways, (ii) induced G1 cycle arrest and (iii) enhanced apoptosis.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	64-68
23632475-10	2013	Metformin and IR mediate their action through an ATM-AMPK-dependent pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	53-57
23228442-2	2013	Recent studies suggest that metformin attenuates mTORC1 signalling by the activation of 5" adenosine monophosphate-activated protein kinase (AMPK) in the presence or absence of a functional hamartin/tuberin (TSC1/TSC2) complex.	Metformin	28-37	CREB regulated transcription coactivator 1	Mus musculus	49-55
23228442-2	2013	Recent studies suggest that metformin attenuates mTORC1 signalling by the activation of 5" adenosine monophosphate-activated protein kinase (AMPK) in the presence or absence of a functional hamartin/tuberin (TSC1/TSC2) complex.	Metformin	28-37	TSC complex subunit 1	Mus musculus	208-212
23228442-3	2013	Metformin has also been reported to inhibit mTORC1 independent of AMPK through p53-dependent regulated in development and DNA damage responses 1 (REDD1) or by inhibiting Rag GTPases.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	44-50
23228442-4	2013	These observations suggest that metformin could have therapeutic potential for tuberous sclerosis, an inherited disorder characterised by the aberrant activation of mTORC1 and the development of tumours in many organs, including the kidneys.	Metformin	32-41	CREB regulated transcription coactivator 1	Mus musculus	165-171
23228442-7	2013	Metformin treatment appeared to attenuate mTORC1 signalling in Tsc1(+/-) kidney tissues but not in renal tumours.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	42-48
23228442-7	2013	Metformin treatment appeared to attenuate mTORC1 signalling in Tsc1(+/-) kidney tissues but not in renal tumours.	Metformin	0-9	TSC complex subunit 1	Mus musculus	63-67
23228442-8	2013	Surprisingly, the expression of the organic cation transporters Slc22a1, Slc22a2 and Slc22a3 essential for the cellular uptake of metformin was highly suppressed in renal tumours.	Metformin	130-139	solute carrier family 22 (organic cation transporter), member 2	Mus musculus	73-80
23228442-10	2013	These data suggest that the epigenetic suppression of the organic cation transporters in Tsc-associated mouse renal tumours may contribute to the lack of response to metformin treatment.	Metformin	166-175	TSC complex subunit 1	Mus musculus	89-92
22773548-9	2013	Cell line studies showed that metformin inhibits hepatocyte proliferation and induces cell cycle arrest at G0/G1 phase via AMP-activated protein kinase and its upstream kinase LKB1 to upregulate p21/Cip1 and p27/Kip1 and downregulate cyclin D1 in a dose-dependent manner, but independent of p53.	Metformin	30-39	cyclin D1	Homo sapiens	234-243
23497197-13	2013	CONCLUSIONS: An antidiabetic treatment with either insulin or metformin in ZDF rats inhibits the development of hypoadiponectinemia and downregulation of APPL1 in mesenteric resistance arteries, but is not able to improve adiponectin induced vasodilation and endothelial dysfunction.	Metformin	62-71	adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1	Rattus norvegicus	154-159
22758368-4	2012	Adenosine monophosphate kinase (AMPK) agonists such as metformin, which inhibits gluconeogenesis by downregulating expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, might be expected to block the glucose dysmetabolism mediated by rapamycin.	Metformin	55-64	glucose-6-phosphatase catalytic subunit 1	Homo sapiens	129-150
22245693-7	2012	Metformin up-regulated the expression of miR-26a, miR-192 and let-7c in a dose-dependent manner.	Metformin	0-9	microRNA 26a-1	Homo sapiens	41-48
22416982-6	2012	After the simultaneous single intravenous administration of both drugs together, the AUCs of each drug were significantly greater than that in each drug alone due to the competitive inhibition for the metabolism of nifedipine by metformin via hepatic CYP3A1/2 and of metformin by nifedipine via hepatic CYP2C6 and 3A1/2.	Metformin	229-238	cytochrome P450, family 3, subfamily a, polypeptide 23-polypeptide 1	Rattus norvegicus	251-257
22416982-7	2012	After the simultaneous single oral administration of both drugs, the significantly greater AUCs of each drug than that in each drug alone could have mainly been due to the competitive inhibition for the metabolism of nifedipine and metformin by each other via intestinal CYP3A1/2 in addition to competitive inhibition for the hepatic metabolism of each drug as same as the intravenous study.	Metformin	232-241	cytochrome P450, family 3, subfamily a, polypeptide 23-polypeptide 1	Rattus norvegicus	271-277
22467081-3	2012	Here, we asked whether metformin, the most widely used medication for the treatment of type II diabetes, which acts in part by stimulating the AMP-activated protein kinase (AMPK) signaling pathway thereby reducing mTORC1 activity, may lower the risk of HNSCC development.	Metformin	23-32	CREB regulated transcription coactivator 1	Mus musculus	214-220
22467081-4	2012	Indeed, we show that metformin reduces the growth of HNSCC cells and diminishes their mTORC1 activity by both AMPK-dependent and -independent mechanisms.	Metformin	21-30	CREB regulated transcription coactivator 1	Mus musculus	86-92
22467081-6	2012	Using this mouse model, we observed that metformin specifically inhibits mTORC1 in the basal proliferating epithelial layer of oral premalignant lesions.	Metformin	41-50	CREB regulated transcription coactivator 1	Mus musculus	73-79
22421144-8	2012	Mechanistically, metformin caused G 1 arrest, which coincided with a decrease in the protein levels of CDKs (2, 4 and 6), cyclins (D1 and E) and CDK inhibitors (p15, p16, p18 and p27), but no change in p19 and p21.	Metformin	17-26	leiomodin 1	Homo sapiens	131-139
22421144-9	2012	Metformin also decreased the levels of oncogenic proteins Skp2 and beta-Trcp.	Metformin	0-9	S-phase kinase associated protein 2	Homo sapiens	58-62
22356767-0	2012	Metformin lowers the threshold for stress-induced senescence: a role for the microRNA-200 family and miR-205.	Metformin	0-9	microRNA 205	Homo sapiens	101-108
22356767-7	2012	Metformin-induced SIS in BJ-1 fibroblasts was accompanied by the striking activation of several microRNAs belonging to the miR-200s family (miR-200a, miR-141 and miR429) and miR-205, thus mimicking a recently described ability of ROS to chemosensitize cancer cells by specifically upregulating anti-EMT (epithelial-to-mesenchymal transition) miR-200s.	Metformin	0-9	microRNA 205	Homo sapiens	174-181
22086681-5	2012	Metformin also decreased the expression of CSC markers,CD44, EpCAM,EZH2, Notch-1, Nanog and Oct4, and caused reexpression of miRNAs (let-7a,let-7b, miR-26a, miR-101, miR-200b, and miR-200c) that are typically lost in pancreatic cancer and especially in pancreatospheres.	Metformin	0-9	microRNA 26a-1	Homo sapiens	148-155
22086681-5	2012	Metformin also decreased the expression of CSC markers,CD44, EpCAM,EZH2, Notch-1, Nanog and Oct4, and caused reexpression of miRNAs (let-7a,let-7b, miR-26a, miR-101, miR-200b, and miR-200c) that are typically lost in pancreatic cancer and especially in pancreatospheres.	Metformin	0-9	microRNA 200c	Homo sapiens	180-188
21567395-6	2012	Pharmacological activation of AMPK by treatment with 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), metformin, or adiponectin lowered TGF-beta-induced expression of COL1A and myofibroblast marker alpha-smooth muscle actin (alpha-SMA).	Metformin	117-126	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	30-34
22048751-5	2012	The hypothesis was disproved, as we have shown that insulin and metformin, like insulin, directly stimulate NO production by endothelium of a conduit artery; this function may be of value in delaying the atherothrombotic process.	Metformin	64-73	insulin	Sus scrofa	80-87
22129484-0	2012	Metformin may antagonize Lin28 and/or Lin28B activity, thereby boosting let-7 levels and antagonizing cancer progression.	Metformin	0-9	lin-28 homolog B	Mus musculus	38-44
22861817-1	2013	BACKGROUND: Recent evidence indicates that metformin, a biguanide used as first-line treatment for type 2 diabetes, prevents the conversion of carcinogen-induced oral dysplasias into head and neck squamous cell carcinomas (HNSCC), most likely by inhibiting mammalian target of rapamycin complex 1 (mTORC1) oncogenic signaling.	Metformin	43-52	CREB regulated transcription coactivator 1	Mus musculus	298-304
22766107-1	2013	Pharmacological activation of AMP activated kinase (AMPK) by metformin has proven to be a beneficial therapeutic approach for the treatment of type II diabetes.	Metformin	61-70	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	30-50
22129484-6	2012	The transcription of Lin28B is promoted by NF-kappaB and by Myc; hence, practical measures which antagonize NF-kappaB or Myc activity may complement the utility of metformin for boosting let-7 expression and controlling cancer stemness; salsalate, antioxidants, tyrosine kinase and cox-2 inhibitors, ribavirin, vitamin D, gamma-secretase inhibitors (when available), and parenteral curcumin may have some utility in this regard.	Metformin	164-173	lin-28 homolog B	Mus musculus	21-27
22189713-3	2012	Because TN cells are particularly sensitive to the anti-diabetic agent metformin, we hypothesized that it may target JAK2/Stat3 signaling.	Metformin	71-80	Janus kinase 2	Homo sapiens	117-121
22994747-3	2012	Our research indicates that metformin displays anticancer activity against HCC through inhibition of the mTOR translational pathway in an AMPK-independent manner, leading to G1 arrest in the cell-cycle and subsequent cell apoptosis through the mitochondrion-dependent pathway.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	138-142
23118742-2	2012	Metabolic status plays an important role in the regulation of FGF21, and we therefore examined whether metformin, an indirect AMPK-activator, regulates FGF21 expression in hepatocytes.	Metformin	103-112	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	126-130
23118742-3	2012	FGF21 mRNA and protein expression were determined after incubation of primary cultured rat and human hepatocytes with metformin for 24 hours.	Metformin	118-127	fibroblast growth factor 21	Rattus norvegicus	0-5
23118742-5	2012	A strong dose-dependent increase in FGF21 expression was observed in both rat and human hepatocytes treated with metformin.	Metformin	113-122	fibroblast growth factor 21	Rattus norvegicus	36-41
23118742-6	2012	This effect was blocked by addition of the AMPK-inhibitor Compound C. The study shows that metformin is a potent inducer of hepatic FGF21 expression and that the effect of metformin seems to be mediated through AMPK activation.	Metformin	91-100	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	43-47
23118742-6	2012	This effect was blocked by addition of the AMPK-inhibitor Compound C. The study shows that metformin is a potent inducer of hepatic FGF21 expression and that the effect of metformin seems to be mediated through AMPK activation.	Metformin	172-181	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	43-47
23118742-6	2012	This effect was blocked by addition of the AMPK-inhibitor Compound C. The study shows that metformin is a potent inducer of hepatic FGF21 expression and that the effect of metformin seems to be mediated through AMPK activation.	Metformin	172-181	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	211-215
21968881-4	2012	Here, we have explored the therapeutic potential of the anti-diabetic drug, metformin (an LKB1/AMPK activator), against both T-cell acute lymphoblastic leukemia (T-ALL) cell lines and primary samples from T-ALL patients displaying mTORC1 activation.	Metformin	76-85	CREB regulated transcription coactivator 1	Mus musculus	231-237
23108012-14	2012	Metformin also reduced the caspase 3-dependent apoptosis induced by albumin.	Metformin	0-9	caspase 3	Rattus norvegicus	27-36
22343549-0	2012	Intracerebroventricular administration of metformin inhibits ghrelin-induced Hypothalamic AMP-kinase signalling and food intake.	Metformin	42-51	ghrelin and obestatin prepropeptide	Rattus norvegicus	61-68
22343549-2	2012	The present study investigated the effects of intracerebroventricular administration of metformin on food intake and hypothalamic appetite-regulating signalling pathways induced by the orexigenic peptide ghrelin.	Metformin	88-97	ghrelin and obestatin prepropeptide	Rattus norvegicus	204-211
22343549-5	2012	RESULTS: Metformin suppressed the increase in food consumption induced by intracerebroventricular ghrelin in a dose-dependent manner.	Metformin	9-18	ghrelin and obestatin prepropeptide	Rattus norvegicus	98-105
22343549-8	2012	Metformin treatment blocked ghrelin-induced activation of hypothalamic AMPK/ACC/Raptor and restored mTOR activity without affecting S6K phosphorylation.	Metformin	0-9	ghrelin and obestatin prepropeptide	Rattus norvegicus	28-35
22343549-8	2012	Metformin treatment blocked ghrelin-induced activation of hypothalamic AMPK/ACC/Raptor and restored mTOR activity without affecting S6K phosphorylation.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	71-75
22343549-8	2012	Metformin treatment blocked ghrelin-induced activation of hypothalamic AMPK/ACC/Raptor and restored mTOR activity without affecting S6K phosphorylation.	Metformin	0-9	regulatory associated protein of MTOR complex 1	Homo sapiens	80-86
22343549-9	2012	Metformin also reduced food consumption induced by the AMPK activator AICAR while the ghrelin-triggered food intake was inhibited by the mTOR activator L-leucine.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	55-59
22343549-10	2012	CONCLUSION: Metformin could reduce food intake by preventing ghrelin-induced AMPK signalling and mTOR inhibition in the hypotalamus.	Metformin	12-21	ghrelin and obestatin prepropeptide	Rattus norvegicus	61-68
22343549-10	2012	CONCLUSION: Metformin could reduce food intake by preventing ghrelin-induced AMPK signalling and mTOR inhibition in the hypotalamus.	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	77-81
21849490-7	2011	In MDCK cells in which AMPK expression was stably knocked down with short hairpin RNA, preactivation of AMPK with metformin did not prevent Na-K-ATPase redistribution in response to energy depletion.	Metformin	114-123	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	104-108
21849490-8	2011	In vivo studies demonstrate that metformin activated renal AMPK and that treatment with metformin before renal ischemia preserved cellular integrity, preserved Na-K-ATPase localization, and led to reduced levels of neutrophil gelatinase-associated lipocalin, a biomarker of tubular injury.	Metformin	33-42	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	59-63
21849490-8	2011	In vivo studies demonstrate that metformin activated renal AMPK and that treatment with metformin before renal ischemia preserved cellular integrity, preserved Na-K-ATPase localization, and led to reduced levels of neutrophil gelatinase-associated lipocalin, a biomarker of tubular injury.	Metformin	88-97	lipocalin 2	Canis lupus familiaris	215-257
22766107-1	2013	Pharmacological activation of AMP activated kinase (AMPK) by metformin has proven to be a beneficial therapeutic approach for the treatment of type II diabetes.	Metformin	61-70	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	52-56
23228696-8	2013	Finally, expression of constitutive activate MKK6 or HA-p38 MAPK vectors in lung cancer cells was able to abrogate ERCC1 downregulation by metformin and paclitaxel as well as cell viability and DNA repair capacity.	Metformin	139-148	reticulon 3	Homo sapiens	53-57
23192487-6	2013	In contrast with the diabetic non-treated hearts, the diabetic hearts treated with metformin showed more organized and elongated mitochondria and demonstrated a significant increase in phosphorylated AMPK and in PGC-1alpha expression.	Metformin	83-92	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	200-204
23229592-10	2013	Metformin inhibited the growth of three ESCC cell lines, and this inhibition may have involved reductions in cyclin D1, Cdk4 and Cdk6.	Metformin	0-9	cyclin D1	Homo sapiens	109-118
23229592-10	2013	Metformin inhibited the growth of three ESCC cell lines, and this inhibition may have involved reductions in cyclin D1, Cdk4 and Cdk6.	Metformin	0-9	cyclin dependent kinase 4	Homo sapiens	120-124
23376854-1	2013	UNLABELLED: Over the last several years, epidemiologic data have suggested that the antidiabetes drug metformin (MET), an adenosine monophosphate-activated protein kinase (AMPK) activator, improves progression-free survival of patients with multiple cancers; more than 30 clinical trials are under way to confirm this finding.	Metformin	102-111	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	122-170
21920351-2	2011	The pleotropic effects of metformin on glucose and lipid metabolism have been proposed to be mediated by the activation of AMP-activated protein kinase (AMPK) and the subsequent up-regulation of small heterodimer partner (SHP).	Metformin	26-35	nuclear receptor subfamily 0 group B member 2	Homo sapiens	222-225
21920351-4	2011	In this study, we hypothesize that metformin suppresses the expression of CYP3A4, a main detoxification enzyme and a target gene of PXR, due to SHP up-regulation.	Metformin	35-44	nuclear receptor subfamily 0 group B member 2	Homo sapiens	144-147
21920351-10	2011	We show that metformin disrupts PXR"s interaction with steroid receptor coactivator-1 (SRC1) in a two-hybrid assay independently of the PXR ligand binding pocket.	Metformin	13-22	nuclear receptor coactivator 1	Homo sapiens	55-85
21920351-10	2011	We show that metformin disrupts PXR"s interaction with steroid receptor coactivator-1 (SRC1) in a two-hybrid assay independently of the PXR ligand binding pocket.	Metformin	13-22	nuclear receptor coactivator 1	Homo sapiens	87-91
21933224-0	2011	Serine racemase rs391300 G/A polymorphism influences the therapeutic efficacy of metformin in Chinese patients with diabetes mellitus type 2.	Metformin	81-90	serine racemase	Homo sapiens	0-15
21933224-2	2011	The aim of this study was to investigate the association of the serine racemase (SRR) rs391300 G/A polymorphism with the risk of diabetes mellitus type 2 (T2DM) and to assess the impacts of the polymorphism on the therapeutic efficacy of metformin in Chinese patients.	Metformin	238-247	serine racemase	Homo sapiens	64-79
21947382-0	2011	Metformin activates AMP-activated protein kinase in primary human hepatocytes by decreasing cellular energy status.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	20-48
21947382-1	2011	AIM/HYPOTHESIS: The glucose-lowering drug metformin has been shown to activate hepatic AMP-activated protein kinase (AMPK), a master kinase regulating cellular energy homeostasis.	Metformin	42-51	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	87-115
21947382-1	2011	AIM/HYPOTHESIS: The glucose-lowering drug metformin has been shown to activate hepatic AMP-activated protein kinase (AMPK), a master kinase regulating cellular energy homeostasis.	Metformin	42-51	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	117-121
21947382-7	2011	Accordingly, metformin only increased AMPKalpha1 activity in human hepatocytes, although both AMPKalpha isoforms were activated in rat hepatocytes.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	38-48
21971158-3	2011	The antidiabetic drug, metformin, is known to increase circulating GLP-1 levels, although its mechanism of action is unknown.	Metformin	23-32	glucagon like peptide 1 receptor	Homo sapiens	67-72
21971158-6	2011	Treatment of rats with metformin (300 mg/kg, per os) or aminoimidazole carboxamide ribonucleotide (250 mg/kg, sc) increased plasma total GLP-1 over 2 h, reaching 37 +- 9 and 29 +- 9 pg/ml (P &lt; 0.001), respectively, compared with basal (7 +- 1 pg/ml).	Metformin	23-32	glucagon like peptide 1 receptor	Homo sapiens	137-142
21907790-2	2011	Metformin exerts cardioprotective actions via AMP-activated protein kinase (AMPK) and increases the expression of adiponectin and its receptors (adipoR1 and adipoR2) in skeletal muscle and adipose tissue, but its effect on cardiac tissue is still unknown.	Metformin	0-9	adiponectin receptor 2	Homo sapiens	157-164
21907790-8	2011	In addition, metformin up-regulated the expression of adiponectin and its receptors, adipoR1 and adipoR2, in cardiomyocytes.	Metformin	13-22	adiponectin receptor 2	Homo sapiens	97-104
21907790-9	2011	In contrast, silencing either adipoR1 or adipoR2 with siRNA inhibited the AMPK activation and the protective effects of metformin.	Metformin	120-129	adiponectin receptor 2	Homo sapiens	41-48
21956618-0	2011	A common 5"-UTR variant in MATE2-K is associated with poor response to metformin.	Metformin	71-80	solute carrier family 47 member 2	Homo sapiens	27-34
21956618-1	2011	Multidrug and toxin extrusion 2 (MATE2-K (SLC47A2)), a polyspecific organic cation exporter, facilitates the renal elimination of the antidiabetes drug metformin.	Metformin	152-161	solute carrier family 47 member 2	Homo sapiens	33-40
21956618-1	2011	Multidrug and toxin extrusion 2 (MATE2-K (SLC47A2)), a polyspecific organic cation exporter, facilitates the renal elimination of the antidiabetes drug metformin.	Metformin	152-161	solute carrier family 47 member 2	Homo sapiens	42-49
21956618-2	2011	In this study, we characterized genetic variants of MATE2-K, determined their association with metformin response, and elucidated their impact by means of a comparative protein structure model.	Metformin	95-104	solute carrier family 47 member 2	Homo sapiens	52-59
21956618-7	2011	Our study showed that MATE2-K plays a role in the antidiabetes response to metformin.	Metformin	75-84	solute carrier family 47 member 2	Homo sapiens	22-29
21725590-8	2011	Interestingly, when gC1qR was overexpressed in C-33A cells, apoptosis was significantly inhibited when cells were treated with metformin, which may protect mitochondrial function.	Metformin	127-136	complement C1q binding protein	Homo sapiens	20-25
21872612-4	2011	KEY FINDINGS: In the acute treatment study, TS-021 and/or metformin significantly improved glucose tolerance and glucagon-like peptide-1 (GLP-1) level, and TS-021 alone or in combination with metformin significantly increased the plasma insulin level after nutrient ingestion.	Metformin	58-67	glucagon	Mus musculus	113-136
21872612-4	2011	KEY FINDINGS: In the acute treatment study, TS-021 and/or metformin significantly improved glucose tolerance and glucagon-like peptide-1 (GLP-1) level, and TS-021 alone or in combination with metformin significantly increased the plasma insulin level after nutrient ingestion.	Metformin	58-67	glucagon	Mus musculus	138-143
21872612-7	2011	SIGNIFICANCE: The present study demonstrated that the coadministration of TS-021 and metformin synergistically improved the islet morphology by increasing the circulating level of biologically active GLP-1, which is thought to result from two different mechanisms (namely, an increase in GLP-1 secretion and DPP-IV inhibition).	Metformin	85-94	glucagon	Mus musculus	200-205
21872612-7	2011	SIGNIFICANCE: The present study demonstrated that the coadministration of TS-021 and metformin synergistically improved the islet morphology by increasing the circulating level of biologically active GLP-1, which is thought to result from two different mechanisms (namely, an increase in GLP-1 secretion and DPP-IV inhibition).	Metformin	85-94	glucagon	Mus musculus	288-293
21338323-6	2011	AMPKalpha1 is involved in metformin-induced HSL phosphorylation at Ser-552.	Metformin	26-35	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-10
23376854-1	2013	UNLABELLED: Over the last several years, epidemiologic data have suggested that the antidiabetes drug metformin (MET), an adenosine monophosphate-activated protein kinase (AMPK) activator, improves progression-free survival of patients with multiple cancers; more than 30 clinical trials are under way to confirm this finding.	Metformin	102-111	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	172-176
21676631-7	2013	Moreover, metformin down-regulated cyclin D1 expression and induced G0/G1 cell cycle arrest in these cells.	Metformin	10-19	cyclin D1	Homo sapiens	35-44
21676631-8	2013	Further study revealed metformin induced the activation of AMP-activated protein kinase (AMPK), and inhibited mammalian target of rapamycin (mTOR), which is a central regulator of protein synthesis and cell growth, and negatively regulated by AMPK.	Metformin	23-32	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	59-87
21676631-8	2013	Further study revealed metformin induced the activation of AMP-activated protein kinase (AMPK), and inhibited mammalian target of rapamycin (mTOR), which is a central regulator of protein synthesis and cell growth, and negatively regulated by AMPK.	Metformin	23-32	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	89-93
21676631-8	2013	Further study revealed metformin induced the activation of AMP-activated protein kinase (AMPK), and inhibited mammalian target of rapamycin (mTOR), which is a central regulator of protein synthesis and cell growth, and negatively regulated by AMPK.	Metformin	23-32	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	243-247
23287468-8	2013	The AMPK agonist metformin, which endows somatic cells with a bioenergetic infrastructure that is protected against reprogramming, was found to drastically elongate fibroblast mitochondria, fully reverse the high IF1/beta-F1-ATPase ratio and downregulate the ACACA/FASN lipogenic enzymes in iPS cells.	Metformin	17-26	ATP synthase inhibitory factor subunit 1	Homo sapiens	213-216
23159620-0	2013	Metformin inhibition of mTORC1 activation, DNA synthesis and proliferation in pancreatic cancer cells: dependence on glucose concentration and role of AMPK.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	24-30
23175691-0	2013	Metformin in obese children and adolescents: the MOCA trial.	Metformin	0-9	dedicator of cytokinesis 3	Homo sapiens	49-53
21618594-0	2011	Metformin stimulates osteoprotegerin and reduces RANKL expression in osteoblasts and ovariectomized rats.	Metformin	0-9	TNF superfamily member 11	Rattus norvegicus	49-54
21618594-7	2011	Most importantly, metformin significantly increased total body bone mineral density, prevented bone loss and decreased TRAP-positive cells in OVX rats proximal tibiae, accompanied with an increase of OPG and decrease of RANKL expression.	Metformin	18-27	TNF superfamily member 11	Rattus norvegicus	220-225
21618594-8	2011	These in vivo and in vitro studies suggest that metformin reduces RANKL and stimulates OPG expression in osteoblasts, further inhibits osteoclast differentiation and prevents bone loss in OVX rats.	Metformin	48-57	TNF superfamily member 11	Rattus norvegicus	66-71
21862237-0	2011	mTORC1 activity as a determinant of cancer risk--rationalizing the cancer-preventive effects of adiponectin, metformin, rapamycin, and low-protein vegan diets.	Metformin	109-118	CREB regulated transcription coactivator 1	Mus musculus	0-6
21862872-10	2011	Metformin disrupts erbB2/IGF-1R complexes, erbB3 and IGF-1R expression and activity, as well as Src kinase and/or PI-3K/Akt signaling.	Metformin	0-9	erb-b2 receptor tyrosine kinase 3	Homo sapiens	43-48
21775752-4	2011	Adjusting for patient characteristics, dose, and metformin use, Cox models yielded hazard ratios (HRs) for incident cancer (breast, prostate, pancreas, colon, any site) associated with three forms of insulin: nonglargine, glargine, or glargine plus nonglargine (combination).	Metformin	49-58	cytochrome c oxidase subunit 8A	Homo sapiens	64-67
21168492-0	2011	Metformin promotes progesterone receptor expression via inhibition of mammalian target of rapamycin (mTOR) in endometrial cancer cells.	Metformin	0-9	progesterone receptor	Homo sapiens	19-40
24082827-19	2013	CONCLUSION: Modification of lifestyle, such as diet and increased physical activity or use of metformin may improve glycemic regulation, reduce obesity and prevent or delay the onset of developing DM 2.	Metformin	94-103	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	197-201
24288442-0	2013	Metformin inhibits expression and secretion of PEDF in adipocyte and hepatocyte via promoting AMPK phosphorylation.	Metformin	0-9	serpin family F member 1	Rattus norvegicus	47-51
24288442-2	2013	The study aims to investigate the effect of metformin, a widely used agent to improve IR, on PEDF production both in vivo and in vitro.	Metformin	44-53	serpin family F member 1	Rattus norvegicus	93-97
24288442-7	2013	In vitro, the IR cells showed enhanced PEDF secretion and expression, whereas metformin lowered PEDF secretion and expression, accompanied with increased glucose uptake.	Metformin	78-87	serpin family F member 1	Rattus norvegicus	96-100
24288442-8	2013	Metformin stimulated AMPK phosphorylation in fat and liver of the obese rats, while in vitro, when combined with AMPK inhibitor, the effect of metformin on PEDF was abrogated.	Metformin	143-152	serpin family F member 1	Rattus norvegicus	156-160
24288442-9	2013	CONCLUSIONS: Metformin inhibits the expression and secretion of PEDF in fat and liver via promoting AMPK phosphorylation, which is closely associated with IR improvement.	Metformin	13-22	serpin family F member 1	Rattus norvegicus	64-68
23437362-8	2013	In contrast, metformin abolished mTORC1 activation without over-stimulating Akt phosphorylation on Ser(473) and prevented mitogen-stimulated ERK activation in PDAC cells.	Metformin	13-22	CREB regulated transcription coactivator 1	Mus musculus	33-39
23437362-10	2013	Thus, the effects of metformin on Akt and ERK activation are strikingly different from allosteric or active-site mTOR inhibitors in PDAC cells, though all these agents potently inhibited the mTORC1/S6K axis.	Metformin	21-30	CREB regulated transcription coactivator 1	Mus musculus	191-197
23525940-1	2012	The gerosuppressant metformin operates as an efficient inhibitor of the mTOR/S6K1 gerogenic pathway due to its ability to ultimately activate the energy-sensor AMPK.	Metformin	20-29	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	160-164
23525940-2	2012	If an aging-related decline in the AMPK sensitivity to cellular stress is a crucial event for mTOR-driven aging and aging-related diseases, including cancer, unraveling new proximal causes through which AMPK activation endows its gerosuppressive effects may offer not only a better understanding of metformin function but also the likely possibility of repositioning our existing gerosuppressant drugs.	Metformin	299-308	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	35-39
23525940-2	2012	If an aging-related decline in the AMPK sensitivity to cellular stress is a crucial event for mTOR-driven aging and aging-related diseases, including cancer, unraveling new proximal causes through which AMPK activation endows its gerosuppressive effects may offer not only a better understanding of metformin function but also the likely possibility of repositioning our existing gerosuppressant drugs.	Metformin	299-308	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	203-207
23141431-6	2012	Metformin with insulin significantly increased mRNA expressions of INSR, IGF-1R, and IRS-1, while metformin alone had no significant effect.	Metformin	0-9	insulin receptor	Homo sapiens	67-71
23141431-7	2012	And metformin with insulin had the significant effect on the protein activity (activation and phosphorylation) of downstream targets of INSR signaling pathway.	Metformin	4-13	insulin receptor	Homo sapiens	136-140
23041548-2	2012	Prior studies suggest that the primary action of metformin is inhibition of oxidative phosphorylation, resulting in reduced mitochondrial ATP production and activation of AMPK.	Metformin	49-58	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	171-175
23061989-6	2012	Regarding adipocytokines, sitagliptin + metformin better reduced RBP-4, visfatin and chemerin levels, compared to placebo + metformin.	Metformin	40-49	nicotinamide phosphoribosyltransferase	Homo sapiens	72-80
22968630-3	2012	Our data showed that the metformin pretreatment strikingly enhanced insulin-stimulated glucose uptake through increasing GLUT4 translocation to the PM in NYGGF4 overexpression adipocytes.	Metformin	25-34	solute carrier family 2 member 4	Homo sapiens	121-126
23653852-0	2012	Anti-angiogenic Effects of Metformin, an AMPK Activator, on Human Umbilical Vein Endothelial Cells and on Granulation Tissue in Rat.	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	41-45
23653852-1	2012	OBJECTIVES: Metformin is well known for activation of AMP-activated protein kinase (AMPK).	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	54-82
23653852-1	2012	OBJECTIVES: Metformin is well known for activation of AMP-activated protein kinase (AMPK).	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	84-88
23653852-11	2012	The inhibitory effects of metformin on the endothelial cell migration were reversed partially by compound C (P&lt;0.01), an inhibitor of AMPK.	Metformin	26-35	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	137-141
23653852-12	2012	CONCLUSION: The present study reported that metformin inhibited endothelial cell migration and angiogenesis in vitro and in vivo, and the effect was partially AMPK dependent.	Metformin	44-53	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	159-163
22982676-4	2012	These signaling events triggered by simulated hyperlipidemia may underlie reduced GLP-1 secretion in diabetic subjects, and metformin lipoprotection by metformin could explain elevated plasma GLP-1 levels in diabetic patients on chronic metformin therapy.	Metformin	124-133	glucagon like peptide 1 receptor	Homo sapiens	192-197
22583697-6	2012	RESULTS: After 12 weeks both dosages of alogliptin + metformin produced significantly greater changes from baseline in HbA1c than placebo (metformin monotherapy: with changes in LS means - 0.55 and - 0.64% vs. 0.22%, respectively; p &lt; 0.0001).	Metformin	53-62	hemoglobin subunit alpha 1	Homo sapiens	119-123
22659400-8	2012	These results indicate that inhibition of complex I by rotenone or metformin and displacement of cyclophilin D by cyclosporin A affect the PTP through a common mechanism; and that cells can modulate their PTP response to complex I inhibition by modifying the expression of cyclophilin D, a finding that has major implications for pore modulation in vivo.	Metformin	67-76	peptidylprolyl isomerase D	Homo sapiens	273-286
21811094-4	2011	Metformin abolished the diet-induced increases in serum insulin level, tumor insulin receptor activation and tumor FDG uptake associated with the high energy diet but had no effect on these measurements in mice on a control diet.	Metformin	0-9	insulin receptor	Mus musculus	77-93
21717584-1	2011	It has been reported that metformin, a biguanide derivative widely used in type II diabetic patients, has antitumor activities in some cancers by activation of AMP-activated protein kinase (AMPK).	Metformin	26-35	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	160-188
21717584-1	2011	It has been reported that metformin, a biguanide derivative widely used in type II diabetic patients, has antitumor activities in some cancers by activation of AMP-activated protein kinase (AMPK).	Metformin	26-35	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	190-194
21717584-4	2011	Further studies revealed that the protein level of cyclin D1 decreased and the percentage of the cells in G0/G1 phase increased by 5 mM metformin treatment.	Metformin	136-145	cyclin D1	Homo sapiens	51-60
21717584-5	2011	Metformin also induced the phosphorylation of AMPK (T172) in a time-dependent manner.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	46-50
21717584-6	2011	Mammalian target of rapamycin complex 1 (mTORC1), which is negatively regulated by AMPK and plays a central role in cell growth and proliferation, was inhibited by metformin, as manifested by dephosphorylation of its downstream targets 40S ribosomal S6 kinase 1 (S6K1) (T389), the eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) (T37/46) and S6 (S235/236) in C666-1 cells.	Metformin	164-173	CREB regulated transcription coactivator 1	Mus musculus	41-47
21717584-6	2011	Mammalian target of rapamycin complex 1 (mTORC1), which is negatively regulated by AMPK and plays a central role in cell growth and proliferation, was inhibited by metformin, as manifested by dephosphorylation of its downstream targets 40S ribosomal S6 kinase 1 (S6K1) (T389), the eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) (T37/46) and S6 (S235/236) in C666-1 cells.	Metformin	164-173	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	83-87
21717584-6	2011	Mammalian target of rapamycin complex 1 (mTORC1), which is negatively regulated by AMPK and plays a central role in cell growth and proliferation, was inhibited by metformin, as manifested by dephosphorylation of its downstream targets 40S ribosomal S6 kinase 1 (S6K1) (T389), the eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) (T37/46) and S6 (S235/236) in C666-1 cells.	Metformin	164-173	eukaryotic translation initiation factor 4E	Homo sapiens	281-324
21717584-7	2011	In a summary, metformin prevents proliferation of C666-1 cells by down-regulating cyclin D1 level and inducing G1 cell cycle arrest.	Metformin	14-23	cyclin D1	Homo sapiens	82-91
21851176-12	2011	The use of safer, but perhaps weaker, indirect mTORC1 inhibitors, such as metformin and resveratrol, may prove useful.	Metformin	74-83	CREB regulated transcription coactivator 1	Mus musculus	47-53
21540236-0	2011	Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	26-30
21455728-0	2011	AMP-activated protein kinase is activated in adipose tissue of individuals with type 2 diabetes treated with metformin: a randomised glycaemia-controlled crossover study.	Metformin	109-118	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-28
21455728-1	2011	AIMS/HYPOTHESIS: The hypoglycaemic actions of metformin have been proposed to be mediated by hepatic AMP-activated protein kinase (AMPK).	Metformin	46-55	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	101-129
21455728-1	2011	AIMS/HYPOTHESIS: The hypoglycaemic actions of metformin have been proposed to be mediated by hepatic AMP-activated protein kinase (AMPK).	Metformin	46-55	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	131-135
21455728-2	2011	As the effects of metformin and the role of AMPK in adipose tissue remain poorly characterised, we examined the effect of metformin on AMPK activity in adipose tissue of individuals with type 2 diabetes in a randomised glycaemia-controlled crossover study.	Metformin	122-131	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	135-139
21455728-8	2011	In parallel, the effect of metformin on AMPK and insulin-signalling pathways was investigated in 3T3-L1 adipocytes.	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	40-44
21455728-12	2011	Adipose AMPK activity was increased following metformin compared with gliclazide therapy (0.057 +- 0.007 vs 0.030 +- 0.005 [mean +- SEM] nmol min(-1) [mg lysate](-1); p &lt; 0.005), independent of AMPK level, glycaemia or plasma adiponectin concentrations.	Metformin	46-55	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	8-12
21455728-12	2011	Adipose AMPK activity was increased following metformin compared with gliclazide therapy (0.057 +- 0.007 vs 0.030 +- 0.005 [mean +- SEM] nmol min(-1) [mg lysate](-1); p &lt; 0.005), independent of AMPK level, glycaemia or plasma adiponectin concentrations.	Metformin	46-55	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	197-201
21455728-14	2011	In 3T3-L1 adipocytes, metformin reduced levels of ACC protein and stimulated phosphorylation of AMPK Thr172 and hormone-sensitive lipase Ser565.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	96-100
21455728-15	2011	CONCLUSIONS: These results provide the first evidence that metformin activates AMPK and reduces ACC protein levels in human adipose tissue in vivo.	Metformin	59-68	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	79-83
21455728-16	2011	Future studies are required to assess the role of adipose AMPK activation in the pharmacological effects of metformin.	Metformin	108-117	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	58-62
20965713-5	2011	A comparison of four AMPK activators (metformin, phenformin, TNF-alpha and t10c12 CLA) found a correlation between AMPK activity and triglyceride reduction.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	21-25
20965713-5	2011	A comparison of four AMPK activators (metformin, phenformin, TNF-alpha and t10c12 CLA) found a correlation between AMPK activity and triglyceride reduction.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	115-119
21501658-5	2011	Chemical activators of AMPK (AICAR [5-aminoimidazole-4-carboxamide riboside], metformin) suppressed Wnt3a-induced TCF-dependent transcriptional activity.	Metformin	78-87	Wnt family member 3A	Homo sapiens	100-105
21368105-5	2011	Suppression of mTORC2 signaling with siRNA rictor, or inhibition of mTORC1 signaling with rapamycin and metformin, while having little effect on other complex activities, inhibited VSM-H and chronic hypoxia-induced human and rat PAVSM cell proliferation.	Metformin	104-113	CREB regulated transcription coactivator 1	Mus musculus	68-74
21576264-8	2011	CPT1C depletion via siRNA suppresses xenograft tumor growth and metformin responsiveness in vivo.	Metformin	64-73	carnitine palmitoyltransferase 1C	Homo sapiens	0-5
22378745-0	2012	A novel inverse relationship between metformin-triggered AMPK-SIRT1 signaling and p53 protein abundance in high glucose-exposed HepG2 cells.	Metformin	37-46	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	57-61
22378745-5	2012	Metformin induced activation of AMPK and SIRT1 and decreased p53 protein abundance.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	32-36
22378745-7	2012	The decrease in p53 abundance caused by metformin was abolished by inhibition of murine double minute 2 (MDM2), a ubiquitin ligase that mediates p53 degradation, as well as by overexpression of a dominant-negative AMPK or a shRNA-mediated knockdown of SIRT1.	Metformin	40-49	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	214-218
22378745-8	2012	In addition, overexpression of p53 decreased SIRT1 gene expression and protein abundance, as well as AMPK activity in metformin-treated cells.	Metformin	118-127	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	101-105
22703658-0	2012	Protective effect of metformin on periapical lesions in rats by decreasing the ratio of receptor activator of nuclear factor kappa B ligand/osteoprotegerin.	Metformin	21-30	TNF superfamily member 11	Rattus norvegicus	88-139
22703658-7	2012	RESULTS: The number of RANKL-positive and tartrate-resistant acid phosphatase (TRAP)-positive cells in the metformin-treated groups decreased on day 14, whereas the number of OPG-positive cells increased on day 28.	Metformin	107-116	TNF superfamily member 11	Rattus norvegicus	23-28
22703658-9	2012	CONCLUSIONS: Metformin inhibits the periapical lesions possibly by lowering the RANKL/OPG ratio, subsequently reducing the number of osteoclasts and bone resorption areas.	Metformin	13-22	TNF superfamily member 11	Rattus norvegicus	80-85
22242910-0	2012	Loss of multidrug and toxin extrusion 1 (MATE1) is associated with metformin-induced lactic acidosis.	Metformin	67-76	solute carrier family 47, member 1	Mus musculus	8-39
22242910-0	2012	Loss of multidrug and toxin extrusion 1 (MATE1) is associated with metformin-induced lactic acidosis.	Metformin	67-76	solute carrier family 47, member 1	Mus musculus	41-46
22242910-3	2012	MATE1 was revealed to be responsible for the tubular and biliary secretion of metformin.	Metformin	78-87	solute carrier family 47, member 1	Mus musculus	0-5
22242910-9	2012	KEY RESULTS: Seven days after metformin administration in drinking water, significantly higher blood lactate, lower pH and HCO(3) (-) levels were observed in Mate1(-/-) mice, but not in Mate1(+/-) mice.	Metformin	30-39	solute carrier family 47, member 1	Mus musculus	158-163
22242910-12	2012	the hepatic concentration of metformin was markedly higher in Mate1(-/-) mice than in Mate1(+/+) mice.	Metformin	29-38	solute carrier family 47, member 1	Mus musculus	62-67
22242910-12	2012	the hepatic concentration of metformin was markedly higher in Mate1(-/-) mice than in Mate1(+/+) mice.	Metformin	29-38	solute carrier family 47, member 1	Mus musculus	86-91
22242910-13	2012	CONCLUSION AND IMPLICATIONS: MATE1 dysfunction caused a marked elevation in the metformin concentration in the liver and led to lactic acidosis, suggesting that the homozygous MATE1 variant could be one of the risk factors for metformin-induced lactic acidosis.	Metformin	80-89	solute carrier family 47, member 1	Mus musculus	29-34
22242910-13	2012	CONCLUSION AND IMPLICATIONS: MATE1 dysfunction caused a marked elevation in the metformin concentration in the liver and led to lactic acidosis, suggesting that the homozygous MATE1 variant could be one of the risk factors for metformin-induced lactic acidosis.	Metformin	80-89	solute carrier family 47, member 1	Mus musculus	176-181
22242910-13	2012	CONCLUSION AND IMPLICATIONS: MATE1 dysfunction caused a marked elevation in the metformin concentration in the liver and led to lactic acidosis, suggesting that the homozygous MATE1 variant could be one of the risk factors for metformin-induced lactic acidosis.	Metformin	227-236	solute carrier family 47, member 1	Mus musculus	29-34
22242910-13	2012	CONCLUSION AND IMPLICATIONS: MATE1 dysfunction caused a marked elevation in the metformin concentration in the liver and led to lactic acidosis, suggesting that the homozygous MATE1 variant could be one of the risk factors for metformin-induced lactic acidosis.	Metformin	227-236	solute carrier family 47, member 1	Mus musculus	176-181
22406476-12	2012	Aspirin and metformin (an activator of AMPK) increased inhibition of mTOR and Akt, as well as autophagy in CRC cells.	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	39-43
22493491-8	2012	Metformin inhibits PTP and improves IFNalpha response in insulin-resistant cells.	Metformin	0-9	protein tyrosine phosphatase receptor type U	Homo sapiens	19-22
22459208-3	2012	It has been reported that the anti-diabetic drug metformin and some natural compounds, such as quercetin, genistein, capsaicin and green tea polyphenol epigallocatechin gallate (EGCG), can activate AMPK and inhibit cancer cell growth.	Metformin	49-58	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	198-202
22246099-0	2012	Effect of metformin on the proliferation, migration, and MMP-2 and -9             expression of human umbilical vein endothelial cells.	Metformin	10-19	matrix metallopeptidase 2	Homo sapiens	57-69
22246099-9	2012	In addition, treatment with metformin demonstrated a strong (P&lt;0.001) suppressive effect on the mRNA levels of MMP-2 and -9 in the endothelial cells.	Metformin	28-37	matrix metallopeptidase 2	Homo sapiens	114-126
22246099-11	2012	The present study reports that metformin considerably inhibited the proliferation, migration, and MMP-2 and -9 expression of HUVECs, and the effect was partially AMPK-dependent.	Metformin	31-40	matrix metallopeptidase 2	Homo sapiens	98-110
22442749-9	2012	In contrast, the anti-diabetic drug metformin antagonizes leucine-mediated mTORC1 signaling.	Metformin	36-45	CREB regulated transcription coactivator 1	Mus musculus	75-81
22333578-3	2012	The indirect and direct activation of AMPK with the antidiabetic biguanide metformin and the thienopyridone A-769662, respectively, impeded the reprogramming of mouse embryonic and human diploid fibroblasts into iPSCs.	Metformin	75-84	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	38-42
22333578-5	2012	Treatment with metformin or A-769662 before the generation of iPSC colonies was sufficient to drastically decrease iPSC generation, suggesting that AMPK activation impedes early stem cell genetic reprogramming.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	148-152
22378068-3	2012	AMPK activator metformin potentially inhibited the growth of B- and T-lymphoma cells.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
22378068-5	2012	Metformin-induced AMPK activation was associated with the inhibition of the mTOR signaling without involving AKT.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	18-22
22378068-7	2012	Pharmacologic and molecular knock-down of AMPK attenuated metformin-mediated lymphoma cell growth inhibition and drug sensitization.	Metformin	58-67	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	42-46
22378068-8	2012	In vivo, metformin induced AMPK activation, mTOR inhibition and remarkably blocked tumor growth in murine lymphoma xenografts.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	27-31
22009334-8	2012	CS activity was comparable between metformin-treated and control participants, but tended to be lower in those receiving sulfonylureas.	Metformin	35-44	citrate synthase	Homo sapiens	0-2
21345512-1	2011	AIM: The combination of metformin and a dipeptidyl peptidase 4 (DPP-4) inhibitor has been shown to be an effective, safe, and well-tolerated treatment for type 2 diabetes.	Metformin	24-33	dipeptidylpeptidase 4	Rattus norvegicus	64-69
20857458-5	2011	Metformin stimulated the phosphorylation of AS160, Akt substrate, and Rab GTPase activating protein (GAP), and also increased the phosphorylation of PKC-zeta, which is a critical molecule for glucose uptake.	Metformin	0-9	TBC1 domain family, member 4	Mus musculus	44-49
20857458-6	2011	Knockdown of AMPK blocked the metformin-induced phosphorylation of AS160/PKC-zeta.	Metformin	30-39	TBC1 domain family, member 4	Mus musculus	67-72
20857458-11	2011	Together, these results demonstrate that metformin induces Rab4 expression via AMPK-AS160-PKC-zeta and modulates insulin-mediated GLUT4 translocation.	Metformin	41-50	TBC1 domain family, member 4	Mus musculus	84-89
21442684-10	2011	After correction for duration of follow-up, Cox regression analysis showed a hazard ratio of 0.84 for any modification in the metformin group compared to the sulfonylureas group.	Metformin	126-135	cytochrome c oxidase subunit 8A	Homo sapiens	44-47
21517658-9	2011	The current consensus statement of the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) cites efficacy and low risk of hypoglycemia in preferring GLP-1 agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors over sulfonylureas and glinides, after initial treatment with metformin.	Metformin	325-334	glucagon like peptide 1 receptor	Homo sapiens	202-207
21205107-8	2011	Vildagliptin"s therapeutic actions are primarily mediated by GLP-1 and metformin enhances vildagliptin"s effect to raise plasma levels of intact GLP-1.	Metformin	71-80	glucagon like peptide 1 receptor	Homo sapiens	145-150
21209024-0	2011	Phosphorylation and activation of AMP-activated protein kinase (AMPK) by metformin in the human ovary requires insulin.	Metformin	73-82	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	34-62
21209024-0	2011	Phosphorylation and activation of AMP-activated protein kinase (AMPK) by metformin in the human ovary requires insulin.	Metformin	73-82	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	64-68
21209024-4	2011	We investigated whether metformin activates AMPK in the human ovary by looking for changes in phosphorylation of AMPK and its downstream target acetyl CoA carboxylase (ACC).	Metformin	24-33	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	44-48
21209024-8	2011	The addition of compound C, an inhibitor of AMPK, negated the effect of metformin in the presence of insulin on pAMPK.	Metformin	72-81	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	44-48
21304820-6	2011	Animals fed the drug metformin, which induces a dietary-restriction like state in animals and activates AMPK in mammalian cell culture, have a higher survival rate when exposed to long-term anoxia.	Metformin	21-30	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	104-108
20980683-6	2011	In PRP, metformin (10 mM) reduced LH and follicle-stimulating hormone (FSH) secretion induced by GnRH (10(-8) M, 3 h), FSH secretion, and mRNA FSHbeta subunit expression induced by activin (10(-8) M, 12 or 24 h).	Metformin	8-17	follicle stimulating hormone subunit beta	Rattus norvegicus	143-150
20980683-10	2011	Metformin decreased activin-induced SMAD2 phosphorylation and GnRH-induced mitogen-activated protein kinase (MAPK) 3/1 (ERK1/2) phosphorylation.	Metformin	0-9	mitogen activated protein kinase 3	Rattus norvegicus	109-113
20980683-10	2011	Metformin decreased activin-induced SMAD2 phosphorylation and GnRH-induced mitogen-activated protein kinase (MAPK) 3/1 (ERK1/2) phosphorylation.	Metformin	0-9	mitogen activated protein kinase 3	Rattus norvegicus	120-126
20980683-12	2011	The adenovirus-mediated production of dominant negative PRKA abolished the effects of metformin on the FSHbeta subunit mRNA and SMAD2 phosphorylation induced by activin and on the MAPK3/1 phosphorylation induced by GnRH.	Metformin	86-95	follicle stimulating hormone subunit beta	Rattus norvegicus	103-110
20980683-13	2011	Thus, in rat pituitary cells, metformin decreases gonadotropin secretion and MAPK3/1 phosphorylation induced by GnRH and FSH release, FSHbeta subunit expression, and SMAD2 phosphorylation induced by activin through PRKA activation.	Metformin	30-39	mitogen activated protein kinase 3	Rattus norvegicus	77-82
20980683-13	2011	Thus, in rat pituitary cells, metformin decreases gonadotropin secretion and MAPK3/1 phosphorylation induced by GnRH and FSH release, FSHbeta subunit expression, and SMAD2 phosphorylation induced by activin through PRKA activation.	Metformin	30-39	follicle stimulating hormone subunit beta	Rattus norvegicus	134-141
21116606-0	2011	New aspects of an old drug: metformin as a glucagon-like peptide 1 (GLP-1) enhancer and sensitiser.	Metformin	28-37	glucagon	Mus musculus	43-66
21116606-0	2011	New aspects of an old drug: metformin as a glucagon-like peptide 1 (GLP-1) enhancer and sensitiser.	Metformin	28-37	glucagon	Mus musculus	68-73
21116606-4	2011	(doi: 10.1007/s00125-010-1937-z) report that metformin acutely increases plasma levels of glucagon-like peptide 1 (GLP-1) in mice.	Metformin	45-54	glucagon	Mus musculus	90-113
21116606-4	2011	(doi: 10.1007/s00125-010-1937-z) report that metformin acutely increases plasma levels of glucagon-like peptide 1 (GLP-1) in mice.	Metformin	45-54	glucagon	Mus musculus	115-120
21116606-5	2011	Moreover, they show that metformin enhances the expression of the genes encoding the receptors for both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in mouse islets and also increases the effects of GIP and GLP-1 on insulin secretion from beta cells.	Metformin	25-34	glucagon	Mus musculus	104-109
21116606-5	2011	Moreover, they show that metformin enhances the expression of the genes encoding the receptors for both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in mouse islets and also increases the effects of GIP and GLP-1 on insulin secretion from beta cells.	Metformin	25-34	glucagon	Mus musculus	223-228
21187071-3	2011	In addition, metformin induced the phosphorylation of Smad1/5/8 and expression of Dlx5 and Runx2, whereas compound C or dominant negative AMPK inhibited these effects.	Metformin	13-22	distal-less homeobox 5	Mus musculus	82-86
21187071-4	2011	Transient transfection studies also showed that metformin increased the BRE-Luc and Runx2-Luc activities, which were inhibited by DN-AMPK or compound C. Down-regulation of Dlx5 expression by siRNA suppressed metformin-induced Runx2 expression.	Metformin	48-57	distal-less homeobox 5	Mus musculus	172-176
21187071-4	2011	Transient transfection studies also showed that metformin increased the BRE-Luc and Runx2-Luc activities, which were inhibited by DN-AMPK or compound C. Down-regulation of Dlx5 expression by siRNA suppressed metformin-induced Runx2 expression.	Metformin	208-217	distal-less homeobox 5	Mus musculus	172-176
21114978-0	2011	Metformin reduces cisplatin-mediated apoptotic death of cancer cells through AMPK-independent activation of Akt.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	77-81
21114978-1	2011	Metformin is an antidiabetic drug with anticancer properties, which mainly acts through induction of AMP-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	101-129
21114978-1	2011	Metformin is an antidiabetic drug with anticancer properties, which mainly acts through induction of AMP-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	131-135
21114978-9	2011	In conclusion, the antidiabetic drug metformin reduces cisplatin in vitro anticancer activity through AMPK-independent upregulation of Akt survival pathway.	Metformin	37-46	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	102-106
21349801-5	2011	Moreover, by activating AMPK, metformin inhibits the mammalian target of rapamycin complex 1 (mTORC1) resulting in decreased cancer cell proliferation.	Metformin	30-39	CREB regulated transcription coactivator 1	Mus musculus	94-100
21931813-8	2011	The decrease in RLIP76 protein expression by rosiglitazone and metformin is associated with an up-regulation of PPARgamma and AMPK.	Metformin	63-72	peroxisome proliferator activated receptor gamma	Mus musculus	112-121
21098287-3	2010	Using murine primary neurons from wild-type and human tau transgenic mice, we show that the antidiabetic drug metformin induces PP2A activity and reduces tau phosphorylation at PP2A-dependent epitopes in vitro and in vivo.	Metformin	110-119	protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform	Mus musculus	128-132
21098287-3	2010	Using murine primary neurons from wild-type and human tau transgenic mice, we show that the antidiabetic drug metformin induces PP2A activity and reduces tau phosphorylation at PP2A-dependent epitopes in vitro and in vivo.	Metformin	110-119	protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform	Mus musculus	177-181
21098287-5	2010	Surprisingly, metformin effects on PP2A activity and tau phosphorylation seem to be independent of AMPK activation, because in our experiments (i) metformin induces PP2A activity before and at lower levels than AMPK activity and (ii) the AMPK activator AICAR does not influence the phosphorylation of tau at the sites analyzed.	Metformin	14-23	protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform	Mus musculus	35-39
21098287-5	2010	Surprisingly, metformin effects on PP2A activity and tau phosphorylation seem to be independent of AMPK activation, because in our experiments (i) metformin induces PP2A activity before and at lower levels than AMPK activity and (ii) the AMPK activator AICAR does not influence the phosphorylation of tau at the sites analyzed.	Metformin	14-23	protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform	Mus musculus	165-169
21098287-5	2010	Surprisingly, metformin effects on PP2A activity and tau phosphorylation seem to be independent of AMPK activation, because in our experiments (i) metformin induces PP2A activity before and at lower levels than AMPK activity and (ii) the AMPK activator AICAR does not influence the phosphorylation of tau at the sites analyzed.	Metformin	147-156	protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform	Mus musculus	165-169
21098287-6	2010	Affinity chromatography and immunoprecipitation experiments together with PP2A activity assays indicate that metformin interferes with the association of the catalytic subunit of PP2A (PP2Ac) to the so-called MID1-alpha4 protein complex, which regulates the degradation of PP2Ac and thereby influences PP2A activity.	Metformin	109-118	protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform	Mus musculus	74-78
21098287-6	2010	Affinity chromatography and immunoprecipitation experiments together with PP2A activity assays indicate that metformin interferes with the association of the catalytic subunit of PP2A (PP2Ac) to the so-called MID1-alpha4 protein complex, which regulates the degradation of PP2Ac and thereby influences PP2A activity.	Metformin	109-118	protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform	Mus musculus	179-183
21098287-6	2010	Affinity chromatography and immunoprecipitation experiments together with PP2A activity assays indicate that metformin interferes with the association of the catalytic subunit of PP2A (PP2Ac) to the so-called MID1-alpha4 protein complex, which regulates the degradation of PP2Ac and thereby influences PP2A activity.	Metformin	109-118	protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform	Mus musculus	179-183
20816671-4	2010	Metformin did not alter GLUT-1 mRNA expression and protein content but increased GLUT-4 mRNA expression and cellular protein content, leading to increased GLUT-4 protein content in the plasma membrane.	Metformin	0-9	solute carrier family 2 member 4	Homo sapiens	81-87
20816671-4	2010	Metformin did not alter GLUT-1 mRNA expression and protein content but increased GLUT-4 mRNA expression and cellular protein content, leading to increased GLUT-4 protein content in the plasma membrane.	Metformin	0-9	solute carrier family 2 member 4	Homo sapiens	155-161
20816671-6	2010	Suppression of metformin-induced AMP-activated protein kinase (AMPK) activity by AMPKalpha1 silencing, however, reduced metformin-associated GLUT-4 expression and stimulation of glucose uptake.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	63-67
20816671-6	2010	Suppression of metformin-induced AMP-activated protein kinase (AMPK) activity by AMPKalpha1 silencing, however, reduced metformin-associated GLUT-4 expression and stimulation of glucose uptake.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	81-91
20816671-6	2010	Suppression of metformin-induced AMP-activated protein kinase (AMPK) activity by AMPKalpha1 silencing, however, reduced metformin-associated GLUT-4 expression and stimulation of glucose uptake.	Metformin	15-24	solute carrier family 2 member 4	Homo sapiens	141-147
20816671-6	2010	Suppression of metformin-induced AMP-activated protein kinase (AMPK) activity by AMPKalpha1 silencing, however, reduced metformin-associated GLUT-4 expression and stimulation of glucose uptake.	Metformin	120-129	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	63-67
20816671-6	2010	Suppression of metformin-induced AMP-activated protein kinase (AMPK) activity by AMPKalpha1 silencing, however, reduced metformin-associated GLUT-4 expression and stimulation of glucose uptake.	Metformin	120-129	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	81-91
20816671-6	2010	Suppression of metformin-induced AMP-activated protein kinase (AMPK) activity by AMPKalpha1 silencing, however, reduced metformin-associated GLUT-4 expression and stimulation of glucose uptake.	Metformin	120-129	solute carrier family 2 member 4	Homo sapiens	141-147
20816671-8	2010	In conclusion, activation of AMPKalpha1 without impairment of cell respiration is crucial for metformin-mediated increase in GLUT-4 protein content and glucose uptake in human adipocytes.	Metformin	94-103	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	29-39
20816671-8	2010	In conclusion, activation of AMPKalpha1 without impairment of cell respiration is crucial for metformin-mediated increase in GLUT-4 protein content and glucose uptake in human adipocytes.	Metformin	94-103	solute carrier family 2 member 4	Homo sapiens	125-131
20868233-5	2010	There were no apparent acute effects of metformin on intracellular Ca2(+) concentrations, but metformin enhanced (p&lt;0.05 to p&lt;0.01) the acute insulinotropic actions of GIP and GLP-1.	Metformin	94-103	glucagon like peptide 1 receptor	Homo sapiens	182-187
21048706-4	2010	In healthy subjects, a DPP-4 inhibitor elevated both active GLP-1 and glucose dependent insulinotropic polypeptide (GIP), metformin increased total GLP-1 (but not GIP), and the combination resulted in additive increases in active GLP-1 plasma concentrations.	Metformin	122-131	glucagon	Mus musculus	148-153
21048706-4	2010	In healthy subjects, a DPP-4 inhibitor elevated both active GLP-1 and glucose dependent insulinotropic polypeptide (GIP), metformin increased total GLP-1 (but not GIP), and the combination resulted in additive increases in active GLP-1 plasma concentrations.	Metformin	122-131	glucagon	Mus musculus	148-153
21048706-6	2010	The study results show that metformin is not a DPP-4 inhibitor but rather enhances precursor GCG expression in the large intestine, resulting in increased total GLP-1 concentrations.	Metformin	28-37	glucagon	Mus musculus	93-96
21048706-6	2010	The study results show that metformin is not a DPP-4 inhibitor but rather enhances precursor GCG expression in the large intestine, resulting in increased total GLP-1 concentrations.	Metformin	28-37	glucagon	Mus musculus	161-166
21048706-7	2010	DPP-4 inhibitors and metformin have complementary mechanisms of action and additive effects with respect to increasing the concentrations of active GLP-1 in plasma.	Metformin	21-30	glucagon	Mus musculus	148-153
21126943-11	2010	A reduction in serum visfatin and resistin levels was shown with metformin treatment, in patients with PCOS.	Metformin	65-74	nicotinamide phosphoribosyltransferase	Homo sapiens	21-29
21054460-7	2010	The patients on metformin also showed significantly higher levels of serum glucose (133 7 +- 9 63 mg/dL vs. 88 35 +- 6 31 mg/dL, P &lt; 0 04) and glycohemoglobin (HbA1-c) (8 23 +- 1 75% vs. 4 38 +- 0 96%, P &lt; 0 02) when compared with control subjects.	Metformin	16-25	hemoglobin subunit alpha 1	Homo sapiens	163-167
22117073-12	2012	Induction of IL1Rn by PGC-1alpha and AMPK may be involved in the beneficial effects of exercise and caloric restriction and putative anti-inflammatory effects of metformin.	Metformin	162-171	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	22-32
22863784-9	2012	Preincubation of endothelial cells with AGE-BSA and metformin, an anti-diabetic drug known to have an mTOR inhibition effect, significantly reduced AGE-stimulated LOX-1 expression.	Metformin	52-61	oxidized low density lipoprotein receptor 1	Homo sapiens	163-168
21964537-9	2012	Seventy eight different genes were overlapping the exercise and AICAR group at 24 h. Ingenuity identified six overlapping genes between the exercise, AICAR, and metformin groups including NR4A3, TNFRSF12A, HBB, PENK, PAP, and MAP4K4.	Metformin	161-170	nuclear receptor subfamily 4, group A, member 3	Rattus norvegicus	188-193
22359576-2	2012	AMPK is activated by changes in the intracellular AMP:ATP ratio when ATP consumption is stimulated by contractile activity but also by AICAR and metformin, compounds that increase glucose transport in mammalian muscle cells.	Metformin	145-154	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-4
20739620-10	2010	In cultured adipose tissue, epinephrine increased p38 and AMPK signaling; however, the direct activation of AMPK by AICAR or metformin led to reductions in PDK4 mRNA levels.	Metformin	125-134	pyruvate dehydrogenase kinase 4	Rattus norvegicus	156-160
20652679-5	2010	Moreover, the repression of AMPK activity by siRNA significantly reversed the inhibition of SAA expression by both AICAR and metformin, indicating that the effect of the agonists is dependent on AMPK.	Metformin	125-134	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	28-32
20966509-6	2010	It has been confirmed that AMPK is an indirect molecular target of the antidiabetic drug metformin, and it is postulated that AMPK may be responsible for health benefits of exercise.	Metformin	89-98	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	27-31
20919907-9	2010	CONCLUSIONS AND CLINICAL RELEVANCE: Metformin reportedly enhances insulin sensitivity of peripheral tissues without stimulating insulin secretion, but bioavailability in horses is low.	Metformin	36-45	INS	Equus caballus	66-73
21966119-5	2010	The antioxidatve effect of 200 mg/kg bw CFP was significantly (P &gt; 0.05) better than 100 mg/kg bw CFP and the reference drugs (tolbutamide and metformin).	Metformin	146-155	complement factor properdin	Rattus norvegicus	40-43
20204498-5	2010	Metformin therapy with the various diets indicated that metformin can be highly effective at suppressing systemic metabolic biomarkers such as IGF-1, insulin and glucose, especially in the high energy diet treated animals.	Metformin	0-9	insulin-like growth factor 1	Mus musculus	143-148
20204498-5	2010	Metformin therapy with the various diets indicated that metformin can be highly effective at suppressing systemic metabolic biomarkers such as IGF-1, insulin and glucose, especially in the high energy diet treated animals.	Metformin	56-65	insulin-like growth factor 1	Mus musculus	143-148
22359576-7	2012	Moreover, exposure of trout myotubes to AICAR and metformin resulted in an increase in AMPK activity (3.8 and 3 fold, respectively).	Metformin	50-59	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	87-91
23236586-4	2012	Mechanistically, metformin appears to suppress the Oct4-driven compartment of malignant stem cells responsible for teratocarcinoma growth while safeguarding an intact, Oct4-independent competency to generate terminally differentiated tissues.	Metformin	17-26	POU domain, class 5, transcription factor 1, related sequence 1	Mus musculus	51-55
23236586-4	2012	Mechanistically, metformin appears to suppress the Oct4-driven compartment of malignant stem cells responsible for teratocarcinoma growth while safeguarding an intact, Oct4-independent competency to generate terminally differentiated tissues.	Metformin	17-26	POU domain, class 5, transcription factor 1, related sequence 1	Mus musculus	168-172
22093824-7	2011	We found that both 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR) and metformin, traditional pharmacological activators of AMPK, inhibited the PR pathway, as evidenced by progesterone response element (PRE)-driven luciferase activity and PR target gene expression.	Metformin	86-95	progesterone receptor	Homo sapiens	159-161
22093824-7	2011	We found that both 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR) and metformin, traditional pharmacological activators of AMPK, inhibited the PR pathway, as evidenced by progesterone response element (PRE)-driven luciferase activity and PR target gene expression.	Metformin	86-95	progesterone receptor	Homo sapiens	218-220
22093824-8	2011	Compound C, an inhibitor of AMPK, partly but significantly reversed the anti-PR effects of AICAR and metformin.	Metformin	101-110	progesterone receptor	Homo sapiens	77-79
21849490-0	2011	Preactivation of AMPK by metformin may ameliorate the epithelial cell damage caused by renal ischemia.	Metformin	25-34	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	17-21
21849490-6	2011	When cells were pretreated with the AMPK activator metformin before energy depletion, basolateral localization of Na-K-ATPase was preserved.	Metformin	51-60	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	36-40
21947382-10	2011	CONCLUSIONS/INTERPRETATION: Activation of hepatic AMPK by metformin results from a decrease in cellular energy status owing to metformin"s AMPK-independent inhibition of the mitochondrial respiratory-chain complex 1.	Metformin	58-67	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	50-54
21947382-10	2011	CONCLUSIONS/INTERPRETATION: Activation of hepatic AMPK by metformin results from a decrease in cellular energy status owing to metformin"s AMPK-independent inhibition of the mitochondrial respiratory-chain complex 1.	Metformin	58-67	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	139-143
21947382-10	2011	CONCLUSIONS/INTERPRETATION: Activation of hepatic AMPK by metformin results from a decrease in cellular energy status owing to metformin"s AMPK-independent inhibition of the mitochondrial respiratory-chain complex 1.	Metformin	127-136	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	50-54
21947382-10	2011	CONCLUSIONS/INTERPRETATION: Activation of hepatic AMPK by metformin results from a decrease in cellular energy status owing to metformin"s AMPK-independent inhibition of the mitochondrial respiratory-chain complex 1.	Metformin	127-136	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	139-143
21971158-8	2011	Pretreatment with the nonspecific muscarinic antagonist, atropine (1 mg/kg, iv), decreased metformin-induced GLP-1 secretion by 55 +- 11% (P &lt; 0.05).	Metformin	91-100	glucagon like peptide 1 receptor	Homo sapiens	109-114
21971158-11	2011	In contrast, pretreatment with the gastrin-releasing peptide antagonist, RC-3095 (100 mug/kg, sc), reduced the GLP-1 response to metformin, by 55 +- 6% (P &lt; 0.01) at 30 min.	Metformin	129-138	glucagon like peptide 1 receptor	Homo sapiens	111-116
21971158-12	2011	These studies elucidate the mechanism underlying metformin-induced GLP-1 secretion and highlight the benefits of using metformin with dipeptidylpeptidase-IV inhibitors in patients with type 2 diabetes.	Metformin	49-58	glucagon like peptide 1 receptor	Homo sapiens	67-72
20490716-0	2011	More favorable progesterone receptor phenotype of breast cancer in diabetics treated with metformin.	Metformin	90-99	progesterone receptor	Homo sapiens	15-36
20490716-5	2011	The frequency of progesterone receptor-positive mammary carcinomas in women who were treated with metformin, irrespective of whether it was combined with sulfonylurea preparations, was significantly higher than in the sulfonylurea only group (P=0.043) and in the combined group of patients treated with either sulfonylurea or insulin (P=0.041).	Metformin	98-107	progesterone receptor	Homo sapiens	17-38
22249159-7	2011	The potential for future clinical-translational applications of AMPK activators such as AICAR, metformin and resveratrol for the treatment of chronic myelogenous leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL) are discussed.	Metformin	95-104	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	64-68
21470048-4	2011	Activation of AMPK by 5-amino-4-imidazolecarboxamide riboside (AICAr) or metformin as well as inactivation of AMPK by compound C (Comp C), siRNA ablation of AMPKalpha2, or exogenous ATP stimulated cardiomyogenesis of ES cells.	Metformin	73-82	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	14-18
22180679-5	2011	We show that metformin treatment activates AMP-activated kinase (AMPK) in vitro and in vivo.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	43-63
20722676-0	2010	Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trial.	Metformin	139-148	glucagon like peptide 1 receptor	Homo sapiens	41-55
20186137-0	2010	Effects of metformin and weight loss on serum alanine aminotransferase activity in the diabetes prevention program.	Metformin	11-20	glutamic--pyruvic transaminase	Homo sapiens	46-70
20186137-2	2010	We investigated whether metformin or changes in metabolic measurements (weight, fasting plasma glucose (FPG), or fasting insulin (FI)) improved serum alanine aminotransferase (ALT) activity, as a marker for NAFLD, in the Diabetes Prevention Program (DPP).	Metformin	24-33	glutamic--pyruvic transaminase	Homo sapiens	150-174
20135346-2	2010	Adenosine 5"- monophosphate-activated protein kinase (AMPK) activators such as metformin have similar actions, in keeping with the TSC2/1 pathway linking activation of AMPK to inhibition of mTOR.	Metformin	79-88	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-52
20135346-2	2010	Adenosine 5"- monophosphate-activated protein kinase (AMPK) activators such as metformin have similar actions, in keeping with the TSC2/1 pathway linking activation of AMPK to inhibition of mTOR.	Metformin	79-88	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	54-58
20135346-2	2010	Adenosine 5"- monophosphate-activated protein kinase (AMPK) activators such as metformin have similar actions, in keeping with the TSC2/1 pathway linking activation of AMPK to inhibition of mTOR.	Metformin	79-88	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	168-172
20135346-5	2010	We show that metformin (but not rapamycin) exposure leads to increased phosphorylation of IRS-1 at Ser(789), a site previously reported to inhibit downstream signaling and to be an AMPK substrate phosphorylated under conditions of cellular energy depletion.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	181-185
20200042-0	2010	Metformin attenuates cardiac fibrosis by inhibiting the TGFbeta1-Smad3 signalling pathway.	Metformin	0-9	SMAD family member 3	Mus musculus	65-70
20200042-7	2010	Metformin suppressed the phosphorylation of Smad3 in response to TGF-beta(1) in CFs.	Metformin	0-9	SMAD family member 3	Mus musculus	44-49
20200042-7	2010	Metformin suppressed the phosphorylation of Smad3 in response to TGF-beta(1) in CFs.	Metformin	0-9	transforming growth factor, beta 1	Mus musculus	65-68
20200042-8	2010	Metformin also inhibited the nuclear translocation and transcriptional activity of Smad3 in CFs.	Metformin	0-9	SMAD family member 3	Mus musculus	83-88
20200042-9	2010	CONCLUSION: Metformin inhibited cardiac fibrosis induced by pressure overload in vivo and inhibited collagen synthesis in CFs probably via inhibition of the TGF-beta(1)-Smad3 signalling pathway.	Metformin	12-21	SMAD family member 3	Mus musculus	169-174
22180679-5	2011	We show that metformin treatment activates AMP-activated kinase (AMPK) in vitro and in vivo.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	65-69
22180679-6	2011	In the acute transplantation model, metformin activation of AMPK resulted in significantly decreased apoptosis in cardiac allografts on postoperative day (POD) 1 and 8.	Metformin	36-45	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	60-64
21852673-11	2011	In ob/ob mice, metformin promoted apical GLUT2 and improved glucose homeostasis.	Metformin	15-24	solute carrier family 2 (facilitated glucose transporter), member 2	Mus musculus	41-46
21168492-7	2011	In parallel, IGF-II increases phosphorylation of AKT and p70S6K, while metformin increases AMPK phosphorylation and decreases p70S6K phosphorylation.	Metformin	71-80	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	91-95
21168492-8	2011	The effects of metformin on PR A/B and p70S6K are partially reversed by an AMPK inhibitor.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	75-79
21168492-10	2011	Our results demonstrate that metformin promotes PR expression, which can be inhibited by overexpressed IGF-II in EC.	Metformin	29-38	progesterone receptor	Homo sapiens	48-50
21945753-5	2011	Metformin also induced AMPK activation in 786-O cells, but this activation was not associated with the cell proliferation inhibition or apoptosis-inducing effect of metformin.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	23-27
21655990-12	2011	By ingenuity pathway analysis, the tumour necrosis factor receptor 1 (TNFR1) signaling pathway was most affected by metformin: TGFB and MEKK were upregulated and cdc42 downregulated; mTOR and AMPK pathways were also affected.	Metformin	116-125	mitogen-activated protein kinase kinase kinase 1	Homo sapiens	136-140
21655990-12	2011	By ingenuity pathway analysis, the tumour necrosis factor receptor 1 (TNFR1) signaling pathway was most affected by metformin: TGFB and MEKK were upregulated and cdc42 downregulated; mTOR and AMPK pathways were also affected.	Metformin	116-125	cell division cycle 42	Homo sapiens	162-167
21111758-2	2011	In addition, many therapeutic agents used in the treatment of diabetes and atherosclerosis such as metformin, thiazolidinediones and statins may exert their vasculoprotective effects through activation of AMPK.	Metformin	99-108	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	205-209
22451888-6	2011	Melatonin, metformin, and their combination normalized LPO level.	Metformin	11-20	lactoperoxidase	Mus musculus	55-58
21572254-2	2011	Besides the discovery of somatic mutations in the LKB1 gene in certain type of cancers, a critical emerging point was that the LKB1/AMPK axis remains generally functional and could be stimulated by pharmacological molecules such as metformin in cancer cells.	Metformin	232-241	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	132-136
20583949-7	2010	The GMR (dutogliptin + metformin/metformin) of AUC(0-12h) at steady state was 0.99 (90% CI: 0.84-1.17; p = 0.93); the GMR of C(max) was 0.91 (90% CI: 0.79-1.04; p = 0.18); T(max) was comparable for metformin with or without dutogliptin.	Metformin	23-32	colony stimulating factor 2 receptor subunit alpha	Homo sapiens	4-7
20583949-7	2010	The GMR (dutogliptin + metformin/metformin) of AUC(0-12h) at steady state was 0.99 (90% CI: 0.84-1.17; p = 0.93); the GMR of C(max) was 0.91 (90% CI: 0.79-1.04; p = 0.18); T(max) was comparable for metformin with or without dutogliptin.	Metformin	33-42	colony stimulating factor 2 receptor subunit alpha	Homo sapiens	4-7
20583949-7	2010	The GMR (dutogliptin + metformin/metformin) of AUC(0-12h) at steady state was 0.99 (90% CI: 0.84-1.17; p = 0.93); the GMR of C(max) was 0.91 (90% CI: 0.79-1.04; p = 0.18); T(max) was comparable for metformin with or without dutogliptin.	Metformin	33-42	colony stimulating factor 2 receptor subunit alpha	Homo sapiens	4-7
21572254-4	2011	Further basic research work should be conducted to elucidate the molecular targets of LKB1/AMPK responsible for its anti-tumor activity in parallel of conducting clinical trials using metformin, AICAR or new AMPK activating agents to explore the potential of the LKB1/AMPK signaling pathway as a new target for anticancer drug development.	Metformin	184-193	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	91-95
21382619-0	2011	Link between metformin and the peroxisome proliferator-activated receptor gamma pathway in the uterine tissue of hyperandrogenized prepubertal mice.	Metformin	13-22	peroxisome proliferator activated receptor gamma	Mus musculus	31-79
21619869-4	2011	Metformin, as an activator of AMPK, induced MUC5B expression in a dose-dependent manner.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	30-34
21619869-4	2011	Metformin, as an activator of AMPK, induced MUC5B expression in a dose-dependent manner.	Metformin	0-9	mucin 5B, oligomeric mucus/gel-forming	Homo sapiens	44-49
21619869-5	2011	Compound C, as an inhibitor of AMPK, inhibited metformin-induced MUC5B expression in a dose-dependent manner.	Metformin	47-56	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	31-35
21619869-5	2011	Compound C, as an inhibitor of AMPK, inhibited metformin-induced MUC5B expression in a dose-dependent manner.	Metformin	47-56	mucin 5B, oligomeric mucus/gel-forming	Homo sapiens	65-70
21619869-6	2011	Metformin significantly activated phosphorylation of AMPK; compound C inhibited metformin-activated phosphorylation of AMPK.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	53-57
21619869-6	2011	Metformin significantly activated phosphorylation of AMPK; compound C inhibited metformin-activated phosphorylation of AMPK.	Metformin	80-89	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	119-123
21619869-8	2011	However, after treatment with metformin, MUC5B mRNA expression was increased in wild-type adenovirus transfected NCI-H292 cells; MUC5B mRNA expression was significantly decreased in Ad-dnAMPK transfected NCI-H292 cells.	Metformin	30-39	mucin 5B, oligomeric mucus/gel-forming	Homo sapiens	41-46
21619869-8	2011	However, after treatment with metformin, MUC5B mRNA expression was increased in wild-type adenovirus transfected NCI-H292 cells; MUC5B mRNA expression was significantly decreased in Ad-dnAMPK transfected NCI-H292 cells.	Metformin	30-39	mucin 5B, oligomeric mucus/gel-forming	Homo sapiens	129-134
21619869-10	2011	SB203580, as an inhibitor of p38 MAPK, significantly inhibited metformin-induced MUC5B mRNA expression, while U0126, as an inhibitor of ERK1/2 MAPK, had no effect.	Metformin	63-72	mucin 5B, oligomeric mucus/gel-forming	Homo sapiens	81-86
21619869-11	2011	In addition, knockdown of p38 MAPK by p38 MAPK siRNA significantly blocked metformin-induced MUC5B mRNA expression.	Metformin	75-84	mucin 5B, oligomeric mucus/gel-forming	Homo sapiens	93-98
21501658-7	2011	LiCl-induced Wnt transactivation was suppressed by addition of metformin.	Metformin	63-72	Wnt family member 3A	Homo sapiens	13-16
20307532-5	2010	We found that the impaired bone density and quality induced by bilateral ovariectomy were significantly improved by the treatment of metformin (both 50 and 100mg/kg/day), and this action could be partly mediated by regulating bone marrow cells development through induction of mechanisms regulating osteoblast markers core binding factor a1 and LDL receptor-related protein 5.	Metformin	133-142	LDL receptor related protein 5	Rattus norvegicus	318-375
21501658-8	2011	Metformin increased the phosphorylation of beta-catenin and decreased beta-catenin protein levels leading to suppression of Wnt/beta-catenin signaling.	Metformin	0-9	Wnt family member 3A	Homo sapiens	124-127
20883471-8	2011	In MDCK-OCT2-MATE1 cells basal to apical MPP(+) and metformin transcellular translocation decreased with increasing pH from 6.0 to 7.5.	Metformin	52-61	solute carrier family 22 member 2	Canis lupus familiaris	8-12
21597332-4	2011	Understanding how the IR/IGF-1R pathway functions in tumors is increasing in importance as the efficacy of drugs that target metabolic pathways, such as metformin, are investigated in prospective clinical trials.	Metformin	153-162	insulin receptor	Homo sapiens	22-24
19338997-12	2010	Amylin levels decreased with metformin but not with rosiglitazone treatment.	Metformin	29-38	islet amyloid polypeptide	Homo sapiens	0-6
19338997-13	2010	CONCLUSION(S): In women with PCOS, [1] there is increased secretion of amylin, [2] insulin and amylin secretion is coregulated in the fasting state, [3] after glucose ingestion, glucose levels regulate amylin release, and [4] the insulin-sensitizing agent metformin, but not rosiglitazone, reduces amylin secretion.	Metformin	256-265	islet amyloid polypeptide	Homo sapiens	95-101
19338997-13	2010	CONCLUSION(S): In women with PCOS, [1] there is increased secretion of amylin, [2] insulin and amylin secretion is coregulated in the fasting state, [3] after glucose ingestion, glucose levels regulate amylin release, and [4] the insulin-sensitizing agent metformin, but not rosiglitazone, reduces amylin secretion.	Metformin	256-265	islet amyloid polypeptide	Homo sapiens	95-101
19338997-13	2010	CONCLUSION(S): In women with PCOS, [1] there is increased secretion of amylin, [2] insulin and amylin secretion is coregulated in the fasting state, [3] after glucose ingestion, glucose levels regulate amylin release, and [4] the insulin-sensitizing agent metformin, but not rosiglitazone, reduces amylin secretion.	Metformin	256-265	islet amyloid polypeptide	Homo sapiens	95-101
20388847-5	2010	Metformin, the most widely used drug in the treatment of type 2 diabetes, activates AMP kinase (AMPK), which negatively regulates mTORC1.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	130-136
10456437-0	1999	Metformin modulates insulin receptor signaling in normal and cholesterol-treated human hepatoma cells (HepG2).	Metformin	0-9	insulin receptor	Homo sapiens	20-36
10337452-5	1999	In 15 patients treated with metformin (CAS 657-24-9) the fasting plasma amylin level was similar to that in healthy individuals (1.64 +/- 0.25 pmol/l), but after glucagon stimulation the increment of plasma amylin was minimal and the relevant mean value was significantly lower when compared with those in healthy individuals and with NIDDM patients treated with glibenclamide.	Metformin	28-37	islet amyloid polypeptide	Homo sapiens	72-78
10337452-5	1999	In 15 patients treated with metformin (CAS 657-24-9) the fasting plasma amylin level was similar to that in healthy individuals (1.64 +/- 0.25 pmol/l), but after glucagon stimulation the increment of plasma amylin was minimal and the relevant mean value was significantly lower when compared with those in healthy individuals and with NIDDM patients treated with glibenclamide.	Metformin	28-37	islet amyloid polypeptide	Homo sapiens	207-213
10337452-7	1999	With the respect to the trophic effect of amyloid deposits in the pancreatic islets and to a hypothetic effect of amylin increasing insulin resistance, the present results emphasize the particular usefulness of metformin in the pharmacological treatment of NIDDM.	Metformin	211-220	islet amyloid polypeptide	Homo sapiens	114-120
10333901-6	1999	Among patients on sulfonylureas at baseline, those starting metformin had significantly lower HbA1c levels 6 months later than those not started, after adjustment for age, sex, and the higher baseline levels in those started (adjusted difference: 0.5%, P &lt; 0.0001).	Metformin	60-69	hemoglobin subunit alpha 1	Homo sapiens	94-98
10576523-5	1999	In addition, metformin can reduce the overall rate of glycogenolysis and decrease the activity of hepatic glucose-6-phosphatase.	Metformin	13-22	glucose-6-phosphatase catalytic subunit 1	Homo sapiens	106-127
21740847-10	2011	Metformin also increased phosphorylation of AMPK and eNOS, and reduced the expression of TGF-beta1, basic fibroblast growth factor (bFGF), and tumor necrosis factor (TNF)-alpha.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	44-48
21740847-11	2011	CONCLUSIONS: Metformin has beneficial effects on cardiomyocytes, and this effect involves activation of the AMPK-eNOS pathway.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	108-112
21566461-0	2011	Metformin activates an ataxia telangiectasia mutated (ATM)/Chk2-regulated DNA damage-like response.	Metformin	0-9	checkpoint kinase 2	Homo sapiens	59-63
21436046-6	2011	However, we found that application of metformin or AICAR, potent AMPK activators, inhibit axogenesis and axon growth in an AMPK-dependent manner.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	65-69
9839093-7	1998	RESULTS: The addition of acarbose to patients on background metformin and diet therapy showed a statistically significant reduction in mean HbA1c of 0.65%.	Metformin	60-69	hemoglobin subunit alpha 1	Homo sapiens	140-144
9972673-6	1998	HbA1 c were similarly reduced by the addition of either bedtime NPH insulin (7.6+/-0.34 vs 8.7+/-0.35, p&lt;0.01) or metformin (7.6+/-0.22 vs 8.6+/-0.31, p&lt;0.01).	Metformin	117-126	hemoglobin subunit alpha 1	Homo sapiens	0-4
9109854-0	1997	Metformin therapy is associated with a decrease in plasma plasminogen activator inhibitor-1, lipoprotein(a), and immunoreactive insulin levels in patients with the polycystic ovary syndrome.	Metformin	0-9	lipoprotein(a)	Homo sapiens	93-107
9021342-20	1996	On metformin, the HbA1 was reduced by 0.3% and the BMI by 0.9 kg/m2 even 12 months later.	Metformin	3-12	hemoglobin subunit alpha 1	Homo sapiens	18-22
21436046-6	2011	However, we found that application of metformin or AICAR, potent AMPK activators, inhibit axogenesis and axon growth in an AMPK-dependent manner.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	123-127
21325438-9	2011	The antidiabetic drug metformin (which is derived from an herbal remedy) works in part by activating AMPK, whereas many xenobiotics or "nutraceuticals," including resveratrol, quercetin, and berberine, are also AMPK activators.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	101-105
21325438-9	2011	The antidiabetic drug metformin (which is derived from an herbal remedy) works in part by activating AMPK, whereas many xenobiotics or "nutraceuticals," including resveratrol, quercetin, and berberine, are also AMPK activators.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	211-215
21091653-0	2011	Metformin inhibits HMGB1 release in LPS-treated RAW 264.7 cells and increases survival rate of endotoxaemic mice.	Metformin	0-9	high mobility group box 1	Mus musculus	19-24
21091653-2	2011	This study investigated the effect of metformin on the expression of pro-inflammatory cytokines including high mobility group box 1 (HMGB1) in lipopolysaccharide (LPS)-treated animals and cells.	Metformin	38-47	high mobility group box 1	Mus musculus	106-131
21091653-2	2011	This study investigated the effect of metformin on the expression of pro-inflammatory cytokines including high mobility group box 1 (HMGB1) in lipopolysaccharide (LPS)-treated animals and cells.	Metformin	38-47	high mobility group box 1	Mus musculus	133-138
21091653-3	2011	EXPERIMENTAL APPROACH: We investigated whether metformin inhibits the release of HMGB1 in LPS-treated RAW 264.7 cells and increases survival rate in endotoxaemic mice (lethal endotoxaemia was induced by an i.p.	Metformin	47-56	high mobility group box 1	Mus musculus	81-86
21091653-6	2011	KEY RESULTS: Both pre- and post-treatment with metformin significantly improved survival of animals during lethal endotoxaemia (survival rate was monitored up to 2 weeks), decreased serum levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta, HMGB1 expression and myeloperoxidase activity in lungs.	Metformin	47-56	high mobility group box 1	Mus musculus	259-264
21091653-8	2011	In an in vitro study, metformin dose-dependently inhibited production of pro-inflammatory cytokines and HMGB1 release.	Metformin	22-31	high mobility group box 1	Mus musculus	104-109
21091653-12	2011	Metformin improved survival in a mouse model of lethal endotoxaemia by inhibiting HMGB1 release.	Metformin	0-9	high mobility group box 1	Mus musculus	82-87
21228273-5	2011	AMP-activated protein kinase (AMPK) is the main ATP/AMP sensor of mammalian cells, and we mimicked an energy stress by treating human aortic smooth muscle cells (AoSMCs) with the AMPK activators 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside and metformin.	Metformin	254-263	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-28
21228273-5	2011	AMP-activated protein kinase (AMPK) is the main ATP/AMP sensor of mammalian cells, and we mimicked an energy stress by treating human aortic smooth muscle cells (AoSMCs) with the AMPK activators 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside and metformin.	Metformin	254-263	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	30-34
21228273-5	2011	AMP-activated protein kinase (AMPK) is the main ATP/AMP sensor of mammalian cells, and we mimicked an energy stress by treating human aortic smooth muscle cells (AoSMCs) with the AMPK activators 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside and metformin.	Metformin	254-263	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	179-183
21102522-2	2011	We treated both tumor LKB1 expression and host diet as variables, and observed that metformin inhibited tumor growth and reduced insulin receptor activation in tumors of mice with diet-induced hyperinsulinemia, independent of tumor LKB1 expression.	Metformin	84-93	insulin receptor	Mus musculus	129-145
21054339-0	2011	Metformin inhibits P-glycoprotein expression via the NF-kappaB pathway and CRE transcriptional activity through AMPK activation.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	112-116
21054339-8	2011	Moreover, transduction of MCF-7/adr cells with the p65 subunit of NF-kappaB induced MDR1 promoter activity and expression, and this effect was attenuated by metformin.	Metformin	157-166	RELA proto-oncogene, NF-kB subunit	Homo sapiens	51-75
21054339-9	2011	The suppression of MDR1 promoter activity and protein expression was mediated through metformin-induced activation of AMP-activated protein kinase (AMPK).	Metformin	86-95	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	118-146
21054339-9	2011	The suppression of MDR1 promoter activity and protein expression was mediated through metformin-induced activation of AMP-activated protein kinase (AMPK).	Metformin	86-95	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	148-152
21054339-10	2011	Small interfering RNA methods confirmed that reduction of AMPK levels attenuates the inhibition of MDR1 activation associated with metformin exposure.	Metformin	131-140	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	58-62
21054339-11	2011	Furthermore, the inhibitory effects of metformin on MDR1 expression and cAMP-responsive element binding protein (CREB) phosphorylation were reversed by overexpression of a dominant-negative mutant of AMPK.	Metformin	39-48	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	200-204
21054339-12	2011	CONCLUSIONS AND IMPLICATIONS: These results suggest that metformin activates AMPK and suppresses MDR1 expression in MCF-7/adr cells by inhibiting the activation of NF-kappaB and CREB.	Metformin	57-66	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	77-81
22303065-5	2011	The overall objective of this study was to develop an oral sustained release metformin hydrochloride tablet by using hydrophilic Eudragit RSPO alone or its combination with hydrophobic natural polymers Gum copal and gum damar as rate controlling factor.	Metformin	77-100	R-spondin 1	Homo sapiens	138-142
8852272-6	1995	In alloxan-induced diabetes metformin (Met) treatment led to an increase in insulin receptor number in liver plasma membranes (before Met: 46.50 +/- 2.69, after Met: 76.00 +/- 3.39 fmol/mg, p &lt; 0.001) and a decrease in plasma lipid peroxidation levels compared to the non-treated group (before Met: 1.85 +/- 0.53, after Met: 1.10 +/- 0.09 nmol MDA/ml, p &lt; 0.05).	Metformin	28-37	insulin receptor	Rattus norvegicus	76-92
1505458-8	1992	Western blot analysis using antisera reactive with the GLUT1 and GLUT4 isoforms of glucose transporters showed that metformin caused a reduction in GLUT1 content in the IM fraction and a concomitant increase in the PM.	Metformin	116-125	solute carrier family 2 member 4	Homo sapiens	65-70
1543016-0	1992	Metformin ameliorates extreme insulin resistance in a patient with anti-insulin receptor antibodies: description of insulin receptor and postreceptor effects in vivo and in vitro.	Metformin	0-9	insulin receptor	Homo sapiens	72-88
1543016-0	1992	Metformin ameliorates extreme insulin resistance in a patient with anti-insulin receptor antibodies: description of insulin receptor and postreceptor effects in vivo and in vitro.	Metformin	0-9	insulin receptor	Homo sapiens	116-132
1543016-9	1992	It is suggested that metformin increases, possibly through a change in the spatial conformation of insulin receptor within the plasma membrane, the availability of pre-existing receptors to insulin binding and/or decreases the availability of specific epitopes to antibody anchoring.	Metformin	21-30	insulin receptor	Homo sapiens	99-115
21209036-11	2011	Metformin in the presence of insulin activated Akt and this was dependent on phosphoinositide-3 kinase, as was translocation of Glut-4 to the membrane.	Metformin	0-9	solute carrier family 2 member 4	Homo sapiens	128-134
21209036-12	2011	Metformin was able to substantially enhance the insulin-stimulated translocation of Glut-4 transporters from the cytosol to the membrane.	Metformin	0-9	solute carrier family 2 member 4	Homo sapiens	84-90
21386129-2	2011	Antidiabetic biguanides such as metformin decrease glucose, insulin and IGF-1 level.	Metformin	32-41	insulin-like growth factor 1	Mus musculus	72-77
20972533-2	2011	Although it reduces hepatic glucose production, clinical studies show that metformin may reduce plasma dipeptidyl peptidase-4 activity and increase circulating levels of glucagon-like peptide 1 (GLP-1).	Metformin	75-84	glucagon	Mus musculus	170-193
20972533-2	2011	Although it reduces hepatic glucose production, clinical studies show that metformin may reduce plasma dipeptidyl peptidase-4 activity and increase circulating levels of glucagon-like peptide 1 (GLP-1).	Metformin	75-84	glucagon	Mus musculus	195-200
20972533-7	2011	RESULTS: In wild-type mice, metformin acutely increased plasma levels of GLP-1, but not those of gastric inhibitory polypeptide or peptide YY; it also improved oral glucose tolerance and reduced gastric emptying.	Metformin	28-37	glucagon	Mus musculus	73-78
21199270-0	2011	Phosphoprotein enriched in diabetes gene product (Ped/pea-15) is increased in omental adipose tissue of women with the polycystic ovary syndrome: ex vivo regulation of ped/pea-15 by glucose, insulin and metformin.	Metformin	203-212	OCA2 melanosomal transmembrane protein	Homo sapiens	50-53
21199270-6	2011	Importantly, glucose and insulin increased whereas metformin significantly decreased Ped/pea-15 levels in human omental AT explants.	Metformin	51-60	OCA2 melanosomal transmembrane protein	Homo sapiens	85-88
21084384-7	2011	A 24 h exposure to metformin stimulated AMP-activated protein kinase (AMPK), suppressed activation of translation factors- both the mammalian target of rapamycin (mTOR; also known as mechanistic target of rapamycin, MTOR)-dependent ones (eukaryotic initiation factor 4E-binding protein 1 and ribosomal protein S6) and the mTOR-independent eukaryotic elongation factor 2-, and inhibited protein synthesis; a 72 h exposure resulted in 50% dead cells.	Metformin	19-28	ribosomal protein S6	Homo sapiens	292-312
21123367-4	2011	We found that in LKB1-null A549 lung adenocarcinoma cells, an AMPK activator, metformin, failed to block the nuclear export of PTEN, and the reintroduction of functional LKB1 into these cells restored the metformin-mediated inhibition of the nuclear export of PTEN.	Metformin	78-87	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	62-66
21123367-6	2011	Although the nuclear export of PTEN is blocked by metformin in MCF-7 breast cancer cells carrying wild-type LKB1, this inhibition could not be reversed by an AMPK inhibitor, suggesting that LKB1 could regulate the nuclear export of PTEN by bypassing AMPK alpha1/2.	Metformin	50-59	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	250-261
21426695-9	2011	Moreover, degree of hepatic steatosis was significantly lower and sPLA2 mRNA expression was also significantly decreased by metformin.	Metformin	124-133	phospholipase A2 group IIA	Rattus norvegicus	66-71
21265739-8	2011	Because of its ability to switch cellular metabolism from anabolic to catabolic mode, AMPK has become a key drug target to combat metabolic disorders associated with overnutrition such as Type 2 diabetes, and some existing anti-diabetic drugs (e.g. metformin) and many "nutraceuticals" work by activating AMPK, usually via inhibition of mitochondrial ATP production.	Metformin	249-258	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	86-90
22071265-3	2011	AMPK is activated by the antidiabetic drug metformin, and by many natural products including "nutraceuticals" and compounds used in traditional medicines.	Metformin	43-52	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
21647332-5	2011	AMPK activation by either AICAR or metformin decreases Srebp-1c promoter activity by about 75%.	Metformin	35-44	sterol regulatory element binding transcription factor 1	Rattus norvegicus	55-63
21647332-7	2011	When endogenous LXR ligand production was blocked by the potent HMG CoA reductase inhibitor compactin, T0901317-induced Srebp-1c promoter activity was decreased by AICAR or metformin treatment.	Metformin	173-182	sterol regulatory element binding transcription factor 1	Rattus norvegicus	120-128
21318055-7	2011	Metformin, an insulin sensitizing agent, its known to lower insulin resistance and enhance metabolic profile, with an additional weight reduction capacity, via activation of AMPK.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	174-178
21961686-11	2011	In one study in adolescents metformin treatment showed a reduction of HbA1c by 0.6% (95% CI: -1.16-0.04) and a slight decrease in daily total insulin dose.	Metformin	28-37	hemoglobin subunit alpha 1	Homo sapiens	70-74
21048706-0	2010	Dipeptidyl peptidase-4 inhibitors administered in combination with metformin result in an additive increase in the plasma concentration of active GLP-1.	Metformin	67-76	glucagon	Mus musculus	146-151
21048706-3	2010	In mice, metformin increased Gcg expression in the large intestine and elevated the plasma concentrations of inactive glucagon-like peptide 1 (GLP-1) (9-36) and glucagon.	Metformin	9-18	glucagon	Mus musculus	118-141
21048706-3	2010	In mice, metformin increased Gcg expression in the large intestine and elevated the plasma concentrations of inactive glucagon-like peptide 1 (GLP-1) (9-36) and glucagon.	Metformin	9-18	glucagon	Mus musculus	143-148
21126943-6	2010	Following metformin treatment, a significant decrease was observed in visfatin levels compared to the baseline.	Metformin	10-19	nicotinamide phosphoribosyltransferase	Homo sapiens	70-78
20860661-0	2010	Pharmacokinetic interaction between itraconazole and metformin in rats: competitive inhibition of metabolism of each drug by each other via hepatic and intestinal CYP3A1/2.	Metformin	53-62	cytochrome P450, family 3, subfamily a, polypeptide 23-polypeptide 1	Rattus norvegicus	163-171
20860661-10	2010	The metabolism of itraconazole and metformin was significantly inhibited by each other via CYP3A1 and 3A2 in rat and 3A4 in human microsomes.	Metformin	35-44	cytochrome P450, family 3, subfamily a, polypeptide 23-polypeptide 1	Rattus norvegicus	91-105
20854376-0	2010	Metformin action on AMP-activated protein kinase: a translational research approach to understanding a potential new therapeutic target.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	20-48
20854376-3	2010	It has recently been proposed that metformin-mediated stimulation of hepatic AMP-activated protein kinase (AMPK) underlies the hypoglycaemic effects of metformin.	Metformin	35-44	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	77-105
20854376-3	2010	It has recently been proposed that metformin-mediated stimulation of hepatic AMP-activated protein kinase (AMPK) underlies the hypoglycaemic effects of metformin.	Metformin	35-44	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	107-111
20854376-3	2010	It has recently been proposed that metformin-mediated stimulation of hepatic AMP-activated protein kinase (AMPK) underlies the hypoglycaemic effects of metformin.	Metformin	152-161	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	77-105
20854376-3	2010	It has recently been proposed that metformin-mediated stimulation of hepatic AMP-activated protein kinase (AMPK) underlies the hypoglycaemic effects of metformin.	Metformin	152-161	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	107-111
20854392-0	2010	Using a PCT-wide electronic system called the Deadly Trio database to provide safety alerts about prescribing of metformin in renal disease.	Metformin	113-122	trio Rho guanine nucleotide exchange factor	Homo sapiens	53-57
20615625-4	2010	METHODS AND MATERIALS: Lung, prostate, and breast cancer cells were treated with IR (2-8 Gy) after incubation with either ATM or AMPK inhibitors or the AMPK activator metformin.	Metformin	167-176	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	152-156
20615625-10	2010	Compound C caused resistance to IR, increasing the surviving fraction after 2 Gy, but the anti-diabetic drug metformin enhanced IR activation of AMPK and lowered the surviving fraction after 2 Gy further.	Metformin	109-118	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	145-149
20615625-12	2010	AMPK appears to (1) participate in an ATM-AMPK-p21(waf/cip) pathway, (2) be involved in regulation of the IR-induced G2/M checkpoint, and (3) may be targeted by metformin to enhance IR responses.	Metformin	161-170	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
20135346-6	2010	siRNA methods confirmed that reduction of AMPK levels attenuates both the IRS-1 Ser(789) phosphorylation and the inhibition of AKT activation associated with metformin exposure.	Metformin	158-167	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	42-46
20135346-7	2010	Although both rapamycin and metformin inhibit mTOR (the former directly and the latter through AMPK signaling), our results demonstrate previously unrecognized differences between these agents.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	95-99
20200042-0	2010	Metformin attenuates cardiac fibrosis by inhibiting the TGFbeta1-Smad3 signalling pathway.	Metformin	0-9	transforming growth factor, beta 1	Mus musculus	56-64
20560107-0	2010	Metformin attenuates production of nitric oxide in response to lipopolysaccharide by inhibiting MyD88-independent pathway.	Metformin	0-9	MYD88 innate immune signal transduction adaptor	Homo sapiens	96-101
20813708-6	2010	The expression of cyclin D1 in metformin-treated cells were lowered significantly as compared with that in the control cells.	Metformin	31-40	cyclin D1	Homo sapiens	18-27
20813708-7	2010	Telomerase activity was also decreased significantly in the cells after treatment with 5 mmol/L metformin for 72 h. CONCLUSION: Metformin can inhibit the growth of SW-480 cells mainly by blocking the cell cycle at G0/G1, down-regulating the expression of cyclin D1 and decreasing telomerase activity.	Metformin	96-105	cyclin D1	Homo sapiens	255-264
20813708-7	2010	Telomerase activity was also decreased significantly in the cells after treatment with 5 mmol/L metformin for 72 h. CONCLUSION: Metformin can inhibit the growth of SW-480 cells mainly by blocking the cell cycle at G0/G1, down-regulating the expression of cyclin D1 and decreasing telomerase activity.	Metformin	128-137	cyclin D1	Homo sapiens	255-264
20559023-0	2010	The combination of metformin and 2-deoxyglucose inhibits autophagy and induces AMPK-dependent apoptosis in prostate cancer cells.	Metformin	19-28	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	79-83
20583965-0	2010	Influence of metformin on GLUT1 gene and protein expression in rat streptozotocin diabetes mellitus model.	Metformin	13-22	solute carrier family 2 member 1	Rattus norvegicus	26-31
20583965-3	2010	OBJECTIVE: To study the action of metformin on expression of GLUT1 glucose transporter in rat streptozotocin model of diabetes mellitus.	Metformin	34-43	solute carrier family 2 member 1	Rattus norvegicus	61-66
20577046-0	2010	An energetic tale of AMPK-independent effects of metformin.	Metformin	49-58	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	21-25
20577046-3	2010	Metformin impairs ATP production, activating the conserved sensor of nutritional stress AMP-activated protein kinase (AMPK), thus providing a plausible and generally accepted model for suppression of gluconeogenic gene expression and glucose output.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	88-116
20577046-3	2010	Metformin impairs ATP production, activating the conserved sensor of nutritional stress AMP-activated protein kinase (AMPK), thus providing a plausible and generally accepted model for suppression of gluconeogenic gene expression and glucose output.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	118-122
20577053-7	2010	Metformin decreased expression of the gene encoding the catalytic subunit of glucose-6-phosphatase (G6Pase), while cytosolic phosphoenolpyruvate carboxykinase (Pepck) gene expression was unaffected in wild-type, AMPK-deficient, and LKB1-deficient hepatocytes.	Metformin	0-9	glucose-6-phosphatase, catalytic	Mus musculus	100-106
20577053-10	2010	Moreover, metformin-induced inhibition of glucose production was preserved under forced expression of gluconeogenic genes through PPARgamma coactivator 1alpha (PGC-1alpha) overexpression, indicating that metformin suppresses gluconeogenesis via a transcription-independent process.	Metformin	10-19	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	130-158
2162756-6	1990	Potential sites of action of metformin are the insulin receptor and the glucose transporters.	Metformin	29-38	insulin receptor	Rattus norvegicus	47-63
20577053-10	2010	Moreover, metformin-induced inhibition of glucose production was preserved under forced expression of gluconeogenic genes through PPARgamma coactivator 1alpha (PGC-1alpha) overexpression, indicating that metformin suppresses gluconeogenesis via a transcription-independent process.	Metformin	10-19	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	160-170
20577053-10	2010	Moreover, metformin-induced inhibition of glucose production was preserved under forced expression of gluconeogenic genes through PPARgamma coactivator 1alpha (PGC-1alpha) overexpression, indicating that metformin suppresses gluconeogenesis via a transcription-independent process.	Metformin	204-213	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	130-158
20577053-10	2010	Moreover, metformin-induced inhibition of glucose production was preserved under forced expression of gluconeogenic genes through PPARgamma coactivator 1alpha (PGC-1alpha) overexpression, indicating that metformin suppresses gluconeogenesis via a transcription-independent process.	Metformin	204-213	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	160-170
20572306-8	2010	Antidiabetic treatment with metformin was more common among cirrhotic and control DM2 subjects than among cases with HCC.	Metformin	28-37	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	82-85
29614026-10	2018	The protective effects of prenatal metformin therapy on HFR/HFA-induced hypertension, including downregulation of the renin-angiotensin system, decrease in uric acid level, and reduction of oxidative stress.	Metformin	35-44	renin	Rattus norvegicus	118-123
20572306-12	2010	CONCLUSION: In patients with preexisting DM2, the risk of HCC is positively associated with poor chronic glycemic control and significantly decreased by metformin therapy.	Metformin	153-162	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	41-44
20228137-7	2010	Furthermore, the administration of metformin led to the activation of AMPK, the inhibitory phosphorylation of acetyl-CoA carboxylase, the upregulation of BNIP3 and increased apoptosis as estimated by poly (ADP-ribose) polymerase (PARP) cleavage.	Metformin	35-44	BCL2/adenovirus E1B interacting protein 3	Mus musculus	154-159
24843413-9	2010	We also found that metformin and pioglitazone promote mitochondrial biogenesis through the same AMPK-PGC-1alpha pathway.	Metformin	19-28	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	101-111
34801693-8	2022	Neither weight loss induced by VSG nor improved glucose tolerance by metformin treatment could revert hepatic Fgf21 DNA methylation or expression.	Metformin	69-78	fibroblast growth factor 21	Mus musculus	110-115
20610860-9	2010	In addition, metformin reduced the glucose-induced abundance of SGLT-1 in BBM and increased those of GLUT2, concomitantly increasing the phosphorylation of intracellular AMPKalpha2.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	170-180
34427052-0	2022	A 24-month metformin treatment study of children with obesity: Changes in circulating GDF-15 and associations with changes in body weight and visceral fat.	Metformin	11-20	FAT atypical cadherin 1	Homo sapiens	151-154
34427052-1	2022	BACKGROUND: Metformin treatment for 24 months in children with obesity lowers body mass index (BMI), reduces liver fat, and normalizes endocrine-metabolic parameters.	Metformin	12-21	FAT atypical cadherin 1	Homo sapiens	115-118
34427052-2	2022	OBJECTIVE: Here we study whether circulating GDF-15 levels were raised by such metformin treatment and whether they related to changes in body weight and visceral fat in children with obesity.	Metformin	79-88	FAT atypical cadherin 1	Homo sapiens	163-166
20610860-13	2010	In conclusion, metformin slightly increases intestinal glucose absorption by inducing a re-distribution of glucose transporters in BBM through AMPK control in enterocyte.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	143-147
20015525-8	2010	There were no significant variations of ADN, R, or TNF-alpha with sitagliptin, whereas a significant increase of ADN and a significant decrease of R and TNF-alpha values were recorded with metformin.	Metformin	189-198	complement factor D	Homo sapiens	113-116
34806449-9	2022	Moreover, metformin reduced gene expression of key inflammatory markers and both gene and protein expression of kidney injury marker-1 and cyclin-dependent kinase-1 vs. untreated controls.	Metformin	10-19	cyclin-dependent kinase 1	Mus musculus	139-164
20363874-9	2010	Cells overexpressing TSC2/S1345A (the site of AMPK phosphorylation) were less responsive to metformin-induced inhibition of p70S6 kinase.	Metformin	92-101	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	46-50
20363874-10	2010	These findings are relevant to whole animal physiology because administration of metformin to mice resulted in inhibition of IGF-I-stimulated phosphorylation of Akt/mTOR/p70S6K.	Metformin	81-90	insulin-like growth factor 1	Mus musculus	125-130
20444419-0	2010	Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	41-47
34191257-6	2022	RESULTS: The effect of the therapy on the islet cells varied depending on the drug and included enhanced pancreatic islet beta-cell proliferation, in case of metformin and rosiglitazone; de-differentiation of alpha-cells and beta-cell apoptosis with tolbutamide; increased relative number of beta-cells and bi-hormonal insulin + glucagon + cells with metformin.	Metformin	351-360	glucagon	Mus musculus	329-337
20444419-3	2010	It is thought that agents that increase the cellular AMP/ATP ratio, such as the antidiabetic biguanides metformin and phenformin, inhibit mTORC1 through AMPK activation of TSC1/2-dependent or -independent mechanisms.	Metformin	104-113	CREB regulated transcription coactivator 1	Mus musculus	138-144
34879473-4	2022	Given that metformin acts on multiple intracellular signaling pathways, including adenosine monophosphate (AMP)-activated protein kinase (AMPK) activation, and that AMPK and its downstream intracellular signaling control the activation and differentiation of T and B cells and inflammatory responses, metformin may exert immunomodulatory and anti- inflammatory effects.	Metformin	11-20	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	138-142
34879473-4	2022	Given that metformin acts on multiple intracellular signaling pathways, including adenosine monophosphate (AMP)-activated protein kinase (AMPK) activation, and that AMPK and its downstream intracellular signaling control the activation and differentiation of T and B cells and inflammatory responses, metformin may exert immunomodulatory and anti- inflammatory effects.	Metformin	301-310	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	165-169
20444419-3	2010	It is thought that agents that increase the cellular AMP/ATP ratio, such as the antidiabetic biguanides metformin and phenformin, inhibit mTORC1 through AMPK activation of TSC1/2-dependent or -independent mechanisms.	Metformin	104-113	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	153-157
20444419-5	2010	Consistent with these observations, in two distinct preclinical models of cancer and diabetes, metformin acts to suppress mTORC1 signaling in an AMPK-independent manner.	Metformin	95-104	CREB regulated transcription coactivator 1	Mus musculus	122-128
34637881-10	2022	Altogether our results suggest that metformin impairs PCC cellular proliferation.	Metformin	36-45	crystallin gamma D	Homo sapiens	54-57
20444419-5	2010	Consistent with these observations, in two distinct preclinical models of cancer and diabetes, metformin acts to suppress mTORC1 signaling in an AMPK-independent manner.	Metformin	95-104	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	145-149
20331505-11	2010	In DM2 patients with HCC, metformin therapy is associated with a reduced HCC risk and seems to have a protective effect on HCC development.	Metformin	26-35	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	3-6
20123087-12	2010	AMPK activity was increased by metformin in NG and HG (from 0.58+/-0.07 to.	Metformin	31-40	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
20123087-14	2010	The effects of metformin on the activities of NAD(P)H oxidase and AMPK were abolished in the presence of AMPK inhibitor, compound C. We have shown that metformin decreases production of ROS through reduction of NAD(P)H oxidase activity.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	66-70
20123087-14	2010	The effects of metformin on the activities of NAD(P)H oxidase and AMPK were abolished in the presence of AMPK inhibitor, compound C. We have shown that metformin decreases production of ROS through reduction of NAD(P)H oxidase activity.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	105-109
20123087-14	2010	The effects of metformin on the activities of NAD(P)H oxidase and AMPK were abolished in the presence of AMPK inhibitor, compound C. We have shown that metformin decreases production of ROS through reduction of NAD(P)H oxidase activity.	Metformin	152-161	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	66-70
20123087-14	2010	The effects of metformin on the activities of NAD(P)H oxidase and AMPK were abolished in the presence of AMPK inhibitor, compound C. We have shown that metformin decreases production of ROS through reduction of NAD(P)H oxidase activity.	Metformin	152-161	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	105-109
20053525-5	2010	Metformin treatment attenuated the main components of the fibrovascular tissue, wet weight, vascularization (Hb content), macrophage recruitment (NAG activity), collagen deposition and the levels of transforming growth factor (TGF-beta1) intraimplant.	Metformin	0-9	transforming growth factor, beta 1	Mus musculus	227-236
20222801-7	2010	In keeping with in vitro studies, recent epidemiological studies indicate that the incidence of cancer is reduced in Type 2 diabetes treated with metformin, an AMPK activator.	Metformin	146-155	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	160-164
20470935-6	2010	Differentiation of 3T3-L1 cells in the presence of palmitic acid did not alter adiponectin receptor proteins but metformin and fenofibrate upregulated AdipoR2 within 24 h of incubation.	Metformin	113-122	adiponectin receptor 2	Mus musculus	151-158
19111298-0	2010	Effect of metformin on serum visfatin levels in patients with polycystic ovary syndrome.	Metformin	10-19	nicotinamide phosphoribosyltransferase	Homo sapiens	29-37
19111298-1	2010	OBJECTIVE: To evaluate serum visfatin levels and to determine the effects of metformin treatment on visfatin levels in patients with polycystic ovary syndrome (PCOS).	Metformin	77-86	nicotinamide phosphoribosyltransferase	Homo sapiens	100-108
19111298-12	2010	CONCLUSION(S): Circulating visfatin levels were higher in patients with PCOS than healthy controls, and metformin treatment significantly reduced circulating visfatin concentrations after 3 months of therapy.	Metformin	104-113	nicotinamide phosphoribosyltransferase	Homo sapiens	158-166
19625456-4	2010	Drugs that activate AMPK, namely metformin and thiazolidinediones, are often used to treat metabolic disorders.	Metformin	33-42	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	20-24
19906888-5	2010	Treatment with metformin (10 mM) for 24 h reduced cell proliferation and the levels of cyclin D2 and E, and increased the associations cyclin D2/p21 and cyclin D2/p27 without affecting cell viability in response to IGF1 (10(-8) M).	Metformin	15-24	cyclin D2	Bos taurus	87-96
19906888-5	2010	Treatment with metformin (10 mM) for 24 h reduced cell proliferation and the levels of cyclin D2 and E, and increased the associations cyclin D2/p21 and cyclin D2/p27 without affecting cell viability in response to IGF1 (10(-8) M).	Metformin	15-24	cyclin D2	Bos taurus	135-144
19906888-5	2010	Treatment with metformin (10 mM) for 24 h reduced cell proliferation and the levels of cyclin D2 and E, and increased the associations cyclin D2/p21 and cyclin D2/p27 without affecting cell viability in response to IGF1 (10(-8) M).	Metformin	15-24	cyclin D2	Bos taurus	135-144
19906888-7	2010	Interestingly, metformin treatment for 1 h decreased MAPK3/1 (ERK1/2) and P90RSK phosphorylation without affecting AKT phosphorylation in response to IGF1.	Metformin	15-24	mitogen-activated protein kinase 3	Bos taurus	53-60
19906888-7	2010	Interestingly, metformin treatment for 1 h decreased MAPK3/1 (ERK1/2) and P90RSK phosphorylation without affecting AKT phosphorylation in response to IGF1.	Metformin	15-24	mitogen-activated protein kinase 3	Bos taurus	62-68
19906888-9	2010	It also eliminated the inhibitory effects of metformin on MAPK3/1 and P90RSK phosphorylation.	Metformin	45-54	mitogen-activated protein kinase 3	Bos taurus	58-65
19906888-10	2010	Taken together, our results strongly suggest that metformin reduces cell growth, protein synthesis, MAPK3/1, and P90RSK phosphorylation in response to IGF1 through an AMPK-dependent mechanism in cultured bovine granulosa cells.	Metformin	50-59	mitogen-activated protein kinase 3	Bos taurus	100-105
20804053-6	2010	However, progesterone receptor-positive (PR+) tumors in metformin-treated patients were revealed more often than in those receiving SU alone (p = 0.43) or with insulin (p = 0.041), respectively.	Metformin	56-65	progesterone receptor	Homo sapiens	9-30
19725053-9	2009	Metformin significantly inhibited gene expression of Runx2 along with osteoblast differentiation markers including osteocalcin (Ocn), bone sialo protein (Bsp), and osteopontin (Opn).	Metformin	0-9	secreted phosphoprotein 1	Mus musculus	164-175
19725053-9	2009	Metformin significantly inhibited gene expression of Runx2 along with osteoblast differentiation markers including osteocalcin (Ocn), bone sialo protein (Bsp), and osteopontin (Opn).	Metformin	0-9	secreted phosphoprotein 1	Mus musculus	177-180
19570618-3	2009	Clinical AMPK activators such as metformin and berberine may thus have potential in the clinical management of ADPKD.	Metformin	33-42	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	9-13
19664596-4	2009	Interestingly, in contrast to rotenone treatment, G6pc mRNA down-regulation was observed in the NDI1 expressing cells after metformin treatment.	Metformin	124-133	NADH-ubiquinone reductase (H(+)-translocating) NDI1	Saccharomyces cerevisiae S288C	96-100
19664596-5	2009	Since NDI1 can functionally complement the complex I under the presence of metformin or rotenone, our results indicate that metformin induces down-regulation of G6pc expression through an inhibition of complex I and an activation of AMPK-independent mechanism.	Metformin	75-84	NADH-ubiquinone reductase (H(+)-translocating) NDI1	Saccharomyces cerevisiae S288C	6-10
19664596-5	2009	Since NDI1 can functionally complement the complex I under the presence of metformin or rotenone, our results indicate that metformin induces down-regulation of G6pc expression through an inhibition of complex I and an activation of AMPK-independent mechanism.	Metformin	124-133	NADH-ubiquinone reductase (H(+)-translocating) NDI1	Saccharomyces cerevisiae S288C	6-10
19579180-0	2009	Regulation of glucose-6-phosphatase gene expression by insulin and metformin.	Metformin	67-76	glucose-6-phosphatase catalytic subunit 1	Homo sapiens	14-35
19579180-3	2009	Since the mechanisms of metformin action are only partially understood at the molecular level, we studied the regulation of the gene promoter activity of glucose-6-phosphatase (G6Pase), the central hepatic gluconeogenic enzyme, by this drug.	Metformin	24-33	glucose-6-phosphatase catalytic subunit 1	Homo sapiens	154-175
19579180-3	2009	Since the mechanisms of metformin action are only partially understood at the molecular level, we studied the regulation of the gene promoter activity of glucose-6-phosphatase (G6Pase), the central hepatic gluconeogenic enzyme, by this drug.	Metformin	24-33	glucose-6-phosphatase catalytic subunit 1	Homo sapiens	177-183
19579180-4	2009	We have found that both metformin and insulin inhibit the basal and dexamethasone/cAMP-stimulated G6Pase promoter activity in hepatoma cells.	Metformin	24-33	glucose-6-phosphatase catalytic subunit 1	Homo sapiens	98-104
19579180-5	2009	Since one of the pharmacological targets of metformin is AMP-activated protein kinase (AMPK) and activation of AMPK is known to inhibit hepatic glucose production by the suppression of G6Pase gene transcription, we studied the effect of AMPK in this context.	Metformin	44-53	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	87-91
19579180-6	2009	Under nonstimulated conditions, the inhibitory effect of both insulin and metformin was partially counteracted to a similar extent by treatment with compound C, a specific inhibitor of AMPK.	Metformin	74-83	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	185-189
19644919-4	2009	Metformin, one of the most widely prescribed anti-diabetic drugs, exerts its actions by AMPK activation.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	88-92
19571378-4	2009	The mRNA and protein expression of GAPD, detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively, decreased upon treatment of the cells with 10 mM metformin for 24 h. Under the conditions, metformin induced phosphorylation of AMP-activated protein kinase (AMPK).	Metformin	205-214	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	284-312
19571378-4	2009	The mRNA and protein expression of GAPD, detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively, decreased upon treatment of the cells with 10 mM metformin for 24 h. Under the conditions, metformin induced phosphorylation of AMP-activated protein kinase (AMPK).	Metformin	205-214	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	314-318
19571378-4	2009	The mRNA and protein expression of GAPD, detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively, decreased upon treatment of the cells with 10 mM metformin for 24 h. Under the conditions, metformin induced phosphorylation of AMP-activated protein kinase (AMPK).	Metformin	247-256	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	284-312
19571378-4	2009	The mRNA and protein expression of GAPD, detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively, decreased upon treatment of the cells with 10 mM metformin for 24 h. Under the conditions, metformin induced phosphorylation of AMP-activated protein kinase (AMPK).	Metformin	247-256	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	314-318
19571378-10	2009	These results suggest that signal transducers, adenylate cyclase (AC), protein kinase A (PKA), and AMPK, are involved in the signaling pathway triggered by metformin and CRE-binding protein is one of the transcription factors for the GAPD gene down-regulated by metformin.	Metformin	156-165	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	99-103
19571378-10	2009	These results suggest that signal transducers, adenylate cyclase (AC), protein kinase A (PKA), and AMPK, are involved in the signaling pathway triggered by metformin and CRE-binding protein is one of the transcription factors for the GAPD gene down-regulated by metformin.	Metformin	262-271	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	99-103
19440038-7	2009	At the molecular level, metformin increases P-AMPK, reduces P-EGFR, EGFR, P-MAPK, P-Src, cyclin D1 and cyclin E (but not cyclin A or B, p27 or p21), and induces PARP cleavage in a dose- and time-dependent manner.	Metformin	24-33	cyclin D1	Homo sapiens	89-98
19440038-7	2009	At the molecular level, metformin increases P-AMPK, reduces P-EGFR, EGFR, P-MAPK, P-Src, cyclin D1 and cyclin E (but not cyclin A or B, p27 or p21), and induces PARP cleavage in a dose- and time-dependent manner.	Metformin	24-33	collagen type XI alpha 2 chain	Homo sapiens	161-165
19494326-2	2009	Metformin is the most widely used drug for diabetes and mediates its action via activating AMP-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	121-125
19494326-4	2009	Furthermore, the AMPK activity and lipids alterations (total phospholipids and in free fatty acids) were restored by metformin treatment in the CNS of treated EAE animals, suggesting the possible involvement of AMPK.	Metformin	117-126	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	17-21
19494326-4	2009	Furthermore, the AMPK activity and lipids alterations (total phospholipids and in free fatty acids) were restored by metformin treatment in the CNS of treated EAE animals, suggesting the possible involvement of AMPK.	Metformin	117-126	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	211-215
19494326-5	2009	Metformin activated AMPK in macrophages and thereby inhibited biosynthesis of phospholipids as well as neutral lipids and also down-regulated the expression of endotoxin (LPS)-induced proinflammatory cytokines and their mediators (iNOS and cyclooxygenase 2).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	20-24
19372741-0	2009	Genome-wide inhibitory impact of the AMPK activator metformin on [kinesins, tubulins, histones, auroras and polo-like kinases] M-phase cell cycle genes in human breast cancer cells.	Metformin	52-61	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	37-41
19372741-2	2009	Using Database for Annotation, Visualization and Integrated Discovery bioinformatics (DAVID) resources we herein reveal that, at doses that lead to activation of the AMP-activated protein kinase (AMPK), metformin not only downregulates genes coding for ribosomal proteins (i.e., protein and macromolecule biosynthesis) but unexpectedly suppresses numerous mitosis-related gene families including kinesins, tubulins, histones, auroras and polo-like kinases.	Metformin	203-212	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	166-194
19372741-2	2009	Using Database for Annotation, Visualization and Integrated Discovery bioinformatics (DAVID) resources we herein reveal that, at doses that lead to activation of the AMP-activated protein kinase (AMPK), metformin not only downregulates genes coding for ribosomal proteins (i.e., protein and macromolecule biosynthesis) but unexpectedly suppresses numerous mitosis-related gene families including kinesins, tubulins, histones, auroras and polo-like kinases.	Metformin	203-212	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	196-200
19243571-3	2009	AMPK activators, metformin and thiazolidinediones, are used for the treatment of type II diabetes.	Metformin	17-26	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
19153119-0	2009	The antidiabetic drug metformin: a pharmaceutical AMPK activator to overcome breast cancer resistance to HER2 inhibitors while decreasing risk of cardiomyopathy.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	50-54
19125418-6	2009	We found that AMPK is robustly activated in rat hepatoma McA-RH7777 cells treated with two widely used AMPK activators, AICAR and metformin, and AMPK activation sharply suppresses SREBP-1c mRNA and nuclear SREBP-1c protein, but not SREBP-1a mRNA derived from the same gene.	Metformin	130-139	sterol regulatory element binding transcription factor 1	Rattus norvegicus	180-188
19125418-6	2009	We found that AMPK is robustly activated in rat hepatoma McA-RH7777 cells treated with two widely used AMPK activators, AICAR and metformin, and AMPK activation sharply suppresses SREBP-1c mRNA and nuclear SREBP-1c protein, but not SREBP-1a mRNA derived from the same gene.	Metformin	130-139	sterol regulatory element binding transcription factor 1	Rattus norvegicus	206-214
19125418-7	2009	These inhibitory effects are reversed by the AMPK inhibitor Compound C or 8-BrAMP, demonstrating the requirement of AMPK in the suppression of SREBP-1c mRNA and nuclear SREBP-1c protein by AICAR and metformin.	Metformin	199-208	sterol regulatory element binding transcription factor 1	Rattus norvegicus	143-151
19125418-7	2009	These inhibitory effects are reversed by the AMPK inhibitor Compound C or 8-BrAMP, demonstrating the requirement of AMPK in the suppression of SREBP-1c mRNA and nuclear SREBP-1c protein by AICAR and metformin.	Metformin	199-208	sterol regulatory element binding transcription factor 1	Rattus norvegicus	169-177
19096023-11	2009	This study demonstrates that metformin significantly improves left ventricular function and survival via activation of AMPK and its downstream mediators, eNOS and PGC-1alpha, in a murine model of heart failure.	Metformin	29-38	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	163-173
19084501-2	2009	We previously demonstrated that hyperglycemia-induced production of reactive oxygen species from mitochondria (mtROS) contributed to the development of diabetic complications, and metformin normalized mt ROS production by induction of MnSOD and promotion of mitochondrial biogenesis by activating the PGC-1alpha pathway.	Metformin	180-189	superoxide dismutase 2	Homo sapiens	235-240
18256928-4	2009	Stimulation of AMPK by metformin resulted in a significant repression of cell proliferation and active MAPK1/2 in both estrogen receptor alpha (ERalpha) negative (MDA-MB-231, MDA-MB-435) and positive (MCF-7, T47D) human breast cancer cell lines.	Metformin	23-32	mitogen-activated protein kinase 12	Homo sapiens	103-110
18972094-5	2009	RESULTS: Following combined thiazolidinedione-metformin therapy, increases in glucose disposal and increases in sub-maximal and maximal insulin-induced activities of all four muscle signalling factors, IR, IRS-1-dependent PI3K (IRS-1/PI3K), aPKC and PKBbeta, were observed.	Metformin	46-55	insulin receptor	Homo sapiens	202-204
18641273-6	2008	Metformin did not alter the protein expressions of endothelial nitric oxide synthase (eNOS), phospho-eNOS (Ser1177), or COX-1, but it increased COX-2 protein.	Metformin	0-9	cytochrome c oxidase II, mitochondrial	Rattus norvegicus	144-149
18670165-5	2008	Metformin induced modest expression changes, including G6pc in the liver as previously reported.	Metformin	0-9	glucose-6-phosphatase, catalytic	Mus musculus	55-59
18212742-0	2008	The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level.	Metformin	22-31	cyclin D1	Homo sapiens	104-113
18212742-10	2008	Similar, to the in vitro study, metformin led to a strong reduction of cyclin D1 protein level in tumors providing evidence for a mechanism that may contribute to the antineoplastic effects of metformin suggested by recent epidemiological studies.	Metformin	32-41	cyclin D1	Homo sapiens	71-80
18212742-10	2008	Similar, to the in vitro study, metformin led to a strong reduction of cyclin D1 protein level in tumors providing evidence for a mechanism that may contribute to the antineoplastic effects of metformin suggested by recent epidemiological studies.	Metformin	193-202	cyclin D1	Homo sapiens	71-80
18387000-5	2008	In contrast, activating the AMPK pathway by administration of metformin, phenformin or A-769662 to PTEN(+/-) mice significantly delayed tumour onset.	Metformin	62-71	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	28-32
18387000-9	2008	Most importantly, our results demonstrate the potential of AMPK activators, such as clinically approved metformin, as anticancer agents, which will suppress tumour development by triggering a physiological signalling pathway that potently inhibits cell growth.	Metformin	104-113	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	59-63
18198220-7	2008	Metformin, a known AMPK regulator, prevented the corticosteroid-induced effects on AMPK in human adipocytes and rat hypothalamic neurons.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	19-23
18198220-7	2008	Metformin, a known AMPK regulator, prevented the corticosteroid-induced effects on AMPK in human adipocytes and rat hypothalamic neurons.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	83-87
18693456-1	2008	This study was aimed to compare the effect of insulin plus rosiglitazone with that of insulin plus metformin on the level of serum N-terminal pro-brain natriuretic peptide (NT-BNP) in patients with type 2 diabetes mellitus, and to find out whether serum NT-BNP can be used as an index for predicting heart failure induced by rosiglitazone in the cases of type 2 diabetes mellitus.	Metformin	99-108	natriuretic peptide B	Homo sapiens	176-179
18334179-11	2008	Recent studies show that AMPK is involved in the mechanism of action of metformin.	Metformin	72-81	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	25-29
18250273-0	2008	Phosphorylation of LKB1 at serine 428 by protein kinase C-zeta is required for metformin-enhanced activation of the AMP-activated protein kinase in endothelial cells.	Metformin	79-88	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	116-144
18250273-1	2008	BACKGROUND: Metformin, one of most commonly used antidiabetes drugs, is reported to exert its therapeutic effects by activating AMP-activated protein kinase (AMPK); however, the mechanism by which metformin activates AMPK is poorly defined.	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	128-156
18250273-1	2008	BACKGROUND: Metformin, one of most commonly used antidiabetes drugs, is reported to exert its therapeutic effects by activating AMP-activated protein kinase (AMPK); however, the mechanism by which metformin activates AMPK is poorly defined.	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	158-162
18250273-1	2008	BACKGROUND: Metformin, one of most commonly used antidiabetes drugs, is reported to exert its therapeutic effects by activating AMP-activated protein kinase (AMPK); however, the mechanism by which metformin activates AMPK is poorly defined.	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	217-221
17615555-7	2008	Moreover, another AMPK activator metformin was not able to mimic the effects of AICAR.	Metformin	33-42	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	18-22
18345405-3	2008	The Diabetes Prevention Program Research Group studies have shown that metformin administration and lifestyle-intervention (diet and exercise) reduce the incidence of Diabetes Mellitus type 2 (DM2).	Metformin	71-80	CCHC-type zinc finger nucleic acid binding protein	Homo sapiens	167-191
18345405-3	2008	The Diabetes Prevention Program Research Group studies have shown that metformin administration and lifestyle-intervention (diet and exercise) reduce the incidence of Diabetes Mellitus type 2 (DM2).	Metformin	71-80	CCHC-type zinc finger nucleic acid binding protein	Homo sapiens	193-196
18345405-6	2008	On the other hand, several experimental evidences indicate that AMPK may be an important target of metformin action.	Metformin	99-108	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	64-68
18345405-7	2008	This paper discusses various ways for AMPK regulation, suggesting a possible mechanism for its activation by metformin that involves the production of reactive nitrogen species.	Metformin	109-118	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	38-42
18345405-10	2008	The finding of AMPK activation by metformin draws attention to this enzyme as an important pharmacological target.	Metformin	34-43	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	15-19
17687118-11	2008	Roscovitine, U0126, and metformin inhibited meiotic divisions; they all induced a decrease of CCNB1 and phospho-MAPK3/1 levels and prevented CPEB degradation.	Metformin	24-33	cyclin B1	Bos taurus	94-99
17687118-12	2008	However, only metformin depleted AURKA.	Metformin	14-23	aurora kinase A	Bos taurus	33-38
17909097-6	2008	Metformin-induced SHP gene expression was abolished by adenovirus containing the dominant negative form of AMPK (Ad-DN-AMPK), as well as by compound C. Metformin inhibited hepatocyte nuclear factor-4alpha-or FoxA2-mediated promoter activity of PEPCK and G6Pase, and the inhibition was blocked with siRNA SHP.	Metformin	0-9	glucose-6-phosphatase, catalytic	Mus musculus	254-260
17909097-6	2008	Metformin-induced SHP gene expression was abolished by adenovirus containing the dominant negative form of AMPK (Ad-DN-AMPK), as well as by compound C. Metformin inhibited hepatocyte nuclear factor-4alpha-or FoxA2-mediated promoter activity of PEPCK and G6Pase, and the inhibition was blocked with siRNA SHP.	Metformin	152-161	glucose-6-phosphatase, catalytic	Mus musculus	254-260
18237462-1	2008	Metformin is metabolized primarily via hepatic microsomal cytochrome P450 (CYP)2C11, CYP2D1 and CYP3A1/2 in rats.	Metformin	0-9	cytochrome P450, family 3, subfamily a, polypeptide 23-polypeptide 1	Rattus norvegicus	96-102
18022388-3	2008	Drugs that activate AMPK indirectly (metformin and thiazolidinediones) are now the mainstay of treatment for type 2 diabetes, but more direct AMPK activators may have fewer side effects.	Metformin	37-46	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	20-24
18217246-3	2007	When used in combination with metformin, sulfonylureas, or TZDs, GLP-1 analogs such as exenatide and DPP-IV inhibitors such as sitagliptin reduce A1C, fasting glucose levels, and postprandial glucose levels with few additional adverse events.	Metformin	30-39	glucagon like peptide 1 receptor	Homo sapiens	65-70
18006825-2	2007	The effects of metformin are explained by the activation of AMP-activated protein kinase (AMPK), which regulates cellular energy metabolism.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	60-88
18006825-2	2007	The effects of metformin are explained by the activation of AMP-activated protein kinase (AMPK), which regulates cellular energy metabolism.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	90-94
18006825-8	2007	The decrease in translation caused by metformin was associated with mammalian target of rapamycin (mTOR) inhibition, and a decrease in the phosphorylation of S6 kinase, ribosomal protein S6, and eIF4E-binding protein 1.	Metformin	38-47	ribosomal protein S6	Homo sapiens	169-189
18006825-9	2007	The effects of metformin on translation were mediated by AMPK, as treatment of cells with the AMPK inhibitor compound C prevented the inhibition of translation.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	57-61
18006825-9	2007	The effects of metformin on translation were mediated by AMPK, as treatment of cells with the AMPK inhibitor compound C prevented the inhibition of translation.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	94-98
18006825-11	2007	These results show that metformin-mediated AMPK activation leads to inhibition of mTOR and a reduction in translation initiation, thus providing a possible mechanism of action of metformin in the inhibition of cancer cell growth.	Metformin	24-33	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	43-47
18006825-11	2007	These results show that metformin-mediated AMPK activation leads to inhibition of mTOR and a reduction in translation initiation, thus providing a possible mechanism of action of metformin in the inhibition of cancer cell growth.	Metformin	179-188	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	43-47
17567959-8	2007	Metformin decreased AURKA and CCNB1 protein levels in oocytes.	Metformin	0-9	aurora kinase A	Bos taurus	20-25
17567959-8	2007	Metformin decreased AURKA and CCNB1 protein levels in oocytes.	Metformin	0-9	cyclin B1	Bos taurus	30-35
17567959-9	2007	Moreover, after 1 h of IVM, metformin decreased RPS6 phosphorylation and increased EEF2 phosphorylation, suggesting that protein synthesis rates were lower in oocytes from metformin-treated COCs.	Metformin	28-37	eukaryotic translation elongation factor 2	Bos taurus	83-87
17567959-9	2007	Moreover, after 1 h of IVM, metformin decreased RPS6 phosphorylation and increased EEF2 phosphorylation, suggesting that protein synthesis rates were lower in oocytes from metformin-treated COCs.	Metformin	172-181	eukaryotic translation elongation factor 2	Bos taurus	83-87
17567959-11	2007	Thus, in bovine COCs, metformin blocks meiotic progression at the GV stage, activates PRKAA, and inhibits MAPK3/1 phosphorylation in both the oocytes and cumulus cells during IVM.	Metformin	22-31	mitogen-activated protein kinase 3	Bos taurus	106-111
18062354-7	2007	Metformin, Thiazolidinediones and Acarbose are anti-hyperglycemic drugs of choice: they reduce the incidence of DM2 and IR (or improve insulin sensitivity) and they decrease or stabilize the visceral adipose tissue mass (Thiazolidinediones increases subcutaneous fat only).	Metformin	0-9	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	112-122
17712875-12	2007	A mixed model analysis of variance on the 178 patients who started with combination therapy, either immediately or after a 3-6 month period on diet, showed that metformin plus gliclazide, repaglinide, or pioglitazone was associated with a gradual increase in HbA1c values.	Metformin	161-170	hemoglobin subunit alpha 1	Homo sapiens	259-263
17339833-1	2007	BACKGROUND AND PURPOSE: Two mechanisms have been proposed to explain the insulin-sensitising properties of metformin in peripheral tissues: (a) inhibition of electron transport chain complex I, and (b) activation of the AMP activated protein kinase (AMPK).	Metformin	107-116	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	250-254
17339833-11	2007	CONCLUSIONS AND IMPLICATIONS: AMPK activation can partly be attributed to metformin"s inhibitory action on mitochondrial complex I. Anaplerotic fuel metabolism via complex II rescued beta-cells from metformin-associated toxicity.	Metformin	74-83	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	30-34
17339833-11	2007	CONCLUSIONS AND IMPLICATIONS: AMPK activation can partly be attributed to metformin"s inhibitory action on mitochondrial complex I. Anaplerotic fuel metabolism via complex II rescued beta-cells from metformin-associated toxicity.	Metformin	199-208	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	30-34
17458042-6	2007	(3) In a randomised double-blind placebo-controlled trial involving 82 children, the mean reduction in HbA1c level with metformin was statistically significant after 8 weeks of treatment (about 1% in absolute values, versus no change in the placebo group).	Metformin	120-129	hemoglobin subunit alpha 1	Homo sapiens	103-107
17123942-6	2007	In granulosa cells from small follicles, metformin (10 mM) reduced production of both progesterone and estradiol and decreased the abundance of HSD3B, CYP11A1, and STAR proteins in presence or absence of FSH (10(-8) M) and IGF1 (10(-8) M).	Metformin	41-50	cholesterol side-chain cleavage enzyme, mitochondrial	Bos taurus	151-158
17123942-10	2007	Metformin decreased phosphorylation levels of MAPK3/MAPK1 and MAPK14 in a dose- and time-dependent manner.	Metformin	0-9	mitogen-activated protein kinase 3	Bos taurus	46-51
17123942-12	2007	Thus, in bovine granulosa cells, metformin decreases steroidogenesis and MAPK3/MAPK1 phosphorylation through AMPK activation.	Metformin	33-42	mitogen-activated protein kinase 3	Bos taurus	73-78
17496363-8	2007	The two leading diabetic drugs namely, metformin and rosiglitazone, show their metabolic effects partially through AMPK.	Metformin	39-48	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	115-119
19888409-13	2007	Metformin increased visfatin concentrations.	Metformin	0-9	nicotinamide phosphoribosyltransferase	Homo sapiens	20-28
17135357-4	2007	We report that when S122 on NDPK-A is phosphorylated by AMPK alpha1 in vivo, (i.e., stimulation of AMPK using either metformin or phenformin) initiating the substrate channeling mechanism, the catalytic subunit of CK2 (CK2alpha) is expelled from the complex and translocates to bind NDPK-B, a closely related but independent isoform of NDPK.	Metformin	117-126	NME/NM23 nucleoside diphosphate kinase 1	Homo sapiens	28-34
17135357-4	2007	We report that when S122 on NDPK-A is phosphorylated by AMPK alpha1 in vivo, (i.e., stimulation of AMPK using either metformin or phenformin) initiating the substrate channeling mechanism, the catalytic subunit of CK2 (CK2alpha) is expelled from the complex and translocates to bind NDPK-B, a closely related but independent isoform of NDPK.	Metformin	117-126	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	56-67
17135357-4	2007	We report that when S122 on NDPK-A is phosphorylated by AMPK alpha1 in vivo, (i.e., stimulation of AMPK using either metformin or phenformin) initiating the substrate channeling mechanism, the catalytic subunit of CK2 (CK2alpha) is expelled from the complex and translocates to bind NDPK-B, a closely related but independent isoform of NDPK.	Metformin	117-126	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	56-60
18399062-1	2007	A case-control study was carried out on a sample of 15 Mexican patients (40-56 years old) with type 2 diabetes mellitus (DM2) that had developed five years and been treated with oral hypoglycemic drugs (sulfonylurea and/or metformin), with no microvascular or macrovascular complications.	Metformin	223-232	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	121-124
16902066-7	2006	Metformin increased the hexokinase activity in the white gastrocnemius, the citrate synthase activity in all three muscles, and the beta-hydroxyacyl-CoA dehydrogenase activity in the soleus.	Metformin	0-9	citrate synthase	Rattus norvegicus	76-92
16807400-7	2006	hMATE2-K also transported cimetidine, 1-methyl-4-phenylpyridinium (MPP), procainamide, metformin, and N1-methylnicotinamide.	Metformin	87-96	solute carrier family 47 member 2	Homo sapiens	0-6
34752810-3	2022	The present study aimed to evaluate the anti-androgenic effects of quercetin (Q) in comparison with metformin (MET) on hyperandrogenism and ovarian dysfunction in a DHEA-induced PCOS rat model.	Metformin	100-109	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	111-114
34890968-6	2022	Metformin-treated preosteoblasts increased osteopontin (OPN) expression that upon silencing, reduced subsequent myeloma cell adherence.	Metformin	0-9	secreted phosphoprotein 1	Mus musculus	43-54
34890968-6	2022	Metformin-treated preosteoblasts increased osteopontin (OPN) expression that upon silencing, reduced subsequent myeloma cell adherence.	Metformin	0-9	secreted phosphoprotein 1	Mus musculus	56-59
34890968-9	2022	Metformin-pretreated mice had an increase in tumour burden, associated with an increase in osteolytic bone lesions and elevated OPN expression in the bone marrow.	Metformin	0-9	secreted phosphoprotein 1	Mus musculus	128-131
34890968-10	2022	Collectively, we show that metformin increases OPN expression in preosteoblasts, increasing myeloma cell adherence.	Metformin	27-36	secreted phosphoprotein 1	Mus musculus	47-50
16807400-8	2006	Kinetic analyses demonstrated that the Michaelis-Menten constants for the hMATE2-K-mediated transport of TEA, MPP, cimetidine, metformin, and procainamide were 0.83 mM, 93.5 microM, 0.37 mM, 1.05 mM, and 4.10 mM, respectively.	Metformin	127-136	solute carrier family 47 member 2	Homo sapiens	74-80
16807400-9	2006	Ammonium chloride-induced intracellular acidification significantly stimulated the hMATE2-K-dependent transport of organic cations such as TEA, MPP, procainamide, metformin, N1-methylnicotinamide, creatinine, guanidine, quinidine, quinine, thiamine, and verapamil.	Metformin	163-172	solute carrier family 47 member 2	Homo sapiens	83-89
16809378-8	2006	Metformin administered together with DHEA was able to prevent the increase of ovarian iNOS and COX2 expressions and to enhance the activation of phosphorylated AMPK-alpha expression.	Metformin	0-9	cytochrome c oxidase II, mitochondrial	Mus musculus	95-99
17132543-1	2006	In the present study, we focused on the insulin-receptor binding in circulating erythrocytes of N-benzoyl-D-phenylalanine (NBDP) and metformin in neonatal streptozotocin (nSTZ)-induced male Wistar rats.	Metformin	133-142	insulin receptor	Rattus norvegicus	40-56
16752183-5	2006	RESULTS: This analysis identified 14 genes that showed at least a 1.5-fold difference in expression following metformin treatment, including a reduction of glucose-6-phosphatase gene expression.	Metformin	110-119	glucose-6-phosphatase, catalytic	Mus musculus	156-177
16752183-7	2006	Enzymatic activity of glucose-6-phosphatase was also reduced in metformin-treated liver.	Metformin	64-73	glucose-6-phosphatase, catalytic	Mus musculus	22-43
16752183-9	2006	CONCLUSIONS/INTERPRETATION: These results suggest that reduction of glucose-6-phosphatase activity, as well as suppression of mRNA expression levels of this gene, in liver is of prime importance for controlling blood glucose levels in vivo, at least at early time points after metformin treatment.	Metformin	277-286	glucose-6-phosphatase, catalytic	Mus musculus	68-89
16644802-5	2006	Medical interest in the AMPK system has recently increased with the demonstration that AMPK could mediate some of the effects of the fat cell-derived adiponectin and the antidiabetic drugs metformin and thiazolidinediones.	Metformin	189-198	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	24-28
16644802-5	2006	Medical interest in the AMPK system has recently increased with the demonstration that AMPK could mediate some of the effects of the fat cell-derived adiponectin and the antidiabetic drugs metformin and thiazolidinediones.	Metformin	189-198	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	87-91
16784971-8	2006	Metformin vs placebo treatment of diabetic pigs (twice 1.5 g/d) for 2 weeks during isoenergetic feeding (1045 kJ/kg body weight(0.75)) resulted in a reduction in both fasting and postprandial hyperglycemia (14.7 +/- 1.5 vs 19.4 +/- 0.6 and 24.9 +/- 2.2 vs 35.5 +/- 4.9 mmol/L), a reduction in daily urinary glucose excretion (approximately 250 vs approximately 350 g/kg food), and an increase in insulin-stimulated glucose disposal (9.4 +/- 2.2 vs 5.8 +/- 1.7 mg kg(-1) min(-1); P &lt; .05), respectively.	Metformin	0-9	insulin	Sus scrofa	396-403
16489446-9	2006	Metformin stimulated IPF1 nuclear accumulation and DNA binding activity in a time-dependent manner, with maximal effects observed after 2 h. CONCLUSIONS/INTERPRETATION: Metformin and rosiglitazone have direct effects on beta cell gene expression, suggesting that these agents may play a previously unrecognised role in the direct regulation of pancreatic beta cell function.	Metformin	0-9	pancreatic and duodenal homeobox 1	Mus musculus	21-25
34972763-2	2021	Medications that affect ACE2 expression or function such as angiotensin receptor blockers (ARBs) and ACE inhibitors (ACE-I) and metformin have the potential to counter the dysregulation of ACE2 by the virus and protect against viral injury.	Metformin	128-137	angiotensin converting enzyme 2	Homo sapiens	24-28
34972763-2	2021	Medications that affect ACE2 expression or function such as angiotensin receptor blockers (ARBs) and ACE inhibitors (ACE-I) and metformin have the potential to counter the dysregulation of ACE2 by the virus and protect against viral injury.	Metformin	128-137	angiotensin converting enzyme 2	Homo sapiens	189-193
34895136-13	2021	AMPK activation and NF-kappaB inhibition could inhibit AVICs calcification induced by PM treatment; however, AMPK and AKT inhibition reversed the protective effect of metformin.	Metformin	167-176	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
34895136-13	2021	AMPK activation and NF-kappaB inhibition could inhibit AVICs calcification induced by PM treatment; however, AMPK and AKT inhibition reversed the protective effect of metformin.	Metformin	167-176	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	109-113
34698884-10	2021	Notably, pleiotropic drugs, like statins, liraglutide and metformin, affect miR-34a expression.	Metformin	58-67	microRNA 34a	Homo sapiens	76-83
34432352-0	2021	Pretreatment with metformin prevents microcystin-LR-induced tau hyperphosphorylation via mTOR-dependent PP2A and GSK-3beta activation.	Metformin	18-27	glycogen synthase kinase 3 alpha	Homo sapiens	113-122
34432352-4	2021	The results showed that metformin effectively prevented tau hyperphosphorylation at Ser202 caused by MC-LR through PP2A and GSK-3b activity.	Metformin	24-33	glycogen synthase kinase 3 beta	Homo sapiens	124-130
34432352-7	2021	In sum, the results suggested that metformin can ameliorate the MC-LR-induced AD-like phenotype by preventing tau phosphorylation at Ser202, which was mainly mediated by mTOR-dependent PP2A and GSK-3beta activation.	Metformin	35-44	glycogen synthase kinase 3 alpha	Homo sapiens	194-203
34887262-7	2021	We determined the efficacy of low-dose SN-38 or metformin in sensitizing unresponsive tumors to respond to anti-PD-1 therapy in a syngeneic tumor system.	Metformin	48-57	programmed cell death 1	Homo sapiens	112-116
34688695-10	2021	Our results revealed that blunting p38 MAPKalpha and ERK1/2 activities by empagliflozin enhanced the antifibrotic effect of metformin and augmented its AMPK-induced NF-kappaB inactivation.	Metformin	124-133	mitogen-activated protein kinase 3	Mus musculus	53-59
34884312-0	2021	The Antidiabetic Agent Metformin Inhibits IL-23 Production in Murine Bone-Marrow-Derived Dendritic Cells.	Metformin	23-32	interleukin 23, alpha subunit p19	Mus musculus	42-47
34884312-9	2021	Since NF-kappaB signaling regulates Nfkbiz expression and the anti-diabetic agent metformin reportedly modulates NF-kappaB signaling, we examined the effect of metformin treatment on IL-36gamma-induced IL-23 production.	Metformin	82-91	interleukin 23, alpha subunit p19	Mus musculus	202-207
34884312-9	2021	Since NF-kappaB signaling regulates Nfkbiz expression and the anti-diabetic agent metformin reportedly modulates NF-kappaB signaling, we examined the effect of metformin treatment on IL-36gamma-induced IL-23 production.	Metformin	160-169	interleukin 23, alpha subunit p19	Mus musculus	202-207
34884312-10	2021	Metformin treatment impaired the phosphorylation of NF-kappaB induced by IL-36gamma stimulation with the subsequent downregulation of Nfkbiz, resulting in the inhibition of IL-23 production in BMDCs.	Metformin	0-9	interleukin 23, alpha subunit p19	Mus musculus	173-178
34884312-11	2021	These data provided evidence that metformin treatment can inhibit IL-36gamma-mediated IL-23 production in BMDCs, which might contribute to the prevention of psoriasis.	Metformin	34-43	interleukin 23, alpha subunit p19	Mus musculus	86-91
34837101-0	2021	Metformin inhibits human non-small cell lung cancer by regulating AMPK-CEBPB-PDL1 signaling pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	66-70
34837101-0	2021	Metformin inhibits human non-small cell lung cancer by regulating AMPK-CEBPB-PDL1 signaling pathway.	Metformin	0-9	CCAAT enhancer binding protein beta	Homo sapiens	71-76
34837101-10	2021	Western blotting showed that metformin could regulate the function of NSCLC cells via AMPK-CEBPB-PDL1 signaling.	Metformin	29-38	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	86-90
34837101-10	2021	Western blotting showed that metformin could regulate the function of NSCLC cells via AMPK-CEBPB-PDL1 signaling.	Metformin	29-38	CCAAT enhancer binding protein beta	Homo sapiens	91-96
34837101-14	2021	In conclusion, metformin inhibited the proliferation of NSCLC cells and played an anti-tumor role in an AMPK-CEBPB-PDL1 signaling-dependent manner.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	104-108
34837101-14	2021	In conclusion, metformin inhibited the proliferation of NSCLC cells and played an anti-tumor role in an AMPK-CEBPB-PDL1 signaling-dependent manner.	Metformin	15-24	CCAAT enhancer binding protein beta	Homo sapiens	109-114
34779127-0	2022	Metformin induces insulin secretion by preserving pancreatic aquaporin 7 expression in type 2 diabetes mellitus.	Metformin	0-9	aquaporin 7	Homo sapiens	61-72
34464747-0	2021	Metformin protects against diclofenac-induced toxicity in primary rat hepatocytes by preserving mitochondrial integrity via a pathway involving EPAC.	Metformin	0-9	Rap guanine nucleotide exchange factor 3	Rattus norvegicus	144-148
34464747-13	2021	Metformin restored mitochondrial morphology in an EPAC-independent manner.	Metformin	0-9	Rap guanine nucleotide exchange factor 3	Rattus norvegicus	50-54
34464747-14	2021	DF-induced mitochondrial dysfunction which was demonstrated by decreased oxygen consumption rate, an increased ROS production and a reduced MnSOD level, were all reversed by metformin in an EPAC-dependent manner.	Metformin	174-183	Rap guanine nucleotide exchange factor 3	Rattus norvegicus	190-194
34649197-6	2021	The selective glucose deprivation would not only disrupt tumor energy metabolism, but also upregulate the PP2A regulatory subunit B56delta and sensitize tumor cells to the metformin-induced CIP2A inhibition, leading to efficient apoptosis induction via PP2A-GSK3beta-MCL-1 axis with negligible side effects.	Metformin	172-181	glycogen synthase kinase 3 alpha	Homo sapiens	258-266
16489446-9	2006	Metformin stimulated IPF1 nuclear accumulation and DNA binding activity in a time-dependent manner, with maximal effects observed after 2 h. CONCLUSIONS/INTERPRETATION: Metformin and rosiglitazone have direct effects on beta cell gene expression, suggesting that these agents may play a previously unrecognised role in the direct regulation of pancreatic beta cell function.	Metformin	169-178	pancreatic and duodenal homeobox 1	Mus musculus	21-25
16567505-0	2006	5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside and metformin inhibit hepatic glucose phosphorylation by an AMP-activated protein kinase-independent effect on glucokinase translocation.	Metformin	59-68	glucokinase	Rattus norvegicus	166-177
16567505-8	2006	Finally, AICAR, metformin, and oligomycin were found to inhibit the glucose-induced translocation of glucokinase from the nucleus to the cytosol by a mechanism that could be related to the decrease in intracellular ATP concentrations observed in these conditions.	Metformin	16-25	glucokinase	Rattus norvegicus	101-112
16443786-5	2006	Furthermore, administration of metformin as well as 5-aminoimidazole-4-carboxamide ribonucleoside, an AMPK agonist, significantly increased eNOS Ser1179 phosphorylation, NO bioactivity, and coimmunoprecipitation of eNOS with hsp90 in wild-type C57BL6 mice but not in AMPK-alpha1 knockout mice, suggesting that AMPK is required for metformin-enhanced eNOS activation in vivo.	Metformin	31-40	heat shock protein 86, pseudogene 1	Mus musculus	225-230
16622294-10	2006	AMPK activation is also involved in the mechanism of action of metformin and adiponectin.	Metformin	63-72	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-4
16515522-5	2006	Recent studies have shown that AMPK is the cellular mediator for many of the metabolic effects of drugs such as metformin and thiazolidinediones, as well as the insulin sensitizing adipocytokines leptin and adiponectin.	Metformin	112-121	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	31-35
16380484-4	2006	Treatment with metformin and AICAR inhibited hyperglycemia-induced intracellular and mtROS production, stimulated AMP-activated protein kinase (AMPK) activity, and increased the expression of peroxisome proliferator-activated response-gamma coactivator-1alpha (PGC-1alpha) and manganese superoxide dismutase (MnSOD) mRNAs.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	114-142
16380484-4	2006	Treatment with metformin and AICAR inhibited hyperglycemia-induced intracellular and mtROS production, stimulated AMP-activated protein kinase (AMPK) activity, and increased the expression of peroxisome proliferator-activated response-gamma coactivator-1alpha (PGC-1alpha) and manganese superoxide dismutase (MnSOD) mRNAs.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	144-148
16380484-4	2006	Treatment with metformin and AICAR inhibited hyperglycemia-induced intracellular and mtROS production, stimulated AMP-activated protein kinase (AMPK) activity, and increased the expression of peroxisome proliferator-activated response-gamma coactivator-1alpha (PGC-1alpha) and manganese superoxide dismutase (MnSOD) mRNAs.	Metformin	15-24	superoxide dismutase 2	Homo sapiens	277-307
16380484-4	2006	Treatment with metformin and AICAR inhibited hyperglycemia-induced intracellular and mtROS production, stimulated AMP-activated protein kinase (AMPK) activity, and increased the expression of peroxisome proliferator-activated response-gamma coactivator-1alpha (PGC-1alpha) and manganese superoxide dismutase (MnSOD) mRNAs.	Metformin	15-24	superoxide dismutase 2	Homo sapiens	309-314
16380484-5	2006	The dominant negative form of AMPKalpha1 diminished the effects of metformin and AICAR on these events, and an overexpression of PGC-1alpha completely blocked the hyperglycemia-induced mtROS production.	Metformin	67-76	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	30-40
16380484-6	2006	In addition, metformin and AICAR increased the mRNA expression of nuclear respiratory factor-1 and mitochondrial DNA transcription factor A (mtTFA) and stimulated the mitochondrial proliferation.	Metformin	13-22	nuclear respiratory factor 1	Homo sapiens	66-94
16380484-7	2006	Dominant negative-AMPK also reduced the effects of metformin and AICAR on these observations.	Metformin	51-60	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	18-22
16380484-8	2006	These results suggest that metformin normalizes hyperglycemia-induced mtROS production by induction of MnSOD and promotion of mitochondrial biogenesis through the activation of AMPK-PGC-1alpha pathway.	Metformin	27-36	superoxide dismutase 2	Homo sapiens	103-108
16380484-8	2006	These results suggest that metformin normalizes hyperglycemia-induced mtROS production by induction of MnSOD and promotion of mitochondrial biogenesis through the activation of AMPK-PGC-1alpha pathway.	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	177-181
16930507-6	2006	Experiment 2 was designed to investigate the effects of administration of the insulin-sensitising drug metformin hydrochloride on insulin sensitivity and the characteristics of the oestrous cycle in obese mares.	Metformin	103-126	INS	Equus caballus	78-85
34517004-0	2021	Metformin attenuates the epithelial-mesenchymal transition of lens epithelial cells through the AMPK/TGF-beta/Smad2/3 signalling pathway.	Metformin	0-9	transforming growth factor alpha	Homo sapiens	101-109
34517004-0	2021	Metformin attenuates the epithelial-mesenchymal transition of lens epithelial cells through the AMPK/TGF-beta/Smad2/3 signalling pathway.	Metformin	0-9	SMAD family member 2	Homo sapiens	110-117
34815353-10	2021	However, we observed an increased number of CD8 T cells expressing PD-1, Ki-67, Tim-3, and CD62L as well as increased effector cytokine production after treatment with metformin and tumor membrane vesicle vaccine.	Metformin	168-177	hepatitis A virus cellular receptor 2	Mus musculus	80-85
34428594-11	2021	Treatment with dapsone and metformin reversed the effects of testosterone in the DAP and MET groups.	Metformin	27-36	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	89-92
34478829-0	2021	Metformin and exenatide upregulate hepatocyte nuclear factor-4alpha, sex hormone binding globulin levels and improve hepatic triglyceride deposition in polycystic ovary syndrome with insulin resistance rats.	Metformin	0-9	sex hormone binding globulin	Rattus norvegicus	69-97
34216348-0	2021	Metformin alleviates monoamine oxidase-related vascular oxidative stress and endothelial dysfunction in rats with diet-induced obesity.	Metformin	0-9	monoamine oxidase A	Rattus norvegicus	21-38
34216348-4	2021	The present study was purported to assess the effects of METF on MAO expression, ROS production and vasomotor function of aortas isolated from rats with diet-induced obesity.	Metformin	57-61	monoamine oxidase A	Rattus norvegicus	65-68
34216348-9	2021	In conclusion, METF elicited vascular protective effects via the mitigation of MAO-related oxidative stress in the rat model of diet-induced obesity.	Metformin	15-19	monoamine oxidase A	Rattus norvegicus	79-82
34716862-5	2021	Metformin, a diabetic drug is an AMPK activator and has recently proved to be involved in preventing or treating several types of cancer.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	33-37
34716862-8	2021	Downregulation of ERK signaling, upregulation of AMPK pathway and precision in epithelial-mesenchymal transition (EMT) pathway which were assessed by RT-PCR and Western blot provide the evidence that the combination of drugs involved in the precision of altered molecular signaling Further our results suggest that Metformin act as a demethylating agent in anaplastic thyroid cancer cells by inducing the expression of NIS and TSHR.	Metformin	315-324	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	49-53
34452975-2	2021	We found that in vitro and in a streptozotocin diabetes model in vivo, metformin at diabetes-therapeutic concentrations (1 to 50 microM) protects tissue-intact and cultured vascular endothelial cells from hyperglycaemia/ROS-induced dysfunction, typified by reduced agonist-stimulated endothelium-dependent, NO-mediated vasorelaxation in response to muscarinic or Proteinase-activated-receptor-2 (PAR2) agonists.	Metformin	71-80	F2R like trypsin receptor 1	Homo sapiens	363-394
34452975-2	2021	We found that in vitro and in a streptozotocin diabetes model in vivo, metformin at diabetes-therapeutic concentrations (1 to 50 microM) protects tissue-intact and cultured vascular endothelial cells from hyperglycaemia/ROS-induced dysfunction, typified by reduced agonist-stimulated endothelium-dependent, NO-mediated vasorelaxation in response to muscarinic or Proteinase-activated-receptor-2 (PAR2) agonists.	Metformin	71-80	F2R like trypsin receptor 1	Homo sapiens	396-400
34773184-0	2021	Berberine Improves the Protective Effects of Metformin on Diabetic Nephropathy in db/db Mice through Trib1-dependent Inhibiting Inflammation.	Metformin	45-54	tribbles pseudokinase 1	Mus musculus	101-106
34481229-5	2021	SC proliferation-inhibiting effect of metformin exposure was regulated by decreasing adenosine triphosphate level and respiratory enzyme activity in the mitochondria; this process was possibly mediated by the adenosine monophosphate-activated protein kinase (AMPK)/tuberous sclerosis complex 2 (TSC2)/mammalian target of rapamycin (mTOR) signaling pathway, which was regulated by the down-expressed miR-1764 and by the decreased antioxidant enzyme activity and excessive reactive oxygen species generation.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	209-257
34481229-5	2021	SC proliferation-inhibiting effect of metformin exposure was regulated by decreasing adenosine triphosphate level and respiratory enzyme activity in the mitochondria; this process was possibly mediated by the adenosine monophosphate-activated protein kinase (AMPK)/tuberous sclerosis complex 2 (TSC2)/mammalian target of rapamycin (mTOR) signaling pathway, which was regulated by the down-expressed miR-1764 and by the decreased antioxidant enzyme activity and excessive reactive oxygen species generation.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	259-263
34481229-8	2021	Our findings suggest appropriate dose of exogenous 17beta-estradiol treatment can ameliorate the inhibitory effect of metformin on SC proliferation via the regulation of AMPK/TSC2/mTOR signaling pathway, this might reduce the risk of poor male fertility caused by the abuse of anti-diabetic agents.	Metformin	118-127	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	170-174
34479029-2	2021	The anti-diabetic agent metformin (MET) and the aspirin metabolite salicylate (SAL) are shown to activate AMP-activated protein kinase (AMPK), suppress de novo lipogenesis (DNL), the mammalian target of rapamycin (mTOR) pathway and reduce PrCa proliferation in-vitro.	Metformin	24-33	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	106-134
34479029-2	2021	The anti-diabetic agent metformin (MET) and the aspirin metabolite salicylate (SAL) are shown to activate AMP-activated protein kinase (AMPK), suppress de novo lipogenesis (DNL), the mammalian target of rapamycin (mTOR) pathway and reduce PrCa proliferation in-vitro.	Metformin	24-33	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	136-140
34841171-2	2021	Synthetic sesquiterpene derivatives were investigated to identify novel AMPK activators as anti-diabetic drugs because the leading drugs like metformin and thiazolidinediones (TZDs) activate AMPK by inhibiting the synthesis of adenosine 5"-triphosphate and thus are associated with some side effects.	Metformin	142-151	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	72-76
34841171-2	2021	Synthetic sesquiterpene derivatives were investigated to identify novel AMPK activators as anti-diabetic drugs because the leading drugs like metformin and thiazolidinediones (TZDs) activate AMPK by inhibiting the synthesis of adenosine 5"-triphosphate and thus are associated with some side effects.	Metformin	142-151	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	191-195
34689705-5	2022	Treatment of OZ rats with metformin, an activator of AMPK that blocks JNK activity, augments ZO-2 and claudin-1 expression in the liver, reduces the paracellular permeability of hepatocytes, and serum bile acid content.	Metformin	26-35	tight junction protein 2	Rattus norvegicus	93-97
34332919-11	2021	Furthermore, elevated SIRT1 expression and decreased NF-kappaB p65 acetylation were found in the beneficial effects of metformin.	Metformin	119-128	RELA proto-oncogene, NF-kB subunit	Homo sapiens	53-66
34681615-8	2021	Carfilzomib led to an increased Bip expression and decreased AMPKalpha phosphorylation, while metformin coadministration partially decreased Bip expression and induced AMPKalpha phosphorylation, leading to enhanced myocardial LC3B-dependent autophagy.	Metformin	94-103	microtubule-associated protein 1 light chain 3 beta	Mus musculus	226-230
16930507-6	2006	Experiment 2 was designed to investigate the effects of administration of the insulin-sensitising drug metformin hydrochloride on insulin sensitivity and the characteristics of the oestrous cycle in obese mares.	Metformin	103-126	INS	Equus caballus	130-137
16930507-7	2006	In a dose-response trial, metformin increased insulin sensitivity after 30 days following administration of 3 g day(-1), but not 6 or 9 g day(-1), compared with controls receiving vehicle only.	Metformin	26-35	INS	Equus caballus	46-53
15793252-0	2005	Metformin prevents glucose-induced protein kinase C-beta2 activation in human umbilical vein endothelial cells through an antioxidant mechanism.	Metformin	0-9	potassium calcium-activated channel subfamily M regulatory beta subunit 2	Homo sapiens	52-57
15793252-3	2005	Therefore, we assessed the role of metformin in glucose-induced activation of PKC-beta2 and determined the mechanism of its effect in human umbilical venous endothelial cells grown to either normo- (5 mmol/l) or hyperglycemia (10 mmol/l) and moderately and acutely exposed to 25 mmol/l glucose.	Metformin	35-44	potassium calcium-activated channel subfamily M regulatory beta subunit 2	Homo sapiens	82-87
15793252-6	2005	Metformin (20 micromol/l) prevented hyperglycemia-induced PKC-beta2-GFP translocation.	Metformin	0-9	potassium calcium-activated channel subfamily M regulatory beta subunit 2	Homo sapiens	62-67
15793252-9	2005	We show that in endothelial cells, metformin inhibits hyperglycemia-induced PKC-beta2 translocation because of a direct antioxidant effect.	Metformin	35-44	protein kinase C beta	Homo sapiens	76-84
15807992-7	2005	NBDP and metformin were able to restore the altered serum lipids, lipoproteins, lipid peroxidation marker levels and glucose-6-phosphate dehydrogenase activity to almost control levels.	Metformin	9-18	glucose-6-phosphate dehydrogenase	Rattus norvegicus	117-150
15823720-2	2005	In addition, pharmacological activation of endothelial AMP-activated kinase (AMPK), as with the drug metformin, has the potential to decrease the FFA content of endothelial cells by stimulating fat oxidation; AMPK may also suppress endothelial de novo synthesis of diacylglycerol by inhibiting glycerol-3-phosphate acyltransferase.	Metformin	101-110	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	55-75
15823720-2	2005	In addition, pharmacological activation of endothelial AMP-activated kinase (AMPK), as with the drug metformin, has the potential to decrease the FFA content of endothelial cells by stimulating fat oxidation; AMPK may also suppress endothelial de novo synthesis of diacylglycerol by inhibiting glycerol-3-phosphate acyltransferase.	Metformin	101-110	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	77-81
15823720-2	2005	In addition, pharmacological activation of endothelial AMP-activated kinase (AMPK), as with the drug metformin, has the potential to decrease the FFA content of endothelial cells by stimulating fat oxidation; AMPK may also suppress endothelial de novo synthesis of diacylglycerol by inhibiting glycerol-3-phosphate acyltransferase.	Metformin	101-110	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	209-213
15823720-4	2005	More generally, metformin - or, preferably, better tolerated activators of AMPK - may have considerable potential for promoting vascular health in the large proportion of the adult population afflicted with insulin resistance syndrome.	Metformin	16-25	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	75-79
15578517-6	2004	Moreover, activation of AMPK by metformin or AICAR largely blocked the ability of ethanol to increase levels of mature SREBP-1 protein.	Metformin	32-41	sterol regulatory element binding transcription factor 1	Rattus norvegicus	119-126
15324515-4	2004	At the end of the study, changes in HbA1c from baseline were -1.28% points and -0.67% points for repaglinide/metformin and nateglinide/metformin, respectively.	Metformin	109-118	hemoglobin subunit alpha 1	Homo sapiens	36-40
15324515-4	2004	At the end of the study, changes in HbA1c from baseline were -1.28% points and -0.67% points for repaglinide/metformin and nateglinide/metformin, respectively.	Metformin	135-144	hemoglobin subunit alpha 1	Homo sapiens	36-40
15039452-2	2004	We previously found that the biguanide metformin, an antidiabetic agent, causes a significant increase of plasma active GLP-1 level in the presence of dipeptidyl peptidase IV (DPPIV) inhibitor in normal rats.	Metformin	39-48	dipeptidylpeptidase 4	Rattus norvegicus	151-174
15039452-2	2004	We previously found that the biguanide metformin, an antidiabetic agent, causes a significant increase of plasma active GLP-1 level in the presence of dipeptidyl peptidase IV (DPPIV) inhibitor in normal rats.	Metformin	39-48	dipeptidylpeptidase 4	Rattus norvegicus	176-181
15059968-10	2004	Prolonged fasting and treatment with metformin significantly decreased Grb14 expression in peri-epidydimal adipose tissue, while there was only a trend to a diminution after TZD treatment.	Metformin	37-46	growth factor receptor bound protein 14	Mus musculus	71-76
34351835-4	2021	Drugs targeting mTOR and AMPK, such as sirolimus, rapamycin, and metformin, have shown some efficacy and tolerability in clinical trials on patients with SLE, but have not led to breakthroughs.	Metformin	65-74	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	25-29
34429755-0	2021	Metformin mitigates PLCepsilon gene expression and modulates the Notch1/Hes and androgen receptor signaling pathways in castration-resistant prostate cancer xenograft models.	Metformin	0-9	phospholipase C like 1 (inactive)	Homo sapiens	20-30
34429755-1	2021	The present study aimed to establish a mouse model of patient-derived castration-resistant prostate cancer (CRPC) xenograft tumors, and to evaluate the effects of various doses of metformin on phospholipase Cepsilon (PLCepsilon) expression and the neurogenic locus notch homolog protein 1 (Notch1)/hairy and enhancer of split 1 and androgen receptor (AR) signaling pathways via western blotting and reverse transcription-quantitative PCR.	Metformin	180-189	phospholipase C like 1 (inactive)	Homo sapiens	193-215
34429755-1	2021	The present study aimed to establish a mouse model of patient-derived castration-resistant prostate cancer (CRPC) xenograft tumors, and to evaluate the effects of various doses of metformin on phospholipase Cepsilon (PLCepsilon) expression and the neurogenic locus notch homolog protein 1 (Notch1)/hairy and enhancer of split 1 and androgen receptor (AR) signaling pathways via western blotting and reverse transcription-quantitative PCR.	Metformin	180-189	phospholipase C like 1 (inactive)	Homo sapiens	217-227
34429755-3	2021	The results confirmed that metformin may serve critical roles in CRPC by significantly inhibiting the occurrence, growth and proliferation of CRPC tumors by decreasing PLCepsilon/Notch1 expression and AR nucleation.	Metformin	27-36	phospholipase C like 1 (inactive)	Homo sapiens	168-178
34291435-4	2021	We delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKalpha/beta signaling that leads to phosphorylation of Ser85 of the key mediator of CMA, Hsc70, and its activation.	Metformin	47-56	mitogen-activated protein kinase kinase kinase 7	Mus musculus	81-85
34291435-4	2021	We delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKalpha/beta signaling that leads to phosphorylation of Ser85 of the key mediator of CMA, Hsc70, and its activation.	Metformin	47-56	heat shock protein 8	Mus musculus	177-182
34291435-8	2021	Our study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKalpha/beta-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases, such as AD, where such therapeutic intervention could be beneficial.	Metformin	61-70	mitogen-activated protein kinase kinase kinase 7	Mus musculus	71-75
34291435-8	2021	Our study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKalpha/beta-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases, such as AD, where such therapeutic intervention could be beneficial.	Metformin	61-70	heat shock protein 8	Mus musculus	90-95
34659562-0	2021	Metformin exerts a synergistic effect with venetoclax by downregulating Mcl-1 protein in acute myeloid leukemia.	Metformin	0-9	myeloid cell leukemia sequence 1	Mus musculus	72-77
34659562-11	2021	Furthermore, after a short incubation time, ABT-199 swiftly increased the expression level of the anti-apoptotic protein Mcl-1, while the combined use of metformin and ABT-199 significantly reduced the level of Mcl-1.	Metformin	154-163	myeloid cell leukemia sequence 1	Mus musculus	211-216
34659562-12	2021	Notably, Metformin significantly downregulates the level of Mcl-1 protein by inhibiting its protein production.	Metformin	9-18	myeloid cell leukemia sequence 1	Mus musculus	60-65
34659562-13	2021	To less extent, metformin can also downregulate the expression of another anti-apoptotic protein, BCL-xl.	Metformin	16-25	BCL2-like 1	Mus musculus	98-104
34659562-14	2021	Conclusion: Metformin downregulates the expression of anti-apoptotic proteins Mcl-1 and Bcl-xl by inhibiting protein production, and shows a synergistic anti-tumor effect with ABT-199 in acute myeloid leukemia.	Metformin	12-21	myeloid cell leukemia sequence 1	Mus musculus	78-83
34659562-14	2021	Conclusion: Metformin downregulates the expression of anti-apoptotic proteins Mcl-1 and Bcl-xl by inhibiting protein production, and shows a synergistic anti-tumor effect with ABT-199 in acute myeloid leukemia.	Metformin	12-21	BCL2-like 1	Mus musculus	88-94
34368808-11	2021	Secondary objective was to evaluate the effects of metformin on the expression of CSC markers by measuring relative mRNA levels of CD133, OCT4 and NANOG by RT-PCR and immunohistochemistry.	Metformin	51-60	prominin 1	Homo sapiens	131-136
34368808-16	2021	Comparison of markers of CCSC results showed that expression of CD133, OCT4 and NANOG expression were decreased following metformin.	Metformin	122-131	prominin 1	Homo sapiens	64-69
34531248-0	2021	Mitochondrial reactive oxygen species trigger metformin-dependent antitumor immunity via activation of Nrf2/mTORC1/p62 axis in tumor-infiltrating CD8T lymphocytes.	Metformin	46-55	CREB regulated transcription coactivator 1	Mus musculus	108-114
34383246-9	2021	CONCLUSIONS: Although the SLC47A2 gene variants allow predicting favorable response to the metformin treatment in Mexican populations, the probable high frequency of ineffectiveness should be discarded in Huichols.	Metformin	91-100	solute carrier family 47 member 2	Homo sapiens	26-33
34062070-0	2021	The role of AMPK/mTOR signaling pathway in anticancer activity of metformin.	Metformin	66-75	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	12-16
34502314-7	2021	Metformin treatment markedly reduced postinfarction fibrotic remodeling and CD68-positive cell population in mice.	Metformin	0-9	CD68 antigen	Mus musculus	76-80
34502314-8	2021	Moreover, metformin resulted in reduced expression of COL3A1, alphaSMA and CD68 after 14 days of reperfusion.	Metformin	10-19	CD68 antigen	Mus musculus	75-79
15134207-6	2004	In multivariate analysis duration of diabetes was significantly associated with survival and Metformin treatment only, and Sulphonylurea &amp; Metformin treatment together (P = 0.003, and 0.026, Multivariate Cox model, respectively).	Metformin	143-152	cytochrome c oxidase subunit 8A	Homo sapiens	208-211
34502168-11	2021	In addition, the review explores possible new AhR-mediated mechanisms of several drugs used for treatment of ASD, such as sulforaphane, resveratrol, haloperidol, and metformin.	Metformin	166-175	aryl hydrocarbon receptor	Homo sapiens	46-49
15732245-5	2004	Various therapeutical interventions for the improvement of insulin sensitivity, including weight loss, physical exercise, as well as metformin and glitazones, increase AMPK activity.	Metformin	133-142	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	168-172
14765727-13	2004	The results of this study suggest that metformin is beneficial only in those diabetic cats with detectable concentrations of insulin at the time metformin treatment is initiated.	Metformin	39-48	insulin	Felis catus	125-132
14765727-13	2004	The results of this study suggest that metformin is beneficial only in those diabetic cats with detectable concentrations of insulin at the time metformin treatment is initiated.	Metformin	145-154	insulin	Felis catus	125-132
15236798-4	2004	Metformin"s antidiabetic efficacy is now known to reflect activation of AMP-activated kinase (AMPK); AMPK can stimulate eNOS, which is expressed in hepatocytes.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	72-92
15236798-4	2004	Metformin"s antidiabetic efficacy is now known to reflect activation of AMP-activated kinase (AMPK); AMPK can stimulate eNOS, which is expressed in hepatocytes.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	94-98
15236798-4	2004	Metformin"s antidiabetic efficacy is now known to reflect activation of AMP-activated kinase (AMPK); AMPK can stimulate eNOS, which is expressed in hepatocytes.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	101-105
15236799-7	2004	In non-diabetics, metformin therapy is indeed reported to reduce plasma levels of insulin and of free IGF-I; indeed, this is thought to be the mechanism whereby metformin suppresses excess androgen production in PCOS.	Metformin	18-27	insulin-like growth factor 1	Mus musculus	102-107
15236799-7	2004	In non-diabetics, metformin therapy is indeed reported to reduce plasma levels of insulin and of free IGF-I; indeed, this is thought to be the mechanism whereby metformin suppresses excess androgen production in PCOS.	Metformin	161-170	insulin-like growth factor 1	Mus musculus	102-107
12960015-7	2003	The AMPK cascade is the probable target for the antidiabetic drug metformin, and current indications are that it is responsible for many of the beneficial effects of exercise in the treatment and prevention of type 2 diabetes and the metabolic syndrome.	Metformin	66-75	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	4-8
14500570-7	2003	Recent studies suggest that the ability of leptin, adiponectin, 5"-aminoimidazole 4-carboxamide riboside (AICAR), adrenergic agonists, and metformin to diminish adiposity may be mediated, at least in part, by AMPK activation in peripheral tissues.	Metformin	139-148	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	209-213
34429434-5	2021	Interestingly, distinct from its reported function as an activator of AMPK in tumor cells, the type 2 diabetes drug metformin enhances the membrane dissociation of PD-L1-CD by disrupting the electrostatic interaction, thereby decreasing the cellular abundance of PD-L1.	Metformin	116-125	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	70-74
34514098-0	2021	Metformin inhibits gastric cancer cell proliferation by regulation of a novel Loc100506691-CHAC1 axis.	Metformin	0-9	long intergenic non-protein coding RNA 2985	Homo sapiens	78-90
34514098-3	2021	In this study, we identified an oncogenic lncRNA, Loc100506691, the expression of which was decreased in gastric cancer cells with metformin treatment.	Metformin	131-140	long intergenic non-protein coding RNA 2985	Homo sapiens	50-62
34514098-8	2021	We concluded that anti-proliferative effects of metformin in gastric cancer may be partially caused by suppression of the Loc100506691-miR-26a-5p/miR-330-5p-CHAC1 axis.	Metformin	48-57	long intergenic non-protein coding RNA 2985	Homo sapiens	122-134
34439897-5	2021	In particular, in vitro and in vivo experimental studies recently documented that metformin selectively inhibits the uptake of 2-(18F)-Fluoro-2-Deoxy-D-Glucose (FDG), via an impaired catalytic function of the enzyme hexose-6P-dehydrogenase (H6PD).	Metformin	82-91	hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase	Homo sapiens	216-239
34439897-5	2021	In particular, in vitro and in vivo experimental studies recently documented that metformin selectively inhibits the uptake of 2-(18F)-Fluoro-2-Deoxy-D-Glucose (FDG), via an impaired catalytic function of the enzyme hexose-6P-dehydrogenase (H6PD).	Metformin	82-91	hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase	Homo sapiens	241-245
34439897-7	2021	Regardless of its exploitability in the clinical setting, this metformin action might configure the ER metabolism as a potential target for innovative therapeutic strategies in patients with solid cancers and potentially modifies the current interpretative model of FDG uptake, attributing PET/CT capability to predict cancer aggressiveness to the activation of H6PD catalytic function.	Metformin	63-72	hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase	Homo sapiens	362-366
34483906-7	2021	In addition, metformin also alleviated adiposity and hepatic steatosis, and greatly upregulated uncoupling protein 1 (UCP1) expression in adipose tissues of DIO mice.	Metformin	13-22	uncoupling protein 1 (mitochondrial, proton carrier)	Mus musculus	96-116
34483906-7	2021	In addition, metformin also alleviated adiposity and hepatic steatosis, and greatly upregulated uncoupling protein 1 (UCP1) expression in adipose tissues of DIO mice.	Metformin	13-22	uncoupling protein 1 (mitochondrial, proton carrier)	Mus musculus	118-122
34483906-9	2021	However, SIRT1-deficiency remarkably impaired the effects of metformin on lowering serum transaminases levels, downregulating the mRNA expression of proinflammatory factors, and increasing the protein level of hepatic Cholesterol 25-Hydroxylase (CH25H), a cholesterol hydroxylase in cholesterol catabolism.	Metformin	61-70	cholesterol 25-hydroxylase	Mus musculus	218-244
34483906-9	2021	However, SIRT1-deficiency remarkably impaired the effects of metformin on lowering serum transaminases levels, downregulating the mRNA expression of proinflammatory factors, and increasing the protein level of hepatic Cholesterol 25-Hydroxylase (CH25H), a cholesterol hydroxylase in cholesterol catabolism.	Metformin	61-70	cholesterol 25-hydroxylase	Mus musculus	246-251
34421611-0	2021	Metformin Attenuates Bone Cancer Pain by Reducing TRPV1 and ASIC3 Expression.	Metformin	0-9	transient receptor potential cation channel, subfamily V, member 1	Rattus norvegicus	50-55
34421611-7	2021	What"s more, intraperitoneally injection of Metformin or Vinorelbine markedly elevated the PWT of BCP rats, but reduced the expression of TRPV1 and ASIC3 in L4-6 DRGs and decreased the TRPV1 expression in SDH (*p < 0.05, **p < 0.01 vs. BCP + NS).	Metformin	44-53	transient receptor potential cation channel, subfamily V, member 1	Rattus norvegicus	138-143
34421611-7	2021	What"s more, intraperitoneally injection of Metformin or Vinorelbine markedly elevated the PWT of BCP rats, but reduced the expression of TRPV1 and ASIC3 in L4-6 DRGs and decreased the TRPV1 expression in SDH (*p < 0.05, **p < 0.01 vs. BCP + NS).	Metformin	44-53	transient receptor potential cation channel, subfamily V, member 1	Rattus norvegicus	185-190
34421611-8	2021	Collectively, these results suggest an effective analgesic effect of Metformin on mechanical allodynia of BCP rats, which may be mediated by the downregulation of ASIC3 and TRPV1.	Metformin	69-78	transient receptor potential cation channel, subfamily V, member 1	Rattus norvegicus	173-178
34340683-0	2021	Correction to: Inhibition of mTORC1 through ATF4-induced REDD1 and Sestrin2 expression by Metformin.	Metformin	90-99	CREB regulated transcription coactivator 1	Mus musculus	29-35
34340683-0	2021	Correction to: Inhibition of mTORC1 through ATF4-induced REDD1 and Sestrin2 expression by Metformin.	Metformin	90-99	sestrin 2	Homo sapiens	67-75
34415985-8	2021	Treatment of lens epithelial cells with metformin reduced the level of the EMT markers  -SMA and pERK induced by TGF-beta2.	Metformin	40-49	survival of motor neuron 1, telomeric	Homo sapiens	89-92
34116022-7	2021	Metformin HCl could reverse the inhibitory effects of ADAM7 knockdown on the p38MAPK signaling pathway and the proliferation of HTR-8 and B6Tert-1 cells.	Metformin	0-13	ADAM metallopeptidase domain 7	Homo sapiens	54-59
34303707-8	2021	In addition, metformin upregulated AQP7 expression as well as inhibited activation of p38 and JNK MAPKs both in vivo and in vitro.	Metformin	13-22	mitogen activated protein kinase 14	Rattus norvegicus	86-89
34303707-10	2021	Our findings demonstrate a new mechanism by which metformin suppresses the p38 and JNK pathways, thereby upregulating pancreatic AQP7 expression, and promoting glycerol influx into pancreatic beta-cells and subsequent insulin secretion in T2DM.	Metformin	50-59	mitogen activated protein kinase 14	Rattus norvegicus	75-78
34164906-5	2021	The expression of lncRNA MALAT1, HOTAIR, DICER1-AS1, LINC01121 and TUG1 was up-regulated by metformin treatment.	Metformin	92-101	prostaglandin D2 receptor	Homo sapiens	48-51
34164906-5	2021	The expression of lncRNA MALAT1, HOTAIR, DICER1-AS1, LINC01121 and TUG1 was up-regulated by metformin treatment.	Metformin	92-101	long intergenic non-protein coding RNA 1121	Homo sapiens	53-62
34164906-5	2021	The expression of lncRNA MALAT1, HOTAIR, DICER1-AS1, LINC01121 and TUG1 was up-regulated by metformin treatment.	Metformin	92-101	taurine up-regulated 1	Homo sapiens	67-71
34164906-7	2021	The expression of Beclin1, VDAC1, LC3-II, CHOP and Bip was promoted in the cells received combinatorial treatment of metformin and MALAT1 knock-down.	Metformin	117-126	voltage dependent anion channel 1	Homo sapiens	27-32
34282122-6	2021	Moreover, both AMP-activated protein kinase (AMPK) agonist metformin and two mammalian targets of rapamycin (mTOR) inhibitors (INK128 and rapamycin) inhibited the percentage of M-MDSCs in lupus mice as well as in the TLR7- and IFN-alpha-induced bone marrow (BM) differentiation into MDSCs in vitro.	Metformin	59-68	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	15-43
34282122-6	2021	Moreover, both AMP-activated protein kinase (AMPK) agonist metformin and two mammalian targets of rapamycin (mTOR) inhibitors (INK128 and rapamycin) inhibited the percentage of M-MDSCs in lupus mice as well as in the TLR7- and IFN-alpha-induced bone marrow (BM) differentiation into MDSCs in vitro.	Metformin	59-68	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	45-49
12852706-10	2003	At study end, an HbA1c level &lt; 7.0% was achieved in approximately 4-fold more patients who were treated with glipizide/metformin (36.3%) compared with glipizide (8.9%) or metformin (9.9%) monotherapies.	Metformin	122-131	hemoglobin subunit alpha 1	Homo sapiens	17-21
12852706-10	2003	At study end, an HbA1c level &lt; 7.0% was achieved in approximately 4-fold more patients who were treated with glipizide/metformin (36.3%) compared with glipizide (8.9%) or metformin (9.9%) monotherapies.	Metformin	174-183	hemoglobin subunit alpha 1	Homo sapiens	17-21
12629126-0	2003	Metformin rapidly increases insulin receptor activation in human liver and signals preferentially through insulin-receptor substrate-2.	Metformin	0-9	insulin receptor	Homo sapiens	28-44
12629126-7	2003	Metformin (1 micro g/ml) increased IR tyrosine phosphorylation by 78% (P = 0.0007) in 30 min in human hepatocytes and Huh7 cells and increased IRS-2 but not IRS-1 activation, and the downstream increase in deoxyglucose uptake was mediated via increased translocation of GLUT-1 to the plasma membrane.	Metformin	0-9	insulin receptor	Homo sapiens	35-37
12629126-9	2003	Metformin increased basal IR-KA by 150% (P = 0.0001).	Metformin	0-9	insulin receptor	Homo sapiens	26-28
12629126-11	2003	This study demonstrates that the mechanism of action of metformin in liver involves IR activation, followed by selective IRS-2 activation, and increased glucose uptake via increased GLUT-1 translocation.	Metformin	56-65	insulin receptor	Homo sapiens	84-86
12629126-12	2003	The effect of metformin was completely blocked by an IR inhibitor.	Metformin	14-23	insulin receptor	Homo sapiens	53-55
12502670-18	2003	CONCLUSIONS: Metformin treatment lowered HbA1c and decreased insulin dosage with no weight gain in teens with type 1 diabetes in poor metabolic control.	Metformin	13-22	hemoglobin subunit alpha 1	Homo sapiens	41-45
12406033-7	2002	RESULTS: Both strengths of glyburide/metformin equally reduced mean HbA1c by 1.7% more than did glyburide alone (p &lt; 0.001), and by 1.9% more than did metformin alone (p &lt; 0.001).	Metformin	37-46	hemoglobin subunit alpha 1	Homo sapiens	68-72
34298652-0	2021	Metformin and Niclosamide Synergistically Suppress Wnt and YAP in APC-Mutated Colorectal Cancer.	Metformin	0-9	Yes1 associated transcriptional regulator	Homo sapiens	59-62
34298652-0	2021	Metformin and Niclosamide Synergistically Suppress Wnt and YAP in APC-Mutated Colorectal Cancer.	Metformin	0-9	APC regulator of WNT signaling pathway	Homo sapiens	66-69
34307505-12	2021	Furthermore, we found that LOXL2 and LOXL4 was inhibited by metformin and losartan in HASMCs, which indicated that LOXL2 and LOXL4 are the potential targets that involved in the therapeutic effects of metformin and losartan on aortic or aneurysm expansion.	Metformin	60-69	lysyl oxidase like 4	Homo sapiens	37-42
34307505-12	2021	Furthermore, we found that LOXL2 and LOXL4 was inhibited by metformin and losartan in HASMCs, which indicated that LOXL2 and LOXL4 are the potential targets that involved in the therapeutic effects of metformin and losartan on aortic or aneurysm expansion.	Metformin	60-69	lysyl oxidase like 4	Homo sapiens	125-130
34234193-3	2021	Metformin increased AMPK, p-AMPK (Thr172), FOXO3a, p-FOXO3a (Ser413), and MnSOD levels in HDF, but not in AsPC-1 cells.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	20-24
34234193-3	2021	Metformin increased AMPK, p-AMPK (Thr172), FOXO3a, p-FOXO3a (Ser413), and MnSOD levels in HDF, but not in AsPC-1 cells.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	28-32
34234193-3	2021	Metformin increased AMPK, p-AMPK (Thr172), FOXO3a, p-FOXO3a (Ser413), and MnSOD levels in HDF, but not in AsPC-1 cells.	Metformin	0-9	superoxide dismutase 2	Homo sapiens	74-79
34234193-4	2021	p-AMPK and p-FOXO3a also translocated from the cytosol to the nucleus by metformin in HDF, but not in AsPC-1 cells.	Metformin	73-82	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	2-6
34234193-10	2021	Our results suggest that metformin in cancer cells differentially regulates cellular ROS levels via AMPK-FOXO3a-MnSOD pathway and combination of metformin/apigenin exerts anticancer activity through DNA damage-induced apoptosis, autophagy and necroptosis by cancer cell-specific ROS amplification.	Metformin	25-34	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	100-104
34197485-3	2021	GWAS identified SNPs associated with metformin treatment success at a locus containing the NPAT (nuclear protein, ataxia-telangiectasia locus) and ATM (ataxia-telangiectasia mutated) genes.	Metformin	37-46	ataxia telangiectasia mutated	Mus musculus	147-181
34335967-11	2021	Furthermore, metformin, an anti-diabetic drug, could upregulate miR-185-5p expression to suppress G6Pase, leading to hepatic gluconeogenesis inhibition.	Metformin	13-22	glucose-6-phosphatase, catalytic	Mus musculus	98-104
34335967-13	2021	We further identified that the /G6Pase axis mediated the inhibitory effect of metformin on hepatic gluconeogenesis.	Metformin	78-87	glucose-6-phosphatase, catalytic	Mus musculus	32-38
34162423-0	2021	Metformin induces Ferroptosis by inhibiting UFMylation of SLC7A11 in breast cancer.	Metformin	0-9	solute carrier family 7 (cationic amino acid transporter, y+ system), member 11	Mus musculus	58-65
34162423-10	2021	Specifically, metformin reduces the protein stability of SLC7A11, which is a critical ferroptosis regulator, by inhibiting its UFMylation process.	Metformin	14-23	solute carrier family 7 (cationic amino acid transporter, y+ system), member 11	Mus musculus	57-64
34235153-9	2021	The in vitro results showed that the combination of metformin and pemetrexed exhibited an antiproliferative effect in reducing cell viability and colony formation, the downregulation of cyclin D1 and A2 and the upregulation of CDKN1B, which are involved in the G1/S phase.	Metformin	52-61	cyclin D1	Homo sapiens	186-195
34168429-3	2021	The present research aimed to evaluate the therapeutic effects of the combination of oral hypoglycemic drug metformin (MET) and a natural product malvidin (MAL) on hepatic damage in HFD/STZ-induced diabetic rats.	Metformin	108-117	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	119-122
34117280-10	2021	AMPK activators, including metformin, stimulate Parkin-independent autophagy and bacterial killing in leukocytes from post-shock patients and in lungs of sepsis-immunosuppressed mice.	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	22-31	interferon induced protein 44	Homo sapiens	347-350
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	217-226	interferon induced protein 44	Homo sapiens	347-350
34078517-3	2021	High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation.	Metformin	318-327	interferon induced protein 44	Homo sapiens	347-350
34217162-8	2021	Four hub genes (C3, THBS1, CXCL1, and TTN) were identified after treatment of Metformin (P<0.05, T-test).	Metformin	78-87	titin	Homo sapiens	38-41
34141868-7	2021	Moreover, blockade of TRAIL binding to DR4/DR5 or specific knockdown of TRAIL expression significantly attenuated metformin-induced apoptosis.	Metformin	114-123	TNF receptor superfamily member 10a	Homo sapiens	39-42
12380632-3	2002	A previous 32-week, randomized, double-blind, placebo-controlled trial found that treatment with glyburide/metformin tablets was associated with greater reductions in HbA1c values compared with glyburide monotherapy, metformin monotherapy, and placebo.	Metformin	107-116	hemoglobin subunit alpha 1	Homo sapiens	167-171
34124601-3	2021	Here, we find that AMPK agonists, A769662, and Metformin, can inhibit GLI1 activity and synergize with Vismodegib to suppress MB cell growth in vitro and in vivo.	Metformin	47-56	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	19-23
34124601-5	2021	This is the first report demonstrating that combining AMPK agonist (Metformin) and SHH pathway inhibitor (Vismodegib) confers synergy for MB treatment and provides an effective chemotherapeutic regimen that can be used to overcome resistance to Vismodegib in SHH-driven cancers.	Metformin	68-77	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	54-58
12145153-0	2002	The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	46-74
34617056-10	2021	Metformin reduced total cholesterol and mRNA expression of SPP1 (encoding osteopontin), MMP12, and the glycoprotein genes Gpnmb and Clec7a.	Metformin	0-9	secreted phosphoprotein 1	Mus musculus	59-63
34617056-10	2021	Metformin reduced total cholesterol and mRNA expression of SPP1 (encoding osteopontin), MMP12, and the glycoprotein genes Gpnmb and Clec7a.	Metformin	0-9	secreted phosphoprotein 1	Mus musculus	74-85
34617056-10	2021	Metformin reduced total cholesterol and mRNA expression of SPP1 (encoding osteopontin), MMP12, and the glycoprotein genes Gpnmb and Clec7a.	Metformin	0-9	matrix metallopeptidase 12	Mus musculus	88-93
34561980-0	2021	Metformin ameliorates neuronal necroptosis after intracerebral hemorrhage by activating AMPK.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	88-92
34561980-5	2021	RESULTS: In the present study, we found that metformin, a first-line medication for the treatment of type 2 diabetes, can effectively inhibit neuronal necroptosis after ICH through activating AMPK related pathway, thereby significantly improving neurological function scores and reducing brain edema.	Metformin	45-54	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	192-196
34966196-1	2021	Introduction: Metformin has known mechanistic benefits on COVID-19 infection due to its anti-inflammatory effects and its action on the ACE2 receptor.	Metformin	14-23	angiotensin converting enzyme 2	Homo sapiens	136-140
12145153-1	2002	Metformin, a drug widely used to treat type 2 diabetes, was recently shown to activate the AMP-activated protein kinase (AMPK) in intact cells and in vivo.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	91-119
12145153-1	2002	Metformin, a drug widely used to treat type 2 diabetes, was recently shown to activate the AMP-activated protein kinase (AMPK) in intact cells and in vivo.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	121-125
12145153-3	2002	In intact cells, metformin stimulated phosphorylation of the key regulatory site (Thr-172) on the catalytic (alpha) subunit of AMPK.	Metformin	17-26	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	127-131
12145153-5	2002	Metformin has been reported to be an inhibitor of complex 1 of the respiratory chain, but we present evidence that activation of AMPK in two different cell types is not a consequence of depletion of cellular energy charge via this mechanism.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	129-133
12145153-6	2002	Whereas we have not established the definitive mechanism by which metformin activates AMPK, our results show that the mechanism is different from that of the existing AMPK-activating agent, 5-aminoimidazole-4-carboxamide (AICA) riboside.	Metformin	66-75	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	86-90
12145153-7	2002	Metformin therefore represents a useful new tool to study the consequences of AMPK activation in intact cells and in vivo.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	78-82
12118200-4	2002	MATERIAL/METHODS: The SUR1 polymorphism was genotyped in 68 type 2 diabetic patients who required insulin treatment and had known diabetes duration L 5 years, compared to 99 patients receiving oral agents (sulfonylurea alone or in combination with metformin or acarbose) with known diabetes duration of at least 15 years.	Metformin	248-257	ATP binding cassette subfamily C member 8	Homo sapiens	22-26
11855850-3	2002	We hypothesized that correction of insulin resistance with metformin might also restore anabolic effects of GH.	Metformin	59-68	gonadotropin releasing hormone receptor	Rattus norvegicus	108-110
11855850-11	2002	GH increased muscle glycogen by 40%, but the effect was reversed by metformin.	Metformin	68-77	gonadotropin releasing hormone receptor	Rattus norvegicus	0-2
34859817-8	2022	Metformin and rapamycin elicited similar effects, which were blocked by pharmacological inhibition of AMPK.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	102-106
35588955-4	2022	Although metformin"s effect against T2DM, cancers, and ageing, are believed mostly attributed to the activation of AMP-activated protein kinase (AMPK), the cellular responses involving metformin-ROS-Nrf2 axis might be another natural asset to improve healthspan and lifespan.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	115-143
35588955-4	2022	Although metformin"s effect against T2DM, cancers, and ageing, are believed mostly attributed to the activation of AMP-activated protein kinase (AMPK), the cellular responses involving metformin-ROS-Nrf2 axis might be another natural asset to improve healthspan and lifespan.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	145-149
35605453-9	2022	Analysis of AMPK phosphorylation revealed that its activation was decreased in the PBMCs of type 2 diabetic patients, an effect which was reversed, once again, by metformin.	Metformin	163-172	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	12-16
35605453-11	2022	These results demonstrate that metformin improves mitochondrial function, restores the levels of ETC complexes, and enhances AMPK activation and mitophagy, suggesting beneficial clinical implications in the treatment of type 2 diabetes.	Metformin	31-40	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	125-129
11855850-13	2002	GH increased TNF in visceral fat and the effect was augmented by metformin (144% increase).	Metformin	65-74	gonadotropin releasing hormone receptor	Rattus norvegicus	0-2
11855850-15	2002	The latter may, in part, be explained by the failure of metformin to prevent GH-induced elevation of TNF in visceral fat.	Metformin	56-65	gonadotropin releasing hormone receptor	Rattus norvegicus	77-79
11720083-1	2001	Genetically obese (ob/ob) mice were employed for the study of the effect of metformin on activity and expression of nitric oxide synthase (NOS ) in vitro and in vivo.	Metformin	76-85	nitric oxide synthase 1, neuronal	Mus musculus	116-137
11703422-10	2001	There was a significant decrease in HbA1c on adding miglitol to metformin compared to adding placebo (miglitol treatment effect, - 0.21%; placebo treatment effect, + 0.22%; p = 0.011).	Metformin	64-73	hemoglobin subunit alpha 1	Homo sapiens	36-40
11532475-8	2001	Western blot analysis revealed that metformin significantly inhibited the expression of steroidogenic acute regulatory (StAR) protein and 17 alpha-hydroxylase (CYP17) expression in cells stimulated with forskolin compared with forskolin treatment alone.	Metformin	36-45	steroidogenic acute regulatory protein	Homo sapiens	88-118
11532475-8	2001	Western blot analysis revealed that metformin significantly inhibited the expression of steroidogenic acute regulatory (StAR) protein and 17 alpha-hydroxylase (CYP17) expression in cells stimulated with forskolin compared with forskolin treatment alone.	Metformin	36-45	steroidogenic acute regulatory protein	Homo sapiens	120-124
11532475-8	2001	Western blot analysis revealed that metformin significantly inhibited the expression of steroidogenic acute regulatory (StAR) protein and 17 alpha-hydroxylase (CYP17) expression in cells stimulated with forskolin compared with forskolin treatment alone.	Metformin	36-45	cytochrome P450 family 17 subfamily A member 1	Homo sapiens	160-165
11532475-10	2001	Northern analysis revealed a significant decrease in the expression of CYP17 mRNA in forskolin-stimulated cells treated with metformin (200 microM) compared with forskolin-only-treated cells, however, there was no significant change in steroidogenic acute regulatory protein mRNA expression.	Metformin	125-134	cytochrome P450 family 17 subfamily A member 1	Homo sapiens	71-76
11192132-16	2000	In the extension study, patients treated with open-label pioglitazone + metformin for 72 weeks had mean changes from baseline of -1.36% in HbA1c and -63.0 mg/dL in FPG.	Metformin	72-81	hemoglobin subunit alpha 1	Homo sapiens	139-143
11068185-0	2000	Inhibition of leptin secretion by insulin and metformin in cultured rat adipose tissue.	Metformin	46-55	leptin	Rattus norvegicus	14-20
35633523-3	2022	In this study, the effects of metformin were investigated on the FAK gene expression levels, pFAK protein values, cell viability and migration rate of VSMCs in high glucose conditions.	Metformin	30-39	protein tyrosine kinase 2	Homo sapiens	65-68
35633523-4	2022	MATERIALS AND METHODS: The FAK gene expression levels and pFAK protein values were evaluated in VSMCs treated with different doses of metformin (1, 5 and 7 mM), based on cell viability using RT-qPCR, western blotting and MTT techniques.	Metformin	134-143	protein tyrosine kinase 2	Homo sapiens	27-30
35633523-6	2022	RESULTS: The FAK gene expression levels reduced significantly in metformin-treated VSMCs at 24 h and 48 h periods (p < .0008 and p < .0001, respectively).	Metformin	65-74	protein tyrosine kinase 2	Homo sapiens	13-16
35633523-9	2022	CONCLUSION: The results showed that metformin may suppress the proliferation and migration of VSMCs via FAK-related pathways and may retard the progression of vessel stenosis in diabetes.	Metformin	36-45	protein tyrosine kinase 2	Homo sapiens	104-107
35621546-13	2022	Immunohistochemical staining showed that significantly more osteocalcin-positive cells were located at the newly formed bones treated with metformin than at the no-metformin control site at week 4 (P < .05).	Metformin	139-148	bone gamma-carboxyglutamate protein	Canis lupus familiaris	60-71
35619086-8	2022	The 181T>C and 1222A>G changes were further found to alter OCT-1 structure in silico and affect metformin transport in vitro which was illustrated by their effect on the activation of AMPK, the marker for metformin activity.	Metformin	96-105	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	184-188
35619086-8	2022	The 181T>C and 1222A>G changes were further found to alter OCT-1 structure in silico and affect metformin transport in vitro which was illustrated by their effect on the activation of AMPK, the marker for metformin activity.	Metformin	205-214	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	184-188
35606343-0	2022	Metabolic regulation by the intestinal metformin-AMPK axis.	Metformin	39-48	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	49-53
11068185-9	2000	Metformin inhibited basal and dexamethasone-stimulated leptin secretion in a dose dependent manner (50% inhibition occurred at 1 mM metformin) while glibenclamide was ineffective.	Metformin	0-9	leptin	Rattus norvegicus	55-61
11068185-9	2000	Metformin inhibited basal and dexamethasone-stimulated leptin secretion in a dose dependent manner (50% inhibition occurred at 1 mM metformin) while glibenclamide was ineffective.	Metformin	132-141	leptin	Rattus norvegicus	55-61
10977010-10	2000	CONCLUSIONS: Patients receiving metformin have diminished B12 absorption and low serum total vitamin B12 and TCII-B12 levels because of a calcium-dependent ileal membrane antagonism, an effect reversed with supplemental calcium.	Metformin	32-41	transcobalamin 2	Homo sapiens	109-113
35594738-3	2022	Our research group has shown that the combined treatment of metformin (MTF) and exercise has beneficial effects for preventing muscle loss and fat accumulation, by modulating the redox state.	Metformin	60-69	FAT atypical cadherin 1	Rattus norvegicus	143-146
10611182-0	2000	Metformin treatment reduces ovarian cytochrome P-450c17alpha response to human chorionic gonadotrophin in women with insulin resistance-related polycystic ovary syndrome.	Metformin	0-9	cytochrome P450 family 17 subfamily A member 1	Homo sapiens	36-60
10611182-9	2000	The present study gives a direct demonstration that metformin leads to a reduction in stimulated ovarian cytochrome P-450c17alpha activity in women with polycystic ovary syndrome.	Metformin	52-61	cytochrome P450 family 17 subfamily A member 1	Homo sapiens	105-129
10630028-1	1999	OBJECTIVES: Principal: to show that the addition of metformin to insulin treatment in type-2 DM obese patients with poor metabolic control (HbA1c &gt; 7.5%) causes a 50% increase after one year in the number of patients with acceptable (HbA1c &lt; or = 7.5%) or good (HbA1c &lt; 6.5%) control, and to determine how many patients reduced their HbA1c by a point.	Metformin	52-61	hemoglobin subunit alpha 1	Homo sapiens	140-144
10456437-9	1999	Overall, the results suggest that metformin may interact with the insulin receptor and/or a component involved in the early steps of insulin signal transduction.	Metformin	34-43	insulin receptor	Homo sapiens	66-82
35534773-0	2022	Attenuation of exercise conditioning by metformin-a consequence of HSF1 inhibition.	Metformin	40-49	heat shock transcription factor 1	Homo sapiens	67-71
35561893-12	2022	Moreover, metformin activated the EPCR, ERK 1/2, p38 MAPK and NF-kappaB pathways but miR-532 mimic suppressed the activation of pathways.	Metformin	10-19	protein C receptor	Homo sapiens	34-38
35570489-7	2022	RESULTS: Patients with two PAX4 R192H risk alleles showed significantly lower attention index score (beta= -8.46, 95% CI (-13.71, -3.21), p = 0.002) than patients with wild-type alleles after adjusting for age, gender, diabetes onset age, HbA1c, body-mass index, renal function, lipid profiles, systolic blood pressure, metformin usage, smoking history, education level, Geriatric Depression Scale score, and presence of APOEe4 allele.	Metformin	320-329	paired box 4	Homo sapiens	27-31
10448935-0	1999	Metformin interaction with insulin-regulated glucose uptake, using the Xenopus laevis oocyte model expressing the mammalian transporter GLUT4.	Metformin	0-9	solute carrier family 2 member 4	Homo sapiens	136-141
10448935-6	1999	Parathyroid hormone (PTH), which is known to impair the intrinsic activity of GLUT4, prevented the stimulatory effect of metformin in both kinds of oocytes whereas cytochalasin D, which interferes with the translocation of carriers, was without effect.	Metformin	121-130	solute carrier family 2 member 4	Homo sapiens	78-83
10448935-7	1999	These results suggest that metformin combined with insulin can maintain glucose homeostasis by increasing the catalytic activity of some hexose carriers or by improving the affinity of GLUT4 for glucose.	Metformin	27-36	solute carrier family 2 member 4	Homo sapiens	185-190
8936123-0	1996	Re: TDE article, pharmacy update, "metformin: a biquanide".	Metformin	35-44	serine incorporator 3	Homo sapiens	4-7
8056180-5	1994	Metformin treatment significantly elevated GLUT 1 in control rats (p &lt; 0.05) and tended to decrease GLUT 1 in diabetic rats (p &lt; 0.075).	Metformin	0-9	solute carrier family 2 member 1	Rattus norvegicus	43-49
8056180-5	1994	Metformin treatment significantly elevated GLUT 1 in control rats (p &lt; 0.05) and tended to decrease GLUT 1 in diabetic rats (p &lt; 0.075).	Metformin	0-9	solute carrier family 2 member 1	Rattus norvegicus	103-109
1936476-10	1991	Withdrawal of metformin resulted in a rise in fasting blood glucose, HbA1, serum total and low density lipoprotein (LDL) cholesterol.	Metformin	14-23	hemoglobin subunit alpha 1	Homo sapiens	69-73
33773207-0	2021	The AMPK modulator metformin as adjunct to methotrexate in patients with rheumatoid arthritis: A proof-of-concept, randomized, double-blind, placebo-controlled trial.	Metformin	19-28	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	4-8
34890997-13	2022	Both metformin and fluoxetine increased neurogenesis by increasing KI67, but only the combined treatment increased neuronal survival by NeuN positive cells in the hippocampus.	Metformin	5-14	RNA binding protein, fox-1 homolog (C. elegans) 3	Mus musculus	136-140
34841893-7	2022	Results: Over a lifetime, Core Diabetes Model projected 8.78 and 8.75 quality-adjusted life-years and a total cost of DKK 447,633 and DKK 387,786; thereby, generating an incremental cost-effectiveness ratio of DKK 1,930,548 for oral semaglutide+metformin versus empagliflozin+metformin.	Metformin	245-254	dickkopf WNT signaling pathway inhibitor 1	Homo sapiens	210-215
34713937-0	2022	Metformin functionalized dendritic fibrous nanosilica (KCC-1-nPr-Met) as an innovative and green nanocatalyst for the efficient synthesis of tetrahydro-4H-chromene derivatives.	Metformin	0-9	neuronal pentraxin receptor	Homo sapiens	61-64
34713937-1	2022	An innovative nanocatalyst (KCC-1-nPr-Met) has been prepared from the covalent attachment of metformin on the channels and the pores of n-propyl amine functionalized dendritic fibrous nanosilica (DFNS) and used towards efficient, green, and high yield synthesis of tetrahydro-4H-chromenes derivatives by one-pot three-component reaction of aromatic aldehydes, malononitrile, and dimedone in H2 O-EtOH at room temperature.	Metformin	93-102	neuronal pentraxin receptor	Homo sapiens	34-37
34637881-5	2022	We then addressed metformin"s effects on the AMPK-AKT-mTOR-HIFA pathway on two human primary cultures: one from a VHL-mutant PCC and other from a sporadic PCC.	Metformin	18-27	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	45-49
34895136-0	2021	Metformin alleviates the calcification of aortic valve interstitial cells through activating the PI3K/AKT pathway in an AMPK dependent way.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	120-124
34895136-3	2021	Many studies showed that metformin exerted beneficial effects on multiple cardiovascular diseases by mediating multiple proteins such as AMPK, NF-kappaB, and AKT.	Metformin	25-34	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	137-141
34862928-3	2021	In this study, we designed a new composite scaffold loading metformin (MET) by using the freeze-drying method, which was composed of beta-tricalcium phosphate (beta-TCP), chitosan (CTS) and the mesoporous silica (SBA-15).	Metformin	60-69	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	71-74
34808525-0	2021	Sex-specific effects of metformin and liraglutide on renal pathology and expression of connexin 45 and pannexin 1 following long-term high-fat high-sugar diet.	Metformin	24-33	gap junction protein, gamma 1	Rattus norvegicus	87-98
34424816-13	2021	Metformin also reduced the expression of CXCL12 and CXCR4 in mdx mice.	Metformin	0-9	chemokine (C-X-C motif) ligand 12	Mus musculus	41-47
34628168-6	2021	Interestingly, metformin, an extensively used antidiabetic drug, inhibits mTOR by affecting the activity of AMPK.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	108-112
34432321-10	2021	Consistent with this, metformin directly inhibited LATS1/2 and activated Mst1/2, phosphorylated YAP1 in vitro.	Metformin	22-31	large tumor suppressor	Mus musculus	51-58
34432321-10	2021	Consistent with this, metformin directly inhibited LATS1/2 and activated Mst1/2, phosphorylated YAP1 in vitro.	Metformin	22-31	yes-associated protein 1	Mus musculus	96-100
34688695-0	2021	Blunting p38 MAPKalpha and ERK1/2 activities by empagliflozin enhances the antifibrotic effect of metformin and augments its AMPK-induced NF-kappaB inactivation in mice intoxicated with carbon tetrachloride.	Metformin	98-107	mitogen-activated protein kinase 3	Mus musculus	27-33
34664036-7	2021	Maintaining proper blood glucose levels using oral antidiabetic drugs like Metformin reduced the detrimental effects of COVID-19 by different possible mechanisms such as Metformin-mediated anti-inflammatory and immunomodulatory activities; effect on viral entry and ACE2 stability; inhibition of virus infection; alters virus survival and endosomal pH; mTOR inhibition; and influence on gut microbiota.	Metformin	75-84	angiotensin converting enzyme 2	Homo sapiens	266-270
34570348-7	2021	Moreover, metformin treatment significantly downregulated the expression of pro-inflammatory associated genes (iNOS, H2-Aa, and TNF-alpha) in the corpus callosum, whereas expression of anti-inflammatory markers (Arg1, Mrc1, and IL10) was not promoted, compared to CPZ mice.	Metformin	10-19	arginase, liver	Mus musculus	212-216
34733370-8	2021	Specifically, metformin induced cell cycle arrest in the G0/G1 phases, accompanied by increased expression of p21 and p27, and decreased expression of cyclin D1 and cyclin-dependent kinase 4.	Metformin	14-23	cyclin dependent kinase inhibitor 1B	Canis lupus familiaris	118-121
35507395-9	2022	At therapeutically achievable concentrations metformin acted as a senostatic neither via inhibition of mitochondrial complex I, nor via improvement of mitophagy or mitochondrial function, but by reducing non-mitochondrial ROS production via NOX4 inhibition in senescent cells.	Metformin	45-54	NADPH oxidase 4	Mus musculus	241-245
34753372-3	2022	One of the medications widely used in the treatment of T2DM is biguanide derivative, metformin, which exerts promising anticancer properties principally through activation of adenosine monophosphate kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) pathways.	Metformin	85-94	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	175-205
34753372-3	2022	One of the medications widely used in the treatment of T2DM is biguanide derivative, metformin, which exerts promising anticancer properties principally through activation of adenosine monophosphate kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) pathways.	Metformin	85-94	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	207-211
34825068-10	2021	Metformin treatment also found to modulate the expression of fat metabolizing and anti-inflammatory genes including PPAR--gamma, C/EBP-alpha, SREBP1c, FAS, AMPK and GLUT-4.	Metformin	0-9	sterol regulatory element binding transcription factor 1	Rattus norvegicus	142-149
34873484-0	2021	Dual anticancer role of metformin: an old drug regulating AMPK dependent/independent pathways in metabolic, oncogenic/tumorsuppresing and immunity context.	Metformin	24-33	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	58-62
34873484-6	2021	Here, we described anticancer activity of metformin on the AMPK dependent/independent mechanisms regulating metabolism, oncogene/tumor suppressor signaling pathways together with the issue of clinical studies.	Metformin	42-51	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	59-63
34858397-8	2021	Finally, pre-treatment of monocytes with metformin strongly suppressed spike protein-mediated cytokine production and metabolic reprogramming.	Metformin	41-50	surface glycoprotein	Severe acute respiratory syndrome coronavirus 2	71-76
35603556-0	2022	Metformin suppresses lung adenocarcinoma by downregulating long non-coding RNA (lncRNA) AFAP1-AS1 and secreted phosphoprotein 1 (SPP1) while upregulating miR-3163.	Metformin	0-9	microRNA 3163	Homo sapiens	154-162
35390687-6	2022	Importantly, metformin blunts PFOA-induced fetal growth retardation (FGR) and such protective effect could be recapitulated by transplantation of fecal material and pharmacological activation of AMPK.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	195-199
35405526-0	2022	Metformin alleviates nickel-refining fumes-induced aerobic glycolysis via AMPK/GOLPH3 pathway in vitro and in vivo.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	74-78
35405526-6	2022	Our findings indicated that Ni fumes expose evoked aerobic glycolysis by AMPK/GOLPH3, while metformin attenuated Ni particles-promoted GOLPH3-mediated aerobic glycolysis by p-AMPK expression increase.	Metformin	92-101	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	175-179
35405526-11	2022	The results indicated that metformin decreased the protein levels of GOLPH3, LDHA, HK2, MCT-4 and improved p-AMPK expression.	Metformin	27-36	hexokinase 2	Homo sapiens	83-86
35405526-11	2022	The results indicated that metformin decreased the protein levels of GOLPH3, LDHA, HK2, MCT-4 and improved p-AMPK expression.	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	109-113
35405526-12	2022	Thus, our findings demonstrated metformin antagonized Ni-refining fumes-caused aerobic glycolysis via AMPK/GOLPH3.	Metformin	32-41	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	102-106
34858397-10	2021	In summary, the SARS-CoV-2 spike protein induces a pro-inflammatory immunometabolic response in monocytes that can be suppressed by metformin, and metformin likewise suppresses inflammatory responses to live SARS-CoV-2.	Metformin	132-141	surface glycoprotein	Severe acute respiratory syndrome coronavirus 2	27-32
34927008-7	2021	Metformin activates the LKB1/AMPK pathway to interact with several intracellular signaling pathways and molecular mechanisms.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	29-33
34607979-7	2021	Metformin diminished the phosphorylation of mTOR, p70S6K and 4E-BP1 by accelerating adenosine monophosphateactivated kinase (AMPK) in HeLa cancer cells, but it did not affect other cell lines.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	84-123
34607979-7	2021	Metformin diminished the phosphorylation of mTOR, p70S6K and 4E-BP1 by accelerating adenosine monophosphateactivated kinase (AMPK) in HeLa cancer cells, but it did not affect other cell lines.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	125-129
34705249-3	2021	AIM: To evaluate the effect of glucagon-like peptide 1 receptor agonists on major cardiovascular events (MACE) and mortality in metformin-naive patients with type 2 diabetes.	Metformin	128-137	glucagon like peptide 1 receptor	Homo sapiens	31-63
34727651-11	2021	After metformin intervention, the expression of E-Cad was significantly increased, the expression levels of Vimentin and alpha-SMA were significantly decreased (P<0.05) .	Metformin	6-15	vimentin	Rattus norvegicus	108-116
34486387-8	2021	While 0.1mM/L metformin upregulated the expression of BECLIN1 and LC3 I/II gene and inhibited the expression of mTOR and GSK3beta, contribute to reverse the osteogenesis inhibition of ASCs caused by high glucose.	Metformin	14-23	glycogen synthase kinase 3 alpha	Homo sapiens	121-129
34626114-8	2022	Expression of AMPK and SIRT1 was reduced in gut of 6-month-old fish with poly I:C-treatment, and feeding metformin reversed these declines.	Metformin	105-114	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	14-18
34626114-9	2022	Taken together, the present study suggested that poly I:C-injection led to aging-like phenomena in gut and metformin activated AMPK and SIRT1 to reduce NF-kappaB mediated inflammation and resist oxidative stress via enhanced expression of FoxO3a and PGC-1alpha, and finally delayed gut aging in vertebrates.	Metformin	107-116	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	127-131
34375763-10	2021	Metformin treatment decreased ATXN7L3B-induced tumor-initiating ability in a HCC mouse model, implying that metformin may inhibit cancer stemness by downregulating ATXN7L3B.	Metformin	0-9	ataxin 7-like 3B	Mus musculus	30-38
34375763-10	2021	Metformin treatment decreased ATXN7L3B-induced tumor-initiating ability in a HCC mouse model, implying that metformin may inhibit cancer stemness by downregulating ATXN7L3B.	Metformin	0-9	ataxin 7-like 3B	Mus musculus	164-172
34375763-10	2021	Metformin treatment decreased ATXN7L3B-induced tumor-initiating ability in a HCC mouse model, implying that metformin may inhibit cancer stemness by downregulating ATXN7L3B.	Metformin	108-117	ataxin 7-like 3B	Mus musculus	30-38
34375763-10	2021	Metformin treatment decreased ATXN7L3B-induced tumor-initiating ability in a HCC mouse model, implying that metformin may inhibit cancer stemness by downregulating ATXN7L3B.	Metformin	108-117	ataxin 7-like 3B	Mus musculus	164-172
34690937-8	2021	Furthermore, metformin attenuated plasma glucose levels and improved sensorimotor gating in Tmem108 mutant mice.	Metformin	13-22	transmembrane protein 108	Mus musculus	92-99
34676202-11	2021	In metformin-treated samples, the CEBPA, TP53 and USF1 transcription factors appeared to be involved in the regulation of several factors (SOD1, SOD2, CAT, GLRX, GSTP1) blocking ROS.	Metformin	3-12	superoxide dismutase 2	Homo sapiens	145-149
35143848-2	2022	Recently, the position of metformin as first choice glucose-lowering agent has been supplanted to some extent by the emergence of newer classes of antidiabetic therapy, namely the sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists.	Metformin	26-35	glucagon like peptide 1 receptor	Homo sapiens	260-275
35625721-0	2022	Metformin Protects against Diabetic Cardiomyopathy: An Association between Desmin-Sarcomere Injury and the iNOS/mTOR/TIMP-1 Fibrosis Axis.	Metformin	0-9	desmin	Rattus norvegicus	75-81
35462933-5	2022	For example, metformin promotes thermogenesis and alleviates obesity by activating the AMPK/alphaKG/PRDM16 signaling pathway; rosiglitazone alleviates obesity under the synergistic effect of PRDM16; resveratrol plays an antiobesity role by inducing the expression of PRDM16; liraglupeptide improves insulin resistance by inducing the expression of PRDM16; and mulberry leaves play an anti-inflammatory and antidiabetes role by activating the expression of brown fat cell marker genes (including PRDM16).	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	87-91
35462933-5	2022	For example, metformin promotes thermogenesis and alleviates obesity by activating the AMPK/alphaKG/PRDM16 signaling pathway; rosiglitazone alleviates obesity under the synergistic effect of PRDM16; resveratrol plays an antiobesity role by inducing the expression of PRDM16; liraglupeptide improves insulin resistance by inducing the expression of PRDM16; and mulberry leaves play an anti-inflammatory and antidiabetes role by activating the expression of brown fat cell marker genes (including PRDM16).	Metformin	13-22	PR/SET domain 16	Homo sapiens	100-106
35462933-5	2022	For example, metformin promotes thermogenesis and alleviates obesity by activating the AMPK/alphaKG/PRDM16 signaling pathway; rosiglitazone alleviates obesity under the synergistic effect of PRDM16; resveratrol plays an antiobesity role by inducing the expression of PRDM16; liraglupeptide improves insulin resistance by inducing the expression of PRDM16; and mulberry leaves play an anti-inflammatory and antidiabetes role by activating the expression of brown fat cell marker genes (including PRDM16).	Metformin	13-22	PR/SET domain 16	Homo sapiens	267-273
35462933-5	2022	For example, metformin promotes thermogenesis and alleviates obesity by activating the AMPK/alphaKG/PRDM16 signaling pathway; rosiglitazone alleviates obesity under the synergistic effect of PRDM16; resveratrol plays an antiobesity role by inducing the expression of PRDM16; liraglupeptide improves insulin resistance by inducing the expression of PRDM16; and mulberry leaves play an anti-inflammatory and antidiabetes role by activating the expression of brown fat cell marker genes (including PRDM16).	Metformin	13-22	PR/SET domain 16	Homo sapiens	348-354
35462933-5	2022	For example, metformin promotes thermogenesis and alleviates obesity by activating the AMPK/alphaKG/PRDM16 signaling pathway; rosiglitazone alleviates obesity under the synergistic effect of PRDM16; resveratrol plays an antiobesity role by inducing the expression of PRDM16; liraglupeptide improves insulin resistance by inducing the expression of PRDM16; and mulberry leaves play an anti-inflammatory and antidiabetes role by activating the expression of brown fat cell marker genes (including PRDM16).	Metformin	13-22	PR/SET domain 16	Homo sapiens	495-501
35455439-3	2022	By reducing mitochondrial oxidative phosphorylation and adenosine triphosphate (ATP) production, metformin increased AMP (adenosine monophosphate)-activated protein kinase (AMPK) activity and altered cellular redox state with reduced glucagon activity, endogenous glucose production, lipogenesis, and protein synthesis.	Metformin	97-106	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	173-177
35455439-5	2022	By increasing the relative abundance of mucin-producing and short-chain-fatty-acid-producing gut microbes, metformin further improved the host inflammatory and metabolic milieu.	Metformin	107-116	LOC100508689	Homo sapiens	40-45
35378172-12	2022	LAY SUMMARY: Non-alcoholic fatty liver disease impairs motility, metabolic function and response to anti-PD-1 treatment of hepatic CD8+ T cells, which can be rescued by metformin treatment.	Metformin	169-178	programmed cell death 1	Homo sapiens	105-109
35183887-10	2022	Notably, serum LCA level in the co-administration group was increased by 34% and 39% after multiple-dose (7 and 14 consecutive days, respectively) administration compared to the metformin alone group.	Metformin	178-187	clathrin, light chain A	Rattus norvegicus	15-18
35414608-9	2022	Metformin reduced immunoglobulin G and complement C3 deposition in glomeruli.	Metformin	0-9	complement component 3	Mus musculus	39-52
35414608-12	2022	In addition, metformin alleviated the necroptosis of HK-2 cells stimulated by LPS and TNF-alpha, evidencing by a decrease in the expression of necroptosis markers p-RIPK1, p-RIPK3 and p-MLKL, and the inflammasome-related markers NLRP3 (NLR family pyrin domain containing 3), ASC (apoptosis-associated speck-like protein containing a CARD), caspase-1.	Metformin	13-22	caspase 1	Mus musculus	340-349
35104674-3	2022	Metformin (MET) has anti-oxidant, anti-inflammatory, anti-apoptotic and neuroprotective properties, which may exert a potential therapeutic effect on SCI.	Metformin	0-9	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	11-14
35354137-1	2022	OBJECTIVE: The present study evaluates the neuroprotective effect of alpha lipoic acid (ALA) and/or metformin (MET) on the behavioral and neurochemical changes induced by hypothyroidism.	Metformin	111-114	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	100-109
35328696-7	2022	Proteomics was used to construct protein profiles in neural differentiation, and the results showed that chitosan hydrogels containing metformin promoted the upregulation of neural regeneration-related proteins, including ATP5F1, ATP5J, NADH dehydrogenase (ubiquinone) Fe-S protein 3 (NDUFS3), and Glutamate Dehydrogenase 1 (GLUD1).	Metformin	135-144	ATP synthase peripheral stalk-membrane subunit b	Homo sapiens	222-228
35370636-12	2022	Notably, our data showed that the regulative effects of FPS, both in vivo and in vitro, on the key signaling molecules, such as p-AMPK and p-raptor, in the AMPK/mTORC1/NLRP3 signaling axis were superior to those of RAP, but similar to those of metformin, an AMPK agonist, in vitro.	Metformin	244-253	CREB regulated transcription coactivator 1	Mus musculus	161-167
35278160-2	2022	Here, we show that metformin relieves bortezomib (BTZ)-evoked induction and maintenance of neuropathic pain by preventing the reduction in the expression of Beclin-1, an autophagy marker, in the spinal dorsal horn.	Metformin	19-28	beclin 1	Rattus norvegicus	157-165
35278160-4	2022	Co-application of 3-methyladenine and metformin partially inhibited the effect of metformin in recovering Beclin-1 expression and in reducing the pain behavior in rats subjected to BTZ treatment.	Metformin	38-47	beclin 1	Rattus norvegicus	106-114
35278160-4	2022	Co-application of 3-methyladenine and metformin partially inhibited the effect of metformin in recovering Beclin-1 expression and in reducing the pain behavior in rats subjected to BTZ treatment.	Metformin	82-91	beclin 1	Rattus norvegicus	106-114
35241643-6	2022	Additionally, miR-146a overexpression weakened the metformin-mediated upregulation of NAMPT expression, NAD+ synthesis, SIRT activity, and senescence protection, whereas treatment with the miR-146a inhibitor reversed this effect.	Metformin	51-60	nicotinamide phosphoribosyltransferase	Homo sapiens	86-91
35241643-9	2022	AMPK activators metformin and 5-aminoimidazole-4-carboxamide (AICAR) hindered miR-146a expression at the transcriptional level by promoting IkappaB kinase (IKK) phosphorylation to attenuate nuclear factor-kappaB (NF-kappaB) activity.	Metformin	16-25	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
35236827-0	2022	Metformin suppresses the growth of colorectal cancer by targeting INHBA to inhibit TGF-beta/PI3K/AKT signaling transduction.	Metformin	0-9	transforming growth factor alpha	Homo sapiens	83-91
35236827-6	2022	In mechanism, INHBA is an important ligand of TGF-beta signaling and metformin blocked the activation of TGF-beta signaling by targeting INHBA, and then down-regulated the activity of PI3K/Akt pathway, leading to the reduction of cyclinD1 and cell cycle arrest.	Metformin	69-78	transforming growth factor alpha	Homo sapiens	46-54
35236827-6	2022	In mechanism, INHBA is an important ligand of TGF-beta signaling and metformin blocked the activation of TGF-beta signaling by targeting INHBA, and then down-regulated the activity of PI3K/Akt pathway, leading to the reduction of cyclinD1 and cell cycle arrest.	Metformin	69-78	transforming growth factor alpha	Homo sapiens	105-113
35236827-6	2022	In mechanism, INHBA is an important ligand of TGF-beta signaling and metformin blocked the activation of TGF-beta signaling by targeting INHBA, and then down-regulated the activity of PI3K/Akt pathway, leading to the reduction of cyclinD1 and cell cycle arrest.	Metformin	69-78	cyclin D1	Homo sapiens	230-238
35236827-7	2022	Together, these findings indicate that metformin down-regulates the expression of INHBA, then attenuating TGF-beta/PI3K/Akt signaling transduction, thus inhibiting the proliferation of CRC.	Metformin	39-48	transforming growth factor alpha	Homo sapiens	106-114
35222699-11	2022	Regarding the mechanism, in cartilage, metformin increased the expression of Col II and decreased the expression of MMP-13, NLRP3, caspase-1, GSDMD and IL-1beta.	Metformin	39-48	matrix metallopeptidase 13	Mus musculus	116-122
35222699-11	2022	Regarding the mechanism, in cartilage, metformin increased the expression of Col II and decreased the expression of MMP-13, NLRP3, caspase-1, GSDMD and IL-1beta.	Metformin	39-48	caspase 1	Mus musculus	131-140
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	lysosomal associated membrane protein 1	Homo sapiens	673-678
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	lysosomal associated membrane protein 1	Homo sapiens	680-719
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	microtubule associated protein 1 light chain 3 beta	Homo sapiens	721-729
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	microtubule associated protein 1 light chain 3 beta	Homo sapiens	735-786
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	ribosomal protein S6	Homo sapiens	1113-1119
35281267-13	2022	Conclusion: Metformin combining PD-1 inhibitor enhanced anti-tumor efficacy in STK11 mutant lung cancer through inhibition of RNF5-mediated K48-linked ubiquitination of STING, which was dependent on AXIN-1.	Metformin	12-21	programmed cell death 1	Homo sapiens	32-36
35123389-14	2022	CONCLUSION: Elevated RIF1 in oocytes caused by maternal obesity may mediate abnormal embryonic epigenetic remodeling and increase metabolic risk in offspring by regulating histone modifications on MuERV-L, which can be partially rescued by metformin treatment.	Metformin	240-249	endogenous retroviral sequence 4 (with leucine tRNA primer)	Mus musculus	197-204
35007850-0	2022	Metformin and MiR-365 synergistically promote the apoptosis of gastric cancer cells via MiR-365-PTEN-AMPK axis.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	101-105
35007850-4	2022	Notably, Metformin enhanced gastriccell apoptosis via modulating AMPK signaling.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	65-69
35007850-5	2022	Furthermore, Metformin and miR-365 synergistically promote the apoptosis of gastric cancer cells by miR-365-PTEN-AMPK axis.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	113-117
34676202-11	2021	In metformin-treated samples, the CEBPA, TP53 and USF1 transcription factors appeared to be involved in the regulation of several factors (SOD1, SOD2, CAT, GLRX, GSTP1) blocking ROS.	Metformin	3-12	glutaredoxin	Homo sapiens	156-160
34671273-0	2021	Adverse Effects of Metformin From Diabetes to COVID-19, Cancer, Neurodegenerative Diseases, and Aging: Is VDAC1 a Common Target?	Metformin	19-28	voltage dependent anion channel 1	Homo sapiens	106-111
35203528-0	2022	Metformin Inhibits ROS Production by Human M2 Macrophages via the Activation of AMPK.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	80-84
35203528-8	2022	Interestingly, metformin with LPS induced activation of the adenosine-monophosphate-activated protein kinase (AMPK) and pharmacological activation of AMPK by AICAR, a known AMPK activator, decreased ROS production, whereas the deletion of AMPK in mice dramatically enhanced ROS production in different types of immune cells.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	110-114
35203528-8	2022	Interestingly, metformin with LPS induced activation of the adenosine-monophosphate-activated protein kinase (AMPK) and pharmacological activation of AMPK by AICAR, a known AMPK activator, decreased ROS production, whereas the deletion of AMPK in mice dramatically enhanced ROS production in different types of immune cells.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	150-154
35203528-8	2022	Interestingly, metformin with LPS induced activation of the adenosine-monophosphate-activated protein kinase (AMPK) and pharmacological activation of AMPK by AICAR, a known AMPK activator, decreased ROS production, whereas the deletion of AMPK in mice dramatically enhanced ROS production in different types of immune cells.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	173-177
35203528-8	2022	Interestingly, metformin with LPS induced activation of the adenosine-monophosphate-activated protein kinase (AMPK) and pharmacological activation of AMPK by AICAR, a known AMPK activator, decreased ROS production, whereas the deletion of AMPK in mice dramatically enhanced ROS production in different types of immune cells.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	239-243
35203528-9	2022	These results suggest that metformin exhibits anti-inflammatory effects by inhibiting the differentiation of human monocytes into M1 macrophages and by limiting ROS production by macrophages via the activation of AMPK.	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	213-217
35079096-4	2022	We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1).	Metformin	18-27	killer cell lectin like receptor K1	Homo sapiens	50-69
35079096-4	2022	We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1).	Metformin	18-27	killer cell lectin like receptor K1	Homo sapiens	71-76
35079096-4	2022	We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1).	Metformin	18-27	integrin subunit alpha L	Homo sapiens	159-199
35079096-4	2022	We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1).	Metformin	18-27	integrin subunit alpha L	Homo sapiens	201-206
35163187-0	2022	Metformin and Insulin Resistance: A Review of the Underlying Mechanisms behind Changes in GLUT4-Mediated Glucose Transport.	Metformin	0-9	solute carrier family 2 member 4	Homo sapiens	90-95
35163187-3	2022	Therefore, the observed increase in peripheral glucose utilization after metformin treatment most likely comes from the induction of GLUT4 expression and its increased translocation to the plasma membrane.	Metformin	73-82	solute carrier family 2 member 4	Homo sapiens	133-138
35013152-4	2022	This study aimed to assess the underlying mechanism of the formation of ARC and investigate the potential anti-ageing effect of metformin (MET) on ARC.	Metformin	128-137	activity regulated cytoskeleton associated protein	Homo sapiens	147-150
35013155-4	2022	The NLRP3 inflammasome, mitochondrial dynamics and morphology, oxidative stress, and cell injury markers were examined in RTECs treated by TGF-beta1 with or without Ppargc1a plasmid, PGC-1alpha activator (metformin), and siPGC-1alpha.	Metformin	205-214	transforming growth factor, beta 1	Mus musculus	139-148
35013155-8	2022	PGC-1alpha induction with the plasmid and metformin improved mitochondrial dynamics and morphology and attenuated the NLRP3 inflammasome and cell injury.	Metformin	42-51	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	0-10
34714980-0	2022	Metformin protects against abdominal aortic aneurysm by Atg7-induced autophagy.	Metformin	0-9	autophagy related 7	Homo sapiens	56-60
34714980-8	2022	The Atg7 expression was regulated by overexpressed plasmid, siRNA (small interfering RNA), or metformin, and cell proliferation, migration, apoptosis and autophagy caused by Ang-II were examined.	Metformin	94-103	autophagy related 7	Homo sapiens	4-8
34714980-10	2022	The Ang-II also induced the expression of Atg7, and metformin reversed this effect both in vivo and in vitro.	Metformin	52-61	autophagy related 7	Homo sapiens	42-46
34714980-13	2022	The Atg7-mediated autophagy was also attenuated by metformin.	Metformin	51-60	autophagy related 7	Homo sapiens	4-8
34714980-14	2022	CONCLUSIONS: Metformin reduced autophagy in AAA and this effect was mediated by Atg7, suggesting that Atg7 is a potential downstream effector of metformin in protecting against the pathophysiology of AAA.	Metformin	13-22	autophagy related 7	Homo sapiens	80-84
34714980-14	2022	CONCLUSIONS: Metformin reduced autophagy in AAA and this effect was mediated by Atg7, suggesting that Atg7 is a potential downstream effector of metformin in protecting against the pathophysiology of AAA.	Metformin	13-22	autophagy related 7	Homo sapiens	102-106
34714980-14	2022	CONCLUSIONS: Metformin reduced autophagy in AAA and this effect was mediated by Atg7, suggesting that Atg7 is a potential downstream effector of metformin in protecting against the pathophysiology of AAA.	Metformin	145-154	autophagy related 7	Homo sapiens	102-106
35300567-1	2022	Dietary capsaicin (CAP), the main irritant component in pepper, can reduce the incidence of diabetes, while metformin (MET) is a first-line oral hypoglycemic drug.	Metformin	119-122	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	108-117
35000900-6	2022	Metformin may have a role in the treatment of type A insulin resistance syndrome due to heterozygous mutation of the INSR gene.	Metformin	0-9	insulin receptor	Homo sapiens	117-121
35350904-0	2022	Plantamajoside promotes metformin-induced apoptosis, autophagy and proliferation arrest of liver cancer cells via suppressing Akt/GSK3beta signaling.	Metformin	24-33	glycogen synthase kinase 3 alpha	Homo sapiens	130-138
35316895-0	2022	The UCA1 and microRNA-18a signaling pathway mediates the irisin-lowering effect of metformin in the management of polycystic ovary syndrome.	Metformin	83-92	urothelial cancer associated 1	Homo sapiens	4-8
35370738-7	2022	Modulation by metformin of the cell-surface ACE2 protein (a key binding target for SARS-CoV 2 spike protein) via the AMP kinase pathway may be involved.	Metformin	14-23	angiotensin converting enzyme 2	Homo sapiens	44-48
34671273-3	2021	In this review, we focus on the important aspects of mitochondrial dysfunction in energy metabolism and cell death with their gatekeeper VDAC1 (voltage-dependent anion channel 1) as a possible metformin target, and summarize metformin"s effects in several diseases and gut microbiota.	Metformin	193-202	voltage dependent anion channel 1	Homo sapiens	137-142
34671273-5	2021	Interestingly, metformin"s adverse effects in many diseases all show VDAC1 involvement, suggesting that it is a common factor in metformin-affecting diseases.	Metformin	15-24	voltage dependent anion channel 1	Homo sapiens	69-74
34671273-5	2021	Interestingly, metformin"s adverse effects in many diseases all show VDAC1 involvement, suggesting that it is a common factor in metformin-affecting diseases.	Metformin	129-138	voltage dependent anion channel 1	Homo sapiens	69-74
34671273-6	2021	The findings that metformin has an opposite effect on various diseases are consistent with the fact that VDAC1 controls cell life and death, supporting the idea that it is a target for metformin.	Metformin	18-27	voltage dependent anion channel 1	Homo sapiens	105-110
34671273-6	2021	The findings that metformin has an opposite effect on various diseases are consistent with the fact that VDAC1 controls cell life and death, supporting the idea that it is a target for metformin.	Metformin	185-194	voltage dependent anion channel 1	Homo sapiens	105-110
34601503-5	2021	Mechanistically, metformin not only transcriptionally represses DHFR via E2F4 but also promotes lysosomal degradation of the DHFR protein.	Metformin	17-26	E2F transcription factor 4	Homo sapiens	73-77
34274355-6	2021	Furthermore, a key molecule of the antidiabetic mechanism of action of metformin is adenosine 5"-monophospate-activated protein kinase (AMPK), as the metformin-induced activation of AMPK is well documented.	Metformin	71-80	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	84-134
34274355-6	2021	Furthermore, a key molecule of the antidiabetic mechanism of action of metformin is adenosine 5"-monophospate-activated protein kinase (AMPK), as the metformin-induced activation of AMPK is well documented.	Metformin	71-80	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	136-140
34274355-6	2021	Furthermore, a key molecule of the antidiabetic mechanism of action of metformin is adenosine 5"-monophospate-activated protein kinase (AMPK), as the metformin-induced activation of AMPK is well documented.	Metformin	71-80	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	182-186
34274355-6	2021	Furthermore, a key molecule of the antidiabetic mechanism of action of metformin is adenosine 5"-monophospate-activated protein kinase (AMPK), as the metformin-induced activation of AMPK is well documented.	Metformin	150-159	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	84-134
34274355-6	2021	Furthermore, a key molecule of the antidiabetic mechanism of action of metformin is adenosine 5"-monophospate-activated protein kinase (AMPK), as the metformin-induced activation of AMPK is well documented.	Metformin	150-159	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	136-140
34274355-6	2021	Furthermore, a key molecule of the antidiabetic mechanism of action of metformin is adenosine 5"-monophospate-activated protein kinase (AMPK), as the metformin-induced activation of AMPK is well documented.	Metformin	150-159	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	182-186
34473417-1	2021	Metformin (Met) is a commonly used drug in the treatment of type 2 diabetes.	Metformin	11-14	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	0-9
34384564-0	2021	Metformin suppresses phenylephrine-induced hypertrophic responses by inhibiting p300-HAT activity in cardiomyocytes.	Metformin	0-9	E1A binding protein p300	Homo sapiens	80-84
2682123-10	1989	In the overweight and in the obese metformin significantly improved glycaemic profiles and reduced HbA1 levels.	Metformin	35-44	hemoglobin subunit alpha 1	Homo sapiens	99-103
34384564-5	2021	Metformin directly inhibited p300-mediated acetylation of histone-H3K9.	Metformin	0-9	E1A binding protein p300	Homo sapiens	29-33
34384564-9	2021	Metformin significantly suppressed p300-induced hypertrophic responses and acetylation of histone-H3K9.	Metformin	0-9	E1A binding protein p300	Homo sapiens	35-39
34384564-10	2021	CONCLUSIONS: The study demonstrates that metformin can suppress PE-induced and p300-mediated hypertrophic responses.	Metformin	41-50	E1A binding protein p300	Homo sapiens	79-83
34584119-5	2021	Metformin upregulated the human antimicrobial peptides cathelicidin LL-37 and RNase7 via modulation of the TRPA1 channel and AMPK pathway.	Metformin	0-9	ribonuclease A family member 7	Homo sapiens	78-84
34584119-5	2021	Metformin upregulated the human antimicrobial peptides cathelicidin LL-37 and RNase7 via modulation of the TRPA1 channel and AMPK pathway.	Metformin	0-9	transient receptor potential cation channel subfamily A member 1	Homo sapiens	107-112
34584119-6	2021	Interestingly, metformin stimulation enriched both LL-37 and TRPA1 in lysosomes.	Metformin	15-24	transient receptor potential cation channel subfamily A member 1	Homo sapiens	61-66
34684418-6	2021	Maternal metformin reduced plasma insulin, leptin, triglyceride and cholesterol levels in male and female offspring.	Metformin	9-18	leptin	Rattus norvegicus	43-49
34646263-12	2021	We observed that the antidiabetic biguanide metformin, a putative anti-inflammatory agent, also upregulates ACE2 expression in Calu-3 and endothelial cells.	Metformin	44-53	angiotensin converting enzyme 2	Homo sapiens	108-112
34572149-8	2021	In addition, metformin, a potential inhibitor of TLR4, also decreased expression of COX-2 and IL-6 induced by co-incubation with IL-26 and palmitate.	Metformin	13-22	interleukin 26	Homo sapiens	129-134
34572586-0	2021	Dual Blockade of Lactate/GPR81 and PD-1/PD-L1 Pathways Enhances the Anti-Tumor Effects of Metformin.	Metformin	90-99	programmed cell death 1	Homo sapiens	35-39
2647992-2	1989	Withdrawal of metformin resulted in a rise of fasting blood glucose, HbA1, serum total and low density lipoprotein (LDL) cholesterol.	Metformin	14-23	hemoglobin subunit alpha 1	Homo sapiens	69-73
2901378-7	1988	These studies suggest, therefore, that metformin may influence cellular metabolism by potentiating certain insulin actions through mechanisms that may be beyond insulin receptor binding.	Metformin	39-48	insulin receptor	Rattus norvegicus	161-177
3075902-4	1988	Although metformin may increase insulin-receptor binding, its main effect appears to be directed at the postreceptor level of insulin action.	Metformin	9-18	insulin receptor	Homo sapiens	32-48
3552772-3	1987	We suggest that metformin can correct down regulation of the insulin receptor.	Metformin	16-25	insulin receptor	Homo sapiens	61-77
6360756-0	1983	Insulin receptor binding to monocytes, insulin secretion, and glucose tolerance following metformin treatment.	Metformin	90-99	insulin receptor	Homo sapiens	0-16
6864442-4	1983	In alloxan diabetic rats, gut GLI levels were significantly correlated to the logarithm of tissue metformin levels, calculated from serum metformin levels.	Metformin	98-107	GLI family zinc finger 1	Rattus norvegicus	30-33
6864442-4	1983	In alloxan diabetic rats, gut GLI levels were significantly correlated to the logarithm of tissue metformin levels, calculated from serum metformin levels.	Metformin	138-147	GLI family zinc finger 1	Rattus norvegicus	30-33
6864442-5	1983	The blood lactate, pyruvate and plasma glucose levels were also linearly related to gut GLI levels, after metformin administration.	Metformin	106-115	GLI family zinc finger 1	Rattus norvegicus	88-91
6864442-7	1983	It is reasonable to consider that the effect of metformin on the gut GLI level is the primal effect, and that other pharmacologic effects such as plasma glucose lowering, blood lactate and pyruvate increasing effects are the consequences of the primal effect, at least in alloxan diabetic rats.	Metformin	48-57	GLI family zinc finger 1	Rattus norvegicus	69-72
6864442-9	1983	These results indicated that the effect of gut GLI was entirely masked by endogeneous insulin, which might be secreted by metformin administration.	Metformin	122-131	GLI family zinc finger 1	Rattus norvegicus	47-50
33850553-0	2021	Metformin prevents PFKFB3-related aerobic glycolysis from enhancing collagen synthesis in lung fibroblasts by regulating AMPK/mTOR pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	121-125
33850553-7	2021	The effects of metformin in AMP-activated protein kinase (AMPK) activation was assessed by mitochondrial complex I activity kits.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	28-56
33850553-7	2021	The effects of metformin in AMP-activated protein kinase (AMPK) activation was assessed by mitochondrial complex I activity kits.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	58-62
33850553-9	2021	Metformin significantly decreased mitochondrial complex I activity and upregulated the expression of p-AMPK/AMPK protein in a concentration-dependent manner.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	101-112
33850553-11	2021	However, this inhibitory role of metformin on PFKFB3-meditaed aerobic glycolysis and collagen synthesis was prevented by treatments with 3BDO and compound C, which are specific mTOR activator and AMPK inhibitor, respectively.	Metformin	33-42	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	196-200
33850553-12	2021	Taken together, the findings from this study suggested that metformin may prevent PFKFB3-associated aerobic glycolysis from enhancing collagen synthesis in lung fibroblasts via regulating the AMPK/mTOR pathway.	Metformin	60-69	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	192-196
34057870-6	2021	Hence, regulatory effects of metformin on membranous ACE2, and DPP4 can modulate immune reaction against Sars-cov2.	Metformin	29-38	angiotensin converting enzyme 2	Homo sapiens	53-57
34002012-10	2021	When cells were treated with metformin (an AMPK activator), the CRBN-induced activation of SMAD3 and upregulation of alpha-SMA and collagen expression were significantly suppressed, suggesting that increased TGF-beta1-induced activation of SMAD3 via CRBN overexpression is associated with AMPKalpha1 inactivation.	Metformin	29-38	SMAD family member 3	Mus musculus	91-96
34002012-10	2021	When cells were treated with metformin (an AMPK activator), the CRBN-induced activation of SMAD3 and upregulation of alpha-SMA and collagen expression were significantly suppressed, suggesting that increased TGF-beta1-induced activation of SMAD3 via CRBN overexpression is associated with AMPKalpha1 inactivation.	Metformin	29-38	transforming growth factor, beta 1	Mus musculus	208-217
34002012-10	2021	When cells were treated with metformin (an AMPK activator), the CRBN-induced activation of SMAD3 and upregulation of alpha-SMA and collagen expression were significantly suppressed, suggesting that increased TGF-beta1-induced activation of SMAD3 via CRBN overexpression is associated with AMPKalpha1 inactivation.	Metformin	29-38	SMAD family member 3	Mus musculus	240-245
34004440-0	2021	Metformin prevents BAFF activation of Erk1/2 from B-cell proliferation and survival by impeding mTOR-PTEN/Akt signaling pathway.	Metformin	0-9	TNF superfamily member 13b	Homo sapiens	19-23
34004440-4	2021	Here, we show that metformin attenuated human soluble BAFF (hsBAFF)-induced cell proliferation and survival by blocking the Erk1/2 pathway in normal and B-lymphoid (Raji) cells.	Metformin	19-28	TNF superfamily member 13b	Homo sapiens	54-58
34004440-9	2021	These results indicate that metformin prevents BAFF activation of Erk1/2 from cell proliferation and survival by impeding mTOR-PTEN/Akt signaling pathway in normal and neoplastic B-lymphoid cells.	Metformin	28-37	TNF superfamily member 13b	Homo sapiens	47-51
34004440-10	2021	Our findings support that metformin has a great potential for prevention of excessive BAFF-induced aggressive B-cell malignancies and autoimmune diseases.	Metformin	26-35	TNF superfamily member 13b	Homo sapiens	86-90
33982074-10	2021	Along with the upregulation of phosphorylated AMPKalpha and ACCalpha, metformin at 1.5 and 3 mM inactivated NF-kappaB signalling components (p65 and IkappaBalpha) and the inflammatory genes (TNFA, IL6, IL1B and COX-2) which were activated by BHBA.	Metformin	70-79	synaptotagmin 1	Bos taurus	141-144
33982074-10	2021	Along with the upregulation of phosphorylated AMPKalpha and ACCalpha, metformin at 1.5 and 3 mM inactivated NF-kappaB signalling components (p65 and IkappaBalpha) and the inflammatory genes (TNFA, IL6, IL1B and COX-2) which were activated by BHBA.	Metformin	70-79	interferon beta-2	Bos taurus	197-200
33982074-10	2021	Along with the upregulation of phosphorylated AMPKalpha and ACCalpha, metformin at 1.5 and 3 mM inactivated NF-kappaB signalling components (p65 and IkappaBalpha) and the inflammatory genes (TNFA, IL6, IL1B and COX-2) which were activated by BHBA.	Metformin	70-79	interleukin 1 beta	Bos taurus	202-206
33982074-14	2021	Compared to BHBA treated cells, the protein expression of COX-2 and IL-1beta were decreased by the pretreatment with metformin, and the inhibitory effect of metformin was released by compound C. The bound of NF-kappaB onto IL1B promoter displayed higher in BHBA group and this was suppressed by pretreatment with metformin (P < 0.05).	Metformin	117-126	interleukin 1 alpha	Bos taurus	68-76
33982074-14	2021	Compared to BHBA treated cells, the protein expression of COX-2 and IL-1beta were decreased by the pretreatment with metformin, and the inhibitory effect of metformin was released by compound C. The bound of NF-kappaB onto IL1B promoter displayed higher in BHBA group and this was suppressed by pretreatment with metformin (P < 0.05).	Metformin	157-166	interleukin 1 beta	Bos taurus	223-227
33982074-14	2021	Compared to BHBA treated cells, the protein expression of COX-2 and IL-1beta were decreased by the pretreatment with metformin, and the inhibitory effect of metformin was released by compound C. The bound of NF-kappaB onto IL1B promoter displayed higher in BHBA group and this was suppressed by pretreatment with metformin (P < 0.05).	Metformin	157-166	interleukin 1 beta	Bos taurus	223-227
33760349-9	2021	Metformin showed an apparent effect on restoring CagA-induced elevation of PTEN promoter methylation, thus attenuating the PTEN expression.	Metformin	0-9	S100 calcium binding protein A8	Homo sapiens	49-53
33634460-10	2021	Metformin normalized the alterations in the expression of glucose metabolism-related genes (PGC-1alpha, G6pc, Pepck, Gck, PYGL, Gys2, PKLR, GLUT4) and insulin resistance-related genes (AdipoR1, AdipoR2) in the muscles and livers of rats induced by CORT.	Metformin	0-9	glucokinase	Rattus norvegicus	117-120
33634460-10	2021	Metformin normalized the alterations in the expression of glucose metabolism-related genes (PGC-1alpha, G6pc, Pepck, Gck, PYGL, Gys2, PKLR, GLUT4) and insulin resistance-related genes (AdipoR1, AdipoR2) in the muscles and livers of rats induced by CORT.	Metformin	0-9	glycogen synthase 2	Rattus norvegicus	128-132
33922757-8	2021	The MEK1/2 inhibitor, U0126, reduced the neuroprotective effect of metformin.	Metformin	67-76	mitogen activated protein kinase kinase 1	Rattus norvegicus	4-10
33886150-9	2021	Moreover, cotreating the cells with metformin (30 mM) and pitavastatin (10 muM) could preserve mitochondrial function, activate AMPK, and inhibit PI3K/mTOR than treatment with metformin or pitavastatin alone.	Metformin	36-45	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	128-132
33886150-10	2021	These findings clearly indicated that metformin plus pitavastatin had a synergistic anticancer effect on pancreatic cancer cells, potentially caused due to the activation of AMPK and inhibition of PI3K/mTOR signaling.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	174-178
33997311-7	2021	KDM individuals on metformin treatment exhibited lower levels of TIMP-1, -2 and -4 at baseline and of TIMP-4 at post-treatment.	Metformin	19-28	TIMP metallopeptidase inhibitor 4	Homo sapiens	102-108
33724959-9	2021	Metformin, another AMPK activator, can cause hypoglycemia.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	19-23
33888740-4	2021	In this sense, Metformin (MET), an FDA-approved drug used for the treatment of type 2 diabetes, has shown an anti-DENV effect in vitro by activating AMPK and reducing HMGCR activity.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	149-153
33141769-2	2021	In this study, we examined the antifibrotic effect of metformin as a suppressor of TGF-beta signaling pathways in human dermal fibroblasts (HDFs) and keloid spheroids.	Metformin	54-63	transforming growth factor alpha	Homo sapiens	83-91
33141769-8	2021	Collagen types I and III and p-Smad2/3 complex proteins were decreased in metformin-treated keloid spheroids.	Metformin	74-83	SMAD family member 2	Homo sapiens	31-38
33141769-9	2021	These findings indicated that metformin inhibits the expression of ECM components in TGF-beta-stimulated HDFs and keloid spheroids.	Metformin	30-39	transforming growth factor alpha	Homo sapiens	85-93
33650651-0	2021	Metformin inhibits mTOR and c-Myc by decreasing YAP protein expression in OSCC cells.	Metformin	0-9	Yes1 associated transcriptional regulator	Homo sapiens	48-51
33650651-2	2021	However, few studies have explored the role of Yes-associated protein (YAP), a vital factor contributing to OSCC biology, in metformin-induced anticancer activity in OSCC cells.	Metformin	125-134	Yes1 associated transcriptional regulator	Homo sapiens	47-69
33650651-2	2021	However, few studies have explored the role of Yes-associated protein (YAP), a vital factor contributing to OSCC biology, in metformin-induced anticancer activity in OSCC cells.	Metformin	125-134	Yes1 associated transcriptional regulator	Homo sapiens	71-74
33650651-3	2021	Thus, the purpose of the present study was to investigate the molecular relationship between metformin and YAP in OSCC cells.	Metformin	93-102	Yes1 associated transcriptional regulator	Homo sapiens	107-110
33650651-8	2021	Alteration of YAP protein expression affected metformin-mediated changes in the cell cycle and apoptosis of CAL27 and SCC25 cells.	Metformin	46-55	Yes1 associated transcriptional regulator	Homo sapiens	14-17
33650651-9	2021	In addition, compared to the control treatment, metformin treatment decreased the protein levels of YAP, mTOR, p-mTOR and c-Myc.	Metformin	48-57	Yes1 associated transcriptional regulator	Homo sapiens	100-103
33650651-10	2021	The overexpression of YAP alleviated the inhibitory effect of metformin on the protein expression of mTOR, p-mTOR and c-Myc.	Metformin	62-71	Yes1 associated transcriptional regulator	Homo sapiens	22-25
33650651-12	2021	Therefore, the results of the present study suggest that metformin suppresses OSCC by inhibiting YAP protein expression and by suppressing the YAP-mediated effects of metformin on the protein expression of mTOR and c-Myc.	Metformin	57-66	Yes1 associated transcriptional regulator	Homo sapiens	97-100
33650651-12	2021	Therefore, the results of the present study suggest that metformin suppresses OSCC by inhibiting YAP protein expression and by suppressing the YAP-mediated effects of metformin on the protein expression of mTOR and c-Myc.	Metformin	57-66	Yes1 associated transcriptional regulator	Homo sapiens	143-146
33650651-12	2021	Therefore, the results of the present study suggest that metformin suppresses OSCC by inhibiting YAP protein expression and by suppressing the YAP-mediated effects of metformin on the protein expression of mTOR and c-Myc.	Metformin	167-176	Yes1 associated transcriptional regulator	Homo sapiens	143-146
34572586-6	2021	In addition, considering that 3-OBA could recover the inhibitory effects of metformin on PD-1 expression, we further determined the dual blockade effects of PD-1/PD-L1 and lactate/GPR81 on the antitumor activity of metformin.	Metformin	76-85	programmed cell death 1	Homo sapiens	89-93
34572586-6	2021	In addition, considering that 3-OBA could recover the inhibitory effects of metformin on PD-1 expression, we further determined the dual blockade effects of PD-1/PD-L1 and lactate/GPR81 on the antitumor activity of metformin.	Metformin	76-85	programmed cell death 1	Homo sapiens	157-161
34572586-6	2021	In addition, considering that 3-OBA could recover the inhibitory effects of metformin on PD-1 expression, we further determined the dual blockade effects of PD-1/PD-L1 and lactate/GPR81 on the antitumor activity of metformin.	Metformin	215-224	programmed cell death 1	Homo sapiens	89-93
34572586-6	2021	In addition, considering that 3-OBA could recover the inhibitory effects of metformin on PD-1 expression, we further determined the dual blockade effects of PD-1/PD-L1 and lactate/GPR81 on the antitumor activity of metformin.	Metformin	215-224	programmed cell death 1	Homo sapiens	157-161
34573418-0	2021	Metformin Triggers Apoptosis and Induction of the G0/G1 Switch 2 Gene in Macrophages.	Metformin	0-9	G0/G1 switch 2	Homo sapiens	50-64
34573418-1	2021	Metformin is a widely used antidiabetic drug for the treatment of type 2 diabetes and has been recently demonstrated to possess anti-inflammatory properties via AMPK-mediated modulation of M2 macrophage activation.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	161-165
34573418-6	2021	The G0/G1 switch 2 gene (G0S2) was robustly up-regulated by metformin in macrophages.	Metformin	60-69	G0/G1 switch 2	Homo sapiens	4-18
34573418-6	2021	The G0/G1 switch 2 gene (G0S2) was robustly up-regulated by metformin in macrophages.	Metformin	60-69	G0/G1 switch 2	Homo sapiens	25-29
34573418-7	2021	Overexpression of G0S2 significantly induced apoptosis of macrophages in a dose-dependent manner and blunted the function of the crucial anti-apoptotic gene Bcl-2, which was significantly reduced by metformin.	Metformin	199-208	G0/G1 switch 2	Homo sapiens	18-22
34573418-8	2021	These findings show that metformin promoted apoptosis of macrophages, especially M1 macrophages, via G0S2 induction and provides a novel anti-inflammatory mechanism of metformin through induction of macrophage apoptosis.	Metformin	25-34	G0/G1 switch 2	Homo sapiens	101-105
34576192-11	2021	Metformin and DCA inhibited mTOR complex I signaling through upregulated AMPK-independent REDD1.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	73-77
34528900-0	2021	Metformin-induced chemosensitization to cisplatin depends on P53 status and is inhibited by Jarid1b overexpression in non-small cell lung cancer cells.	Metformin	0-9	lysine demethylase 5B	Homo sapiens	92-99
34528900-6	2021	The effects of metformin were tested both in vitro and in vivo and related to the ability of cells to accumulate Jarid1b, a histone demethylase involved in cisplatin resistance in different cancers.	Metformin	15-24	lysine demethylase 5B	Homo sapiens	113-120
34528900-8	2021	Treatment with a sub-lethal dose of cisplatin increased Jarid1b expression, yet downregulated P53 levels, protecting A549Res cells from metformin-induced chemosensitization to cisplatin and favored a glycolytic phenotype.	Metformin	136-145	lysine demethylase 5B	Homo sapiens	56-63
34116042-9	2021	High-dextrose and TM increased IRE1alpha and PERK phosphorylation and ATF6 and GRP78 expression, while treatment with metformin, liraglutide (a GLP-1 receptor agonist) and dapagliflozin (a SGLT-2 inhibitor), suppressed IRE1alpha and PERK phosphorylation as well as ATF6 and GRP78 expression.	Metformin	118-127	endoplasmic reticulum to nucleus signaling 1	Homo sapiens	31-40
34116042-9	2021	High-dextrose and TM increased IRE1alpha and PERK phosphorylation and ATF6 and GRP78 expression, while treatment with metformin, liraglutide (a GLP-1 receptor agonist) and dapagliflozin (a SGLT-2 inhibitor), suppressed IRE1alpha and PERK phosphorylation as well as ATF6 and GRP78 expression.	Metformin	118-127	glucagon like peptide 1 receptor	Homo sapiens	144-158
34116042-9	2021	High-dextrose and TM increased IRE1alpha and PERK phosphorylation and ATF6 and GRP78 expression, while treatment with metformin, liraglutide (a GLP-1 receptor agonist) and dapagliflozin (a SGLT-2 inhibitor), suppressed IRE1alpha and PERK phosphorylation as well as ATF6 and GRP78 expression.	Metformin	118-127	endoplasmic reticulum to nucleus signaling 1	Homo sapiens	219-228
34399755-0	2021	Metformin exerts anti-AR-negative prostate cancer activity via AMPK/autophagy signaling pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	63-67
33649289-0	2021	Metformin targets Clusterin to control lipogenesis and inhibit the growth of bladder cancer cells through SREBP-1c/FASN axis.	Metformin	0-9	clusterin	Homo sapiens	18-27
34399755-10	2021	Metformin also induced the activation of AMPK, markedly promoted expression of LC3II, and down-regulated the expression of p62/SQSTM1.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	41-45
34399755-11	2021	Animal experiments showed that the tumor volume of metformin group was smaller, meanwhile, the levels of p-AMPK (Thr172) and LC3B were up-regulated and the Ki-67 level was down-regulated, without abnormalities in biochemical indicators.	Metformin	51-60	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	107-111
34399755-11	2021	Animal experiments showed that the tumor volume of metformin group was smaller, meanwhile, the levels of p-AMPK (Thr172) and LC3B were up-regulated and the Ki-67 level was down-regulated, without abnormalities in biochemical indicators.	Metformin	51-60	microtubule associated protein 1 light chain 3 beta	Homo sapiens	125-129
34399790-7	2021	Besides, metformin (range 2-10 mM) reversed SiO2-induced cell toxicity, oxidative stress, and epithelial-mesenchymal transition process in epithelial cells (A549 and HBE), inhibited inflammation response in macrophages (THP-1), and alleviated TGF-beta1-stimulated fibroblast activation in lung fibroblasts (MRC-5) via an AMPK-dependent pathway.	Metformin	9-18	transforming growth factor, beta 1	Mus musculus	243-252
34484117-6	2021	Metformin significantly decreased the risk of body weight gain and increased INSR expression in F1 female offspring in PCOS-IR rats, contributing to the improvement in obesity, hyperinsulinemia, and IR.	Metformin	0-9	insulin receptor	Rattus norvegicus	77-81
34484117-11	2021	The results of this study could be used as a theoretical basis in support of using metformin in the treatment of PCOS-IR patients.	Metformin	83-92	insulin receptor	Homo sapiens	118-120
34434111-7	2021	Besides, metformin increased the expression levels of phosphorylated adenosine 5"-monophosphate (AMP)-activated protein kinase (p-AMPK), microtubule-associated protein (MAP) light chain 3B (LC3B) and Beclin1 proteins, and reduced levels of phosphorylated mammalian target of rapamycin (p-mTOR) and p62 proteins in vivo and in vitro.	Metformin	9-18	microtubule associated protein 1 light chain 3 beta	Homo sapiens	174-188
33045408-4	2021	At concentrations <= 2.5 mM, metformin significantly increased oxygen consumption rate (OCR) in the hiPSC-CMs by activating AMPK-dependent signaling and enhancing mitochondrial biogenesis.	Metformin	29-38	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	124-128
33045408-9	2021	Thus, in human heart, metformin might improve cardioprotection due to its biphasic effect on mitochondria: at low concentrations, it activates mitochondrial biogenesis via AMPK signaling and increases the OCR; at high concentrations, it inhibits the respiration by directly affecting the activity of complex I, reduces oxidative stress and delays mPTP formation.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	172-176
33476677-7	2021	Besides, the analysis based on Comparative Toxicogenomics Database (CTD) suggested that metformin targeting ACSL1 can be used as a potential drug for further research.	Metformin	88-97	acyl-CoA synthetase long chain family member 1	Homo sapiens	108-113
33476677-9	2021	Furthermore, overexpression of miR-19a significantly strengthened the beneficial effect of metformin on H/R-induced AC16 cells injury, which can be reversed by upregulation of ACSL1.	Metformin	91-100	acyl-CoA synthetase long chain family member 1	Homo sapiens	176-181
33517853-9	2021	Patients who took metformin regularly before infarction had lower miR-34a levels and lower serum CKMB activity.	Metformin	18-27	microRNA 34a	Homo sapiens	66-73
32841353-7	2021	Validation in ampler cohorts revealed that miR-4454 levels were consistently higher in obesity, associated with insulin-resistance (HOMA-IR/insulin) and modulated by medical (metformin/statins) and surgical (bariatric surgery) strategies.	Metformin	175-184	microRNA 4454	Homo sapiens	43-51
33323505-7	2021	Absence of PTP-PEST also blocked hypoxia-induced autophagy (LC3 degradation and puncta formation) which was rescued by AMPK activator, metformin (500 microM).	Metformin	135-144	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	119-123
33431790-0	2021	Metformin exhibits antiproliferation activity in breast cancer via miR-483-3p/METTL3/m6A/p21 pathway.	Metformin	0-9	methyltransferase like 3	Mus musculus	78-84
33431790-0	2021	Metformin exhibits antiproliferation activity in breast cancer via miR-483-3p/METTL3/m6A/p21 pathway.	Metformin	0-9	methyltransferase like 3	Mus musculus	85-88
33431790-3	2021	We found that metformin could suppress the N6-methyladenosine (m6A) level in breast cancer cells significantly.	Metformin	14-23	methyltransferase like 3	Mus musculus	63-66
33431790-6	2021	We then performed qRT-PCR, western blot, MeRIP, dual-luciferase reporter assay, and others to explore the m6A-dependent pathway associated with metformin.	Metformin	144-153	methyltransferase like 3	Mus musculus	106-109
33431790-9	2021	Metformin could reduce the m6A level via decreasing METTL3 expression mediated by miR-483-3p in breast cancer.	Metformin	0-9	methyltransferase like 3	Mus musculus	27-30
33431790-9	2021	Metformin could reduce the m6A level via decreasing METTL3 expression mediated by miR-483-3p in breast cancer.	Metformin	0-9	methyltransferase like 3	Mus musculus	52-58
33431790-12	2021	To specify, this study exhibited that metformin can inhibit breast cancer cell proliferation through the pathway miR-483-3p/METTL3/m6A/p21.	Metformin	38-47	methyltransferase like 3	Mus musculus	124-130
33431790-12	2021	To specify, this study exhibited that metformin can inhibit breast cancer cell proliferation through the pathway miR-483-3p/METTL3/m6A/p21.	Metformin	38-47	methyltransferase like 3	Mus musculus	131-134
33431790-13	2021	Our findings suggest that METTL3 may be considered as a potential therapeutic target of metformin for breast cancer.	Metformin	88-97	methyltransferase like 3	Mus musculus	26-32
33487223-0	2021	Retraction notice to "The antineoplastic drug metformin downregulates YAP by interfering with IRF-1 binding to the YAP promoter in NSCLC" [EBioMedicine 37 (2018) 188-204].	Metformin	46-55	Yes1 associated transcriptional regulator	Homo sapiens	70-73
33487223-0	2021	Retraction notice to "The antineoplastic drug metformin downregulates YAP by interfering with IRF-1 binding to the YAP promoter in NSCLC" [EBioMedicine 37 (2018) 188-204].	Metformin	46-55	Yes1 associated transcriptional regulator	Homo sapiens	115-118
33365058-0	2021	Metformin alleviates beta-glycerophosphate-induced calcification of vascular smooth muscle cells via AMPK/mTOR-activated autophagy.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	101-105
33365058-6	2021	Metformin increased the number of autophagosomes, green fluorescent LC3 puncta and the levels of LC3II/I, beclin 1, alpha-SMA and phosphorylated (p)-AMPK in the VSMCs that were treated with beta-glycerophosphate when compared to controls; whereas, calcium deposition and the expression levels of RUNX2 and p-mTOR were found to be decreased.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	149-153
33365058-8	2021	The results of the present study suggested that metformin may alleviate beta-glycerophosphate-induced calcification of VSMCs, which may be attributed to the activation of AMPK/mTOR signaling pathway-dependent autophagy.	Metformin	48-57	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	171-175
33210670-4	2020	Interestingly, the metformin (MET) loaded multifunctional nanoparticles (MET-HMSN-CeO2) with a special size exhibited significantly increased kidney accumulation over free MET.	Metformin	19-28	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	30-33
33210670-4	2020	Interestingly, the metformin (MET) loaded multifunctional nanoparticles (MET-HMSN-CeO2) with a special size exhibited significantly increased kidney accumulation over free MET.	Metformin	19-28	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	73-76
33210670-4	2020	Interestingly, the metformin (MET) loaded multifunctional nanoparticles (MET-HMSN-CeO2) with a special size exhibited significantly increased kidney accumulation over free MET.	Metformin	19-28	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	73-76
32970287-0	2020	Metformin downregulates miR223 expression in insulin-resistant 3T3L1 cells and human diabetic adipose tissue.	Metformin	0-9	microRNA 223	Mus musculus	24-30
32970287-2	2020	This study set up to determine the effect of metformin on miR223 expression and content of AKT/GLUT4 proteins in insulin resistant signaling in 3T3L1 cells and adipocyte of human diabetic patients.	Metformin	45-54	microRNA 223	Mus musculus	58-64
33049108-0	2020	Metformin enhances osteogenic differentiation of stem cells from human exfoliated deciduous teeth through AMPK pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	106-110
33049108-8	2020	Metformin (10-200 muM) did not affect the viability and proliferation of SHEDs, but significantly increased the expression of osteogenic genes, alkaline phosphatase activity, matrix mineralization, and p-AMPK level expression in SHEDs.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	204-208
33049108-9	2020	Compound C, a specific inhibitor of the AMPK pathway, abolished metformin-induced osteogenic differentiation of SHEDs.	Metformin	64-73	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	40-44
33049108-10	2020	Moreover, metformin treatment enhanced the expression of pro-angiogenic/osteogenic growth factors BMP2 and VEGF but reduced the osteoclastogenic factor RANKL/OPG expression in SHEDs.	Metformin	10-19	bone morphogenetic protein 2	Homo sapiens	98-102
33049108-11	2020	In conclusion, metformin could induce the osteogenic differentiation of SHEDs by activating the AMPK pathway and regulates the expression of pro-angiogenic/osteogenic growth factors and osteoclastogenic factors in SHEDs.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	96-100
33174032-0	2020	Metformin protects high glucose-cultured cardiomyocytes from oxidative stress by promoting NDUFA13 expression and mitochondrial biogenesis via the AMPK signaling pathway.	Metformin	0-9	NADH:ubiquinone oxidoreductase subunit A13, pseudogene 1	Rattus norvegicus	91-98
33174032-10	2020	In addition, metformin stimulated mitochondrial biogenesis, as indicated by increased expression levels of mitochondrial genes (NDUFA1, NDUFA2, NDUFA13 and manganese superoxide dismutase) and mitochondrial biogenesis-related transcription factors [peroxisome proliferator-activated receptor-gamma coactivator-1alpha, nuclear respiratory factor (NRF)-1, and NRF-2] in the metformin + HG group compared with the HG group.	Metformin	13-22	NADH:ubiquinone oxidoreductase subunit A13, pseudogene 1	Rattus norvegicus	144-151
33174032-11	2020	Moreover, metformin promoted mitochondrial NDUFA13 protein expression via the AMPK signaling pathway, which was abolished by pretreatment with the AMPK inhibitor, Compound C. The results suggested that metformin protected cardiomyocytes against HG-induced oxidative stress via a mechanism involving AMPK, NDUFA13 and mitochondrial biogenesis.	Metformin	10-19	NADH:ubiquinone oxidoreductase subunit A13, pseudogene 1	Rattus norvegicus	43-50
33174032-11	2020	Moreover, metformin promoted mitochondrial NDUFA13 protein expression via the AMPK signaling pathway, which was abolished by pretreatment with the AMPK inhibitor, Compound C. The results suggested that metformin protected cardiomyocytes against HG-induced oxidative stress via a mechanism involving AMPK, NDUFA13 and mitochondrial biogenesis.	Metformin	10-19	NADH:ubiquinone oxidoreductase subunit A13, pseudogene 1	Rattus norvegicus	305-312
33174032-11	2020	Moreover, metformin promoted mitochondrial NDUFA13 protein expression via the AMPK signaling pathway, which was abolished by pretreatment with the AMPK inhibitor, Compound C. The results suggested that metformin protected cardiomyocytes against HG-induced oxidative stress via a mechanism involving AMPK, NDUFA13 and mitochondrial biogenesis.	Metformin	202-211	NADH:ubiquinone oxidoreductase subunit A13, pseudogene 1	Rattus norvegicus	43-50
33174032-11	2020	Moreover, metformin promoted mitochondrial NDUFA13 protein expression via the AMPK signaling pathway, which was abolished by pretreatment with the AMPK inhibitor, Compound C. The results suggested that metformin protected cardiomyocytes against HG-induced oxidative stress via a mechanism involving AMPK, NDUFA13 and mitochondrial biogenesis.	Metformin	202-211	NADH:ubiquinone oxidoreductase subunit A13, pseudogene 1	Rattus norvegicus	305-312
33385163-4	2020	CDC25B depletion leads to metformin resistance by inhibiting metformin-induced AMPK activation.	Metformin	26-35	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	79-83
33385163-4	2020	CDC25B depletion leads to metformin resistance by inhibiting metformin-induced AMPK activation.	Metformin	61-70	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	79-83
33294120-11	2020	Further, serum estrogen level and liver estrogen receptor-alpha expression were increased after dietary metformin supplementation in D580 hens.	Metformin	104-113	estrogen receptor 1	Gallus gallus	40-63
33575476-0	2021	Metformin enhances anti-cancer effects of cisplatin in meningioma through AMPK-mTOR signaling pathways.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	74-78
33575476-5	2021	Additionally, metformin activated adenosine monophosphate activated protein kinase (AMPK) and repressed the mammalian target of rapamycin (mTOR) signaling pathways via an AMPK-dependent mechanism.	Metformin	14-23	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	34-82
33575476-5	2021	Additionally, metformin activated adenosine monophosphate activated protein kinase (AMPK) and repressed the mammalian target of rapamycin (mTOR) signaling pathways via an AMPK-dependent mechanism.	Metformin	14-23	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	84-88
33575476-5	2021	Additionally, metformin activated adenosine monophosphate activated protein kinase (AMPK) and repressed the mammalian target of rapamycin (mTOR) signaling pathways via an AMPK-dependent mechanism.	Metformin	14-23	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	171-175
33575476-6	2021	Furthermore, our xenograft murine model confirmed that metformin enhanced cisplatin"s anti-cancer effect by upregulation of AMPK and downregulation of mTOR signaling pathways.	Metformin	55-64	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	124-128
33575476-8	2021	These results demonstrate metformin enhanced the anti-cancer effect of cisplatin in meningioma in vitro and in vivo, an effect mediated through the activation of AMPK and repression of mTOR signaling pathways.	Metformin	26-35	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	162-166
33172126-5	2020	The inhibitory effect of metformin was reversed when 10 microM MPA was combined, which was significantly inhibited again after treatment of MMP-2/9 inhibitor and/or TGF-beta inhibitor.	Metformin	25-34	matrix metallopeptidase 2	Homo sapiens	140-147
33172126-5	2020	The inhibitory effect of metformin was reversed when 10 microM MPA was combined, which was significantly inhibited again after treatment of MMP-2/9 inhibitor and/or TGF-beta inhibitor.	Metformin	25-34	transforming growth factor alpha	Homo sapiens	165-173
32868904-7	2020	It appears that metformin, at least in part, has an antitumor effect through activation of the 5" adenosine monophosphate-activated protein kinase (AMPK) signaling pathway.	Metformin	16-25	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	98-146
32868904-7	2020	It appears that metformin, at least in part, has an antitumor effect through activation of the 5" adenosine monophosphate-activated protein kinase (AMPK) signaling pathway.	Metformin	16-25	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	148-152
32926965-0	2020	Metformin-induced suppression of Nemo-like kinase improves erythropoiesis in preclinical models of Diamond-Blackfan anemia through induction of miR-26a.	Metformin	0-9	microRNA 26a-1	Homo sapiens	144-151
32926965-7	2020	We propose that induction of miR-26a is a potentially novel approach to treatment of DBA and could improve anemia in DBA patients without the potentially adverse side effects of metformin in a DBA patient population.	Metformin	178-187	microRNA 26a-1	Homo sapiens	29-36
34434111-7	2021	Besides, metformin increased the expression levels of phosphorylated adenosine 5"-monophosphate (AMP)-activated protein kinase (p-AMPK), microtubule-associated protein (MAP) light chain 3B (LC3B) and Beclin1 proteins, and reduced levels of phosphorylated mammalian target of rapamycin (p-mTOR) and p62 proteins in vivo and in vitro.	Metformin	9-18	microtubule associated protein 1 light chain 3 beta	Homo sapiens	190-194
34422646-1	2021	Objectives: Anti-diabetic biguanide drugs such as metformin may have anti-tumorigenic effects by behaving as AMPK activators and mTOR inhibitors.	Metformin	50-59	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	109-113
34129225-0	2021	Metformin reverses the effects of high glucose on human dermal fibroblasts of aged skin via downregulating RELA/p65 expression.	Metformin	0-9	RELA proto-oncogene, NF-kB subunit	Homo sapiens	107-111
34129225-0	2021	Metformin reverses the effects of high glucose on human dermal fibroblasts of aged skin via downregulating RELA/p65 expression.	Metformin	0-9	RELA proto-oncogene, NF-kB subunit	Homo sapiens	112-115
34129225-8	2021	The expression of COL3A1 and RELA/p65 were upregulated (P < 0.01 for COL3A1), and percentage of late apoptotic cells increased significantly by HG without metformin (P < 0.001) while it decreased in two concentrations of metformin dramatically compared with 5.5 mM glucose (P < 0.01 for expressions and < 0.001 for apoptosis).	Metformin	155-164	RELA proto-oncogene, NF-kB subunit	Homo sapiens	29-33
34129225-8	2021	The expression of COL3A1 and RELA/p65 were upregulated (P < 0.01 for COL3A1), and percentage of late apoptotic cells increased significantly by HG without metformin (P < 0.001) while it decreased in two concentrations of metformin dramatically compared with 5.5 mM glucose (P < 0.01 for expressions and < 0.001 for apoptosis).	Metformin	155-164	RELA proto-oncogene, NF-kB subunit	Homo sapiens	34-37
34129225-8	2021	The expression of COL3A1 and RELA/p65 were upregulated (P < 0.01 for COL3A1), and percentage of late apoptotic cells increased significantly by HG without metformin (P < 0.001) while it decreased in two concentrations of metformin dramatically compared with 5.5 mM glucose (P < 0.01 for expressions and < 0.001 for apoptosis).	Metformin	221-230	RELA proto-oncogene, NF-kB subunit	Homo sapiens	29-33
34129225-8	2021	The expression of COL3A1 and RELA/p65 were upregulated (P < 0.01 for COL3A1), and percentage of late apoptotic cells increased significantly by HG without metformin (P < 0.001) while it decreased in two concentrations of metformin dramatically compared with 5.5 mM glucose (P < 0.01 for expressions and < 0.001 for apoptosis).	Metformin	221-230	RELA proto-oncogene, NF-kB subunit	Homo sapiens	34-37
34129225-9	2021	Metformin not only significantly downregulated RELA/p65 expression, but also inhibited the apoptosis of HDFs from aged human skin at toxic glucose concentrations which could be inversely mediated via COL1A1 and COL3A1 expression.	Metformin	0-9	RELA proto-oncogene, NF-kB subunit	Homo sapiens	47-51
34129225-9	2021	Metformin not only significantly downregulated RELA/p65 expression, but also inhibited the apoptosis of HDFs from aged human skin at toxic glucose concentrations which could be inversely mediated via COL1A1 and COL3A1 expression.	Metformin	0-9	RELA proto-oncogene, NF-kB subunit	Homo sapiens	52-55
34302119-0	2021	Correction: Repurposing dextromethorphan and metformin for treating nicotine-induced cancer by directly targeting CHRNA7 to inhibit JAK2/STAT3/SOX2 signaling.	Metformin	45-54	Janus kinase 2	Homo sapiens	132-136
34118692-10	2021	The mitochondrial complex I inhibitor metformin exerted dose-dependent inhibitory effects on PGL-626 cells via cooperative down-regulation of NDUFA2, 4, and 10, with a significant decrease in the levels of reactive oxygen species and mitochondrial membrane potential.	Metformin	38-47	NADH:ubiquinone oxidoreductase subunit A2	Homo sapiens	142-148
34354368-14	2021	Notably, six hub genes (STAT1, IFIT3, RSAD2, ISG15, IFI44, IFI6) were down-regulated in cells exposed to both metformin and Mycobacterium tuberculosis antigens.	Metformin	110-119	radical S-adenosyl methionine domain containing 2	Homo sapiens	38-43
33194016-0	2020	Metformin upregulates the expression of Gli1 in vascular endothelial cells in hyperoxia-exposed neonatal mice.	Metformin	0-9	GLI-Kruppel family member GLI1	Mus musculus	40-44
33194016-14	2020	Furthermore, both immunofluorescence staining and FCM demonstrated that metformin increased Gli1 expression in vascular endothelial cells.	Metformin	72-81	GLI-Kruppel family member GLI1	Mus musculus	92-96
33194016-16	2020	These results indicated that metformin enhanced lung vascular development and upregulated the expression of Gli1 in the pulmonary vascular endothelial cells in hyperoxic neonatal mice.	Metformin	29-38	GLI-Kruppel family member GLI1	Mus musculus	108-112
34354368-14	2021	Notably, six hub genes (STAT1, IFIT3, RSAD2, ISG15, IFI44, IFI6) were down-regulated in cells exposed to both metformin and Mycobacterium tuberculosis antigens.	Metformin	110-119	ISG15 ubiquitin like modifier	Homo sapiens	45-50
34354368-14	2021	Notably, six hub genes (STAT1, IFIT3, RSAD2, ISG15, IFI44, IFI6) were down-regulated in cells exposed to both metformin and Mycobacterium tuberculosis antigens.	Metformin	110-119	interferon induced protein 44	Homo sapiens	52-57
34440108-0	2021	Metformin Therapy Effects on the Expression of Sodium-Glucose Cotransporter 2, Leptin, and SIRT6 Levels in Pericoronary Fat Excised from Pre-Diabetic Patients with Acute Myocardial Infarction.	Metformin	0-9	sirtuin 6	Homo sapiens	91-96
34440108-4	2021	In addition, we evaluated in PDM patients the effects of metformin therapy on SIRT6 expression, leptin, and SGLT2 levels, and assessed its beneficial effect on nitrotyrosine and inflammatory cytokine levels.	Metformin	57-66	sirtuin 6	Homo sapiens	78-83
34440108-12	2021	CONCLUSIONS: metformin therapy might ameliorate cardiovascular outcomes by reducing inflammatory parameters, SGLT2, and leptin levels, and finally improving SIRT6 levels in AMI-PDM patients treated with CABG.	Metformin	13-22	sirtuin 6	Homo sapiens	157-162
34485814-0	2021	Cancer Antigen 15-3/Mucin 1 Levels in CCTG MA.32: A Breast Cancer Randomized Trial of Metformin vs Placebo.	Metformin	86-95	mucin 1, cell surface associated	Homo sapiens	0-19
34485814-0	2021	Cancer Antigen 15-3/Mucin 1 Levels in CCTG MA.32: A Breast Cancer Randomized Trial of Metformin vs Placebo.	Metformin	86-95	mucin 1, cell surface associated	Homo sapiens	20-27
34485814-1	2021	Background: Circulating levels of cancer antigen (CA) 15-3, a tumor marker and regulator of cellular metabolism, were reduced by metformin in a nonrandomized neoadjuvant study.	Metformin	129-138	mucin 1, cell surface associated	Homo sapiens	34-58
34485814-5	2021	Absolute and relative change of CA 15-3 (metformin vs placebo) were compared using Wilcoxon rank and t tests.	Metformin	41-50	mucin 1, cell surface associated	Homo sapiens	32-39
34485814-11	2021	At 6 months, CA 15-3 was statistically significantly reduced in metformin vs placebo arms (absolute geometric mean reduction in CA 15-3 = 7.7% vs 2.0%, P < .001; relative metformin: placebo level of CA 15-3 (adjusted for age, baseline body mass index, and baseline CA 15-3) = 0.94, 95% confidence interval = 0.92 to 0.96).	Metformin	64-73	mucin 1, cell surface associated	Homo sapiens	13-20
34485814-11	2021	At 6 months, CA 15-3 was statistically significantly reduced in metformin vs placebo arms (absolute geometric mean reduction in CA 15-3 = 7.7% vs 2.0%, P < .001; relative metformin: placebo level of CA 15-3 (adjusted for age, baseline body mass index, and baseline CA 15-3) = 0.94, 95% confidence interval = 0.92 to 0.96).	Metformin	64-73	mucin 1, cell surface associated	Homo sapiens	128-135
34485814-11	2021	At 6 months, CA 15-3 was statistically significantly reduced in metformin vs placebo arms (absolute geometric mean reduction in CA 15-3 = 7.7% vs 2.0%, P < .001; relative metformin: placebo level of CA 15-3 (adjusted for age, baseline body mass index, and baseline CA 15-3) = 0.94, 95% confidence interval = 0.92 to 0.96).	Metformin	64-73	mucin 1, cell surface associated	Homo sapiens	265-272
34485814-11	2021	At 6 months, CA 15-3 was statistically significantly reduced in metformin vs placebo arms (absolute geometric mean reduction in CA 15-3 = 7.7% vs 2.0%, P < .001; relative metformin: placebo level of CA 15-3 (adjusted for age, baseline body mass index, and baseline CA 15-3) = 0.94, 95% confidence interval = 0.92 to 0.96).	Metformin	171-180	mucin 1, cell surface associated	Homo sapiens	13-20
34485814-11	2021	At 6 months, CA 15-3 was statistically significantly reduced in metformin vs placebo arms (absolute geometric mean reduction in CA 15-3 = 7.7% vs 2.0%, P < .001; relative metformin: placebo level of CA 15-3 (adjusted for age, baseline body mass index, and baseline CA 15-3) = 0.94, 95% confidence interval = 0.92 to 0.96).	Metformin	171-180	mucin 1, cell surface associated	Homo sapiens	199-206
34485814-13	2021	Conclusions: Our observation that metformin reduces CA 15-3 by approximately 6% was corroborated in a large placebo-controlled randomized trial.	Metformin	34-43	mucin 1, cell surface associated	Homo sapiens	52-59
34436421-0	2021	Metformin Decreases 2-HG Production through the MYC-PHGDH Pathway in Suppressing Breast Cancer Cell Proliferation.	Metformin	0-9	phosphoglycerate dehydrogenase	Homo sapiens	52-57
34436421-7	2021	We also showed that metformin"s inhibitory effect on the PHGDH-2HG axis may occur through the regulation of the AMPK-MYC pathway.	Metformin	20-29	phosphoglycerate dehydrogenase	Homo sapiens	57-62
34436421-7	2021	We also showed that metformin"s inhibitory effect on the PHGDH-2HG axis may occur through the regulation of the AMPK-MYC pathway.	Metformin	20-29	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	112-116
34368251-0	2021	Metformin Suppresses the Progress of Diabetes-Accelerated Atherosclerosis by Inhibition of Vascular Smooth Muscle Cell Migration Through AMPK-Pdlim5 Pathway.	Metformin	0-9	PDZ and LIM domain 5	Mus musculus	142-148
34368251-4	2021	In order to investigate whether the AMPK-Pdlim5 pathway is involved in the protective function of metformin against atherosclerosis, we utilized ApoE-/- male mice to investigate whether metformin could suppress diabetes-accelerated atherosclerosis by inhibition of VSMC migration via the AMPK-Pdlim5 pathway.	Metformin	98-107	PDZ and LIM domain 5	Mus musculus	41-47
34368251-8	2021	Results: It was found that metformin could induce the phosphorylation of Pdlim5 and inhibit cell migration as a result.	Metformin	27-36	PDZ and LIM domain 5	Mus musculus	73-79
34368251-11	2021	The data of ApoE-/- mice showed that increased plasma lipids and aggravated vascular smooth muscle cell infiltration into the atherosclerotic lesion in diabetic mice were observed Metformin alleviated diabetes-induced metabolic disorders and atherosclerosis and also reduced VSMC infiltration in atherosclerotic plaques, while the Pdlim5 phospho-abolished mutant that carried adenovirus S177A-Pdlim5 undermines the protective function of metformin.	Metformin	180-189	PDZ and LIM domain 5	Mus musculus	331-337
34368251-11	2021	The data of ApoE-/- mice showed that increased plasma lipids and aggravated vascular smooth muscle cell infiltration into the atherosclerotic lesion in diabetic mice were observed Metformin alleviated diabetes-induced metabolic disorders and atherosclerosis and also reduced VSMC infiltration in atherosclerotic plaques, while the Pdlim5 phospho-abolished mutant that carried adenovirus S177A-Pdlim5 undermines the protective function of metformin.	Metformin	438-447	PDZ and LIM domain 5	Mus musculus	331-337
34368251-11	2021	The data of ApoE-/- mice showed that increased plasma lipids and aggravated vascular smooth muscle cell infiltration into the atherosclerotic lesion in diabetic mice were observed Metformin alleviated diabetes-induced metabolic disorders and atherosclerosis and also reduced VSMC infiltration in atherosclerotic plaques, while the Pdlim5 phospho-abolished mutant that carried adenovirus S177A-Pdlim5 undermines the protective function of metformin.	Metformin	438-447	PDZ and LIM domain 5	Mus musculus	393-399
34368251-12	2021	Conclusions: The activation of the AMPK-Pdlim5 pathway by metformin could interrupt the migratory machine of VSMCs and inhibit cell migration in vitro and in vivo.	Metformin	58-67	PDZ and LIM domain 5	Mus musculus	40-46
34285531-5	2021	Results: After six months of active treatment using monotherapy with an intensive dose of metformin, only 11.43% of patients achieved the target levels of HBA1c below 7%.	Metformin	90-99	hemoglobin subunit alpha 1	Homo sapiens	155-159
33116621-0	2020	Metformin Increases the Chemosensitivity of Pancreatic Cancer Cells to Gemcitabine by Reversing EMT Through Regulation DNA Methylation of miR-663.	Metformin	0-9	microRNA 663a	Homo sapiens	138-145
33116621-8	2020	We further explored the possible molecular mechanisms and it was demonstrated that CpG islands of miR-663 were hypomethylated and relative expression level of miR-663 was up-regulated after treatment of metformin.	Metformin	203-212	microRNA 663a	Homo sapiens	98-105
33116621-8	2020	We further explored the possible molecular mechanisms and it was demonstrated that CpG islands of miR-663 were hypomethylated and relative expression level of miR-663 was up-regulated after treatment of metformin.	Metformin	203-212	microRNA 663a	Homo sapiens	159-166
33116621-10	2020	Moreover, we identified that metformin increased the chemosensitivity through up-regulating expression of miR-663.	Metformin	29-38	microRNA 663a	Homo sapiens	106-113
33116621-11	2020	Conclusion: We demonstrated that metformin increased the chemosensitivity of pancreatic cancer cells to gemcitabine by reversing EMT through regulation DNA methylation of miR-663.	Metformin	33-42	microRNA 663a	Homo sapiens	171-178
33162888-0	2020	Metformin Ameliorates Gestational Diabetes Mellitus-Induced Endothelial Dysfunction via Downregulation of p65 and Upregulation of Nrf2.	Metformin	0-9	RELA proto-oncogene, NF-kB subunit	Homo sapiens	106-109
33025801-11	2021	Metformin slightly reduced expression in ADAMTS5 (beta = 0.34, P = 0.04), HIF-1a (beta = 0.39, P = 0.04), IL4 (beta = 0.30, P = 0.02), MMP1 (beta = 0.47, P < 0.01), and SOX9 (beta = 0.37, P = 0.03).	Metformin	0-9	SRY-box transcription factor 9	Homo sapiens	169-173
33098389-3	2020	Therefore, this study aimed to investigate the impacts of diabetes and insulin, metformin and pioglitazone on Muc1 expression at the time of implantation.	Metformin	80-89	mucin 1, cell surface associated	Homo sapiens	110-114
33098389-15	2020	Also, treatment with metformin and pioglitazone can restore Muc1 expression to near normal levels and has beneficial effects on implantation.	Metformin	21-30	mucin 1, cell surface associated	Homo sapiens	60-64
32562591-6	2020	The well-known AMPK activator metformin increased LC3-II levels, which were augmented by MAC cotreatment.	Metformin	30-39	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	15-19
32589349-0	2020	Effects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells.	Metformin	11-20	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	67-71
32384961-7	2020	RT-qPCR and immunoblotting were used to detect the effects of metformin on the expression of TXNIP and autophagy associated genes-BECN1 and LC3B in the sciatic nerves of pain model mice.	Metformin	62-71	microtubule-associated protein 1 light chain 3 beta	Mus musculus	140-144
32982447-7	2020	In addition, metformin"s effects in the prevention and treatment for GC involve multiple pathways mainly via AMPK and IGF-1R.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	109-113
32646922-10	2020	In ESCC mouse model, short-term metformin treatment reprogrammed the TIME in a similar fashion to humans, whereas long-term treatment further shifted the TIME towards an active state (e.g., reduction in CD4+ FoxP3+ Tregs) and inhibited ESCC growth.	Metformin	32-41	forkhead box P3	Homo sapiens	208-213
34335751-0	2021	Metformin Inhibits the Development of Hypopharyngeal Squamous Cell Carcinoma through Circ_0003214-Mediated MiR-489-3p-ADAM10 Pathway.	Metformin	0-9	ADAM metallopeptidase domain 10	Homo sapiens	118-124
34335751-9	2021	Moreover, metformin blocked tumor growth via the circ_0003214-miR-489-3p-ADAM10 axis in vivo.	Metformin	10-19	ADAM metallopeptidase domain 10	Homo sapiens	73-79
34335751-10	2021	Conclusion: Metformin inhibits HSCC progression through the circ_0003214/miR-489-3p/ADAM10 pathway.	Metformin	12-21	ADAM metallopeptidase domain 10	Homo sapiens	84-90
34253170-0	2021	Inhibition of mTORC1 through ATF4-induced REDD1 and Sestrin2 expression by Metformin.	Metformin	75-84	CREB regulated transcription coactivator 1	Mus musculus	14-20
34253170-0	2021	Inhibition of mTORC1 through ATF4-induced REDD1 and Sestrin2 expression by Metformin.	Metformin	75-84	sestrin 2	Homo sapiens	52-60
34253170-1	2021	BACKGROUND: Although the major anticancer effect of metformin involves AMPK-dependent or AMPK-independent mTORC1 inhibition, the mechanisms of action are still not fully understood.	Metformin	52-61	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	71-75
34253170-1	2021	BACKGROUND: Although the major anticancer effect of metformin involves AMPK-dependent or AMPK-independent mTORC1 inhibition, the mechanisms of action are still not fully understood.	Metformin	52-61	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	89-93
34253170-1	2021	BACKGROUND: Although the major anticancer effect of metformin involves AMPK-dependent or AMPK-independent mTORC1 inhibition, the mechanisms of action are still not fully understood.	Metformin	52-61	CREB regulated transcription coactivator 1	Mus musculus	106-112
34253170-2	2021	METHODS: To investigate the molecular mechanisms underlying the effect of metformin on the mTORC1 inhibition, MTT assay, RT-PCR, and western blot analysis were performed.	Metformin	74-83	CREB regulated transcription coactivator 1	Mus musculus	91-97
34253170-3	2021	RESULTS: Metformin induced the expression of ATF4, REDD1, and Sestrin2 concomitant with its inhibition of mTORC1 activity.	Metformin	9-18	sestrin 2	Homo sapiens	62-70
34253170-3	2021	RESULTS: Metformin induced the expression of ATF4, REDD1, and Sestrin2 concomitant with its inhibition of mTORC1 activity.	Metformin	9-18	CREB regulated transcription coactivator 1	Mus musculus	106-112
34253170-4	2021	Treatment with REDD1 or Sestrin2 siRNA reversed the mTORC1 inhibition induced by metformin, indicating that REDD1 and Sestrin2 are important for the inhibition of mTORC1 triggered by metformin treatment.	Metformin	81-90	sestrin 2	Homo sapiens	24-32
34253170-4	2021	Treatment with REDD1 or Sestrin2 siRNA reversed the mTORC1 inhibition induced by metformin, indicating that REDD1 and Sestrin2 are important for the inhibition of mTORC1 triggered by metformin treatment.	Metformin	81-90	CREB regulated transcription coactivator 1	Mus musculus	52-58
34253170-4	2021	Treatment with REDD1 or Sestrin2 siRNA reversed the mTORC1 inhibition induced by metformin, indicating that REDD1 and Sestrin2 are important for the inhibition of mTORC1 triggered by metformin treatment.	Metformin	81-90	sestrin 2	Homo sapiens	118-126
34253170-4	2021	Treatment with REDD1 or Sestrin2 siRNA reversed the mTORC1 inhibition induced by metformin, indicating that REDD1 and Sestrin2 are important for the inhibition of mTORC1 triggered by metformin treatment.	Metformin	81-90	CREB regulated transcription coactivator 1	Mus musculus	163-169
34253170-4	2021	Treatment with REDD1 or Sestrin2 siRNA reversed the mTORC1 inhibition induced by metformin, indicating that REDD1 and Sestrin2 are important for the inhibition of mTORC1 triggered by metformin treatment.	Metformin	183-192	sestrin 2	Homo sapiens	24-32
34253170-4	2021	Treatment with REDD1 or Sestrin2 siRNA reversed the mTORC1 inhibition induced by metformin, indicating that REDD1 and Sestrin2 are important for the inhibition of mTORC1 triggered by metformin treatment.	Metformin	183-192	CREB regulated transcription coactivator 1	Mus musculus	52-58
34253170-4	2021	Treatment with REDD1 or Sestrin2 siRNA reversed the mTORC1 inhibition induced by metformin, indicating that REDD1 and Sestrin2 are important for the inhibition of mTORC1 triggered by metformin treatment.	Metformin	183-192	sestrin 2	Homo sapiens	118-126
34253170-4	2021	Treatment with REDD1 or Sestrin2 siRNA reversed the mTORC1 inhibition induced by metformin, indicating that REDD1 and Sestrin2 are important for the inhibition of mTORC1 triggered by metformin treatment.	Metformin	183-192	CREB regulated transcription coactivator 1	Mus musculus	163-169
34253170-5	2021	Moreover, REDD1- and Sestrin2-mediated mTORC1 inhibition in response to metformin was independent of AMPK activation.	Metformin	72-81	sestrin 2	Homo sapiens	21-29
34253170-5	2021	Moreover, REDD1- and Sestrin2-mediated mTORC1 inhibition in response to metformin was independent of AMPK activation.	Metformin	72-81	CREB regulated transcription coactivator 1	Mus musculus	39-45
34253170-6	2021	Additionally, lapatinib enhances cell sensitivity to metformin, and knockdown of REDD1 and Sestrin2 decreased cell sensitivity to metformin and lapatinib.	Metformin	130-139	sestrin 2	Homo sapiens	91-99
34253170-7	2021	CONCLUSIONS: ATF4-induced REDD1 and Sestrin2 expression in response to metformin plays an important role in mTORC1 inhibition independent of AMPK activation, and this signalling pathway could have therapeutic value.	Metformin	71-80	sestrin 2	Homo sapiens	36-44
34253170-7	2021	CONCLUSIONS: ATF4-induced REDD1 and Sestrin2 expression in response to metformin plays an important role in mTORC1 inhibition independent of AMPK activation, and this signalling pathway could have therapeutic value.	Metformin	71-80	CREB regulated transcription coactivator 1	Mus musculus	108-114
34335983-0	2021	CCDC65 as a new potential tumor suppressor induced by metformin inhibits activation of AKT1 via ubiquitination of ENO1 in gastric cancer.	Metformin	54-63	coiled-coil domain containing 65	Homo sapiens	0-6
34335983-10	2021	Finally, we observed that metformin, a new anti-cancer drug, can significantly induce CCDC65 to suppress ENO1-AKT1 complex-mediated cell proliferation and EMT signals and finally suppresses the malignant phenotypes of gastric cancer cells.	Metformin	26-35	coiled-coil domain containing 65	Homo sapiens	86-92
34335983-11	2021	Conclusion: These results firstly highlight a critical role of CCDC65 in suppressing ENO1-AKT1 pathway to reduce the progression of gastric cancer and reveals a new molecular mechanism for metformin in suppressing gastric cancer.	Metformin	189-198	coiled-coil domain containing 65	Homo sapiens	63-69
34307505-12	2021	Furthermore, we found that LOXL2 and LOXL4 was inhibited by metformin and losartan in HASMCs, which indicated that LOXL2 and LOXL4 are the potential targets that involved in the therapeutic effects of metformin and losartan on aortic or aneurysm expansion.	Metformin	201-210	lysyl oxidase like 4	Homo sapiens	37-42
34307505-12	2021	Furthermore, we found that LOXL2 and LOXL4 was inhibited by metformin and losartan in HASMCs, which indicated that LOXL2 and LOXL4 are the potential targets that involved in the therapeutic effects of metformin and losartan on aortic or aneurysm expansion.	Metformin	201-210	lysyl oxidase like 4	Homo sapiens	125-130
34243629-6	2021	Metformin may alter miRs levels in the treatment of various diseases by AMPK-dependent or AMPK-independent mechanisms.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	72-76
34243629-6	2021	Metformin may alter miRs levels in the treatment of various diseases by AMPK-dependent or AMPK-independent mechanisms.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	90-94
34096218-0	2021	Metformin Reduces Vascular Assembly in High Glucose-Treated Human Microvascular Endothelial Cells in An AMPK-Independent Manner.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	104-108
34096218-1	2021	Objective: The aim is to examine the effect of metformin in human microvascular endothelial cells exposed to high glucose (HG) concentration and compare them with the effects of other 5" adenosine monophosphate-activated protein kinase (AMPK) modulators under the same condition.	Metformin	47-56	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	187-235
34097256-0	2021	Effect of Omecamtiv Mecarbil on the Pharmacokinetics of Metformin, a Probe Substrate for MATE1/MATE2-K, in Healthy Subjects.	Metformin	56-65	solute carrier family 47 member 2	Homo sapiens	95-102
34144086-2	2021	AIMS: To explore the effect of background treatment with metformin on the efficacy of GLP-1 receptor agonists (GLP-1 RAs) on cardiovascular outcomes in type 2 diabetes.	Metformin	57-66	glucagon like peptide 1 receptor	Homo sapiens	86-100
33041865-3	2020	This review summarizes the evidence for the cardioprotective benefits induced by antidiabetic agents, including sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP1-RA), along with sometimes conversely discussed effects of dipeptidyl peptidase-4 inhibitor (DPP4i) and metformin in patients with high cardiovascular risk with or without type 2 diabetes.	Metformin	316-325	glucagon like peptide 1 receptor	Homo sapiens	208-212
34152528-2	2021	Metformin has in-vitro anti-cancer activity, through AMPK activation and mTOR inhibition.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	53-57
34293965-2	2021	The present study investigated the potential curative effect of metformin loaded on gold nanoparticles (MET AuNPs) in attenuating KBrO3-induced nephrotoxicity.	Metformin	64-73	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	104-107
32816782-0	2020	Correction: Metformin limits osteoarthritis development and progression through activation of AMPK signalling.	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	94-98
32996739-13	2020	Instead, in tumors treated with MTF alone and in combination with DCA the total CD68+ TAMs count was almost 27% (p < 0.05) and 43% lower (p < 0.05) correspondingly than that in control, but this decrease was not accompanied by redistribution of CD68+/CD206+ and CD68+/D206- subsets.	Metformin	32-35	CD68 antigen	Mus musculus	80-84
32996739-13	2020	Instead, in tumors treated with MTF alone and in combination with DCA the total CD68+ TAMs count was almost 27% (p < 0.05) and 43% lower (p < 0.05) correspondingly than that in control, but this decrease was not accompanied by redistribution of CD68+/CD206+ and CD68+/D206- subsets.	Metformin	32-35	CD68 antigen	Mus musculus	245-249
32996739-13	2020	Instead, in tumors treated with MTF alone and in combination with DCA the total CD68+ TAMs count was almost 27% (p < 0.05) and 43% lower (p < 0.05) correspondingly than that in control, but this decrease was not accompanied by redistribution of CD68+/CD206+ and CD68+/D206- subsets.	Metformin	32-35	CD68 antigen	Mus musculus	245-249
33029084-0	2020	Metformin reverses the drug resistance of cisplatin in irradiated CNE-1 human nasopharyngeal carcinoma cells through PECAM-1 mediated MRPs down-regulation.	Metformin	0-9	platelet and endothelial cell adhesion molecule 1	Homo sapiens	117-124
33029084-6	2020	Furthermore, metformin down-regulates the PECAM-1 expression, which could regulate Multi-drug Resistance-associate Proteins (MRPs) expression leading to cisplatin resistance of irradiated CNE-1 cells.	Metformin	13-22	platelet and endothelial cell adhesion molecule 1	Homo sapiens	42-49
33029084-8	2020	Conclusions: Metformin, due to its independent effects on PECAM-1, had a unique anti-proliferative effect on irradiated CNE-1 cells.	Metformin	13-22	platelet and endothelial cell adhesion molecule 1	Homo sapiens	58-65
32017070-9	2020	It is possible to find drugs like metformin that can prevent and treat pancreatic cancer by targeting the TGF-beta signaling pathway.	Metformin	34-43	transforming growth factor alpha	Homo sapiens	106-114
31593308-0	2020	Metformin effects on FOXP3+ and CD8+ T cell infiltrates of head and neck squamous cell carcinoma.	Metformin	0-9	forkhead box P3	Homo sapiens	21-26
31593308-8	2020	RESULTS: Metformin treatment was associated with a 41.4% decrease in FOXP3+ T cells in intratumor regions of interest (P = .004) and a 66.5% increase in stromal CD8+ T cells at the leading edge of the tumor (P = .021) when compared to pretreatment biopsies.	Metformin	9-18	forkhead box P3	Homo sapiens	69-74
34220516-9	2021	This study found obvious changes in the pharmacokinetics of acetaminophen and metformin hydrochloride in rats after exposure to simulated high altitude hypoxia, and they might be due to significant decreases in the expressions of UGT1A1 and OCT2.	Metformin	78-101	UDP glucuronosyltransferase family 1 member A1	Rattus norvegicus	230-236
34139918-4	2022	Areas of ongoing investigation focus on metformin"s ability to activate adenosine monophosphate kinase (AMPK), in addition to its effect on Myc mRNA, monocarboxylate transporter 1 (MCT1), hypoxia-inducible factor 1 (HIF1), mammalian target of rapamycin (mTOR), and human epidermal growth factor receptor 2 (HER2).	Metformin	40-49	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	72-102
34139918-4	2022	Areas of ongoing investigation focus on metformin"s ability to activate adenosine monophosphate kinase (AMPK), in addition to its effect on Myc mRNA, monocarboxylate transporter 1 (MCT1), hypoxia-inducible factor 1 (HIF1), mammalian target of rapamycin (mTOR), and human epidermal growth factor receptor 2 (HER2).	Metformin	40-49	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	104-108
34139918-8	2022	In order to design anticancer drugs that mimic metformin"s mechanism of action, binding assay studies must be conducted to fully understand and utilize the AMPK-dependent and independent mechanisms.	Metformin	47-56	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	156-160
34211461-3	2021	Metformin, an antidiabetic drug and an inducer of AMPK, upregulated the level of SMILE in human intestinal epithelial cells and the number of SMILE-expressing cells in colon tissues from DSS-induced colitis mice compared to control mice.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	50-54
34211461-7	2021	Metformin increased the levels of SMILE, AMPK, and Foxp3 but decreased the number of interleukin (IL)-17-producing T cells among PBMCs from patients with UC.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	41-45
34211461-7	2021	Metformin increased the levels of SMILE, AMPK, and Foxp3 but decreased the number of interleukin (IL)-17-producing T cells among PBMCs from patients with UC.	Metformin	0-9	forkhead box P3	Homo sapiens	51-56
34208360-6	2021	Furthermore, we identified that metformin suppresses glucagon-induced HGP through inhibiting the PKA Foxo1 signaling pathway.	Metformin	32-41	glucagon	Mus musculus	53-61
34208360-7	2021	In both cells and mice, Foxo1-S273D or A mutation abolished the suppressive effect of metformin on glucagon or fasting-induced HGP.	Metformin	86-95	glucagon	Mus musculus	99-107
34115034-4	2021	We conducted a systematic review and meta-analysis to compare the effects between GLP-1 receptor agonists and metformin, and between GLP-1 receptor agonist-metformin combination and GLP-1 receptor agonists in overweight/obese women with PCOS on anthropometric, metabolic, reproductive outcomes.	Metformin	156-165	glucagon like peptide 1 receptor	Homo sapiens	133-147
34169079-5	2021	Some clinical studies found that metformin, the first-line antidiabetic drug and the canonical AMPK activator, has therapeutic efficacy during treatment of early-stage PH.	Metformin	33-42	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	95-99
32629071-9	2020	SLNs containing metformin showed anti-senescence effects on UVB-induced senescence of human dermal fibroblasts, this effect was confirmed by senescence-associated beta-galactosidase staining, RT q-PCR and cell cycle analyses.	Metformin	16-25	galactosidase beta 1	Homo sapiens	163-181
33747526-11	2021	Regulation of the CD39/CD73/adenosine pathway using metformin may represent a therapeutic option to reverse HBV-induced immune pathogenesis.	Metformin	52-61	5'-nucleotidase ecto	Homo sapiens	23-27
33042258-7	2020	Pharmacological mTORC1 inhibition by RAD001 and metformin increased internalization of [177Lu]Lu-PP-F11N in A431/CCKBR and in AR42J cells.	Metformin	48-57	CREB regulated transcription coactivator 1	Mus musculus	16-22
32974191-12	2020	Importantly, the increase in fold of PTEN expression and decrease in folds of Akt phosphorylation level and MMP2 and MMP9 expressions in the treated HCC cells with metformin on 16-kPa stiffness substrate were evidently weakened compared with those in the controls on the 6-kPa stiffness substrate.	Metformin	164-173	matrix metallopeptidase 2	Homo sapiens	108-112
32838195-4	2020	Firstly, AMPK mediated phosphorylation of ACE-2 by metformin as well as the drug"s alkaline properties may interrupt the natural disease progression.	Metformin	51-60	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	9-13
32838195-4	2020	Firstly, AMPK mediated phosphorylation of ACE-2 by metformin as well as the drug"s alkaline properties may interrupt the natural disease progression.	Metformin	51-60	angiotensin converting enzyme 2	Homo sapiens	42-47
32782332-4	2020	Metformin is the first line of treatment for type 2 diabetes, and one of the underlying mechanisms for the anti-diabetic effect of metformin is mediated by the stimulation of AMP-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	175-203
32782332-4	2020	Metformin is the first line of treatment for type 2 diabetes, and one of the underlying mechanisms for the anti-diabetic effect of metformin is mediated by the stimulation of AMP-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	205-209
32782332-4	2020	Metformin is the first line of treatment for type 2 diabetes, and one of the underlying mechanisms for the anti-diabetic effect of metformin is mediated by the stimulation of AMP-activated protein kinase (AMPK).	Metformin	131-140	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	175-203
32782332-4	2020	Metformin is the first line of treatment for type 2 diabetes, and one of the underlying mechanisms for the anti-diabetic effect of metformin is mediated by the stimulation of AMP-activated protein kinase (AMPK).	Metformin	131-140	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	205-209
32782332-5	2020	Because the activation of AMPK is crucial for the initiation of autophagy, we hypothesize that metformin reduces the accumulation of lipid droplets by increasing autophagic flux in vascular endothelial cells.	Metformin	95-104	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	26-30
32480011-0	2020	Metformin ameliorates the NLPP3 inflammasome mediated pyroptosis by inhibiting the expression of NEK7 in diabetic periodontitis.	Metformin	0-9	NIMA (never in mitosis gene a)-related expressed kinase 7	Mus musculus	97-101
32953746-16	2020	The combination of curcumol and metformin also suppressed tumor growth, EMT marker expression, and the activation of Wnt2/beta-Catenin signaling during in vivo experiments.	Metformin	32-41	Wnt family member 2	Homo sapiens	117-121
34163481-3	2021	The mechanisms by which metformin regulates the function of macrophages include AMPK, AMPK independent targets, NF-kappaB, ABCG5/8, Sirt1, FOXO1/FABP4 and HMGB1.	Metformin	24-33	high mobility group box 1	Homo sapiens	155-160
34204936-3	2021	We demonstrate for the first time that binary metformin/amylin and tertiary copper (II)/amylin/metformin complexes of high cellular toxicity are formed and lead to the formation of aggregated multi-level lamellar structures on the cell membrane.	Metformin	46-55	islet amyloid polypeptide	Homo sapiens	56-62
34204936-3	2021	We demonstrate for the first time that binary metformin/amylin and tertiary copper (II)/amylin/metformin complexes of high cellular toxicity are formed and lead to the formation of aggregated multi-level lamellar structures on the cell membrane.	Metformin	95-104	islet amyloid polypeptide	Homo sapiens	88-94
34204936-4	2021	Considering the increased concentration of amylin, copper (II) and metformin in kidneys of T2DM patients, our findings on the toxicity of amylin and its adducts may be correlated with diabetic nephropathy development.	Metformin	67-76	islet amyloid polypeptide	Homo sapiens	138-144
33929389-0	2021	Metformin attenuates hypoxia-induced endothelial cell injury by activating the AMPK pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	79-83
33929389-10	2021	Following metformin treatment, p-AMPK and p-eNOS expression increased, while p-mTOR expression decreased.	Metformin	10-19	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	33-37
33929389-12	2021	In conclusion, metformin can attenuate endothelial injuries and suppress EndMT of HCMECs under hypoxic conditions, owing to its ability to activate the AMPK pathway, increase p-AMPK/t-AMPK, and inhibit mTOR.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	152-156
33929389-12	2021	In conclusion, metformin can attenuate endothelial injuries and suppress EndMT of HCMECs under hypoxic conditions, owing to its ability to activate the AMPK pathway, increase p-AMPK/t-AMPK, and inhibit mTOR.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	177-181
33929389-12	2021	In conclusion, metformin can attenuate endothelial injuries and suppress EndMT of HCMECs under hypoxic conditions, owing to its ability to activate the AMPK pathway, increase p-AMPK/t-AMPK, and inhibit mTOR.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	184-188
34000911-1	2021	PURPOSE: The purpose of this study was to examine the development and preliminary effectiveness of a novel Prediabetes Decision Aid on adoption of intensive lifestyle interventions (ILIs) and metformin.	Metformin	192-201	activation induced cytidine deaminase	Homo sapiens	128-131
34124444-0	2021	Proteomic Analysis Reveals That Metformin Suppresses PSMD2, STIP1, and CAP1 for Preventing Gastric Cancer AGS Cell Proliferation and Migration.	Metformin	32-41	cyclase associated actin cytoskeleton regulatory protein 1	Homo sapiens	71-75
34124444-6	2021	Using small-scale quantitative proteomics, we identified 177 differentially expressed proteins upon metformin treatment; among these, nine proteins such as 26S proteasome non-ATPase regulatory subunit 2 (PSMD2), stress-induced phosphoprotein 1 (STIP1), and adenylyl cyclase-associated protein 1 (CAP1) were significantly altered.	Metformin	100-109	cyclase associated actin cytoskeleton regulatory protein 1	Homo sapiens	257-294
34124444-6	2021	Using small-scale quantitative proteomics, we identified 177 differentially expressed proteins upon metformin treatment; among these, nine proteins such as 26S proteasome non-ATPase regulatory subunit 2 (PSMD2), stress-induced phosphoprotein 1 (STIP1), and adenylyl cyclase-associated protein 1 (CAP1) were significantly altered.	Metformin	100-109	cyclase associated actin cytoskeleton regulatory protein 1	Homo sapiens	296-300
34107698-5	2021	A positive control group was treated with metformin (MET).	Metformin	42-51	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	53-56
31764404-7	2020	The adjusted Cox proportional hazards model showed that metformin usage significantly improved OS [hazard ratio: 0.558, 95% confidence interval (CI): 0.385-0.810].	Metformin	56-65	cytochrome c oxidase subunit 8A	Homo sapiens	13-16
32391614-0	2020	Metformin inhibits extracellular matrix accumulation, inflammation and proliferation of mesangial cells in diabetic nephropathy by regulating H19/miR-143-3p/TGF-beta1 axis.	Metformin	0-9	transforming growth factor, beta 1	Mus musculus	157-166
32389830-9	2020	The expression of Cx43 shows a significant downregulation(about 38%, P<0.001) after chronic pacing and treating with metformin could alleviate this decrease(P<0.01).	Metformin	117-126	gap junction protein alpha 1	Canis lupus familiaris	18-22
32389830-12	2020	These pacing-induced lateralize Cx43 could be alleviated by the metformin (48.4 +- 8.62 vs. 60.8 +- 9.13%, P<0.05).	Metformin	64-73	gap junction protein alpha 1	Canis lupus familiaris	32-36
32389830-13	2020	Additionally, metformin could affect the interactions of ZO-1 with p-Src/Cx43 via decrease the abnormal cAMP level after pacing (84.04 +- 4.58 vs. 69.34 +- 4.5 nmol/L, P<0.001).	Metformin	14-23	SRC proto-oncogene, non-receptor tyrosine kinase	Canis lupus familiaris	69-72
32389830-13	2020	Additionally, metformin could affect the interactions of ZO-1 with p-Src/Cx43 via decrease the abnormal cAMP level after pacing (84.04 +- 4.58 vs. 69.34 +- 4.5 nmol/L, P<0.001).	Metformin	14-23	gap junction protein alpha 1	Canis lupus familiaris	73-77
32389830-14	2020	CONCLUSIONS: Metformin could alleviate the vulnerability of AF and attenuate the downregulation of gap junction under pacing condition via AMPK pathway and decreasing the P-Src level.	Metformin	13-22	SRC proto-oncogene, non-receptor tyrosine kinase	Canis lupus familiaris	173-176
32903813-8	2020	Besides, the inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2)/AMP-activated protein kinase (AMPK) and the competition of organic cation transporters (OCTs) effectively reduced the anti-fibrotic capability of metformin.	Metformin	224-233	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	108-112
32818905-6	2020	Metformin is a widely available anti-diabetic agent that has an excellent safety profile, and clinical and preclinical data suggest metformin may offer cardiopulmonary protection in COVID-19 via enhanced ACE2 expression.	Metformin	0-9	angiotensin converting enzyme 2	Homo sapiens	204-208
32818905-6	2020	Metformin is a widely available anti-diabetic agent that has an excellent safety profile, and clinical and preclinical data suggest metformin may offer cardiopulmonary protection in COVID-19 via enhanced ACE2 expression.	Metformin	132-141	angiotensin converting enzyme 2	Homo sapiens	204-208
34113829-5	2021	In addition, similar to the antidiabetic drug metformin, we observed that in db/db mice, DHODH inhibitors elevate levels of circulating GDF15 and reduce food intake.	Metformin	46-55	dihydroorotate dehydrogenase	Mus musculus	89-94
35460908-2	2022	Metformin (Met) is a promising drug for tumor treatment that targets hexokinase 2 (HK2) to block the glycolytic process, thereby further disrupting the metabolism of cancer cells.	Metformin	0-9	hexokinase 2	Homo sapiens	69-81
35460908-2	2022	Metformin (Met) is a promising drug for tumor treatment that targets hexokinase 2 (HK2) to block the glycolytic process, thereby further disrupting the metabolism of cancer cells.	Metformin	0-9	hexokinase 2	Homo sapiens	83-86
35427821-10	2022	In conclusion, our data show that metformin inhibits TGF-beta-induced expression of fibrotic markers and contraction in hand-derived fibroblasts.	Metformin	34-43	transforming growth factor alpha	Homo sapiens	53-61
34997207-5	2022	Upstream, NSP6 impaired lysosome acidification to inhibit autophagic flux, whose restoration by 1alpha,25-dihydroxyvitamin D3, metformin or polydatin abrogated NSP6-induced pyroptosis.	Metformin	127-136	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	10-14
34997207-5	2022	Upstream, NSP6 impaired lysosome acidification to inhibit autophagic flux, whose restoration by 1alpha,25-dihydroxyvitamin D3, metformin or polydatin abrogated NSP6-induced pyroptosis.	Metformin	127-136	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	160-164
35341775-0	2022	Metformin alleviates dexamethasone-induced apoptosis by regulating autophagy via AMPK/mTOR/p70S6K in osteoblasts.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	81-85
35341775-14	2022	Furthermore, sh-AMPK transfection and the mTOR activator MHY1485 impaired metformin-mediated inhibition of osteoblast apoptosis and promotion of autophagy.	Metformin	74-83	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	16-20
35341775-15	2022	The AMPK/mTOR/p70S6K signaling pathway plays a role in metformin-mediated apoptosis suppression and autophagy promotion.	Metformin	55-64	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	4-8
35341775-16	2022	In conclusion, metformin can alleviate Dex-induced osteoblast apoptosis by inducing autophagy via the AMPK/mTOR/p70S6K pathway.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	102-106
35419709-0	2022	The role of AMPK-dependent pathways in cellular and molecular mechanisms of metformin: a new perspective for treatment and prevention of diseases.	Metformin	76-85	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	12-16
35419709-1	2022	Metformin can suppress gluconeogenesis and reduce blood sugar by activating adenosine monophosphate-activated protein kinase (AMPK) and inducing small heterodimer partner (SHP) expression in the liver cells.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	76-124
35419709-1	2022	Metformin can suppress gluconeogenesis and reduce blood sugar by activating adenosine monophosphate-activated protein kinase (AMPK) and inducing small heterodimer partner (SHP) expression in the liver cells.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	126-130
35419709-1	2022	Metformin can suppress gluconeogenesis and reduce blood sugar by activating adenosine monophosphate-activated protein kinase (AMPK) and inducing small heterodimer partner (SHP) expression in the liver cells.	Metformin	0-9	nuclear receptor subfamily 0 group B member 2	Homo sapiens	172-175
35419709-2	2022	The main mechanism of metformin"s action is related to its activation of the AMPK enzyme and regulation of the energy balance.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	77-81
35419709-6	2022	Several studies have indicated that apart from its significant role in the reduction of blood glucose level, metformin activates the AMPK enzyme that in turn has various efficient impacts on the regulation of various processes, including controlling inflammatory conditions, altering the differentiation pathway of immune and non-immune cell pathways, and the amelioration of various cancers, liver diseases, inflammatory bowel disease (IBD), kidney diseases, neurological disorders, etc.	Metformin	109-118	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	133-137
35419709-7	2022	Metformin"s activation of AMPK enables it to control inflammatory conditions, improve oxidative status, regulate the differentiation pathways of various cells, change the pathological process in various diseases, and finally have positive therapeutic effects on them.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	26-30
35419709-8	2022	Due to the activation of AMPK and its role in regulating several subcellular signalling pathways, metformin can be effective in altering the cells" proliferation and differentiation pathways and eventually in the prevention and treatment of certain diseases.	Metformin	98-107	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	25-29
35471628-9	2022	Therefore, targeting of the HMGB1 pathway by anti-HMGB1 agents, such as heparin, resveratrol and metformin, may decrease COVID-19 severity.	Metformin	97-106	high mobility group box 1	Homo sapiens	28-33
35471628-9	2022	Therefore, targeting of the HMGB1 pathway by anti-HMGB1 agents, such as heparin, resveratrol and metformin, may decrease COVID-19 severity.	Metformin	97-106	high mobility group box 1	Homo sapiens	50-55
35266920-2	2022	In contrast, the common anti-diabetic agent metformin has demonstrated cardioprotection via indirect AMPK activation.	Metformin	44-53	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	101-105
32792951-9	2020	After eight weeks, metformin restored surgery-induced upregulation of MMP13 and downregulation of type II collagen in the joint cartilage.	Metformin	19-28	matrix metallopeptidase 13	Mus musculus	70-75
32774666-0	2020	Protective Effect of Metformin against Hydrogen Peroxide-Induced Oxidative Damage in Human Retinal Pigment Epithelial (RPE) Cells by Enhancing Autophagy through Activation of AMPK Pathway.	Metformin	21-30	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	175-179
32774666-8	2020	Autophagy was stimulated by metformin, and inhibition of autophagy by 3-methyladenine (3-MA) and chloroquine (CQ) or knockdown of Beclin1 and LC3B blocked the protective effects of metformin.	Metformin	181-190	microtubule associated protein 1 light chain 3 beta	Homo sapiens	142-146
32774666-9	2020	In addition, we showed that metformin could activate the AMPK pathway, whereas both pharmacological and genetic inhibitions of AMPK blocked the autophagy-stimulating and protective effects of metformin.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	57-61
32774666-9	2020	In addition, we showed that metformin could activate the AMPK pathway, whereas both pharmacological and genetic inhibitions of AMPK blocked the autophagy-stimulating and protective effects of metformin.	Metformin	192-201	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	127-131
32774666-11	2020	Taken together, these results demonstrate that metformin could protect RPE cells from H2O2-induced oxidative damage by stimulating autophagy via the activation of the AMPK pathway, supporting its potential use in the prevention and treatment of AMD.	Metformin	47-56	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	167-171
32685191-6	2020	There are many common compounds that can increase the expression of the ACE2 receptor including Vitamin C, Metformin, Resveratrol, Vitamin B3 and Vitamin D.	Metformin	107-116	angiotensin converting enzyme 2	Homo sapiens	72-76
32695253-15	2020	Metformin exerted its protection against oxidative stress possibly via activating AMPK/Sirt1 and increasing TXNIP.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	82-86
35266920-11	2022	The MTT assay demonstrated an increase in the EC50-value during co-administration of metformin with sunitinib compared to sunitinib mono-therapy in HepG2 and HL-60 cell lines, demonstrating the impact and complexity of metformin co-administration and the possible role of AMPK signalling.	Metformin	85-94	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	272-276
35132891-4	2022	Metformin is a widely prescribed glucose-lowering agent for patients with diabetes and in preclinical studies, has been shown to suppress cell viability, induce apoptosis, and downregulate the mTORC1 signaling pathway in imatinib resistant CML cell lines (K562R).	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	193-199
30270666-1	2020	Objective: The aim was to evaluate if maternal treatment with metformin (MET) during pregnancy and lactation could be safe for metabolic and cardiovascular parameters of adult male and female offspring.Materials and methods: Wistar female rats were treated with MET (293 mg/kg/d) or tap water, by gavage during gestation (METG or CTRG) or gestation and lactation (METGL or CTRGL).Results: At 75 days of life, male and female MET offspring presented similar blood pressure when compared with their CTR.	Metformin	62-71	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	73-76
32779431-8	2020	Results: Treatment with metformin decreased murine sepsis score (MSS), lactate, platelet lymphocyte ratio (PLR), and high mobility group box (HMGB1) levels.	Metformin	24-33	high mobility group box 1	Mus musculus	142-147
32779431-9	2020	The expression levels of claudin 3 (Cldn3) and claudin 5 (Cldn5) were increased following treatment with metformin.	Metformin	105-114	claudin 5	Rattus norvegicus	47-56
32779431-9	2020	The expression levels of claudin 3 (Cldn3) and claudin 5 (Cldn5) were increased following treatment with metformin.	Metformin	105-114	claudin 5	Rattus norvegicus	58-63
31678650-10	2020	The results showed that Met could significantly inhibit the Hcy-induced upregulation of endothelin receptors (including ETA and ETB receptor) protein expression and endothelin receptor-mediated vasoconstriction, and it recovered the Hcy-induced decrease in silent information regulator 1 (Sirt1) in a dosage-dependent manner in SMA.	Metformin	24-27	endothelin receptor type A	Rattus norvegicus	120-123
31678650-10	2020	The results showed that Met could significantly inhibit the Hcy-induced upregulation of endothelin receptors (including ETA and ETB receptor) protein expression and endothelin receptor-mediated vasoconstriction, and it recovered the Hcy-induced decrease in silent information regulator 1 (Sirt1) in a dosage-dependent manner in SMA.	Metformin	24-27	endothelin receptor type B	Rattus norvegicus	128-131
35367225-9	2022	Metformin is a pleiotropic drug, modulating different targets such as AMPK, insulin signalling and many others.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	70-74
35631452-4	2022	While metformin is a known adenosine monophosphate-activated protein kinase (AMPK) agonist and an inhibitor of the electron transport chain complex I, its mechanism of action in cancer cells as well as its effect on cancer metabolism is not clearly established.	Metformin	6-15	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	27-75
35631452-4	2022	While metformin is a known adenosine monophosphate-activated protein kinase (AMPK) agonist and an inhibitor of the electron transport chain complex I, its mechanism of action in cancer cells as well as its effect on cancer metabolism is not clearly established.	Metformin	6-15	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	77-81
35512849-7	2022	The results showed that the treatment of overweight/obese patients without diabetes with GLP-1RAs including liraglutide, exenatide and semaglutide significantly achieved greater weight loss than placebo (WMD=-5.39,95%CI (-6.82, -3.96)) and metformin (WMD=-5.46,95%CI (-5.87, -5.05)).	Metformin	240-249	glucagon like peptide 1 receptor	Homo sapiens	89-94
35182540-4	2022	Our findings indicate the importance of insulin receptor-mediated activation of the MAPK signalling pathway in the proliferation and growth of the bladder wall of the racemose cyst and its susceptibility to metformin action.	Metformin	207-216	insulin receptor	Homo sapiens	40-56
35090865-1	2022	The aim of this study was to investigate the contributions of multiple transport mechanisms to the intestinal absorption of metformin, focusing on OCT3, PMAT, THTR2, SERT and OCTN2.	Metformin	124-133	solute carrier family 19 member 3	Homo sapiens	159-164
35090865-3	2022	Uptake studies with MDCKII cells expressing OCT3, PMAT, THTR2 or SERT confirmed that metformin is a substrate of these transporters.	Metformin	85-94	solute carrier family 19 member 3	Homo sapiens	56-61
35090865-5	2022	7-Cyclopentyl inhibited OCT3- and THTR2-mediated uptake of metformin.	Metformin	59-68	solute carrier family 19 member 3	Homo sapiens	34-39
35090865-6	2022	AG835, thiamine and paroxetine specifically inhibited PMAT-, THTR2- and SERT-mediated uptake of metformin, respectively.	Metformin	96-105	solute carrier family 19 member 3	Homo sapiens	61-66
35090865-7	2022	Using these inhibitors, the relative contributions of OCT3, PMAT, THTR2, SERT, OCTN2 and others to the intestinal permeation of metformin across Caco-2 cells were estimated to be 9.77%, 9.68%, 22.2%, 1.52%, 0% and 0.66%, respectively.	Metformin	128-137	solute carrier family 19 member 3	Homo sapiens	66-71
35090865-7	2022	Using these inhibitors, the relative contributions of OCT3, PMAT, THTR2, SERT, OCTN2 and others to the intestinal permeation of metformin across Caco-2 cells were estimated to be 9.77%, 9.68%, 22.2%, 1.52%, 0% and 0.66%, respectively.	Metformin	128-137	solute carrier family 22 member 5	Homo sapiens	79-84
35090865-8	2022	Concentration-dependent analysis of metformin uptake by Caco-2 cells revealed nonlinear kinetics with the similar Km(app) value to the value for THTR2.	Metformin	36-45	solute carrier family 19 member 3	Homo sapiens	145-150
35090865-10	2022	The present study indicated that THTR2 is the major determinant of the nonlinear absorption of metformin, although multiple transport mechanisms contribute to its intestinal absorption.	Metformin	95-104	solute carrier family 19 member 3	Homo sapiens	33-38
35563167-7	2022	Berberine, such as the drug metformin, is a clinically useful activator of AMPK.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	75-79
35545589-10	2022	Immunofluorescence experiments showed that compared with the noise exposure group, the fluorescence intensity of insulin-like growth factor 1 receptor (IGF1R) in the metformin+noise exposure group was increased, and the fluorescence intensity of eukaryotic translation initiation factor 4E binding protein 1 (eIF4EBP1) was decreased.	Metformin	166-175	insulin-like growth factor 1 receptor	Rattus norvegicus	113-150
35545589-10	2022	Immunofluorescence experiments showed that compared with the noise exposure group, the fluorescence intensity of insulin-like growth factor 1 receptor (IGF1R) in the metformin+noise exposure group was increased, and the fluorescence intensity of eukaryotic translation initiation factor 4E binding protein 1 (eIF4EBP1) was decreased.	Metformin	166-175	insulin-like growth factor 1 receptor	Rattus norvegicus	152-157
35428362-8	2022	Metformin and PGC-1alpha inhibitor reversed IRX5-induced adipogenesis and glycolytic inhibition.	Metformin	0-9	iroquois homeobox 5	Homo sapiens	44-48
31920356-7	2019	Metformin treatment reverted hNAA40, NAMPT, and SIRT-1 expression levels to normal levels.	Metformin	0-9	nicotinamide phosphoribosyltransferase	Homo sapiens	37-42
31822720-0	2019	Metformin activates KDM2A to reduce rRNA transcription and cell proliferation by dual regulation of AMPK activity and intracellular succinate level.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	100-104
31822720-2	2019	Metformin activates AMP-activated kinase (AMPK), which may contribute to the action of metformin.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	20-40
31822720-2	2019	Metformin activates AMP-activated kinase (AMPK), which may contribute to the action of metformin.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	42-46
31822720-2	2019	Metformin activates AMP-activated kinase (AMPK), which may contribute to the action of metformin.	Metformin	87-96	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	20-40
31822720-2	2019	Metformin activates AMP-activated kinase (AMPK), which may contribute to the action of metformin.	Metformin	87-96	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	42-46
31822720-6	2019	AMPK activity was required for activation of KDM2A by metformin.	Metformin	54-63	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
31676687-9	2019	In addition, we found that treatment with metformin inhibited NLRC4 phosphorylation and remarkably decreased cellular senescence and SASP in the context of hyperglycemia.	Metformin	42-51	NLR family, CARD domain containing 4	Mus musculus	62-67
31557380-10	2019	Metformin led to an increase in AMPK signaling, and a trend for blunted increases in mTORC1 signaling in response to PRT.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	32-36
31620963-7	2019	RESULTS: Our finding indicated that consumption of metformin during the recovery period potentially induced an active form of AMPK (p-AMPK) and promoted repopulation of mature OLGs (MOG+ cells, MBP+ cells) in CC through up-regulation of BDNF, CNTF, and NGF as well as down-regulation of NogoA and recruitment of Olig2+ precursor cells.	Metformin	51-60	myelin basic protein	Mus musculus	194-197
31620963-7	2019	RESULTS: Our finding indicated that consumption of metformin during the recovery period potentially induced an active form of AMPK (p-AMPK) and promoted repopulation of mature OLGs (MOG+ cells, MBP+ cells) in CC through up-regulation of BDNF, CNTF, and NGF as well as down-regulation of NogoA and recruitment of Olig2+ precursor cells.	Metformin	51-60	ciliary neurotrophic factor	Mus musculus	243-247
31744691-0	2019	Metformin inhibits cell proliferation in SKM-1 cells via AMPK-mediated cell cycle arrest.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	57-61
31744691-8	2019	Metformin promoted the expression of p-AMPK, P53, P21CIP1 and P27KIP1, while inhibited the expression of CDK4 and CyclinD1.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	39-43
31744691-8	2019	Metformin promoted the expression of p-AMPK, P53, P21CIP1 and P27KIP1, while inhibited the expression of CDK4 and CyclinD1.	Metformin	0-9	cyclin dependent kinase 4	Homo sapiens	105-109
31744691-8	2019	Metformin promoted the expression of p-AMPK, P53, P21CIP1 and P27KIP1, while inhibited the expression of CDK4 and CyclinD1.	Metformin	0-9	cyclin D1	Homo sapiens	114-122
31744691-9	2019	AMPK knockdown attenuated the effects of metformin on SKM-1 cells.	Metformin	41-50	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-4
31744691-10	2019	These findings suggested that metformin inhibited proliferation of SKM-1 cells, potentially through an AMPK-mediated cell cycle arrest.	Metformin	30-39	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	103-107
32694674-0	2019	Teaching an old dog new tricks: metformin induces body-weight loss via GDF15.	Metformin	32-41	growth differentiation factor 15	Canis lupus familiaris	71-76
31871550-0	2019	Metformin Ameliorates Testicular Damage in Male Mice with Streptozotocin-Induced Type 1 Diabetes through the PK2/PKR Pathway.	Metformin	0-9	prokineticin 2	Mus musculus	109-112
31582211-9	2019	Taken together, we found that administration of metformin prevents pre-eclampsia by suppressing migration of trophoblast cells via modulating the signaling pathway of UCA1/miR-204/MMP-9.	Metformin	48-57	urothelial cancer associated 1	Homo sapiens	167-171
31703101-5	2019	Significantly elevated faecal sIgA levels during administration of metformin, and its correlation with the expression of genes associated with immune response (CXCR4, HLA-DQA1, MAP3K14, TNFRSF21, CCL4, ACVR1B, PF4, EPOR, CXCL8) supports a novel hypothesis of strong association between metformin and intestinal immune system, and for the first time provide evidence for altered RNA expression as a contributing mechanism of metformin"s action.	Metformin	67-76	major histocompatibility complex, class II, DQ alpha 1	Homo sapiens	167-175
31703101-5	2019	Significantly elevated faecal sIgA levels during administration of metformin, and its correlation with the expression of genes associated with immune response (CXCR4, HLA-DQA1, MAP3K14, TNFRSF21, CCL4, ACVR1B, PF4, EPOR, CXCL8) supports a novel hypothesis of strong association between metformin and intestinal immune system, and for the first time provide evidence for altered RNA expression as a contributing mechanism of metformin"s action.	Metformin	67-76	platelet factor 4	Homo sapiens	210-213
31698699-7	2019	Additionally, treatment with metformin and 2DG (5 mM) inhibited the Akt/mTOR pathway and down-regulated the cell-cycle-related proteins such as p-cyclin B1 (S147) and cyclins D1 and D2 when compared to cells that were treated with either 2DG or metformin alone.	Metformin	29-38	cyclin B1	Mus musculus	146-155
31416838-6	2019	In a murine xenograft model, combining metformin or shCDX1 with cisplatin reduced tumor growth, increased caspase-3 cleavage, and reduced expression of CD44 and MMP-9 to a greater degree than cisplatin alone.	Metformin	39-48	matrix metallopeptidase 9	Mus musculus	161-166
31708777-9	2019	GRT increased Abcc2 expression and metformin downregulated Abcb1a expression while the combination of GRT with atorvastatin or metformin did not significantly alter the expression of Slco1b1 or Oct1 did not significantly alter the expression of Sclo1b2 or Oct1.	Metformin	35-44	ATP binding cassette subfamily B member 1A	Rattus norvegicus	59-65
31483294-7	2019	We show that metformin, an FDA-approved eIF4E inhibitor, suppresses intractable epilepsy.	Metformin	13-22	eukaryotic translation initiation factor 4E	Homo sapiens	40-45
31620247-0	2019	Correction: Metformin sensitizes anticancer effect of dasatinib in head and neck squamous cell carcinoma cells through AMPK-dependent ER stress.	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	119-123
35454162-1	2022	Dual Blockade of Lactate/GPR81 and PD-1/PD-L1 Pathways Enhances the Anti-Tumor Effects of Metformin.	Metformin	90-99	programmed cell death 1	Homo sapiens	35-39
31473186-2	2019	Both metformin and canagliflozin indirectly activate AMPK by inhibiting mitochondrial function, while salsalate is a direct AMPK activator.	Metformin	5-14	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	53-57
31473186-4	2019	Although metformin treatment had been shown to attenuate experimental cystic kidney disease, there are concerns that therapeutic AMPK activation in human kidney might require a higher oral metformin dose than can be achieved clinically.	Metformin	189-198	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	129-133
31203154-0	2019	Metformin exhibits its therapeutic effect in the treatment of pre-eclampsia via modulating the Met/H19/miR-148a-5p/P28 and Met/H19/miR-216-3p/EBI3 signaling pathways.	Metformin	0-9	Epstein-Barr virus induced 3	Rattus norvegicus	142-146
35480097-0	2022	Metformin Regulates TET2 Expression to Inhibit Endometrial Carcinoma Proliferation: A New Mechanism.	Metformin	0-9	tet methylcytosine dioxygenase 2	Homo sapiens	20-24
31273952-0	2019	Metformin mediates induction of miR-708 to inhibit self-renewal and chemoresistance of breast cancer stem cells through targeting CD47.	Metformin	0-9	microRNA 708	Homo sapiens	32-39
31273952-3	2019	Herein, we evaluated the role of miR-708 and metformin in BCSCs, and found that the expression of miR-708 is significantly down-regulated in BCSCs and tumour tissues, and correlates with chemotherapy response and prognosis.	Metformin	45-54	microRNA 708	Homo sapiens	98-105
31273952-7	2019	In addition, the anti-type II diabetes drug metformin are found to be involved in the miR-708/CD47 signalling pathway.	Metformin	44-53	microRNA 708	Homo sapiens	86-93
31273952-8	2019	Therefore, our study demonstrated that miR-708 plays an important tumour suppressor role in BCSCs self-renewal and chemoresistance, and the miR-708/CD47 regulatory axis may represent a novel therapeutic mechanism of metformin in BCSCs.	Metformin	216-225	microRNA 708	Homo sapiens	39-46
31273952-8	2019	Therefore, our study demonstrated that miR-708 plays an important tumour suppressor role in BCSCs self-renewal and chemoresistance, and the miR-708/CD47 regulatory axis may represent a novel therapeutic mechanism of metformin in BCSCs.	Metformin	216-225	microRNA 708	Homo sapiens	140-147
30945296-3	2019	Herein, we investigated the anti-inflammatory effects of metformin on the NIMA-related kinase 7 (Nek7)/nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) pathway both in vivo and in vitro in experimental diabetic periodontitis.	Metformin	57-66	NIMA (never in mitosis gene a)-related expressed kinase 7	Mus musculus	74-95
30945296-3	2019	Herein, we investigated the anti-inflammatory effects of metformin on the NIMA-related kinase 7 (Nek7)/nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) pathway both in vivo and in vitro in experimental diabetic periodontitis.	Metformin	57-66	NIMA (never in mitosis gene a)-related expressed kinase 7	Mus musculus	97-101
30945296-12	2019	Furthermore, after stimulation with the mTOR inhibitor rapamycin, additional metformin treatment could still downregulate Nek7/NLRP3.	Metformin	77-86	NIMA (never in mitosis gene a)-related expressed kinase 7	Mus musculus	122-126
30945296-14	2019	Metformin suppressed the inflammatory state by inhibiting Nek7 expression to decrease NLRP3 inflammasome activity.	Metformin	0-9	NIMA (never in mitosis gene a)-related expressed kinase 7	Mus musculus	58-62
30945296-16	2019	The observed Nek7 reduction could be related to metformin-mediated cell cycle arrest.	Metformin	48-57	NIMA (never in mitosis gene a)-related expressed kinase 7	Mus musculus	13-17
31273790-0	2019	AMPK-SIRT1-independent inhibition of ANGPTL3 gene expression is a potential lipid-lowering mechanism of metformin.	Metformin	104-113	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-4
31273790-6	2019	The role of AMPK-SIRT1 pathway in metformin regulation of ANGPTL3 was determined using pharmacological, RNAi and reporter assays.	Metformin	34-43	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	12-16
31273790-8	2019	KEY FINDINGS: Metformin and pharmacological activators of AMPK and SIRT1 inhibited the expression of ANGPTL3 in HepG2 cells.	Metformin	14-23	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	58-62
31273790-12	2019	CONCLUSIONS: Metformin inhibits ANGPTL3 expression in the liver in an AMPK-SIRT1-independent manner as a potential mechanism to regulate LPL and lower plasma lipids.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	70-74
31181215-12	2019	CONCLUSION: Metformin-activated AMPK decreases hepatic PPP1R3C expression, leading to the suppression of hepatic gluconeogenesis through blocking cAMP-stimulated TORC2 dephosphorylation.	Metformin	12-21	CREB regulated transcription coactivator 2	Mus musculus	162-167
31535033-0	2019	Metformin Can Alleviate the Symptom of Patient with Diabetic Nephropathy Through Reducing the Serum Level of Hcy and IL-33.	Metformin	0-9	interleukin 33	Homo sapiens	117-122
31535033-1	2019	Background: Interleukin-33 (IL-33) and homocysteine (Hcy) were found to be up-regulated in patients with diabetic nephropathy (DN), and the present study aimed to investigate whether metformin (MT) can influence the serum levels of IL-33 and Hcy in patients with DN.	Metformin	183-192	interleukin 33	Homo sapiens	28-33
31535033-9	2019	Conclusion: Metformin could alleviate the symptom of patient with DN through decreasing the serum level of IL-33 and Hcy.	Metformin	12-21	interleukin 33	Homo sapiens	107-112
31467666-9	2019	In addition, metformin significantly suppressed the activation of the PI3K/AKT/mToR pathway and decreased the mRNA and protein levels of LC3B and Beclin1, which were induced by Ang-II.	Metformin	13-22	microtubule-associated protein 1 light chain 3 beta	Mus musculus	137-141
31455378-0	2019	Metformin targets a YAP1-TEAD4 complex via AMPKalpha to regulate CCNE1/2 in bladder cancer cells.	Metformin	0-9	Yes1 associated transcriptional regulator	Homo sapiens	20-24
31455378-2	2019	But there are few reports on the roles of Yap1, the key molecule of Hippo pathway, in the metformin induced inhibition of bladder cancer (BLCA).	Metformin	90-99	Yes1 associated transcriptional regulator	Homo sapiens	42-46
31455378-3	2019	We are wondering if the inhibitory effect of metformin on bladder cancer is fulfilled via Yap1 and exploring the related mechanism.	Metformin	45-54	Yes1 associated transcriptional regulator	Homo sapiens	90-94
31455378-6	2019	Western Blot was performed to detect the expressions of AMPKalpha, Yap1, CCND1, CCNE1/2 and CDK2/4/6 in the metformin-treated BLCA cell lines.	Metformin	108-117	Yes1 associated transcriptional regulator	Homo sapiens	67-71
31455378-6	2019	Western Blot was performed to detect the expressions of AMPKalpha, Yap1, CCND1, CCNE1/2 and CDK2/4/6 in the metformin-treated BLCA cell lines.	Metformin	108-117	cyclin D1	Homo sapiens	73-78
31455378-6	2019	Western Blot was performed to detect the expressions of AMPKalpha, Yap1, CCND1, CCNE1/2 and CDK2/4/6 in the metformin-treated BLCA cell lines.	Metformin	108-117	cyclin dependent kinase 2	Homo sapiens	92-100
31455378-12	2019	And metformin upregulated the phosphorylated AMPKalpha and decreased the expressions of Yap1 and CCND1, CCNE1/2 and CDK4/6.	Metformin	4-13	Yes1 associated transcriptional regulator	Homo sapiens	88-92
31455378-12	2019	And metformin upregulated the phosphorylated AMPKalpha and decreased the expressions of Yap1 and CCND1, CCNE1/2 and CDK4/6.	Metformin	4-13	cyclin D1	Homo sapiens	97-102
31455378-12	2019	And metformin upregulated the phosphorylated AMPKalpha and decreased the expressions of Yap1 and CCND1, CCNE1/2 and CDK4/6.	Metformin	4-13	cyclin dependent kinase 4	Homo sapiens	116-122
31455378-13	2019	AMPK inhibition by compound C (CC) restored the cell proliferation and the G1 cell cycle arrest induced by metformin, in vivo.	Metformin	107-116	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
31455378-17	2019	Furthermore, we observed that metformin inhibited the cell proliferation by decreasing the expressions of Yap1 and both CCNE1 and CCNE2 in xenograft model.	Metformin	30-39	Yes1 associated transcriptional regulator	Homo sapiens	106-110
31455378-17	2019	Furthermore, we observed that metformin inhibited the cell proliferation by decreasing the expressions of Yap1 and both CCNE1 and CCNE2 in xenograft model.	Metformin	30-39	cyclin E2	Homo sapiens	130-135
31455378-18	2019	CONCLUSIONS: The results of our study reveal a new potential regulatory pathway in which metformin inhibits cell proliferation via AMPKalpha/Yap1/TEAD4/CCNE1/2 axis in BLCA cells, providing new insights into novel molecular therapeutic targets for BLCA.	Metformin	89-98	Yes1 associated transcriptional regulator	Homo sapiens	141-145
31501716-0	2019	Downregulation of IL-18 Expression in the Gut by Metformin-induced Gut Microbiota Modulation.	Metformin	49-58	interleukin 18	Mus musculus	18-23
31501716-4	2019	In this study, fecal microbiota transplantation (FMT) using fecal material from metformin-treated mice was found to upregulate the expression of GLP-1 and pattern-recognition receptors TLR1 and TLR4 for the improvement in hyperglycemia caused by a high-fat diet.	Metformin	80-89	glucagon	Mus musculus	145-150
30445633-8	2019	Immunohistochemistry and western blotting showed that without interfering the metabolism of NMBzA, metformin inhibited the inflammation of esophagi via reducing the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6).	Metformin	99-108	prostaglandin-endoperoxide synthase 2	Rattus norvegicus	220-236
30445633-8	2019	Immunohistochemistry and western blotting showed that without interfering the metabolism of NMBzA, metformin inhibited the inflammation of esophagi via reducing the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6).	Metformin	99-108	prostaglandin-endoperoxide synthase 2	Rattus norvegicus	238-243
31142603-7	2019	Our data show that metformin increased IL-10 and IDO expression in Ad-hMSCs and decreased high-mobility group box 1 protein, IL-1beta, and IL-6 expression.	Metformin	19-28	indoleamine 2,3-dioxygenase 1	Rattus norvegicus	49-52
31142603-9	2019	In cocultures, metformin-stimulated Ad-hMSCs inhibited the mRNA expression of RUNX2, COL X, VEGF, MMP1, MMP3, and MMP13 in IL-1beta-stimulated OA chondrocytes and increased the expression of TIMP1 and TIMP3.	Metformin	15-24	TIMP metallopeptidase inhibitor 3	Rattus norvegicus	201-206
31231590-6	2019	Aims: To investigate the influence of SLC22A1 rs622342 (A&gt;C) and ABCC8 rs757110 (A&gt;C) genetic variants on the efficacy of metformin and glimepiride combination therapy in Egyptian T2DM patients.	Metformin	128-137	ATP binding cassette subfamily C member 8	Homo sapiens	68-73
31025080-6	2019	On the contrary, the CaMKII inhibitor KN-93 (50 nmol/L), PKA inhibitor H89 (1 micromol/L), and AMPK activators metformin (2 mmol/L) and 5-aminoimidazole-4-carboxamide 1-b-D-ribofuranoside (2 mmol/L) presented negligible effects.	Metformin	111-120	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	95-99
31002870-0	2019	Metformin ameliorates endotoxemia-induced endothelial pro-inflammatory responses via AMPK-dependent mediation of HDAC5 and KLF2.	Metformin	0-9	Kruppel-like factor 2 (lung)	Mus musculus	123-127
31002870-5	2019	The results showed that metformin pretreatment increased the phosphorylation of HDAC5 at serine 498, leading to the upregulation of KLF2, and eliminated lipopolysaccharide (LPS) and tumor necrosis factor   (TNF )-induced upregulation of vascular cell adhesion molecule 1 (VCAM1).	Metformin	24-33	Kruppel-like factor 2 (lung)	Mus musculus	132-136
31002870-8	2019	Our findings revealed that AMPK activation-mediated HDAC5 phosphorylation and KLF2 restoration is, at least partially, responsible to the anti-inflammatory effects of metformin in endotoxemia-induced endothelial cells, which has important implications for the future development of interfering therapies of sepsis.	Metformin	167-176	Kruppel-like factor 2 (lung)	Mus musculus	78-82
30334569-5	2019	Metformin also significantly ( p < 0.05) inhibited TAA-induced HIF-1alpha, mTOR, the profibrogenic biomarker alpha-smooth muscle actin, tissue inhibitor of metalloproteinases-1, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase in harvested liver homogenates and blood samples.	Metformin	0-9	glutamic--pyruvic transaminase	Homo sapiens	241-265
31042624-0	2019	Metformin Regulates the Expression of CD133 Through the AMPK-CEBPbeta Pathway in Hepatocellular Carcinoma Cell Lines.	Metformin	0-9	prominin 1	Homo sapiens	38-43
31042624-2	2019	Metformin, one of the biguanides used for the treatment of diabetes, is also known to reduce the risk of cancer development and cancer stem-like cells (CSCs), including the expression of CD133.	Metformin	0-9	prominin 1	Homo sapiens	187-192
31042624-3	2019	However, the mechanism underlying the reduction of the expression of CD133 by metformin is not yet understood.	Metformin	78-87	prominin 1	Homo sapiens	69-74
31042624-4	2019	This study shows that metformin suppressed CD133 expression mainly by affecting the CD133 P1 promoter via adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling but not the mammalian target of rapamycin (mTOR).	Metformin	22-31	prominin 1	Homo sapiens	43-48
31042624-4	2019	This study shows that metformin suppressed CD133 expression mainly by affecting the CD133 P1 promoter via adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling but not the mammalian target of rapamycin (mTOR).	Metformin	22-31	prominin 1	Homo sapiens	84-89
31042624-5	2019	AMPK inhibition rescued the reduction of CD133 by metformin.	Metformin	50-59	prominin 1	Homo sapiens	41-46
31042624-6	2019	Further experiments demonstrated that CCAAT/enhancer-binding protein beta (CEBPbeta) was upregulated by metformin and that two isoforms of CEBPbeta reciprocally regulated the expression of CD133.	Metformin	104-113	CCAAT enhancer binding protein beta	Homo sapiens	38-73
31042624-6	2019	Further experiments demonstrated that CCAAT/enhancer-binding protein beta (CEBPbeta) was upregulated by metformin and that two isoforms of CEBPbeta reciprocally regulated the expression of CD133.	Metformin	104-113	prominin 1	Homo sapiens	189-194
31042624-9	2019	Our results indicated that metformin-AMPK-CEBPbeta signaling plays a crucial role in regulating the gene expression of CD133.	Metformin	27-36	prominin 1	Homo sapiens	119-124
30771436-0	2019	Metformin induces human esophageal carcinoma cell pyroptosis by targeting the miR-497/PELP1 axis.	Metformin	0-9	microRNA 497	Homo sapiens	78-85
30771436-5	2019	Intriguingly, metformin treatment leads to gasdermin D (GSDMD)-mediated pyroptosis, which is abrogated by forced expression of PELP1.	Metformin	14-23	gasdermin D	Homo sapiens	43-54
30771436-5	2019	Intriguingly, metformin treatment leads to gasdermin D (GSDMD)-mediated pyroptosis, which is abrogated by forced expression of PELP1.	Metformin	14-23	gasdermin D	Homo sapiens	56-61
30771436-6	2019	Mechanistically, metformin induces pyroptosis of ESCC by targeting miR-497/PELP1 axis.	Metformin	17-26	microRNA 497	Homo sapiens	67-74
31191828-0	2019	Correction: Metformin sensitizes anticancer effect of dasatinib in head and neck squamous cell carcinoma cells through AMPK-dependent ER stress.	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	119-123
31031016-0	2019	Combination of Hypoglycemia and Metformin Impairs Tumor Metabolic Plasticity and Growth by Modulating the PP2A-GSK3beta-MCL-1 Axis.	Metformin	32-41	glycogen synthase kinase 3 beta	Homo sapiens	111-119
31031016-4	2019	Synergistic anti-neoplastic effects of the metformin/hypoglycemia combination were mediated by glycogen synthase kinase 3beta (GSK3beta) activation downstream of PP2A, leading to a decline in the pro-survival protein MCL-1, and cell death.	Metformin	43-52	glycogen synthase kinase 3 beta	Homo sapiens	95-125
31031016-4	2019	Synergistic anti-neoplastic effects of the metformin/hypoglycemia combination were mediated by glycogen synthase kinase 3beta (GSK3beta) activation downstream of PP2A, leading to a decline in the pro-survival protein MCL-1, and cell death.	Metformin	43-52	glycogen synthase kinase 3 beta	Homo sapiens	127-135
31031016-5	2019	Mechanistically, specific activation of the PP2A-GSK3beta axis was the sum of metformin-induced inhibition of CIP2A, a PP2A suppressor, and of upregulation of the PP2A regulatory subunit B56delta by low glucose, leading to an active PP2A-B56delta complex with high affinity toward GSK3beta.	Metformin	78-87	glycogen synthase kinase 3 beta	Homo sapiens	49-57
31031016-5	2019	Mechanistically, specific activation of the PP2A-GSK3beta axis was the sum of metformin-induced inhibition of CIP2A, a PP2A suppressor, and of upregulation of the PP2A regulatory subunit B56delta by low glucose, leading to an active PP2A-B56delta complex with high affinity toward GSK3beta.	Metformin	78-87	glycogen synthase kinase 3 beta	Homo sapiens	281-289
35480097-7	2022	Western blotting and real-time PCR were used to detect the effect of metformin on TET2 expression and to explore whether AMPK is involved in metformin-mediated TET2 regulation.	Metformin	69-78	tet methylcytosine dioxygenase 2	Homo sapiens	82-86
35480097-7	2022	Western blotting and real-time PCR were used to detect the effect of metformin on TET2 expression and to explore whether AMPK is involved in metformin-mediated TET2 regulation.	Metformin	141-150	tet methylcytosine dioxygenase 2	Homo sapiens	160-164
35480097-16	2022	AMPK was involved in the regulation of TET2 by metformin.	Metformin	47-56	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
35480097-16	2022	AMPK was involved in the regulation of TET2 by metformin.	Metformin	47-56	tet methylcytosine dioxygenase 2	Homo sapiens	39-43
35480097-18	2022	Moreover, TET2 may be involved in a novel mechanism by which metformin inhibits EC cell proliferation.	Metformin	61-70	tet methylcytosine dioxygenase 2	Homo sapiens	10-14
35410372-11	2022	The downregulation of CRYGD and F2R was completely restored by additional 4-PBA, an inhibitor of ER stress, and partially restored by metformin or NAC.	Metformin	134-143	crystallin gamma D	Homo sapiens	22-27
35090900-7	2022	Moreover, the metformin administration increased the levels of transcriptional factor NRF-1 and TFAM, mtDNA, and most mitochondrial complex subunits in apoE-TR mice.	Metformin	14-23	transcription factor A, mitochondrial	Mus musculus	96-100
35414746-0	2022	Single Nucleotide Polymorphism in the 3" Untranslated Region of PRKAA2 on Cardiometabolic Parameters in Type 2 Diabetes Mellitus Patients Who Received Metformin.	Metformin	151-160	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	64-70
34990285-0	2022	Metformin exerts anti-tumor effects via Sonic hedgehog signaling pathway by targeting AMPK in HepG2 cells.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	86-90
34990285-10	2022	Silencing of AMPK in the presence of metformin revealed that metformin could exert its inhibitory effect via AMPK.	Metformin	37-46	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	13-17
34990285-10	2022	Silencing of AMPK in the presence of metformin revealed that metformin could exert its inhibitory effect via AMPK.	Metformin	37-46	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	109-113
34990285-10	2022	Silencing of AMPK in the presence of metformin revealed that metformin could exert its inhibitory effect via AMPK.	Metformin	61-70	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	13-17
34990285-10	2022	Silencing of AMPK in the presence of metformin revealed that metformin could exert its inhibitory effect via AMPK.	Metformin	61-70	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	109-113
34990285-11	2022	Our findings demonstrate that metformin can suppress the migration and invasion of HepG2 cells via AMPK-mediated inhibition of the Shh pathway.	Metformin	30-39	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	99-103
35390228-19	2022	We found that degradation of cardiac GATA4 by Bmi-1 was mainly dependent on autophagy rather than proteasome, and autophagy agonists metformin and rapamycin could ameliorate the SA-PCH, suggesting that activation of autophagy with metformin or rapamycin could also be a promising method to prevent SA-PCH.	Metformin	133-142	BMI1 proto-oncogene, polycomb ring finger	Homo sapiens	46-51
35390228-19	2022	We found that degradation of cardiac GATA4 by Bmi-1 was mainly dependent on autophagy rather than proteasome, and autophagy agonists metformin and rapamycin could ameliorate the SA-PCH, suggesting that activation of autophagy with metformin or rapamycin could also be a promising method to prevent SA-PCH.	Metformin	231-240	BMI1 proto-oncogene, polycomb ring finger	Homo sapiens	46-51
35351535-0	2022	Effect of Metformin as an add-on therapy on neuregulin-4 levels and vascular-related complications in adolescents with type 1 diabetes: A randomized controlled trial.	Metformin	10-19	neuregulin 4	Homo sapiens	44-56
35351535-4	2022	OBJECTIVES: We assessed the effect of oral supplementation with metformin on glycemic control, neuregulin-4 levels and carotid intima media thickness (CIMT) as a marker for subclinical atherosclerosis in adolescents with type 1 diabetes mellitus (T1DM) and microvascular complications.	Metformin	64-73	neuregulin 4	Homo sapiens	95-107
35351535-8	2022	After 24-weeks, metformin therapy for the intervention group resulted in a significant decrease of HbA1c, CRP, UACR, total cholesterol and CIMT while Nrg-4 levels were increased compared with baseline levels (p<0.001) and with placebo group(p<0.001).	Metformin	16-25	neuregulin 4	Homo sapiens	150-155
35351535-11	2022	CONCLUSIONS: Oral metformin supplementation once daily for 24 weeks as an adjuvant therapy to intensive insulin in pediatric T1DM was safe and effective in improving glycemic control, dyslipidemia and Nrg-4 levels; hence, it decreased inflammation, microvascular complications and subclinical atherosclerosis.	Metformin	18-27	neuregulin 4	Homo sapiens	201-206
35433698-7	2022	Furthermore, the biguanide diabetes drug metformin, treatment with which enhances autophagy via AMPK-mediated mTOR inactivation, has been reported to reduce the risk of EC.	Metformin	41-50	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	96-100
35344814-4	2022	Metformin upregulated BAX activation with facilitation of BIM, BAD and PUMA; downregulated Bcl-2 and Bcl-xl, but did not affect Mcl-1.	Metformin	0-9	BCL2 binding component 3	Mus musculus	71-75
31077199-0	2019	Metformin regulates lipid metabolism in a canine model of atrial fibrillation through AMPK/PPAR-alpha/VLCAD pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	86-90
31077199-3	2019	MET (Metformin), an AMPK (AMP-activated protein kinase) activator, has been found to be associated with a decreased risk of AF in patients with type 2 diabetes.	Metformin	5-14	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	20-24
31077199-3	2019	MET (Metformin), an AMPK (AMP-activated protein kinase) activator, has been found to be associated with a decreased risk of AF in patients with type 2 diabetes.	Metformin	5-14	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	26-54
31077199-12	2019	Metformin reduces lipid accumulation and promotes beta-oxidation of FA in AF models partially through AMPK/PPAR-alpha/VLCAD pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	102-106
35344814-4	2022	Metformin upregulated BAX activation with facilitation of BIM, BAD and PUMA; downregulated Bcl-2 and Bcl-xl, but did not affect Mcl-1.	Metformin	0-9	BCL2-like 1	Mus musculus	101-107
35344814-5	2022	Additionally, metformin induced cytochrome c release from mitochondria into the cytoplasm, directly triggering caspase-9-mediated mitochondrial apoptosis.	Metformin	14-23	caspase 9	Mus musculus	111-120
35339661-7	2022	Non-obese type 2 Diabetic mice (MKR) were used and treated with a CYP4A-inhibitor (HET0016) or AMPK-activator (Metformin).	Metformin	111-120	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	95-99
30703397-6	2019	At the molecular level, we found that metformin pretreatment not only prevented the changes of FOS, JUNB and BDNF at both mRNA and protein levels, but also increased the expression of the postsynaptic scaffold genes HOMER and PSD95 after exposure to hypobaric hypoxia.	Metformin	38-47	discs large MAGUK scaffold protein 4	Rattus norvegicus	226-231
31091555-4	2019	Metformin, an anti-diabetes drug, has positive effects on metabolism and can exert anti-inflammatory and anti-cancer effects via adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	129-177
31091555-4	2019	Metformin, an anti-diabetes drug, has positive effects on metabolism and can exert anti-inflammatory and anti-cancer effects via adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	179-183
31091555-4	2019	Metformin, an anti-diabetes drug, has positive effects on metabolism and can exert anti-inflammatory and anti-cancer effects via adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	199-203
31091555-9	2019	Both metformin and CO can differentially induce several protein factors, including fibroblast growth factor 21 (FGF21) and sestrin2 (SESN2), which maintain metabolic homeostasis; nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of the antioxidant response; and REDD1, which exhibits an anticancer effect.	Metformin	5-14	sestrin 2	Homo sapiens	123-131
31091555-9	2019	Both metformin and CO can differentially induce several protein factors, including fibroblast growth factor 21 (FGF21) and sestrin2 (SESN2), which maintain metabolic homeostasis; nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of the antioxidant response; and REDD1, which exhibits an anticancer effect.	Metformin	5-14	sestrin 2	Homo sapiens	133-138
31091555-11	2019	Metformin stimulates p53- and AMPK-dependent pathways whereas CO can selectively trigger the PERK-dependent signaling pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	30-34
31967029-6	2019	The combination of insulin degludec and sitagliptin/metformin resulted in a decrease of HbA1c; however, this was followed by a subsequent gradual increase in HbA1c and positive glutamic acid decarboxylase auto-antibodies.	Metformin	52-61	hemoglobin subunit alpha 1	Homo sapiens	88-92
30995468-2	2019	AMPK is activated by biguanides, such as metformin and phenformin, and metformin use in diabetics has been associated with reduced cancer risk.	Metformin	41-50	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-4
30995468-2	2019	AMPK is activated by biguanides, such as metformin and phenformin, and metformin use in diabetics has been associated with reduced cancer risk.	Metformin	71-80	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-4
31105845-7	2019	In this study, we found that AMPK activator metformin suppresses T cell proliferation and inhibits the differentiation of Th1 and Th17 cells while promoting the development of Tregs in vitro in a dose-dependent manner.	Metformin	44-53	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	29-33
31205529-10	2019	Hyperglycemia impaired metformin-induced AMPKThr172 activation and enhanced phosphorylation of AMPK at serine-485 (AMPKSer485).	Metformin	23-32	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	41-45
35339661-10	2022	AMPK activation via Metformin restored nerve integrity, reduced ROS production, and regulated autophagy.	Metformin	20-29	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-4
35301425-7	2022	Interestingly, the antidiabetic drug metformin reversed mTORC1 hyperactivation and alleviated major behavioral and PC deficits in Bmal1 KO mice.	Metformin	37-46	CREB regulated transcription coactivator 1	Mus musculus	56-62
35264157-0	2022	Novel sequential therapy with metformin enhances the effects of cisplatin in testicular germ cell tumours via YAP1 signalling.	Metformin	30-39	Yes1 associated transcriptional regulator	Homo sapiens	110-114
35264157-12	2022	Further study showed that metformin blocked the cells in G1 phase by inducing phosphorylated YAP1 and reducing the expression of cyclin D1, CDK6, CDK4 and RB, which enhanced the chemosensitivity of cisplatin and activated the expression of cleaved caspase 3 in TGCTs.	Metformin	26-35	Yes1 associated transcriptional regulator	Homo sapiens	93-97
35264157-12	2022	Further study showed that metformin blocked the cells in G1 phase by inducing phosphorylated YAP1 and reducing the expression of cyclin D1, CDK6, CDK4 and RB, which enhanced the chemosensitivity of cisplatin and activated the expression of cleaved caspase 3 in TGCTs.	Metformin	26-35	cyclin D1	Homo sapiens	129-138
35264157-12	2022	Further study showed that metformin blocked the cells in G1 phase by inducing phosphorylated YAP1 and reducing the expression of cyclin D1, CDK6, CDK4 and RB, which enhanced the chemosensitivity of cisplatin and activated the expression of cleaved caspase 3 in TGCTs.	Metformin	26-35	cyclin dependent kinase 4	Homo sapiens	146-150
35264157-13	2022	CONCLUSIONS: Our study discovers the important role of YAP1 in TGCTs and reports a new treatment strategy that employs the sequential administration of metformin and cisplatin, which can reduce the required cisplatin dose and enhance the sensitivity of TGCT cells to cisplatin.	Metformin	152-161	Yes1 associated transcriptional regulator	Homo sapiens	55-59
35220243-1	2022	BACKGROUND/AIM: Recent evidence suggests potential synergistic antitumor effects of the combination of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors with the oral hypoglycemic agent metformin.	Metformin	225-234	programmed cell death 1	Homo sapiens	103-121
35220243-1	2022	BACKGROUND/AIM: Recent evidence suggests potential synergistic antitumor effects of the combination of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors with the oral hypoglycemic agent metformin.	Metformin	225-234	programmed cell death 1	Homo sapiens	123-127
35207174-7	2022	This was confirmed in the Preeclampsia Intervention 2 with metformin trial where levels of SPINT1 in maternal circulation were reduced in SGA pregnancies (n = 95, median = 57,764 pg/mL, IQR 42,212-91,356 pg/mL, p < 0.0001) compared to AGA controls (n = 40, median = 107,062 pg/mL, IQR 70,183-176,532 pg/mL).	Metformin	59-68	serine peptidase inhibitor, Kunitz type 1	Homo sapiens	91-97
35114702-2	2022	In this prospective study, the effects of metformin on blood vitamin B12, serum methylmalonic acid (MMA), homocysteine and holo-transcobalamin-II (holo-TC-II) levels were assessed in pediatric age group.	Metformin	42-51	transcobalamin 2	Homo sapiens	152-157
35114702-14	2022	CONCLUSION: Although no significant changes in the serum vitamin B12, homocysteine, MMA or holo-TC-II levels with metformin therapy were detected, long-term prospective studies with high-dose metformin treatment in pediatric population are needed to confirm our results.	Metformin	192-201	transcobalamin 2	Homo sapiens	96-101
35044756-5	2022	Additionally, combined metformin and anthocyanin treatment suppressed protein tyrosine phosphatase 1B expression and regulated the PI3K/AKT/GSK3beta pathway.	Metformin	23-32	glycogen synthase kinase 3 alpha	Homo sapiens	140-148
35023320-4	2022	It reports a metabolic reprogramming strategy (MRS) that pharmaceutical induction of glucose import and glycolysis with metformin and NF-kappaB inhibitor (NF-kappaBi) while blocking the export of excessive lactate via inhibiting monocarboxylate transporter 4 (MCT4) leads to a metabolic crisis within the cancer cells.	Metformin	120-129	solute carrier family 16 (monocarboxylic acid transporters), member 3	Mus musculus	229-258
30456918-5	2019	Metformin is the first-line medication in the management of T2DM and evidence from animal and human studies has suggested that it may be useful in reducing liver fat via inhibition of lipogenesis and increased fatty acid oxidation.	Metformin	0-9	FAT atypical cadherin 1	Homo sapiens	162-165
30456918-6	2019	Findings from the majority of studies undertaken in rodent models clearly suggest that metformin may be a powerful therapeutic agent specifically to reduce liver fat accumulation; data from human studies are less convincing.	Metformin	87-96	FAT atypical cadherin 1	Homo sapiens	162-165
30456918-7	2019	In the present review we discuss the evidence for the specific effects of metformin treatment on liver fat accumulation in animal and human studies, as well as the underlying proposed mechanisms, to try and understand and reconcile the difference in findings between rodent and human work in this area.	Metformin	74-83	FAT atypical cadherin 1	Homo sapiens	103-106
30765435-0	2019	Antisense Inhibition of Glucagon Receptor by IONIS-GCGRRx Improves Type 2 Diabetes Without Increase in Hepatic Glycogen Content in Patients With Type 2 Diabetes on Stable Metformin Therapy.	Metformin	171-180	glucagon receptor	Homo sapiens	24-41
30877090-9	2019	With diabetes development based on HbA1c, metformin was more effective in subjects with higher baseline HbA1c by RD, with metformin RD -1.03 cases/100 person-years with baseline HbA1c &lt;6.0% (42 mmol/mol) and -3.88 cases/100 person-years with 6.0-6.4% (P = 0.0001).	Metformin	42-51	hemoglobin subunit alpha 1	Homo sapiens	35-39
29319171-10	2018	Two target genes of Metformin were significantly interacted with six hub genes (HADHB, NDUFS3, TAF1, MYC, HNFF4A, and MAX) with significant changes in expression values (P &lt; 0.05, t-test).	Metformin	20-29	TATA-box binding protein associated factor 1	Homo sapiens	95-99
30188871-0	2018	Metformin Regulates the Expression of SK2 and SK3 in the Atria of Rats With Type 2 Diabetes Mellitus Through the NOX4/p38MAPK Signaling Pathway.	Metformin	0-9	potassium calcium-activated channel subfamily N member 3	Rattus norvegicus	46-49
30188871-1	2018	We previously found that metformin regulates the ion current conducted by the small conductance calcium-activated potassium channels (SK channels) in the atria of rats with type 2 diabetes mellitus (T2DM) as well as the mRNA and protein expression of the SK2 and SK3 subtypes of SK channels.	Metformin	25-34	potassium calcium-activated channel subfamily N member 3	Rattus norvegicus	263-266
30188871-2	2018	In this study, we hypothesized that the nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4)/p38 mitogen-activated protein kinase (p38MAPK) signaling pathway was involved in the metformin-mediated regulation of SK2 and SK3 expression in the atria of rats with T2DM.	Metformin	186-195	mitogen activated protein kinase 14	Rattus norvegicus	101-137
30188871-2	2018	In this study, we hypothesized that the nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4)/p38 mitogen-activated protein kinase (p38MAPK) signaling pathway was involved in the metformin-mediated regulation of SK2 and SK3 expression in the atria of rats with T2DM.	Metformin	186-195	potassium calcium-activated channel subfamily N member 3	Rattus norvegicus	227-230
30188871-7	2018	The 8-week treatment with metformin markedly reduced the expression levels of NOX4 mRNA and protein and p-p38MAPK protein, upregulated the SK2 expression, and downregulated the SK3 expression.	Metformin	26-35	potassium calcium-activated channel subfamily N member 3	Rattus norvegicus	177-180
30188871-12	2018	Long-term metformin treatment upregulates SK2 protein expression and downregulates SK3 protein expression by inhibiting the NOX4/p38MAPK signaling pathway.	Metformin	10-19	potassium calcium-activated channel subfamily N member 3	Rattus norvegicus	83-86
30188871-12	2018	Long-term metformin treatment upregulates SK2 protein expression and downregulates SK3 protein expression by inhibiting the NOX4/p38MAPK signaling pathway.	Metformin	10-19	mitogen activated protein kinase 14	Rattus norvegicus	129-132
35023320-4	2022	It reports a metabolic reprogramming strategy (MRS) that pharmaceutical induction of glucose import and glycolysis with metformin and NF-kappaB inhibitor (NF-kappaBi) while blocking the export of excessive lactate via inhibiting monocarboxylate transporter 4 (MCT4) leads to a metabolic crisis within the cancer cells.	Metformin	120-129	solute carrier family 16 (monocarboxylic acid transporters), member 3	Mus musculus	260-264
35139776-5	2022	By activating farnesoid X receptor (FXR), metformin increases the expression of vascular endothelial growth factor-A (VEGF-A) and endothelial nitric oxide synthase (eNOS), improves the production of nitric oxide (NO) and decreases the production of ROS.	Metformin	42-51	nuclear receptor subfamily 1 group H member 4	Homo sapiens	14-34
35139776-5	2022	By activating farnesoid X receptor (FXR), metformin increases the expression of vascular endothelial growth factor-A (VEGF-A) and endothelial nitric oxide synthase (eNOS), improves the production of nitric oxide (NO) and decreases the production of ROS.	Metformin	42-51	nuclear receptor subfamily 1 group H member 4	Homo sapiens	36-39
35139776-7	2022	Thus, metformin appears to regulate islet microvascular endothelial cell (IMEC) proliferation, apoptosis and oxidative stress by activating the FXR/VEGF-A/eNOS pathway.	Metformin	6-15	nuclear receptor subfamily 1 group H member 4	Homo sapiens	144-147
35156512-11	2022	Metformin also inhibited PDK1, HIF-1alpha expression, including downstream inflammatory mediators, HMGB1 and TNF-alpha.	Metformin	0-9	high mobility group box 1	Mus musculus	99-104
35528855-0	2022	Metformin attenuates V-domain Ig suppressor of T-cell activation through the aryl hydrocarbon receptor pathway in Melanoma: In Vivo and In Vitro Studies.	Metformin	0-9	aryl hydrocarbon receptor	Homo sapiens	77-102
35528855-5	2022	This study aims to investigate the inhibitory effect of metformin on VISTA via AHR in melanoma cells (CHL-1, B16) and animal models.	Metformin	56-65	V-set immunoregulatory receptor	Homo sapiens	69-74
35528855-5	2022	This study aims to investigate the inhibitory effect of metformin on VISTA via AHR in melanoma cells (CHL-1, B16) and animal models.	Metformin	56-65	aryl hydrocarbon receptor	Homo sapiens	79-82
35528855-7	2022	Here, metformin significantly decreased VISTA and AHR levels in vitro and in vivo.	Metformin	6-15	V-set immunoregulatory receptor	Homo sapiens	40-45
35528855-7	2022	Here, metformin significantly decreased VISTA and AHR levels in vitro and in vivo.	Metformin	6-15	aryl hydrocarbon receptor	Homo sapiens	50-53
35528855-8	2022	Furthermore, metformin inhibited all AHR-regulated genes.	Metformin	13-22	aryl hydrocarbon receptor	Homo sapiens	37-40
35528855-13	2022	These findings demonstrate for the first time that VISTA is suppressed by metformin and identified a new regulatory mechanism through AHR.	Metformin	74-83	V-set immunoregulatory receptor	Homo sapiens	51-56
35158846-8	2022	In endometriosis, metformin might modify the stroma-epithelium communication via Wnt2/beta-catenin.	Metformin	18-27	Wnt family member 2	Homo sapiens	81-85
35072253-4	2022	The mechanism of the antitumor action of metformin is pleiotropic and involves several signalling pathways, including AMPK/mTOR (mitogen activated protein kinase/mammalian target rapamycin), STAT3 (signal transducer and activator of transcription) and numerous factors: NF-KB (nuclear factor kappa), HIF-1 alpha (hypoxia inducible factor 1), IGF-1 (insulin-like growth factor-1), which affect cell proliferation and apoptosis.	Metformin	41-50	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	118-122
35153777-7	2022	Additionally, the activity of 5"-adenosine monophosphate-activated protein kinase a (AMPKalpha) in the lungs from OVA-challenged mice was remarkably lower than control ones, while after metformin treatment, the ratio of p-AMPKalpha to AMPKalpha was upregulated and new blood vessels in the sub-epithelial area as evidenced by CD31 staining were effectively suppressed.	Metformin	186-195	platelet/endothelial cell adhesion molecule 1	Mus musculus	326-330
35096812-11	2021	Metformin inhibited osteoclast formation and accordingly downregulated the genes involved in osteoclastogenesis: RANKL, macrophage colony stimulating factor (M-CSF) and osteoclast fusion gene DC-STAMP.	Metformin	0-9	dendrocyte expressed seven transmembrane protein	Homo sapiens	192-200
30149143-8	2018	Moreover, metformin prevented the development of acquired tumor resistance to 5 consecutive cycles of cisplatin treatment (75% response rate with metformin-cisplatin as compared to 0% response rate with cisplatin), while reducing CD133+ cells.	Metformin	10-19	prominin 1	Homo sapiens	230-235
30149143-10	2018	Metformin synergizes with cisplatin against KRAS/LKB1 co-mutated tumors, and may prevent or delay the onset of resistance to cisplatin by targeting CD133+ cancer stem cells.	Metformin	0-9	prominin 1	Homo sapiens	148-153
30221473-0	2018	Metformin blocks MYC protein synthesis in colorectal cancer via mTOR-4EBP-eIF4E and MNK1-eIF4G-eIF4E signaling.	Metformin	0-9	eukaryotic translation initiation factor 4E	Homo sapiens	74-79
30221473-8	2018	Repression of protein synthesis by metformin preferentially affects cell cycle-associated proteins, by altering signaling through the mTOR-4EBP-eIF4E and MNK1-eIF4G-eIF4E axes.	Metformin	35-44	eukaryotic translation initiation factor 4E	Homo sapiens	144-149
30221732-8	2018	These results demonstrated that metformin and BBR could improve NAFLD, which may be via the activation of AMPK signaling, and the high expression of CCL19 in NAFLD was significantly reduced by metformin and BBR.	Metformin	32-41	C-C motif chemokine ligand 19	Homo sapiens	149-154
30221732-8	2018	These results demonstrated that metformin and BBR could improve NAFLD, which may be via the activation of AMPK signaling, and the high expression of CCL19 in NAFLD was significantly reduced by metformin and BBR.	Metformin	193-202	C-C motif chemokine ligand 19	Homo sapiens	149-154
30333878-4	2018	The results indicated that Nrf2, glutathione S-transferase alpha 1 (GSTA1) and ATP-binding cassette subfamily C member 1 (ABCC1) were dose-dependently reduced by metformin, and that the effect in A549 cells was greater than that in A549/DDP cells.	Metformin	162-171	glutathione S-transferase alpha 1	Homo sapiens	33-66
30333878-4	2018	The results indicated that Nrf2, glutathione S-transferase alpha 1 (GSTA1) and ATP-binding cassette subfamily C member 1 (ABCC1) were dose-dependently reduced by metformin, and that the effect in A549 cells was greater than that in A549/DDP cells.	Metformin	162-171	glutathione S-transferase alpha 1	Homo sapiens	68-73
30333878-10	2018	In conclusion, metformin inhibits the phosphoinositide-3 kinase/Akt and ERK1/2 signaling pathways in A549 cells to reduce the expression of Nrf2, GSTA1 and ABCC1.	Metformin	15-24	glutathione S-transferase alpha 1	Homo sapiens	146-151
30378162-11	2018	Western blot analysis showed increased protein levels of pTie-2/Tie2 and Pakt/AKT in cEPCs harvested from T2DM, treated with insulin metformin plus.	Metformin	133-142	TEK receptor tyrosine kinase	Homo sapiens	64-68
30337733-3	2018	qRT-PCR and Western blot were used to detect the effect of different concentrations of metformin on the changes of adiponectin receptors (AdipoR1 and AdipoR2) of the EC cells both in mRNA and protein level and the role of compound C, an adenosine monophosphate-activated protein kinase (AMPK) inhibitor, on the above effects.	Metformin	87-96	adiponectin receptor 2	Homo sapiens	150-157
30416652-10	2018	The Western blotting results revealed that metformin and cisplatin co-treatment inhibited TGFbeta1 expression and Smad2 and Smad3 phosphorylation.	Metformin	43-52	SMAD family member 2	Homo sapiens	114-119
30416652-10	2018	The Western blotting results revealed that metformin and cisplatin co-treatment inhibited TGFbeta1 expression and Smad2 and Smad3 phosphorylation.	Metformin	43-52	SMAD family member 3	Homo sapiens	124-129
30364350-9	2018	Similarly, metformin treated specimens showed an increased FoxP3+ regulatory T cell infiltrate (mean 9%) compared to non-treated archival specimens (mean 5%) (p = 0.019).	Metformin	11-20	forkhead box P3	Homo sapiens	59-64
30364350-11	2018	Moreover, we present the first in vivo human evidence that metformin may also trigger increased CD8+ Teff and FoxP3+ Tregs in the TME, suggesting an immunomodulatory effect in HNSCC.	Metformin	59-68	forkhead box P3	Homo sapiens	110-115
30356719-10	2018	Metformin treatment in T2DM reverted CD11c, CD169, IL-6, iNOS, TNFalpha, and CD36 to levels comparable to lean subjects.	Metformin	0-9	integrin subunit alpha X	Homo sapiens	37-42
30356719-11	2018	CD206 mRNA expression was significantly upregulated in PBMC of T2DM while Metformin treatment inhibited CD206 expression levels.	Metformin	74-83	mannose receptor C-type 1	Homo sapiens	104-109
30275441-2	2018	This study investigated whether metformin increases the incidence of cardiac rupture after myocardial infarction through the AMPK-MTOR/PGC-1alpha signaling pathway.	Metformin	32-41	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	135-145
30275441-10	2018	Moreover, high-dose metformin (Met 2.0 nM) reduces the proportion of NT-PGC-1alpha/PGC-1alpha in primary cardiomyocytes of SD mice (SD-NRVCs [Neonatal rat ventricular cardiomyocytes]), and its effect was inhibited by Compound C (AMPK inhibitor).	Metformin	20-29	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	72-82
30275441-10	2018	Moreover, high-dose metformin (Met 2.0 nM) reduces the proportion of NT-PGC-1alpha/PGC-1alpha in primary cardiomyocytes of SD mice (SD-NRVCs [Neonatal rat ventricular cardiomyocytes]), and its effect was inhibited by Compound C (AMPK inhibitor).	Metformin	20-29	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	83-93
30275441-13	2018	With the increase in metformin concentration, the expression level of myocardial LC3b gradually increased in MI mice, suggesting that metformin enhances the autophagy of cardiomyocytes.	Metformin	21-30	microtubule-associated protein 1 light chain 3 beta	Mus musculus	81-85
30275441-13	2018	With the increase in metformin concentration, the expression level of myocardial LC3b gradually increased in MI mice, suggesting that metformin enhances the autophagy of cardiomyocytes.	Metformin	134-143	microtubule-associated protein 1 light chain 3 beta	Mus musculus	81-85
30275441-14	2018	CONCLUSIONS These results suggest that metformin increases cardiac rupture after myocardial infarction through the AMPK-MTOR/PGC-1alpha signaling pathway.	Metformin	39-48	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	125-135
30003335-10	2018	In conclusion, metformin or L-citrulline supplementation to BMD patients results in remarkable antidromic changes of the AGAT and GAMT pathways.	Metformin	15-24	guanidinoacetate N-methyltransferase	Homo sapiens	130-134
30093416-3	2018	[14C]-Metformin uptake clearance in OCT2-expressing cells was determined and scaled to in vivo CLr,sec by using OCT2 expression in the cells versus the human kidney cortex.	Metformin	6-15	solute carrier family 22 member 2	Canis lupus familiaris	36-40
30259865-5	2018	Metformin is shown to negatively regulate PI3K through AMPK induced IRS1 phosphorylation and this brings about a reversal of AKT bistablity in codimension-1 bifurcation diagram from S-shaped, related to cell proliferation in the absence of drug metformin, to Z-shaped, related to apoptosis in the presence of drug metformin.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	55-59
30259865-5	2018	Metformin is shown to negatively regulate PI3K through AMPK induced IRS1 phosphorylation and this brings about a reversal of AKT bistablity in codimension-1 bifurcation diagram from S-shaped, related to cell proliferation in the absence of drug metformin, to Z-shaped, related to apoptosis in the presence of drug metformin.	Metformin	245-254	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	55-59
30259865-5	2018	Metformin is shown to negatively regulate PI3K through AMPK induced IRS1 phosphorylation and this brings about a reversal of AKT bistablity in codimension-1 bifurcation diagram from S-shaped, related to cell proliferation in the absence of drug metformin, to Z-shaped, related to apoptosis in the presence of drug metformin.	Metformin	314-323	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	55-59
30637228-1	2018	Sulfonylurea (SUR) agents are the second and most used oral hypoglycemic drugs after metformin and they still as an imperative tool for most favorable of glucose control.	Metformin	85-94	ATP binding cassette subfamily C member 8	Homo sapiens	14-17
30918874-9	2018	In the multivariate analysis, metformin use and age were independent predictors of the b/T ratio in both DM1 and DM2 patients, while the type of basal insulin was an independent predictor only in DM1.	Metformin	30-39	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	113-116
30307162-8	2018	Presence of metformin during 7-day culture with palmitate normalized the level of p-AMPK, p-EIF2alpha, CHOP and cleaved caspase 3 but significantly increased the level of sorcin.	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	84-88
30150001-4	2018	Metformin inhibits the electron transport chain (ETC) and ATP synthesis; however, recent data reveal that metformin regulates AMP-activated protein kinase (AMPK) and the mechanistic target of rapamycin complex 1 (mTORC1) by multiple, mutually nonexclusive mechanisms that do not necessarily depend on the inhibition of ETC and the cellular ATP level.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	213-219
30150001-4	2018	Metformin inhibits the electron transport chain (ETC) and ATP synthesis; however, recent data reveal that metformin regulates AMP-activated protein kinase (AMPK) and the mechanistic target of rapamycin complex 1 (mTORC1) by multiple, mutually nonexclusive mechanisms that do not necessarily depend on the inhibition of ETC and the cellular ATP level.	Metformin	106-115	CREB regulated transcription coactivator 1	Mus musculus	213-219
35052471-9	2022	Quantitive PCR revealed that Diane-35 and metformin decreased androgen receptor (AR) expression but elevated GLUT4 expression.	Metformin	42-51	solute carrier family 2 member 4	Homo sapiens	109-114
34994666-9	2022	Furthermore, the increasing protein levels of LC3-II, BECLIN 1, autophagy related 5 (ATG5) and AMP-activated protein kinase suggested activated autophagy-associated intracellular signalling AMPK and mTOR pathways upon DMBG treated.	Metformin	218-222	beclin 1	Rattus norvegicus	54-62
34983356-9	2022	Metformin and statins through immunomodulatory activities, Orlistat by reducing viral replication, and thiazolidinediones by upregulating ACE2 expression have potential beneficial effects against COVID-19.	Metformin	0-9	angiotensin converting enzyme 2	Homo sapiens	138-142
30222592-0	2018	Antioxidant modifications induced by the new metformin derivative HL156A regulate metabolic reprogramming in SAMP1/kl (-/-) mice.	Metformin	45-54	transmembrane protein 201	Mus musculus	109-114
30222592-2	2018	In this study, a metabolomics approach was used to identify novel metabolic pathways that are perturbed in a mouse model of accelerated aging (SAMP1/kl-/-) and to gain new insights into the metabolic associations of the metformin derivative HL156A.	Metformin	220-229	transmembrane protein 201	Mus musculus	143-148
30210899-7	2018	These results identify a previously unknown role of Alpl in the regulation of ATP-mediated AMPKalpha alterations that maintain MSC stemness and prevent bone ageing and show that metformin offers a potential therapeutic option.	Metformin	178-187	alkaline phosphatase, biomineralization associated	Homo sapiens	52-56
30206377-7	2018	We were able to show in vivo that reducing phospho-STAT3-miR-21 levels in C57/BL6 mice liver, by long-term treatment with metformin, protected mice from aging-dependent hepatic vesicular steatosis.	Metformin	122-131	microRNA 21a	Mus musculus	57-63
33663305-0	2022	Effects of metformin on lipopolysaccharide induced inflammation by activating fibroblast growth factor 21.	Metformin	11-20	fibroblast growth factor 21	Rattus norvegicus	78-105
33663305-2	2022	Metformin (MET) is a widely used hypoglycemic drug that exhibits anti-inflammatory properties.	Metformin	0-9	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	11-14
35065585-0	2022	Radiotherapy and high bilirubin may be metformin like effect on lung cancer via possible AMPK pathway modulation.	Metformin	39-48	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	89-93
35065585-5	2022	Radiotherapy and bilirubin can produce an effect similar to metformin via AMPK pathway.	Metformin	60-69	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	74-78
35075807-1	2022	OBJECTIVE: To explore the therapeutic potential and the underlying mechanism of metformin, an adenosine monophosphate-activated kinase (AMPK) activator, in ocular melanoma.	Metformin	80-89	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	94-134
35075807-1	2022	OBJECTIVE: To explore the therapeutic potential and the underlying mechanism of metformin, an adenosine monophosphate-activated kinase (AMPK) activator, in ocular melanoma.	Metformin	80-89	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	136-140
34375188-11	2022	RESULTS: Astaxanthin and metformin have anti-obesity and antioxidant actions and significantly decreased the weight of the body, glucose, insulin, triglycerides, total cholesterol, triglycerides and leptin, as well as plasma calprotectin & IL-6 and increased HDL-C and adiponectin.	Metformin	25-34	leptin	Rattus norvegicus	199-205
3126223-3	1987	Glibenclamide (2 microM) and metformin (1-10 microM) induced a 13-28% reduction in insulin receptor down regulation in fibroblasts exposed to 1.7 x 10(-8)M-insulin, the loss of binding on exposure to insulin decreasing from 55% to 40-48%.	Metformin	29-38	insulin receptor	Homo sapiens	83-99
3817337-0	1986	Effects of metformin on insulin receptor tyrosine kinase activity in rat adipocytes.	Metformin	11-20	insulin receptor	Rattus norvegicus	24-40
3770275-3	1986	Soleus muscles of metformin treated mice showed a 41% increase in total insulin receptor number, and a 20% increase in 3-0-methylglucose uptake at both submaximally and maximally stimulating insulin concentrations.	Metformin	18-27	insulin receptor	Mus musculus	72-88
30206977-4	2018	The inactivation of mTORC1 by rapamycin pretreatment or rotenone-induced mitochondrial complex inhibition showed a similar effect because of the metformin treatment on the proliferation and apoptosis of HaCaT keratinocytes.	Metformin	145-154	CREB regulated transcription coactivator 1	Mus musculus	20-26
30206977-5	2018	Overexpression of mTORC1 almost reversed the antiproliferation and proapoptosis effects induced by metformin.	Metformin	99-108	CREB regulated transcription coactivator 1	Mus musculus	18-24
30206977-6	2018	This study showed that the metformin treatment inhibited HaCaT cells proliferation and promoted apoptosis by affecting the mitochondrial-mTORC1 signaling and elevated the ACAD10 expression.	Metformin	27-36	CREB regulated transcription coactivator 1	Mus musculus	137-143
30017187-3	2018	In human granulosa cells, it was found that metformin treatment suppressed phosphorylation of Smad1/5/9 activated by BMP-15 compared with that induced by other BMP ligands.	Metformin	44-53	SMAD family member 1	Homo sapiens	94-101
30017187-5	2018	Thus, the mechanism by which metformin suppresses BMP-15-induced Smad1/5/9 phosphorylation is likely, at least in part, to be upregulation of inhibitory Smad6 expression in granulosa cells.	Metformin	29-38	SMAD family member 1	Homo sapiens	65-72
30191328-3	2018	METHODS: The inhibition by select compounds on the uptake of the probe substrate metformin was assessed in HEK293 cells overexpressing human OCT2, OCT1, MATE1, MATE2-K, and mouse Oct2, Oct1, and Mate1.	Metformin	81-90	solute carrier family 47 member 2	Homo sapiens	160-167
30191328-3	2018	METHODS: The inhibition by select compounds on the uptake of the probe substrate metformin was assessed in HEK293 cells overexpressing human OCT2, OCT1, MATE1, MATE2-K, and mouse Oct2, Oct1, and Mate1.	Metformin	81-90	solute carrier family 47, member 1	Mus musculus	195-200
30017802-9	2018	For the [SNAIL/miR-34]:[ZEB/miR-200] system, metformin increased miR-200a, miR-200c and miR-429 levels and decreased miR-34a, SNAIL1 and ZEB1 levels in the TGF-beta-induced EMT.	Metformin	45-54	microRNA 34a	Homo sapiens	15-21
30017802-9	2018	For the [SNAIL/miR-34]:[ZEB/miR-200] system, metformin increased miR-200a, miR-200c and miR-429 levels and decreased miR-34a, SNAIL1 and ZEB1 levels in the TGF-beta-induced EMT.	Metformin	45-54	microRNA 200c	Homo sapiens	75-83
30017802-9	2018	For the [SNAIL/miR-34]:[ZEB/miR-200] system, metformin increased miR-200a, miR-200c and miR-429 levels and decreased miR-34a, SNAIL1 and ZEB1 levels in the TGF-beta-induced EMT.	Metformin	45-54	microRNA 34a	Homo sapiens	117-124
30017802-11	2018	Metformin may perform bidirectional regulations of the [SNAIL/miR-34]:[ZEB/miR-200] system in the EMT process for colorectal cancer.	Metformin	0-9	microRNA 34a	Homo sapiens	62-68
30150719-4	2018	Here we report that the AMP-inhibited enzyme fructose-1,6-bisphosphatase-1 (FBP1), a rate-controlling enzyme in gluconeogenesis, functions as a major contributor to the therapeutic action of metformin.	Metformin	191-200	fructose bisphosphatase 1	Mus musculus	45-74
30150719-4	2018	Here we report that the AMP-inhibited enzyme fructose-1,6-bisphosphatase-1 (FBP1), a rate-controlling enzyme in gluconeogenesis, functions as a major contributor to the therapeutic action of metformin.	Metformin	191-200	fructose bisphosphatase 1	Mus musculus	76-80
30150719-5	2018	We identified a point mutation in FBP1 that renders it insensitive to AMP while sparing regulation by fructose-2,6-bisphosphate (F-2,6-P2), and knock-in (KI) of this mutant in mice significantly reduces their response to metformin treatment.	Metformin	221-230	fructose bisphosphatase 1	Mus musculus	34-38
30150719-8	2018	Collectively, we show a new mechanism of action for metformin and provide further evidence that molecular targeting of FBP1 can have antihyperglycemic effects.	Metformin	52-61	fructose bisphosphatase 1	Mus musculus	119-123
29956804-0	2018	Metformin suppresses the invasive ability of pancreatic cancer cells by blocking autocrine TGF-beta1 signaling.	Metformin	0-9	transforming growth factor, beta 1	Mus musculus	91-100
29956804-3	2018	Our previous studies revealed that metformin suppressed desmoplasia in PDAC by reducing TGF-beta1 production in cancer cells.	Metformin	35-44	transforming growth factor, beta 1	Mus musculus	88-97
29956804-6	2018	Furthermore, metformin reduced TGF-beta1 production and Smad2/3 phosphorylation in pancreatic cancer cells.	Metformin	13-22	transforming growth factor, beta 1	Mus musculus	31-40
29956804-7	2018	In addition, treatment with recombinant TGF-beta1 recovered the metformin-mediated invasion inhibition and EMT changes.	Metformin	64-73	transforming growth factor, beta 1	Mus musculus	40-49
29956804-8	2018	Treatment with metformin also suppressed tumor growth, invasion and EMT in LSL-KrasG12D/+, Trp53fl/+and Pdx1-Cre (KPC) transgenic mice that harbor spontaneous pancreatic cancer.	Metformin	15-24	pancreatic and duodenal homeobox 1	Mus musculus	104-112
29956804-9	2018	Collectively, our study revealed a new possible mechanism for the antitumor effects of metformin via autocrine TGF-beta1/Smad2/3 signaling in PDAC.	Metformin	87-96	transforming growth factor, beta 1	Mus musculus	111-120
30186236-4	2018	These effects are primarily due to metformin"s action on mitochondria, which requires the activation of metabolic checkpoint AMP-activated protein kinase (AMPK).	Metformin	35-44	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	125-153
30186236-4	2018	These effects are primarily due to metformin"s action on mitochondria, which requires the activation of metabolic checkpoint AMP-activated protein kinase (AMPK).	Metformin	35-44	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	155-159
30186236-5	2018	AMPK is implicated in several pathways, and following metformin activation, it decreases protein synthesis and cell proliferation.	Metformin	54-63	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
30084684-1	2018	A growing body of data, guideline recommendations, algorithms, and position papers supports the use of glucagon-like peptide-1 (GLP-1) receptor agonists in type 2 diabetes (T2D), given their beneficial effects on glycemic control, weight, lipid parameters, and blood pressure, and low risk for hypoglycemia when used in patients who have not achieved glycemic goals with metformin and lifestyle interventions.	Metformin	371-380	glucagon like peptide 1 receptor	Homo sapiens	128-143
29975542-5	2018	Transcellular, basal-to-apical metformin net transport was reduced by 89.1, 74.5, and 91.0% in MDCK-OCT2-MATE1 cells after the addition of cimetidine (100 muM) to the basal, the apical, or both compartments ( p &lt; 0.001).	Metformin	31-40	solute carrier family 22 member 2	Canis lupus familiaris	100-104
29975542-6	2018	In MDCK-MATE1 and MDCK-OCT2-MATE1 cells, transcellular net transport of metformin was inhibited by cimetidine with IC50 values of 8.0 and 6.6 muM, respectively.	Metformin	72-81	solute carrier family 22 member 2	Canis lupus familiaris	23-27
29975542-7	2018	Our data confirm the relevance of MATE1 and suggest the relevance of OCT2 for the cimetidine-metformin interaction, primarily because OCT2 mediates uptake of the perpetrator cimetidine into renal proximal tubular cells and thereby to the site of the metformin exporter MATE1.	Metformin	93-102	solute carrier family 22 member 2	Canis lupus familiaris	69-73
29975542-7	2018	Our data confirm the relevance of MATE1 and suggest the relevance of OCT2 for the cimetidine-metformin interaction, primarily because OCT2 mediates uptake of the perpetrator cimetidine into renal proximal tubular cells and thereby to the site of the metformin exporter MATE1.	Metformin	93-102	solute carrier family 22 member 2	Canis lupus familiaris	134-138
29975542-7	2018	Our data confirm the relevance of MATE1 and suggest the relevance of OCT2 for the cimetidine-metformin interaction, primarily because OCT2 mediates uptake of the perpetrator cimetidine into renal proximal tubular cells and thereby to the site of the metformin exporter MATE1.	Metformin	250-259	solute carrier family 22 member 2	Canis lupus familiaris	134-138
33711726-3	2021	In this in vitro study, we hypothesized that metformin with an effective dose can inhibit tumor cell proliferation and metastasis by modulating the expressions of MMP-2 and -9 and interfering with NF-kB signaling in primary breast cancer cells (PBCCs).	Metformin	45-54	matrix metallopeptidase 2	Homo sapiens	163-175
33689478-4	2021	Commonly accepted mechanisms of metformin action include AMPK activation and inhibition of mTOR pathways, which are evaluated in multiple diseases.	Metformin	32-41	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	57-61
33524789-6	2021	First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3.	Metformin	32-41	unc-51 like autophagy activating kinase 1	Homo sapiens	187-191
33524789-6	2021	First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3.	Metformin	32-41	glycogen synthase kinase 3 alpha	Homo sapiens	278-286
33609419-11	2021	Metformin decreased the expression of Myc and pyruvate kinase isozyme 2 (PKM2), leading to metabolism reprogramming.	Metformin	0-9	myelocytomatosis oncogene	Mus musculus	38-41
33609419-11	2021	Metformin decreased the expression of Myc and pyruvate kinase isozyme 2 (PKM2), leading to metabolism reprogramming.	Metformin	0-9	pyruvate kinase, muscle	Mus musculus	46-71
33609419-11	2021	Metformin decreased the expression of Myc and pyruvate kinase isozyme 2 (PKM2), leading to metabolism reprogramming.	Metformin	0-9	pyruvate kinase, muscle	Mus musculus	73-77
33509804-3	2021	We performed a randomized, double-blind, controlled trial to evaluate the efficacy of metformin on the regression of colorectal and duodenal adenoma in patients with FAP.	Metformin	86-95	fibroblast activation protein alpha	Homo sapiens	166-169
33631404-0	2021	The aberrant expression of CD69 on peripheral T-helper cells in diet-induced inflammation is ameliorated by low-dose aspirin and metformin treatment.	Metformin	129-138	CD69 molecule	Homo sapiens	27-31
29659168-0	2018	Metformin alleviates human cellular aging by upregulating the endoplasmic reticulum glutathione peroxidase 7.	Metformin	0-9	glutathione peroxidase 7	Homo sapiens	84-108
29659168-4	2018	We report that a low dose of metformin upregulates the endoplasmic reticulum-localized glutathione peroxidase 7 (GPx7).	Metformin	29-38	glutathione peroxidase 7	Homo sapiens	87-111
29659168-4	2018	We report that a low dose of metformin upregulates the endoplasmic reticulum-localized glutathione peroxidase 7 (GPx7).	Metformin	29-38	glutathione peroxidase 7	Homo sapiens	113-117
29659168-6	2018	We also indicate that metformin increases the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2), which binds to the antioxidant response elements in the GPX7 gene promoter to induce its expression.	Metformin	22-31	glutathione peroxidase 7	Homo sapiens	178-182
29659168-7	2018	Moreover, the metformin-Nrf2-GPx7 pathway delays aging in worms.	Metformin	14-23	glutathione peroxidase 7	Homo sapiens	29-33
29659168-8	2018	Our study provides mechanistic insights into the beneficial effects of metformin on human cellular aging and highlights the importance of the Nrf2-GPx7 pathway in pro-longevity signaling.	Metformin	71-80	glutathione peroxidase 7	Homo sapiens	147-151
30116349-8	2018	Furthermore, secretion of TNF-alpha, IL-1alpha, M-CSF and TCA-3 into the conditioned media was significantly decreased by metformin (5 and 10 mM; P&lt;0.05).	Metformin	122-131	chemokine (C-C motif) ligand 1	Mus musculus	58-63
30061832-0	2018	Activating AMPK to Restore Tight Junction Assembly in Intestinal Epithelium and to Attenuate Experimental Colitis by Metformin.	Metformin	117-126	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	11-15
30061832-3	2018	Activation of AMPK by metformin significantly controls the progression of colitis, which is associated with the maintenance of tight junction in colonic epithelium in mice.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	14-18
30061832-4	2018	Moreover, our in vitro data in colonic epithelial Caco2 cells shows that metformin promotes expression and assembly of tight junctions via an AMPK-dependent way.	Metformin	73-82	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	142-146
30061832-5	2018	Overall, our results suggested that activating AMPK by a clinically safe drug metformin could be a beneficial choice for colitis treatment.	Metformin	78-87	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	47-51
28962892-7	2018	Finally, metformin was still able to induce AMPK activation and to inhibit cell growth in cells treated with forskolin and in transfected cells overexpressing GHRH-receptor and treated with GHRH.	Metformin	9-18	growth hormone releasing hormone	Rattus norvegicus	159-163
29988028-7	2018	Pharmacological activation of AMPK by metformin significantly abrogated the loss of RUNX2-S118 phosphorylation and protected from tunicamycin-induced endoplasmic reticulum stress, high glucose-induced in vitro adipogenesis and streptozotocin-induced in vivo bone adiposity and bone phenotype.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	30-34
29996289-13	2018	The level of TGF-beta(1) in plasma, BALF and lung tissue were also decreased in mice treated with metformin compared with bleomycin model mice [(2.32+-0.68) vs (4.59+-0.45) ng/ml, (0.81+-0.09) vs (1.40+-0.06) ng/ml, (17.12+-0.83) vs (21.25+-0.69) ng/mg, all P&lt;0.05].	Metformin	98-107	transforming growth factor, beta 1	Mus musculus	13-24
29580688-7	2018	Moreover, treatment with metformin or SIRT3 overexpression increased activation of AMP-activated protein kinase (AMPK), a major sensor of cellular energy status.	Metformin	25-34	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	83-111
29580688-7	2018	Moreover, treatment with metformin or SIRT3 overexpression increased activation of AMP-activated protein kinase (AMPK), a major sensor of cellular energy status.	Metformin	25-34	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	113-117
29540537-0	2018	Metformin inhibits inflammatory signals in the gut by controlling AMPK and p38 MAP kinase activation.	Metformin	0-9	mitogen-activated protein kinase 14	Mus musculus	75-78
29540537-6	2018	Indeed, metformin down-regulated p38 MAP kinase activation in colitic mice through an AMP-activated protein kinase-independent mechanism.	Metformin	8-17	mitogen-activated protein kinase 14	Mus musculus	33-36
29546579-7	2018	RESULTS: Metformin, as compared to placebo, significantly reduced the concentrations of NET components elastase, proteinase-3, histones and double strand DNA, whereas glucose control with insulin or dapagliflozin exerted no significant effect.	Metformin	9-18	proteinase 3	Homo sapiens	103-111
29546579-7	2018	RESULTS: Metformin, as compared to placebo, significantly reduced the concentrations of NET components elastase, proteinase-3, histones and double strand DNA, whereas glucose control with insulin or dapagliflozin exerted no significant effect.	Metformin	9-18	proteinase 3	Homo sapiens	113-125
29567539-0	2018	Metformin inhibits glioma cells stemness and epithelial-mesenchymal transition via regulating YAP activity.	Metformin	0-9	Yes1 associated transcriptional regulator	Homo sapiens	94-97
29567539-2	2018	Here, we found that metformin suppressed glioma cells spheroid formation and size, inhibited the expression of glioma stemness-related marker, CD133.	Metformin	20-29	prominin 1	Homo sapiens	143-148
29567539-4	2018	Mechanistically, metformin inhibited the nuclear abundance of YAP, a key effector of Hippo pathway, subsequently leading to its cytoplasmic retention, and thus reduced YAP transcriptional modulating activity.	Metformin	17-26	Yes1 associated transcriptional regulator	Homo sapiens	62-65
29567539-4	2018	Mechanistically, metformin inhibited the nuclear abundance of YAP, a key effector of Hippo pathway, subsequently leading to its cytoplasmic retention, and thus reduced YAP transcriptional modulating activity.	Metformin	17-26	Yes1 associated transcriptional regulator	Homo sapiens	168-171
29567539-5	2018	Importantly, overexpression of a mutant form of YAP (YAP-5SA) attenuated the inhibition of metformin on glioma cells stemness and epithelial-mesenchymal transition.	Metformin	91-100	Yes1 associated transcriptional regulator	Homo sapiens	48-51
29567539-5	2018	Importantly, overexpression of a mutant form of YAP (YAP-5SA) attenuated the inhibition of metformin on glioma cells stemness and epithelial-mesenchymal transition.	Metformin	91-100	Yes1 associated transcriptional regulator	Homo sapiens	53-60
29567539-6	2018	Thus, metformin inhibits glioma cells stemness and epithelial-mesenchymal transition via regulating YAP activity.	Metformin	6-15	Yes1 associated transcriptional regulator	Homo sapiens	100-103
29698747-11	2018	In addition, metformin inhibited the translocation of NF-kappaB p65 from cytoplasm into the nucleus, as well as the phosphorylation of ERK1/2 and p38 MAPK.	Metformin	13-22	mitogen activated protein kinase 3	Rattus norvegicus	135-141
29620187-5	2018	Metformin treatment significantly promoted the phosphorylation of AMP-activated protein kinase (AMPK), and reduced histone H3 lysine 27 trimethylation (H3K27me3) and polycomb repressor complex 2 (PRC2) levels.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	66-94
29620187-5	2018	Metformin treatment significantly promoted the phosphorylation of AMP-activated protein kinase (AMPK), and reduced histone H3 lysine 27 trimethylation (H3K27me3) and polycomb repressor complex 2 (PRC2) levels.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	96-100
29620187-7	2018	Similar to metformin, another AMPK agonist, 2-deoxy-D-glucose, reduced the H3K27me3 level and PRC2 expression.	Metformin	11-20	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	30-34
29620187-9	2018	Metformin-mediated AMPK activation and H3K27me3 inhibition were more robust in cells exposed to low glucose (5.5 mM) compared with those exposed to high glucose (25 mM).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	19-23
29620187-10	2018	These findings implicate H3K27me3 repression mediated by AMPK phosphorylation in the antitumor effect of metformin in ovarian cancer, indicating that metformin alters epigenetic modifications by targeting PRC2 and supports the use of metformin in treatment of patients with epithelial ovarian cancer without diabetes.	Metformin	105-114	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	57-61
29620187-10	2018	These findings implicate H3K27me3 repression mediated by AMPK phosphorylation in the antitumor effect of metformin in ovarian cancer, indicating that metformin alters epigenetic modifications by targeting PRC2 and supports the use of metformin in treatment of patients with epithelial ovarian cancer without diabetes.	Metformin	150-159	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	57-61
29620187-10	2018	These findings implicate H3K27me3 repression mediated by AMPK phosphorylation in the antitumor effect of metformin in ovarian cancer, indicating that metformin alters epigenetic modifications by targeting PRC2 and supports the use of metformin in treatment of patients with epithelial ovarian cancer without diabetes.	Metformin	150-159	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	57-61
29231260-0	2018	Metformin inhibits tumorigenesis in HBV-induced hepatocellular carcinoma by suppressing HULC overexpression caused by HBX.	Metformin	0-9	hepatocellular carcinoma up-regulated long non-coding RNA	Homo sapiens	88-92
29231260-1	2018	We aimed to understand whether metformin imposes the inhibitory effect on the HBV-associated tumorigenesis by regulating the HULC and its downstream signaling pathway.	Metformin	31-40	hepatocellular carcinoma up-regulated long non-coding RNA	Homo sapiens	125-129
29231260-2	2018	Luciferase assay, RT-PCR, and Western-blot, MTT and flow cytometry analysis were performed to understand and the mechanism, by which metformin enhance the inhibitory effect on the HBV-associated tumorigenesis by regulating the HULC and its downstream signaling pathway.	Metformin	133-142	hepatocellular carcinoma up-regulated long non-coding RNA	Homo sapiens	227-231
29231260-8	2018	This study indicated that metformin imposed inhibitory effect on the HBV-associated HCC by negatively regulating the HULC/p18/miR-200a/ZEB1 signaling pathway.	Metformin	26-35	hepatocellular carcinoma up-regulated long non-coding RNA	Homo sapiens	117-121
29520103-0	2018	Metformin suppresses melanoma progression by inhibiting KAT5-mediated SMAD3 acetylation, transcriptional activity and TRIB3 expression.	Metformin	0-9	K(lysine) acetyltransferase 5	Mus musculus	56-60
29520103-0	2018	Metformin suppresses melanoma progression by inhibiting KAT5-mediated SMAD3 acetylation, transcriptional activity and TRIB3 expression.	Metformin	0-9	SMAD family member 3	Mus musculus	70-75
29520103-7	2018	Metformin suppresses SMAD3 phosphorylation and decreases the KAT5/SMAD3 interaction, to attenuate the KAT5-mediated K333 acetylation of SMAD3, reduce the SMAD3 transcriptional activity and subsequent TRIB3 expression, thereby antagonizes melanoma progression.	Metformin	0-9	SMAD family member 3	Mus musculus	21-26
29520103-7	2018	Metformin suppresses SMAD3 phosphorylation and decreases the KAT5/SMAD3 interaction, to attenuate the KAT5-mediated K333 acetylation of SMAD3, reduce the SMAD3 transcriptional activity and subsequent TRIB3 expression, thereby antagonizes melanoma progression.	Metformin	0-9	K(lysine) acetyltransferase 5	Mus musculus	61-65
29520103-7	2018	Metformin suppresses SMAD3 phosphorylation and decreases the KAT5/SMAD3 interaction, to attenuate the KAT5-mediated K333 acetylation of SMAD3, reduce the SMAD3 transcriptional activity and subsequent TRIB3 expression, thereby antagonizes melanoma progression.	Metformin	0-9	SMAD family member 3	Mus musculus	66-71
29520103-7	2018	Metformin suppresses SMAD3 phosphorylation and decreases the KAT5/SMAD3 interaction, to attenuate the KAT5-mediated K333 acetylation of SMAD3, reduce the SMAD3 transcriptional activity and subsequent TRIB3 expression, thereby antagonizes melanoma progression.	Metformin	0-9	K(lysine) acetyltransferase 5	Mus musculus	102-106
29520103-7	2018	Metformin suppresses SMAD3 phosphorylation and decreases the KAT5/SMAD3 interaction, to attenuate the KAT5-mediated K333 acetylation of SMAD3, reduce the SMAD3 transcriptional activity and subsequent TRIB3 expression, thereby antagonizes melanoma progression.	Metformin	0-9	SMAD family member 3	Mus musculus	66-71
29520103-7	2018	Metformin suppresses SMAD3 phosphorylation and decreases the KAT5/SMAD3 interaction, to attenuate the KAT5-mediated K333 acetylation of SMAD3, reduce the SMAD3 transcriptional activity and subsequent TRIB3 expression, thereby antagonizes melanoma progression.	Metformin	0-9	SMAD family member 3	Mus musculus	66-71
29520103-8	2018	Together, our study not only defines a molecular mechanism by which metformin protects against melanoma progression by disturbing the KAT5/TRIB3/SMAD3 positive feedback loop in diabetes and non-diabetes mice, but also suggests a candidate diverse utility of metformin in tumour prevention and therapy because of suppressing stress protein TRIB3 expression.	Metformin	68-77	K(lysine) acetyltransferase 5	Mus musculus	134-138
29520103-8	2018	Together, our study not only defines a molecular mechanism by which metformin protects against melanoma progression by disturbing the KAT5/TRIB3/SMAD3 positive feedback loop in diabetes and non-diabetes mice, but also suggests a candidate diverse utility of metformin in tumour prevention and therapy because of suppressing stress protein TRIB3 expression.	Metformin	68-77	SMAD family member 3	Mus musculus	145-150
29665787-11	2018	However, the addition of VPA dramatically upregulated histone H3 acetylation, increased the sensibility of AKT and inhibited pSMAD3/SMAD4, letting the combination of VPA and metformin remarkably reappear the anti-tumour effects of metformin in 786-M-R cells.	Metformin	174-183	SMAD family member 4	Homo sapiens	132-137
29654226-3	2018	Metformin (MTF) has been reported to target NLK (Nemo-like kinase) to inhibit non-small lung cancer cells.	Metformin	0-9	nemo like kinase	Mus musculus	44-47
29654226-3	2018	Metformin (MTF) has been reported to target NLK (Nemo-like kinase) to inhibit non-small lung cancer cells.	Metformin	0-9	nemo like kinase	Mus musculus	49-65
29636010-8	2018	In the atrial myocytes from control, GK and metformin-treated GK rats, the expression of KCa2.2 (SK2 channel) was down-regulated and the expression of KCa2.3 (SK3 channel) was up-regulated in the atrium of GK rats as compared with that of control rats, and metformin reversed diabetes-induced alterations in atrial SK channel expression.	Metformin	44-53	potassium calcium-activated channel subfamily N member 3	Rattus norvegicus	151-157
29636010-8	2018	In the atrial myocytes from control, GK and metformin-treated GK rats, the expression of KCa2.2 (SK2 channel) was down-regulated and the expression of KCa2.3 (SK3 channel) was up-regulated in the atrium of GK rats as compared with that of control rats, and metformin reversed diabetes-induced alterations in atrial SK channel expression.	Metformin	44-53	potassium calcium-activated channel subfamily N member 3	Rattus norvegicus	159-162
29383869-8	2018	While each tissue had a signature reflecting its own function, we identified a cascade of predictive upstream transcriptional regulators, including mTORC1, MYC, TNF, TGFss1, and miRNA-29b that may explain tissue-specific transcriptomic changes in response to metformin treatment.	Metformin	259-268	CREB regulated transcription coactivator 1	Mus musculus	148-154
33631404-7	2021	However, its combination with metformin ameliorated the levels of inflammation and up-regulated the expression of CD69 although it had no therapeutic effect on the levels of PD-1 expression.	Metformin	30-39	CD69 molecule	Homo sapiens	114-118
33742560-2	2021	In addition, the biguanide derivative phenformin exhibits antitumor activity superior to that of the AMPK activator metformin.	Metformin	116-125	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	101-105
33277775-4	2021	Metformin and exercise training share many pathways that could potentially contrast SAMS and NOD.	Metformin	0-9	atrophin 1	Homo sapiens	93-96
33929675-0	2021	Crocin and Metformin suppress metastatic breast cancer progression via VEGF and MMP9 downregulations: in vitro and in vivo studies.	Metformin	11-20	matrix metallopeptidase 9	Mus musculus	80-84
33929675-9	2021	While crocin alone restored the mice"s weight reduction, crocin, metformin, and their combination significantly reduced the tumor volume size and enhanced animal survival rate in murine breast cancer model, responses that were associated with VEGF and MMP9 down-regulation.	Metformin	65-74	matrix metallopeptidase 9	Mus musculus	252-256
33350292-0	2021	Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism.	Metformin	0-9	cyclin D1	Homo sapiens	81-90
33350292-1	2021	AIM: In the present study we aimed to figure out the effect of metformin on the expression of AMPK-alpha, cyclin D1 and Tp53, and apoptosis in primary breast cancer cells (PBCCs).	Metformin	63-72	cyclin D1	Homo sapiens	106-115
33350292-7	2021	PBCCs treated with 25 mM metformin had lower cyclin D1 expression compared with non-treated cells, however, the difference was not statistically significant.	Metformin	25-34	cyclin D1	Homo sapiens	45-54
33350292-10	2021	CONCLUSION: Metformin can modulate cyclin D1 and p53 expression through AMPK-alpha independent mechanism in breast cancer cells, leading to cell proliferation inhibition and apoptosis induction.	Metformin	12-21	cyclin D1	Homo sapiens	35-44
33915173-9	2021	Importantly, enhancing TET2 stability using Metformin and VitaminC/ascorbic acid (AA) restores 5hmc and GATA6 levels, reverting squamous-like tumor phenotypes and WNT-dependence in vitro and in vivo.	Metformin	44-53	tet methylcytosine dioxygenase 2	Homo sapiens	23-27
32667970-0	2021	Metformin directly suppresses atherosclerosis in normoglycemic mice via haematopoietic Adenosine Monophosphate-Activated Protein Kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	137-141
32667970-3	2021	The anti-diabetic drug metformin may also activate AMPK-dependent signalling.	Metformin	23-32	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	51-55
32667970-4	2021	HYPOTHESIS: Metformin systematically induces atheroprotective genes in macrophages via AMPK and ATF1, and thereby suppresses atherogenesis.	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	87-91
32667970-4	2021	HYPOTHESIS: Metformin systematically induces atheroprotective genes in macrophages via AMPK and ATF1, and thereby suppresses atherogenesis.	Metformin	12-21	activating transcription factor 1	Mus musculus	96-100
32667970-6	2021	Bone marrow transplantation from AMPK-deficient mice demonstrated that metformin-related atheroprotection required haematopoietic AMPK (ANOVA, p < 0.03).	Metformin	71-80	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	33-37
32667970-6	2021	Bone marrow transplantation from AMPK-deficient mice demonstrated that metformin-related atheroprotection required haematopoietic AMPK (ANOVA, p < 0.03).	Metformin	71-80	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	130-134
32667970-7	2021	Metformin at a clinically relevant concentration (10muM) evoked AMPK-dependent and ATF1-dependent increases in Hmox1, Nr1h2 (Lxrb), Abca1, Apoe, Igf1 and Pdgf, increases in several M2-markers and decreases in Nos2, in murine bone marrow macrophages.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	64-68
32667970-7	2021	Metformin at a clinically relevant concentration (10muM) evoked AMPK-dependent and ATF1-dependent increases in Hmox1, Nr1h2 (Lxrb), Abca1, Apoe, Igf1 and Pdgf, increases in several M2-markers and decreases in Nos2, in murine bone marrow macrophages.	Metformin	0-9	activating transcription factor 1	Mus musculus	83-87
32667970-7	2021	Metformin at a clinically relevant concentration (10muM) evoked AMPK-dependent and ATF1-dependent increases in Hmox1, Nr1h2 (Lxrb), Abca1, Apoe, Igf1 and Pdgf, increases in several M2-markers and decreases in Nos2, in murine bone marrow macrophages.	Metformin	0-9	insulin-like growth factor 1	Mus musculus	145-149
32667970-10	2021	Metformin induced lesional macrophage expression of p-AMPK, p-ATF1 and downstream M2-like protective effects.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	54-58
32667970-11	2021	CONCLUSION: Metformin activates a conserved AMPK-ATF1-M2-like pathway in mouse and human macrophages, and results in highly suppressed atherogenesis in hyperlipidemic mice via haematopoietic AMPK.	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	44-48
32667970-11	2021	CONCLUSION: Metformin activates a conserved AMPK-ATF1-M2-like pathway in mouse and human macrophages, and results in highly suppressed atherogenesis in hyperlipidemic mice via haematopoietic AMPK.	Metformin	12-21	activating transcription factor 1	Mus musculus	49-53
32667970-11	2021	CONCLUSION: Metformin activates a conserved AMPK-ATF1-M2-like pathway in mouse and human macrophages, and results in highly suppressed atherogenesis in hyperlipidemic mice via haematopoietic AMPK.	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	191-195
32667970-12	2021	TRANSLATIONAL PERSPECTIVE: The work shows that oral antidiabetic drug metformin may suppress atherosclerotic lesion development via hematopoietic AMPK at clinically relevant concentrations, rather than via a hypoglycemic effect.	Metformin	70-79	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	146-150
32667970-13	2021	Activating Transcription Factor 1 (ATF1) may mediate induction of key atheroprotective genes by metformin.	Metformin	96-105	activating transcription factor 1	Mus musculus	0-33
32667970-13	2021	Activating Transcription Factor 1 (ATF1) may mediate induction of key atheroprotective genes by metformin.	Metformin	96-105	activating transcription factor 1	Mus musculus	35-39
33968030-4	2021	We then demonstrated that metformin reduced mTORC1 activity in T cells from infected mice, as evidenced by decreased phosphorylation of ribosome protein S6 (p-S6).	Metformin	26-35	CREB regulated transcription coactivator 1	Mus musculus	44-50
33968030-5	2021	The inhibitory effects on the mTORC1 signaling by metformin was dependent on the tuberous sclerosis complex 1 (TSC1).	Metformin	50-59	CREB regulated transcription coactivator 1	Mus musculus	30-36
33968030-5	2021	The inhibitory effects on the mTORC1 signaling by metformin was dependent on the tuberous sclerosis complex 1 (TSC1).	Metformin	50-59	TSC complex subunit 1	Mus musculus	81-109
33968030-5	2021	The inhibitory effects on the mTORC1 signaling by metformin was dependent on the tuberous sclerosis complex 1 (TSC1).	Metformin	50-59	TSC complex subunit 1	Mus musculus	111-115
33968030-6	2021	Mechanistically, metformin treatment modulated the phosphorylation of dynamin-related protein 1 (Drp-1) and mitochondrial fission 1 protein (FIS1), resulting in increased mass in effector T cells.	Metformin	17-26	fission, mitochondrial 1	Mus musculus	108-139
33968030-6	2021	Mechanistically, metformin treatment modulated the phosphorylation of dynamin-related protein 1 (Drp-1) and mitochondrial fission 1 protein (FIS1), resulting in increased mass in effector T cells.	Metformin	17-26	fission, mitochondrial 1	Mus musculus	141-145
33968030-8	2021	Together, our results revealed a protective role and therapeutic potential of metformin against liver injury in acute viral hepatitis via modulating effector T cell activation via regulating the mTORC1 pathway and mitochondrial functions.	Metformin	78-87	CREB regulated transcription coactivator 1	Mus musculus	195-201
33880815-4	2021	Glucagon like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 (SGLT2) inhibitors improve glycemic control, lower body weight and blood pressure, are recommended after lifestyle and metformin as initial therapy for diabetic patients with cardiovascular or kidney comorbidities regarding their cardiorenal benefits.	Metformin	206-215	glucagon like peptide 1 receptor	Homo sapiens	0-32
33887464-9	2021	Metformin treatment prompted apoptosis upon miR-17-overexpression only in LKB1WT cell lines, as well as in LWT/miR17H PDXs.	Metformin	0-9	microRNA 17	Homo sapiens	44-50
33887464-9	2021	Metformin treatment prompted apoptosis upon miR-17-overexpression only in LKB1WT cell lines, as well as in LWT/miR17H PDXs.	Metformin	0-9	microRNA 17	Homo sapiens	111-116
33513084-3	2021	Metformin is an AMP Kinase (AMPK) activator, the widest used anti-diabetic drug.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	28-32
33652909-8	2021	The cell-based analysis further indicated that metformin treatment regulated p38/JNK pathway to reduce Cyclin D1 and Bcl-2 expressions.	Metformin	47-56	cyclin D1	Homo sapiens	103-112
33747367-1	2021	The main anti-diabetic effect of metformin mediated through stimulation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) is the inhibition of hepatic gluconeogenesis and triggering glucose uptake in skeletal muscles.	Metformin	33-42	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	131-135
33747367-2	2021	Additionally, some new pathways, besides the AMPK activation, were discovered, that can explain wide-range properties of metformin.	Metformin	121-130	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	45-49
33643408-10	2021	In addition, we found that the prevented CAR transfer into the nucleus by metformin was partially an AMPK-dependent event.	Metformin	74-83	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	101-105
33643408-11	2021	Conclusion: The present study indicated that the activation of AMPK-CAR pathway mediated the suppression of SULT2A1 by metformin.	Metformin	119-128	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	63-67
33668426-6	2021	The anti-diabetic effects of metformin are mediated mainly via activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), which is an energy sensing enzyme activated directly by an increase in the AMP/ATP ratio under conditions of metabolic stress.	Metformin	29-38	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	133-137
33668426-9	2021	We also address the adaptive use of metformin, a known AMPK activator, as a new drug for treatment of patients with OA and T2DM.	Metformin	36-45	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	55-59
33578894-2	2021	Metformin significantly reduced H3K4me3 level at the promoters of positive cell cycle regulatory genes such as CCNB2, CDK1, CDK6, and E2F8.	Metformin	0-9	cyclin-dependent kinase 1	Mus musculus	118-122
33578894-2	2021	Metformin significantly reduced H3K4me3 level at the promoters of positive cell cycle regulatory genes such as CCNB2, CDK1, CDK6, and E2F8.	Metformin	0-9	cyclin-dependent kinase 6	Mus musculus	124-128
33578894-4	2021	Metformin suppressed the expression of H3K4 methyltransferases MLL1, MLL2, and WDR82.	Metformin	0-9	WD repeat domain 82	Homo sapiens	79-84
33578894-8	2021	The present study suggests that metformin reduces H3K4me3 levels at the promoters of positive cell cycle regulatory genes through MLL2 downregulation in lung cancer cells.	Metformin	32-41	lysine methyltransferase 2B	Homo sapiens	130-134
33561890-6	2021	RESULTS: Participants using metformin had lower odds of musculoskeletal pain for back [recent OR 0.91, 95%CI 0.85 to 0.97; chronic OR 0.87, 95%CI 0.81 to 0.93], knee [recent OR 0.91, 95%CI 0.85 to 0.97; chronic OR 0.87, 95%CI 0.81 to 0.94], and neck/shoulder regions [chronic OR 0.92, 95%CI 0.85 to 0.99] but not hip pain.	Metformin	28-37	hedgehog interacting protein	Homo sapiens	313-316
33345855-10	2021	Omeprazole and metformin were found to decrease stomach acidity and ulcer index, restored the histological features and increased mucin levels.	Metformin	15-24	LOC100508689	Homo sapiens	130-135
33614642-0	2021	Metformin Attenuates Renal Fibrosis in a Mouse Model of Adenine-Induced Renal Injury Through Inhibiting TGF-beta1 Signaling Pathways.	Metformin	0-9	transforming growth factor, beta 1	Mus musculus	104-113
33614642-8	2021	Moreover, treatment with metformin inhibited the phosphorylation of Smad3, ERK1/2, and P38 and was associated with activation of the AMP-activated protein kinase (AMPK) in the kidneys of adenine-treated mice.	Metformin	25-34	SMAD family member 3	Mus musculus	68-73
33614642-8	2021	Moreover, treatment with metformin inhibited the phosphorylation of Smad3, ERK1/2, and P38 and was associated with activation of the AMP-activated protein kinase (AMPK) in the kidneys of adenine-treated mice.	Metformin	25-34	mitogen-activated protein kinase 3	Mus musculus	75-81
33614642-8	2021	Moreover, treatment with metformin inhibited the phosphorylation of Smad3, ERK1/2, and P38 and was associated with activation of the AMP-activated protein kinase (AMPK) in the kidneys of adenine-treated mice.	Metformin	25-34	mitogen-activated protein kinase 14	Mus musculus	87-90
33614642-9	2021	These results indicate that metformin attenuates adenine-induced renal fibrosis through inhibition of TGF-beta1 signaling pathways and activation of AMPK, independent of its glucose-lowering action.	Metformin	28-37	transforming growth factor, beta 1	Mus musculus	102-111
32654569-9	2021	Metformin exhibited therapeutic potential for treating inflammatory conditions of the colon by targeting the immunoregulatory cytokine, TGF-beta1.	Metformin	0-9	transforming growth factor, beta 1	Mus musculus	136-145
32594364-10	2021	Moreover, the metformin/MCC950 leads to the induction of autophagy by AMP-activated protein kinase (AMPK)-dependent mechanisms leading to the accumulation of Beclin-1 and a substantial decline in the levels of p62 SQSTM1 (effect of metformin).	Metformin	14-23	beclin 1	Rattus norvegicus	158-166
32594364-10	2021	Moreover, the metformin/MCC950 leads to the induction of autophagy by AMP-activated protein kinase (AMPK)-dependent mechanisms leading to the accumulation of Beclin-1 and a substantial decline in the levels of p62 SQSTM1 (effect of metformin).	Metformin	14-23	KH RNA binding domain containing, signal transduction associated 1	Rattus norvegicus	210-213
32951009-9	2021	RESULTS: Metformin treatment lowered weight gain, fat mass, caloric intake, and serum leptin levels.	Metformin	9-18	leptin	Rattus norvegicus	86-92
32067559-8	2021	SGLT-2 inhibitors and GLP-1 agonists should be considered when patients" diabetes is no longer well controlled with metformin.	Metformin	116-125	glucagon like peptide 1 receptor	Homo sapiens	22-27
32737864-0	2021	Metformin inhibits pancreatic cancer metastasis caused by SMAD4 deficiency and consequent HNF4G upregulation.	Metformin	0-9	SMAD family member 4	Homo sapiens	58-63
32737864-6	2021	We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency.	Metformin	19-28	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	59-63
32737864-6	2021	We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency.	Metformin	19-28	SMAD family member 4	Homo sapiens	197-202
32737864-7	2021	Furthermore, Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC (log-rank P = 0.022; HR = 0.31, 95% CI = 0.14-0.68) but not in patients with SMAD4-normal PDAC.	Metformin	13-22	SMAD family member 4	Homo sapiens	103-108
32737864-7	2021	Furthermore, Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC (log-rank P = 0.022; HR = 0.31, 95% CI = 0.14-0.68) but not in patients with SMAD4-normal PDAC.	Metformin	13-22	SMAD family member 4	Homo sapiens	201-206
32737864-9	2021	These results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.	Metformin	180-189	SMAD family member 4	Homo sapiens	28-33
33510216-5	2021	Metformin increased expression of Slc2a1 (GLUT1), decreased expression of Slc2a2 (GLUT2) and Slc5a1 (SGLT1) whilst increasing GLUT-dependent glucose uptake and glycolytic rate as observed by live cell imaging of genetically encoded metabolite sensors and measurement of oxygen consumption and extracellular acidification rates.	Metformin	0-9	solute carrier family 2 (facilitated glucose transporter), member 2	Mus musculus	74-80
33510216-5	2021	Metformin increased expression of Slc2a1 (GLUT1), decreased expression of Slc2a2 (GLUT2) and Slc5a1 (SGLT1) whilst increasing GLUT-dependent glucose uptake and glycolytic rate as observed by live cell imaging of genetically encoded metabolite sensors and measurement of oxygen consumption and extracellular acidification rates.	Metformin	0-9	solute carrier family 2 (facilitated glucose transporter), member 2	Mus musculus	82-87
33227290-10	2021	We therefore measured levels of IGF-1 in plasma taken from mice treated with metformin, but found no difference between the drug treatment and control groups.	Metformin	77-86	insulin-like growth factor 1	Mus musculus	32-37
33601368-1	2021	BACKGROUND AND OBJECTIVE: Epidemiological evidence suggests that the antidiabetic drug metformin (MET) can also inhibit abdominal aortic aneurysm (AAA) formation.	Metformin	87-96	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	98-101
32994182-5	2021	In cultured mouse mammary and human breast cancer cells, metformin suppressed DPP-4 inhibitor KR62436 (KR)-induced EMT and cell migration via suppression of the mTOR pathway associated with AMPK activation.	Metformin	57-66	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	190-194
32657143-8	2021	In the metformin treated group, the expression of Bax and PUMA genes was enhanced while the expression of Bcl-2, hTERT, mTOR, and p53 genes declined.	Metformin	7-16	BCL2 binding component 3	Homo sapiens	58-62
32862004-0	2021	Protective effect of metformin on BPA-induced liver toxicity in rats through upregulation of cystathionine beta synthase and cystathionine gamma lyase expression.	Metformin	21-30	cystathionine gamma-lyase	Rattus norvegicus	125-150
32862004-10	2021	Additionally, metformin significantly increased cystathionine beta synthase (CBS) and cystathionine gamma lyase (CSE), thus reducing serum levels of homocysteine and increasing hepatic levels of cysteine and glutathione in BPA-treated rats.	Metformin	14-23	cystathionine gamma-lyase	Rattus norvegicus	86-111
33375185-9	2020	AMPK pharmacological activation plays a key role, with metformin inhibiting inflammation and improving ED.	Metformin	55-64	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-4
29374065-0	2018	Metformin-Induced Reduction of CD39 and CD73 Blocks Myeloid-Derived Suppressor Cell Activity in Patients with Ovarian Cancer.	Metformin	0-9	5'-nucleotidase ecto	Homo sapiens	40-44
29374065-2	2018	We show here that metformin treatment blocks the suppressive function of myeloid-derived suppressor cells (MDSC) in patients with ovarian cancer by downregulating the expression and ectoenzymatic activity of CD39 and CD73 on monocytic and polymononuclear MDSC subsets.	Metformin	18-27	5'-nucleotidase ecto	Homo sapiens	217-221
29374065-3	2018	Metformin triggered activation of AMP-activated protein kinase alpha and subsequently suppressed hypoxia-inducible factor alpha, which was critical for induction of CD39/CD73 expression in MDSC.	Metformin	0-9	5'-nucleotidase ecto	Homo sapiens	170-174
29374065-4	2018	Furthermore, metformin treatment correlated with longer overall survival in diabetic patients with ovarian cancer, which was accompanied by a metformin-induced reduction in the frequency of circulating CD39+CD73+ MDSC and a concomitant increase in the antitumor activities of circulating CD8+ T cells.	Metformin	13-22	5'-nucleotidase ecto	Homo sapiens	207-211
29374065-4	2018	Furthermore, metformin treatment correlated with longer overall survival in diabetic patients with ovarian cancer, which was accompanied by a metformin-induced reduction in the frequency of circulating CD39+CD73+ MDSC and a concomitant increase in the antitumor activities of circulating CD8+ T cells.	Metformin	142-151	5'-nucleotidase ecto	Homo sapiens	207-211
29374065-5	2018	Our results highlight a direct effect of metformin on MDSC and suggest that metformin may yield clinical benefit through improvement of antitumor T-cell immunity by dampening CD39/CD73-dependent MDSC immunosuppression in ovarian cancer patients.Significance: The antitumor activity of an antidiabetes drug is attributable to reduced immunosuppressive activity of myeloid-derived tumor suppressor cells.	Metformin	76-85	5'-nucleotidase ecto	Homo sapiens	180-184
29272251-3	2018	In vivo and in vitro cancer cell culture studies demonstrate that metformin induces both AMPK-dependent and AMPK-independent genes/pathways that result in inhibition of cancer cell growth and migration and induction of apoptosis.	Metformin	66-75	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	89-93
29272251-3	2018	In vivo and in vitro cancer cell culture studies demonstrate that metformin induces both AMPK-dependent and AMPK-independent genes/pathways that result in inhibition of cancer cell growth and migration and induction of apoptosis.	Metformin	66-75	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	108-112
29554968-0	2018	Metformin induces autophagy and G0/G1 phase cell cycle arrest in myeloma by targeting the AMPK/mTORC1 and mTORC2 pathways.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	90-94
29554968-0	2018	Metformin induces autophagy and G0/G1 phase cell cycle arrest in myeloma by targeting the AMPK/mTORC1 and mTORC2 pathways.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	95-101
29554968-0	2018	Metformin induces autophagy and G0/G1 phase cell cycle arrest in myeloma by targeting the AMPK/mTORC1 and mTORC2 pathways.	Metformin	0-9	CREB regulated transcription coactivator 2	Mus musculus	106-112
29554968-10	2018	Metformin activated AMPK and repressed both mTORC1 and mTORC2 signaling pathways in myeloma cells as well as downstream molecular signaling pathways, such as p-4EBP1 and p-AKT.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	20-24
29554968-10	2018	Metformin activated AMPK and repressed both mTORC1 and mTORC2 signaling pathways in myeloma cells as well as downstream molecular signaling pathways, such as p-4EBP1 and p-AKT.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	44-50
29554968-10	2018	Metformin activated AMPK and repressed both mTORC1 and mTORC2 signaling pathways in myeloma cells as well as downstream molecular signaling pathways, such as p-4EBP1 and p-AKT.	Metformin	0-9	CREB regulated transcription coactivator 2	Mus musculus	55-61
29554968-12	2018	In addition, metformin inhibited myeloma cell growth in an AMPK-dependent manner.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	59-63
29554968-13	2018	The xenograft mouse model further confirmed that metformin inhibited tumor growth by upregulation of AMPK and downregulation of mTOR.	Metformin	49-58	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	101-105
29559078-4	2018	Metformin also increases plasma concentrations of the glucose-lowering gut incretin hormone glucagon-like peptide-1 (GLP-1).	Metformin	0-9	glucagon like peptide 1 receptor	Homo sapiens	117-122
29559078-5	2018	This metformin-induced GLP-1 increment may constitute an important link between the gut and the glucose-lowering effect of metformin.	Metformin	5-14	glucagon like peptide 1 receptor	Homo sapiens	23-28
29559078-5	2018	This metformin-induced GLP-1 increment may constitute an important link between the gut and the glucose-lowering effect of metformin.	Metformin	123-132	glucagon like peptide 1 receptor	Homo sapiens	23-28
29593575-8	2018	Western blot demonstrated that both DZF and metformin activated 5" AMP-activated protein kinase (AMPK) but inhibited Notch intracellular domain (NICD) and Hairy/enhancer-of-split 1 (Hes1) of Notch signaling pathway in the liver.	Metformin	44-53	hes family bHLH transcription factor 1	Mus musculus	155-180
29593575-8	2018	Western blot demonstrated that both DZF and metformin activated 5" AMP-activated protein kinase (AMPK) but inhibited Notch intracellular domain (NICD) and Hairy/enhancer-of-split 1 (Hes1) of Notch signaling pathway in the liver.	Metformin	44-53	hes family bHLH transcription factor 1	Mus musculus	182-186
29348175-11	2018	We also noted that MafA overexpression prevents metformin-induced decreases in insulin and GSIS-related gene expression.	Metformin	48-57	v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (avian)	Mus musculus	19-23
29513760-5	2018	Its anti-angiogenic activity was confirmed in vivo that metformin significantly reduced spontaneous intraretinal neovascularization in a very-low-density lipoprotein receptor knockout mutant mouse (p&lt;0.05).	Metformin	56-65	very low density lipoprotein receptor	Mus musculus	137-174
29513760-6	2018	Several inflammatory molecules upregulated by tumor necrosis factor-alpha in human retinal vascular endothelial cells were markedly reduced by metformin, including nuclear factor kappa B p65 (NFkappaB p65), intercellular adhesion molecule-1 (ICAM-1), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8).	Metformin	143-152	RELA proto-oncogene, NF-kB subunit	Homo sapiens	187-190
29513760-6	2018	Several inflammatory molecules upregulated by tumor necrosis factor-alpha in human retinal vascular endothelial cells were markedly reduced by metformin, including nuclear factor kappa B p65 (NFkappaB p65), intercellular adhesion molecule-1 (ICAM-1), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8).	Metformin	143-152	RELA proto-oncogene, NF-kB subunit	Homo sapiens	201-204
33347618-22	2020	Using long protocol GnRH-agonist stimulation, metformin may increase clinical pregnancy rate per woman compared with placebo/no treatment (RR 1.32, 95% CI 1.08 to 1.63; 10 RCTs; 915 women; I2 = 13%; low-quality evidence).	Metformin	46-55	gonadotropin releasing hormone 1	Homo sapiens	20-24
33347618-30	2020	In a short GnRH-antagonist protocol, metformin may reduce live birth rates, although we are uncertain about the effect of metformin on clinical pregnancy rate.	Metformin	37-46	gonadotropin releasing hormone 1	Homo sapiens	11-15
33411680-5	2020	METHODS AND RESULTS: Metformin increased lncRNA-ANRIL expression and AMPK activity in cultured VSMCs, and inhibited the phenotypic switching of VSMCs to the synthetic phenotype induced by platelet-derived growth factor (PDGF).	Metformin	21-30	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	69-73
33411680-7	2020	While, gene knockdown of lncRNA-ANRIL by adenovirus or silence of AMPKgamma through siRNA abolished AMPK activation induced by metformin in VSMCs.	Metformin	127-136	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	66-70
33411680-12	2020	CONCLUSION: Metformin activates AMPK to suppress the formation of atherosclerotic plaque through upregulation of lncRNA-ANRIL.	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	32-36
33008889-2	2020	SLC19A2 and SLC19A3 are also known to transport structurally unrelated cationic drugs, such as metformin, but whether this charge selectivity extends to other molecules, such as pyridoxine (vitamin B6), is unknown.	Metformin	95-104	solute carrier family 19 member 2	Homo sapiens	0-7
33008889-2	2020	SLC19A2 and SLC19A3 are also known to transport structurally unrelated cationic drugs, such as metformin, but whether this charge selectivity extends to other molecules, such as pyridoxine (vitamin B6), is unknown.	Metformin	95-104	solute carrier family 19 member 3	Homo sapiens	12-19
33302986-11	2020	(2) Completer analyses: compared with the baseline, the weight, BMI, and waist-hip ratio in the topiramate group at week 4-16 were markedly decreased, whereas only waist-hip ratio with metformin was significantly decreased at week 4.	Metformin	185-194	hedgehog interacting protein	Homo sapiens	170-173
32516360-10	2020	Of note, either nicotine treatment or activation of AMPK by intracerebroventricular infusion of metformin reduced LPS-induced impairment of fear memory reconsolidation, and ameliorated inflammation factor TNF-alpha and IL-1beta as well as the expression of CRTC1.	Metformin	96-105	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	52-56
32516360-10	2020	Of note, either nicotine treatment or activation of AMPK by intracerebroventricular infusion of metformin reduced LPS-induced impairment of fear memory reconsolidation, and ameliorated inflammation factor TNF-alpha and IL-1beta as well as the expression of CRTC1.	Metformin	96-105	CREB regulated transcription coactivator 1	Homo sapiens	257-262
32970287-7	2020	Metformin treatment downregulated miR223 expression in both adipocytes and human diabetic adipose tissue.	Metformin	0-9	microRNA 223	Homo sapiens	34-40
32970287-8	2020	In contrast the IRS/PI3-K/AKT pathway signaling components, Akt and GLUT4 increased in insulin-resistant 3T3L1 adipocytes and human diabetic adipose tissue after three months of metformin treatment.	Metformin	178-187	solute carrier family 2 member 4	Homo sapiens	68-73
32970287-9	2020	CONCLUSIONS: Metformin reduced insulin resistance in adipocytes by reduction of miR223 expression and improving of IRS/Akt/GLUT4 signaling pathways.	Metformin	13-22	microRNA 223	Homo sapiens	80-86
32970287-9	2020	CONCLUSIONS: Metformin reduced insulin resistance in adipocytes by reduction of miR223 expression and improving of IRS/Akt/GLUT4 signaling pathways.	Metformin	13-22	solute carrier family 2 member 4	Homo sapiens	123-128
32970287-10	2020	Plasma miR223 expression of human diabetic patients was reduced by metformin treatment.	Metformin	67-76	microRNA 223	Homo sapiens	7-13
33230189-3	2020	Expression levels of key TCA cycle enzymes and the autophagy-related protein light chain 3b (LC3b) were determined in raw 264.7 cells treated with lipopolysaccharide (LPS) and metformin (Met).	Metformin	176-185	microtubule-associated protein 1 light chain 3 beta	Mus musculus	93-97
33221742-8	2020	We suspected that metformin may play a neuroprotective role in early AD by increasing NEAT1 expression and through FZD3/GSK3beta/p-tau pathway.	Metformin	18-27	frizzled class receptor 3	Homo sapiens	115-119
33221742-8	2020	We suspected that metformin may play a neuroprotective role in early AD by increasing NEAT1 expression and through FZD3/GSK3beta/p-tau pathway.	Metformin	18-27	glycogen synthase kinase 3 alpha	Homo sapiens	120-128
33208818-6	2020	AMPK agonist Epi determined direct effects on the alpha1-AR, metformin was used as an activator for AMPK, while buthionine sulphoximine (BSO) and N-acetyl cysteine (NAC) assessed GSH inhibition and supplementation respectively.	Metformin	61-70	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
33208818-6	2020	AMPK agonist Epi determined direct effects on the alpha1-AR, metformin was used as an activator for AMPK, while buthionine sulphoximine (BSO) and N-acetyl cysteine (NAC) assessed GSH inhibition and supplementation respectively.	Metformin	61-70	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	100-104
33200330-1	2020	Metformin is an activator of the AMPK and Nrf2 pathways which are important in the pathology of several complex pulmonary diseases with unmet medical needs.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	33-37
33067969-6	2020	CONCLUSION: Metformin inhibits the proliferation of SKM-1 cells, which may relate with AMPK-induced cell cycle arrest.	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	87-91
32991321-8	2020	Finally, metformin, an anti-aging agent, activated the YAP-CDK6 pathway and suppressed D-gal-induced senescence of C6 cells.	Metformin	9-18	Yes1 associated transcriptional regulator	Homo sapiens	55-58
33178015-5	2020	Metformin induces its beneficial effects in diabetes through the activation of a master switch kinase named AMP-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	108-136
28730645-7	2018	Metformin pre-treatment reduced MDA and caspase-3 levels and normalised antioxidant enzyme activities 4 hr after detorsion, and germ cell apoptosis was significantly decreased, and the MSTD, as well as sperm functions, was significantly improved.	Metformin	0-9	caspase 3	Rattus norvegicus	40-49
29456855-1	2018	Metformin, the drug of choice in the treatment of type 2 diabetes mellitus (DM2), in addition to aspirin (ASA), the drug prescribed for cardioprotection of diabetic and non-diabetic patients, have an inhibitory effect on cancer cell survival.	Metformin	0-9	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	76-79
29456855-5	2018	A total of 515 CRC patients without DM2 and 156 with DM2 treated with metformin were enrolled in the study.	Metformin	70-79	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	53-56
29456855-7	2018	The five-year relative survival for stage III CRC was 101% [95% confidence interval (CI)=76-126] in the 18 patients with DM2 treated with metformin and ASA, 55% (95% CI=31-78) in the 23 without DM2 treated with ASA, 55% (95% CI=45-65) in the 150 without DM2 not taking ASA, and 29% (95% CI=13-45) in the 43 with DM2 treated with metformin, however not with ASA.	Metformin	138-147	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	121-124
29162538-0	2018	Metformin promotes the proliferation and differentiation of murine preosteoblast by regulating the expression of sirt6 and oct4.	Metformin	0-9	POU domain, class 5, transcription factor 1, related sequence 1	Mus musculus	123-127
29162538-4	2018	In our research, we show that metformin can promote proliferation of murine preosteoblast by regulating AMPK-mTORC2 and AKT-mTORC1 signaling axis.	Metformin	30-39	CREB regulated transcription coactivator 2	Mus musculus	109-115
29162538-4	2018	In our research, we show that metformin can promote proliferation of murine preosteoblast by regulating AMPK-mTORC2 and AKT-mTORC1 signaling axis.	Metformin	30-39	CREB regulated transcription coactivator 1	Mus musculus	124-130
29472557-6	2018	Metformin reduced cyclin D1 expression and RB, STAT3, STAT5, ERK1/2 and p70S6K phosphorylation.	Metformin	0-9	cyclin D1	Homo sapiens	18-27
29472557-9	2018	In conclusion, metformin exerts multitarget antileukemia activity in MPN: downregulation of JAK2/STAT signaling and mitochondrial activity.	Metformin	15-24	Janus kinase 2	Homo sapiens	92-96
29449537-2	2018	Metformin acts mainly by phosphorylation of AMPK.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	44-48
28935544-10	2018	In vivo, we discovered that metformin not only decreased the serum level of the pro-inflammatory cytokines IL-6 and TNF-alpha but also lowered the expression of the M1 macrophage markers CD11c and MCP-1 in adipose tissue.	Metformin	28-37	integrin alpha X	Mus musculus	187-192
33178015-5	2020	Metformin induces its beneficial effects in diabetes through the activation of a master switch kinase named AMP-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	138-142
33178015-8	2020	Since metformin is a disease-modifying drug in type 2 diabetes, which reduces the mTORC1 signaling to induce its effects on neuronal plasticity, it was proposed that these mechanisms could also explain the antinociceptive effect of this drug in several models of chronic pain.	Metformin	6-15	CREB regulated transcription coactivator 1	Mus musculus	82-88
33173745-7	2020	Moreover, treatment with metformin decreases NR2F6 expression in obese mice, resulting in suppression of CD36 and reduced hepatic TG contents.	Metformin	25-34	nuclear receptor subfamily 2, group F, member 6	Mus musculus	45-50
32800550-6	2020	Inhibition of AMPK by siRNA adversely affected the anti-calcification effects of metformin, resveratrol, and exendin-4 and reversed the reduction of the expression of Rankl by metformin and exendin-4 in the Pi-treated VSMCs.	Metformin	176-185	TNF superfamily member 11	Rattus norvegicus	167-172
32911743-0	2020	Metformin Suppresses Cancer Stem Cells through AMPK Activation and Inhibition of Protein Prenylation of the Mevalonate Pathway in Colorectal Cancer.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	47-51
32911743-1	2020	Metformin is a well-known AMPK (AMP-activated protein kinase) activator that suppresses cancer stem cells (CSCs) in some cancers.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	26-30
32911743-1	2020	Metformin is a well-known AMPK (AMP-activated protein kinase) activator that suppresses cancer stem cells (CSCs) in some cancers.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	32-60
32911743-11	2020	Metformin treatment increased p-AMPK and decreased mTOR (pS6) expression; these effects were reversed by addition of mevalonate.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	32-36
32911743-15	2020	In conclusion, the CSC-suppressive effect of metformin was associated with AMPK activation and repression of protein prenylation through MVA pathway suppression in colorectal cancer.	Metformin	45-54	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	75-79
32899806-1	2020	Metformin is an oral antihyperglycemic drug widely used to treat type 2 diabetes, acting via indirect activation of 5" Adenosine Monophosphate-activated Protein Kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	119-167
32899806-1	2020	Metformin is an oral antihyperglycemic drug widely used to treat type 2 diabetes, acting via indirect activation of 5" Adenosine Monophosphate-activated Protein Kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	169-173
32899806-4	2020	The current understanding of these AMPK effects provides a strong rationale for metformin repurposing in the management of autoimmune and inflammatory conditions.	Metformin	80-89	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	35-39
33042621-0	2020	Metformin activates the STING/IRF3/IFN-beta pathway by inhibiting AKT phosphorylation in pancreatic cancer.	Metformin	0-9	interferon regulatory factor 3	Mus musculus	30-34
33042621-4	2020	Metformin also activated the STING/IRF3/IFN-beta pathway by inhibiting AKT signaling in PDAC cells.	Metformin	0-9	interferon regulatory factor 3	Mus musculus	35-39
33081905-12	2020	The possible mechanism is that metformin could inhibit cytokine storm via suppressing interleukin-6 (IL-6) signaling, prevent the process of lung fibrosis, suppress endocytosis, thereby elevating angiotensin converting enzyme 2 (ACE2) expression.	Metformin	31-40	angiotensin converting enzyme 2	Homo sapiens	196-227
33081905-12	2020	The possible mechanism is that metformin could inhibit cytokine storm via suppressing interleukin-6 (IL-6) signaling, prevent the process of lung fibrosis, suppress endocytosis, thereby elevating angiotensin converting enzyme 2 (ACE2) expression.	Metformin	31-40	angiotensin converting enzyme 2	Homo sapiens	229-233
32825760-4	2020	Among the latter, the antidiabetic drug metformin exerts antitumor activity via the activation of AMPK and the subsequent inhibition of mTOR signaling.	Metformin	40-49	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	98-102
32780768-4	2020	The longitudinal blood-derived transcriptome analysis revealed metformin-induced differential expression of novel and previously described genes involved in cholesterol homeostasis (SLC46A1 and LRP1), cancer development (CYP1B1, STAB1, CCR2, TMEM176B), and immune responses (CD14, CD163) after administration of metformin for three months.	Metformin	63-72	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	221-227
32780768-4	2020	The longitudinal blood-derived transcriptome analysis revealed metformin-induced differential expression of novel and previously described genes involved in cholesterol homeostasis (SLC46A1 and LRP1), cancer development (CYP1B1, STAB1, CCR2, TMEM176B), and immune responses (CD14, CD163) after administration of metformin for three months.	Metformin	63-72	CD14 molecule	Homo sapiens	275-279
32472157-3	2020	Hepatic and renal uptake of metformin is mediated by organic cation transporter 1 (OCT1) and OCT2, respectively, and its renal excretion by multidrug and toxin extrusion 1 (MATE1) and MATE2-K.	Metformin	28-37	solute carrier family 47 member 2	Homo sapiens	184-191
32321715-0	2020	AMPK activation by metformin promotes survival of dormant ER+ breast cancer cells.	Metformin	19-28	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
32321715-7	2020	While the anti-diabetes AMPK-activating drug metformin slowed the estrogen-driven growth of cells and tumors, metformin promoted the persistence of estrogen-deprived cells and tumors through increased mitochondrial respiration driven by fatty acid oxidation.	Metformin	45-54	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	24-28
32765083-0	2020	Metformin Induces Autophagy via the AMPK-mTOR Signaling Pathway in Human Hepatocellular Carcinoma Cells.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	36-40
32765083-2	2020	Our study was designed to determine the effect of metformin on the cell autophagy and autophagic flux via the AMPK-mTOR signaling pathway in human hepatocellular carcinoma (HCC) cells.	Metformin	50-59	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	110-114
32765083-8	2020	In metformin-induced autophagy, AMPK expression was activated, and the phosphorylation levels of mTOR and p70 S6 Kinase were inhibited.	Metformin	3-12	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	32-36
32765083-9	2020	Metformin treatment and mCherry-GFP-LC3B plasmid transfection showed that metformin could induce the autophagic flux.	Metformin	74-83	microtubule associated protein 1 light chain 3 beta	Homo sapiens	36-40
32765083-11	2020	Conclusion: Metformin could induce the autophagy, autophagic flux, and activate the AMPK-mTOR signaling pathway in human HCC cells.	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	84-88
32631337-15	2020	CONCLUSION: In a nationwide cohort of metformin-treated T2D patients and no history of cardiovascular events, the addition of either GLP-1 RA or SGLT-2 inhibitor to metformin treatment was associated with a similar risk of hospitalisation for HF and death, and a lower risk of MACE for GLP-1 RA when compared with add-on DPP-4 inhibitors.	Metformin	38-47	glucagon like peptide 1 receptor	Homo sapiens	133-138
32627027-12	2020	Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells.	Metformin	145-154	SMAD family member 2	Homo sapiens	49-56
32627027-12	2020	Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells.	Metformin	172-181	SMAD family member 2	Homo sapiens	49-56
32609649-7	2020	An association was also found between the GA genotype of SLC47A2 rs12943590 and a decreased response to metformin therapy after correction (OR=2.29, 95% CI [1.01-5.21], p-value=0.01).	Metformin	104-113	solute carrier family 47 member 2	Homo sapiens	57-64
32681778-7	2020	An association was also found between the GA genotype of SLC47A2 rs12943590 and a decreased response to metformin therapy after correction (OR=2.29, 95% CI [1.01-5.21], p-value=0.01).	Metformin	104-113	solute carrier family 47 member 2	Homo sapiens	57-64
32556103-7	2020	Taken together, these observations confirm that UA is involved in the aetiology of metabolic abnormalities in adipose tissue by regulating leptin-AMPK pathway,and metformin could lessen HUA-induced serum FFA elevation and insulin resistance by improving adipose tissue function via AMPK activation.	Metformin	163-172	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	282-286
32670025-5	2020	We also identified the underlying molecular and cellular mechanism that metformin prevented Cdk5 hyper-activation by inhibiting the calpain-dependent cleavage of p35 into p25.	Metformin	72-81	cyclin-dependent kinase 5, regulatory subunit 1 (p35)	Mus musculus	162-165
32670025-5	2020	We also identified the underlying molecular and cellular mechanism that metformin prevented Cdk5 hyper-activation by inhibiting the calpain-dependent cleavage of p35 into p25.	Metformin	72-81	cyclin-dependent kinase 5, regulatory subunit 1 (p35)	Mus musculus	171-174
32670025-6	2020	Moreover, chronic metformin treatment rescued the core phenotypes in APP/PS1 mice as evidenced by restored spine density, surface GluA1 trafficking, Long-term potentiation (LTP) expression, and spatial memory.	Metformin	18-27	glutamate receptor, ionotropic, AMPA1 (alpha 1)	Mus musculus	130-135
32728616-8	2020	These findings demonstrate that c-Myc activates, whereas AMPK inhibits, TDG-mediated DNA demethylation of the SREBP1 promoter in insulin-promoted and metformin-suppressed cancer progression, respectively.	Metformin	150-159	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	57-61
32360359-0	2020	Metformin inhibits the activation of melanocortin receptors 2 and 3 in vitro: A possible mechanism for its anti-androgenic and weight balancing effects in vivo?	Metformin	0-9	melanocortin 3 receptor	Homo sapiens	37-67
29386513-0	2018	Hexokinase-2 depletion inhibits glycolysis and induces oxidative phosphorylation in hepatocellular carcinoma and sensitizes to metformin.	Metformin	127-136	hexokinase 2	Homo sapiens	0-12
29371695-0	2018	Metformin ameliorates experimental-obesity-associated autoimmune arthritis by inducing FGF21 expression and brown adipocyte differentiation.	Metformin	0-9	fibroblast growth factor 21	Mus musculus	87-92
29371695-8	2018	In addition, metformin increased the production of pAMPK and FGF21.	Metformin	13-22	fibroblast growth factor 21	Mus musculus	61-66
29351188-8	2018	Metformin promoted HUVEC migration and inhibited apoptosis via upregulation of vascular endothelial growth factor (VEGF) receptors (VEGFR1/R2), fatty acid binding protein 4 (FABP4), ERK/mitogen-activated protein kinase signaling, chemokine ligand 8, lymphocyte antigen 96, Rho kinase 1 (ROCK1), matrix metalloproteinase 16 (MMP16) and tissue factor inhibitor-2 under hyperglycemia-chemical hypoxia.	Metformin	0-9	Rho associated coiled-coil containing protein kinase 1	Homo sapiens	287-292
29351188-9	2018	Therefore, metformin"s dual effect in hyperglycemia-chemical hypoxia is mediated by direct effect on VEGFR1/R2 leading to activation of cell migration through MMP16 and ROCK1 upregulation, and inhibition of apoptosis by increase in phospho-ERK1/2 and FABP4, components of VEGF signaling cascades.	Metformin	11-20	Rho associated coiled-coil containing protein kinase 1	Homo sapiens	169-174
28689771-8	2018	Therapeutic interventions with tacrolimus or metformin normalized the expression of decidual IFNgamma, PGR and FKBP52, increased co-localization of protein inhibitor of activated STATy (PIASy) to PGR and resulted in the upregulation of uterine IL11and LIF.	Metformin	45-54	FK506 binding protein 4	Mus musculus	111-117
30471658-6	2018	The maximum concentrations of metformin and guanylurea in surface water samples were as high as 59,000 and 4502ngL-1, respectively.	Metformin	30-39	Netrin-G1 ligand	Salmo salar	111-116
30786670-3	2018	Metformin improved cell viability, reduced the fraction of apoptotic nuclei, and inhibited the activation of the executive caspase-3.	Metformin	0-9	caspase 3	Rattus norvegicus	123-132
29131093-0	2018	Metformin for Rapidly Maturing Girls with Central Adiposity: Less Liver Fat and Slower Bone Maturation.	Metformin	0-9	FAT atypical cadherin 1	Homo sapiens	72-75
29131093-6	2018	Metformin-treated girls gained more height per bone-age year and had less visceral and hepatic fat.	Metformin	0-9	FAT atypical cadherin 1	Homo sapiens	95-98
29148173-0	2018	Metformin protects against intestinal barrier dysfunction via AMPKalpha1-dependent inhibition of JNK signalling activation.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	62-72
29148173-4	2018	We showed that metformin alleviated dextran sodium sulphate (DSS)-induced decreases in transepithelial electrical resistance, FITC-dextran hyperpermeability, loss of the tight junction (TJ) proteins occludin and ZO-1 and bacterial translocation in Caco-2 cell monolayers or in colitis mice models.	Metformin	15-24	occludin	Homo sapiens	199-207
29148173-7	2018	In addition, metformin suppressed DSS-induced JNK activation, an effect dependent on AMP-activated protein kinase alpha1 (AMPKalpha1) activation.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	85-120
29148173-7	2018	In addition, metformin suppressed DSS-induced JNK activation, an effect dependent on AMP-activated protein kinase alpha1 (AMPKalpha1) activation.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	122-132
32048246-0	2020	Metformin accelerates myelin recovery and ameliorates behavioral deficits in the animal model of multiple sclerosis via adjustment of AMPK/Nrf2/mTOR signaling and maintenance of endogenous oligodendrogenesis during brain self-repairing period.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	134-138
32048246-4	2020	RESULTS: MET remarkably increased the localization of precursor OLGs (NG2+/O4+ cells) and subsequently the renewal of mature OLGs (MOG+ cells) in the corpus callosum via AMPK/mammalian target of rapamycin (mTOR) pathway.	Metformin	9-12	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	170-174
32048246-8	2020	Molecular modeling studies, likewise, confirmed that MET exerts its effects via direct interaction with AMPK.	Metformin	53-56	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	104-108
32048246-9	2020	CONCLUSIONS: Altogether, our study reveals that MET effectively induces lesion reduction and elevated molecular processes that support myelin recovery via direct activation of AMPK and indirect regulation of AMPK/Nrf2/mTOR pathway in OLGs.	Metformin	48-51	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	176-180
32048246-9	2020	CONCLUSIONS: Altogether, our study reveals that MET effectively induces lesion reduction and elevated molecular processes that support myelin recovery via direct activation of AMPK and indirect regulation of AMPK/Nrf2/mTOR pathway in OLGs.	Metformin	48-51	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	208-212
31904843-8	2020	RESULTS: Metformin enhanced the immunomodulatory functions of Ad-MSCs including IDO, IL-10 and TGF-beta.	Metformin	9-18	transforming growth factor, beta 1	Mus musculus	95-103
31904843-10	2020	STAT1 inhibition by siRNA strongly diminished IDO, IL-10, TGF-beta in metformin-treated Ad-MSCs.	Metformin	70-79	transforming growth factor, beta 1	Mus musculus	58-66
32189544-9	2020	Furthermore, 50mg/kg metformin markedly down-regulated the expression of proinflammatory cytokines (TNF-alpha and IL-1beta) and ER stress related genes (ATF4, ATF6, XBP1, Grp78 and CHOP) in rotenone-induced PD mice.	Metformin	21-30	activating transcription factor 6	Mus musculus	159-163
32460900-0	2020	Elevated de novo protein synthesis in FMRP-deficient human neurons and its correction by metformin treatment.	Metformin	89-98	nuclear FMR1 interacting protein 2	Homo sapiens	38-42
32460900-11	2020	We find that treatment with metformin attenuates the increase in proliferation of FMRP-deficient neural progenitor cells but not the neuronal deficits in neurite outgrowth.	Metformin	28-37	nuclear FMR1 interacting protein 2	Homo sapiens	82-86
32446297-13	2020	Oral administration of a HMG-CoA reductase inhibitor, simvastatin, or an AMPK activator, metformin, to young HFD offspring reversed maternal HFD-programmed increase in AT1R and decreases in SIRT1, PGC-1alpha and TFAM; alleviated ROS production in RVLM, and attenuated sympathoexcitation and hypertension.	Metformin	89-98	angiotensin II receptor, type 1a	Rattus norvegicus	168-172
32446297-13	2020	Oral administration of a HMG-CoA reductase inhibitor, simvastatin, or an AMPK activator, metformin, to young HFD offspring reversed maternal HFD-programmed increase in AT1R and decreases in SIRT1, PGC-1alpha and TFAM; alleviated ROS production in RVLM, and attenuated sympathoexcitation and hypertension.	Metformin	89-98	transcription factor A, mitochondrial	Rattus norvegicus	212-216
32444674-4	2020	These actions depend on metformin-mediated activation of AMP kinase (AMPK).	Metformin	24-33	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	57-67
32444674-4	2020	These actions depend on metformin-mediated activation of AMP kinase (AMPK).	Metformin	24-33	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	69-73
32444674-11	2020	The transcription factor downstream of AMPK that is relevant to cAMP signaling is CREB; decreased levels of phospho-CREB seem to mediate the observed effects of metformin on NaCT.	Metformin	161-170	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	39-43
32433500-8	2020	Metformin treatment on male diabetic placental explant activated AMPK and stimulated PGC-1alpha expression, concomitant with increased H3K27 acetylation and decreased PGC-1alpha promoter methylation.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	65-69
32433500-9	2020	In vivo, we show that maternal metformin treatment along with maternal high fat diet significantly increased mouse placental abundance of PGC-1alpha expression and downstream mitochondrial transcription factor A (TFAM) and inhibited maternal high fat diet-impaired placental efficiency and glucose tolerance in offspring.	Metformin	31-40	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	138-148
32433500-9	2020	In vivo, we show that maternal metformin treatment along with maternal high fat diet significantly increased mouse placental abundance of PGC-1alpha expression and downstream mitochondrial transcription factor A (TFAM) and inhibited maternal high fat diet-impaired placental efficiency and glucose tolerance in offspring.	Metformin	31-40	transcription factor A, mitochondrial	Mus musculus	213-217
32508669-0	2020	Metformin Ameliorates Diabetic Cardiomyopathy by Activating the PK2/PKR Pathway.	Metformin	0-9	prokineticin 2	Mus musculus	64-67
32407182-5	2020	Cell viability was reduced by 50% after 24 h. Data showed that metformin treatment down-regulated YAP and TAZ (p = .002) expressions and enhanced YAP phosphorylation (p < .001).	Metformin	63-72	Yes1 associated transcriptional regulator	Homo sapiens	98-101
32407182-5	2020	Cell viability was reduced by 50% after 24 h. Data showed that metformin treatment down-regulated YAP and TAZ (p = .002) expressions and enhanced YAP phosphorylation (p < .001).	Metformin	63-72	Yes1 associated transcriptional regulator	Homo sapiens	146-149
32407182-8	2020	This study showed the effects of metformin on the inhibition of oncogenic YAP and TAZ in the proliferation of melanoma cells.	Metformin	33-42	Yes1 associated transcriptional regulator	Homo sapiens	74-77
32483456-7	2020	Furthermore, we performed in vivo adult neurogenesis assay with BrdU/EdU labelling and Morris water maze task in both animal models following pharmacological treatments to show the key role of Mgll in metformin-corrected neurogenesis and spatial memory deficits of AD through reactivating the aPKC-CBP pathway.	Metformin	201-210	monoglyceride lipase	Mus musculus	193-197
32483456-12	2020	However, we find that metformin-stimulated aPKC-CBP pathway decreases Mgll expression to recover these deficits in 3xTg-AD.	Metformin	22-31	monoglyceride lipase	Mus musculus	70-74
32523353-0	2020	Metformin Suppresses the Proliferation and Promotes the Apoptosis of Colon Cancer Cells Through Inhibiting the Expression of Long Noncoding RNA-UCA1.	Metformin	0-9	urothelial cancer associated 1	Homo sapiens	144-148
32523353-9	2020	Suppressing UCA1 expression by siRNA or shRNA could further enhance the metformin-mediated anticancer effects against colon cancer in vitro and in vivo.	Metformin	72-81	urothelial cancer associated 1	Homo sapiens	12-16
32523353-10	2020	Metformin decreased the UCA1 expression and further inhibited the proliferation and promoted the apoptosis of the colon cancer cells, which were associated with inactivation of the PI3K/AKT and ERK signaling pathways in vitro and in the tumor tissues obtained from the mice.	Metformin	0-9	urothelial cancer associated 1	Homo sapiens	24-28
32523353-11	2020	Conclusion: These results indicated that metformin has potential anticancer properties and revealed the anticancer mechanisms of metformin against colon cancer via regulating lncRNA-UCA1.	Metformin	41-50	urothelial cancer associated 1	Homo sapiens	182-186
32523353-11	2020	Conclusion: These results indicated that metformin has potential anticancer properties and revealed the anticancer mechanisms of metformin against colon cancer via regulating lncRNA-UCA1.	Metformin	129-138	urothelial cancer associated 1	Homo sapiens	182-186
32404204-6	2020	In contrast, metformin and SGLT2 inhibitors activate SIRT1 and/or AMPK and promote autophagic flux to varying degrees in cardiomyocytes, which may explain their benefits in experimental cardiomyopathy.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	66-70
29614701-4	2018	Numerous dietary supplements and pharmaceuticals (e.g., metformin) that increase AMPK activity are available for use in humans, but clinical studies of their effects in PD patients are limited.	Metformin	56-65	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	81-85
29343628-13	2018	Indeed, some existing drugs such as metformin and aspirin, which were derived from traditional herbal remedies, appear to work, in part, by activating AMPK.	Metformin	36-45	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	151-155
30684325-1	2018	OBJECTIVE: Introduction: The paper presents the findings of our own study on the changes of the systemic inflammation in patients with type 2 diabetes mellitus (DM2) and ischemic heart disease (IHD) during the combination treatment with metformin and pioglitazone.	Metformin	237-246	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	161-164
28964787-0	2017	Negative regulation of Sirtuin 1 by AMP-activated protein kinase promotes metformin-induced senescence in hepatocellular carcinoma xenografts.	Metformin	74-83	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	36-64
28964787-2	2017	Our previous in vitro studies have demonstrated that a low dose of metformin promoted hepatoma cell senescence instead of apoptosis via activation of AMP-activated protein kinase (AMPK) and inactivation of Sirtuin 1 (SIRT1) deacetylase activity.	Metformin	67-76	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	150-178
28964787-2	2017	Our previous in vitro studies have demonstrated that a low dose of metformin promoted hepatoma cell senescence instead of apoptosis via activation of AMP-activated protein kinase (AMPK) and inactivation of Sirtuin 1 (SIRT1) deacetylase activity.	Metformin	67-76	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	180-184
28964787-4	2017	We showed here that persistent exposure to a low concentration of metformin led to AMPK activation in a mouse xenograft model of human hepatocellular carcinoma (HCC), resulting in senescence.	Metformin	66-75	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	83-87
28964787-5	2017	Intriguingly, AMPK counter-regulated SIRT1 via direct phosphorylation in metformin-mediated senescence in hepatoma cells.	Metformin	73-82	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	14-18
28964787-6	2017	Taken together, these findings suggest that a low dose of metformin could potentially be used as a TIS-inducing therapeutic drug for HCC, and that this occurs by inducing senescence of HCC cells via the AMPK-SIRT1 pathway.	Metformin	58-67	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	203-213
29241458-6	2017	Tumors of human ovarian cancer cell lines CP70 and A2780 were established by subcutaneous transplantation of cells in nude mice and the effect of metformin on MRP2 expression and tumor inhibition assessed.	Metformin	146-155	prolactin family 2, subfamily c, member 3	Mus musculus	159-163
29215608-3	2017	Here we report that metformin-exposed mouse fetuses exhibit elevated expression of the H19 long noncoding RNA, which induces hypomethylation and increased expression of hepatocyte nuclear factor 4alpha (HNF4alpha).	Metformin	20-29	H19, imprinted maternally expressed transcript	Mus musculus	87-90
28643448-10	2017	Metformin synchronized the apoptotic proteins such as FasL and antiapoptotic proteins such as Bcl2, Bcl-xL and p21 which can be attributed as the major mechanism of cardioprotection.	Metformin	0-9	Fas ligand	Rattus norvegicus	54-58
28643448-10	2017	Metformin synchronized the apoptotic proteins such as FasL and antiapoptotic proteins such as Bcl2, Bcl-xL and p21 which can be attributed as the major mechanism of cardioprotection.	Metformin	0-9	Bcl2-like 1	Rattus norvegicus	100-106
29040598-11	2017	Metformin had a beneficial effect on HbA1c at 3 months (P = 0.001) and difference in adjusted HbA1c between groups during 12 months was 1.0%; 95% CI 0.4, 1.5 (10.9 mmol/mol; 95% CI 4.4, 16.4), P = 0.001.	Metformin	0-9	hemoglobin subunit alpha 1	Homo sapiens	37-41
29167573-6	2017	The anti-proliferative action of metformin was mediated by two different mechanisms: AMPK activation and increase in the production of reactive oxygen species, which suppressed the mTOR pathway and its downstream targets S6 and 4EBP1.	Metformin	33-42	ribosomal protein S6	Homo sapiens	221-233
29113111-9	2017	Interestingly, the anti-diabetic drug metformin inhibited MXL-3 activation and subsequently prevented glucose-dependent fat accumulation.	Metformin	38-47	Protein mxl-3	Caenorhabditis elegans	58-63
29113111-10	2017	These findings highlight the importance of the MXL-3/SBP-1 axis in the regulation of lipid metabolism during nutritional excess and provide new insight into the mechanism by which metformin prevents lipid accumulation.	Metformin	180-189	Protein mxl-3	Caenorhabditis elegans	47-52
29285270-0	2017	Metformin alleviates nickel-induced autophagy and apoptosis via inhibition of hexokinase-2, activating lipocalin-2, in human bronchial epithelial cells.	Metformin	0-9	hexokinase 2	Homo sapiens	78-90
29285270-5	2017	We attempted to investigate the effects of the antidiabetic drug metformin on HK2 expression and lung cancer chemoprevention.	Metformin	65-74	hexokinase 2	Homo sapiens	78-81
29285270-6	2017	Our results showed that metformin decreases nickel-induced autophagy and activation of apoptosis through inhibition of HK2 gene, protein and activity.	Metformin	24-33	hexokinase 2	Homo sapiens	119-122
29285270-12	2017	Taken together, our results demonstrated that metformin alleviates NiCl2-induced autophagy and apoptosis via HK2-driven LCN2 activation in human bronchial epithelial cells.	Metformin	46-55	hexokinase 2	Homo sapiens	109-112
29122080-1	2017	PURPOSE: Activation of adenosine monophosphate-activated protein kinase (AMPK) by metformin, as a master regulator of metabolism, is involved in airway tissue remodeling.	Metformin	82-91	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	23-71
29122080-1	2017	PURPOSE: Activation of adenosine monophosphate-activated protein kinase (AMPK) by metformin, as a master regulator of metabolism, is involved in airway tissue remodeling.	Metformin	82-91	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	73-77
29122080-7	2017	RESULTS: Metformin, an activator of AMPK, significantly inhibited cell migration in NPDFs in a dose-dependent manner.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	36-40
29122080-8	2017	Compound C, an inhibitor of AMPK, partially reversed the inhibitory effect of metformin.	Metformin	78-87	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	28-32
29122080-9	2017	Metformin also significantly decreased contractile activity, with a concomitant reduction in the production of MMP-1 and MMP-2 but not of MMP-9.	Metformin	0-9	matrix metallopeptidase 2	Homo sapiens	121-126
28828705-0	2017	Glucotoxicity promotes aberrant activation and mislocalization of Ras-related C3 botulinum toxin substrate 1 [Rac1] and metabolic dysfunction in pancreatic islet beta-cells: reversal of such metabolic defects by metformin.	Metformin	212-221	Rac family small GTPase 1	Rattus norvegicus	110-114
28828705-7	2017	Finally, our findings suggest that metformin, a biguanide anti-diabetic drug, at a clinically relevant concentration, prevents beta-cell defects [Rac1 activation, nuclear association, CD36 expression, stress kinase and caspase-3 activation, and loss in metabolic viability] under the duress of glucotoxicity.	Metformin	35-44	Rac family small GTPase 1	Rattus norvegicus	146-150
28791738-0	2017	Metformin promotes neuronal differentiation and neurite outgrowth through AMPK activation in human bone marrow-mesenchymal stem cells.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	74-78
28791738-1	2017	Metformin is an AMP-activated kinase (AMPK) activator that plays a role in glucose energy metabolism and cell protection.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	16-36
28791738-1	2017	Metformin is an AMP-activated kinase (AMPK) activator that plays a role in glucose energy metabolism and cell protection.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	38-42
28791738-3	2017	In this study, we investigated whether AMPK activation upon treatment with metformin may promote neurite outgrowth during the progression of neuronal differentiation in human bone marrow-mesenchymal stem cells (hBM-MSCs).	Metformin	75-84	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	39-43
28791738-9	2017	Thus, metformin treatment promotes neuronal differentiation and neurite outgrowth in hBM-MSCs through AMPK activation.	Metformin	6-15	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	102-106
28985579-1	2017	PURPOSE: In 2015, we published a study on a small series of patients with hepatocellular carcinoma (HCC) treated chronically with metformin for type II diabetes mellitus (DM2) who showed a poorer response to sorafenib.	Metformin	130-139	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	171-174
29063276-4	2017	Studies that compared SUs to metformin or newer agents, like GLP-1 agonists and SGLT2 inhibitors, suggest a difference in cardiovascular events, yet this is likely the result of beneficial effects of the latter.	Metformin	29-38	glucagon like peptide 1 receptor	Homo sapiens	61-66
29047344-1	2017	BACKGROUND: Metformin is usually prescribed as first line therapy for type 2 diabetes mellitus (DM2).	Metformin	12-21	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	96-99
29047344-3	2017	This systematic review examined the available evidence on the safety and efficacy of metformin in the management of DM2 in older adults.	Metformin	85-94	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	116-119
29047344-7	2017	Studies were included if they reported safety or efficacy outcomes with metformin (alone or in combination) for the management of DM2 compared to placebo, usual or no treatment, or other antidiabetics.	Metformin	72-81	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	130-133
29047344-14	2017	Four recommendations were developed suggesting to discontinue the use of metformin for the management of DM2 in older adults with risk factors such as age &gt; 80, gastrointestinal complaints during the last year and/or GFR &lt;=60 ml/min.	Metformin	73-82	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	105-108
29047344-15	2017	CONCLUSIONS: On the evidence available, the safety and efficacy profiles of metformin appear to be better, and certainly no worse, than other treatments for the management of DM2 in older adults.	Metformin	76-85	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	175-178
29027899-3	2017	Using a pure in vitro reconstitution system, we demonstrate that metformin acts through the v-ATPase-Ragulator lysosomal pathway to coordinate mTORC1 and AMPK, two hubs governing metabolic programs.	Metformin	65-74	CREB regulated transcription coactivator 1	Mus musculus	143-149
29027899-4	2017	We further show in Caenorhabditis elegans that both v-ATPase-mediated TORC1 inhibition and v-ATPase-AXIN/LKB1-mediated AMPK activation contribute to the lifespan extension effect of metformin.	Metformin	182-191	CREB regulated transcription coactivator 1	Mus musculus	70-75
29254204-9	2017	Metformin treatment also inhibited the expression of fibrotic genes and decreased the phosphorylation of smad2/3 and extracellular signal-regulated kinase (ERK) 1/2.	Metformin	0-9	mitogen activated protein kinase 3	Rattus norvegicus	117-164
28797524-9	2017	CONCLUSION: The combined therapy of SGLT2 inhibitor along with metformin is more effective in HbA1c reduction and weight reduction as compared to monotherapy using metformin alone.	Metformin	63-72	hemoglobin subunit alpha 1	Homo sapiens	94-98
28797524-9	2017	CONCLUSION: The combined therapy of SGLT2 inhibitor along with metformin is more effective in HbA1c reduction and weight reduction as compared to monotherapy using metformin alone.	Metformin	164-173	hemoglobin subunit alpha 1	Homo sapiens	94-98
28664399-12	2017	Furthermore, metformin downregulated the levels of apoptotic factors (p-JNK3, p-c-Jun and cleaved caspase-3) as well as pro-inflammatory cytokines (IL-1beta, IL-4 and IL-6 and TNF-alpha).	Metformin	13-22	interleukin 4	Rattus norvegicus	158-162
32404204-8	2020	Whereas metformin primarily acts as an agonist of AMPK, SGLT2 inhibitors induce a fasting-like state that is accompanied by ketogenesis, a biomarker of enhanced SIRT1 signaling.	Metformin	8-17	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	50-54
32518807-7	2020	An AMPK activator, metformin, inhibited FLS proliferation at higher but not lower concentrations, whereas the inhibitor dorsomorphin promoted the proliferation of RA-FLSs.	Metformin	19-28	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	3-7
32518807-9	2020	After metformin treatment, expression of interleukin 6 (IL-6), TNF-alpha, and IL-1beta were significantly downregulated in RA-FLSs; however, increased expression of p-AMPK-alpha1, protein kinase A (PKA)-alpha1, and HAPLN1 (hyaluronan and proteoglycan link protein 1) was observed.	Metformin	6-15	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	167-178
32393385-8	2020	However, direct activation of AMPK in EOC cells using oligomycin and metformin was insufficient to induce autophagy.	Metformin	69-78	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	30-34
32375255-0	2020	The Metformin Mechanism on Gluconeogenesis and AMPK Activation: The Metabolite Perspective.	Metformin	4-13	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	47-51
32375255-4	2020	The activation of AMPK by metformin could be consequent to Complex 1 inhibition and raised AMP through the canonical adenine nucleotide pathway or alternatively by activation of the lysosomal AMPK pool by other mechanisms involving the aldolase substrate fructose 1,6-bisphosphate or perturbations in the lysosomal membrane.	Metformin	26-35	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	18-22
32375255-4	2020	The activation of AMPK by metformin could be consequent to Complex 1 inhibition and raised AMP through the canonical adenine nucleotide pathway or alternatively by activation of the lysosomal AMPK pool by other mechanisms involving the aldolase substrate fructose 1,6-bisphosphate or perturbations in the lysosomal membrane.	Metformin	26-35	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	192-196
32375255-7	2020	The metabolite changes caused by metformin may also have a prominent role in counteracting G6pc gene regulation in conditions of compromised intracellular homeostasis.	Metformin	33-42	glucose-6-phosphatase catalytic subunit 1	Homo sapiens	91-95
31944615-8	2020	These concentrations of metformin also elevated the levels of phosphorylated AMPK and tyrosine phosphorylation in human spermatozoa.	Metformin	24-33	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	77-81
31944615-9	2020	In addition, activation of AMPK by A769662 (an AMPK activator) had similar effects to metformin on human spermatozoa, while inhibition of AMPK by compound C (an AMPK inhibitor) suppressed the enhancement of metformin on human spermatozoa.	Metformin	207-216	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	27-31
31944615-10	2020	CONCLUSION: Our findings indicate that metformin activates human sperm function through an AMPK-related mechanism which increases tyrosine phosphorylation at therapeutically relevant concentrations, thereby suggesting its improvement on human sperm function when treating subfertile males of type 2 diabetes.	Metformin	39-48	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	91-95
32156705-0	2020	Metformin limits osteoarthritis development and progression through activation of AMPK signalling.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	82-86
32156705-8	2020	RESULTS: Metformin upregulated phosphorylated and total AMPK expression in articular cartilage tissue.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	56-60
32229156-7	2020	Since most of the DM2 patients are treated with drugs to reduce glycemia, we investigated whether glyburide, metformin or insulin were able to induce any change regarding RNase 7 production.	Metformin	109-118	ribonuclease A family member 7	Homo sapiens	171-178
32229156-8	2020	Results showed that metformin reduces the expression of RNase 7 in in vitro treated keratinocytes, suggesting that the chronic use of metformin should be evaluated in DFU patients, whereas calcitriol, phenyl butyrate and L-isoleucine did not increase the RNase 7 production.	Metformin	20-29	ribonuclease A family member 7	Homo sapiens	56-63
32229156-8	2020	Results showed that metformin reduces the expression of RNase 7 in in vitro treated keratinocytes, suggesting that the chronic use of metformin should be evaluated in DFU patients, whereas calcitriol, phenyl butyrate and L-isoleucine did not increase the RNase 7 production.	Metformin	20-29	ribonuclease A family member 7	Homo sapiens	255-262
32229156-8	2020	Results showed that metformin reduces the expression of RNase 7 in in vitro treated keratinocytes, suggesting that the chronic use of metformin should be evaluated in DFU patients, whereas calcitriol, phenyl butyrate and L-isoleucine did not increase the RNase 7 production.	Metformin	134-143	ribonuclease A family member 7	Homo sapiens	56-63
32070877-6	2020	Moreover, we also observed the involvement of ARL4C in metformin-inhibited cellular proliferation of endometrial cancer.	Metformin	55-64	ADP ribosylation factor like GTPase 4C	Homo sapiens	46-51
28754674-10	2017	High-dose metformin inhibited GM-CSF and MMP9 release from WAT progenitors in in vitro and xenograft models.	Metformin	10-19	matrix metallopeptidase 9	Mus musculus	41-45
28754674-11	2017	In obese syngeneic mice, metformin treatment mimicked the effects observed with GM-CSF neutralization and MMP9 inhibition, suggesting these proteins as new targets for metformin.	Metformin	25-34	matrix metallopeptidase 9	Mus musculus	106-110
28754674-11	2017	In obese syngeneic mice, metformin treatment mimicked the effects observed with GM-CSF neutralization and MMP9 inhibition, suggesting these proteins as new targets for metformin.	Metformin	168-177	matrix metallopeptidase 9	Mus musculus	106-110
28755883-0	2017	Metformin: Insights into its anticancer potential with special reference to AMPK dependent and independent pathways.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	76-80
28755883-3	2017	Metformin targets many pathways that play an important role in cancer cell proliferation and angiogenesis, mTORC1 signaling is a crucial pathway among them.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	107-113
28755883-4	2017	Metformin inhibits mTORC1 via AMPK dependent and AMPK independent pathways, thereby inhibiting cancer cell growth and development.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	19-25
28755883-4	2017	Metformin inhibits mTORC1 via AMPK dependent and AMPK independent pathways, thereby inhibiting cancer cell growth and development.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	30-34
28755883-4	2017	Metformin inhibits mTORC1 via AMPK dependent and AMPK independent pathways, thereby inhibiting cancer cell growth and development.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	49-53
28755883-7	2017	Here, we review both AMPK dependent and AMPK independent mechanisms involved in anticancer activity of metformin along with the outcome of preclinical and clinical studies.	Metformin	103-112	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	21-25
28755883-7	2017	Here, we review both AMPK dependent and AMPK independent mechanisms involved in anticancer activity of metformin along with the outcome of preclinical and clinical studies.	Metformin	103-112	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	40-44
28776086-5	2017	Metformin has been shown to act via both AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms; by inhibition of mitochondrial respiration but also perhaps by inhibition of mitochondrial glycerophosphate dehydrogenase, and a mechanism involving the lysosome.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	41-69
28776086-5	2017	Metformin has been shown to act via both AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms; by inhibition of mitochondrial respiration but also perhaps by inhibition of mitochondrial glycerophosphate dehydrogenase, and a mechanism involving the lysosome.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	71-75
28776086-5	2017	Metformin has been shown to act via both AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms; by inhibition of mitochondrial respiration but also perhaps by inhibition of mitochondrial glycerophosphate dehydrogenase, and a mechanism involving the lysosome.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	91-95
28776086-6	2017	In the last 10 years, we have moved from a simple picture, that metformin improves glycaemia by acting on the liver via AMPK activation, to a much more complex picture reflecting its multiple modes of action.	Metformin	64-73	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	120-124
28589542-5	2017	Drug-naive people with T2D do often show surprisingly strong reductions in HbA1c with metformin-based dual-agent oral treatment approaches; a recent report showed that even with baseline HbA1c &gt;11%, the combination of metformin with a sulfonylurea, pioglitazone, or sitagliptin was associated with reduction in HbA1c from 11.6% to 6.0%.	Metformin	86-95	hemoglobin subunit alpha 1	Homo sapiens	75-79
28589542-5	2017	Drug-naive people with T2D do often show surprisingly strong reductions in HbA1c with metformin-based dual-agent oral treatment approaches; a recent report showed that even with baseline HbA1c &gt;11%, the combination of metformin with a sulfonylurea, pioglitazone, or sitagliptin was associated with reduction in HbA1c from 11.6% to 6.0%.	Metformin	221-230	hemoglobin subunit alpha 1	Homo sapiens	75-79
32258714-0	2017	Metformin interferes with glucose cellular uptake by both estrogen and progesterone receptor-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer cell lines: PS156.	Metformin	0-9	progesterone receptor	Homo sapiens	71-92
29100387-6	2017	Results indicate that 2DG alone or in combination with metformin was effective at inducing cell death in EWS cell lines.	Metformin	55-64	EWS RNA binding protein 1	Homo sapiens	105-108
28900501-0	2017	Metformin Sensitizes Leukemia Cells to Vincristine via Activation of AMP-activated Protein Kinase.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	69-97
28900501-8	2017	We further demonstrated that metformin sensitized leukemia cells to vincristine-induced apoptosis in an AMPK-dependent manner.	Metformin	29-38	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	104-108
28900501-9	2017	In addition, knockdown of AMPKalpha1 significantly reduced the effects of metformin on vincristine-induced apoptosis.	Metformin	74-83	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	26-36
28900501-10	2017	Taken together, these results indicate that AMPK activation is critical in metformin effects on vincristine-induced apoptosis and suggest a putative strategy of a combination therapy using metformin and vincristine in treatment of leukemia.	Metformin	75-84	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	44-48
28900501-10	2017	Taken together, these results indicate that AMPK activation is critical in metformin effects on vincristine-induced apoptosis and suggest a putative strategy of a combination therapy using metformin and vincristine in treatment of leukemia.	Metformin	189-198	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	44-48
28827783-4	2017	The CCDC3 expression is markedly reduced in TAp63-null mouse embryonic fibroblasts and brown adipose tissues and by tumor necrosis factor alpha that reduces p63 transcriptional activity, but induced by metformin, an anti-diabetic drug that activates p63.	Metformin	202-211	coiled-coil domain containing 3	Mus musculus	4-9
28801373-1	2017	Metformin has been proposed as a novel anti-cancer drug for adrenocortical carcinoma (ACC) based upon Poli"s recent preclinical studies that 1.	Metformin	0-9	DNA polymerase iota	Homo sapiens	102-106
28733377-2	2017	GLP-1 RAs Should Replace Metformin in the Type 2 Diabetes Algorithm.	Metformin	25-34	glucagon like peptide 1 receptor	Homo sapiens	0-5
28359870-7	2017	The adsorption kinetic experiments revealed that almost 80% removal of metformin was achieved within 20 min for all the doses studied, corresponding to the relatively high k1 (0.232 min-1) and k2 (0.007 g mg-1 min-1) values in the kinetic models.	Metformin	71-80	mucin 5B, oligomeric mucus/gel-forming	Homo sapiens	205-215
28438778-10	2017	Furthermore, KBP-042 was efficient in combination with metformin and had additional effects compared with either therapy alone.	Metformin	55-64	serine (or cysteine) proteinase inhibitor, clade A, member 3C	Rattus norvegicus	13-16
28438778-11	2017	In conclusion, KBP-042 is a highly relevant therapeutic candidate against type 2 diabetes, effective both as an add-on therapy to metformin and as a stand-alone therapy.	Metformin	130-139	serine (or cysteine) proteinase inhibitor, clade A, member 3C	Rattus norvegicus	15-18
31990206-2	2020	The objective of this retrospective observational cohort study is to better characterize the distance between HbA1c target and patient"s actual HbA1c level (the distance to goal), using a target HbA1c of 7.0% (53 mmol/mol), in patients with T2DM who have started metformin monotherapy.Methods: We used data from the GE Centricity Electronic Medical Record database by IQVIA in the United States (US) to identify adults with T2DM who started metformin monotherapy (MM) and received at least 90 days of treatment.	Metformin	263-272	hemoglobin subunit alpha 1	Homo sapiens	110-114
29026839-4	2017	FINDINGS: Baseline metformin use provided significant OS and DFS benefit in ST but not in AML (KM: PST-OS= 0.003; PST-DFS= 0.002; PAML-OS= 0.961; PAML-DFS= 0.943).	Metformin	19-28	sulfotransferase family 1A member 1	Homo sapiens	99-102
29026839-6	2017	In ST, metformin nonusers had shorter median survival, 57.7 versus 86 months, and poorer outcomes (HRST-OS= 1.33; PST-OS= 0.002; HRST-DFS= 1.32; PST-DFS= 0.002).	Metformin	7-16	sulfotransferase family 1A member 1	Homo sapiens	114-117
29026839-6	2017	In ST, metformin nonusers had shorter median survival, 57.7 versus 86 months, and poorer outcomes (HRST-OS= 1.33; PST-OS= 0.002; HRST-DFS= 1.32; PST-DFS= 0.002).	Metformin	7-16	sulfotransferase family 1A member 1	Homo sapiens	145-148
27167128-7	2017	But, metformin treatment attenuated the accumulation of p62 and ubiquitinated proteins, suggesting a stimulative effect of autophagy flux by metformin.	Metformin	5-14	KH RNA binding domain containing, signal transduction associated 1	Rattus norvegicus	56-59
28323512-4	2017	The cost associated with a 1% placebo-adjusted HbA1c reduction with each SGLT2 inhibitor as add-on to metformin was calculated based on NMA results and UAE drug costs.	Metformin	102-111	hemoglobin subunit alpha 1	Homo sapiens	47-51
28404659-0	2017	Early Glycemic Control and Magnitude of HbA1c Reduction Predict Cardiovascular Events and Mortality: Population-Based Cohort Study of 24,752 Metformin Initiators.	Metformin	141-150	hemoglobin subunit alpha 1	Homo sapiens	40-44
31990206-2	2020	The objective of this retrospective observational cohort study is to better characterize the distance between HbA1c target and patient"s actual HbA1c level (the distance to goal), using a target HbA1c of 7.0% (53 mmol/mol), in patients with T2DM who have started metformin monotherapy.Methods: We used data from the GE Centricity Electronic Medical Record database by IQVIA in the United States (US) to identify adults with T2DM who started metformin monotherapy (MM) and received at least 90 days of treatment.	Metformin	441-450	hemoglobin subunit alpha 1	Homo sapiens	110-114
32372097-0	2020	Metformin inhibits testosterone-induced endoplasmic reticulum stress in ovarian granulosa cells via inactivation of p38 MAPK.	Metformin	0-9	mitogen-activated protein kinase 14	Mus musculus	116-124
32372097-2	2020	SUMMARY ANSWER: Metformin inhibits testosterone-induced ER stress and unfolded protein response (UPR) activation by suppressing p38 MAPK phosphorylation in ovarian GCs.	Metformin	16-25	mitogen-activated protein kinase 14	Mus musculus	128-136
32372097-17	2020	Metformin inhibited ER stress activation was associated with decreased p-p38 MAPK levels.	Metformin	0-9	mitogen-activated protein kinase 14	Mus musculus	73-81
32372097-20	2020	These effects were reversed by treatment with metformin, an ER stress inhibitor or by knockdown of p38 MAPK.	Metformin	46-55	mitogen-activated protein kinase 14	Mus musculus	99-107
31525254-9	2020	Given this finding, we treated these animals with metformin, which enhances AMPK activity.	Metformin	50-59	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	76-80
31525254-10	2020	Here, we show for the first time, metformin activates AMPK signaling and inhibits tumor growth of Nischarin lacking PyMT tumors suggesting a potential use for metformin as a cancer therapeutic, particularly in the case of Nischarin-deficient breast cancers.	Metformin	34-43	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	54-58
32276962-7	2020	Metformin is an established AMPK agonist that can promote autophagy, but its effects on the course of CKD have been demonstrated only in the experimental setting.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	28-32
32281270-3	2020	Metformin (MET), a first-line diabetes medication that also has anti-tumour activities, induces AMP-activated protein kinase (AMPK), directly phosphorylates YAP and inhibits YAP transcriptional activity.	Metformin	0-9	Yes1 associated transcriptional regulator	Homo sapiens	157-160
32281270-3	2020	Metformin (MET), a first-line diabetes medication that also has anti-tumour activities, induces AMP-activated protein kinase (AMPK), directly phosphorylates YAP and inhibits YAP transcriptional activity.	Metformin	0-9	Yes1 associated transcriptional regulator	Homo sapiens	174-177
32092034-9	2020	Metformin reduced the expression levels of renal cortical FOXO1 and CREB.	Metformin	0-9	forkhead box O1	Rattus norvegicus	58-63
32221038-0	2020	Metformin Enhances the Antitumor Activity of CD8+ T Lymphocytes via the AMPK-miR-107-Eomes-PD-1 Pathway.	Metformin	0-9	programmed cell death 1	Homo sapiens	91-95
32221038-5	2020	In addition, AMP-activated protein kinase (AMPK) activation decreased microRNA-107 expression, thus enhancing Eomesodermin expression, which suppressed the transcription of PDCD1 in metformin-treated CD8+ T cells.	Metformin	182-191	microRNA 107	Homo sapiens	70-82
32221038-5	2020	In addition, AMP-activated protein kinase (AMPK) activation decreased microRNA-107 expression, thus enhancing Eomesodermin expression, which suppressed the transcription of PDCD1 in metformin-treated CD8+ T cells.	Metformin	182-191	programmed cell death 1	Homo sapiens	173-178
32086387-5	2020	Pharmacological activation of AMPK using 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), metformin, and a specific AMPKalpha activator (GSK621) attenuated ZIKV replication.	Metformin	96-105	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	30-34
32500011-6	2020	Results: OPN increased significantly in the diabetic group in comparison with control (p<0.001), metformin-treated (p=0.008) and pioglitazone-treated groups (p< 0.001).	Metformin	97-106	secreted phosphoprotein 1	Rattus norvegicus	9-12
32500011-9	2020	Treatment with pioglitazone and metformin improved the level of OPN and alpha3beta1 integrin proteins while pioglitazone was more effective.	Metformin	32-41	secreted phosphoprotein 1	Rattus norvegicus	64-67
32269725-0	2020	Metformin ameliorates bleomycin-induced pulmonary fibrosis in mice by suppressing IGF-1.	Metformin	0-9	insulin-like growth factor 1	Mus musculus	82-87
32269725-3	2020	Metformin, a commonly used oral antidiabetic agent, is known to inhibit IGF-1 by the reversal of hyperinsulinemia.	Metformin	0-9	insulin-like growth factor 1	Mus musculus	72-77
31974165-1	2020	The chronic effects of metformin on liver gluconeogenesis involve repression of the G6pc gene, which is regulated by the carbohydrate-response element-binding protein through raised cellular intermediates of glucose metabolism.	Metformin	23-32	glucose-6-phosphatase, catalytic	Mus musculus	84-88
28407669-10	2017	Furthermore, metformin reduced serum insulin as well as IGF-1, and also suppressed expression of insulin receptor, IGF-1, IGF-1 receptor and several pro-inflammatory cytokines mRNAs in stomach of db/db mice, but did not significantly influence IGF-2 and IGF-2 receptor expressions.	Metformin	13-22	insulin-like growth factor 1	Mus musculus	56-61
28407669-10	2017	Furthermore, metformin reduced serum insulin as well as IGF-1, and also suppressed expression of insulin receptor, IGF-1, IGF-1 receptor and several pro-inflammatory cytokines mRNAs in stomach of db/db mice, but did not significantly influence IGF-2 and IGF-2 receptor expressions.	Metformin	13-22	insulin receptor	Mus musculus	97-113
28407669-10	2017	Furthermore, metformin reduced serum insulin as well as IGF-1, and also suppressed expression of insulin receptor, IGF-1, IGF-1 receptor and several pro-inflammatory cytokines mRNAs in stomach of db/db mice, but did not significantly influence IGF-2 and IGF-2 receptor expressions.	Metformin	13-22	insulin-like growth factor 1	Mus musculus	115-120
28407669-10	2017	Furthermore, metformin reduced serum insulin as well as IGF-1, and also suppressed expression of insulin receptor, IGF-1, IGF-1 receptor and several pro-inflammatory cytokines mRNAs in stomach of db/db mice, but did not significantly influence IGF-2 and IGF-2 receptor expressions.	Metformin	13-22	insulin-like growth factor 1	Mus musculus	115-120
28407669-11	2017	The results show that metformin can prevent the risk of gastric cancer in type 2 diabetes and the protective mechanisms may involve in an inhibitory effect of metformin on insulin as well as IGF-1 signals and cancer related pro-inflammatory cytokines.	Metformin	22-31	insulin-like growth factor 1	Mus musculus	191-196
28410530-0	2017	Metformin attenuated endotoxin-induced acute myocarditis via activating AMPK.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	72-76
28410530-4	2017	Treatment with metformin also alleviated the histological abnormalities in the heart, suppressed the upregulation of myeloperoxidase (MPO), decreased the elevation of creatinine kinase-myocardial band (CK-MB) and brain natriuretic peptide (BNP).	Metformin	15-24	natriuretic peptide B	Homo sapiens	213-238
28410530-4	2017	Treatment with metformin also alleviated the histological abnormalities in the heart, suppressed the upregulation of myeloperoxidase (MPO), decreased the elevation of creatinine kinase-myocardial band (CK-MB) and brain natriuretic peptide (BNP).	Metformin	15-24	natriuretic peptide B	Homo sapiens	240-243
28410530-5	2017	Treatment with metformin promoted the phosphorylation of the catalytic alpha subunit of adenosine 5"-monophosphate-activated protein kinase (AMPKalpha), co-administration of AMPK inhibitor suppressed the stimulatory effects of metformin on AMPKalpha phosphorylation.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	141-145
28410530-5	2017	Treatment with metformin promoted the phosphorylation of the catalytic alpha subunit of adenosine 5"-monophosphate-activated protein kinase (AMPKalpha), co-administration of AMPK inhibitor suppressed the stimulatory effects of metformin on AMPKalpha phosphorylation.	Metformin	227-236	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	141-145
28410530-6	2017	Meanwhile, the suppressive effects of metformin on MPO, TNF-alpha, CK-MB and BNP were reversed by the AMPK inhibitor.	Metformin	38-47	natriuretic peptide B	Homo sapiens	77-80
28410530-6	2017	Meanwhile, the suppressive effects of metformin on MPO, TNF-alpha, CK-MB and BNP were reversed by the AMPK inhibitor.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	102-106
28410530-7	2017	On the contrary, administration of AMPK activator mimicked the effects of metformin on AMPKalpha phosphorylation, MPO upregulation, CK-MB release and BNP elevation.	Metformin	74-83	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	35-39
28410530-7	2017	On the contrary, administration of AMPK activator mimicked the effects of metformin on AMPKalpha phosphorylation, MPO upregulation, CK-MB release and BNP elevation.	Metformin	74-83	natriuretic peptide B	Homo sapiens	150-153
28410530-8	2017	These evidence suggested that metformin might provide beneficial effects in endotoxin-induced acute myocarditis via activating AMPK-dependent anti-inflammatory mechanism.	Metformin	30-39	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	127-131
28440424-6	2017	Importantly, metformin reduced the expression of cyclin D1, cyclin E, cyclin-dependent kinase 4, and phosphorylated retinoblastoma protein, which resulted in cell cycle arrest at the G0/G1 phase.	Metformin	13-22	cyclin D1	Homo sapiens	49-58
28440424-6	2017	Importantly, metformin reduced the expression of cyclin D1, cyclin E, cyclin-dependent kinase 4, and phosphorylated retinoblastoma protein, which resulted in cell cycle arrest at the G0/G1 phase.	Metformin	13-22	cyclin dependent kinase 4	Homo sapiens	70-95
31974165-3	2020	Cell metformin loads in the therapeutic range lowered cell G6P but not ATP and decreased G6pc mRNA at high glucose.	Metformin	5-14	glucose-6-phosphatase, catalytic	Mus musculus	89-93
31974165-4	2020	The G6P lowering by metformin was mimicked by a complex 1 inhibitor (rotenone) and an uncoupler (dinitrophenol) and by overexpression of mGPDH, which lowers glycerol 3-phosphate and G6P and also mimics the G6pc repression by metformin.	Metformin	20-29	glucose-6-phosphatase, catalytic	Mus musculus	206-210
31977586-10	2020	It was also shown that LPS increased the mRNA expression levels of Lcn-2 and inflammation-related molecules such as IL-1beta in the amygdala tissue, which could be alleviated by metformin.	Metformin	178-187	lipocalin 2	Mus musculus	67-72
31977586-11	2020	Taken together, metformin mitigates LPS-induced depressive-like behavior in mice by regulating the expression level of Lcn-2 and inflammation-related molecules, including IL-1beta, IL-6 and vWF.Video abstract: http://links.lww.com/WNR/A568.	Metformin	16-25	lipocalin 2	Mus musculus	119-124
31225649-2	2020	Metformin, widely recommended in the management of T2DM, exerts its pleiotropic effects via 5"-AMP-activated protein kinase (AMPK); however, its effect on mitophagy remains elusive.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	125-129
31225649-5	2020	In addition, pretreatment with compound C (an AMPK inhibitor) significantly decreased the expression of mitophagy markers in metformin-treated cells, indicating that metformin induces mitophagy via the AMPK pathway.	Metformin	125-134	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	46-50
31225649-5	2020	In addition, pretreatment with compound C (an AMPK inhibitor) significantly decreased the expression of mitophagy markers in metformin-treated cells, indicating that metformin induces mitophagy via the AMPK pathway.	Metformin	125-134	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	202-206
31225649-5	2020	In addition, pretreatment with compound C (an AMPK inhibitor) significantly decreased the expression of mitophagy markers in metformin-treated cells, indicating that metformin induces mitophagy via the AMPK pathway.	Metformin	166-175	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	46-50
31225649-5	2020	In addition, pretreatment with compound C (an AMPK inhibitor) significantly decreased the expression of mitophagy markers in metformin-treated cells, indicating that metformin induces mitophagy via the AMPK pathway.	Metformin	166-175	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	202-206
32355773-11	2020	Restoration of TET2 following 5-AZA, metformin or VC exposure impaired cell proliferation and migration in vitro.	Metformin	37-46	tet methylcytosine dioxygenase 2	Homo sapiens	15-19
32355824-9	2020	All of the 10 hub genes (CCNA2, CCNB1, MAD2L1, BU1B, RACGAP1, CHEK1, BUB1, ASPM, NCAPG and TTK) have a strong association with lower overall survival in liver cancer patients and four genes (CCNA2, CCNB1, CHEK1 and BUB1) have reduced expression in metformin-treated samples.	Metformin	248-257	non-SMC condensin I complex subunit G	Homo sapiens	81-86
32355824-9	2020	All of the 10 hub genes (CCNA2, CCNB1, MAD2L1, BU1B, RACGAP1, CHEK1, BUB1, ASPM, NCAPG and TTK) have a strong association with lower overall survival in liver cancer patients and four genes (CCNA2, CCNB1, CHEK1 and BUB1) have reduced expression in metformin-treated samples.	Metformin	248-257	TTK protein kinase	Homo sapiens	91-94
31786336-11	2020	In addition, metformin and rotenone (0.1 mumol/L) also reduces reactive oxygen species (ROS) production and increase superoxide dismutase 2 (SOD2) expression.	Metformin	13-22	superoxide dismutase 2	Homo sapiens	117-139
31786336-11	2020	In addition, metformin and rotenone (0.1 mumol/L) also reduces reactive oxygen species (ROS) production and increase superoxide dismutase 2 (SOD2) expression.	Metformin	13-22	superoxide dismutase 2	Homo sapiens	141-145
31786336-12	2020	Our results establish that metformin AMPK-independently protects against palmitate-induced hepatic cell death by moderate inhibition of the mitochondrial respiratory chain, recovering mitochondrial function, decreasing cellular ROS production, and inducing SOD2 expression, indicating that metformin may have beneficial actions beyond its glucose-lowering effect and also suggests that mitochondrial complex I may be a therapeutic target in NAFLD.	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	37-41
31786336-12	2020	Our results establish that metformin AMPK-independently protects against palmitate-induced hepatic cell death by moderate inhibition of the mitochondrial respiratory chain, recovering mitochondrial function, decreasing cellular ROS production, and inducing SOD2 expression, indicating that metformin may have beneficial actions beyond its glucose-lowering effect and also suggests that mitochondrial complex I may be a therapeutic target in NAFLD.	Metformin	27-36	superoxide dismutase 2	Homo sapiens	257-261
31786336-12	2020	Our results establish that metformin AMPK-independently protects against palmitate-induced hepatic cell death by moderate inhibition of the mitochondrial respiratory chain, recovering mitochondrial function, decreasing cellular ROS production, and inducing SOD2 expression, indicating that metformin may have beneficial actions beyond its glucose-lowering effect and also suggests that mitochondrial complex I may be a therapeutic target in NAFLD.	Metformin	290-299	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	37-41
31922237-0	2020	Metformin attenuates the D-galactose-induced aging process via the UPR through the AMPK/ERK1/2 signaling pathways.	Metformin	0-9	mitogen activated protein kinase 3	Rattus norvegicus	88-94
31922237-3	2020	In this study, we aimed to cells to investigate whether metformin protects against age-related pathologies and to elucidate the underlying mechanisms; specifically, we focused on the role of unfolded protein response (UPR) via the AMPK/ERK1/2 signaling pathways.	Metformin	56-65	mitogen activated protein kinase 3	Rattus norvegicus	236-242
31922237-7	2020	We found that metformin treatment markedly affected the UPR and the AMPK/ERK1/2 signaling pathway, and maintained the auditory brainstem response (ABR) threshold during the aging process.	Metformin	14-23	mitogen activated protein kinase 3	Rattus norvegicus	73-79
31922237-8	2020	The results indicated that the regulation of the UPR and AMPK/ERK1/2 signaling pathway by metformin significantly attenuated hearing loss, cell apoptosis and age-related neurodegeneration.	Metformin	90-99	mitogen activated protein kinase 3	Rattus norvegicus	62-68
32068959-2	2020	Aging-related pathways such as mTOR and AMPK, which are major targets of anti-aging interventions including rapamcyin, metformin, and exercise, either directly regulate or intersect with metabolic pathways.	Metformin	119-128	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	40-44
31926250-0	2020	Inhibition of mTORC1/P70S6K pathway by Metformin synergistically sensitizes Acute Myeloid Leukemia to Ara-C.	Metformin	39-48	CREB regulated transcription coactivator 1	Mus musculus	14-20
31926250-6	2020	KEY FINDINGS: We found that metformin could synergistically sensitize AML cells to Ara-C via inhibiting mTORC1/P70S6K pathway.	Metformin	28-37	CREB regulated transcription coactivator 1	Mus musculus	104-110
32041944-0	2020	Metformin reduces HGF-induced resistance to alectinib via the inhibition of Gab1.	Metformin	0-9	hepatocyte growth factor	Homo sapiens	18-21
32041944-7	2020	The antidiabetic drug metformin combined with alectinib overcame alectinib resistance triggered by HGF/MET through disrupting the complex between MET and Gab1, thereby inhibiting Gab1 phosphorylation and the activation of downstream signal transduction pathways.	Metformin	22-31	hepatocyte growth factor	Homo sapiens	99-102
32041944-8	2020	These results suggest that metformin combined with alectinib may be useful for overcoming alectinib resistance induced by the activation of the HGF/MET signalling pathway and improving the efficacy of alectinib.	Metformin	27-36	hepatocyte growth factor	Homo sapiens	144-147
33728270-7	2021	Results and conclusion: APE, like glibenclamide and metformin, showed significant hypoglycaemic effect.	Metformin	52-61	apurinic/apyrimidinic endonuclease 1	Mus musculus	24-27
32099330-11	2020	Conclusion: Taken together, our data demonstrate that metformin might function to prevent AS by activating the AMPK/mTOR pathway via lncRNA TUG1.	Metformin	54-63	taurine up-regulated 1	Rattus norvegicus	140-144
31699707-7	2020	In the time-dependent Cox regression model, after multivariable adjustment, the risk for the development of cancer among metformin users was not significantly different from that among controls (HR = 0.96; 95% confidence interval, 0.89-1.03; P = 0.250).	Metformin	121-130	cytochrome c oxidase subunit 8A	Homo sapiens	22-25
31989218-8	2020	In contrast, in the celastrol and celastrol + metformin groups, the apoptotic potential was amplified, as revealed by the increase in the caspase-9 and caspase-3 levels and Bax:BCL-2 ratio.	Metformin	46-55	caspase 9	Mus musculus	138-147
31423743-8	2020	Mechanistically, our results demonstrated that autophagy activation by AMPK activator metformin or mTOR inhibitor rapamycin obviously promotes cell survival and autophagy flux, improved mitochondrial ultrastructure, and reduced expression of Cyt-C and caspase-3 in CORT-induced PC12 cells.	Metformin	86-95	caspase 3	Rattus norvegicus	252-261
31954752-9	2020	In particular, the focus was on metformin action on RAS/RAF/MAPK pathway.	Metformin	32-41	zinc fingers and homeoboxes 2	Homo sapiens	56-59
31905162-7	2020	The effects of the hypoglycemic agent metformin, which is an indirect AMPK activator, are discussed.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	70-74
31905162-8	2020	The multiple effects of metformin on cell metabolism and cell signalling and ultimately on cell function may be either dependent- or independent of AMPK.	Metformin	24-33	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	148-152
31786316-7	2020	Potential therapeutic approaches to target this pathway include exercise to alter kynurenine production or molecules such as metformin or resveratrol that may suppress Ahr activity.	Metformin	125-134	aryl hydrocarbon receptor	Homo sapiens	168-171
28498475-2	2017	We suppressed HK2 expression and/or function by shRNA and/or metformin and found HK2 inhibition enhanced cells apoptosis with accelerating expression of cleaved PARP and caspase-3.	Metformin	61-70	hexokinase 2	Homo sapiens	14-17
27957796-3	2017	Mechanistically, we demonstrated that activation of AMPK with its activators such as AICAR and metformin decreased the expression of MAD2B, indicating a role of AMPK in regulating the expression of MAD2B.	Metformin	95-104	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	52-56
27957796-3	2017	Mechanistically, we demonstrated that activation of AMPK with its activators such as AICAR and metformin decreased the expression of MAD2B, indicating a role of AMPK in regulating the expression of MAD2B.	Metformin	95-104	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	161-165
28504725-3	2017	Here we show that metformin, the most widely used drug for type 2 diabetes, rescues core phenotypes in Fmr1-/y mice and selectively normalizes ERK signaling, eIF4E phosphorylation and the expression of MMP-9.	Metformin	18-27	matrix metallopeptidase 9	Mus musculus	202-207
27897089-10	2017	Metformin supplementation downregulated the d-galactose induced expressions of sirtuin-2, IL-6, and TNF-alpha expression, whereas upregulated the Beclin-1 expression.	Metformin	0-9	beclin 1	Rattus norvegicus	146-154
28641488-8	2017	Metformin downregulated both endogenous and exogenous UCA1 expression, leading to the inhibition of mammalian target of rapamycin-signal transducer and activator of transcription 3-hexokinase 2 signaling pathway.	Metformin	0-9	urothelial cancer associated 1	Homo sapiens	54-58
28641488-9	2017	Our study provided the first evidence that metformin inhibited proliferation and glycolysis in cancer cells through regulation of long non-coding RNA UCA1.	Metformin	43-52	urothelial cancer associated 1	Homo sapiens	150-154
28413172-13	2017	The altered glucose and lipid profiles by metformin treatment may be associated with the increased circulating FGF21 and tissue-specific expressions of FGFR1.	Metformin	42-51	fibroblast growth factor 21	Rattus norvegicus	111-116
28389241-2	2017	To date, the molecular mechanism of metformin in modulating SHP-1 expression has remained elusive.	Metformin	36-45	protein tyrosine phosphatase, non-receptor type 6	Mus musculus	60-65
28389241-4	2017	We observed that metformin treatment significantly reduced SHP-1 activity in obese mice, leading to improved insulin sensitivity.	Metformin	17-26	protein tyrosine phosphatase, non-receptor type 6	Mus musculus	59-64
28389241-5	2017	Additionally, metformin down regulated inflammatory markers like TLR2, TLR4, CD80, CD86, NF-kappaB, STAT1 and suppressed adipose tissue inflammation by efficiently polarizing adipose tissue macrophages toward anti-inflammatory state by way of indirect inhibition of SHP-1 mRNA and protein expressions.	Metformin	14-23	toll-like receptor 2	Mus musculus	65-69
28389241-5	2017	Additionally, metformin down regulated inflammatory markers like TLR2, TLR4, CD80, CD86, NF-kappaB, STAT1 and suppressed adipose tissue inflammation by efficiently polarizing adipose tissue macrophages toward anti-inflammatory state by way of indirect inhibition of SHP-1 mRNA and protein expressions.	Metformin	14-23	protein tyrosine phosphatase, non-receptor type 6	Mus musculus	266-271
28389241-6	2017	Our study suggests that metformin exerts its insulin sensitizing effects via inhibition of SHP-1 activity and expression.	Metformin	24-33	protein tyrosine phosphatase, non-receptor type 6	Mus musculus	91-96
28373282-0	2017	Metformin directly binds the alarmin HMGB1 and inhibits its proinflammatory activity.	Metformin	0-9	high mobility group box 1	Homo sapiens	37-42
28373282-4	2017	Here we identified HMGB1 as a novel metformin-binding protein by affinity purification using a biotinylated metformin analogue.	Metformin	36-45	high mobility group box 1	Homo sapiens	19-24
28373282-5	2017	Metformin directly bound to the C-terminal acidic tail of HMGB1.	Metformin	0-9	high mobility group box 1	Homo sapiens	58-63
28373282-6	2017	Both in vitro and in vivo, metformin inhibited inflammatory responses induced by full-length HMGB1 but not by HMGB1 lacking the acidic tail.	Metformin	27-36	high mobility group box 1	Homo sapiens	93-98
28373282-7	2017	In an acetaminophen-induced acute liver injury model in which HMGB1 released from injured cells exacerbates the initial injury, metformin effectively reduced liver injury and had no additional inhibitory effects when the extracellular HMGB1 was blocked by anti-HMGB1-neutralizing antibody.	Metformin	128-137	high mobility group box 1	Homo sapiens	235-240
28373282-7	2017	In an acetaminophen-induced acute liver injury model in which HMGB1 released from injured cells exacerbates the initial injury, metformin effectively reduced liver injury and had no additional inhibitory effects when the extracellular HMGB1 was blocked by anti-HMGB1-neutralizing antibody.	Metformin	128-137	high mobility group box 1	Homo sapiens	235-240
28373282-8	2017	In summary, we report for the first time that metformin suppresses inflammation by inhibiting the extracellular activity of HMGB1.	Metformin	46-55	high mobility group box 1	Homo sapiens	124-129
28427181-0	2017	Metformin inhibits ALK1-mediated angiogenesis via activation of AMPK.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	64-68
28427181-4	2017	Thus, we treated human umbilical vein endothelial cells with metformin as well as other pharmacological AMPK activators and showed that activation of AMPK inhibited Smad1/5 phosphorylation and tube formation induced by BMP9.	Metformin	61-70	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	150-154
28427181-4	2017	Thus, we treated human umbilical vein endothelial cells with metformin as well as other pharmacological AMPK activators and showed that activation of AMPK inhibited Smad1/5 phosphorylation and tube formation induced by BMP9.	Metformin	61-70	SMAD family member 1	Homo sapiens	165-172
28427181-12	2017	This may offer us a new avenue for the treatment of related diseases using clinically used pharmacological AMPK activators like metformin in combination with other strategies to enhance the treatment efficacy or in the case of anti-VEGF resistance.	Metformin	128-137	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	107-111
28303721-8	2017	At week 24, significant reductions in mean (+-SD) HbA1c were observed in the vildagliptin (-1.47 +- 0.79%) and vildagliptin + metformin (-1.62 +- 0.82%) groups (both p &lt; 0.0001) from baseline HbA1c of 8.1% and 8.4%, respectively.	Metformin	126-135	hemoglobin subunit alpha 1	Homo sapiens	50-54
28075066-6	2017	The least-squares mean change in HbA1c from baseline to Week 26 was -0.19% with placebo, -0.86% with alogliptin, -1.04% with metformin and -1.53% with alogliptin + metformin FDC.	Metformin	125-134	hemoglobin subunit alpha 1	Homo sapiens	33-37
28339020-0	2017	Metformin inhibits endothelial progenitor cell migration by decreasing matrix metalloproteinases, MMP-2 and MMP-9, via the AMPK/mTOR/autophagy pathway.	Metformin	0-9	matrix metallopeptidase 2	Homo sapiens	98-103
28339020-0	2017	Metformin inhibits endothelial progenitor cell migration by decreasing matrix metalloproteinases, MMP-2 and MMP-9, via the AMPK/mTOR/autophagy pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	123-127
28339020-5	2017	Metformin treatment significantly downregulated matrix metalloproteinase-2 (MMP-2) and MMP-9 expression, and subsequently decreased the migration of EPCs.	Metformin	0-9	matrix metallopeptidase 2	Homo sapiens	48-74
28339020-5	2017	Metformin treatment significantly downregulated matrix metalloproteinase-2 (MMP-2) and MMP-9 expression, and subsequently decreased the migration of EPCs.	Metformin	0-9	matrix metallopeptidase 2	Homo sapiens	76-81
28339020-7	2017	The AMPK inhibitor compound C reversed the effect exerted by metformin.	Metformin	61-70	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	4-8
28339020-8	2017	In conclusion, our results showed that metformin inhibited the migration of EPCs by decreasing MMP-2 and MMP-9.	Metformin	39-48	matrix metallopeptidase 2	Homo sapiens	95-100
28579909-7	2017	Our data suggested that metformin alleviates capillary injury during ALI via AMPK-alpha1.	Metformin	24-33	protein kinase AMP-activated catalytic subunit alpha 1	Rattus norvegicus	77-88
28502303-5	2017	The expressions of P21 and c-caspase-3 increased, meanwhile, the expressions of CDK4, cyclin D1, caspase-3 and Bcl-2 decreased by metformin.	Metformin	130-139	caspase 3	Rattus norvegicus	29-38
28502303-5	2017	The expressions of P21 and c-caspase-3 increased, meanwhile, the expressions of CDK4, cyclin D1, caspase-3 and Bcl-2 decreased by metformin.	Metformin	130-139	caspase 3	Rattus norvegicus	97-106
28502303-7	2017	Furthermore, the expressions of IGF-1R, p-AKT and p-ERK descended after metformin treatment.	Metformin	72-81	insulin-like growth factor 1 receptor	Rattus norvegicus	32-38
28502303-8	2017	Conclusion Metformin could inhibit cell proliferation, induce cell cycle arrest and apoptosis in MMQ cells by activating AMPK/mTOR signaling pathway and inhibiting IGF-1R signaling pathway.	Metformin	11-20	protein kinase AMP-activated catalytic subunit alpha 1	Rattus norvegicus	121-125
28502303-8	2017	Conclusion Metformin could inhibit cell proliferation, induce cell cycle arrest and apoptosis in MMQ cells by activating AMPK/mTOR signaling pathway and inhibiting IGF-1R signaling pathway.	Metformin	11-20	insulin-like growth factor 1 receptor	Rattus norvegicus	164-170
28302481-10	2017	Myocardial mitochondrial respiratory function and membrane potential were decreased after myocardial infarction, and metformin treatment significantly improved the mitochondrial respiratory function and mitochondrial membrane potential; Metformin up-regulated the expression of Sirt3 and the activity of PGC-1alpha in myocardial tissue of heart failure after myocardial infarction.	Metformin	117-126	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	304-314
28302481-10	2017	Myocardial mitochondrial respiratory function and membrane potential were decreased after myocardial infarction, and metformin treatment significantly improved the mitochondrial respiratory function and mitochondrial membrane potential; Metformin up-regulated the expression of Sirt3 and the activity of PGC-1alpha in myocardial tissue of heart failure after myocardial infarction.	Metformin	237-246	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	304-314
28302481-11	2017	Metformin decreases the acetylation level of PGC-1alpha through up-regulating Sirt3, mitigates the damage to mitochondrial membrane potential of model of heart failure after myocardial infarction and improves the respiratory function of mitochondria, thus improving the cardiac function of mice.	Metformin	0-9	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	45-55
27775072-4	2017	Metformin acts by upregulating microRNA let-7 through AMPK activation, leading to degradation of H19 long noncoding RNA, which normally binds to and inactivates SAHH.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	54-58
28915708-6	2017	Metformin, a well-tolerated anti-diabetic agent, which blocks mitochondria oxidative phosphorylation complex I, became the poster child agent to elicit AMPK activity and tumor suppression.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	152-156
28480051-0	2017	Metformin suppresses triple-negative breast cancer stem cells by targeting KLF5 for degradation.	Metformin	0-9	Kruppel like factor 5	Homo sapiens	75-79
28480051-4	2017	In this study, we demonstrated that metformin decreased the percentage of TNBC stem cells partially through the downregulation of the expression of the stem cell transcription factor Kruppel-like factor 5 (KLF5) and its downstream target genes, such as Nanog and FGF-BP1, in TNBC cell lines.	Metformin	36-45	Kruppel like factor 5	Homo sapiens	183-204
28480051-4	2017	In this study, we demonstrated that metformin decreased the percentage of TNBC stem cells partially through the downregulation of the expression of the stem cell transcription factor Kruppel-like factor 5 (KLF5) and its downstream target genes, such as Nanog and FGF-BP1, in TNBC cell lines.	Metformin	36-45	Kruppel like factor 5	Homo sapiens	206-210
28480051-5	2017	Metformin induced glycogen synthase kinase-3beta (GSK3beta)-mediated KLF5 protein phosphorylation and degradation through the inhibition of protein kinase A (PKA) activity in TNBC cells.	Metformin	0-9	glycogen synthase kinase 3 beta	Homo sapiens	18-48
28480051-5	2017	Metformin induced glycogen synthase kinase-3beta (GSK3beta)-mediated KLF5 protein phosphorylation and degradation through the inhibition of protein kinase A (PKA) activity in TNBC cells.	Metformin	0-9	glycogen synthase kinase 3 beta	Homo sapiens	50-58
28480051-5	2017	Metformin induced glycogen synthase kinase-3beta (GSK3beta)-mediated KLF5 protein phosphorylation and degradation through the inhibition of protein kinase A (PKA) activity in TNBC cells.	Metformin	0-9	Kruppel like factor 5	Homo sapiens	69-73
28480051-8	2017	These findings suggest that metformin suppresses TNBC stem cells partially through the PKA-GSK3beta-KLF5 signaling pathway.	Metformin	28-37	glycogen synthase kinase 3 beta	Homo sapiens	91-99
28480051-8	2017	These findings suggest that metformin suppresses TNBC stem cells partially through the PKA-GSK3beta-KLF5 signaling pathway.	Metformin	28-37	Kruppel like factor 5	Homo sapiens	100-104
28423712-0	2017	Model-based unsupervised learning informs metformin-induced cell-migration inhibition through an AMPK-independent mechanism in breast cancer.	Metformin	42-51	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	97-101
28423712-4	2017	This analysis corroborates known studies of metformin action: a) pathway analysis indicated known mechanisms related to metformin action, including the citric acid (TCA) cycle, oxidative phosphorylation, and mitochondrial dysfunction (p-value &lt; 1E-9); b) 70% of these 230 genes were functionally implicated in metformin response; c) among remaining lesser functionally-studied genes for metformin-response was CDC42, down-regulated in breast cancer treated with metformin.	Metformin	44-53	cell division cycle 42	Homo sapiens	413-418
28423712-4	2017	This analysis corroborates known studies of metformin action: a) pathway analysis indicated known mechanisms related to metformin action, including the citric acid (TCA) cycle, oxidative phosphorylation, and mitochondrial dysfunction (p-value &lt; 1E-9); b) 70% of these 230 genes were functionally implicated in metformin response; c) among remaining lesser functionally-studied genes for metformin-response was CDC42, down-regulated in breast cancer treated with metformin.	Metformin	120-129	cell division cycle 42	Homo sapiens	413-418
28423712-4	2017	This analysis corroborates known studies of metformin action: a) pathway analysis indicated known mechanisms related to metformin action, including the citric acid (TCA) cycle, oxidative phosphorylation, and mitochondrial dysfunction (p-value &lt; 1E-9); b) 70% of these 230 genes were functionally implicated in metformin response; c) among remaining lesser functionally-studied genes for metformin-response was CDC42, down-regulated in breast cancer treated with metformin.	Metformin	120-129	cell division cycle 42	Homo sapiens	413-418
28423712-4	2017	This analysis corroborates known studies of metformin action: a) pathway analysis indicated known mechanisms related to metformin action, including the citric acid (TCA) cycle, oxidative phosphorylation, and mitochondrial dysfunction (p-value &lt; 1E-9); b) 70% of these 230 genes were functionally implicated in metformin response; c) among remaining lesser functionally-studied genes for metformin-response was CDC42, down-regulated in breast cancer treated with metformin.	Metformin	120-129	cell division cycle 42	Homo sapiens	413-418
28423712-4	2017	This analysis corroborates known studies of metformin action: a) pathway analysis indicated known mechanisms related to metformin action, including the citric acid (TCA) cycle, oxidative phosphorylation, and mitochondrial dysfunction (p-value &lt; 1E-9); b) 70% of these 230 genes were functionally implicated in metformin response; c) among remaining lesser functionally-studied genes for metformin-response was CDC42, down-regulated in breast cancer treated with metformin.	Metformin	120-129	cell division cycle 42	Homo sapiens	413-418
28423712-5	2017	However, CDC42"s mechanisms in metformin response remained unclear.	Metformin	31-40	cell division cycle 42	Homo sapiens	9-14
28423712-6	2017	Our functional studies showed that CDC42 was involved in metformin-induced inhibition of cell proliferation and cell migration mediated through an AMPK-independent mechanism.	Metformin	57-66	cell division cycle 42	Homo sapiens	35-40
28423712-6	2017	Our functional studies showed that CDC42 was involved in metformin-induced inhibition of cell proliferation and cell migration mediated through an AMPK-independent mechanism.	Metformin	57-66	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	147-151
28423712-7	2017	Our results points to 230 genes that might serve as metformin response signatures, which needs to be tested in patients treated with metformin and, further investigation of CDC42 and AMPK-independence"s role in metformin"s anticancer mechanisms.	Metformin	52-61	cell division cycle 42	Homo sapiens	173-178
28423712-7	2017	Our results points to 230 genes that might serve as metformin response signatures, which needs to be tested in patients treated with metformin and, further investigation of CDC42 and AMPK-independence"s role in metformin"s anticancer mechanisms.	Metformin	52-61	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	183-187
28580278-9	2017	Lastly, we assessed whether FGF21 exerted its effects through the AMPK/ACC axis, which is critical in the therapeutic benefits of the anti-diabetic medication metformin.	Metformin	159-168	fibroblast growth factor 21	Mus musculus	28-33
29871302-8	2017	The combination of metformin and 5-fluorouracil produced an antagonism action in Hep-2 cells.Western blot assay showed that metformin, cisplatin, 5-fluorouracil could have caused the increase of expression level of AMPK-alpha, P21 and Cyclin D1 in Hep-2 cells while Paclitaxel could have cause the decrease of expression level of Cyclin D1.	Metformin	19-28	cyclin D1	Homo sapiens	235-244
29871302-8	2017	The combination of metformin and 5-fluorouracil produced an antagonism action in Hep-2 cells.Western blot assay showed that metformin, cisplatin, 5-fluorouracil could have caused the increase of expression level of AMPK-alpha, P21 and Cyclin D1 in Hep-2 cells while Paclitaxel could have cause the decrease of expression level of Cyclin D1.	Metformin	19-28	cyclin D1	Homo sapiens	330-339
29871302-8	2017	The combination of metformin and 5-fluorouracil produced an antagonism action in Hep-2 cells.Western blot assay showed that metformin, cisplatin, 5-fluorouracil could have caused the increase of expression level of AMPK-alpha, P21 and Cyclin D1 in Hep-2 cells while Paclitaxel could have cause the decrease of expression level of Cyclin D1.	Metformin	124-133	cyclin D1	Homo sapiens	235-244
29871302-8	2017	The combination of metformin and 5-fluorouracil produced an antagonism action in Hep-2 cells.Western blot assay showed that metformin, cisplatin, 5-fluorouracil could have caused the increase of expression level of AMPK-alpha, P21 and Cyclin D1 in Hep-2 cells while Paclitaxel could have cause the decrease of expression level of Cyclin D1.	Metformin	124-133	cyclin D1	Homo sapiens	330-339
29871302-11	2017	Metformin has an antagonism on the anticancer effect to 5-fluorouracil in Hep-2 cells, and this antagonistic effect occurred partially through molecular signal pathways of AMPK-alpha, P21 and Cyclin D1 and it"s significantly related to the cell cycle arrest.	Metformin	0-9	cyclin D1	Homo sapiens	192-201
31894313-0	2020	Metformin alleviates endometrial hyperplasia through the UCA1/miR-144/TGF-beta1/AKT signaling pathway.	Metformin	0-9	urothelial cancer associated 1	Homo sapiens	57-61
31894313-2	2020	Reverse transcription-quantitative polymerase chain reaction, western blot and immunohistochemistry (IHC) assays were used to study the effects of Met and tamoxifen on the expression levels of urothelial cancer associated 1 (UCA1), microRNA-144 (miR-144) and other factors along the transforming growth factor-beta1 (TGF-beta1)/protein kinase B (AKT) signaling pathway.	Metformin	147-150	urothelial cancer associated 1	Homo sapiens	193-223
31894313-2	2020	Reverse transcription-quantitative polymerase chain reaction, western blot and immunohistochemistry (IHC) assays were used to study the effects of Met and tamoxifen on the expression levels of urothelial cancer associated 1 (UCA1), microRNA-144 (miR-144) and other factors along the transforming growth factor-beta1 (TGF-beta1)/protein kinase B (AKT) signaling pathway.	Metformin	147-150	urothelial cancer associated 1	Homo sapiens	225-229
31894313-6	2020	By contrast, Met reduced cell viability, promoted cell apoptosis, and reduced the expression levels of UCA1, TGF-beta and p-AKT, while upregulating the expression of miR-144 and active Caspase-3 in a dose-dependent manner.	Metformin	13-16	urothelial cancer associated 1	Homo sapiens	103-107
31894313-11	2020	In conclusion, the current study suggested that Met reduces the risk of EH by reducing the expression levels of UCA1, TGF-beta and p-AKT, while increasing the levels of miR-144 and active Caspase-3 in a dose-dependent manner.	Metformin	48-51	urothelial cancer associated 1	Homo sapiens	112-116
31843673-7	2020	Regarding the underlying molecular mechanisms, metformin has been shown to inhibit alpha-synuclein (SNCA) phosphorylation and aggregation, prevent mitochondrial dysfunction, attenuate oxidative stress, modulate autophagy mainly via AMP-activated protein kinase (AMPK) activation, as well as prevent neurodegeneration and neuroinflammation.	Metformin	47-56	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	232-260
31843673-7	2020	Regarding the underlying molecular mechanisms, metformin has been shown to inhibit alpha-synuclein (SNCA) phosphorylation and aggregation, prevent mitochondrial dysfunction, attenuate oxidative stress, modulate autophagy mainly via AMP-activated protein kinase (AMPK) activation, as well as prevent neurodegeneration and neuroinflammation.	Metformin	47-56	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	262-266
32095186-6	2020	Results: The rate of lymph node metastasis and the level of Ki-67/MMP-2 in the metformin group were significantly lower than those in the control group (P &lt; 0.05).	Metformin	79-88	matrix metallopeptidase 2	Homo sapiens	66-71
28186975-6	2017	Elastase injection was performed to induce mouse emphysema, and these mice were treated with a specific AMPK activator metformin as well as Compound C. AICAR reduced, whereas Compound C increased CSE-induced increase in IL-8 and IL-6 release and expression of genes involved in cellular senescence.	Metformin	119-128	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	104-108
28186975-8	2017	Prophylactic administration of an AMPK activator metformin (50 and 250 mg/kg) reduced while Compound C (4 and 20 mg/kg) aggravated elastase-induced airspace enlargement, inflammatory responses and cellular senescence in mice.	Metformin	49-58	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	34-38
28237861-1	2017	AIMS: The glucagon receptor antagonist PF-06291874 has demonstrated robust glucose reductions in subjects with type 2 diabetes mellitus (T2DM) on background metformin.	Metformin	157-166	glucagon receptor	Homo sapiens	10-27
27981392-6	2017	Metformin also reduced sclerostin expression and improved the immunolocalization of dentin matrix protein 1 in osteocytes of type 2 diabetes rats.	Metformin	0-9	dentin matrix acidic phosphoprotein 1	Rattus norvegicus	84-107
32083006-0	2020	Hexokinase 2 Depletion Confers Sensitization to Metformin and Inhibits Glycolysis in Lung Squamous Cell Carcinoma.	Metformin	48-57	hexokinase 2	Homo sapiens	0-12
32023702-14	2020	The intracellular aspartate aminotransferase and alanine aminotransferase were decreased significantly after the treatment with low and high-dose metformin, which were (32.44 +- 4.08)U/L, (19.31 +- 3.03) U/L, (26.00 +- 3.11) U/L and (15.11 +- 4.11) U/L, respectively and the differences were statistically significant (P < 0.05).	Metformin	146-155	glutamic--pyruvic transaminase	Homo sapiens	49-73
31945013-6	2020	In addition, metformin treatment decreased p16INK4a levels in OA chondrocytes, and enhanced polarization of AMPK and inhibition of mTORC1 in OA mice and chondrocytes in a dose-dependent manner.	Metformin	13-22	CREB regulated transcription coactivator 1	Mus musculus	131-137
31647955-0	2020	Metformin alleviates oxidative stress and enhances autophagy in diabetic kidney disease via AMPK/SIRT1-FoxO1 pathway.	Metformin	0-9	forkhead box O1	Rattus norvegicus	103-108
31647955-3	2020	We found that metformin effectively alleviated the disorders of glycolipid metabolism, renal function injury in diabetic rats, and relieved oxidative stress, enhanced autophagy and slowed down abnormal cell proliferation in high glucose cultured RMCs through AMPK/SIRT1-FoxO1 pathway, indicating the protective role of metformin against the pathological process of DKD.	Metformin	14-23	forkhead box O1	Rattus norvegicus	270-275
31901295-0	2020	Corrigendum to "Metformin promotes autophagy in ischemia/reperfusion myocardium via cytoplasmic AMPKalpha1 and nuclear AMPKalpha2 pathways" [Life Sci.	Metformin	16-25	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	96-106
31901295-0	2020	Corrigendum to "Metformin promotes autophagy in ischemia/reperfusion myocardium via cytoplasmic AMPKalpha1 and nuclear AMPKalpha2 pathways" [Life Sci.	Metformin	16-25	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	119-129
27652986-7	2017	Metformin and glitazones are pure stimulators of AMPK.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	49-53
28157701-7	2017	Additionally, through increasing AMPK and p65 phosphorylation, metformin treatment activated AMPK-NF-kappaB signaling of cancer cells that participate in regulating M1 and M2 inducing cytokines expression.	Metformin	63-72	RELA proto-oncogene, NF-kB subunit	Homo sapiens	42-45
28183460-0	2017	Corrigendum to "Metformin suppresses adipogenesis through both AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms" [Mol.	Metformin	16-25	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	63-91
28183460-0	2017	Corrigendum to "Metformin suppresses adipogenesis through both AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms" [Mol.	Metformin	16-25	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	93-97
28183460-0	2017	Corrigendum to "Metformin suppresses adipogenesis through both AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms" [Mol.	Metformin	16-25	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	113-117
28253329-13	2017	In 3T3 cells, the secretion of IGF-1 was significantly inhibited by metformin from 574.31pg/ml to 197.61pg/ml.	Metformin	68-77	insulin-like growth factor 1	Mus musculus	31-36
28258677-1	2017	The generally accepted mechanism of metformin"s effect is stimulation of adenosine monophosphate (AMP)-activated protein kinase (AMPK).	Metformin	36-45	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	129-133
28258677-3	2017	Lately, many novel pathways, besides AMPK induction, have been revealed, which can explain some of metformin"s beneficial effects.	Metformin	99-108	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	37-41
28177677-0	2017	mTORC1 inhibitors rapamycin and metformin affect cardiovascular markers differentially in ZDF rats.	Metformin	32-41	CREB regulated transcription coactivator 1	Mus musculus	0-6
28177677-1	2017	Mammalian target for rapamycin complex 1 (mTORC1) is a common target for the action of immunosuppressant macrolide rapamycin and glucose-lowering metformin.	Metformin	146-155	CREB regulated transcription coactivator 1	Mus musculus	42-48
27860132-13	2017	CONCLUSIONS: GLP-1 RAs are associated with gastrointestinal AEs that are related to dose and background medications (especially metformin) and may vary in a compound-specific manner.	Metformin	128-137	glucagon like peptide 1 receptor	Homo sapiens	13-18
27862873-1	2017	AIMS: To investigate, in the Carotid Atherosclerosis: Metformin for Insulin Resistance (CAMERA) trial (NCT00723307), whether the influence of metformin on the glucagon-like peptide (GLP)-1 axis in individuals with and without type 2 diabetes (T2DM) is sustained and related to changes in glycaemia or weight, and to investigate basal and post-meal GLP-1 levels in patients with T2DM in the cross-sectional Diabetes Research on Patient Stratification (DIRECT) study.	Metformin	142-151	glucagon like peptide 1 receptor	Homo sapiens	159-188
27862873-3	2017	Using 6-monthly fasted total GLP-1 levels over 18 months, we evaluated metformin"s effect on total GLP-1 with repeated-measures analysis and analysis of covariance.	Metformin	71-80	glucagon like peptide 1 receptor	Homo sapiens	99-104
27862873-5	2017	RESULTS: In CAMERA, metformin increased total GLP-1 at 6 (+20.7%, 95% confidence interval [CI] 4.7-39.0), 12 (+26.7%, 95% CI 10.3-45.6) and 18 months (+18.7%, 95% CI 3.8-35.7), an overall increase of 23.4% (95% CI 11.2-36.9; P &lt; .0001) vs placebo.	Metformin	20-29	glucagon like peptide 1 receptor	Homo sapiens	46-51
27862873-7	2017	In the DIRECT study, metformin was associated with higher fasting active (39.1%, 95% CI 21.3-56.4) and total GLP-1 (14.1%, 95% CI 1.2-25.9) but not post-meal incremental GLP-1.	Metformin	21-30	glucagon like peptide 1 receptor	Homo sapiens	109-114
27862873-7	2017	In the DIRECT study, metformin was associated with higher fasting active (39.1%, 95% CI 21.3-56.4) and total GLP-1 (14.1%, 95% CI 1.2-25.9) but not post-meal incremental GLP-1.	Metformin	21-30	glucagon like peptide 1 receptor	Homo sapiens	170-175
27862873-9	2017	CONCLUSIONS: In people without diabetes, metformin increases total GLP-1 in a sustained manner and independently of changes in weight or glycaemia.	Metformin	41-50	glucagon like peptide 1 receptor	Homo sapiens	67-72
27862873-10	2017	Metformin-treated patients with T2DM also have higher fasted GLP-1 levels, independently of weight and glycaemia.	Metformin	0-9	glucagon like peptide 1 receptor	Homo sapiens	61-66
27891757-3	2017	The least squares (LS) mean (standard error) change in HbA1c from baseline to the end of treatment (week 24) was 0.16 (0.072)% in alogliptin alone, -0.49 (0.049)% in alogliptin/metformin once daily, and -0.60 (0.049)% in alogliptin/metformin twice daily.	Metformin	177-186	hemoglobin subunit alpha 1	Homo sapiens	55-59
27891757-3	2017	The least squares (LS) mean (standard error) change in HbA1c from baseline to the end of treatment (week 24) was 0.16 (0.072)% in alogliptin alone, -0.49 (0.049)% in alogliptin/metformin once daily, and -0.60 (0.049)% in alogliptin/metformin twice daily.	Metformin	232-241	hemoglobin subunit alpha 1	Homo sapiens	55-59
28241849-14	2017	Mechanistically, the antibody array revealed that ERK3 exhibited the highest variation in CCLP-1 cells after treatment with metformin and ATO.	Metformin	124-133	mitogen-activated protein kinase 12	Homo sapiens	50-54
28241849-15	2017	Results of western blot confirm that metformin and ATO cooperated to inhibit mTORC1, activate AMP-activated protein kinase (AMPK), and upregulate ERK3.	Metformin	37-46	CREB regulated transcription coactivator 1	Mus musculus	77-83
28241849-15	2017	Results of western blot confirm that metformin and ATO cooperated to inhibit mTORC1, activate AMP-activated protein kinase (AMPK), and upregulate ERK3.	Metformin	37-46	mitogen-activated protein kinase 12	Homo sapiens	146-150
28241849-17	2017	Inactivation of p38 MAPK by SB203580 or specific short interfering RNA (siRNA) promoted the inactivation of mTORC1 in ICC cells treated with metformin and ATO.	Metformin	141-150	CREB regulated transcription coactivator 1	Mus musculus	108-114
28241849-23	2017	CONCLUSIONS: Metformin sensitizes arsenic trioxide to suppress intrahepatic cholangiocarcinoma via the regulation of AMPK/p38 MAPK-ERK3/mTORC1 pathways.	Metformin	13-22	mitogen-activated protein kinase 12	Homo sapiens	126-135
28241849-23	2017	CONCLUSIONS: Metformin sensitizes arsenic trioxide to suppress intrahepatic cholangiocarcinoma via the regulation of AMPK/p38 MAPK-ERK3/mTORC1 pathways.	Metformin	13-22	CREB regulated transcription coactivator 1	Mus musculus	136-142
30603334-2	2017	The changes in HbA1c from baseline to the final evaluation visit were -1.32 +- 0.76% for metformin monotherapy and -1.29 +- 0.81% for metformin plus SU, both significantly lower than baseline.	Metformin	89-98	hemoglobin subunit alpha 1	Homo sapiens	15-19
30603334-2	2017	The changes in HbA1c from baseline to the final evaluation visit were -1.32 +- 0.76% for metformin monotherapy and -1.29 +- 0.81% for metformin plus SU, both significantly lower than baseline.	Metformin	134-143	hemoglobin subunit alpha 1	Homo sapiens	15-19
28099155-1	2017	Metformin, as an AMP-activated protein kinase (AMPK) activator, can activate autophagy.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	17-45
28099155-1	2017	Metformin, as an AMP-activated protein kinase (AMPK) activator, can activate autophagy.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	47-51
28099155-6	2017	The underlying mechanisms in this process included a reduction in Src-mediated CEBPD protein degradation and an increase in CEBPD-regulated LC3B and ATG3 gene transcription under metformin treatment.	Metformin	179-188	microtubule associated protein 1 light chain 3 beta	Homo sapiens	140-144
28099155-7	2017	We also found that AMPK is involved in metformin-induced CEBPD expression.	Metformin	39-48	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	19-23
28099155-8	2017	Combined treatment with metformin and rapamycin can enhance autophagic cell death through the AMPK-dependent and AMPK-independent pathway, respectively.	Metformin	24-33	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	94-98
28099155-8	2017	Combined treatment with metformin and rapamycin can enhance autophagic cell death through the AMPK-dependent and AMPK-independent pathway, respectively.	Metformin	24-33	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	113-117
28209925-4	2017	Accumulating evidence since has shown that pharmacologic activation of AMPK by Metformin protects the epithelial barrier against multiple environmental and pathological stressful states and suppresses tumorigenesis.	Metformin	79-88	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	71-75
28209925-7	2017	Here we review the fundamentals of this specialized signaling pathway that buttresses cell-cell junctions against stress-induced collapse and discuss its pathophysiologic relevance in the context of a variety of diseases, including cancers, diabetes, aging, and the growing list of beneficial effects of the AMPK-activator, Metformin.	Metformin	324-333	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	308-312
28089566-0	2017	Metformin Inhibits Hepatic mTORC1 Signaling via Dose-Dependent Mechanisms Involving AMPK and the TSC Complex.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	27-33
28089566-5	2017	Here we show that metformin robustly inhibits mTORC1 in mouse liver tissue and primary hepatocytes.	Metformin	18-27	CREB regulated transcription coactivator 1	Mus musculus	46-52
28089566-6	2017	Using mouse genetics, we find that at the lowest concentrations of metformin that inhibit hepatic mTORC1 signaling, this inhibition is dependent on AMPK and the tuberous sclerosis complex (TSC) protein complex (TSC complex).	Metformin	67-76	CREB regulated transcription coactivator 1	Mus musculus	98-104
28089566-7	2017	Finally, we show that metformin profoundly inhibits hepatocyte protein synthesis in a manner that is largely dependent on its ability to suppress mTORC1 signaling.	Metformin	22-31	CREB regulated transcription coactivator 1	Mus musculus	146-152
27305912-9	2017	RESULTS: After adjusting for multiple comparisons in the 32 tumors from metformin-treated patients vs. 34 untreated historical controls, 11 proteins were significantly different between cases vs. CONTROLS: increases in Raptor, C-Raf, Cyclin B1, Cyclin D1, TRFC, and Syk; and reductions in pMAPKpT202,Y204, JNKpT183,pT185, BadpS112, PKC.alphapS657, and SrcpY416.	Metformin	72-81	regulatory associated protein of MTOR complex 1	Homo sapiens	219-225
27305912-9	2017	RESULTS: After adjusting for multiple comparisons in the 32 tumors from metformin-treated patients vs. 34 untreated historical controls, 11 proteins were significantly different between cases vs. CONTROLS: increases in Raptor, C-Raf, Cyclin B1, Cyclin D1, TRFC, and Syk; and reductions in pMAPKpT202,Y204, JNKpT183,pT185, BadpS112, PKC.alphapS657, and SrcpY416.	Metformin	72-81	Raf-1 proto-oncogene, serine/threonine kinase	Homo sapiens	227-232
27305912-9	2017	RESULTS: After adjusting for multiple comparisons in the 32 tumors from metformin-treated patients vs. 34 untreated historical controls, 11 proteins were significantly different between cases vs. CONTROLS: increases in Raptor, C-Raf, Cyclin B1, Cyclin D1, TRFC, and Syk; and reductions in pMAPKpT202,Y204, JNKpT183,pT185, BadpS112, PKC.alphapS657, and SrcpY416.	Metformin	72-81	cyclin D1	Homo sapiens	245-254
27305912-10	2017	Cyclin D1 change after metformin by IHC was not observed.	Metformin	23-32	cyclin D1	Homo sapiens	0-9
28143456-2	2017	Metformin is weight neutral, yet it could enhance the therapeutic index of GLP-1 agonist.	Metformin	0-9	glucagon like peptide 1 receptor	Homo sapiens	75-80
27856330-0	2017	Metformin suppresses adipogenesis through both AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	47-75
27856330-0	2017	Metformin suppresses adipogenesis through both AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	77-81
27856330-0	2017	Metformin suppresses adipogenesis through both AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	97-101
27856330-4	2017	Here we investigate the involvement of the metabolic enzyme, AMP-activated protein kinase (AMPK), in these protective actions of metformin.	Metformin	129-138	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	61-89
27856330-4	2017	Here we investigate the involvement of the metabolic enzyme, AMP-activated protein kinase (AMPK), in these protective actions of metformin.	Metformin	129-138	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	91-95
27856330-8	2017	Further activation of AMPK in wild type MEFS, with either metformin or the AMPK-specific activator, A769662, was also associated with suppression of adipogenesis.	Metformin	58-67	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	22-26
27856330-9	2017	It appears, therefore, that basal AMPK activity is required for adipogenesis and that metformin can inhibit adipogenesis through AMPK-dependent or -independent mechanisms, depending on the cellular context.	Metformin	86-95	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	129-133
27999002-0	2017	Metformin Is Associated With Higher Relative Abundance of Mucin-Degrading Akkermansia muciniphila and Several Short-Chain Fatty Acid-Producing Microbiota in the Gut.	Metformin	0-9	LOC100508689	Homo sapiens	58-63
27999002-3	2017	On the basis of previous research, we hypothesized that metformin is associated with higher levels of short-chain fatty acid (SCFA)-producing and mucin-degrading microbiota.	Metformin	56-65	LOC100508689	Homo sapiens	146-151
27999002-8	2017	Compared with participants without diabetes, participants with diabetes taking metformin had higher relative abundance of Akkermansia muciniphila, a microbiota known for mucin degradation, and several gut microbiota known for production of SCFAs, including Butyrivibrio, Bifidobacterium bifidum, Megasphaera, and an operational taxonomic unit of Prevotella.	Metformin	79-88	LOC100508689	Homo sapiens	134-139
27999002-10	2017	CONCLUSIONS: Our results support the hypothesis that metformin shifts gut microbiota composition through the enrichment of mucin-degrading A. muciniphila as well as several SCFA-producing microbiota.	Metformin	53-62	LOC100508689	Homo sapiens	123-128
31764942-8	2020	Several oral drugs, including metformin, were predicted to have intestinal concentrations that may result in ThTR-2-mediated drug-nutrient interactions.	Metformin	30-39	solute carrier family 19 member 3	Homo sapiens	109-115
31892560-8	2020	Immunohistochemical analysis of tumor tissues revealed down-regulation of cyclin D1 and proliferating cell nuclear antigen in the metformin-treated group.	Metformin	130-139	cyclin D1	Homo sapiens	74-83
31892560-9	2020	Additionally, metformin induced apoptosis, and the expression of survivin and claspin were decreased in metformin-treated QGP-1 cells according to the apoptosis array.	Metformin	104-113	claspin	Homo sapiens	78-85
31958303-9	2020	CONCLUSIONS: Initial triple combination therapy with the DPP4 inhibitor, metformin, and thiazolidinedione showed a higher achievement of the target HbA1c goal with a lower risk of hypoglycemia, better restoration of beta-cell function, and multiple metabolic benefits, implying durable glycemic control.	Metformin	73-82	hemoglobin subunit alpha 1	Homo sapiens	148-152
31694861-0	2020	Efficacy and Safety of the Glucagon Receptor Antagonist RVT-1502 in Type 2 Diabetes Uncontrolled on Metformin Monotherapy: A 12-Week Dose-Ranging Study.	Metformin	100-109	glucagon receptor	Homo sapiens	27-44
27754854-15	2017	An alternative pathway by which metformin exerted its action was through downregulation of IGFBP-2 in DU145 and LNCaP cells, independently of AMPK.	Metformin	32-41	insulin like growth factor binding protein 2	Homo sapiens	91-98
27754854-15	2017	An alternative pathway by which metformin exerted its action was through downregulation of IGFBP-2 in DU145 and LNCaP cells, independently of AMPK.	Metformin	32-41	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	142-146
27814614-0	2017	Metformin suppresses CRC growth by inducing apoptosis via ADORA1.	Metformin	0-9	adenosine A1 receptor	Homo sapiens	58-64
27814614-4	2017	Notably, metformin treatment significantly up-regulated adenosine A1 receptor (ADORA1) expression in human colorectal cancer cells, while suppression of ADORA1 activity by its specific inhibitor rescued the growth inhibition induced by metformin.	Metformin	9-18	adenosine A1 receptor	Homo sapiens	79-85
27814614-4	2017	Notably, metformin treatment significantly up-regulated adenosine A1 receptor (ADORA1) expression in human colorectal cancer cells, while suppression of ADORA1 activity by its specific inhibitor rescued the growth inhibition induced by metformin.	Metformin	236-245	adenosine A1 receptor	Homo sapiens	153-159
27814614-5	2017	Moreover, ADORA1-mediated growth inhibition and apoptosis induced by metformin is AMPK-mTOR pathway dependent in human colorectal cancer cells.	Metformin	69-78	adenosine A1 receptor	Homo sapiens	10-16
27814614-6	2017	Taken together, these results indicate that metformin suppresses human colorectal cancer growth by inducing apoptosis via ADORA1, which provide evidence the anti-neoplastic effects of metformin in the treatment of human colorectal cancer.	Metformin	44-53	adenosine A1 receptor	Homo sapiens	122-128
27814614-6	2017	Taken together, these results indicate that metformin suppresses human colorectal cancer growth by inducing apoptosis via ADORA1, which provide evidence the anti-neoplastic effects of metformin in the treatment of human colorectal cancer.	Metformin	184-193	adenosine A1 receptor	Homo sapiens	122-128
28409163-13	2017	AICAR and metformin treatment effectively mitigated albuminuria and renal histopathology and decreased the expression of TGFbeta1 and alphaSMA in the kidneys of diabetic mice.	Metformin	10-19	transforming growth factor, beta 1	Mus musculus	121-129
31851935-4	2019	Inhibition of tumor-stromal crosstalk by metformin is caused by the reduced expression of the tricarboxylic acid (TCA) enzyme succinyl CoA ligase (SUCLG2).	Metformin	41-50	succinate-CoA ligase GDP-forming subunit beta	Homo sapiens	147-153
31805999-0	2019	PTPRD-inactivation-induced CXCL8 promotes angiogenesis and metastasis in gastric cancer and is inhibited by metformin.	Metformin	108-117	protein tyrosine phosphatase receptor type D	Homo sapiens	0-5
31805999-13	2019	Additionally, metformin was found to efficiently inhibit PTPRD-loss-induced angiogenesis, decrease cell viability in PTPRD-inactivated cancers, and reverse the decrease in PTPRD expression.	Metformin	14-23	protein tyrosine phosphatase receptor type D	Homo sapiens	57-62
31805999-13	2019	Additionally, metformin was found to efficiently inhibit PTPRD-loss-induced angiogenesis, decrease cell viability in PTPRD-inactivated cancers, and reverse the decrease in PTPRD expression.	Metformin	14-23	protein tyrosine phosphatase receptor type D	Homo sapiens	117-122
31805999-13	2019	Additionally, metformin was found to efficiently inhibit PTPRD-loss-induced angiogenesis, decrease cell viability in PTPRD-inactivated cancers, and reverse the decrease in PTPRD expression.	Metformin	14-23	protein tyrosine phosphatase receptor type D	Homo sapiens	117-122
31805999-15	2019	Hence, we propose that the therapeutic efficacy of metformin in PTPRD-inactivated cancers should be further investigated.	Metformin	51-60	protein tyrosine phosphatase receptor type D	Homo sapiens	64-69
31870092-0	2019	Metformin Inhibit Cervical Cancer Migration by Suppressing the FAK/Akt Signaling Pathway.	Metformin	0-9	protein tyrosine kinase 2	Homo sapiens	63-66
31870092-7	2019	The suppression of migration mediated through the regulatory proteins such as focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (Akt), Rac1 and RhoA after metformin treatment.	Metformin	164-173	protein tyrosine kinase 2	Homo sapiens	78-99
31870092-7	2019	The suppression of migration mediated through the regulatory proteins such as focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (Akt), Rac1 and RhoA after metformin treatment.	Metformin	164-173	protein tyrosine kinase 2	Homo sapiens	101-104
31870092-8	2019	CONCLUSION: Metformin displays antimigration effects in cervical cancer cells by inhibiting filopodia and lamellipodia formation through the suppression of FAK, Akt and its downstream Rac1 and RhoA protein.	Metformin	12-21	protein tyrosine kinase 2	Homo sapiens	156-159
31529536-6	2019	Further, lutein and oxidised lutein augmented the AMPK phosphorylation and activation of mitochondrion signalling molecule TFAM (protein expression) and mRNA expression of PGC-1alpha, TFAM, and NRF1 (responsible for mitochondria biogenesis) along with lowered ROS in HG compared to control and metformin groups.	Metformin	294-303	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	50-54
29082261-7	2017	Several other factors (BMI, glucagon, age, and nonesterified fatty acids (NEFA)), including medications (metformin), may also influence the secretion of GLP-1.	Metformin	105-114	glucagon like peptide 1 receptor	Homo sapiens	153-158
27920093-8	2017	18F-FDG uptake reduced after metformin treatment in a dose-dependent manner, corresponding to the reduced expression level of HK2 and GLUT1 in vitro Xenograft model of PTC using BCPAP cells was achieved successfully.	Metformin	29-38	hexokinase 2	Homo sapiens	126-129
27920093-10	2017	Immunohistochemistry staining further confirmed the reduction of HK2 and GLUT1 expression in the tumor tissue of metformin-treated PTC xenograft model.	Metformin	113-122	hexokinase 2	Homo sapiens	65-68
28298952-7	2017	Antihyperglycemic agent metformin and newly found free radicals scavengers, Sirt1 and CTRP9, may serve as promising pharmacological therapeutic targets.	Metformin	24-33	C1q and TNF related 9	Homo sapiens	86-91
29694764-3	2017	Recent literature has explored metformin as an option in pain management, given its role in the AMP-activated protein kinase (AMPK) pathway and its ability to modulate pain in animal models.	Metformin	31-40	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	96-124
29694764-3	2017	Recent literature has explored metformin as an option in pain management, given its role in the AMP-activated protein kinase (AMPK) pathway and its ability to modulate pain in animal models.	Metformin	31-40	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	126-130
29694764-5	2017	The activation of AMPK with metformin has led to decreased pain in neuropathic and postsurgical pain models, suggesting that these drugs and this mechanism of actin might be effective in humans.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	18-22
27871888-7	2017	Cd2+ could inhibit the uptake of metformin, a substrate of MATE transporters, with the half maximal inhibitory concentration (IC50) of 97.5+-6.0muM, 20.2+-2.6muM, and 49.9+-6.9muM in HEK-hMATE1, HEK-hMATE2-K, and HEK-mMate1 cells, respectively.	Metformin	33-42	solute carrier family 47 member 2	Homo sapiens	199-205
27871888-7	2017	Cd2+ could inhibit the uptake of metformin, a substrate of MATE transporters, with the half maximal inhibitory concentration (IC50) of 97.5+-6.0muM, 20.2+-2.6muM, and 49.9+-6.9muM in HEK-hMATE1, HEK-hMATE2-K, and HEK-mMate1 cells, respectively.	Metformin	33-42	solute carrier family 47, member 1	Mus musculus	213-223
27984715-3	2016	A key transcriptional target, ACAD10, is activated when metformin induces nuclear exclusion of the GTPase RagC, thereby inhibiting mTORC1 through an unexpected mechanism.	Metformin	56-65	CREB regulated transcription coactivator 1	Mus musculus	131-137
27865164-1	2016	OBJECTIVE: This study aimed to investigate the role of MTP on lipid metabolism disorders in insulin-resistant rats and the potential mechanism through which metformin can improve lipid metabolism disorders.	Metformin	157-166	microsomal triglyceride transfer protein	Rattus norvegicus	55-58
27865164-9	2016	Metformin also decreased MTP level in the liver [(7.65+-1.31) vs. (13.79+-1.47), p&lt;0.01].	Metformin	0-9	microsomal triglyceride transfer protein	Rattus norvegicus	25-28
27865164-10	2016	CONCLUSIONS: MTP may be associated with the lipid metabolism disorder in OLETF rats and metformin could improve lipid metabolism through reducing the expression of MTP.	Metformin	88-97	microsomal triglyceride transfer protein	Rattus norvegicus	164-167
27339044-2	2016	Metformin is a well-known substrate for OCT, and recently, we demonstrated that positron emission tomography (PET) with 11C-labelled metformin ((11)C-metformin) is a promising approach to evaluate the function of OCT.	Metformin	0-9	plexin A2	Mus musculus	40-43
27339044-2	2016	Metformin is a well-known substrate for OCT, and recently, we demonstrated that positron emission tomography (PET) with 11C-labelled metformin ((11)C-metformin) is a promising approach to evaluate the function of OCT.	Metformin	0-9	plexin A2	Mus musculus	213-216
27339044-2	2016	Metformin is a well-known substrate for OCT, and recently, we demonstrated that positron emission tomography (PET) with 11C-labelled metformin ((11)C-metformin) is a promising approach to evaluate the function of OCT.	Metformin	133-142	plexin A2	Mus musculus	40-43
27339044-2	2016	Metformin is a well-known substrate for OCT, and recently, we demonstrated that positron emission tomography (PET) with 11C-labelled metformin ((11)C-metformin) is a promising approach to evaluate the function of OCT.	Metformin	133-142	plexin A2	Mus musculus	213-216
27339044-2	2016	Metformin is a well-known substrate for OCT, and recently, we demonstrated that positron emission tomography (PET) with 11C-labelled metformin ((11)C-metformin) is a promising approach to evaluate the function of OCT.	Metformin	150-159	plexin A2	Mus musculus	40-43
27339044-2	2016	Metformin is a well-known substrate for OCT, and recently, we demonstrated that positron emission tomography (PET) with 11C-labelled metformin ((11)C-metformin) is a promising approach to evaluate the function of OCT.	Metformin	150-159	plexin A2	Mus musculus	213-216
27576133-7	2016	Second, metformin activates protein tyrosine phosphatase PP2A, a negative regulator of JAK2V617F.	Metformin	8-17	Janus kinase 2	Homo sapiens	87-91
27576133-10	2016	Finally, we determined that metformin enhances the antileukemic action of ruxolitinib in HEL and SET-2 cells.	Metformin	28-37	SET domain containing 2, histone lysine methyltransferase	Homo sapiens	97-102
27779693-5	2016	Metformin upregulated the expression of p21Waf1 and p27kip1, and downregulated the expression of cyclin D1, a key protein required for cell cycle progression.	Metformin	0-9	cyclin D1	Homo sapiens	97-106
27779693-7	2016	Administration of metformin enhanced the efficacy of gemcitabine and cisplatin to suppress the growth of cholangiocarcinoma tumors established in experimental models by inhibiting cell proliferation and inducing cell apoptosis through their effects on AMPK, cyclin D1 and caspase-3.	Metformin	18-27	cyclin D1	Homo sapiens	258-267
27645247-8	2016	Moxifloxacin was the only TB drug identified as a potent inhibitor (DDI index of &gt;0.1) of MATE1- and MATE2K-mediated metformin transport, with IC50s of 12 muM (95% confidence intervals [CI], 5.1 to 29 muM) and 7.6 muM (95% CI, 0.2 to 242 muM), respectively.	Metformin	120-129	solute carrier family 47 member 2	Homo sapiens	104-110
27600020-3	2016	Pre-incubation of cells with metformin, an AMPK activator, blocked PDGF-induced activation of mTOR and its downstream targets changes of Skp2 and p27 without changing Akt phosphorylation and inhibited ASMCs proliferation.	Metformin	29-38	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	43-47
27600020-3	2016	Pre-incubation of cells with metformin, an AMPK activator, blocked PDGF-induced activation of mTOR and its downstream targets changes of Skp2 and p27 without changing Akt phosphorylation and inhibited ASMCs proliferation.	Metformin	29-38	S-phase kinase associated protein 2	Homo sapiens	137-141
27600020-4	2016	Transfection of ASMCs with AMPK alpha2-specific small interfering RNA (siRNA) reversed the effect of metformin on mTOR phosphorylation, Skp2 and p27 protein expression and cell proliferation.	Metformin	101-110	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	27-38
27600020-4	2016	Transfection of ASMCs with AMPK alpha2-specific small interfering RNA (siRNA) reversed the effect of metformin on mTOR phosphorylation, Skp2 and p27 protein expression and cell proliferation.	Metformin	101-110	S-phase kinase associated protein 2	Homo sapiens	136-140
27830724-0	2016	Activation of AMPKalpha mediates additive effects of solamargine and metformin on suppressing MUC1 expression in castration-resistant prostate cancer cells.	Metformin	69-78	mucin 1, cell surface associated	Homo sapiens	94-98
27919027-7	2016	Clinically used AMPK activators metformin and salicylate enhanced the inhibitory phosphorylation of endogenous JAK1 and inhibited STAT3 phosphorylation in primary vascular endothelial cells.	Metformin	32-41	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	16-20
27820841-0	2016	Metformin Ameliorates Dysfunctional Traits of Glibenclamide- and Glucose-Induced Insulin Secretion by Suppression of Imposed Overactivity of the Islet Nitric Oxide Synthase-NO System.	Metformin	0-9	nitric oxide synthase 1, neuronal	Mus musculus	151-172
27820841-3	2016	We speculated that metformin might positively influence insulin secretion through impacting the beta-cell nitric oxide synthase (NOS)-NO system, a negative modulator of glucose-stimulated insulin release.	Metformin	19-28	nitric oxide synthase 1, neuronal	Mus musculus	106-127
27813479-2	2016	AMPK, a key sensor of metabolic stress stabilizes cell-cell junctions and maintains epithelial polarity; its activation by Metformin protects the epithelial barrier against stress and suppresses tumorigenesis.	Metformin	123-132	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
27813479-6	2016	This work defines a fundamental homeostatic mechanism by which the AMPK-GIV axis reinforces cell junctions against stress-induced collapse and also provides mechanistic insight into the tumor-suppressive action of Metformin.	Metformin	214-223	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	67-71
26551391-9	2016	Statins and metformin are known to inhibit mTORC1 indirectly via 5" adenosine monophosphate-activated protein kinase (AMPK) activation and may hold the key to exploit the full potential of mTORC1 inhibition in the treatment of atherosclerosis.	Metformin	12-21	CREB regulated transcription coactivator 1	Mus musculus	43-49
26551391-9	2016	Statins and metformin are known to inhibit mTORC1 indirectly via 5" adenosine monophosphate-activated protein kinase (AMPK) activation and may hold the key to exploit the full potential of mTORC1 inhibition in the treatment of atherosclerosis.	Metformin	12-21	CREB regulated transcription coactivator 1	Mus musculus	189-195
27389807-10	2016	In contrast, the AMPK activator metformin decreased beta-arrestin 1 expression and attenuated cardiac fibrosis in both young and old mice upon ISO exposure.	Metformin	32-41	arrestin, beta 1	Mus musculus	52-67
27415606-0	2016	A Longitudinal HbA1c Model Elucidates Genes Linked to Disease Progression on Metformin.	Metformin	77-86	hemoglobin subunit alpha 1	Homo sapiens	15-19
31687710-7	2019	Moreover, treatment with honey or combination of honey and metformin significantly enhanced glucokinase (GK) activity (p < 0.05), and meanwhile suppressed the activities of glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), pyruvate carboxylase (PC) and pyruvate dehydrogenase kinases (PDK) (p < 0.05) in diabetic mice.	Metformin	59-68	glucokinase	Mus musculus	92-103
31687710-7	2019	Moreover, treatment with honey or combination of honey and metformin significantly enhanced glucokinase (GK) activity (p < 0.05), and meanwhile suppressed the activities of glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), pyruvate carboxylase (PC) and pyruvate dehydrogenase kinases (PDK) (p < 0.05) in diabetic mice.	Metformin	59-68	glucokinase	Mus musculus	105-107
31687710-7	2019	Moreover, treatment with honey or combination of honey and metformin significantly enhanced glucokinase (GK) activity (p < 0.05), and meanwhile suppressed the activities of glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), pyruvate carboxylase (PC) and pyruvate dehydrogenase kinases (PDK) (p < 0.05) in diabetic mice.	Metformin	59-68	glucose-6-phosphatase, catalytic	Mus musculus	173-194
31687710-7	2019	Moreover, treatment with honey or combination of honey and metformin significantly enhanced glucokinase (GK) activity (p < 0.05), and meanwhile suppressed the activities of glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), pyruvate carboxylase (PC) and pyruvate dehydrogenase kinases (PDK) (p < 0.05) in diabetic mice.	Metformin	59-68	glucose-6-phosphatase, catalytic	Mus musculus	196-202
31687710-7	2019	Moreover, treatment with honey or combination of honey and metformin significantly enhanced glucokinase (GK) activity (p < 0.05), and meanwhile suppressed the activities of glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), pyruvate carboxylase (PC) and pyruvate dehydrogenase kinases (PDK) (p < 0.05) in diabetic mice.	Metformin	59-68	pyruvate carboxylase	Mus musculus	248-268
30989649-0	2019	Metformin treatment alleviates polycystic ovary syndrome by decreasing the expression of MMP-2 and MMP-9 via H19/miR-29b-3p and AKT/mTOR/autophagy signaling pathways.	Metformin	0-9	matrix metallopeptidase 2	Rattus norvegicus	89-94
30989649-1	2019	In this study, we aimed to investigate the molecular pathway(s) underlying the effect of metformin (MET) on the expression of matrix metalloproteinase (MMP)-2 and MMP-9.	Metformin	89-98	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	100-103
30989649-1	2019	In this study, we aimed to investigate the molecular pathway(s) underlying the effect of metformin (MET) on the expression of matrix metalloproteinase (MMP)-2 and MMP-9.	Metformin	89-98	matrix metallopeptidase 2	Rattus norvegicus	126-158
30988378-6	2019	Metformin specifically decreased IL-6R expression which is mediated via AMPK, mTOR, and miR34a.	Metformin	0-9	microRNA 34a	Homo sapiens	88-94
31737069-11	2019	Results: In HepG2 cells, metformin dose-dependently enhanced the transcriptional activity of FXR and MAFG and inhibited the expression of CYP8B1.	Metformin	25-34	nuclear receptor subfamily 1 group H member 4	Homo sapiens	93-96
31737069-15	2019	Conclusion: Changes in CA synthesis after metformin treatment may be associated with inhibition of CYP8B1.	Metformin	42-51	cytochrome P450 family 8 subfamily B member 1	Rattus norvegicus	99-105
31021474-4	2019	Additionally, metformin induces increased secretion of GLP-1 from intestinal L-cells.	Metformin	14-23	glucagon like peptide 1 receptor	Homo sapiens	55-60
31319131-6	2019	We found that the metformin pretreatment alleviated the lung injury and decreased the levels of TNF-a, IL-1beta and IL-6 in the bronchoalveolar lavage fluid (BALF) and in lung tissues, as well as the levels of NLRP3, NLRC4 and cleaved caspase-1 associated with LPS-induced ALI in old mice.	Metformin	18-27	NLR family, CARD domain containing 4	Mus musculus	217-222
31319131-7	2019	Furthermore, the in vitro study showed metformin dose-dependently suppressed NLRC4 inflammasome expression.	Metformin	39-48	NLR family, CARD domain containing 4	Mus musculus	77-82
31319131-10	2019	In conclusion, our data indicated that metformin may inhibit NLRC4 inflammasome activation in LPS-induced ALI in old mice through AMPK signaling, and further understanding of the AMPK/NLRC4 axis may provide a novel therapeutic strategy for LPS-induced ALI in the future.	Metformin	39-48	NLR family, CARD domain containing 4	Mus musculus	61-66
31319131-10	2019	In conclusion, our data indicated that metformin may inhibit NLRC4 inflammasome activation in LPS-induced ALI in old mice through AMPK signaling, and further understanding of the AMPK/NLRC4 axis may provide a novel therapeutic strategy for LPS-induced ALI in the future.	Metformin	39-48	NLR family, CARD domain containing 4	Mus musculus	184-189
31335763-6	2019	We further demonstrated that the anti-fibrotic effects of metformin in kidneys treated with cyclosporine A were associated with decreased phosphorylation of ERK1/2.	Metformin	58-67	mitogen activated protein kinase 3	Rattus norvegicus	157-163
31335763-7	2019	CONCLUSIONS: In conclusion, our study revealed new therapeutic potential of metformin to attenuate calcineurin inhibitor-induced renal fibrosis, which was closely related to the suppression of MEK/ERK1/2 pathway.	Metformin	76-85	mitogen activated protein kinase 3	Rattus norvegicus	197-203
31121159-11	2019	Moreover, the increased level of phosphorylation of Akt and GSK3beta in the frontal cortex induced by MK-801 was normalized by metformin.	Metformin	127-136	glycogen synthase kinase 3 beta	Rattus norvegicus	60-68
31325582-0	2019	Metformin reduces c-Fos and ATF3 expression in the dorsal root ganglia and protects against oxaliplatin-induced peripheral sensory neuropathy in mice.	Metformin	0-9	activating transcription factor 3	Mus musculus	28-32
31325582-10	2019	In addition, the oxaliplatin-associated nociception was significantly attenuated by metformin (P &lt; 0.05), which also reduced the expression of c-Fos and ATF3 (P &lt; 0.05).	Metformin	84-93	activating transcription factor 3	Mus musculus	156-160
31325582-11	2019	Therefore, metformin protected from the peripheral sensory neuropathy induced by oxaliplatin, which was confirmed by the reduction of c-Fos and ATF3 expression, two known neuronal activation and damage markers, respectively.	Metformin	11-20	activating transcription factor 3	Mus musculus	144-148
31292160-4	2019	To investigate the tumor cell autonomous effects of metformin, we engineered representative HPV- and HPV+ HNSCC cells harboring typical genetic alternations to express the yeast mitochondrial NADH dehydrogenase (NDI1) protein, which is insensitive to metformin.	Metformin	52-61	NADH-ubiquinone reductase (H(+)-translocating) NDI1	Saccharomyces cerevisiae S288C	212-216
31292160-5	2019	NDI1 expression rescued the inhibitory effects of metformin on mitochondrial complex I, abolished the ability of metformin to activate AMP-activated protein kinase, and inhibited mTOR signaling both in vitro and in vivo, and was sufficient to render metformin ineffective to prevent HNSCC tumor growth.	Metformin	50-59	NADH-ubiquinone reductase (H(+)-translocating) NDI1	Saccharomyces cerevisiae S288C	0-4
31292160-5	2019	NDI1 expression rescued the inhibitory effects of metformin on mitochondrial complex I, abolished the ability of metformin to activate AMP-activated protein kinase, and inhibited mTOR signaling both in vitro and in vivo, and was sufficient to render metformin ineffective to prevent HNSCC tumor growth.	Metformin	113-122	NADH-ubiquinone reductase (H(+)-translocating) NDI1	Saccharomyces cerevisiae S288C	0-4
31292160-5	2019	NDI1 expression rescued the inhibitory effects of metformin on mitochondrial complex I, abolished the ability of metformin to activate AMP-activated protein kinase, and inhibited mTOR signaling both in vitro and in vivo, and was sufficient to render metformin ineffective to prevent HNSCC tumor growth.	Metformin	113-122	NADH-ubiquinone reductase (H(+)-translocating) NDI1	Saccharomyces cerevisiae S288C	0-4
27808040-11	2016	Furthermore, metformin has been shown to increase circulating GLP-1 levels but although the exact mechanism is not fully elucidated it may involve metformin-induced inhibition of bile acid reuptake from the small intestines.	Metformin	13-22	glucagon like peptide 1 receptor	Homo sapiens	62-67
27808040-11	2016	Furthermore, metformin has been shown to increase circulating GLP-1 levels but although the exact mechanism is not fully elucidated it may involve metformin-induced inhibition of bile acid reuptake from the small intestines.	Metformin	147-156	glucagon like peptide 1 receptor	Homo sapiens	62-67
27808040-16	2016	We hypothesized that metformin-induced GLP-1 secretion - at least partly - would be dependent on gallbladder emptying and the presence of bile acids in the gut.	Metformin	21-30	glucagon like peptide 1 receptor	Homo sapiens	39-44
27808040-28	2016	Finally, study IV showed that both CCK-induced gallbladder emptying and metformin alone elicited significant GLP-1 responses that were additive upon combination.	Metformin	72-81	glucagon like peptide 1 receptor	Homo sapiens	109-114
27808040-33	2016	In addition, the observed gut hormone responses following CCK-induced gallbladder emptying and metformin, make suggest that bile acid release into the small intestines with subsequent TGR5 and FXR involvement contributes to stimulation of GLP-1 secretion and, therefore, that metformin"s mode of action encompasses both bile acid-dependent and independent stimulation of gut hormone secretion.	Metformin	95-104	glucagon like peptide 1 receptor	Homo sapiens	239-244
27808040-33	2016	In addition, the observed gut hormone responses following CCK-induced gallbladder emptying and metformin, make suggest that bile acid release into the small intestines with subsequent TGR5 and FXR involvement contributes to stimulation of GLP-1 secretion and, therefore, that metformin"s mode of action encompasses both bile acid-dependent and independent stimulation of gut hormone secretion.	Metformin	276-285	glucagon like peptide 1 receptor	Homo sapiens	239-244
27551045-12	2016	In kidney, metformin increased the activation of AMP-activated protein kinase (AMPK) and decreased inflammatory markers (COX-2 and IL-1beta) and apoptotic markers (poly(ADP-ribose) polymerase (PARP) and caspase 3).	Metformin	11-20	cytochrome c oxidase II, mitochondrial	Rattus norvegicus	121-126
27551045-12	2016	In kidney, metformin increased the activation of AMP-activated protein kinase (AMPK) and decreased inflammatory markers (COX-2 and IL-1beta) and apoptotic markers (poly(ADP-ribose) polymerase (PARP) and caspase 3).	Metformin	11-20	caspase 3	Rattus norvegicus	203-212
31581911-4	2019	Metformin increased p27 and LC3II expression and AMP-activated protein kinase (AMPK) phosphorylation, and decreased p62 expression, while miR-221 overexpression reversed the effects of metformin.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	49-77
31581911-4	2019	Metformin increased p27 and LC3II expression and AMP-activated protein kinase (AMPK) phosphorylation, and decreased p62 expression, while miR-221 overexpression reversed the effects of metformin.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	79-83
31195189-7	2019	However, treatment with 200 mg of metformin was more effective in increasing neurotrophic (myelin basic protein and neural growth factor), angiogenic (vascular endothelial growth factor) and anti-inflammatory (inhibitor kappa B-alpha and interleukin 10) factors.	Metformin	34-43	myelin basic protein	Mus musculus	91-111
30916407-7	2019	Drugs used in the treatment of diabetes, such as metformin, are also known to act through regulation of AMPK.	Metformin	49-58	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	104-108
31339921-7	2019	Besides, organoids are clearly more sensitive in the first stage (Apc mutated) to metformin than current chemotherapeutic drugs such as fluorouracil (5-FU).	Metformin	82-91	APC regulator of WNT signaling pathway	Homo sapiens	66-69
31339921-8	2019	Metformin performs an independent "Warburg effect" blockade to cancer progression and is able to reduce crypt stem cell markers expression such as LGR5+.	Metformin	0-9	leucine rich repeat containing G protein-coupled receptor 5	Homo sapiens	147-151
31044492-2	2019	Metformin, through inhibition of mTORC1 may improve acne.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	33-39
30867601-2	2019	While exercise, caloric restriction, metformin and many natural products increase AMPK activity and exert a multitude of health benefits, developing direct activators of AMPK to elicit beneficial effects has been challenging.	Metformin	37-46	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	82-86
27641099-5	2016	Remarkably, postnatal AMPK activation with AICAR or metformin rescued obesity-induced suppression of brown adipogenesis and thermogenesis.	Metformin	52-61	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	22-26
27732831-0	2016	Metformin Activates AMPK through the Lysosomal Pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	20-24
27459533-2	2016	Given the regulation of the cortisol-regenerating enzyme 11betahydroxysteroid dehydrogenase 1 (11betaHSD1) by insulin and the limited efficacy of selective 11betaHSD1 inhibitors to lower blood glucose when co-prescribed with metformin, we hypothesized that metformin reduces 11betaHSD1 activity.	Metformin	257-266	RNA, U1 small nuclear 1	Homo sapiens	28-105
31231998-3	2019	Recent reports show that inhibition of metformin (a first-line drug) on hepatic glucose in patients with hyperglycemia is associated with AMPK pathway, suggesting that targeting AMPK may be one of the effective strategies for the prevention and treatment of a variety of chronic diseases.	Metformin	39-48	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	138-142
31231998-3	2019	Recent reports show that inhibition of metformin (a first-line drug) on hepatic glucose in patients with hyperglycemia is associated with AMPK pathway, suggesting that targeting AMPK may be one of the effective strategies for the prevention and treatment of a variety of chronic diseases.	Metformin	39-48	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	178-182
30851273-0	2019	Metformin reduced NLRP3 inflammasome activity in Ox-LDL stimulated macrophages through adenosine monophosphate activated protein kinase and protein phosphatase 2A.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	87-135
30851273-2	2019	Previous researches showed that metformin activates Adenosine Monophosphate Activated Protein Kinase (AMPK) and Protein Phosphatase 2A (PP2A).	Metformin	32-41	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	52-100
30851273-2	2019	Previous researches showed that metformin activates Adenosine Monophosphate Activated Protein Kinase (AMPK) and Protein Phosphatase 2A (PP2A).	Metformin	32-41	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	102-106
30760033-3	2019	Results: We showed that metformin can improve the depression-like behavior in spatial restraint stress model; then we found that metformin through AMPK/Tet2 pathway increasing the expression of BDNF to antidepression.	Metformin	129-138	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	147-151
30760033-3	2019	Results: We showed that metformin can improve the depression-like behavior in spatial restraint stress model; then we found that metformin through AMPK/Tet2 pathway increasing the expression of BDNF to antidepression.	Metformin	129-138	tet methylcytosine dioxygenase 2	Homo sapiens	152-156
30760033-4	2019	Conclusion: Our study provided evidences that metformin plays a role of antidepressant effects through the AMPK/Tet2/BDNF pathway.	Metformin	46-55	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	107-111
30760033-4	2019	Conclusion: Our study provided evidences that metformin plays a role of antidepressant effects through the AMPK/Tet2/BDNF pathway.	Metformin	46-55	tet methylcytosine dioxygenase 2	Homo sapiens	112-116
30617965-4	2019	METHODS: Effect of the H6PD inhibitor metformin on brain 18F-FDG accumulation was studied, in vivo, by microPET imaging.	Metformin	38-47	hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase	Homo sapiens	23-27
30896786-7	2019	The specific mechanism underlying the function of metformin in EPCs was further elucidated by transfecting miR-130a mimics and inhibitor to overexpress and inhibit the expression of miR-130a in EPCs, respectively.	Metformin	50-59	microRNA 130a	Homo sapiens	107-115
30896786-7	2019	The specific mechanism underlying the function of metformin in EPCs was further elucidated by transfecting miR-130a mimics and inhibitor to overexpress and inhibit the expression of miR-130a in EPCs, respectively.	Metformin	50-59	microRNA 130a	Homo sapiens	182-190
30896786-10	2019	By contrast, downregulating the expression of miR-130a with a miR-130a inhibitor reversed the metformin-mediated protection.	Metformin	94-103	microRNA 130a	Homo sapiens	46-54
30896786-10	2019	By contrast, downregulating the expression of miR-130a with a miR-130a inhibitor reversed the metformin-mediated protection.	Metformin	94-103	microRNA 130a	Homo sapiens	62-70
30896786-11	2019	These results demonstrate the beneficial effect of miR-130a/PTEN on EPC functions, which can be regulated by metformin.	Metformin	109-118	microRNA 130a	Homo sapiens	51-59
30896786-12	2019	The effects of metformin on improving PA-induced EPC dysfunction are mediated by miR-130a and PTEN, which may assist in the prevention and/or treatment of diabetic vascular disease.	Metformin	15-24	microRNA 130a	Homo sapiens	81-89
30998979-7	2019	Metformin administration improved post-MI cardiac remodeling, an effect that was associated with increased IL-33 and reduced sST2 levels in the myocardium.	Metformin	0-9	interleukin 33	Rattus norvegicus	107-112
30998979-8	2019	The anti-remodeling effects of metformin were also associated with a decrease in the transcription factor Yy1 intranuclear level and lower levels of phosphorylated HDAC4 within the cytoplasmic space.	Metformin	31-40	histone deacetylase 4	Rattus norvegicus	164-169
30998979-10	2019	Metformin blocked the HDAC4 phosphorylation induced by MI, preventing its export from the nucleus to the cytosol.	Metformin	0-9	histone deacetylase 4	Rattus norvegicus	22-27
30896853-8	2019	The levels of microalbumin and serum beta2-microglobulin in GDM mice during late pregnancy were decreased following treatment with metformin.	Metformin	131-140	beta-2 microglobulin	Mus musculus	37-56
29848180-5	2019	Cellular proliferation was determined by the 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay, and in both cell lines, metformin decreased cell proliferation in a dose-dependent (10-200 micromol/L) manner and induced apoptosis as measured by cleaved PARP.	Metformin	137-146	collagen type XI alpha 2 chain	Homo sapiens	268-272
29848180-8	2019	Estrogen receptor alpha protein levels significantly decreased across all metformin doses tested, which resulted in a significant decrease in the expression of the ER targets genes Keratin-19 and Wnt-1 inducible signaling pathway 2.	Metformin	74-83	keratin 19	Homo sapiens	181-191
31008492-4	2019	In addition, the biological activities of metformin and adiponectin are closely related to activation of AMPK.	Metformin	42-51	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	105-109
31249600-8	2019	We correlate the metformin-induced delay in satellite cell activation with the inhibition of the ribosome protein RPS6, one of the downstream effectors of the mTOR pathway.	Metformin	17-26	ribosomal protein S6	Homo sapiens	114-118
30594717-4	2019	In the F0 generation, metformin significantly elevated gene expression for cytochrome P450 19a (CYP19a) and estrogen receptor alpha (ERalpha) in male fish; in female fish, the treatment decreased gene expression of vitellogenin (VTG2) and ERbeta1, suggesting endocrine disruption (one-way ANOVA, p <  0.05).	Metformin	22-31	estrogen receptor	Oryzias latipes	133-140
29934960-0	2019	Metformin inhibits TGF-beta 1-induced MCP-1 expression through BAMBI-mediated suppression of MEK/ERK1/2 signalling.	Metformin	0-9	mitogen activated protein kinase 3	Rattus norvegicus	97-103
30849634-0	2019	Metformin Augments Panobinostat"s Anti-Bladder Cancer Activity by Activating AMP-Activated Protein Kinase.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	77-105
30849634-3	2019	The antidiabetic drug metformin is also a potent AMPK activator and we investigated whether it augmented panobinostat"s antineoplastic activity in bladder cancer cells (UMUC3, J82, T24 and MBT-2).	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	49-53
30849634-5	2019	As expected, metformin increased the phosphorylation of AMPK and decreased the panobinostat-caused phosphorylation of S6 ribosomal protein, thus inhibiting the panobinostat-activated mTOR pathway.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	56-60
30849634-7	2019	Furthermore, the AMPK activation by metformin enhanced panobinostat-induced histone and non-histone acetylation.	Metformin	36-45	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	17-21
31114318-6	2019	Our unpublished data have demonstrated that Clusterin is overexpressed in bladder cancer and metformin, a well-known metabolism modulator specifically targets Clusterin by inhibiting migration of bladder cancer cells.	Metformin	93-102	clusterin	Homo sapiens	44-53
31114318-6	2019	Our unpublished data have demonstrated that Clusterin is overexpressed in bladder cancer and metformin, a well-known metabolism modulator specifically targets Clusterin by inhibiting migration of bladder cancer cells.	Metformin	93-102	clusterin	Homo sapiens	159-168
30649892-5	2019	Metformin counteracted glucose-dependent effects, and downregulated glutamate dehydrogenase, alanine aminotransferase, and mammalian target of rapamycin 5 h posttreatment in the absence of a glucose load, leading to decreased long-term activity of PFK1 and IDH.	Metformin	0-9	glutamic--pyruvic transaminase	Homo sapiens	93-117
30218617-0	2019	Cystatin C measurement leads to lower metformin dosage in elderly type 2 diabetic patients.	Metformin	38-47	cystatin C	Homo sapiens	0-10
30218617-1	2019	The aim of this study was to provide evidence for the hypothesis that estimated glomerular filtration rate from serum Cystatin C (eGFRcys) is better to be determined for all elderly type 2 diabetes mellitus (T2DM) patients based on eGFRcys upward and downward reclassification rate for hypothetical metformin dose reduction by eGFRcys at the GFR decision point of 45 mL/min/1.73 m2 .	Metformin	299-308	cystatin C	Homo sapiens	118-128
30218617-13	2019	Cystatin C-based eGFR selects more complicated patients, where lower doses of metformin are possibly advisable.	Metformin	78-87	cystatin C	Homo sapiens	0-10
30841429-8	2019	Metformin also enhanced thermogenic markers in the BAT (uncoupling protein type 1, peroxisome proliferator-activated receptor gamma coactivator-1 alpha) through adrenergic stimuli and fibroblast growth factor 21.	Metformin	0-9	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	75-151
30841429-8	2019	Metformin also enhanced thermogenic markers in the BAT (uncoupling protein type 1, peroxisome proliferator-activated receptor gamma coactivator-1 alpha) through adrenergic stimuli and fibroblast growth factor 21.	Metformin	0-9	fibroblast growth factor 21	Mus musculus	184-211
30599373-0	2019	Possible role of GLP-1 in antidepressant effects of metformin and exercise in CUMS mice.	Metformin	52-61	glucagon	Mus musculus	17-22
30599373-3	2019	As an enhancer and sensitiser of GLP-1, metformin has been reported to be safe for the neurodevelopment.	Metformin	40-49	glucagon	Mus musculus	33-38
30599373-4	2019	The present study aimed to determine whether and how GLP-1 mediates antidepressant effects of metformin and exercise in mice.	Metformin	94-103	glucagon	Mus musculus	53-58
30599373-13	2019	CONCLUSIONS: Our findings have demonstrated that protein levels of pERK and BAX may be relevant to the role of GLP-1 in antidepressant effects of metformin and exercise, which may provide a novel topic for future clinical research.	Metformin	146-155	glucagon	Mus musculus	111-116
30146703-3	2019	Metformin activates 5" adenosine monophosphate-activated protein kinase (AMPK) which directly suppresses the mTOR complex 1 signaling pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	23-71
30146703-3	2019	Metformin activates 5" adenosine monophosphate-activated protein kinase (AMPK) which directly suppresses the mTOR complex 1 signaling pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	73-77
30146703-4	2019	On the other hand, metformin can also inhibit mTOR directly and in an AMPK-independent manner.	Metformin	19-28	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	70-74
31041232-7	2019	Results: The cost-effectiveness for per unit reduction in HbA1c and FPG was significant in metformin plus glimepiride group as compared to the metformin plus teneligliptin group though it was comparable for both the groups for per unit PPG reduction.	Metformin	91-100	hemoglobin subunit alpha 1	Homo sapiens	58-62
31041232-7	2019	Results: The cost-effectiveness for per unit reduction in HbA1c and FPG was significant in metformin plus glimepiride group as compared to the metformin plus teneligliptin group though it was comparable for both the groups for per unit PPG reduction.	Metformin	143-152	hemoglobin subunit alpha 1	Homo sapiens	58-62
31041232-9	2019	Conclusion: Compared to metformin plus teneligliptin, metformin plus glimepiride is a significantly cost-effective therapy when used as an initial combination therapy in patients of T2DM in lowering HbA1c and FPG.	Metformin	54-63	hemoglobin subunit alpha 1	Homo sapiens	199-203
30628691-12	2019	The results demonstrated that metformin inhibited NF-kappaB mRNA expression and the nuclear translocation of NF-kappaB p65.	Metformin	30-39	RELA proto-oncogene, NF-kB subunit	Homo sapiens	119-122
30411223-10	2019	Finally, we showed that metformin administration restores the level of midbrain pAMPK and PGC-1alpha expression in Parkin-deficient mice.	Metformin	24-33	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	90-100
30854043-1	2019	Metformin can suppress cell proliferation and viability by altering mitochondrial energy metabolism and by the activation of 5"-adenosine monophosphate-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	125-176
30854043-1	2019	Metformin can suppress cell proliferation and viability by altering mitochondrial energy metabolism and by the activation of 5"-adenosine monophosphate-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	178-182
30854043-2	2019	The current study demonstrated that metformin-induced suppression of cell proliferation is further potentiated by AMPK-mediated suppression of beta-catenin-dependent wingless-type (Wnt) signaling.	Metformin	36-45	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	114-118
30854043-3	2019	Treatment with metformin reduced mitochondrial oxidative phosphorylation and glycolysis, leading to an energy imbalance that may induce AMPK phosphorylation in RKO cells.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	136-140
30854043-8	2019	Furthermore, metformin-induced suppression of cell proliferation was partially recovered by AMPK inhibition, while metformin inhibited Wnt-mediated cell proliferation and beta-catenin expression.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	92-96
30854043-9	2019	The present results suggest that AMPK activation can suppress beta-catenin-dependent Wnt signaling by cytoplasmic sequestering of beta-catenin through AMPK, which further decreases cell proliferation in addition to metformin-induced mitochondrial dysfunction.	Metformin	215-224	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	33-37
30854043-9	2019	The present results suggest that AMPK activation can suppress beta-catenin-dependent Wnt signaling by cytoplasmic sequestering of beta-catenin through AMPK, which further decreases cell proliferation in addition to metformin-induced mitochondrial dysfunction.	Metformin	215-224	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	151-155
30682184-12	2019	Metformin use, in 44% overall, was particularly associated with diarrhea (in 36% vs 17%, p = 0.02), and a lower median FGF19 (74 vs 105 pg/mL, p < 0.05).	Metformin	0-9	fibroblast growth factor 19	Homo sapiens	119-124
30682184-14	2019	Metformin use was an important factor in a subgroup, lowering FGF19, and resulting in bile acid diarrhea.	Metformin	0-9	fibroblast growth factor 19	Homo sapiens	62-67
30733676-5	2019	Results: After a 6-week experiment, non-fasting and fasting blood glucose levels and oral glucose tolerance test results showed that TB-2+BBR treatments (100 mg/kg/day) displayed significantly anti-diabetic efficacy in GK rats, comparable to that on metformin treatments.	Metformin	250-259	receptor accessory protein 5	Homo sapiens	133-137
30745857-5	2019	Using endometrial tissues from PCOS patients with hyperplasia, we found that in response to metformin treatment in vitro, hexokinase 2 (HK2) expression was decreased, whereas phosphofructokinase (PFK), PKM2, and lactate dehydrogenase A (LDHA) expression was increased compared to controls.	Metformin	92-101	hexokinase 2	Homo sapiens	122-134
30745857-5	2019	Using endometrial tissues from PCOS patients with hyperplasia, we found that in response to metformin treatment in vitro, hexokinase 2 (HK2) expression was decreased, whereas phosphofructokinase (PFK), PKM2, and lactate dehydrogenase A (LDHA) expression was increased compared to controls.	Metformin	92-101	hexokinase 2	Homo sapiens	136-139
30666163-0	2019	Metformin induces apoptotic cytotoxicity depending on AMPK/PKA/GSK-3beta-mediated c-FLIPL degradation in non-small cell lung cancer.	Metformin	0-9	glycogen synthase kinase 3 beta	Homo sapiens	63-72
30666163-2	2019	The aim of the present study was to investigate the role of cellular FADD-like IL-1beta-converting enzyme (FLICE)-inhibitory protein large (c-FLIPL) in metformin-induced anticancer activity in non-small cell lung cancer (NSCLC) in vitro.	Metformin	152-161	caspase 8	Homo sapiens	69-105
30666163-2	2019	The aim of the present study was to investigate the role of cellular FADD-like IL-1beta-converting enzyme (FLICE)-inhibitory protein large (c-FLIPL) in metformin-induced anticancer activity in non-small cell lung cancer (NSCLC) in vitro.	Metformin	152-161	caspase 8	Homo sapiens	107-112
30666163-10	2019	Furthermore, metformin significantly activated Adenosine 5"-monophosphate (AMP)-activated protein kinase (AMPK) and its downstream glycogen synthase kinase 3beta (GSK-3beta), block the expression of AMPK, and GSK-3beta with siRNA partially reversed metformin-induced cytotoxicity and restored the expression of c-FLIPL in lung cancer cells.	Metformin	13-22	glycogen synthase kinase 3 beta	Homo sapiens	131-161
30666163-10	2019	Furthermore, metformin significantly activated Adenosine 5"-monophosphate (AMP)-activated protein kinase (AMPK) and its downstream glycogen synthase kinase 3beta (GSK-3beta), block the expression of AMPK, and GSK-3beta with siRNA partially reversed metformin-induced cytotoxicity and restored the expression of c-FLIPL in lung cancer cells.	Metformin	13-22	glycogen synthase kinase 3 beta	Homo sapiens	163-172
30666163-10	2019	Furthermore, metformin significantly activated Adenosine 5"-monophosphate (AMP)-activated protein kinase (AMPK) and its downstream glycogen synthase kinase 3beta (GSK-3beta), block the expression of AMPK, and GSK-3beta with siRNA partially reversed metformin-induced cytotoxicity and restored the expression of c-FLIPL in lung cancer cells.	Metformin	13-22	glycogen synthase kinase 3 beta	Homo sapiens	209-218
30666163-12	2019	Conclusion: This study provided evidence that metformin killed NSCLC cells through AMPK/PKA/GSK-3beta axis-mediated c-FLIPL degradation.	Metformin	46-55	glycogen synthase kinase 3 beta	Homo sapiens	92-101
30625181-6	2019	Similarly, metformin treatment suppressed expressions of anti-apoptotic genes BCL2 and Bcl-xL, and mesenchymal genes vimentin, N-cadherin, Zeb1 and Zeb2 with simultaneous enhancement of apoptotic caspase 3 and Bax, and epithelial genes E-cadherin and keratin 19 expressions, confirming an inhibitory effect of metformin in tumorigenesis.	Metformin	11-20	keratin 19	Homo sapiens	251-261
30625181-9	2019	Similarly, cholesterol treatment inverted metformin-reduced several gene expressions (e.g., Bcl-xL, BCL2, Zeb1, vimentin, and BMI-1).	Metformin	42-51	BMI1 proto-oncogene, polycomb ring finger	Homo sapiens	126-131
30621095-7	2019	Treatment with metformin resulted in a dose-dependent induction of the stem cell genes CD44, BMI-1, OCT-4, and NANOG.	Metformin	15-24	BMI1 proto-oncogene, polycomb ring finger	Homo sapiens	93-98
30551411-0	2019	Metformin inhibits estradiol and progesterone-induced decidualization of endometrial stromal cells by regulating expression of progesterone receptor, cytokines and matrix metalloproteinases.	Metformin	0-9	progesterone receptor	Homo sapiens	127-148
30551411-11	2019	Metformin suppressed EP-induced MMP-2 and MMP-9 upregulation.	Metformin	0-9	matrix metallopeptidase 2	Homo sapiens	32-37
30551411-14	2019	CONCLUSION: Metformin alleviated EP-induced decidualization of endometrial stromal cells by modulating secretion of multiple cytokines, inhibiting expression of MMP-2 and MMP-9, activating p38-MAPK signaling and reducing PGR expression, providing a deep insight into the molecular basis of metfromin therapy for PCOS patients.	Metformin	12-21	matrix metallopeptidase 2	Homo sapiens	161-166
27688683-6	2016	Results Metformin significantly inhibited FaDu cell proliferation in a dose- (25-100 mmol/l) and time-dependent manner (12 h-36 h), significantly downregulated miR-21-5p, and upregulated PDCD4 mRNA and protein expression.	Metformin	8-17	programmed cell death 4	Homo sapiens	187-192
27688683-7	2016	Conclusions Metformin significantly inhibited FaDu cell proliferation , possibly via downregulation of miR-21-5p and upregulation of PDCD4.	Metformin	12-21	programmed cell death 4	Homo sapiens	133-138
27681875-0	2016	Neuropeptide Y Overexpressing Female and Male Mice Show Divergent Metabolic but Not Gut Microbial Responses to Prenatal Metformin Exposure.	Metformin	120-129	neuropeptide Y	Mus musculus	0-14
30318707-12	2019	AMP-activated protein kinase (AMPK) activated by metformin-induced stimulation of forkhead box O3a (FoxO3a) transcriptional activity, followed by increased expression of GABAA receptor-associated protein (GABARAP) and its binding to GABAA receptors finally resulted in the membrane insertion of GABAA receptors.	Metformin	49-58	forkhead box O3	Rattus norvegicus	82-98
30318707-12	2019	AMP-activated protein kinase (AMPK) activated by metformin-induced stimulation of forkhead box O3a (FoxO3a) transcriptional activity, followed by increased expression of GABAA receptor-associated protein (GABARAP) and its binding to GABAA receptors finally resulted in the membrane insertion of GABAA receptors.	Metformin	49-58	forkhead box O3	Rattus norvegicus	100-106
30318707-13	2019	CONCLUSIONS AND IMPLICATIONS: Metformin increased mIPSCs by up-regulating the membrane insertion of GABAA receptors, via a pathway involving AMPK, FoxO3a, and the GABAA receptor-associated protein.	Metformin	30-39	forkhead box O3	Rattus norvegicus	147-153
30520054-5	2019	Immunofluorescence staining and western blot analysis showed that metformin inhibited the nuclear localization of p65, a subunit of nuclear factor NF-kappaB.	Metformin	66-75	RELA proto-oncogene, NF-kB subunit	Homo sapiens	114-117
30959381-11	2019	Metformin improved insulin sensitivity, decreased Cer and DAG levels, and attenuated the phosphorylation of HSL in both fat depots.	Metformin	0-9	lipase E, hormone sensitive type	Rattus norvegicus	108-111
27564915-1	2016	Ion transfer voltammetry is used to estimate the acid dissociation constants Ka1 and Ka2 of the mono- and diprotonated forms of the biguanide drugs metformin (MF), phenformin (PF), and 1-phenylbiguanide (PB) in an aqueous solution.	Metformin	148-157	glutamate ionotropic receptor kainate type subunit 5	Homo sapiens	85-88
27564915-1	2016	Ion transfer voltammetry is used to estimate the acid dissociation constants Ka1 and Ka2 of the mono- and diprotonated forms of the biguanide drugs metformin (MF), phenformin (PF), and 1-phenylbiguanide (PB) in an aqueous solution.	Metformin	159-161	glutamate ionotropic receptor kainate type subunit 5	Homo sapiens	85-88
27640062-15	2016	Insulin-metformin CT compared with IM showed a MD in HbA1c of -0.9% (95% CI -1.2 to -0.5); P &lt; 0.01; 698 participants; 9 trials; low-quality evidence.	Metformin	8-17	hemoglobin subunit alpha 1	Homo sapiens	53-57
27725874-5	2016	Further analysis showed that metformin may induce VEGF-A mRNA splicing to VEGF120 isoform to reduce its activation of the VEGFR2.	Metformin	29-38	kinase insert domain protein receptor	Mus musculus	122-128
30320344-5	2019	However, the effect of metformin on gastric TAFs and TAF-associated cancer progression has remained to be elucidated.	Metformin	23-32	TATA-box binding protein associated factor 8	Homo sapiens	44-47
30097812-11	2018	Increased CX3CR1 protein content in the placental lysates was observed in subgroups B and C. The two higher metformin concentrations significantly decreased the levels of NF-kappaBp65 protein content in both groups.	Metformin	108-117	RELA proto-oncogene, NF-kB subunit	Homo sapiens	171-183
30317407-5	2018	In addition metformin had improved the density of the significantly decreased arteriolar (alphaSMA+) and capillary (CD31+) coronary microvasculature compared to that of the DCM and non-diabetics (ND) with downregulation of the significantly increased expression (p &lt; 0.05) of COL-I, III, TGF-beta, CTGF, ICAM and VCAM genes.	Metformin	12-21	cellular communication network factor 2	Homo sapiens	301-305
30459620-8	2018	In addition, we found that adenosine monophosphate-activated protein kinase (AMPK) activation is involved in CREB/BDNF regulation in HG-incubated HUVECs treated with metformin and that an AMPK inhibitor impaired the protective effects of metformin on HG-treated HUVECs.	Metformin	166-175	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	27-75
30459620-8	2018	In addition, we found that adenosine monophosphate-activated protein kinase (AMPK) activation is involved in CREB/BDNF regulation in HG-incubated HUVECs treated with metformin and that an AMPK inhibitor impaired the protective effects of metformin on HG-treated HUVECs.	Metformin	166-175	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	77-81
30459620-8	2018	In addition, we found that adenosine monophosphate-activated protein kinase (AMPK) activation is involved in CREB/BDNF regulation in HG-incubated HUVECs treated with metformin and that an AMPK inhibitor impaired the protective effects of metformin on HG-treated HUVECs.	Metformin	238-247	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	27-75
30459620-8	2018	In addition, we found that adenosine monophosphate-activated protein kinase (AMPK) activation is involved in CREB/BDNF regulation in HG-incubated HUVECs treated with metformin and that an AMPK inhibitor impaired the protective effects of metformin on HG-treated HUVECs.	Metformin	238-247	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	77-81
30459620-8	2018	In addition, we found that adenosine monophosphate-activated protein kinase (AMPK) activation is involved in CREB/BDNF regulation in HG-incubated HUVECs treated with metformin and that an AMPK inhibitor impaired the protective effects of metformin on HG-treated HUVECs.	Metformin	238-247	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	188-192
30459620-9	2018	In conclusion, this study demonstrated that metformin affects cell proliferation and apoptosis via the AMPK/CREB/BDNF pathway in HG-incubated HUVECs.	Metformin	44-53	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	103-107
30607342-14	2018	Treatment with metformin caused suppression of upregulated genes and IL-4 cytokine level, associated with amelioration of pathological changes.	Metformin	15-24	interleukin 4	Rattus norvegicus	69-73
30607342-16	2018	Treatment with metformin showed ability to attenuate upregulation of IL-4-DUOX2 pathway and other pathological damages to the lung after exposure to a high dose of IR.	Metformin	15-24	interleukin 4	Rattus norvegicus	69-73
30396946-2	2018	The anti-diabetic drug metformin exerts various antitumor effects via the 5"-adenosine monophosphate-activated protein kinase (AMPK) pathway and nuclear factor-kappa B (NF-kB).	Metformin	23-32	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	127-131
30098371-10	2018	Although the increase in DNA pol beta was not significant, XRCC1 and p53 levels were significantly upregulated with metformin treatment in type 2 diabetes patients.	Metformin	116-125	DNA polymerase beta	Homo sapiens	25-37
30294927-0	2018	Co-administration of nuciferine reduces the concentration of metformin in liver via differential inhibition of hepatic drug transporter OCT1 and MATE1.	Metformin	61-70	solute carrier family 47, member 1	Mus musculus	145-150
30294927-3	2018	Since nuciferine and metformin are likely to be co-administered, the aim of the present study was to evaluate whether co-administration of nuciferine would influence the liver (target tissue) distribution and the anti-diabetic effect of metformin by inhibiting hepatic organic cation transporter 1 (OCT1) and multidrug and toxin extrusion 1 (MATE1).	Metformin	237-246	solute carrier family 47, member 1	Mus musculus	309-340
30294927-3	2018	Since nuciferine and metformin are likely to be co-administered, the aim of the present study was to evaluate whether co-administration of nuciferine would influence the liver (target tissue) distribution and the anti-diabetic effect of metformin by inhibiting hepatic organic cation transporter 1 (OCT1) and multidrug and toxin extrusion 1 (MATE1).	Metformin	237-246	solute carrier family 47, member 1	Mus musculus	342-347
30294927-7	2018	Therefore, nuciferine influenced the liver concentration and glucose-lowering effect of metformin only for a period of time after dose, administration of nuciferine and metformin with an interval might prevent the drug-drug interaction mediated by OCT1 and MATE1.	Metformin	88-97	solute carrier family 47, member 1	Mus musculus	257-262
30294927-7	2018	Therefore, nuciferine influenced the liver concentration and glucose-lowering effect of metformin only for a period of time after dose, administration of nuciferine and metformin with an interval might prevent the drug-drug interaction mediated by OCT1 and MATE1.	Metformin	169-178	solute carrier family 47, member 1	Mus musculus	257-262
30159732-5	2018	Drug-drug interactions of metformin with proton pump inhibitors and histamine H2-receptor antagonists may be of clinical relevance and pertinent to future research of metformin in pancreatic ductal adenocarcinoma.	Metformin	167-176	histamine receptor H2	Homo sapiens	68-89
27623749-7	2016	Overproduction of KCNC2 decreased ER stress, and treatment with metformin enhanced KCNC2 expression.	Metformin	64-73	potassium voltage-gated channel subfamily C member 2	Homo sapiens	83-88
29630425-10	2018	CONCLUSIONS: Metformin suppressed the production of Th1-related chemokines IP-10 and MCP-1 in THP-1 cells.	Metformin	13-22	chemokine (C-X-C motif) ligand 10	Mus musculus	75-80
30389502-0	2018	The antineoplastic drug metformin downregulates YAP by interfering with IRF-1 binding to the YAP promoter in NSCLC.	Metformin	24-33	Yes1 associated transcriptional regulator	Homo sapiens	48-51
30389502-0	2018	The antineoplastic drug metformin downregulates YAP by interfering with IRF-1 binding to the YAP promoter in NSCLC.	Metformin	24-33	Yes1 associated transcriptional regulator	Homo sapiens	93-96
30389502-3	2018	However, the mechanism through which metformin inhibits tumorigenesis via YAP is poorly understood.	Metformin	37-46	Yes1 associated transcriptional regulator	Homo sapiens	74-77
30389502-10	2018	Interestingly, metformin was able to downregulate YAP mRNA and protein expression in lung cancer cells.	Metformin	15-24	Yes1 associated transcriptional regulator	Homo sapiens	50-53
27486978-4	2016	The treatment effect of metformin (for ever versus never users, and for tertiles of cumulative duration of therapy) was estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score.	Metformin	24-33	cytochrome c oxidase subunit 8A	Homo sapiens	133-136
27494895-4	2016	Drugs with angiopreventive activities, in particular metformin, regulate AMPK in endothelial cells.	Metformin	53-62	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	73-77
27600499-7	2016	Compared with control (placebo, sitagliptin, glimepiride, dulaglutide, insulin glargine, and NPH), liraglutide in combination with metformin resulted in significant reductions in HbA1c, bodyweight, FPG, and PPG, and similar reductions in SBP, and DBP.	Metformin	131-140	selenium binding protein 1	Homo sapiens	238-241
27378194-1	2016	Metformin exerts antitumor effects mainly through AMP-activated protein kinase [AMPK] activation and phosphatidylinositol 3-kinase [PI3K]-Akt-mammalian target of rapamycin [mTOR] inhibition.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	50-78
27378194-1	2016	Metformin exerts antitumor effects mainly through AMP-activated protein kinase [AMPK] activation and phosphatidylinositol 3-kinase [PI3K]-Akt-mammalian target of rapamycin [mTOR] inhibition.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	80-84
27603343-11	2016	CONCLUSION: Metformin treatment in women with PCOS throughout pregnancy could increase the possibility of term delivery, VD and reduce the risk of EPL, preterm labor, pregnancy complications such as GDM and PIH, with no serious side effects.	Metformin	12-21	pregnancy-induced hypertension (pre-eclampsia, eclampsia, toxemia of pregnancy included)	Homo sapiens	207-210
27435670-0	2016	NHX-5, an Endosomal Na+/H+ Exchanger, Is Associated with Metformin Action.	Metformin	57-66	Sodium/hydrogen exchanger	Caenorhabditis elegans	0-5
30389502-11	2018	Mechanistically, we found that metformin depressed YAP promoter by competing with the binding of the transcription factor IRF-1 in lung cancer cells.	Metformin	31-40	Yes1 associated transcriptional regulator	Homo sapiens	51-54
30389502-12	2018	Moreover, combination of metformin and verteporfin synergistically inhibits cell proliferation, promotes apoptosis and suppresses cell migration/invasion by downregulating YAP, therefore reduces the side effects caused by their single use and improve the quality of life for patients with lung cancer.	Metformin	25-34	Yes1 associated transcriptional regulator	Homo sapiens	172-175
30389502-13	2018	INTERPRETATION: we concluded that metformin depresses YAP promoter by interfering with the binding of the transcription factor IRF-1.	Metformin	34-43	Yes1 associated transcriptional regulator	Homo sapiens	54-57
30389502-14	2018	Importantly, verteporfin sensitizes metformin-induced the depression of YAP and inhibition of cell growth and invasion in lung cancer cells.	Metformin	36-45	Yes1 associated transcriptional regulator	Homo sapiens	72-75
30536344-0	2018	Metformin promotes differentiation of human bone marrow derived mesenchymal stem cells into osteoblast via GSK3beta inhibition.	Metformin	0-9	glycogen synthase kinase 3 alpha	Homo sapiens	107-115
30536344-4	2018	Therefore, the aim of this study is to evaluate the role of GSK3beta in metformin-induced osteogenic differentiation of mesenchymal stem cells (MSCs).	Metformin	72-81	glycogen synthase kinase 3 alpha	Homo sapiens	60-68
30536344-7	2018	The expression of GSK3beta, beta-catenin and AMPK were measured by Western blotting in MSCs treated with metformin.	Metformin	105-114	glycogen synthase kinase 3 alpha	Homo sapiens	18-26
30536344-9	2018	Next, we showed that GSK3beta and Wnt signaling pathway are involved in metformin-induced osteogenic differentiation of hBMSCs.	Metformin	72-81	glycogen synthase kinase 3 alpha	Homo sapiens	21-29
30536344-10	2018	Furthermore, osteogenic differentiation of hBMSCs induced by metformin could be eliminated by inhibiting phosphorylation of GSK3beta.	Metformin	61-70	glycogen synthase kinase 3 alpha	Homo sapiens	124-132
30536344-11	2018	CONCLUSIONS: The data suggested that metformin promoted the osteoblast differentiation of MSCs by, at least partly, inhibiting GSK3beta activity.	Metformin	37-46	glycogen synthase kinase 3 alpha	Homo sapiens	127-135
30536344-12	2018	Additionally, we also found that AMPK plays an essential role in the inhibition of GSK3beta by metformin.	Metformin	95-104	glycogen synthase kinase 3 alpha	Homo sapiens	83-91
29380373-10	2018	Folic acid induced nephropathy was associated with the overexpression of inflammatory markers MCP-1, F4/80, type IV collagen, fibronectin and TGF-beta1 compared to control groups, which were partially attenuated by metformin treatment.	Metformin	215-224	transforming growth factor, beta 1	Mus musculus	142-151
29380373-11	2018	In vitro studies confirmed that metformin inhibited TGF-beta1 induced inflammatory and fibrotic responses through Smad3, ERK1/2, and P38 pathways in human renal proximal tubular cells.	Metformin	32-41	SMAD family member 3	Homo sapiens	114-119
30230981-7	2018	We observed that metformin prevented the stimulating effect of LPS on these chemokines as well as IL-1 and IL-6.	Metformin	17-26	interleukin 1 complex	Mus musculus	98-102
30171481-8	2018	Although professional guidelines recommend metformin as the sole first-line agent, GLP-1 RAs can be used as first-line therapy in individuals with type 2 diabetes who either are intolerant to metformin or have high cardiovascular risk factors.	Metformin	192-201	glucagon like peptide 1 receptor	Homo sapiens	83-88
27401566-8	2016	In mouse primary proximal tubular cells, [(3)H]gentamicin uptake was reduced by approximately 40% when the cells were coincubated with the OCT2 substrate metformin.	Metformin	154-163	solute carrier family 22 (organic cation transporter), member 2	Mus musculus	139-143
27418629-3	2016	METHODS AND RESULTS: In primary hepatocytes from healthy animals, metformin and the IKKbeta (inhibitor of kappa B kinase) inhibitor BI605906 both inhibited tumor necrosis factor-alpha-dependent IkappaB degradation and expression of proinflammatory mediators interleukin-6, interleukin-1beta, and CXCL1/2 (C-X-C motif ligand 1/2).	Metformin	66-75	C-X-C motif chemokine ligand 12	Homo sapiens	296-303
27418629-3	2016	METHODS AND RESULTS: In primary hepatocytes from healthy animals, metformin and the IKKbeta (inhibitor of kappa B kinase) inhibitor BI605906 both inhibited tumor necrosis factor-alpha-dependent IkappaB degradation and expression of proinflammatory mediators interleukin-6, interleukin-1beta, and CXCL1/2 (C-X-C motif ligand 1/2).	Metformin	66-75	C-X-C motif chemokine ligand 12	Homo sapiens	305-327
27555891-7	2016	Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters (SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin.	Metformin	310-319	solute carrier family 47 member 2	Homo sapiens	247-254
27323827-0	2016	Metformin mediates resensitivity to 5-fluorouracil in hepatocellular carcinoma via the suppression of YAP.	Metformin	0-9	Yes1 associated transcriptional regulator	Homo sapiens	102-105
27323827-5	2016	Moreover, metformin repressed YAP by both decreasing the total protein expression and accelerating the phosphorylation of YAP.	Metformin	10-19	Yes1 associated transcriptional regulator	Homo sapiens	30-33
27323827-5	2016	Moreover, metformin repressed YAP by both decreasing the total protein expression and accelerating the phosphorylation of YAP.	Metformin	10-19	Yes1 associated transcriptional regulator	Homo sapiens	122-125
27323827-8	2016	Taken together, our findings suggested that metformin may increase sensitivity to chemotherapeutic agents by suppressing YAP in hepatocellular carcinoma.	Metformin	44-53	Yes1 associated transcriptional regulator	Homo sapiens	121-124
27434443-13	2016	When added to metformin and sulfonylurea, GLP-1 receptor agonists were associated with the lowest odds of hypoglycemia (OR, 0.60 [95% CI, 0.39 to 0.94]; RD, -10% [95% CI, -18% to -2%]).	Metformin	14-23	glucagon like peptide 1 receptor	Homo sapiens	42-56
28881582-1	2017	Metformin inhibits the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, which is frequently upregulated in hepatocellular carcinoma (HCC).	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	64-70
28881582-3	2017	Here, we investigate whether metformin-induced apoptosis in HCC is mediated by the downstream mTORC1 effectors eukaryotic initiation factor 4E and (eIF4E)-binding proteins (4E-BPs).	Metformin	29-38	CREB regulated transcription coactivator 1	Mus musculus	94-100
28881582-3	2017	Here, we investigate whether metformin-induced apoptosis in HCC is mediated by the downstream mTORC1 effectors eukaryotic initiation factor 4E and (eIF4E)-binding proteins (4E-BPs).	Metformin	29-38	eukaryotic translation initiation factor 4E	Homo sapiens	111-142
28881582-5	2017	A genetic HCC mouse model was employed to assess the ability of metformin to reduce tumor formation, induce apoptosis, and control 4E-BP1 activation and Mcl-1 protein expression.	Metformin	64-73	myeloid cell leukemia sequence 1	Mus musculus	153-158
27217398-12	2016	Importantly, long-term treatment with metformin, an AMPK activator, significantly attenuated hypoxia-induced PH in mice.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	52-56
26869171-5	2016	The relation of thiazolidinediones- and metformin- induced post-treatment serum levels of fetuin-A and OPG to changes in CV risk requires more investigations.	Metformin	40-49	TNF receptor superfamily member 11b	Homo sapiens	103-106
27181910-4	2016	RESULTS: Co-administration of teneligliptin (5 to 40 mg) with metformin demonstrated dose-related and statistically significant reductions in HbA1c after 24 weeks (-0.30 to -0.63% placebo adjusted) of double-blind treatment.	Metformin	62-71	hemoglobin subunit alpha 1	Homo sapiens	142-146
27282867-5	2016	Given evidence that COMT modifies some drug responses, we examined association with type 2 diabetes and randomized metformin and aspirin treatment.	Metformin	115-124	catechol-O-methyltransferase	Homo sapiens	20-24
27144291-6	2016	Glucose also induced CRCT-2 translocation into the nucleus and the AMPK activator metformin decreased basal and glucose-induced CRE activity, suggesting a role for AMPK/CRTC-2 in glucose-induced CRE activation.	Metformin	82-91	CREB regulated transcription coactivator 2	Mus musculus	169-175
27199291-5	2016	Interestingly, several potential antiobesity and/or antidiabetic agents, some of which are currently in clinical use such as metformin and liraglutide, exert some of their actions by acting on AMPK.	Metformin	125-134	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	193-197
27076180-7	2016	Conversely, DPP-4 inhibitors and GLP-1 receptor agonists gained market shares due to their efficacy in glycemic control as an add-on treatment to metformin.	Metformin	146-155	glucagon like peptide 1 receptor	Homo sapiens	33-47
26993065-6	2016	In contrast, inhibition of MATE1 with pyrimethamine caused accumulation of metformin in the liver but did not affect distribution in the small intestine.	Metformin	75-84	solute carrier family 47, member 1	Mus musculus	27-32
27035650-8	2016	Activation of AMPK by metformin inhibited ID effects both in vivo and in vitro.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	14-18
27035653-11	2016	Finally, treatment of INS-1E cells with metformin for 24 h resulted in inhibition of SREBP-1C expression, increased PDX-1 and GLP-1 receptor levels, consequently, enhancement of exendin-4-induced insulin release.	Metformin	40-49	sterol regulatory element binding transcription factor 1	Rattus norvegicus	85-93
27109601-6	2016	Metformin also upregulated DNA repair as evidenced by the increase in expression of p53R2.	Metformin	0-9	ribonucleotide reductase regulatory TP53 inducible subunit M2B	Homo sapiens	84-89
27109601-9	2016	However, resveratrol displayed synergism when combined with metformin as shown by the downregulation of p53/gammaH2AX/p-chk2.	Metformin	60-69	checkpoint kinase 2	Homo sapiens	120-124
29851159-6	2018	Metformin-based regimens were associated with significantly lower adjusted all-cause (aHR 0.18 0.410.91 ), malignancy-related (aHR 0.45 0.450.99 ), and infection-related (aHR 0.12 0.320.85 ) mortality, and nonsignificant trends toward lower cardiovascular mortality, graft failure, and acute rejection.	Metformin	0-9	aryl hydrocarbon receptor	Homo sapiens	86-89
29851159-6	2018	Metformin-based regimens were associated with significantly lower adjusted all-cause (aHR 0.18 0.410.91 ), malignancy-related (aHR 0.45 0.450.99 ), and infection-related (aHR 0.12 0.320.85 ) mortality, and nonsignificant trends toward lower cardiovascular mortality, graft failure, and acute rejection.	Metformin	0-9	aryl hydrocarbon receptor	Homo sapiens	127-130
29851159-6	2018	Metformin-based regimens were associated with significantly lower adjusted all-cause (aHR 0.18 0.410.91 ), malignancy-related (aHR 0.45 0.450.99 ), and infection-related (aHR 0.12 0.320.85 ) mortality, and nonsignificant trends toward lower cardiovascular mortality, graft failure, and acute rejection.	Metformin	0-9	aryl hydrocarbon receptor	Homo sapiens	127-130
30178862-16	2018	After NR8383 was treated with metformin and LPS, the expression of SIRT1 was higher than that of LPS treatment alone, but the expression of p-p38, p-ERK, and p-NF-kappaB was significantly decreased.	Metformin	30-39	mitogen-activated protein kinase 14	Mus musculus	142-145
29865970-0	2018	Inhibiting ROS-TFE3-dependent autophagy enhances the therapeutic response to metformin in breast cancer.	Metformin	77-86	transcription factor binding to IGHM enhancer 3	Homo sapiens	15-19
29865970-7	2018	Mechanistically, metformin-induced TFE3(Ser321) dephosphorylation activated TFE3 nuclear translocation and increased of TFE3 reporter activity, which contributed to lysosomal biogenesis and the expression of autophagy-related genes and, subsequently, initiated autophagy in MCF-7 cells.	Metformin	17-26	transcription factor binding to IGHM enhancer 3	Homo sapiens	35-39
29865970-7	2018	Mechanistically, metformin-induced TFE3(Ser321) dephosphorylation activated TFE3 nuclear translocation and increased of TFE3 reporter activity, which contributed to lysosomal biogenesis and the expression of autophagy-related genes and, subsequently, initiated autophagy in MCF-7 cells.	Metformin	17-26	transcription factor binding to IGHM enhancer 3	Homo sapiens	76-80
29865970-7	2018	Mechanistically, metformin-induced TFE3(Ser321) dephosphorylation activated TFE3 nuclear translocation and increased of TFE3 reporter activity, which contributed to lysosomal biogenesis and the expression of autophagy-related genes and, subsequently, initiated autophagy in MCF-7 cells.	Metformin	17-26	transcription factor binding to IGHM enhancer 3	Homo sapiens	76-80
29865970-9	2018	Furthermore, N-acetyl-l-cysteine (NAC), a ROS scavenger, abrogated the effects of metformin on TFE3-dependent autophagy.	Metformin	82-91	transcription factor binding to IGHM enhancer 3	Homo sapiens	95-99
29865970-11	2018	Taken together, these data demonstrate that blocking ROS-TFE3-dependent autophagy to enhance the activity of metformin warrants further attention as a treatment strategy for breast cancer.	Metformin	109-118	transcription factor binding to IGHM enhancer 3	Homo sapiens	57-61
31324081-1	2018	Objectives: To compare the safety and efficacy of combination of Glimepiride - Metformin with Vildagliptin - Metformin in type 2 diabetic patients with HbA1c between 7.5to10.	Metformin	109-118	hemoglobin subunit alpha 1	Homo sapiens	152-156
29737584-0	2018	Metformin increases the cytotoxicity of oxaliplatin in human DLD-1 colorectal cancer cells through down-regulating HMGB1 expression.	Metformin	0-9	high mobility group box 1	Homo sapiens	115-120
29737584-7	2018	In this study, we examined whether HMGB1 plays a role in the OXA- and/or metformin-induced cytotoxic effect on CRC cells.	Metformin	73-82	high mobility group box 1	Homo sapiens	35-40
29737584-11	2018	Compared to a single agent, OXA combined with metformin administration resulted in cytotoxicity and cell growth inhibition synergistically, accompanied with reduced HMGB1 level.	Metformin	46-55	high mobility group box 1	Homo sapiens	165-170
30104887-0	2018	Metformin induces miR-378 to downregulate the CDK1, leading to suppression of cell proliferation in hepatocellular carcinoma.	Metformin	0-9	cyclin-dependent kinase 1	Mus musculus	46-50
30104887-9	2018	At the same time, metformin efficiently decreased CDK1 expression and elevated miR-378 level.	Metformin	18-27	cyclin-dependent kinase 1	Mus musculus	50-54
30104887-13	2018	Discussion: Metformin-suppressed HCC cell proliferation was dependent on the inhibitory effect of miR-378 on CDK1 expression.	Metformin	12-21	cyclin-dependent kinase 1	Mus musculus	109-113
30104887-14	2018	Taken together, we concluded that metformin inhibited HCC cell proliferation via modulating miR-378/CDK1 axis.	Metformin	34-43	cyclin-dependent kinase 1	Mus musculus	100-104
30104887-15	2018	Conclusion: Collectively, the current results provide the first evidence, to our knowledge, that miR-378/CDK1 axis is involved in metformin modulating the proliferation of HCC cells, which suggests a novel molecular mechanism underlying the thera peutic effect of metformin on HCC.	Metformin	130-139	cyclin-dependent kinase 1	Mus musculus	105-109
30104887-15	2018	Conclusion: Collectively, the current results provide the first evidence, to our knowledge, that miR-378/CDK1 axis is involved in metformin modulating the proliferation of HCC cells, which suggests a novel molecular mechanism underlying the thera peutic effect of metformin on HCC.	Metformin	264-273	cyclin-dependent kinase 1	Mus musculus	105-109
30022161-7	2018	Treatment with the anti-diabetic drug metformin protects AMPK-mediated phosphorylation of serine 99, thereby increasing TET2 stability and 5hmC levels.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	57-61
30022161-7	2018	Treatment with the anti-diabetic drug metformin protects AMPK-mediated phosphorylation of serine 99, thereby increasing TET2 stability and 5hmC levels.	Metformin	38-47	tet methylcytosine dioxygenase 2	Homo sapiens	120-124
29914345-5	2018	RESULTS: Our association analysis revealed that SLC22A2 rs316019 and SLC47A2 rs12943590 were significantly associated with metformin drug response across co-dominant and dominant models, respectively.	Metformin	123-132	solute carrier family 47 member 2	Homo sapiens	69-76
27226136-5	2016	Other molecular (collagen IV and connective tissue growth factor) and histological (tubulointerstitial total collagen and glomerular collagen IV accumulation) benefits were seen upon dual therapy with metformin.	Metformin	201-210	cellular communication network factor 2	Mus musculus	33-64
27036040-8	2016	In Sawano cells and normal HEEs, a decrease of LSR induced by leptin and an increase of LSR induced by adiponectin and the drugs for type 2 diabetes metformin and berberine were observed via distinct signaling pathways including JAK2/STAT.	Metformin	149-158	Janus kinase 2	Homo sapiens	229-233
29914345-7	2018	CONCLUSION: The present study proposes a role of SLC22A2 rs316019 and SLC47A2 rs12943590 in the pharmacokinetic action of metformin.	Metformin	122-131	solute carrier family 47 member 2	Homo sapiens	70-77
29542325-9	2018	Metformin use reduced MYC levels in Caco2 and consequently, SLC1A5 and GLS expression, with a greater effect in cells dependent on glutaminolytic metabolism.	Metformin	0-9	MYC proto-oncogene, bHLH transcription factor	Rattus norvegicus	22-25
29946147-0	2018	Author Correction: Hexokinase-2 depletion inhibits glycolysis and induces oxidative phosphorylation in hepatocellular carcinoma and sensitizes to metformin.	Metformin	146-155	hexokinase 2	Homo sapiens	19-31
27058422-0	2016	Metformin represses bladder cancer progression by inhibiting stem cell repopulation via COX2/PGE2/STAT3 axis.	Metformin	0-9	cytochrome c oxidase II, mitochondrial	Rattus norvegicus	88-92
27058422-6	2016	More importantly, we found that metformin exerts these anticancer effects by inhibiting COX2, subsequently PGE2 as well as the activation of STAT3.	Metformin	32-41	cytochrome c oxidase II, mitochondrial	Rattus norvegicus	88-92
27058422-7	2016	In conclusion, we are the first to systemically demonstrate in both animal and cell models that metformin inhibits bladder cancer progression by inhibiting stem cell repopulation through the COX2/PGE2/STAT3 axis.	Metformin	96-105	cytochrome c oxidase II, mitochondrial	Rattus norvegicus	191-195
26868993-8	2016	After metformin treatment, PDCD4 expression was distinctly down-regulated for the obese women with PCOS with insulin resistance.	Metformin	6-15	programmed cell death 4	Homo sapiens	27-32
26953870-13	2016	Mean (SD) number of myelin basic protein peptide-specific cells secreting interferon gamma and interleukin (IL)-17 were significantly reduced in patients receiving metformin compared with controls (interferon gamma, 30.3 [11.5] vs 82.8 [18.8], P &lt; .001; IL-17, 212.4 [85.5] vs 553.8 [125.9], P &lt; .001).	Metformin	164-173	myelin basic protein	Homo sapiens	20-40
26953870-15	2016	Both metformin and pioglitazone resulted in a significant increase in the number and regulatory functions of CD4+CD25+FoxP3+ regulatory T cells compared with controls (metformin, 6.7 [1.5] vs 2.1 [1.0], P = .001; pioglitazone, 6.9 [0.8] vs 3.0 [0.8], P = .001).	Metformin	5-14	forkhead box P3	Homo sapiens	118-123
26986571-6	2016	Metformin repressed E2-inducible estrogen response element (ERE) luciferase activity, protein levels and mRNA levels of E2/ERalpha-regulated genes [including c-Myc, cyclin D1, progesterone receptor (PR) and pS2] to a greater degree than tamoxifen, resulting in inhibition of cell proliferation of MCF-7, TR MCF-7 and MDA-MB-361 cells.	Metformin	0-9	cyclin D1	Homo sapiens	165-174
26986571-6	2016	Metformin repressed E2-inducible estrogen response element (ERE) luciferase activity, protein levels and mRNA levels of E2/ERalpha-regulated genes [including c-Myc, cyclin D1, progesterone receptor (PR) and pS2] to a greater degree than tamoxifen, resulting in inhibition of cell proliferation of MCF-7, TR MCF-7 and MDA-MB-361 cells.	Metformin	0-9	progesterone receptor	Homo sapiens	176-197
26986571-6	2016	Metformin repressed E2-inducible estrogen response element (ERE) luciferase activity, protein levels and mRNA levels of E2/ERalpha-regulated genes [including c-Myc, cyclin D1, progesterone receptor (PR) and pS2] to a greater degree than tamoxifen, resulting in inhibition of cell proliferation of MCF-7, TR MCF-7 and MDA-MB-361 cells.	Metformin	0-9	progesterone receptor	Homo sapiens	199-201
27123089-7	2016	The present study provides evidence that activation of AMPK by metformin contributes to radioresistance.	Metformin	63-72	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	55-59
26581908-0	2016	Anti-cancer effect of metformin by suppressing signaling pathway of HER2 and HER3 in tamoxifen-resistant breast cancer cells.	Metformin	22-31	erb-b2 receptor tyrosine kinase 3	Homo sapiens	77-81
26581908-6	2016	Metformin inhibited activation of HER2 (Tyr1248)/HER3 (Tyr1289)/Akt (Ser473) as well as cell proliferation and colony formation by estrogenic promotion in MCF-7 and TR MCF-7 cells.	Metformin	0-9	erb-b2 receptor tyrosine kinase 3	Homo sapiens	49-53
26581908-7	2016	Known as a HER3 ligand, heregulin (HRG)-beta1-induced phosphorylation of HER2, HER3 and Akt, and protein interaction of HER2/HER3 and colony formation were inhibited by metformin in both cells.	Metformin	169-178	erb-b2 receptor tyrosine kinase 3	Homo sapiens	11-15
26581908-8	2016	Consistent with the results in the two cell lines, we identified that metformin inhibited HER2/HER3/Akt signaling axis activated by HRG-beta1 using the HER2 and HER3-overexpressing breast cancer cell line SK-BR-3.	Metformin	70-79	erb-b2 receptor tyrosine kinase 3	Homo sapiens	95-99
26581908-8	2016	Consistent with the results in the two cell lines, we identified that metformin inhibited HER2/HER3/Akt signaling axis activated by HRG-beta1 using the HER2 and HER3-overexpressing breast cancer cell line SK-BR-3.	Metformin	70-79	erb-b2 receptor tyrosine kinase 3	Homo sapiens	161-165
26581908-9	2016	Lastly, lapatinib-induced HER3 upregulation was significantly inhibited by treatment of metformin in HER3 siRNA-transfected TR MCF-7 cells.	Metformin	88-97	erb-b2 receptor tyrosine kinase 3	Homo sapiens	26-30
26581908-9	2016	Lastly, lapatinib-induced HER3 upregulation was significantly inhibited by treatment of metformin in HER3 siRNA-transfected TR MCF-7 cells.	Metformin	88-97	erb-b2 receptor tyrosine kinase 3	Homo sapiens	101-105
26581908-10	2016	These data suggest that metformin might overcome tamoxifen resistance through the inhibition of expression and signaling of receptor tyrosine kinase HER2 and HER3.	Metformin	24-33	erb-b2 receptor tyrosine kinase 3	Homo sapiens	158-162
29914450-2	2018	Clinically, treatment with Zyflamend and/or metformin (activators of AMPK) had benefits in castrate-resistant prostate cancer patients who no longer responded to treatment.	Metformin	44-53	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	69-73
29949432-3	2018	METHODS: Patients with HbA1c &lt;=7% (53 mmol/mol) were discharged on sitagliptin and metformin; patients with HbA1c between 7 and 9% (53-75 mmol/mol) and those &gt;9% (75 mmol/mol) were discharged on sitagliptinmetformin with glargine U-100 at 50% or 80% of the hospital daily dose.	Metformin	86-95	hemoglobin subunit alpha 1	Homo sapiens	23-27
29949432-9	2018	CONCLUSION: The proposed HbA1c-based hospital discharge algorithm using a combination of sitagliptin-metformin was safe and significantly improved glycemic control after hospital discharge in general medicine and surgery patients with T2D.	Metformin	101-110	hemoglobin subunit alpha 1	Homo sapiens	25-29
29549478-0	2018	Metformin Promotes HaCaT Cell Apoptosis through Generation of Reactive Oxygen Species via Raf-1-ERK1/2-Nrf2 Inactivation.	Metformin	0-9	Raf-1 proto-oncogene, serine/threonine kinase	Homo sapiens	90-95
29789508-5	2018	The biphasic effect of different doses of metformin on adipogenesis was accompanied by increasing or decreasing the expression of adipogenic and lipogenic genes including peroxisome proliferator-activated receptor (PPARgamma), CCAAT/enhancer binding protein alpha (C/EBPalpha), and fatty acid synthase (FASN) at both messenger RNA (mRNA) and protein levels.	Metformin	42-51	peroxisome proliferator activated receptor gamma	Mus musculus	215-224
29789508-5	2018	The biphasic effect of different doses of metformin on adipogenesis was accompanied by increasing or decreasing the expression of adipogenic and lipogenic genes including peroxisome proliferator-activated receptor (PPARgamma), CCAAT/enhancer binding protein alpha (C/EBPalpha), and fatty acid synthase (FASN) at both messenger RNA (mRNA) and protein levels.	Metformin	42-51	CCAAT/enhancer binding protein (C/EBP), alpha	Mus musculus	227-263
29789508-5	2018	The biphasic effect of different doses of metformin on adipogenesis was accompanied by increasing or decreasing the expression of adipogenic and lipogenic genes including peroxisome proliferator-activated receptor (PPARgamma), CCAAT/enhancer binding protein alpha (C/EBPalpha), and fatty acid synthase (FASN) at both messenger RNA (mRNA) and protein levels.	Metformin	42-51	CCAAT/enhancer binding protein (C/EBP), alpha	Mus musculus	265-275
29789508-6	2018	Furthermore, only the higher concentrations of metformin induced the phosphorylation of adenosine 5"-monophosphate (AMP)-activated protein kinase (AMPK), p38, and c-Jun N-terminal kinase (JNK) and reduced the phosphorylation of extracellular regulated protein kinases (ERK) and Akt.	Metformin	47-56	mitogen-activated protein kinase 14	Mus musculus	154-157
29654166-5	2018	Both metformin and 991 treatment significantly increased AMPK activation and glucose uptake in muscle cell cultures from both controls and ME/CFS.	Metformin	5-14	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	57-61
27079349-4	2016	We investigated improved survival, lower risks of recurrences, and lower, more stable levels of prostate-specific antigen (PSA) in patients with DM2 along with prostate cancer on metformin.	Metformin	179-188	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	145-148
27079349-5	2016	METHODS: Patients with prostate cancer along with DM2 who remained on metformin were compared with controls who were not on metformin matched by age, weight, race and Gleason score cancer staging.	Metformin	70-79	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	50-53
25663310-5	2016	Increased PARP cleavage and increased LC3B-II with ATG5-ATG12 complex suggested the induction of apoptosis and autophagy, respectively, in metformin-treated ovarian cancer cells.	Metformin	139-148	collagen type XI alpha 2 chain	Homo sapiens	10-14
26681807-6	2016	Similarly, AMPK activation using genetic manipulation and low-dose metformin treatment protects mouse striatal cells expressing full-length mutant Htt (mHtt), counteracting their vulnerability to stress, with reduction of soluble mHtt levels by metformin and compensation of cytotoxicity by AMPKalpha1.	Metformin	67-76	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	11-15
26681807-6	2016	Similarly, AMPK activation using genetic manipulation and low-dose metformin treatment protects mouse striatal cells expressing full-length mutant Htt (mHtt), counteracting their vulnerability to stress, with reduction of soluble mHtt levels by metformin and compensation of cytotoxicity by AMPKalpha1.	Metformin	245-254	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	11-15
26885898-0	2016	Metformin regulates oxLDL-facilitated endothelial dysfunction by modulation of SIRT1 through repressing LOX-1-modulated oxidative signaling.	Metformin	0-9	oxidized low density lipoprotein receptor 1	Homo sapiens	104-109
26885898-3	2016	In this present study, we confirmed that metformin enhanced SIRT1 and AMPK expression in human umbilical vein endothelial cells (HUVECs).	Metformin	41-50	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	70-74
26885898-4	2016	Metformin also inhibited oxLDL-increased LOX-1 expression and oxLDL-collapsed AKT/eNOS levels.	Metformin	0-9	oxidized low density lipoprotein receptor 1	Homo sapiens	41-46
26885898-5	2016	However, silencing SIRT1 and AMPK diminished the protective function of metformin against oxidative injuries.	Metformin	72-81	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	29-33
26998043-3	2016	Currently, the first-line treatment of diabetes is based on metformin, which is an inducer of AMP-activated protein kinase (AMPK) and belongs to the biguanide class of pharmaceuticals.	Metformin	60-69	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	94-122
26998043-3	2016	Currently, the first-line treatment of diabetes is based on metformin, which is an inducer of AMP-activated protein kinase (AMPK) and belongs to the biguanide class of pharmaceuticals.	Metformin	60-69	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	124-128
26921394-6	2016	In addition, we observed that bladder cancer cell lines (RT4, UMUC-3, and J82) with homozygous deletion of either TSC1 or PTEN are more sensitive to metformin than those (TEU2, TCCSUP, and HT1376) with wild-type TSC1 and PTEN genes.	Metformin	149-158	TSC complex subunit 1	Mus musculus	114-118
26921394-6	2016	In addition, we observed that bladder cancer cell lines (RT4, UMUC-3, and J82) with homozygous deletion of either TSC1 or PTEN are more sensitive to metformin than those (TEU2, TCCSUP, and HT1376) with wild-type TSC1 and PTEN genes.	Metformin	149-158	TSC complex subunit 1	Mus musculus	212-216
26802022-8	2016	The results demonstrated that metformin activated AMPK and decreased phosphorylation of Akt and Erk.	Metformin	30-39	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	50-54
26896068-11	2016	Metformin also enhanced the inhibitory effect of 5-ASA on MMP-2 and MMP-9 enzyme activity, indicating a decrease in metastasis.	Metformin	0-9	matrix metallopeptidase 2	Homo sapiens	58-63
29693804-0	2018	Synergistic Growth Inhibitory Effects of Chrysin and Metformin Combination on Breast Cancer Cells through hTERT and Cyclin D1 Suppression Objective: To explore the possibility of a novel chemopreventive strategy for improving breast cancer treatment,the anticancer effects of a combination two natural compounds, Chrysin and Metformin, against T47D breast cancercells were investigated.	Metformin	53-62	cyclin D1	Homo sapiens	116-125
29693804-5	2018	Conclusion: The conmbinationof metformin and chrysin suppressing hTERT and cyclin D1 gene expression might offer an appropriate approach forbreast cancer therapy.	Metformin	31-40	cyclin D1	Homo sapiens	75-84
29610348-0	2018	Activation of AMPK by metformin improves withdrawal signs precipitated by nicotine withdrawal.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	14-18
29610348-5	2018	We show that metformin, a known AMPK activator in the periphery, reduces withdrawal symptoms through a mechanism dependent on the presence of the AMPKalpha subunits within the hippocampus.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	32-36
29654226-3	2018	Metformin (MTF) has been reported to target NLK (Nemo-like kinase) to inhibit non-small lung cancer cells.	Metformin	11-14	nemo like kinase	Mus musculus	44-47
29654226-3	2018	Metformin (MTF) has been reported to target NLK (Nemo-like kinase) to inhibit non-small lung cancer cells.	Metformin	11-14	nemo like kinase	Mus musculus	49-65
29651002-5	2018	After 3 months, metformin prevented HFCD-induced weight gain, hepatic steatosis, depletion of intact acini, formation of advanced PanIN lesions, and stimulation of ERK and mTORC1 in pancreas.	Metformin	16-25	CREB regulated transcription coactivator 1	Mus musculus	172-178
29662316-0	2018	Metformin inhibits proliferation and cytotoxicity and induces apoptosis via AMPK pathway in CD19-chimeric antigen receptor-modified T cells.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	76-80
29662316-0	2018	Metformin inhibits proliferation and cytotoxicity and induces apoptosis via AMPK pathway in CD19-chimeric antigen receptor-modified T cells.	Metformin	0-9	CD19 molecule	Homo sapiens	92-96
29662316-3	2018	However, no report has revealed the direct effect of metformin on CD19-CAR T cell biological function and its underling mechanisms.	Metformin	53-62	CD19 molecule	Homo sapiens	66-70
29662316-4	2018	Purpose: The purpose of this research was to explore the effect of metformin on CD19-CAR T cell biological function and the mechanisms involved.	Metformin	67-76	CD19 molecule	Homo sapiens	80-84
29662316-8	2018	Results: In the current study, it was found that metformin inhibited CD19-CAR T cell proliferation and cytotoxicity and induced apoptosis.	Metformin	49-58	CD19 molecule	Homo sapiens	69-73
29662316-9	2018	Furthermore, our study revealed that metformin activated AMPK and suppressed mTOR and HIF1alpha expression.	Metformin	37-46	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	57-61
29662316-10	2018	By using an AMPK inhibitor, compound C, we demonstrated the crucial roles of AMPK in CD19-CAR T cells when they were treated with metformin.	Metformin	130-139	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	12-16
29662316-10	2018	By using an AMPK inhibitor, compound C, we demonstrated the crucial roles of AMPK in CD19-CAR T cells when they were treated with metformin.	Metformin	130-139	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	77-81
29662316-10	2018	By using an AMPK inhibitor, compound C, we demonstrated the crucial roles of AMPK in CD19-CAR T cells when they were treated with metformin.	Metformin	130-139	CD19 molecule	Homo sapiens	85-89
29662316-11	2018	Finally, we verified that metformin suppressed the cytotoxicity of CD19-CAR T cell in vivo.	Metformin	26-35	CD19 molecule	Homo sapiens	67-71
29662316-12	2018	Conclusion: Taken together, these results indicated that metformin may play an important role in modulating CD19-CAR T cell biological functions in an AMPK-dependent and mTOR/HIF1alpha-independent manner.	Metformin	57-66	CD19 molecule	Homo sapiens	108-112
29662316-12	2018	Conclusion: Taken together, these results indicated that metformin may play an important role in modulating CD19-CAR T cell biological functions in an AMPK-dependent and mTOR/HIF1alpha-independent manner.	Metformin	57-66	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	151-155
29328467-3	2018	Metformin inhibits cell growth by enhancing the tumor suppressive function of transforming growth factor (TGF-beta).	Metformin	0-9	transforming growth factor, beta 1	Mus musculus	106-114
29328467-5	2018	Specifically, we showed that aspirin and metformin enhanced 4T1 cell apoptosis by inducing secretion of TGF-beta1, whereas estradiol weakened the effect.	Metformin	41-50	transforming growth factor, beta 1	Mus musculus	104-113
29117515-0	2018	Metformin and epothilone A treatment up regulate pro-apoptotic PARP-1, Casp-3 and H2AX genes and decrease of AKT kinase level to control cell death of human hepatocellular carcinoma and ovary adenocarcinoma cells.	Metformin	0-9	H2A.X variant histone	Homo sapiens	82-86
29228105-5	2018	Because metformin is known to inhibit mTOR and p38 signaling pathways, Faah-/- females were treated with metformin.	Metformin	8-17	mitogen-activated protein kinase 14	Mus musculus	47-50
29358486-5	2018	Glucose-lowering therapies, such as caloric restriction, exercise, and metformin, all induce an energetic challenge that results in the activation of the cellular energy sensor AMP-activated protein kinase (AMPK).	Metformin	71-80	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	177-205
29358486-5	2018	Glucose-lowering therapies, such as caloric restriction, exercise, and metformin, all induce an energetic challenge that results in the activation of the cellular energy sensor AMP-activated protein kinase (AMPK).	Metformin	71-80	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	207-211
29285650-9	2018	CONCLUSIONS: Our results demonstrate that gemigliptin induces cytotoxic activity, and has a synergistic activity with metformin in inducing cytotoxicity via regulation of Akt and AMPK in thyroid carcinoma cells.	Metformin	118-127	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	179-183
29285650-10	2018	Furthermore, gemigliptin augments the inhibitory effect of metformin on proliferation and migration through involvement of matrix metalloproteinase-2, matrix metalloproteinase-9, p53, p21, VCAM-1, and ERK in thyroid carcinoma cells.	Metformin	59-68	matrix metallopeptidase 2	Homo sapiens	123-177
28494141-7	2018	Inhibition of LKB1 activity, a common upstream AMPK kinase, markedly reversed metformin-induced AMPK activation, RUNX2 expression and nuclear localization.	Metformin	78-87	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	47-51
28494141-7	2018	Inhibition of LKB1 activity, a common upstream AMPK kinase, markedly reversed metformin-induced AMPK activation, RUNX2 expression and nuclear localization.	Metformin	78-87	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	96-100
28494141-9	2018	Collectively, functional OCT-expressing iPSC-MSCs responded to metformin by inducing an osteogenic effect in part mediated by the LKB1/AMPK pathway.	Metformin	63-72	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	135-139
29929422-7	2018	Metformin inhibits SMAD3 phosphorylation and impedes the KAT5-SMAD3 interaction, which attenuates the KAT5-mediated K333 acetylation of SMAD3 to suppress SMAD3 transcriptional activity and TRIB3 expression.	Metformin	0-9	SMAD family member 3	Mus musculus	19-24
29929422-7	2018	Metformin inhibits SMAD3 phosphorylation and impedes the KAT5-SMAD3 interaction, which attenuates the KAT5-mediated K333 acetylation of SMAD3 to suppress SMAD3 transcriptional activity and TRIB3 expression.	Metformin	0-9	K(lysine) acetyltransferase 5	Mus musculus	57-61
29929422-7	2018	Metformin inhibits SMAD3 phosphorylation and impedes the KAT5-SMAD3 interaction, which attenuates the KAT5-mediated K333 acetylation of SMAD3 to suppress SMAD3 transcriptional activity and TRIB3 expression.	Metformin	0-9	SMAD family member 3	Mus musculus	62-67
29929422-7	2018	Metformin inhibits SMAD3 phosphorylation and impedes the KAT5-SMAD3 interaction, which attenuates the KAT5-mediated K333 acetylation of SMAD3 to suppress SMAD3 transcriptional activity and TRIB3 expression.	Metformin	0-9	K(lysine) acetyltransferase 5	Mus musculus	102-106
29929422-7	2018	Metformin inhibits SMAD3 phosphorylation and impedes the KAT5-SMAD3 interaction, which attenuates the KAT5-mediated K333 acetylation of SMAD3 to suppress SMAD3 transcriptional activity and TRIB3 expression.	Metformin	0-9	SMAD family member 3	Mus musculus	62-67
29929422-7	2018	Metformin inhibits SMAD3 phosphorylation and impedes the KAT5-SMAD3 interaction, which attenuates the KAT5-mediated K333 acetylation of SMAD3 to suppress SMAD3 transcriptional activity and TRIB3 expression.	Metformin	0-9	SMAD family member 3	Mus musculus	62-67
29136782-4	2018	The results indicated an improvement effect of MNCs and metformin on STZ-induced DN in rats, which was evidenced by significant decrease in urinary albumin/creatinine ratio, N-acetyl-beta-d-glucosaminidase (NAG), urinary kidney injury molecule-1 (KIM-1), serum urea, serum creatinine and fasting blood glucose and significant increase in C- peptide level, compared to diabetic control group.	Metformin	56-65	O-GlcNAcase	Rattus norvegicus	174-205
29136782-4	2018	The results indicated an improvement effect of MNCs and metformin on STZ-induced DN in rats, which was evidenced by significant decrease in urinary albumin/creatinine ratio, N-acetyl-beta-d-glucosaminidase (NAG), urinary kidney injury molecule-1 (KIM-1), serum urea, serum creatinine and fasting blood glucose and significant increase in C- peptide level, compared to diabetic control group.	Metformin	56-65	O-GlcNAcase	Rattus norvegicus	207-210
29086064-11	2018	Metformin effects on mitochondria led to the activation and phosphorylation of the energetic sensor AMPK along with an upregulation of the pro-survival AKT pathway in both cell populations.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	100-104
30032136-12	2018	Increased levels of apoptosis, activation of caspase-3 and cleavage of PARP were detected after cotreatment with metformin and FTY720.	Metformin	113-122	collagen type XI alpha 2 chain	Homo sapiens	71-75
30481793-9	2018	mRNA and protein levels of MMP-2 and MMP-9 decreased significantly upon treatment with metformin of 10mM for 12, 24 and 48h in a time-dependent manner (p &lt; 0.05).	Metformin	87-96	matrix metallopeptidase 2	Homo sapiens	27-32
30481793-10	2018	In line with in vitro results, in vivo experiments demonstrated that metformin inhibited tumorigenicity, inhibited lung metastasis and down-regulated the expression of MMP-2 and MMP-9.	Metformin	69-78	matrix metallopeptidase 2	Homo sapiens	168-173
30481793-12	2018	CONCLUSION: Our study for the first time demonstrated the anti-invasive and anti-metastatic effects of metformin on human ESCC cells both in vitro and in vivo, which might be associated with the down-regulation of MMP-2 and MMP-9.	Metformin	103-112	matrix metallopeptidase 2	Homo sapiens	214-219
28571536-5	2018	Furthermore, pharmacological activators of AMPK such as metformin have been shown to exert renoprotective effects in experimental studies and improve clinical outcomes in patients with CKD.	Metformin	56-65	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	43-47
28606032-3	2018	RESULTS: Based on the available scientific literature, metformin suppresses immune responses mainly through its direct effect on the cellular functions of various immune cell types by induction of AMPK and subsequent inhibition of mTORC1, and by inhibition of mitochondrial ROS production.	Metformin	55-64	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	197-201
28606032-3	2018	RESULTS: Based on the available scientific literature, metformin suppresses immune responses mainly through its direct effect on the cellular functions of various immune cell types by induction of AMPK and subsequent inhibition of mTORC1, and by inhibition of mitochondrial ROS production.	Metformin	55-64	CREB regulated transcription coactivator 1	Mus musculus	231-237
29663879-6	2018	RESULTS: Adenosine Monophosphate (AMP)-Activated Protein Kinase (AMPK) plays an important role in mechanism of action of metformin.	Metformin	121-130	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	65-69
26956973-0	2016	Tristetraprolin mediates the anti-proliferative effects of metformin in breast cancer cells.	Metformin	59-68	ZFP36 ring finger protein	Homo sapiens	0-15
26956973-2	2016	The aim is to investigate the role of tristetraprolin (TTP), an AU-rich element-binding protein, in anti-proliferative effects of metformin in cancer cells.	Metformin	130-139	ZFP36 ring finger protein	Homo sapiens	38-53
26956973-2	2016	The aim is to investigate the role of tristetraprolin (TTP), an AU-rich element-binding protein, in anti-proliferative effects of metformin in cancer cells.	Metformin	130-139	ZFP36 ring finger protein	Homo sapiens	55-58
26956973-5	2016	Metformin induces the expression of tristetraprolin (TTP) in breast cancer cells in a p53-independent manner.	Metformin	0-9	ZFP36 ring finger protein	Homo sapiens	36-51
26956973-5	2016	Metformin induces the expression of tristetraprolin (TTP) in breast cancer cells in a p53-independent manner.	Metformin	0-9	ZFP36 ring finger protein	Homo sapiens	53-56
26956973-6	2016	Importantly, inhibition of TTP abrogated the anti-proliferation effect of metformin.	Metformin	74-83	ZFP36 ring finger protein	Homo sapiens	27-30
26956973-7	2016	We observed that metformin decreased c-Myc levels, and ectopic expression of c-Myc blocked the effect of metformin on TTP expression and cell proliferation.	Metformin	105-114	ZFP36 ring finger protein	Homo sapiens	118-121
26956973-8	2016	Our data indicate that metformin induces TTP expression by reducing the expression of c-Myc, suggesting a new model whereby TTP acts as a mediator of metformin"s anti-proliferative activity in cancer cells.	Metformin	23-32	ZFP36 ring finger protein	Homo sapiens	41-44
26956973-8	2016	Our data indicate that metformin induces TTP expression by reducing the expression of c-Myc, suggesting a new model whereby TTP acts as a mediator of metformin"s anti-proliferative activity in cancer cells.	Metformin	23-32	ZFP36 ring finger protein	Homo sapiens	124-127
26956973-8	2016	Our data indicate that metformin induces TTP expression by reducing the expression of c-Myc, suggesting a new model whereby TTP acts as a mediator of metformin"s anti-proliferative activity in cancer cells.	Metformin	150-159	ZFP36 ring finger protein	Homo sapiens	41-44
26956973-8	2016	Our data indicate that metformin induces TTP expression by reducing the expression of c-Myc, suggesting a new model whereby TTP acts as a mediator of metformin"s anti-proliferative activity in cancer cells.	Metformin	150-159	ZFP36 ring finger protein	Homo sapiens	124-127
26529121-5	2016	Metformin treatment prompted a delay in delamination of NCC by inhibiting key markers like Sox-1, Sox-9, HNK-1, and p-75.	Metformin	0-9	SRY-box transcription factor 9	Homo sapiens	98-103
26529121-5	2016	Metformin treatment prompted a delay in delamination of NCC by inhibiting key markers like Sox-1, Sox-9, HNK-1, and p-75.	Metformin	0-9	PC4 and SFRS1 interacting protein 1	Homo sapiens	116-120
26529121-6	2016	We then revealed that metformin impedes Wnt axis, a major signaling pathway active during NC formation via DVL-3 inhibition and impairment in nuclear translocation of beta-catenin.	Metformin	22-31	dishevelled segment polarity protein 3	Homo sapiens	107-112
26529121-8	2016	Further studies involving loss and gain of function confirmed that NCC specifiers like Sox-1 and Sox-9 are direct targets of miR-200 and miR-145, respectively and that they are essentially modulated by metformin.	Metformin	202-211	SRY-box transcription factor 9	Homo sapiens	97-102
25913633-5	2016	In contrast, metformin has a positive effect on osteoblast differentiation due to increased activity of Runx2 via the AMPK/USF-1/SHP regulatory cascade resulting in a neutral or potentially protective effect on bone.	Metformin	13-22	nuclear receptor subfamily 0 group B member 2	Homo sapiens	129-132
26919310-6	2016	Mechanistically, metformin blocks endogenous activation of Smad2 and Smad3 and dampens TGF-beta-mediated activation of Smad2, Smad3, and ID1 both at the transcriptional and translational level.	Metformin	17-26	SMAD family member 2	Homo sapiens	59-64
26919310-6	2016	Mechanistically, metformin blocks endogenous activation of Smad2 and Smad3 and dampens TGF-beta-mediated activation of Smad2, Smad3, and ID1 both at the transcriptional and translational level.	Metformin	17-26	SMAD family member 3	Homo sapiens	69-74
26919310-6	2016	Mechanistically, metformin blocks endogenous activation of Smad2 and Smad3 and dampens TGF-beta-mediated activation of Smad2, Smad3, and ID1 both at the transcriptional and translational level.	Metformin	17-26	SMAD family member 2	Homo sapiens	119-124
26919310-6	2016	Mechanistically, metformin blocks endogenous activation of Smad2 and Smad3 and dampens TGF-beta-mediated activation of Smad2, Smad3, and ID1 both at the transcriptional and translational level.	Metformin	17-26	SMAD family member 3	Homo sapiens	126-131
26919310-6	2016	Mechanistically, metformin blocks endogenous activation of Smad2 and Smad3 and dampens TGF-beta-mediated activation of Smad2, Smad3, and ID1 both at the transcriptional and translational level.	Metformin	17-26	inhibitor of DNA binding 1, HLH protein	Homo sapiens	137-140
26521775-8	2016	Given the AMPK-activating ability of metformin, a widely prescribed and well-tolerated drug, these preclinical studies provide a strong rationale for both retrospective and prospective human pain trials with this drug.	Metformin	37-46	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	10-14
27633039-3	2016	Metformin also increases the affinity of the insulin receptor, reduces high insulin levels and improves insulin resistance.	Metformin	0-9	insulin receptor	Homo sapiens	45-61
27633039-10	2016	A study in mice deficient in PON1 showed that in this experimental model, metformin administration increased the severity of steatosis, increased CCL2 expression, did not activate AMPK, and increased the expression of the apoptosis marker caspase-9.	Metformin	74-83	caspase 9	Mus musculus	239-248
26465200-7	2016	Specifically, both DA and metformin reduced cAMP-enhanced recruitment of the orphan nuclear receptor Nur77 to the HSD3B2 promoter, coupled with decreased transcription and protein expression of HSD3B2.	Metformin	26-35	nuclear receptor subfamily 4, group A, member 1	Rattus norvegicus	101-106
26587691-2	2016	The GLP-1 receptor agonists (GLP-1RAs) are established as an option for treatment of T2DM after metformin.	Metformin	96-105	glucagon like peptide 1 receptor	Homo sapiens	4-18
29663879-8	2018	The direct effects of metformin include AMPK-independent and AMPK-dependent effects whereas decrease in glucose level, hyperinsulinemia, and Insulin-like Growth Factor 1 (IGF-1) level are considered its indirect effects.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	40-44
29952416-0	2018	MIF/CD74 axis is a target for metformin therapy in diabetic podocytopathy - real world evidence.	Metformin	30-39	macrophage migration inhibitory factor	Homo sapiens	0-3
29952416-0	2018	MIF/CD74 axis is a target for metformin therapy in diabetic podocytopathy - real world evidence.	Metformin	30-39	CD74 molecule	Homo sapiens	4-8
29952416-1	2018	Introduction:To observe the effects of metformin on urinary excretion of MIF, CD74 and podocalyxin in type 2 diabetics and to explore its possible renoprotective mechanisms.	Metformin	39-48	macrophage migration inhibitory factor	Homo sapiens	73-76
29952416-1	2018	Introduction:To observe the effects of metformin on urinary excretion of MIF, CD74 and podocalyxin in type 2 diabetics and to explore its possible renoprotective mechanisms.	Metformin	39-48	CD74 molecule	Homo sapiens	78-82
29952416-7	2018	CONCLUSIONS: Metformin could present its podocyte-protective capacity in type 2 diabetics and the underlying mechanisms may be partly attributed to its effects in suppressing MIF-CD74 axis mediated inflammatory cascade response.	Metformin	13-22	macrophage migration inhibitory factor	Homo sapiens	175-178
27812974-3	2016	AMPK complexes are regulated by changes in cellular AMP:ATP or ADP:ATP ratios and by a number of neutraceuticals and some of the widely-used diabetes medications such as metformin and thiazolinonediones.	Metformin	170-179	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
26198758-0	2016	Effect of metformin treatment on circulating osteoprotegerin in patients with nonalcoholic fatty liver disease.	Metformin	10-19	TNF receptor superfamily member 11b	Homo sapiens	45-60
29952416-7	2018	CONCLUSIONS: Metformin could present its podocyte-protective capacity in type 2 diabetics and the underlying mechanisms may be partly attributed to its effects in suppressing MIF-CD74 axis mediated inflammatory cascade response.	Metformin	13-22	CD74 molecule	Homo sapiens	179-183
28696014-10	2018	Thus, metformin exerts potent effect on suppression of ossification and inflammation in AS fibroblasts via the activation of Pi3k/Akt and AMPK pathways, which may be developed as a potential agent for treatment of AS.	Metformin	6-15	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	138-142
28722177-5	2018	Metformin treatment also increases deoxycytidine kinase (dCK) expression and, as the chemotherapeutic agent gemcitabine relies on dCK for its efficient activity, we speculated that metformin would enhance the sensitivity of OSCC cells to gemcitabine.	Metformin	0-9	deoxycytidine kinase	Homo sapiens	35-55
26198758-2	2016	The present study"s aim was to examine the impact of metformin treatment on circulating osteoprotegerin (OPG) in patients with NAFLD, a population in which this relationship has not yet been studied.	Metformin	53-62	TNF receptor superfamily member 11b	Homo sapiens	88-103
26198758-2	2016	The present study"s aim was to examine the impact of metformin treatment on circulating osteoprotegerin (OPG) in patients with NAFLD, a population in which this relationship has not yet been studied.	Metformin	53-62	TNF receptor superfamily member 11b	Homo sapiens	105-108
26198758-6	2016	Among metformin-treated patients, significant declines in OPG and alkaline phosphatase were observed.	Metformin	6-15	TNF receptor superfamily member 11b	Homo sapiens	58-61
26198758-8	2016	While at baseline circulating OPG levels did not differ significantly between the groups, by the end of the study OPG was significantly lower in patients treated with metformin than in the placebo group (p &lt; 0.0001).	Metformin	167-176	TNF receptor superfamily member 11b	Homo sapiens	114-117
26198758-9	2016	Delta OPG was significantly greater in the metformin group than the placebo group (p = 0.001).	Metformin	43-52	TNF receptor superfamily member 11b	Homo sapiens	6-9
26198758-10	2016	In the general linear model, metformin treatment was the only significant independent predictor of endpoint and delta OPG.	Metformin	29-38	TNF receptor superfamily member 11b	Homo sapiens	118-121
26198758-11	2016	CONCLUSIONS: Metformin treatment was associated with a significant decrease in OPG levels in patients with NAFLD.	Metformin	13-22	TNF receptor superfamily member 11b	Homo sapiens	79-82
26198758-12	2016	The effect on OPG was associated with exposure to metformin per se.	Metformin	50-59	TNF receptor superfamily member 11b	Homo sapiens	14-17
27579326-0	2016	The Change in HbA1c Associated with Initial Adherence and Subsequent Change in Adherence among Diabetes Patients Newly Initiating Metformin Therapy.	Metformin	130-139	hemoglobin subunit alpha 1	Homo sapiens	14-18
26656173-8	2015	The co-treatment of YC and compound C (an AMPK inhibitor) or metformin (an AMPK activator) also confirmed that YC increases p-AMPKalpha.	Metformin	61-70	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	75-79
26398221-5	2015	Metformin treatment also led to marked decreases in cyclin D1 and cyclin-dependent kinase (Cdk) 4 protein levels and retinoblastoma protein phosphorylation.	Metformin	0-9	cyclin D1	Homo sapiens	52-61
26398221-5	2015	Metformin treatment also led to marked decreases in cyclin D1 and cyclin-dependent kinase (Cdk) 4 protein levels and retinoblastoma protein phosphorylation.	Metformin	0-9	cyclin dependent kinase 4	Homo sapiens	66-97
26164004-4	2015	Metformin suppressed OS MG63 cell proliferation in a dose- and time-dependent manner and markedly blocked anti-metastatic potentials, migration, and invasion, by downregulating matrix metalloproteinase 2 (MMP2) and MMP9.	Metformin	0-9	matrix metallopeptidase 2	Homo sapiens	177-203
26164004-4	2015	Metformin suppressed OS MG63 cell proliferation in a dose- and time-dependent manner and markedly blocked anti-metastatic potentials, migration, and invasion, by downregulating matrix metalloproteinase 2 (MMP2) and MMP9.	Metformin	0-9	matrix metallopeptidase 2	Homo sapiens	205-209
26164004-7	2015	Consistent with this, the positive rates of CD90, CD133, and stage-specific embryonic antigen-4 (SSEA-4) were all observed with reductions in response to metformin exposure.	Metformin	154-163	prominin 1	Homo sapiens	50-55
26548416-6	2015	Several metformin-regulated genes including fatty acid synthase (FASN) were validated as transcriptional targets of SRC-2 with promoters characterized by sterol regulatory element (SRE) binding protein (SREBP) recognition sequences.	Metformin	8-17	fatty acid synthase	Rattus norvegicus	44-63
26548416-6	2015	Several metformin-regulated genes including fatty acid synthase (FASN) were validated as transcriptional targets of SRC-2 with promoters characterized by sterol regulatory element (SRE) binding protein (SREBP) recognition sequences.	Metformin	8-17	fatty acid synthase	Rattus norvegicus	65-69
26548416-8	2015	By suppressing SRC-2 at the transcriptional level, metformin impeded recruitment of SRC-2 and RNA polymerase II to the G6Pc promoter and to SREs of mutual SRC-2/SREBP-1 target gene promoters.	Metformin	51-60	sterol regulatory element binding transcription factor 1	Rattus norvegicus	161-168
26497364-2	2015	Here we found that metformin significantly suppressed IL-13 induced M2-like polarization of macrophages, as illustrated by reduced expression of CD206, down-regulation of M2 marker mRNAs, and inhibition of M2-like macrophages promoted migration of cancer cells and endothelial cells.	Metformin	19-28	mannose receptor C-type 1	Homo sapiens	145-150
26497364-3	2015	Metformin triggered AMPKalpha1 activation in macrophage and silencing of AMPKalpha1 partially abrogated the inhibitory effect of metformin in IL-13 induced M2-like polarization.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	20-30
26497364-3	2015	Metformin triggered AMPKalpha1 activation in macrophage and silencing of AMPKalpha1 partially abrogated the inhibitory effect of metformin in IL-13 induced M2-like polarization.	Metformin	129-138	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	20-30
26497364-3	2015	Metformin triggered AMPKalpha1 activation in macrophage and silencing of AMPKalpha1 partially abrogated the inhibitory effect of metformin in IL-13 induced M2-like polarization.	Metformin	129-138	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	73-83
26497364-8	2015	These findings suggest that metformin is able to block the M2-like polarization of macrophages partially through AMPKalpha1, which plays an important role in metformin inhibited metastasis of Lewis lung cancer.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	113-123
26497364-8	2015	These findings suggest that metformin is able to block the M2-like polarization of macrophages partially through AMPKalpha1, which plays an important role in metformin inhibited metastasis of Lewis lung cancer.	Metformin	158-167	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	113-123
28722177-5	2018	Metformin treatment also increases deoxycytidine kinase (dCK) expression and, as the chemotherapeutic agent gemcitabine relies on dCK for its efficient activity, we speculated that metformin would enhance the sensitivity of OSCC cells to gemcitabine.	Metformin	181-190	deoxycytidine kinase	Homo sapiens	35-55
29467947-7	2018	Our results also showed that metformin significantly suppressed self-renewal capacity of glioblastoma stem cells (GSCs), and expression of stem cell markers Bmi1, Sox2 and Musashi1, indicating that metformin can inhibit cancer stem-like properties of GBM cells.	Metformin	29-38	musashi RNA binding protein 1	Homo sapiens	172-180
29467947-7	2018	Our results also showed that metformin significantly suppressed self-renewal capacity of glioblastoma stem cells (GSCs), and expression of stem cell markers Bmi1, Sox2 and Musashi1, indicating that metformin can inhibit cancer stem-like properties of GBM cells.	Metformin	198-207	BMI1 proto-oncogene, polycomb ring finger	Homo sapiens	157-161
29467947-7	2018	Our results also showed that metformin significantly suppressed self-renewal capacity of glioblastoma stem cells (GSCs), and expression of stem cell markers Bmi1, Sox2 and Musashi1, indicating that metformin can inhibit cancer stem-like properties of GBM cells.	Metformin	198-207	musashi RNA binding protein 1	Homo sapiens	172-180
29025968-0	2017	Activation of AMPK/mTORC1-Mediated Autophagy by Metformin Reverses Clk1 Deficiency-Sensitized Dopaminergic Neuronal Death.	Metformin	48-57	CREB regulated transcription coactivator 1	Mus musculus	19-25
29344225-0	2017	Metformin enhances the chemosensitivity of hepatocarcinoma cells to cisplatin through AMPK pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	86-90
29344225-9	2017	Compared with the control, ratio of p-AMPK/AMPK in metformin group was increased, and ratio of p-AMPK/AMPK in cisplatin + metformin was significantly higher than that in cisplatin group.	Metformin	51-60	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	38-42
29344225-9	2017	Compared with the control, ratio of p-AMPK/AMPK in metformin group was increased, and ratio of p-AMPK/AMPK in cisplatin + metformin was significantly higher than that in cisplatin group.	Metformin	51-60	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	43-47
29344225-9	2017	Compared with the control, ratio of p-AMPK/AMPK in metformin group was increased, and ratio of p-AMPK/AMPK in cisplatin + metformin was significantly higher than that in cisplatin group.	Metformin	51-60	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	43-47
29344225-9	2017	Compared with the control, ratio of p-AMPK/AMPK in metformin group was increased, and ratio of p-AMPK/AMPK in cisplatin + metformin was significantly higher than that in cisplatin group.	Metformin	51-60	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	43-47
29344225-10	2017	Activity of cells in cisplatin + metformin + compound C (AMPK pathway blocker) group was significantly higher than that of cisplatin + metformin, while apoptosis of cells in cisplatin + metformin + compound C (AMPK pathway blocker) was significantly lower than that of cisplatin + metformin group.	Metformin	33-42	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	57-61
29344225-10	2017	Activity of cells in cisplatin + metformin + compound C (AMPK pathway blocker) group was significantly higher than that of cisplatin + metformin, while apoptosis of cells in cisplatin + metformin + compound C (AMPK pathway blocker) was significantly lower than that of cisplatin + metformin group.	Metformin	33-42	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	210-214
29344225-11	2017	In conclusion, metformin can inhibit the proliferation, promote apoptosis and enhance the chemosensitivity of hepatocarcinoma cells to cisplatin through AMPK pathway.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	153-157
28966224-9	2017	Adiponectin and metformin stimulate osteocalcin expression and the differentiation of osteoblasts via AMPK activation.	Metformin	16-25	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	102-106
29696037-6	2018	Metformin is the most widely used drug, together with sodium-glucose co-transporters 2 (SGLT2) inhibitors, amylin analogues, glucagon-like peptide 1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors.	Metformin	0-9	glucagon like peptide 1 receptor	Homo sapiens	150-165
28962017-20	2017	WIDER IMPLICATIONS OF THE FINDINGS: Metformin, an AMPK activator, is widely used to treat type II diabetes and polycystic ovarian disorder (PCOS).	Metformin	36-45	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	50-54
28921708-5	2017	Scopoletin or metformin down-regulated hepatic gene expression of triglyceride (Pparg, Plpp2, and Dgat2) and cholesterol (Hmgcr) synthesis as well as inflammation (Tlr4, Myd88, Nfkb1, Tnfa, and Il6), while it up-regulated Cyp7a1 gene.	Metformin	14-23	peroxisome proliferator activated receptor gamma	Mus musculus	80-85
28921708-5	2017	Scopoletin or metformin down-regulated hepatic gene expression of triglyceride (Pparg, Plpp2, and Dgat2) and cholesterol (Hmgcr) synthesis as well as inflammation (Tlr4, Myd88, Nfkb1, Tnfa, and Il6), while it up-regulated Cyp7a1 gene.	Metformin	14-23	phospholipid phosphatase 2	Mus musculus	87-92
28921708-6	2017	Hepatic PPARgamma and DGAT2 protein levels were also down-regulated in scopoletin or metformin group compared with the control group.	Metformin	85-94	peroxisome proliferator activated receptor gamma	Mus musculus	8-17
29333122-0	2017	Metformin Enhanced in Vitro Radiosensitivity Associates with G2/M Cell Cycle Arrest and Elevated Adenosine-5"-monophosphate-activated Protein Kinase Levels in Glioblastoma.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	97-148
26430787-3	2015	Although the precise molecular mechanisms by which metformin affects various cancers have not been fully elucidated, activation of AMPK-dependent and AMPK-independent pathways along with energy metabolism aberration, cell cycle arrest and apoptosis or autophagy induction have emerged as crucial regulators in this process.	Metformin	51-60	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	131-135
26430787-3	2015	Although the precise molecular mechanisms by which metformin affects various cancers have not been fully elucidated, activation of AMPK-dependent and AMPK-independent pathways along with energy metabolism aberration, cell cycle arrest and apoptosis or autophagy induction have emerged as crucial regulators in this process.	Metformin	51-60	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	150-154
29333122-7	2017	Induction of a G2/M phase cell cycle block through metformin and combined treatments was observed up to 72 h. These findings were associated with elevated levels of activated AMPK levels in LN229 cells but not in LN18 cells after irradiation, metformin, and temozolomide treatment.	Metformin	51-60	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	175-179
29202210-6	2017	Results PAI-1 activity fell in all groups, ADMA fell in higher-dose OCP, PF1 and 2 increased with metformin and higher-dose OCP, TG rose and tPA fell in both OCP groups, plasminogen increased in all and TAFI increased after higher-dose OCP.	Metformin	98-107	PHD finger protein 12	Homo sapiens	73-82
29262637-8	2017	While metformin could repress the bFGF-mediated activation in AKT/GSK-3beta signalling, inhibition on interaction between GSK-3beta and Twist1, enhancement of Twist1 stability.	Metformin	6-15	glycogen synthase kinase 3 beta	Homo sapiens	66-75
29262637-8	2017	While metformin could repress the bFGF-mediated activation in AKT/GSK-3beta signalling, inhibition on interaction between GSK-3beta and Twist1, enhancement of Twist1 stability.	Metformin	6-15	glycogen synthase kinase 3 beta	Homo sapiens	122-131
28821163-7	2017	The restorative effect of metformin on colonic mucosa was accompanied by a marked reduction in the tissue levels of pro-inflammatory mediators and immunoreactivity of COX-2, iNOS and NFkappaB(p65).	Metformin	26-35	cytochrome c oxidase II, mitochondrial	Rattus norvegicus	167-172
27573975-6	2017	Furthermore, the medullary bone around the implants inserted in the metformin-treated animals exhibited an increased number of RANKL-stained cells than that around the implants inserted in the control animals (P &lt; 0.05).	Metformin	68-77	TNF superfamily member 11	Rattus norvegicus	127-132
27573975-7	2017	CONCLUSIONS: Metformin negatively affected osseointegration by reducing the percentages of BIC and BA and increasing the expression of RANKL around titanium implants inserted in non-diabetic rats.	Metformin	13-22	TNF superfamily member 11	Rattus norvegicus	135-140
29085506-0	2017	Role of metformin in inhibiting estrogen-induced proliferation and regulating ERalpha and ERbeta expression in human endometrial cancer cells.	Metformin	8-17	estrogen receptor 2	Homo sapiens	90-96
29085506-7	2017	In addition, metformin significantly inhibited ERalpha expression while increasing ERbeta expression, whereas treatment with compound C reversed these effects.	Metformin	13-22	estrogen receptor 2	Homo sapiens	83-89
28319830-1	2017	Metformin is an oral hypoglycemic drug that has been shown to inhibit cancer cell proliferation via up-regulation of AMPK (AMP-activated protein kinase), and possibly inhibition of mTOR (mammalian target of rapamycin).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	117-121
28319830-1	2017	Metformin is an oral hypoglycemic drug that has been shown to inhibit cancer cell proliferation via up-regulation of AMPK (AMP-activated protein kinase), and possibly inhibition of mTOR (mammalian target of rapamycin).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	123-151
28926637-7	2017	Under glucose-depleted conditions, metformin specifically killed fancc and fancl cells that were deficient in FANCC and FANCL proteins, respectively, which are involved in DNA interstrand cross-link repair.	Metformin	35-44	Fanconi anemia complementation group L	Gallus gallus	75-80
28926637-7	2017	Under glucose-depleted conditions, metformin specifically killed fancc and fancl cells that were deficient in FANCC and FANCL proteins, respectively, which are involved in DNA interstrand cross-link repair.	Metformin	35-44	Fanconi anemia complementation group L	Gallus gallus	120-125
28926637-8	2017	An analysis of chromosomal aberrations in mitotic chromosome spreads revealed that a clinically relevant concentration of metformin induced DNA double-strand breaks (DSBs) in fancc and fancl cells under glucose-depleted conditions.	Metformin	122-131	Fanconi anemia complementation group L	Gallus gallus	185-190
28708400-6	2017	Memantine inhibited OCT2-, MATE1-, and MATE2-K-mediated metformin transport with IC50 values of 3.2, 40.9, and 315.3 muM, respectively.	Metformin	56-65	solute carrier family 22 member 2	Canis lupus familiaris	20-24
28708400-6	2017	Memantine inhibited OCT2-, MATE1-, and MATE2-K-mediated metformin transport with IC50 values of 3.2, 40.9, and 315.3 muM, respectively.	Metformin	56-65	solute carrier family 47 member 2	Homo sapiens	39-46
28614117-8	2017	In addition to drugs such as metformin and 5-aminoimidazole-4-carboxamide ribonucleotide that are classically used as AMPK activators, recent studies have identified the therapeutic potential of other compounds that function at least partly as AMPK activators, such as salicylates, statins, berberine, and resveratrol, in preventing the progression of CKD.	Metformin	29-38	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	118-122
25990477-5	2015	RESULTS: Vascular permeability, VEGF and COX-2 expressions were reduced in animals treated with MI and/or metformin.	Metformin	106-115	cytochrome c oxidase II, mitochondrial	Rattus norvegicus	41-46
25990477-6	2015	While PEDF expression was increased in the groups taking metformin, there was no difference in PEDF expression in the group taking MI and OHSS group.	Metformin	57-66	serpin family F member 1	Rattus norvegicus	6-10
26344902-9	2015	To understand this more, we show activation of AMPK by metformin also prevented palmitate-induced changes in the phosphorylations of raptor and p70S6K, confirming that the mTORC1/p70S6K signaling pathway is responsive to AMPK activity.	Metformin	55-64	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	47-51
26344902-9	2015	To understand this more, we show activation of AMPK by metformin also prevented palmitate-induced changes in the phosphorylations of raptor and p70S6K, confirming that the mTORC1/p70S6K signaling pathway is responsive to AMPK activity.	Metformin	55-64	CREB regulated transcription coactivator 1	Mus musculus	172-178
26344902-9	2015	To understand this more, we show activation of AMPK by metformin also prevented palmitate-induced changes in the phosphorylations of raptor and p70S6K, confirming that the mTORC1/p70S6K signaling pathway is responsive to AMPK activity.	Metformin	55-64	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	221-225
26344902-13	2015	Oleate reverses these effects through a metformin-like facilitation of AMPK.	Metformin	40-49	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	71-75
25925501-5	2015	Meta-analysis of the RCTs showed that metformin had statistically significant effects on pregnancy-induced hypertension [PIH; risk ratio (RR) 0.54; 95% confidence interval (CI) 0.31, 0.91].	Metformin	38-47	pregnancy-induced hypertension (pre-eclampsia, eclampsia, toxemia of pregnancy included)	Homo sapiens	121-124
25925501-7	2015	Our analyses suggest that there is no clinically relevant difference in efficacy or safety between metformin and insulin; however, metformin may be a good choice for GDM because of the lower risk of PIH.	Metformin	131-140	pregnancy-induced hypertension (pre-eclampsia, eclampsia, toxemia of pregnancy included)	Homo sapiens	199-202
25925501-8	2015	The advantages of metformin in terms of glycaemic control, PIH incidence and gestational age at birth are unclear, and should be verified in further trials.	Metformin	18-27	pregnancy-induced hypertension (pre-eclampsia, eclampsia, toxemia of pregnancy included)	Homo sapiens	59-62
26201966-15	2015	The finding of IGF-1R elevation in positive PNBs versus p-AMPK elevation in negative PNBs suggests altered metabolic pathway activation precipitated by metformin use.	Metformin	152-161	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	58-62
26141671-9	2015	Moreover, we found that metformin treatment dramatically induced SIRT1 expression, blocked p65 acetylation, and inhibited NF-kappaB activity and the expression of inflammatory factors in MNCs in vitro.	Metformin	24-33	RELA proto-oncogene, NF-kB subunit	Homo sapiens	91-94
26141671-10	2015	We conclude that metformin has a novel direct protective role to ameliorate the proinflammatory response through SIRT1 induction, p65 acetylation reduction, NF-kappaB inactivation, and inflammatory inhibition in peripheral blood MNCs of patients with carotid artery AS.	Metformin	17-26	RELA proto-oncogene, NF-kB subunit	Homo sapiens	130-133
26503334-14	2015	In addition, both NLK knockdown and metformin treatment reduced the tumor sphere formation capacity and percentage of CD133+ cells.	Metformin	36-45	prominin 1	Homo sapiens	118-123
26473366-1	2015	BACKGROUND: Metformin is effective for the treatment of polycystic ovary syndrome, but conflicting results regarding its effect on adipocytokine levels (adiponectin, resistin, visfatin, and leptin) in patients with polycystic ovary syndrome receiving metformin treatment have been reported.	Metformin	12-21	nicotinamide phosphoribosyltransferase	Homo sapiens	176-184
26473366-7	2015	Metformin treatment was associated with significantly elevated serum adiponectin concentrations (standard mean differences [95% confidence interval], -0.43 [-0.75 to -0.11]) and decreased serum leptin concentrations (0.65 [0.26 to 1.04]), whereas no significant difference in resistin level (-0.01 [-0.49 to 0.45]) or visfatin level (-0.04 [-1.55 to 1.46]) was found.	Metformin	0-9	nicotinamide phosphoribosyltransferase	Homo sapiens	318-326
26692929-0	2015	PGC-1 mediates the regulation of metformin in muscle irisin expression and function.	Metformin	33-42	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	0-5
26692929-6	2015	Mouse skeletal muscle myoblasts C2C12 cells were treated with Metformin for 24 h. The molecules PGC-1alpha, FNDC5, AMPK, and ERK mRNA/proteins were quantified by real-time PCR and western blotting in vivo and in vitro.	Metformin	62-71	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	96-106
26692929-8	2015	PGC-1alpha, p-AMPK and p-ERK protein expression was up-regulated by Metformin in skeletal muscle and C2C12 cells.	Metformin	68-77	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	0-10
28614117-8	2017	In addition to drugs such as metformin and 5-aminoimidazole-4-carboxamide ribonucleotide that are classically used as AMPK activators, recent studies have identified the therapeutic potential of other compounds that function at least partly as AMPK activators, such as salicylates, statins, berberine, and resveratrol, in preventing the progression of CKD.	Metformin	29-38	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	244-248
28930827-14	2017	Ranking results showed that glyburide might be the optimum treatment regarding average glucose control, and metformin is the fastest in glucose control for GDM patients; glyburide have the highest incidence of macrosomia, preeclampsia, hyperbilirubinemia, neonatal hypoglycemia, shortest gestational age at delivery, and lowest mean birth weight; metformin (plus insulin when required) have the lowest incidence of macrosomia, PIH, LGA, RDS, low gestational age at delivery, and low birth weight.	Metformin	108-117	pregnancy-induced hypertension (pre-eclampsia, eclampsia, toxemia of pregnancy included)	Homo sapiens	427-430
28953663-10	2017	CONCLUSION: The results of this meta-analysis indicated that Liraglutide added on to metformin therapy could significantly lower the level of HbA1c and increase body weight loss.	Metformin	85-94	hemoglobin subunit alpha 1	Homo sapiens	142-146
28533436-0	2017	Metformin Synergizes with BCL-XL/BCL-2 Inhibitor ABT-263 to Induce Apoptosis Specifically in p53-Defective Cancer Cells.	Metformin	0-9	BCL2-like 1	Mus musculus	26-32
28533436-3	2017	Metformin has shown anti-neoplastic efficiency partially through suppressing mTORC1.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	77-83
28533436-6	2017	Mechanistic studies revealed that metformin sensitized ABT-263 via attenuating mTORC1-mediated cap-dependent translation of MCL-1 and survivin and weakening internal ribosome entry site (IRES)-dependent translation of XIAP Meanwhile, ABT-263 sensitized metformin through disrupting the BCL-XL/BIM complex.	Metformin	34-43	CREB regulated transcription coactivator 1	Mus musculus	79-85
28533436-6	2017	Mechanistic studies revealed that metformin sensitized ABT-263 via attenuating mTORC1-mediated cap-dependent translation of MCL-1 and survivin and weakening internal ribosome entry site (IRES)-dependent translation of XIAP Meanwhile, ABT-263 sensitized metformin through disrupting the BCL-XL/BIM complex.	Metformin	34-43	myeloid cell leukemia sequence 1	Mus musculus	124-129
28533436-6	2017	Mechanistic studies revealed that metformin sensitized ABT-263 via attenuating mTORC1-mediated cap-dependent translation of MCL-1 and survivin and weakening internal ribosome entry site (IRES)-dependent translation of XIAP Meanwhile, ABT-263 sensitized metformin through disrupting the BCL-XL/BIM complex.	Metformin	34-43	baculoviral IAP repeat-containing 5	Mus musculus	134-142
28533436-6	2017	Mechanistic studies revealed that metformin sensitized ABT-263 via attenuating mTORC1-mediated cap-dependent translation of MCL-1 and survivin and weakening internal ribosome entry site (IRES)-dependent translation of XIAP Meanwhile, ABT-263 sensitized metformin through disrupting the BCL-XL/BIM complex.	Metformin	34-43	X-linked inhibitor of apoptosis	Mus musculus	218-222
28533436-6	2017	Mechanistic studies revealed that metformin sensitized ABT-263 via attenuating mTORC1-mediated cap-dependent translation of MCL-1 and survivin and weakening internal ribosome entry site (IRES)-dependent translation of XIAP Meanwhile, ABT-263 sensitized metformin through disrupting the BCL-XL/BIM complex.	Metformin	34-43	BCL2-like 1	Mus musculus	286-292
29190886-0	2017	Metformin activates type I interferon signaling against HCV via activation of adenosine monophosphate-activated protein kinase.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	78-126
29190886-2	2017	Metformin can activate adenosine monophosphate-activated protein kinase (AMPK) to reduce insulin resistance.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	23-71
29190886-2	2017	Metformin can activate adenosine monophosphate-activated protein kinase (AMPK) to reduce insulin resistance.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	73-77
29190886-7	2017	Metformin enhanced the phosphorylation of AMPK, and the metformin-activated IFN signaling was down-regulated by AMPK inhibitor.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	42-46
29190886-7	2017	Metformin enhanced the phosphorylation of AMPK, and the metformin-activated IFN signaling was down-regulated by AMPK inhibitor.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	112-116
29190886-7	2017	Metformin enhanced the phosphorylation of AMPK, and the metformin-activated IFN signaling was down-regulated by AMPK inhibitor.	Metformin	56-65	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	112-116
29190886-8	2017	After treatment of AMPK inhibitor, the level of HCV core protein decreased by metformin can be rescued.	Metformin	78-87	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	19-23
29190886-9	2017	In conclusion, metformin activates type I interferon signaling and inhibits the replication of HCV via activation of AMPK.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	117-121
27923278-8	2017	Most importantly, the AMPK activator metformin was associated with decreased serum hepcidin content and anemia morbidity in Chinese type 2 diabetes mellitus patients.	Metformin	37-46	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	22-26
26487791-1	2015	In Brief For patients with type 2 diabetes who require add-on therapy to metformin plus basal insulin, GLP-1 receptor agonists may be a favorable option because they effectively manage postprandial glucose, reduce body weight, and have an overall favorable safety profile compared to other agents.	Metformin	73-82	glucagon like peptide 1 receptor	Homo sapiens	103-117
28767685-6	2017	Treatment with metformin enhanced expression TRIC and LSR via AMPK during cell differentiation.	Metformin	15-24	MARVEL (membrane-associating) domain containing 2	Mus musculus	45-49
28206714-9	2017	Metformin counteracted the effect of high glucose on the elevated G6P and fructose 2,6-bisphosphate and on Gck repression, recruitment of Mlx-ChREBP to the G6pc and Pklr promoters and induction of these genes.	Metformin	0-9	glucose-6-phosphatase catalytic subunit 1	Homo sapiens	156-160
28545687-11	2017	Metformin and trametinib increased phosphorylated AMPK expression in LGSOC lines with combination showing stronger expression.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	50-54
28676445-12	2017	Furthermore, metformin reduced the protein expressions of COX-2 and PI3K in liver and COX-1 in lung.	Metformin	13-22	cytochrome c oxidase II, mitochondrial	Rattus norvegicus	58-63
28709719-4	2017	RESULTS: At the cellular level metformin"s produces both AMP-activated kinase (AMPK) dependent and independent effects.	Metformin	31-40	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	57-77
28709719-4	2017	RESULTS: At the cellular level metformin"s produces both AMP-activated kinase (AMPK) dependent and independent effects.	Metformin	31-40	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	79-83
28720775-5	2017	Metformin alleviated NAPDH oxidase- and mitochondria-mediated ROS production with an increase in superoxide dismutase (SOD) activity and SOD2 expression.	Metformin	0-9	superoxide dismutase 2	Homo sapiens	137-141
28720775-6	2017	Metformin inhibited the activation of Smad2/3 and MAPK, GSK-3beta phosphorylation, nuclear translocalization of beta-catenin and Snail in HPMCs.	Metformin	0-9	SMAD family member 2	Homo sapiens	38-45
28720775-6	2017	Metformin inhibited the activation of Smad2/3 and MAPK, GSK-3beta phosphorylation, nuclear translocalization of beta-catenin and Snail in HPMCs.	Metformin	0-9	glycogen synthase kinase 3 beta	Homo sapiens	56-65
28675758-8	2017	At the molecular level, the AMPK signaling pathway was activated, whereas the mTOR and ERK1/2 signaling pathways were inhibited by metformin.	Metformin	131-140	mitogen activated protein kinase 3	Rattus norvegicus	87-93
28819383-0	2017	Metformin Inhibits Tumorigenesis and Tumor Growth of Breast Cancer Cells by Upregulating miR-200c but Downregulating AKT2 Expression.	Metformin	0-9	microRNA 200c	Homo sapiens	89-97
28819383-3	2017	Growing evidence suggests that metformin"s anticancer effects are mediated at least in part by modulating microRNAs, including miR-200c, which has a tumor suppressive role in breast cancer.	Metformin	31-40	microRNA 200c	Homo sapiens	127-135
28819383-4	2017	We hypothesized that miR-200c has a role in the antitumorigenic effects of metformin on breast cancer cells.	Metformin	75-84	microRNA 200c	Homo sapiens	21-29
28819383-10	2017	Metformin treatment was associated with increased miR-200c expression and decreased c-Myc and AKT2 protein expression in both breast cancer cells and tumor tissues.	Metformin	0-9	microRNA 200c	Homo sapiens	50-58
28819383-11	2017	Overexpression of miR-200c exhibited effects on breast cancer cells similar to those of metformin treatment.	Metformin	88-97	microRNA 200c	Homo sapiens	18-26
28819383-13	2017	Conclusion: Metformin inhibits the growth and invasiveness of breast cancer cells by upregulation of miR-200c expression by targeting AKT2.	Metformin	12-21	microRNA 200c	Homo sapiens	101-109
28437189-8	2017	In addition, metformin was found to significantly decrease collagen 1a and TGF-beta expression and inhibit p-Smad2 and p-Smad3 expression compared to that of the irradiated group alone.	Metformin	13-22	SMAD family member 3	Mus musculus	121-126
29145540-9	2017	Three-month treatment with metformin and pioglitazone significantly improved insulin sensitivity and increased orexin concentrations by 26% (p = 0.025) and 14% (p = 0.076), respectively.	Metformin	27-36	hypocretin neuropeptide precursor	Homo sapiens	111-117
29145540-10	2017	Between-group analysis showed that changes in orexin concentrations with metformin and pioglitazone were not significantly different (p = 0.742).	Metformin	73-82	hypocretin neuropeptide precursor	Homo sapiens	46-52
29145540-12	2017	Three-month anti-hyperglycemic treatment with proportionate doses of metformin or pioglitazone increased orexin concentrations via amelioration of insulin resistance and improvement of glycemic control.	Metformin	69-78	hypocretin neuropeptide precursor	Homo sapiens	105-111
28177944-0	2017	Metformin depresses overactivated Notch1/Hes1 signaling in colorectal cancer patients with type 2 diabetes mellitus.	Metformin	0-9	hes family bHLH transcription factor 1	Homo sapiens	41-45
28177944-12	2017	In conclusion, the abnormal cell proliferation and differentiation observed in DM-CRC are correlated with overactivated Notch1/Hes1 signaling, which is potentially relieved by metformin treatment.	Metformin	176-185	hes family bHLH transcription factor 1	Homo sapiens	127-131
26063645-8	2015	Multivariate Cox analysis indicated that metformin use was an independent prognostic factor for long-term outcome (HR = 0.549, 95 % CI 0.198-0.978, p = 0.001).	Metformin	41-50	cytochrome c oxidase subunit 8A	Homo sapiens	13-16
25450818-8	2015	Metformin was only effective in lowering OPG levels in women.	Metformin	0-9	TNF receptor superfamily member 11b	Homo sapiens	41-44
26271140-5	2015	Metformin is an activator of AMPK which inhibits protein synthesis and gluconeogenesis during cellular stress.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	29-33
26426900-5	2015	OCT1-, OCT2-, MATE1- and MATE2-K-mediated metformin uptake was significantly reduced in the presence of green tea and EGCG (P &lt; 0.05).	Metformin	42-51	solute carrier family 47 member 2	Homo sapiens	25-30
26116230-0	2015	Metformin regulates stromal-epithelial cells communication via Wnt2/beta-catenin signaling in endometriosis.	Metformin	0-9	Wnt family member 2	Homo sapiens	63-67
26116230-5	2015	Metformin decreased the expression and secretion of Wnt2 in ESC.	Metformin	0-9	Wnt family member 2	Homo sapiens	52-56
26116230-8	2015	Metformin might regulate the stroma-epithelium communication via Wnt2-mediated signaling in endometriosis.	Metformin	0-9	Wnt family member 2	Homo sapiens	65-69
26225747-0	2015	Metformin decreases growth of pancreatic cancer cells by decreasing reactive oxygen species: Role of NOX4.	Metformin	0-9	NADPH oxidase 4	Homo sapiens	101-105
26225747-9	2015	CONCLUSION: Our findings suggest that metformin decreases cell survival by reducing ROS production, in part through down regulation of NOX4 protein expression.	Metformin	38-47	NADPH oxidase 4	Homo sapiens	135-139
26360050-10	2015	In contrast, metformin treatment increased expression levels of p-AMPK and Foxp3.	Metformin	13-22	forkhead box P3	Homo sapiens	75-80
26265439-7	2015	At doses that were totally ineffective on normal lymphocytes, metformin induced apoptosis of quiescent CLL cells and inhibition of cell cycle entry when CLL were stimulated by CD40-CD40L ligation.	Metformin	62-71	CD40 molecule	Homo sapiens	176-180
26067231-7	2015	Metformin reduced expression of extracellular matrix proteins and profibrotic factor TGFbeta in obstructed kidneys, measured by immunohistochemistry.	Metformin	0-9	transforming growth factor, beta 1	Mus musculus	85-92
26138461-8	2015	Metformin caused a significant reduction in liver fibrosis (Sirius red), hepatic stellate cell activation (alpha-smooth muscle actin, platelet-derived growth factor receptor beta polypeptide, transforming growth factor-betaR1, and Rho kinase), hepatic inflammation (CD68 and CD163), superoxide (dihydroethidium staining), and nitric oxide scavenging (protein nitrotyrosination).	Metformin	0-9	Cd68 molecule	Rattus norvegicus	266-270
26558235-10	2015	Among diabetic patients with cervical LN metastasis of DTC, the metformin subgroup (17.1 years) was associated with longer DFS than the nonmetformin subgroup (8.6 years) (HR 0.16, p = 0.021); metformin treatment was also associated with longer DFS in this subgroup in multivariate analysis after adjusting age, BMI, duration of diabetes, presence of tumor at resection margin, and serum thyroglobulin level at ablation (HR 0.03, p = 0.035).	Metformin	64-73	thyroglobulin	Homo sapiens	387-400
26480253-6	2015	In recent years, new antidiabetic drugs have been marketed (GLP1 analogues, DPP-4 inhibitors, SGLT-2 inhibitors) to ameliorate glycemia in patients nave or treated by means of traditional agents, such as sulfonylureas, metformin, glinides, insulin.	Metformin	219-228	glucagon like peptide 1 receptor	Homo sapiens	60-64
25579456-9	2015	RESULTS: Phospho-AMPK was increased by metformin in all cell lines whilst phospho-Akt and phospho-ERK expressions were decreased in two.	Metformin	39-48	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	17-21
25981877-3	2015	Metformin may harbor a pleiotropic action, (a) decreasing inflammation (via anti COX 2 pathway and other mechanism), (b) decreasing COX 2 and VEGF mediated angiogenesis, (c) increasing negative angiogenic regulation pathway by stimulating SMAD 2/3 expression either directly or via the AMPK pathway and preventing from pulmonary hypertension development and (d) diminushin oxidative stress.	Metformin	0-9	SMAD family member 2	Homo sapiens	239-247
25993908-11	2015	Moreover, treatment of megakaryocytes with metformin enhanced mitochondrial content and in the same cells metformin enhanced the phosphorylation of the Drp-1 on Ser637 via an AMPKalpha1-dependent mechanism.	Metformin	43-52	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	175-185
25993908-11	2015	Moreover, treatment of megakaryocytes with metformin enhanced mitochondrial content and in the same cells metformin enhanced the phosphorylation of the Drp-1 on Ser637 via an AMPKalpha1-dependent mechanism.	Metformin	106-115	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	175-185
26056043-6	2015	Metformin combined with aspirin significantly inhibited the phosphorylation of mTOR and STAT3, and induced apoptosis as measured by caspase-3 and PARP cleavage.	Metformin	0-9	collagen type XI alpha 2 chain	Homo sapiens	146-150
26056043-7	2015	Remarkably, metformin combined with aspirin significantly downregulated the anti-apoptotic proteins Mcl-1 and Bcl-2, and upregulated the pro-apoptotic proteins Bim and Puma, as well as interrupted their interactions.	Metformin	12-21	myeloid cell leukemia sequence 1	Mus musculus	100-105
26056043-9	2015	In a PANC-1 xenograft mouse model, we demonstrated that the combination of metformin and aspirin significantly inhibited tumor growth and downregulated the protein expression of Mcl-1 and Bcl-2 in tumors.	Metformin	75-84	myeloid cell leukemia sequence 1	Mus musculus	178-183
26050920-11	2015	Metformin influences on AMPK/mTOR cell signaling were evaluated by investigating AKT, AMPK and S6 phosphorylation levels.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	24-28
26050920-11	2015	Metformin influences on AMPK/mTOR cell signaling were evaluated by investigating AKT, AMPK and S6 phosphorylation levels.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	86-90
25962562-9	2015	Following treatment with bisperoxopicolinatooxovanadate (BPV) or metformin in the insulin-resistant skeletal muscle cells, there was an increase in the rate of glucose uptake, an increase in GLUT4 expression and its translocation, a reduction in the expression of PTEN and p-PTEN, and a decrease in cell apoptosis compared with untreated insulin-resistant cells.	Metformin	65-74	solute carrier family 2 member 4	Homo sapiens	191-196
26622608-13	2015	Immunohistochemical analysis revealed that downregulation of the expression of specific proteins associated with AMPK promoted xenograft growth and angiogenesis, while western blotting revealed inhibition of the AKT/mTOR signaling pathway in xenografts treated with metformin in combination with cisplatin.	Metformin	266-275	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	113-117
25906350-6	2015	We also investigated the action of metformin, a drug taken to control type 2 diabetes and recently shown to inhibit mTORC1 in vivo.	Metformin	35-44	CREB regulated transcription coactivator 1	Mus musculus	116-122
25715695-0	2015	Quantitative Evaluation of mMate1 Function Based on Minimally Invasive Measurement of Tissue Concentration Using PET with [(11)C]Metformin in Mouse.	Metformin	129-138	solute carrier family 47, member 1	Mus musculus	27-33
25854169-5	2015	Cyclin D1 and c-Myc are important regulators of cancer cell growth, and we observed that treatment of thyroid cancer cells with metformin reduced c-Myc and cyclin D1 expression through suppression of mTOR and subsequent inhibition of P70S6K1 and 4E-BP1 phosphorylation.	Metformin	128-137	cyclin D1	Homo sapiens	0-9
25854169-5	2015	Cyclin D1 and c-Myc are important regulators of cancer cell growth, and we observed that treatment of thyroid cancer cells with metformin reduced c-Myc and cyclin D1 expression through suppression of mTOR and subsequent inhibition of P70S6K1 and 4E-BP1 phosphorylation.	Metformin	128-137	cyclin D1	Homo sapiens	156-165
26196392-0	2015	Metformin Induced AMPK Activation, G0/G1 Phase Cell Cycle Arrest and the Inhibition of Growth of Esophageal Squamous Cell Carcinomas In Vitro and In Vivo.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	18-22
26196392-4	2015	The findings reported herein show that the anti-proliferative action of metformin on ESCC cell lines is partially mediated by AMPK.	Metformin	72-81	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	126-130
26196392-7	2015	Most importantly, the up-regulation of AMPK, p53, p21CIP1, p27KIP1 and the down-regulation of cyclinD1 are involved in the anti-tumor action of metformin in vivo.	Metformin	144-153	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	39-43
26196392-7	2015	Most importantly, the up-regulation of AMPK, p53, p21CIP1, p27KIP1 and the down-regulation of cyclinD1 are involved in the anti-tumor action of metformin in vivo.	Metformin	144-153	cyclin D1	Homo sapiens	94-102
26196392-9	2015	AMPK, p53, p21CIP1, p27KIP1 and cyclinD1 are involved in the inhibition of tumor growth that is induced by metformin and cell cycle arrest in ESCC.	Metformin	107-116	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-4
26196392-9	2015	AMPK, p53, p21CIP1, p27KIP1 and cyclinD1 are involved in the inhibition of tumor growth that is induced by metformin and cell cycle arrest in ESCC.	Metformin	107-116	cyclin D1	Homo sapiens	32-40
26048992-6	2015	AMPK activators (5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside and metformin) decreased intracellular GlcCer levels and synthase activity in mouse fibroblasts.	Metformin	76-85	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
26045616-6	2015	The metformin-treated groups exhibited less severe mitochondrial damage (markers: cytochrome c release, citrate synthase activity, mtDNA copy number, mitochondrial respiration) and apoptosis (caspase 9 and caspase 3 activation).	Metformin	4-13	citrate synthase	Rattus norvegicus	104-120
26045616-6	2015	The metformin-treated groups exhibited less severe mitochondrial damage (markers: cytochrome c release, citrate synthase activity, mtDNA copy number, mitochondrial respiration) and apoptosis (caspase 9 and caspase 3 activation).	Metformin	4-13	caspase 3	Rattus norvegicus	206-215
26236179-3	2015	One of these detectors is AMPK (5" AMP-activated protein kinase), a protein kinase activated by ATP deficiency but also by several natural substances such as polyphenols or synthetic molecules like metformin, used in the treatment of insulin resistance.	Metformin	198-207	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	26-30
25547060-8	2015	CONCLUSION: Metformin can significantly reduce several adverse maternal and neonatal outcomes including PIH rate, incidence of hypoglycemia and NICU, thus it may be an effective and safe alternative or additional treatment to insulin for GDM women.	Metformin	12-21	pregnancy-induced hypertension (pre-eclampsia, eclampsia, toxemia of pregnancy included)	Homo sapiens	104-107
27837308-10	2017	An anti-diabetic drug, metformin, attenuated insulin resistance in PCB-treated 3T3-L1 adipocytes through the reduced expression of Fsp27 protein and LD size.	Metformin	23-32	pyruvate carboxylase	Mus musculus	67-70
28390311-0	2017	Metformin mitigates carbon tetrachloride-induced TGF-beta1/Smad3 signaling and liver fibrosis in mice.	Metformin	0-9	transforming growth factor, beta 1	Mus musculus	49-58
28390311-0	2017	Metformin mitigates carbon tetrachloride-induced TGF-beta1/Smad3 signaling and liver fibrosis in mice.	Metformin	0-9	SMAD family member 3	Mus musculus	59-64
28390311-6	2017	However, treatment with metformin suppressed CCl4-induced expression of transforming growth factor beta 1 (TGF-beta1) and phosphorylation of Smad3, which was accompanied with decreased level of alpha smooth muscle actin (alpha-SMA), a marker for the activated hepatic stellate cells (HSCs).	Metformin	24-33	transforming growth factor, beta 1	Mus musculus	72-105
28390311-6	2017	However, treatment with metformin suppressed CCl4-induced expression of transforming growth factor beta 1 (TGF-beta1) and phosphorylation of Smad3, which was accompanied with decreased level of alpha smooth muscle actin (alpha-SMA), a marker for the activated hepatic stellate cells (HSCs).	Metformin	24-33	transforming growth factor, beta 1	Mus musculus	107-116
28390311-6	2017	However, treatment with metformin suppressed CCl4-induced expression of transforming growth factor beta 1 (TGF-beta1) and phosphorylation of Smad3, which was accompanied with decreased level of alpha smooth muscle actin (alpha-SMA), a marker for the activated hepatic stellate cells (HSCs).	Metformin	24-33	SMAD family member 3	Mus musculus	141-146
28390311-7	2017	These data indicates that metformin could mitigate CCl4-induced liver fibrosis and these beneficial effects might result from suppressed TGF-beta1/Smad3 signaling.	Metformin	26-35	transforming growth factor, beta 1	Mus musculus	137-146
28390311-7	2017	These data indicates that metformin could mitigate CCl4-induced liver fibrosis and these beneficial effects might result from suppressed TGF-beta1/Smad3 signaling.	Metformin	26-35	SMAD family member 3	Mus musculus	147-152
28273365-8	2017	Specifically, metformin significantly reduced UUO-induced transforming growth factor beta1 (TGFbeta1) mRNA and protein expression in WT mice but not in AMPKalpha2-/- mice.	Metformin	14-23	transforming growth factor, beta 1	Mus musculus	58-90
28273365-8	2017	Specifically, metformin significantly reduced UUO-induced transforming growth factor beta1 (TGFbeta1) mRNA and protein expression in WT mice but not in AMPKalpha2-/- mice.	Metformin	14-23	transforming growth factor, beta 1	Mus musculus	92-100
28273365-9	2017	In contrast, metformin reduced UUO-induced TGFbeta1 downstream Smad3 phosphorylation in both WT and AMPKalpha2-/- mice, suggesting that this regulation occurs in an AMPKalpha2-independent manner.	Metformin	13-22	transforming growth factor, beta 1	Mus musculus	43-51
28273365-9	2017	In contrast, metformin reduced UUO-induced TGFbeta1 downstream Smad3 phosphorylation in both WT and AMPKalpha2-/- mice, suggesting that this regulation occurs in an AMPKalpha2-independent manner.	Metformin	13-22	SMAD family member 3	Mus musculus	63-68
28273365-10	2017	In conclusion, the underlying mechanisms for the protective effects of metformin against renal fibrosis include AMPKalpha2-dependent targeting of TGFbeta1 production and AMPKalpha2-independent targeting of TGFbeta1 downstream signalling.	Metformin	71-80	transforming growth factor, beta 1	Mus musculus	146-154
28273365-10	2017	In conclusion, the underlying mechanisms for the protective effects of metformin against renal fibrosis include AMPKalpha2-dependent targeting of TGFbeta1 production and AMPKalpha2-independent targeting of TGFbeta1 downstream signalling.	Metformin	71-80	transforming growth factor, beta 1	Mus musculus	206-214
28364040-6	2017	The down-regulation of HNF4alpha was dependent on the activation of AMP-activated protein kinase (AMPK), and the reduction of HNF4alpha protein expression by metformin, an AMPK activator, and hypoxia was inhibited by the overexpression of a kinase-dead (KD) form of AMPKalpha2.	Metformin	158-167	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	266-276
28322845-7	2017	It has been shown that naringenin exerts its anti-diabetic effects by inhibition of gluconeogenesis through upregulations of AMPK hence metformin-like effects.	Metformin	136-145	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	125-129
28496098-7	2017	Co-treatment of MDA-MB-231 cells with metformin and 2-DG induced a strong activation of AMP-activated protein kinase (AMPK), which was reduced by AMPK inhibitor compound C that prevented detachment of MDA-MB-231 cells.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	88-116
28496098-7	2017	Co-treatment of MDA-MB-231 cells with metformin and 2-DG induced a strong activation of AMP-activated protein kinase (AMPK), which was reduced by AMPK inhibitor compound C that prevented detachment of MDA-MB-231 cells.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	118-122
28496098-7	2017	Co-treatment of MDA-MB-231 cells with metformin and 2-DG induced a strong activation of AMP-activated protein kinase (AMPK), which was reduced by AMPK inhibitor compound C that prevented detachment of MDA-MB-231 cells.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	146-150
28465536-0	2017	Metformin disrupts malignant behavior of oral squamous cell carcinoma via a novel signaling involving Late SV40 factor/Aurora-A.	Metformin	0-9	transcription factor CP2	Homo sapiens	102-118
25779083-0	2015	Metformin and caloric restriction induce an AMPK-dependent restoration of mitochondrial dysfunction in fibroblasts from Fibromyalgia patients.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	44-48
25779083-7	2015	In contrast, AMPK activation by metformin or incubation with serum from caloric restricted mice improved the response to moderate oxidative stress and mitochondrial metabolism in FM fibroblasts.	Metformin	32-41	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	13-17
28465536-0	2017	Metformin disrupts malignant behavior of oral squamous cell carcinoma via a novel signaling involving Late SV40 factor/Aurora-A.	Metformin	0-9	aurora kinase A	Homo sapiens	119-127
28465536-5	2017	Importantly, metformin-restrained tumorigenesis of oral cancer was accompanied with strong decrease of both Aurora-A and Late SV40 Factor (LSF) expressions.	Metformin	13-22	aurora kinase A	Homo sapiens	108-116
28465536-5	2017	Importantly, metformin-restrained tumorigenesis of oral cancer was accompanied with strong decrease of both Aurora-A and Late SV40 Factor (LSF) expressions.	Metformin	13-22	transcription factor CP2	Homo sapiens	121-137
28465536-5	2017	Importantly, metformin-restrained tumorigenesis of oral cancer was accompanied with strong decrease of both Aurora-A and Late SV40 Factor (LSF) expressions.	Metformin	13-22	transcription factor CP2	Homo sapiens	139-142
28465536-8	2017	These findings showed that a novel LSF/Aurora-A-signaling inhibition supports the rationale of using metformin as potential OSCC therapeutics.	Metformin	101-110	transcription factor CP2	Homo sapiens	35-38
28465536-8	2017	These findings showed that a novel LSF/Aurora-A-signaling inhibition supports the rationale of using metformin as potential OSCC therapeutics.	Metformin	101-110	aurora kinase A	Homo sapiens	39-47
28232370-4	2017	The relevance of these data is interesting from a therapeutic point of view as several agents with potential anti-obesity and/or antidiabetic effects, some currently in clinical use, such as nicotine, metformin and liraglutide are known to act through AMPK, either peripherally or centrally.	Metformin	201-210	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	252-256
28238946-0	2017	Involvement of pregnane X receptor in the suppression of carboxylesterases by metformin in vivo and in vitro, mediated by the activation of AMPK and JNK signaling pathway.	Metformin	78-87	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	140-144
28238946-7	2017	Furthermore, metformin significantly suppresses the phosphorylation of AMPK and JNK, and the suppression of carboxylesterases induced by metformin is repeatedly abolished by AMPK inhibitor Compound C and JNK inhibitor SP600125.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	71-75
28238946-7	2017	Furthermore, metformin significantly suppresses the phosphorylation of AMPK and JNK, and the suppression of carboxylesterases induced by metformin is repeatedly abolished by AMPK inhibitor Compound C and JNK inhibitor SP600125.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	174-178
28238946-7	2017	Furthermore, metformin significantly suppresses the phosphorylation of AMPK and JNK, and the suppression of carboxylesterases induced by metformin is repeatedly abolished by AMPK inhibitor Compound C and JNK inhibitor SP600125.	Metformin	137-146	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	71-75
28238946-7	2017	Furthermore, metformin significantly suppresses the phosphorylation of AMPK and JNK, and the suppression of carboxylesterases induced by metformin is repeatedly abolished by AMPK inhibitor Compound C and JNK inhibitor SP600125.	Metformin	137-146	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	174-178
28238946-8	2017	It implies that the activation of AMPK and JNK pathways mediates the suppression of carboxylesterases by metformin.	Metformin	105-114	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	34-38
28494038-10	2017	CONCLUSION: Metformin did not modulate the damaging effect of hyperglycemia on bone healing around implants at histometric levels, but increased the expression of OPG and decreased the RANKL/OPG ratio in the medullary area, yielding some molecular benefits in the osseointegration of implants under the hyperglycemic state.	Metformin	12-21	TNF superfamily member 11	Rattus norvegicus	185-190
28378260-8	2017	Moreover, as compared to donepezil, metformin-treated mice exhibited an enhanced number of post-mitotic NeuN-positive neurons.	Metformin	36-45	RNA binding protein, fox-1 homolog (C. elegans) 3	Mus musculus	104-108
28391030-6	2017	Metformin triggered autophagy (LC3B expression) was identified to interplay with apoptosis to attenuate the drug effect and postpone cancer cell death.	Metformin	0-9	microtubule associated protein 1 light chain 3 beta	Homo sapiens	31-35
28393204-6	2017	The IR expression level was significantly higher in murine subcutaneous flank tumors of the low-carbohydrate diet group and high-carbohydrate diet plus metformin group than of the high-carbohydrate diet group.	Metformin	152-161	insulin receptor	Mus musculus	4-6
25633418-6	2015	Osteoblast-specific PGC-1alpha upregulation by 6-C-beta-d-glucopyranosyl-(2S,3S)-(+)-5,7,3",4"-tetrahydroxydihydroflavonol (GTDF), an adiponectin receptor 1 (AdipoR1) agonist, as well as metformin in db mice that lacked AdipoR1 expression in muscle but not bone restored osteopenia to wt levels without improving diabetes.	Metformin	187-196	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	20-30
25681557-0	2015	Metformin ameliorates acetaminophen hepatotoxicity via Gadd45beta-dependent regulation of JNK signaling in mice.	Metformin	0-9	growth arrest and DNA-damage-inducible 45 beta	Mus musculus	55-65
25681557-5	2015	METHODS: We used APAP- and/or metformin-treated Gadd45beta knockout (KO) mice and wild type (WT) C57BL/6J control mice.	Metformin	30-39	growth arrest and DNA-damage-inducible 45 beta	Mus musculus	48-58
25681557-8	2015	Gadd45beta expression was increased after APAP treatment, and the expression of Gadd45beta was further enhanced by metformin.	Metformin	115-124	growth arrest and DNA-damage-inducible 45 beta	Mus musculus	80-90
25681557-9	2015	The effects of metformin on APAP-induced liver injury and JNK phosphorylation were abolished in Gadd45beta KO mice.	Metformin	15-24	growth arrest and DNA-damage-inducible 45 beta	Mus musculus	96-106
25681557-13	2015	CONCLUSIONS: This study is the first to demonstrate that metformin shows protective and therapeutic effects against APAP overdose-evoked hepatotoxicity via Gadd45beta-dependent JNK regulation.	Metformin	57-66	growth arrest and DNA-damage-inducible 45 beta	Mus musculus	156-166
26111001-6	2015	However, SMMC-7721 cells had higher levels of basal autophagy and mTORC2-mediated feedback activation of Akt than HepG2 cells, which may render SMMC-7721 cells to be more resistant to metformin-induced inhibition of cell growth.	Metformin	184-193	CREB regulated transcription coactivator 2	Mus musculus	66-72
26150733-5	2015	The addition of canagliflozin to metformin resulted in a decrease in HbA1c of 0.73%-0.93%.	Metformin	33-42	hemoglobin subunit alpha 1	Homo sapiens	69-73
25676019-8	2015	Mechanistically, the beneficial effects of metformin on hepatic aspects are mediated through both adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways.	Metformin	43-52	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	98-146
25676019-8	2015	Mechanistically, the beneficial effects of metformin on hepatic aspects are mediated through both adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways.	Metformin	43-52	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	148-152
25676019-8	2015	Mechanistically, the beneficial effects of metformin on hepatic aspects are mediated through both adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways.	Metformin	43-52	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	168-172
25891779-7	2015	In the PA-treated L6 cells, metformin treatment enhanced AMPK phosphorylation, reduced SREBP-1c expression and increased IRS-1 and Akt protein expression, whereas treatment with compound C blocked the effects of metformin on SREBP-1c expression and the IRS-1 and Akt levels.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	57-61
25891779-8	2015	Moreover, metformin suppressed SREBP-1c promoter activity and promoted glucose uptake through AMPK.	Metformin	10-19	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	94-98
25891779-9	2015	The results from this study demonstrate that metformin ameliorates PA-induced insulin resistance through the activation of AMPK and the suppression of SREBP-1c in skeletal muscle cells.	Metformin	45-54	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	123-127
25413451-7	2015	Our results indicated that pretreatment of rats by metformin attenuated cellular levels of nuclear factor-kappaB, Tumor Necrosis Factor alpha and Cyclooxygenase-2 which are considered as three important proteins involved in the inflammation pathway.	Metformin	51-60	prostaglandin-endoperoxide synthase 2	Rattus norvegicus	146-162
28459432-8	2017	We further showed that both metformin treatment and SUV39H1 knockout in PCa cells can reduce integrin alphaV and beta1 proteins, as well as their downstream phosphorylated focal adhesion kinase (FAK) levels, which is essential for functional adhesion signaling and tumor cell migration.	Metformin	28-37	protein tyrosine kinase 2	Homo sapiens	172-193
28459432-8	2017	We further showed that both metformin treatment and SUV39H1 knockout in PCa cells can reduce integrin alphaV and beta1 proteins, as well as their downstream phosphorylated focal adhesion kinase (FAK) levels, which is essential for functional adhesion signaling and tumor cell migration.	Metformin	28-37	protein tyrosine kinase 2	Homo sapiens	195-198
28459432-9	2017	Taken together, metformin reduced SUV39H1 to inhibit migration of PCa cells via disturbing the integrin-FAK signaling.	Metformin	16-25	protein tyrosine kinase 2	Homo sapiens	104-107
28168653-12	2017	High-dose metformin significantly reduced the expression of matrix metalloproteinase-2 (MMP-2) and mechanistic Target of Rapamycin (mTor), regardless of the concentration of dexamethasone and testosterone.	Metformin	10-19	matrix metallopeptidase 2	Homo sapiens	60-86
28168653-12	2017	High-dose metformin significantly reduced the expression of matrix metalloproteinase-2 (MMP-2) and mechanistic Target of Rapamycin (mTor), regardless of the concentration of dexamethasone and testosterone.	Metformin	10-19	matrix metallopeptidase 2	Homo sapiens	88-93
28571222-12	2017	HbA1c level and insulin dosage was significantly reduced (p&lt;0.001) after one month of metformin as an adjunct therapy.	Metformin	89-98	hemoglobin subunit alpha 1	Homo sapiens	0-4
28571222-15	2017	CONCLUSION: Adjunctive metformin therapy reduced HbA1c value and the insulin dosage received in adolescents with T1DM.	Metformin	23-32	hemoglobin subunit alpha 1	Homo sapiens	49-53
28069720-2	2017	As pregnancy increased the renal secretion of metformin, a substrate for OCT2, MATE1, and MATE2-K, we hypothesized that the renal secretion of 1-NMN would be similarly affected.	Metformin	46-55	solute carrier family 47 member 2	Homo sapiens	90-97
28078601-10	2017	Metformin treatment reduced N-cadherin and increased E-cadherin expression in both CF41 and TGF-beta1sh cells.	Metformin	0-9	cadherin 1	Canis lupus familiaris	53-63
28078601-10	2017	Metformin treatment reduced N-cadherin and increased E-cadherin expression in both CF41 and TGF-beta1sh cells.	Metformin	0-9	transforming growth factor beta-1 proprotein	Canis lupus familiaris	92-101
28078601-11	2017	Was demonstrated that metformin treatment reduced the number of lung metastases in animals bearing TGF-beta1sh tumors.	Metformin	22-31	transforming growth factor beta-1 proprotein	Canis lupus familiaris	99-108
28078601-14	2017	To the best of our knowledge, we are the first to report metformin treatment in cells with TGF-beta1 silencing and their effect on EMT.	Metformin	57-66	transforming growth factor beta-1 proprotein	Canis lupus familiaris	91-100
27743302-0	2017	Effect of lifestyle interventions with or without metformin therapy on serum levels of osteoprotegerin and receptor activator of nuclear factor kappa B ligand in patients with prediabetes.	Metformin	50-59	TNF receptor superfamily member 11b	Homo sapiens	87-102
25779963-8	2015	Taken together, our data suggest that the dysregulation of Parkin-PARIS-PGC-1alpha pathway by metabolic malregulation may contribute to the pathogenesis of PD and metformin might exert a neuroprotective effect on PD via the restoration of parkin.	Metformin	163-172	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	72-82
26052399-6	2015	Metformin (through 5"-adenosine monophosphate-activated protein kinase pathway activation) and statins (through 3-hydroxy-3-methylglutaryl coenzyme A inhibition) show anti-tumoral properties modifying several steps of RAS/RAF/MEK/ERK, PI3K/AKT/mTOR and Wnt/beta-catenin signaling cascades.	Metformin	0-9	zinc fingers and homeoboxes 2	Homo sapiens	222-225
25895126-5	2015	Metformin treatment in RD and HED mice resulted in a significant reduction in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by decreased levels of growth factors (IGF-1, insulin and leptin), inflammatory cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet mice.	Metformin	0-9	insulin-like growth factor 1	Mus musculus	193-198
25595658-0	2015	The neuroprotective role of metformin in advanced glycation end product treated human neural stem cells is AMPK-dependent.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	107-111
25595658-2	2015	Metformin, one of the most widely used anti-diabetic drugs, exerts its effects in part by activation of AMP-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	104-132
25595658-2	2015	Metformin, one of the most widely used anti-diabetic drugs, exerts its effects in part by activation of AMP-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	134-138
25595658-10	2015	These findings extend our understanding of the molecular mechanisms of both AGE-induced neuronal toxicity, and AMPK-dependent neuroprotection by metformin.	Metformin	145-154	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	111-115
25667085-12	2015	Upon metformin treatment, NF-kappaB is activated and translocates from the cytoplasm to the nucleus, where it induces increased APP and Pres 1 transcription.	Metformin	5-14	presenilin 1	Homo sapiens	136-142
25667085-13	2015	The use of Bay11-7085 inhibitor suppressed the effect of metformin on APP and Pres 1 expression.	Metformin	57-66	presenilin 1	Homo sapiens	78-84
25497570-8	2015	Treatment with metformin, an activator of AMPK, significantly reduced cartilage matrix formation and inhibited gene expression of sox6, sox9, col2a1 and aggrecan core protein (acp).	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	42-46
25497570-8	2015	Treatment with metformin, an activator of AMPK, significantly reduced cartilage matrix formation and inhibited gene expression of sox6, sox9, col2a1 and aggrecan core protein (acp).	Metformin	15-24	SRY-box transcription factor 6	Homo sapiens	130-134
25497570-8	2015	Treatment with metformin, an activator of AMPK, significantly reduced cartilage matrix formation and inhibited gene expression of sox6, sox9, col2a1 and aggrecan core protein (acp).	Metformin	15-24	SRY-box transcription factor 9	Homo sapiens	136-140
25053715-12	2015	Among the KLF5/GATA4/GATA6 direct target genes relevant for cancer development, one target gene, HNF4alpha, was also required for GC proliferation and could be targeted by the antidiabetic drug metformin, revealing a therapeutic opportunity for KLF5/GATA4/GATA6 amplified GCs.	Metformin	194-203	Kruppel-like factor 5	Mus musculus	10-14
25053715-12	2015	Among the KLF5/GATA4/GATA6 direct target genes relevant for cancer development, one target gene, HNF4alpha, was also required for GC proliferation and could be targeted by the antidiabetic drug metformin, revealing a therapeutic opportunity for KLF5/GATA4/GATA6 amplified GCs.	Metformin	194-203	GATA binding protein 6	Mus musculus	21-26
25053715-12	2015	Among the KLF5/GATA4/GATA6 direct target genes relevant for cancer development, one target gene, HNF4alpha, was also required for GC proliferation and could be targeted by the antidiabetic drug metformin, revealing a therapeutic opportunity for KLF5/GATA4/GATA6 amplified GCs.	Metformin	194-203	Kruppel-like factor 5	Mus musculus	245-249
25053715-12	2015	Among the KLF5/GATA4/GATA6 direct target genes relevant for cancer development, one target gene, HNF4alpha, was also required for GC proliferation and could be targeted by the antidiabetic drug metformin, revealing a therapeutic opportunity for KLF5/GATA4/GATA6 amplified GCs.	Metformin	194-203	GATA binding protein 6	Mus musculus	256-261
26034806-24	2015	When they are combined with metformin, two injectable GLP-1 analogues, exenatide and liraglutide, have a glucose-lowering potency similar to one or two daily insulin injections.	Metformin	28-37	glucagon like peptide 1 receptor	Homo sapiens	54-59
25812084-5	2015	Recent epidemiological studies indicate that treatment with metformin, an AMPK activator reduces the incidence of cancer.	Metformin	60-69	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	74-78
25785990-9	2015	VEGF expression levels did not differ between metformin- and saline-treated OIR groups at P17 and P21, but Flk1 levels were significantly reduced in the metformin group compared with saline-treated OIR group.	Metformin	153-162	kinase insert domain protein receptor	Mus musculus	107-111
25785990-10	2015	Moreover, metformin inhibited VEGF-induced cell proliferation and decreased levels of Flk1 and pFlk1, consistent with the interpretation that metformin inhibits vascular growth by reducing Flk1 levels.	Metformin	10-19	kinase insert domain protein receptor	Mus musculus	86-90
25785990-10	2015	Moreover, metformin inhibited VEGF-induced cell proliferation and decreased levels of Flk1 and pFlk1, consistent with the interpretation that metformin inhibits vascular growth by reducing Flk1 levels.	Metformin	10-19	kinase insert domain protein receptor	Mus musculus	96-100
25785990-10	2015	Moreover, metformin inhibited VEGF-induced cell proliferation and decreased levels of Flk1 and pFlk1, consistent with the interpretation that metformin inhibits vascular growth by reducing Flk1 levels.	Metformin	142-151	kinase insert domain protein receptor	Mus musculus	86-90
25785990-10	2015	Moreover, metformin inhibited VEGF-induced cell proliferation and decreased levels of Flk1 and pFlk1, consistent with the interpretation that metformin inhibits vascular growth by reducing Flk1 levels.	Metformin	142-151	kinase insert domain protein receptor	Mus musculus	96-100
25785990-11	2015	CONCLUSION: Metformin exerts anti-angiogenesis effects and delays the normal vessel formation in the recovery phase of OIR in mice, likely by suppressing the levels of Flk1.	Metformin	12-21	kinase insert domain protein receptor	Mus musculus	168-172
25542900-9	2015	Ritonavir and metformin effectively suppressed AKT and mTORC1 phosphorylation and prosurvival BCL-2 family member MCL-1 expression in multiple myeloma cell lines in vitro and in vivo.	Metformin	14-23	CREB regulated transcription coactivator 1	Mus musculus	55-61
25683794-11	2015	The association of glimepiride/metformin, both due to cost as well as effectiveness and safety, may be the preferential treatment for most DM2 patients, and it offers a potential advantage in refractory hyperglycemic populations, tolerant to treatment.	Metformin	31-40	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	139-142
26120598-5	2015	Induction of autophagic flux, through metformin-mediated AMP-activated protein kinase (AMPK) activation and interruption of mammalian target of rapamycin (mTOR) signaling mitigated the inflammation in experimental arthritis.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	57-85
26120598-5	2015	Induction of autophagic flux, through metformin-mediated AMP-activated protein kinase (AMPK) activation and interruption of mammalian target of rapamycin (mTOR) signaling mitigated the inflammation in experimental arthritis.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	87-91
26120598-6	2015	Further investigation into the effects of metformin suggest that the drug directly activates AMPK and dose-dependently suppressed the release of TNF-alpha, IL-6, and MCP-1 by macrophages while enhancing the release of IL-10 in vitro.	Metformin	42-51	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	93-97
27813052-8	2017	Moreover, a significant reduction was observed in the serum levels of FSH (p&gt;0.01), LH (p&gt;0.001), and visfatin (p&gt;0.001) after metformin treatment.	Metformin	136-145	nicotinamide phosphoribosyltransferase	Homo sapiens	108-116
25679763-8	2015	This leads to inhibition of autophagy, activation of mTOR signaling, and hypersensitization to AMPK agonists, such as metformin.	Metformin	118-127	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	95-99
27988363-5	2017	AMPK knockdown by RNA interference, as well as the treatment with the mTORC1 activator leucine, prevented indomethacin-mediated mTORC1 inhibition and cytotoxic action, while AMPK activators metformin and AICAR mimicked the effects of the drug.	Metformin	190-199	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-4
27988363-5	2017	AMPK knockdown by RNA interference, as well as the treatment with the mTORC1 activator leucine, prevented indomethacin-mediated mTORC1 inhibition and cytotoxic action, while AMPK activators metformin and AICAR mimicked the effects of the drug.	Metformin	190-199	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	174-178
27128966-0	2017	Metformin induces degradation of cyclin D1 via AMPK/GSK3beta axis in ovarian cancer.	Metformin	0-9	cyclin D1	Homo sapiens	33-42
27128966-3	2017	Here, we first describe that the anti-cancer effect of metformin is mediated by cyclin D1 deregulation via AMPK/GSK3beta axis in ovarian cancer cells.	Metformin	55-64	cyclin D1	Homo sapiens	80-89
27128966-5	2017	Metformin induced the G1 cell cycle arrest, in parallel with a decrease in the protein expressions of cyclin D1 without affecting its transcriptional levels.	Metformin	0-9	cyclin D1	Homo sapiens	102-111
27128966-6	2017	Using a proteasomal inhibitor, we could address that metformin-induced decrease in cyclin D1 through the ubiquitin/proteasome process.	Metformin	53-62	cyclin D1	Homo sapiens	83-92
27128966-7	2017	Cyclin D1 degradation by metformin requires the activation of GSK3beta, as determined based on the treatment with GSK3beta inhibitors.	Metformin	25-34	cyclin D1	Homo sapiens	0-9
27128966-7	2017	Cyclin D1 degradation by metformin requires the activation of GSK3beta, as determined based on the treatment with GSK3beta inhibitors.	Metformin	25-34	glycogen synthase kinase 3 beta	Homo sapiens	62-70
27128966-7	2017	Cyclin D1 degradation by metformin requires the activation of GSK3beta, as determined based on the treatment with GSK3beta inhibitors.	Metformin	25-34	glycogen synthase kinase 3 beta	Homo sapiens	114-122
27128966-8	2017	The activation of GSK3beta correlated with the inhibitory phosphorylation by Akt as well as p70S6K through AMPK activation in response to metformin.	Metformin	138-147	glycogen synthase kinase 3 beta	Homo sapiens	18-26
27128966-9	2017	These findings suggested that the anticancer effects of metformin was induced due to cyclin D1 degradation via AMPK/GSK3beta signaling axis that involved the ubiquitin/proteasome pathway specifically in ovarian cancer cells.	Metformin	56-65	cyclin D1	Homo sapiens	85-94
27128966-9	2017	These findings suggested that the anticancer effects of metformin was induced due to cyclin D1 degradation via AMPK/GSK3beta signaling axis that involved the ubiquitin/proteasome pathway specifically in ovarian cancer cells.	Metformin	56-65	glycogen synthase kinase 3 beta	Homo sapiens	116-124
28035400-4	2017	In the present study, the AMPK activator metformin impaired breast cancer cell growth by reducing dishevelled segment polarity protein 3 (DVL3) and beta-catenin levels.	Metformin	41-50	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	26-30
28035400-4	2017	In the present study, the AMPK activator metformin impaired breast cancer cell growth by reducing dishevelled segment polarity protein 3 (DVL3) and beta-catenin levels.	Metformin	41-50	dishevelled segment polarity protein 3	Homo sapiens	98-136
28035400-4	2017	In the present study, the AMPK activator metformin impaired breast cancer cell growth by reducing dishevelled segment polarity protein 3 (DVL3) and beta-catenin levels.	Metformin	41-50	dishevelled segment polarity protein 3	Homo sapiens	138-142
28035400-5	2017	Western blotting and immunohistochemistry demonstrated that DVL3 was recurrently upregulated in breast cancer cells that were not treated with metformin, and was significantly associated with enhanced levels of beta-catenin, c-Myc and cyclin D1.	Metformin	143-152	dishevelled segment polarity protein 3	Homo sapiens	60-64
28035400-7	2017	To elucidate the underlying mechanism of these effects, the present study verified that metformin resulted in a downregulation of DVL3 and beta-catenin in a dose-dependent manner, and induced phosphorylation of AMPK.	Metformin	88-97	dishevelled segment polarity protein 3	Homo sapiens	130-134
28035400-7	2017	To elucidate the underlying mechanism of these effects, the present study verified that metformin resulted in a downregulation of DVL3 and beta-catenin in a dose-dependent manner, and induced phosphorylation of AMPK.	Metformin	88-97	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	211-215
28035400-8	2017	Compound C is an AMPK inhibitor, which when administered alongside metformin, significantly abolished the effects of metformin on the reduction of DVL3 and activation of the phosphorylation of AMPK.	Metformin	117-126	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	17-21
28035400-8	2017	Compound C is an AMPK inhibitor, which when administered alongside metformin, significantly abolished the effects of metformin on the reduction of DVL3 and activation of the phosphorylation of AMPK.	Metformin	117-126	dishevelled segment polarity protein 3	Homo sapiens	147-151
28035400-8	2017	Compound C is an AMPK inhibitor, which when administered alongside metformin, significantly abolished the effects of metformin on the reduction of DVL3 and activation of the phosphorylation of AMPK.	Metformin	117-126	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	193-197
28035400-9	2017	Notably, the effects of metformin on the mRNA expression levels of DVL3 remain to be fully elucidated; however, a possible interaction with DVL3 at the post-transcriptional level was observed.	Metformin	24-33	dishevelled segment polarity protein 3	Homo sapiens	67-71
27642000-5	2017	Metformin was the first prescription for 98 957 (80%) patients, with mean HbA1c of 8.68% prior to initiation (95% confidence interval [CI] 8.67, 8.69).	Metformin	0-9	hemoglobin subunit alpha 1	Homo sapiens	74-78
28145471-11	2017	Our findings provide new insights on the interaction between metformin and GLP-1, and provide important information for designing new GLP-1-based therapy strategies in treating type 2 diabetes.	Metformin	61-70	glucagon	Mus musculus	75-80
28145471-11	2017	Our findings provide new insights on the interaction between metformin and GLP-1, and provide important information for designing new GLP-1-based therapy strategies in treating type 2 diabetes.	Metformin	61-70	glucagon	Mus musculus	134-139
28065882-0	2017	Rescue of mutant rhodopsin traffic by metformin-induced AMPK activation accelerates photoreceptor degeneration.	Metformin	38-47	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	56-60
28065882-2	2017	Here, we tested whether the AMPK activator metformin could affect the P23H rhodopsin synthesis and folding.	Metformin	43-52	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	28-32
28068351-7	2017	A gene variant in the THADA locus was associated with response to metformin and metformin was a predicted upstream regulator at the same locus.	Metformin	66-75	THADA armadillo repeat containing	Homo sapiens	22-27
25425574-7	2015	Importantly, metformin, a metabolic stressor and popular anti-diabetic drug, inactivates HSF1 and provokes proteotoxic stress within tumor cells, thereby impeding tumor growth.	Metformin	13-22	heat shock transcription factor 1	Homo sapiens	89-93
28068351-7	2017	A gene variant in the THADA locus was associated with response to metformin and metformin was a predicted upstream regulator at the same locus.	Metformin	80-89	THADA armadillo repeat containing	Homo sapiens	22-27
28068384-7	2017	Importantly, hypoxia-activated mTORC1 was accompanied by the AMPK downregulation, and we found that the AMPK pathway activators Metformin (Met) and 5-Aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR) decreased the mTORC1 activity, cell motility and lateral migration.	Metformin	128-137	CREB regulated transcription coactivator 1	Mus musculus	31-37
28068384-7	2017	Importantly, hypoxia-activated mTORC1 was accompanied by the AMPK downregulation, and we found that the AMPK pathway activators Metformin (Met) and 5-Aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR) decreased the mTORC1 activity, cell motility and lateral migration.	Metformin	128-137	CREB regulated transcription coactivator 1	Mus musculus	225-231
28045889-11	2017	It was shown that metformin downregulates the expression of cyclin D1 and increases the p27KIP1 level.	Metformin	18-27	cyclin D1	Homo sapiens	60-69
28045889-13	2017	Lastly, miRNA34a was found to be upregulated by metformin in ACHN, 769-P, and A498 cells.	Metformin	48-57	microRNA 34a	Homo sapiens	8-16
28045889-14	2017	Subsequently, it was demonstrated that inhibition of miRNA34a could partially attenuate the suppressive effect of metformin on renal cancer cell proliferation.	Metformin	114-123	microRNA 34a	Homo sapiens	53-61
28045889-15	2017	CONCLUSIONS The study data revealed that metformin induced cell growth inhibition and cell cycle arrest partially by upregulating miRNA34a in renal cancer cells.	Metformin	41-50	microRNA 34a	Homo sapiens	130-138
28011481-6	2017	A low dose of metformin significantly increased anoikis and inhibited migration/ invasion of CCA cells that was in concert with the decrease of vimentin, matrix metalloproteinase (MMP)-2 and -7.	Metformin	14-23	matrix metallopeptidase 2	Homo sapiens	154-186
28042775-6	2017	RESULTS: There was a lower protein expression of ROCK-1, vimentin, CD44 and CD24 in both cell lines after treatment with metformin and Y27632.	Metformin	121-130	Rho associated coiled-coil containing protein kinase 1	Homo sapiens	49-55
28546950-2	2017	SLC47A1 (MATE1) and SLC47A2 (MATE2) are major efflux transporters involved in the hepatic and renal excretion of many cationic drugs including metformin.	Metformin	143-152	solute carrier family 47 member 2	Homo sapiens	20-27
28546950-2	2017	SLC47A1 (MATE1) and SLC47A2 (MATE2) are major efflux transporters involved in the hepatic and renal excretion of many cationic drugs including metformin.	Metformin	143-152	solute carrier family 47 member 2	Homo sapiens	29-34
27941003-0	2017	Efficacy of PD-1 Blockade Is Potentiated by Metformin-Induced Reduction of Tumor Hypoxia.	Metformin	44-53	programmed cell death 1	Homo sapiens	12-16
25500743-0	2015	Uncoupling AMPK from autophagy: a foe that hinders the beneficial effects of metformin treatment on metabolic syndrome-associated atherosclerosis?	Metformin	77-86	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	11-15
25534988-9	2015	In turn, major mechanism of metformin action involved increased expression of proteins implicated in mitochondrial biogenesis and metabolism (PGC-1alpha, PPARalpha, COX IV, cytochrome c, HADHSC).	Metformin	28-37	cytochrome c oxidase subunit 4I1	Homo sapiens	165-171
28628912-5	2017	RESULTS: After treatment with LPS, high glucose or both LPS and high glucose, phosphor-AMPK expression was decreased, and moreover, AMPK activation by metformin treatment alleviated the decrease in phosphor-AMPK expression in HUVECs and macrophages as well as in lung tissue.	Metformin	151-160	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	87-91
25468944-9	2015	Glucose rate of disappearance relative to baseline increased more in CON (31 +- 3%) than in DM2 (6 +- 1%) and DM2+Met (21 +- 2%), showing a small increase caused by metformin.	Metformin	165-174	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	92-95
25468944-9	2015	Glucose rate of disappearance relative to baseline increased more in CON (31 +- 3%) than in DM2 (6 +- 1%) and DM2+Met (21 +- 2%), showing a small increase caused by metformin.	Metformin	165-174	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	110-117
28628912-5	2017	RESULTS: After treatment with LPS, high glucose or both LPS and high glucose, phosphor-AMPK expression was decreased, and moreover, AMPK activation by metformin treatment alleviated the decrease in phosphor-AMPK expression in HUVECs and macrophages as well as in lung tissue.	Metformin	151-160	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	132-136
28628912-5	2017	RESULTS: After treatment with LPS, high glucose or both LPS and high glucose, phosphor-AMPK expression was decreased, and moreover, AMPK activation by metformin treatment alleviated the decrease in phosphor-AMPK expression in HUVECs and macrophages as well as in lung tissue.	Metformin	151-160	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	132-136
28628912-7	2017	AMPK activation by metformin administration improved the survival of STZ-induced diabetic mice and db/db diabetic mice, which was associated with reduced lung endothelial hyperpermeability and systemic inflammatory response.	Metformin	19-28	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
27803295-10	2017	In ex vivo tumour slices, metformin treatment led to increased necrosis, decreased cyclin D1 and increased carbonic anhydrase-9 (CA-9).	Metformin	26-35	carbonic anhydrase 9	Mus musculus	107-127
27803295-10	2017	In ex vivo tumour slices, metformin treatment led to increased necrosis, decreased cyclin D1 and increased carbonic anhydrase-9 (CA-9).	Metformin	26-35	carbonic anhydrase 9	Mus musculus	129-133
28714409-11	2017	CONCLUSION: AMPK activation as represented by metformin showed to improve disorders associated with diabetes and metabolic syndrome and became a well-established treatment strategy for these diseases.	Metformin	46-55	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	12-16
27959383-4	2017	Sorafenib effectively reversed the activation status of mTORC2 induced by metformin and enhanced the suppression of the mTORC1 and MAPK pathway by metformin in HCC cells, which may be responsible for reduced proliferation upon combined treatment.	Metformin	74-83	CREB regulated transcription coactivator 2	Mus musculus	56-62
27959383-4	2017	Sorafenib effectively reversed the activation status of mTORC2 induced by metformin and enhanced the suppression of the mTORC1 and MAPK pathway by metformin in HCC cells, which may be responsible for reduced proliferation upon combined treatment.	Metformin	147-156	CREB regulated transcription coactivator 1	Mus musculus	120-126
27959383-5	2017	The metformin and sorafenib combination led to increased impaired proliferation and tumor inhibition of HCC in vitro and in vivo compared to single agent, which was partially bridged by disrupting the mTORC1/mTORC2 feedback loop.	Metformin	4-13	CREB regulated transcription coactivator 1	Mus musculus	201-207
27959383-5	2017	The metformin and sorafenib combination led to increased impaired proliferation and tumor inhibition of HCC in vitro and in vivo compared to single agent, which was partially bridged by disrupting the mTORC1/mTORC2 feedback loop.	Metformin	4-13	CREB regulated transcription coactivator 2	Mus musculus	208-214
28002460-11	2016	In correlation, the mRNA level of differentiation regulator including bmp4, bmpr2 and math1 were also increased in IL10KO mice supplemented with metformin, which likely explains the enhanced epithelial differentiation in IL10KO mice with metformin.	Metformin	145-154	bone morphogenetic protein receptor, type II (serine/threonine kinase)	Mus musculus	76-81
28002460-11	2016	In correlation, the mRNA level of differentiation regulator including bmp4, bmpr2 and math1 were also increased in IL10KO mice supplemented with metformin, which likely explains the enhanced epithelial differentiation in IL10KO mice with metformin.	Metformin	145-154	atonal bHLH transcription factor 1	Mus musculus	86-91
28002460-11	2016	In correlation, the mRNA level of differentiation regulator including bmp4, bmpr2 and math1 were also increased in IL10KO mice supplemented with metformin, which likely explains the enhanced epithelial differentiation in IL10KO mice with metformin.	Metformin	238-247	bone morphogenetic protein receptor, type II (serine/threonine kinase)	Mus musculus	76-81
28002460-11	2016	In correlation, the mRNA level of differentiation regulator including bmp4, bmpr2 and math1 were also increased in IL10KO mice supplemented with metformin, which likely explains the enhanced epithelial differentiation in IL10KO mice with metformin.	Metformin	238-247	atonal bHLH transcription factor 1	Mus musculus	86-91
27959931-0	2016	MATE2 Expression Is Associated with Cancer Cell Response to Metformin.	Metformin	60-69	solute carrier family 47 member 2	Homo sapiens	0-5
25527635-6	2015	We report that metformin leads to a major inhibition of Rac1 GTPase activity by interfering with some of its multiple upstream signaling pathways, namely P-Rex1 (a Guanine nucleotide exchange factor and activator of Rac1), cAMP, and CXCL12/CXCR4, resulting in decreased migration of prostate cancer cells.	Metformin	15-24	C-X-C motif chemokine ligand 12	Homo sapiens	233-239
25305450-6	2015	Western blot showed that metformin activated caspase 3, caspase 9, PARP-1, Bak, and p21 and inactivated Mcl-1, HIAP-1, cyclin D1, CDK4, and CDK6.	Metformin	25-34	cyclin D1	Homo sapiens	119-128
25305450-6	2015	Western blot showed that metformin activated caspase 3, caspase 9, PARP-1, Bak, and p21 and inactivated Mcl-1, HIAP-1, cyclin D1, CDK4, and CDK6.	Metformin	25-34	cyclin dependent kinase 4	Homo sapiens	130-134
27959931-15	2016	High MATE2 expression may result in resistance to the anti-proliferative effect of metformin and should be considered as a negative predictive biomarker in clinical trials.	Metformin	83-92	solute carrier family 47 member 2	Homo sapiens	5-10
27636742-0	2016	Metformin inhibits estrogen-dependent endometrial cancer cell growth by activating the AMPK-FOXO1 signal pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	87-91
27636742-4	2016	Metformin treatment suppressed EC cell growth in a time-dependent manner in vitro; this effect was cancelled by cotreatment with an AMPK inhibitor, compound C. Metformin decreased FOXO1 phosphorylation and increased FOXO1 nuclear localization in Ishikawa and HEC-1B cells, with non-significant increase in FOXO1 mRNA expression.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	132-136
27636742-4	2016	Metformin treatment suppressed EC cell growth in a time-dependent manner in vitro; this effect was cancelled by cotreatment with an AMPK inhibitor, compound C. Metformin decreased FOXO1 phosphorylation and increased FOXO1 nuclear localization in Ishikawa and HEC-1B cells, with non-significant increase in FOXO1 mRNA expression.	Metformin	160-169	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	132-136
27636742-5	2016	Moreover, compound C blocked the metformin-induced changes of FOXO1 and its phosphorylation protein, suggesting that metformin upregulated FOXO1 activity by AMPK activation.	Metformin	33-42	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	157-161
27636742-5	2016	Moreover, compound C blocked the metformin-induced changes of FOXO1 and its phosphorylation protein, suggesting that metformin upregulated FOXO1 activity by AMPK activation.	Metformin	117-126	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	157-161
27636742-8	2016	A xenograft mouse model further revealed that metformin suppressed HEC-1B tumor growth, accompanied by downregulated ki-67 and upregulated AMPK phosphorylation and nuclear FOXO1 protein.	Metformin	46-55	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	139-143
27636742-9	2016	Taken together, these data provide a novel mechanism of antineoplastic effect for metformin through the regulation of FOXO1, and suggest that the AMPK-FOXO1 pathway may be a therapeutic target to the development of new antineoplastic drugs.	Metformin	82-91	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	146-150
27753529-0	2016	Cyclin G2 promotes cell cycle arrest in breast cancer cells responding to fulvestrant and metformin and correlates with patient survival.	Metformin	90-99	cyclin G2	Homo sapiens	0-9
27753529-9	2016	We determined that metformin upregulates CycG2 and potentiates fulvestrant-induced CycG2 expression and cell cycle arrest.	Metformin	19-28	cyclin G2	Homo sapiens	41-46
27753529-9	2016	We determined that metformin upregulates CycG2 and potentiates fulvestrant-induced CycG2 expression and cell cycle arrest.	Metformin	19-28	cyclin G2	Homo sapiens	83-88
27753529-10	2016	CycG2 knockdown blunts the enhanced anti-proliferative effect of metformin on fulvestrant treated cells.	Metformin	65-74	cyclin G2	Homo sapiens	0-5
27613809-7	2016	Importantly, Mfn1 deficiency increased complex I abundance and sensitized animals to the hypoglycemic effect of metformin.	Metformin	112-121	mitofusin 1	Mus musculus	13-17
26745042-5	2015	The AMPK/mTORC1 pathway in intrahepatic CCA cells is targeted by metformin.	Metformin	65-74	CREB regulated transcription coactivator 1	Mus musculus	9-15
25456211-0	2015	AMPK/mTOR-mediated inhibition of survivin partly contributes to metformin-induced apoptosis in human gastric cancer cell.	Metformin	64-73	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-4
25456211-9	2015	AMPK knockdown by siRNA restores metformin-inhibited survivin expression and partially abolishes metformin-induced apoptosis.	Metformin	33-42	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-4
25456211-9	2015	AMPK knockdown by siRNA restores metformin-inhibited survivin expression and partially abolishes metformin-induced apoptosis.	Metformin	97-106	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-4
25456211-12	2015	Xenograft nude mouse experiment also confirmed that AMPK/mTOR-mediated decrease of suvivin is in vivo implicated in metformin-induced apoptosis.	Metformin	116-125	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	52-56
25456211-13	2015	Taken together, these evidences suggest that AMPK/mTOR-mediated inhibition of survivin may partly contribute to metformin-induced apoptosis of gastric cancer cell.	Metformin	112-121	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	45-49
25739726-13	2015	In conclusion, liraglutide and metformin monotherapy showed similar reduction in HbA1c during 24 weeks, with no difference in weight gain or incidence of hypoglycemia in overweight or obese Japanese patients with T2DM.	Metformin	31-40	hemoglobin subunit alpha 1	Homo sapiens	81-85
27695899-10	2016	CONCLUSIONS/INTERPRETATION: Sequential cleavage of IR by calpain 2 and gamma-secretase may contribute to insulin signalling in cells and its inhibition may be partly responsible for the glucose-lowering effects of metformin.	Metformin	214-223	insulin receptor	Homo sapiens	51-53
27405060-10	2016	Metformin treatment improved the metabolic and inflammatory phenotype in Bcl-3Hep mice through modulation of PPARalpha and PGC-1alpha.	Metformin	0-9	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	123-133
27779715-3	2016	Therefore, the present study aimed to explain this phenomenon in regards to the relationship between microRNAs (miRNAs) and their target genes and to predict how AMPKalpha2 may be a downstream target gene of miR-27a, thus exploring the new mechanism of metformin in the treatment of breast cancer regarding miRNAs.	Metformin	253-262	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	162-172
27779715-9	2016	miR-27a was downregulated, and AMPKa2 was upregulated after intervention with metformin, and caspase-3 was activated.	Metformin	78-87	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	31-37
27562556-3	2016	(2015, Metformin ameliorates acetaminophen hepatotoxicity via Gadd45beta-dependent regulation of JNK signaling in mice.	Metformin	7-16	growth arrest and DNA-damage-inducible 45 beta	Mus musculus	62-72
27709225-8	2016	A 24-week rosiglitazone treatment on top of metformin was associated with significant decreases in resistin, DKK-1, 11-dehydro-TXB2 and 8-iso-PGF2alpha, in parallel with HOMA decrease.	Metformin	44-53	dickkopf WNT signaling pathway inhibitor 1	Homo sapiens	109-114
25789330-8	2015	In addition, the combination therapy with OA and metformin significantly increased the phosphorylation of AKT, PI3K, AMPK, and ACC and decreased the protein expression levels of G-6-Pase, PEPCK1, and TORC compared with those for either monotherapy.	Metformin	49-58	glucose-6-phosphatase, catalytic	Mus musculus	178-186
25493642-0	2014	Dose-Dependent AMPK-Dependent and Independent Mechanisms of Berberine and Metformin Inhibition of mTORC1, ERK, DNA Synthesis and Proliferation in Pancreatic Cancer Cells.	Metformin	74-83	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	15-19
25493642-0	2014	Dose-Dependent AMPK-Dependent and Independent Mechanisms of Berberine and Metformin Inhibition of mTORC1, ERK, DNA Synthesis and Proliferation in Pancreatic Cancer Cells.	Metformin	74-83	CREB regulated transcription coactivator 1	Mus musculus	98-104
25493642-9	2014	We propose that berberine and metformin inhibit mitogenic signaling in PDAC cells through dose-dependent AMPK-dependent and independent pathways.	Metformin	30-39	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	105-109
25503637-8	2014	Agonist induction of AMPK activity with AICAR or metformin increased macroautophagy protein LC3 and normalized p62/SQSTM1 expression and mTOR activity.	Metformin	49-58	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	21-25
25456737-5	2014	Metformin-induced activation of the energy-sensor AMPK is well documented, but may not account for all actions of the drug.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	50-54
25456737-6	2014	Here, we summarize current knowledge about the different AMPK-dependent and AMPK-independent mechanisms underlying metformin action.	Metformin	115-124	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	57-61
25456737-6	2014	Here, we summarize current knowledge about the different AMPK-dependent and AMPK-independent mechanisms underlying metformin action.	Metformin	115-124	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	76-80
25674239-19	2014	Agents that may be considered based on existing data include: bortezomib to inhibit NF-kappaB pathway activation; metformin to inhibit both NF-kappaB and mTORC2 and histone deacteylase inhibitors to inhibit mTORC2 pathway signaling.	Metformin	114-123	CREB regulated transcription coactivator 2	Mus musculus	154-160
25158895-13	2014	CONCLUSIONS: HFD could promote TRAMP mouse PCa development and progression and metformin had moderate effect of reducing PCa mortality rate with a decrease in serum IGF-1 level.	Metformin	79-88	insulin-like growth factor 1	Mus musculus	165-170
27902686-4	2016	We identified thousands of metformin responsive AMPK-dependent and AMPK-independent differentially expressed genes and regulatory elements.	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	48-52
27902686-4	2016	We identified thousands of metformin responsive AMPK-dependent and AMPK-independent differentially expressed genes and regulatory elements.	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	67-71
27902686-8	2016	Using ChIP-seq and siRNA knockdown, we further show that activating transcription factor 3 (ATF3), our top metformin upregulated AMPK-dependent gene, could have an important role in gluconeogenesis repression.	Metformin	107-116	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	129-133
27733682-0	2016	Activation of AMP-activated Protein Kinase by Metformin Induces Protein Acetylation in Prostate and Ovarian Cancer Cells.	Metformin	46-55	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	14-42
27733682-7	2016	Here we show that activation of AMPK with the widely used antidiabetic drug metformin or with the AMP mimetic 5-aminoimidazole-4-carboxamide ribonucleotide increases the inhibitory phosphorylation of ACC and decreases the conversion of acetyl-CoA to malonyl-CoA, leading to increased protein acetylation and altered gene expression in prostate and ovarian cancer cells.	Metformin	76-85	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	32-36
27733682-10	2016	Together, our data indicate that AMPK regulates the availability of nucleocytosolic acetyl-CoA for protein acetylation and that AMPK activators, such as metformin, have the capacity to increase protein acetylation and alter patterns of gene expression, further expanding the plethora of metformin"s physiological effects.	Metformin	153-162	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	128-132
27733682-10	2016	Together, our data indicate that AMPK regulates the availability of nucleocytosolic acetyl-CoA for protein acetylation and that AMPK activators, such as metformin, have the capacity to increase protein acetylation and alter patterns of gene expression, further expanding the plethora of metformin"s physiological effects.	Metformin	287-296	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	33-37
27733682-10	2016	Together, our data indicate that AMPK regulates the availability of nucleocytosolic acetyl-CoA for protein acetylation and that AMPK activators, such as metformin, have the capacity to increase protein acetylation and alter patterns of gene expression, further expanding the plethora of metformin"s physiological effects.	Metformin	287-296	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	128-132
27492924-4	2016	We investigated the impact of several AMPK activators on Treg-cell differentiation and found that the direct activator AICAR (5-aminoimidazole-4-carboxamide ribonucleotide), but not the indirect activators metformin and 2-deoxyglucose, strongly enhanced Treg-cell induction by specifically enhancing Treg-cell expansion.	Metformin	206-215	5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase	Homo sapiens	119-124
25138574-8	2014	Metformin also significantly reduced YKL-40 concentrations after 3 months (1.90 +- 17 vs. 1.66 +- 0.15 microg/L, p = 0.019).	Metformin	0-9	chitinase 3 like 1	Homo sapiens	37-43
25138574-10	2014	When compared, metformin was significantly more effective than pioglitazone with respect to YKL-40 reduction in both univariate (p = 0.020, effect size = 6.7%) and multivariate models (p = 0.047, effect size = 5.7%).	Metformin	15-24	chitinase 3 like 1	Homo sapiens	92-98
25138574-11	2014	CONCLUSIONS: Metformin is more effective in reduction of YKL-40 concentration in short term and the effect seems to be independent of degree of glycemic control, or hsCRP reduction.	Metformin	13-22	chitinase 3 like 1	Homo sapiens	57-63
25333332-11	2014	In addition, metformin plus radiation significantly upregulated the expression of p-ATM, p-ATR, gamma-H2AX and downregulated the expression of ATM, ATR, p95/NBS1, Rad50, DNA-PK, Ku70 and Ku80.	Metformin	13-22	RAD50 double strand break repair protein	Homo sapiens	163-168
25333332-11	2014	In addition, metformin plus radiation significantly upregulated the expression of p-ATM, p-ATR, gamma-H2AX and downregulated the expression of ATM, ATR, p95/NBS1, Rad50, DNA-PK, Ku70 and Ku80.	Metformin	13-22	X-ray repair cross complementing 5	Homo sapiens	187-191
25365944-6	2014	In tumors, the activation of Rac1 (GTP-Rac1) and Cdc42 (GTP-Cdc42) was increased while RhoA activation (GTP-RhoA) was decreased by metformin.	Metformin	131-140	ras homolog family member A	Mus musculus	87-91
25365944-6	2014	In tumors, the activation of Rac1 (GTP-Rac1) and Cdc42 (GTP-Cdc42) was increased while RhoA activation (GTP-RhoA) was decreased by metformin.	Metformin	131-140	ras homolog family member A	Mus musculus	108-112
25365944-9	2014	Additionally, inhibition of JNK activity along with Rac1 or Cdc42 attenuated cytotoxic effects of metformin.	Metformin	98-107	Rac family small GTPase 1	Mus musculus	52-56
25365944-9	2014	Additionally, inhibition of JNK activity along with Rac1 or Cdc42 attenuated cytotoxic effects of metformin.	Metformin	98-107	cell division cycle 42	Mus musculus	60-65
25608995-11	2014	Western blot analyses showed that with the increasing concentrations of metformin, the ERa expression was markedly down-regulated, while ERbeta expression was up-regulated in the metformin group at the concentrations of 5 mmol/L and 15 mmol/L, compared to those at the control group, there were significant differences between them, respectively (all P &lt; 0.01).	Metformin	72-81	estrogen receptor 2	Homo sapiens	137-143
25608995-11	2014	Western blot analyses showed that with the increasing concentrations of metformin, the ERa expression was markedly down-regulated, while ERbeta expression was up-regulated in the metformin group at the concentrations of 5 mmol/L and 15 mmol/L, compared to those at the control group, there were significant differences between them, respectively (all P &lt; 0.01).	Metformin	179-188	estrogen receptor 2	Homo sapiens	137-143
25179145-3	2014	To date, metformin regulation of AMPK has not been fully studied in intact arterial smooth muscle, especially during contraction evoked by G protein-coupled receptor (GPCR) agonists.	Metformin	9-18	G protein-coupled bile acid receptor 1	Rattus norvegicus	139-165
25179145-3	2014	To date, metformin regulation of AMPK has not been fully studied in intact arterial smooth muscle, especially during contraction evoked by G protein-coupled receptor (GPCR) agonists.	Metformin	9-18	G protein-coupled bile acid receptor 1	Rattus norvegicus	167-171
25179145-11	2014	Together, these findings suggest that, upon endothelial damage in the vessel wall, metformin uptake by the underlying vascular smooth muscle would accentuate AMPK phosphorylation by GPCR agonists independent of CaMKKbeta to promote vasorelaxation.	Metformin	83-92	G protein-coupled bile acid receptor 1	Rattus norvegicus	182-186
25315906-11	2014	In addition, metformin activated AMPK phosphorylation, inhibited NF-kappaB activation, down-regulated cytokine (IL-1beta, IL-6, TNF-alpha) and ICAM-1 expression following tMCAO (P &lt; 0.05).	Metformin	13-22	intercellular adhesion molecule 1	Mus musculus	143-149
25315906-12	2014	Furthermore, metformin activated AMPK signaling pathway and alleviated oxygen-glucose deprivation-induced ICAM-1 expression in bEND.3 cells (P &lt; 0.05).	Metformin	13-22	intercellular adhesion molecule 1	Mus musculus	106-112
25315906-14	2014	CONCLUSIONS: Metformin down-regulated ICAM-1 in an AMPK-dependent manner, which could effectively prevent ischemia-induced brain injury by alleviating neutrophil infiltration, suggesting that metformin is a promising therapeutic agent in stroke therapy.	Metformin	13-22	intercellular adhesion molecule 1	Mus musculus	38-44
25315906-14	2014	CONCLUSIONS: Metformin down-regulated ICAM-1 in an AMPK-dependent manner, which could effectively prevent ischemia-induced brain injury by alleviating neutrophil infiltration, suggesting that metformin is a promising therapeutic agent in stroke therapy.	Metformin	192-201	intercellular adhesion molecule 1	Mus musculus	38-44
25419360-5	2014	Metformin treatment inhibited RCC cells proliferation by increasing expression of miR-26a in 786-O cells (P &lt; 0.05).	Metformin	0-9	microRNA 26a-1	Homo sapiens	82-89
25419360-6	2014	As a result, protein abundance of Bcl-2 and cyclin D1 was decreased and PTEN was increased in cells exposed to metformin.	Metformin	111-120	cyclin D1	Homo sapiens	44-53
25419360-8	2014	Therefore, these data for the first time provide novel evidence for a mechanism that the anticancer activities of metformin are due to upregulation of miR-26a and affect its downstream target gene.	Metformin	114-123	microRNA 26a-1	Homo sapiens	151-158
25402373-6	2014	Metformin induced AMPK phosphorylation in pancreatic BON1 and midgut GOT1 but suppressed AMPK activity in bronchopulmonary NCI-H727.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	18-22
25402373-6	2014	Metformin induced AMPK phosphorylation in pancreatic BON1 and midgut GOT1 but suppressed AMPK activity in bronchopulmonary NCI-H727.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	89-93
25402373-8	2014	Metformin suppressed mTORC1 signaling in all three tumor cell types, evidenced by suppression of 4EBP1, pP70S6K, and S6 phosphorylation, and was associated with compensatory AKT activity.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	21-27
25110054-0	2014	Metformin suppresses CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating aryl hydrocarbon receptor expression.	Metformin	0-9	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	32-38
25110054-0	2014	Metformin suppresses CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating aryl hydrocarbon receptor expression.	Metformin	0-9	aryl hydrocarbon receptor	Homo sapiens	92-117
25110054-2	2014	Here, we investigated the effects of the anti-diabetes drug metformin on expression of CYP1A1 and CYP1B1 in breast cancer cells under constitutive and inducible conditions.	Metformin	60-69	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	98-104
25110054-3	2014	Our results indicated that metformin down-regulated the expression of CYP1A1 and CYP1B1 in breast cancer cells under constitutive and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced conditions.	Metformin	27-36	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	81-87
25110054-4	2014	Down-regulation of AhR expression was required for metformin-mediated decreases in CYP1A1 and CYP1B1 expression, and the metformin-mediated CYP1A1 and CYP1B1 reduction is irrelevant to estrogen receptor alpha (ERalpha) signaling.	Metformin	51-60	aryl hydrocarbon receptor	Homo sapiens	19-22
25110054-4	2014	Down-regulation of AhR expression was required for metformin-mediated decreases in CYP1A1 and CYP1B1 expression, and the metformin-mediated CYP1A1 and CYP1B1 reduction is irrelevant to estrogen receptor alpha (ERalpha) signaling.	Metformin	51-60	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	94-100
25110054-4	2014	Down-regulation of AhR expression was required for metformin-mediated decreases in CYP1A1 and CYP1B1 expression, and the metformin-mediated CYP1A1 and CYP1B1 reduction is irrelevant to estrogen receptor alpha (ERalpha) signaling.	Metformin	121-130	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	151-157
25110054-6	2014	The use of genetic and pharmacological tools revealed that metformin-mediated down-regulation of AhR expression was mediated through the reduction of Sp1 protein.	Metformin	59-68	aryl hydrocarbon receptor	Homo sapiens	97-100
25110054-7	2014	Metformin inhibited endogenous AhR ligand-induced CYP1A1 and CYP1B1 expression by suppressing tryptophan-2,3-dioxygenase (TDO) expression in MCF-7 cells.	Metformin	0-9	aryl hydrocarbon receptor	Homo sapiens	31-34
25110054-7	2014	Metformin inhibited endogenous AhR ligand-induced CYP1A1 and CYP1B1 expression by suppressing tryptophan-2,3-dioxygenase (TDO) expression in MCF-7 cells.	Metformin	0-9	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	61-67
25110054-9	2014	Our findings demonstrate that metformin reduces CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating AhR signaling.	Metformin	30-39	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	59-65
25110054-9	2014	Our findings demonstrate that metformin reduces CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating AhR signaling.	Metformin	30-39	aryl hydrocarbon receptor	Homo sapiens	119-122
25110054-10	2014	Metformin would be able to act as a potential chemopreventive agent against CYP1A1 and CYP1B1-mediated carcinogenesis and development of cancer.	Metformin	0-9	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	87-93
25201727-0	2014	Metformin inhibits epithelial-mesenchymal transition in prostate cancer cells: involvement of the tumor suppressor miR30a and its target gene SOX4.	Metformin	0-9	microRNA 30a	Homo sapiens	115-121
25201727-8	2014	Notably, we demonstrated significant upregulation of miR30a levels by metformin (P&lt;0.05) and further experiments indicated that miR30a significantly inhibits proliferation and EMT process of Vcap cells.	Metformin	70-79	microRNA 30a	Homo sapiens	53-59
25201727-12	2014	In all, our study suggested that inhibition of EMT by metformin in PCa cells may involve upregulation of miR30a and downregulation of SOX4.	Metformin	54-63	microRNA 30a	Homo sapiens	105-111
25009141-4	2014	Administration of AMPK activators (AICAR and metformin) significantly blocked hypertrophy, accompanied by enhanced autophagy level in the hearts.	Metformin	45-54	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	18-22
24857754-4	2014	As a regulator of cellular energy balance, 5" adenosine monophosphate-activated protein kinase (AMPK) has been suggested as a drug target for DM, including such drugs as metformin.	Metformin	170-179	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	46-94
24857754-4	2014	As a regulator of cellular energy balance, 5" adenosine monophosphate-activated protein kinase (AMPK) has been suggested as a drug target for DM, including such drugs as metformin.	Metformin	170-179	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	96-100
24970682-5	2014	Metformin-induced p53 protein levels in wild-type p53 cancer cells resulted in upregulation of microRNA (miR)-34a.	Metformin	0-9	microRNA 34a	Homo sapiens	95-113
24970682-6	2014	The use of a miR-34a inhibitor confirmed that metformin-induced miR-34a was required for Sirt1 downregulation.	Metformin	46-55	microRNA 34a	Homo sapiens	13-20
24970682-6	2014	The use of a miR-34a inhibitor confirmed that metformin-induced miR-34a was required for Sirt1 downregulation.	Metformin	46-55	microRNA 34a	Homo sapiens	64-71
25089625-1	2014	BACKGROUND: Incretin-based therapies which include glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are recommended by several practice guidelines as second-line agents for add-on therapy to metformin in patients with type 2 diabetes (T2DM) who do not achieve glycemic control with metformin plus lifestyle interventions alone.	Metformin	329-338	glucagon like peptide 1 receptor	Homo sapiens	76-91
24823468-0	2014	Metformin inhibits StAR expression in human endometriotic stromal cells via AMPK-mediated disruption of CREB-CRTC2 complex formation.	Metformin	0-9	steroidogenic acute regulatory protein	Homo sapiens	19-23
24823468-3	2014	OBJECTS: The aim of this study was to investigate the molecular and cellular mechanism by which metformin regulates StAR expression in human endometriotic stromal cells (ESCs).	Metformin	96-105	steroidogenic acute regulatory protein	Homo sapiens	116-120
24823468-7	2014	2) Metformin downregulates the StAR mRNA expression (maximum 31.7%) stimulated by PGE2 (2.4-fold) in ESCs.	Metformin	3-12	steroidogenic acute regulatory protein	Homo sapiens	31-35
27511809-18	2016	If a GnRH-agonist protocol is used, metformin as an adjunct may reduce the risk of ovarian hyperstimulation syndrome.	Metformin	36-45	gonadotropin releasing hormone 1	Homo sapiens	5-9
24823468-11	2014	CONCLUSIONS: We have demonstrated a detailed mechanistic analysis of StAR expression regulated by metformin in ESCs.	Metformin	98-107	steroidogenic acute regulatory protein	Homo sapiens	69-73
24823468-12	2014	Our data highlight a role for CRTC2 in the mechanism by which metformin inhibits StAR expression.	Metformin	62-71	steroidogenic acute regulatory protein	Homo sapiens	81-85
28173075-6	2016	Further study of one top candidate, STUB1, was performed to elucidate the mechanisms by which STUB1 might contribute to metformin action.	Metformin	120-129	STIP1 homology and U-box containing protein 1	Homo sapiens	36-41
28173075-6	2016	Further study of one top candidate, STUB1, was performed to elucidate the mechanisms by which STUB1 might contribute to metformin action.	Metformin	120-129	STIP1 homology and U-box containing protein 1	Homo sapiens	94-99
28173075-10	2016	Mechanistic studies revealed that the E3 ubiquitin ligase, STUB1, could influence metformin response by facilitating proteasome-mediated degradation of cyclin A.	Metformin	82-91	STIP1 homology and U-box containing protein 1	Homo sapiens	59-64
27654259-8	2016	In parallel, the activation of AMPK and suppression of mTOR seemed to play an important role for the effect of metformin in patients with EC.	Metformin	111-120	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	31-35
27599468-11	2016	Metformin inhibited IR-induced phosphorylation of Smad2 and Smad3.	Metformin	0-9	SMAD family member 2	Homo sapiens	50-55
27599468-11	2016	Metformin inhibited IR-induced phosphorylation of Smad2 and Smad3.	Metformin	0-9	SMAD family member 3	Homo sapiens	60-65
28167482-6	2016	Metformin caused a significant reduction in blood pressure with p &lt; 0.05 (i.e. SBP 9.9% &amp; DBP 6.4%) while sitagliptin caused a highly significant p &lt;0.01 reduction in blood pressure (i.e. SBP 15.8% &amp; DBP 12.2%).	Metformin	0-9	selenium binding protein 1	Homo sapiens	82-85
28167482-6	2016	Metformin caused a significant reduction in blood pressure with p &lt; 0.05 (i.e. SBP 9.9% &amp; DBP 6.4%) while sitagliptin caused a highly significant p &lt;0.01 reduction in blood pressure (i.e. SBP 15.8% &amp; DBP 12.2%).	Metformin	0-9	selenium binding protein 1	Homo sapiens	198-201
27787519-8	2016	In addition, metformin was shown to promote the expression of anabolic genes such as Col2a1 and Acan expression while inhibiting the expression of catabolic genes such as Mmp3 and Adamts5 in nucleus pulposus cells.	Metformin	13-22	aggrecan	Rattus norvegicus	96-100
27276511-4	2016	RESULTS: Metformin and resveratrol inhibited ROS-associated mitochondrial fission by upregulating Drp1 phosphorylation (Ser 637) in an AMPK-dependent manner, and then suppressed ER stress indicated by dephosphorylation of IRE1alpha and eIF2alpha in the adipose tissue.	Metformin	9-18	endoplasmic reticulum (ER) to nucleus signalling 1	Mus musculus	222-231
24983318-5	2014	TAK1-deficient hepatocytes exhibited suppressed AMPK activity and autophagy in response to starvation or metformin treatment; however, ectopic activation of AMPK restored autophagy in these cells.	Metformin	105-114	mitogen-activated protein kinase kinase kinase 7	Mus musculus	0-4
25009658-9	2014	AMPK was activated and histone H2B monoubiquitination and downstream gene transcription were inhibited following metformin treatment in the T47D cells.	Metformin	113-122	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-4
25009658-10	2014	The effect of metformin on T47D cell proliferation was dependent on AMPK activity.	Metformin	14-23	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	68-72
25009658-11	2014	It was concluded that metformin can suppress breast cancer cell growth by the activation of AMPK and the inhibition of histone H2B monoubiquitination and downstream gene transcription.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	92-96
25024815-1	2014	AIM: To determine if other molecules reported to modulate AMP-dependent protein kinase (AMPK) activity would have effects resembling those of metformin and phenformin on colon cancer cell proliferation and metabolism.	Metformin	142-151	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	88-92
25024815-5	2014	RESULTS: Investigations with several molecules that have been reported to be associated with AMPK activation (A-769662, 5-aminoimidazole-4-carboxamide-1-b-D-ribofuranoside, EGCG, KU-55933, quercetin, resveratrol and salicylates) or AMPK inhibition (compound C) failed to reveal increased medium acidification and increased glucose uptake in colon cancer cells as previously established with metformin and phenformin.	Metformin	391-400	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	93-97
24687991-8	2014	The antidiabetes drug metformin (1 mM), an established AMPK activator, reduced the mouse SIRT5 protein level by 44% in cultured hepatocytes and by 31% in liver in vivo (300 mg/kg, 7 d).	Metformin	22-31	sirtuin 5	Mus musculus	89-94
24909911-0	2014	Radiosensitization of pancreatic cancer cells by metformin through the AMPK pathway.	Metformin	49-58	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	71-75
24909911-8	2014	Examination of the AMPK pathway showed that pharmacological inhibition of AMPK signaling or RNAi of AMPKalpha1 reversed metformin-mediated radiosensitization.	Metformin	120-129	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	19-23
24909911-8	2014	Examination of the AMPK pathway showed that pharmacological inhibition of AMPK signaling or RNAi of AMPKalpha1 reversed metformin-mediated radiosensitization.	Metformin	120-129	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	74-78
24909911-8	2014	Examination of the AMPK pathway showed that pharmacological inhibition of AMPK signaling or RNAi of AMPKalpha1 reversed metformin-mediated radiosensitization.	Metformin	120-129	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	100-110
24909911-9	2014	These studies show that metformin radiosensitization of pancreatic cancer cells at micromolar concentration acts through AMPK and may affect DNA damage signaling.	Metformin	24-33	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	121-125
25018645-7	2014	Numerous pharmacological agents, natural compounds, and hormones are known to activate AMPK, either directly or indirectly - some of which (for example, metformin and thiazolidinediones) are currently used to treat T2D.	Metformin	153-162	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	87-91
24797033-11	2014	In addition, metformin also increased the circulating adiponectin and liver adiponectin receptor 2 expression.	Metformin	13-22	adiponectin receptor 2	Rattus norvegicus	76-98
24683044-7	2014	Modulation by metformin of 42 of 1281 pulmonary microRNAs in smoke-free mice highlighted a variety of mechanisms, including modulation of AMPK, stress response, inflammation, NFkappaB, Tlr9, Tgf, p53, cell cycle, apoptosis, antioxidant pathways, Ras, Myc, Dicer, angiogenesis, stem cell recruitment, and angiogenesis.	Metformin	14-23	transformation related protein 53, pseudogene	Mus musculus	196-199
24943970-0	2014	The relationship between anticancer effect of metformin and the transcriptional regulation of certain genes (CHOP, CAV-1, HO-1, SGK-1 and Par-4) on MCF-7 cell line.	Metformin	46-55	heme oxygenase 1	Homo sapiens	122-126
24809794-3	2014	The results of the study further indicated that the proliferation of PASMCs stimulated by ET-1 was associated with the increase of Skp2 and decrease of p27, and metformin reversed ET-1-induced Skp2 elevation and raised p27 protein level.	Metformin	161-170	interferon alpha inducible protein 27	Homo sapiens	219-222
24844651-0	2014	Metformin sensitizes prostate cancer cells to radiation through EGFR/p-DNA-PKCS in vitro and in vivo.	Metformin	0-9	epidermal growth factor receptor	Mus musculus	64-68
24844651-8	2014	In addition, the reduced phosphorylation of DNA-PKcs caused by EGFR/PI3K/Akt down-regulation is essential for metformin to induce radiosensitivity in prostate cancer cells.	Metformin	110-119	epidermal growth factor receptor	Mus musculus	63-67
24858012-8	2014	In MCF-7 cells metformin decreased the activation of IRbeta, Akt and ERK1/2, increased p-AMPK, FOXO3a, p27, Bax and cleaved caspase-3, and decreased phosphorylation of p70S6K and Bcl-2 protein expression.	Metformin	15-24	interferon alpha inducible protein 27	Homo sapiens	103-106
24858012-8	2014	In MCF-7 cells metformin decreased the activation of IRbeta, Akt and ERK1/2, increased p-AMPK, FOXO3a, p27, Bax and cleaved caspase-3, and decreased phosphorylation of p70S6K and Bcl-2 protein expression.	Metformin	15-24	ribosomal protein S6 kinase B1	Homo sapiens	168-174
24810045-0	2014	Metformin lowers Ser-129 phosphorylated alpha-synuclein levels via mTOR-dependent protein phosphatase 2A activation.	Metformin	0-9	synuclein alpha	Homo sapiens	40-55
24810045-2	2014	Here we demonstrate that the antidiabetic drug metformin significantly reduces levels of phospho-Ser129 alpha-synuclein and the ratio of phospho-Ser129 alpha-synuclein to total alpha-synuclein.	Metformin	47-56	synuclein alpha	Homo sapiens	104-119
24810045-2	2014	Here we demonstrate that the antidiabetic drug metformin significantly reduces levels of phospho-Ser129 alpha-synuclein and the ratio of phospho-Ser129 alpha-synuclein to total alpha-synuclein.	Metformin	47-56	synuclein alpha	Homo sapiens	152-167
24810045-2	2014	Here we demonstrate that the antidiabetic drug metformin significantly reduces levels of phospho-Ser129 alpha-synuclein and the ratio of phospho-Ser129 alpha-synuclein to total alpha-synuclein.	Metformin	47-56	synuclein alpha	Homo sapiens	152-167
24810045-5	2014	Following metformin exposure, decreased phospho-Ser129 alpha-synuclein was not strictly dependent on induction of AMP-activated protein kinase, a primary target of the drug.	Metformin	10-19	synuclein alpha	Homo sapiens	55-70
24810045-6	2014	On the other hand, metformin-induced phospho-Ser129 alpha-synuclein reduction was consistently associated with inhibition of mammalian target of rapamycin (mTOR) and activation of protein phosphatase 2A (PP2A).	Metformin	19-28	synuclein alpha	Homo sapiens	52-67
24810045-6	2014	On the other hand, metformin-induced phospho-Ser129 alpha-synuclein reduction was consistently associated with inhibition of mammalian target of rapamycin (mTOR) and activation of protein phosphatase 2A (PP2A).	Metformin	19-28	protein phosphatase 2 phosphatase activator	Homo sapiens	204-208
24810045-11	2014	These data reveal a new mechanism leading to alpha-synuclein dephosphorylation that could be targeted for therapeutic intervention by drugs like metformin and rapamycin.	Metformin	145-154	synuclein alpha	Homo sapiens	45-60
24829965-6	2014	Moreover, the use of DPP-4 or SGLT-2 inhibitors significantly decreased risk of diarrhoea compared with placebo, when given concomitantly with metformin.	Metformin	143-152	dipeptidyl peptidase 4	Homo sapiens	21-26
24829965-6	2014	Moreover, the use of DPP-4 or SGLT-2 inhibitors significantly decreased risk of diarrhoea compared with placebo, when given concomitantly with metformin.	Metformin	143-152	solute carrier family 5 member 2	Homo sapiens	30-36
27276511-4	2016	RESULTS: Metformin and resveratrol inhibited ROS-associated mitochondrial fission by upregulating Drp1 phosphorylation (Ser 637) in an AMPK-dependent manner, and then suppressed ER stress indicated by dephosphorylation of IRE1alpha and eIF2alpha in the adipose tissue.	Metformin	9-18	eukaryotic translation initiation factor 2A	Mus musculus	236-245
27424158-12	2016	In conclusion, here, we report that metformin and exenatide inhibit the proinflammatory phenotype of human monocytes/macrophages via influence on MAPK, C/EBP beta, and NFkappaB.	Metformin	36-45	CCAAT enhancer binding protein beta	Homo sapiens	152-162
27627081-8	2016	KEY WORDS: DPP-4 inhibitors - gliflozines - GLP-1 agonists - insulin - metformin - osteoporosis - sulfonylureas - thiazolidinediones - type 2 diabetes mellitus.	Metformin	71-80	glucagon like peptide 1 receptor	Homo sapiens	44-49
24710646-5	2014	However, given the observed increase in Glo1 activity, this reduction is due not only to the scavenging properties of metformin, but the restoration of Glo1 activity.	Metformin	118-127	glyoxalase I	Homo sapiens	40-44
24680596-7	2014	RESULTS: CGRRF1 is significantly induced by metformin treatment in the obese rat endometrium.	Metformin	44-53	cell growth regulator with ring finger domain 1	Rattus norvegicus	9-15
24444314-5	2014	Metformin attenuated AngII-induced activation (cleavage) of caspase 3, Bcl-2 down-regulation and p53 up-regulation.	Metformin	0-9	Wistar clone pR53P1 p53 pseudogene	Rattus norvegicus	97-100
24444314-10	2014	Thus, this study demonstrates that the anti-hypertrophic effects of metformin are associated with AMPK-induced AT1R down-regulation and prevention of mitochondrial dysfunction through the SIRT1/eNOS/p53 pathway.	Metformin	68-77	Wistar clone pR53P1 p53 pseudogene	Rattus norvegicus	199-202
24269733-4	2014	Restoration of AMPK activity by metformin or AICAR reduced the in vitro neurotoxicity of ASYN overexpression, acting independently of the prosurvival kinase Akt or the induction of autophagic response.	Metformin	32-41	synuclein alpha	Homo sapiens	89-93
24269733-5	2014	The conditioned medium from ASYN-overexpressing cells, containing secreted ASYN, as well as dopamine-modified or nitrated recombinant ASYN oligomers, all inhibited AMPK activation in differentiated SH-SY5Y cells and reduced their viability, but not in the presence of metformin or AICAR.	Metformin	268-277	synuclein alpha	Homo sapiens	28-32
24261663-7	2014	KEY RESULTS: Metformin (50 muM) decreased mRNA and protein levels of GLUT1, GLUT3, MCT4 and PFK 1 but did not affect LDH mRNA or protein levels.	Metformin	13-22	solute carrier family 16 member 3	Homo sapiens	83-87
24261663-7	2014	KEY RESULTS: Metformin (50 muM) decreased mRNA and protein levels of GLUT1, GLUT3, MCT4 and PFK 1 but did not affect LDH mRNA or protein levels.	Metformin	13-22	phosphofructokinase, muscle	Homo sapiens	92-97
24569407-1	2014	AIM: Anti-Mullerian hormone (AMG) reduction in women with hyperinsulinemia in therapy with metformin suggests that metformin affects the level of AMH and ovulatory dysfunction through insulin-mediated mechanisms.	Metformin	91-100	anti-Mullerian hormone	Homo sapiens	146-149
24569407-1	2014	AIM: Anti-Mullerian hormone (AMG) reduction in women with hyperinsulinemia in therapy with metformin suggests that metformin affects the level of AMH and ovulatory dysfunction through insulin-mediated mechanisms.	Metformin	115-124	anti-Mullerian hormone	Homo sapiens	146-149
24569407-2	2014	Aim of the study was to assess the effects of metformin hydrochloride (Siofor) on the level of AMH in women with polycystic ovary syndrome and obesity.	Metformin	46-69	anti-Mullerian hormone	Homo sapiens	95-98
24569407-2	2014	Aim of the study was to assess the effects of metformin hydrochloride (Siofor) on the level of AMH in women with polycystic ovary syndrome and obesity.	Metformin	71-77	anti-Mullerian hormone	Homo sapiens	95-98
24484909-9	2014	The inhibitory effect of metformin was mimicked by disruption of the MID1-alpha4/PP2A protein complex by siRNA knockdown of MID1 or alpha4 whereas AMPK activation was not required.	Metformin	25-34	protein phosphatase 2 phosphatase activator	Homo sapiens	81-85
24935589-3	2014	This study aimed to investigate the effects of cisplatin combined with metformin on the proliferation, invasion and migration of HNE1/DDP human nasopharyngeal carcinoma (NPC) cells, and to provide a new target for treating metastasis.	Metformin	71-80	translocase of inner mitochondrial membrane 8A	Homo sapiens	134-137
28480372-5	2016	GP V: Rats were given carnitine and lutein GP VI were given metformin (100mg/kg bw/d) for 6 weeks.	Metformin	60-69	glycoprotein V (platelet)	Rattus norvegicus	0-4
27602077-8	2016	This study suggests that activation of AMPK by metformin inhibits oxidative stress by upregulation of PGC1alpha and SOD1, thereby suppressing the development of ALI/ARDS, and has potential value in the clinical treatment of such conditions.	Metformin	47-56	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	102-111
27423273-4	2016	At a pharmacologically relevant concentration, metformin restored AMPK activation, and inhibited Aldo-induced Nox4/H2O2-dependent TRAF3IP2 induction, pro-inflammatory cytokine expression, and CF migration and proliferation.	Metformin	47-56	NADPH oxidase 4	Mus musculus	110-114
27576730-0	2016	Metformin attenuates lung fibrosis development via NOX4 suppression.	Metformin	0-9	NADPH oxidase 4	Homo sapiens	51-55
27576730-8	2016	Metformin-mediated activation of AMPK was responsible for inhibiting TGF-beta-induced NOX4 expression.	Metformin	0-9	NADPH oxidase 4	Homo sapiens	86-90
27576730-10	2016	BLM treatment induced development of lung fibrosis with concomitantly enhanced NOX4 expression and SMAD phosphorylation, which was efficiently inhibited by metformin.	Metformin	156-165	NADPH oxidase 4	Homo sapiens	79-83
27517917-0	2016	The Antitumor Effect of Metformin Is Mediated by miR-26a in Breast Cancer.	Metformin	24-33	microRNA 26a-1	Homo sapiens	49-56
27517917-3	2016	Our aim was to evaluate if miR-26a and some of its targets could mediate the effect of metformin in breast cancer.	Metformin	87-96	microRNA 26a-1	Homo sapiens	27-34
27517917-10	2016	Metformin treatment reduced breast cancer cell viability, increased miR-26a expression, and led to a reduction in BCL-2, EZH2, and PTEN expression.	Metformin	0-9	microRNA 26a-1	Homo sapiens	68-75
27517917-11	2016	miR-26a inhibition partly prevents the metformin viability effect and the PTEN and EZH2 expression reduction.	Metformin	39-48	microRNA 26a-1	Homo sapiens	0-7
27517917-12	2016	Our results indicate that metformin effectively reduces breast cancer cell viability and suggests that the effects of the drug are mediated by an increase in miR-26a expression and a reduction of its targets, PTEN and EHZ2 Thus, the use of metformin in breast cancer treatment constitutes a promising potential breast cancer therapy.	Metformin	26-35	microRNA 26a-1	Homo sapiens	158-165
27517917-12	2016	Our results indicate that metformin effectively reduces breast cancer cell viability and suggests that the effects of the drug are mediated by an increase in miR-26a expression and a reduction of its targets, PTEN and EHZ2 Thus, the use of metformin in breast cancer treatment constitutes a promising potential breast cancer therapy.	Metformin	240-249	microRNA 26a-1	Homo sapiens	158-165
27587088-3	2016	The effect of metformin (for ever versus never users, and for tertiles of cumulative duration of therapy) was estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score.	Metformin	14-23	cytochrome c oxidase subunit 8A	Homo sapiens	123-126
27174003-9	2016	Treatment with metformin reduced the expression of GFAP, Iba-1 (astrocyte and microglial markers) and the inflammation markers (p-IKB, IL-1 and VEGF), while enhancing p-AMPK and eNOS levels and increasing neuronal survival (Fox-1 and NeuN).	Metformin	15-24	RNA binding protein, fox-1 homolog (C. elegans) 1	Mus musculus	224-229
27174003-9	2016	Treatment with metformin reduced the expression of GFAP, Iba-1 (astrocyte and microglial markers) and the inflammation markers (p-IKB, IL-1 and VEGF), while enhancing p-AMPK and eNOS levels and increasing neuronal survival (Fox-1 and NeuN).	Metformin	15-24	RNA binding protein, fox-1 homolog (C. elegans) 3	Mus musculus	234-238
27207538-3	2016	Here we show that treatment with the antidiabetic drug metformin inhibits excessive ECM deposition in WAT of ob/ob mice and mice with diet-induced obesity, as evidenced by decreased collagen deposition surrounding adipocytes and expression of fibrotic genes including the collagen cross-linking regulator LOX Inhibition of interstitial fibrosis by metformin is likely attributable to the activation of AMPK and the suppression of transforming growth factor-beta1 (TGF-beta1)/Smad3 signaling, leading to enhanced systemic insulin sensitivity.	Metformin	55-64	transforming growth factor, beta 1	Mus musculus	430-462
27207538-3	2016	Here we show that treatment with the antidiabetic drug metformin inhibits excessive ECM deposition in WAT of ob/ob mice and mice with diet-induced obesity, as evidenced by decreased collagen deposition surrounding adipocytes and expression of fibrotic genes including the collagen cross-linking regulator LOX Inhibition of interstitial fibrosis by metformin is likely attributable to the activation of AMPK and the suppression of transforming growth factor-beta1 (TGF-beta1)/Smad3 signaling, leading to enhanced systemic insulin sensitivity.	Metformin	55-64	transforming growth factor, beta 1	Mus musculus	464-473
27207538-3	2016	Here we show that treatment with the antidiabetic drug metformin inhibits excessive ECM deposition in WAT of ob/ob mice and mice with diet-induced obesity, as evidenced by decreased collagen deposition surrounding adipocytes and expression of fibrotic genes including the collagen cross-linking regulator LOX Inhibition of interstitial fibrosis by metformin is likely attributable to the activation of AMPK and the suppression of transforming growth factor-beta1 (TGF-beta1)/Smad3 signaling, leading to enhanced systemic insulin sensitivity.	Metformin	55-64	SMAD family member 3	Mus musculus	475-480
27207538-4	2016	The ability of metformin to repress TGF-beta1-induced fibrogenesis is abolished by the dominant negative AMPK in primary cells from the stromal vascular fraction.	Metformin	15-24	transforming growth factor, beta 1	Mus musculus	36-45
27216492-0	2016	Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials.	Metformin	27-36	glucagon like peptide 1 receptor	Homo sapiens	97-102
27230877-1	2016	PURPOSE: The purpose of the present study is to test whether metformin, aspirin, or diet supplement (DS) BioResponse-3,3"-Diindolylmethane (BR-DIM) can induce AMP-activated protein kinase (AMPK)-dependent potency loss in cultured embryos and whether metformin (Met) + Aspirin (Asa) or BR-DIM causes an AMPK-dependent decrease in embryonic development.	Metformin	61-70	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	159-187
27230877-1	2016	PURPOSE: The purpose of the present study is to test whether metformin, aspirin, or diet supplement (DS) BioResponse-3,3"-Diindolylmethane (BR-DIM) can induce AMP-activated protein kinase (AMPK)-dependent potency loss in cultured embryos and whether metformin (Met) + Aspirin (Asa) or BR-DIM causes an AMPK-dependent decrease in embryonic development.	Metformin	61-70	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	189-193
27230877-1	2016	PURPOSE: The purpose of the present study is to test whether metformin, aspirin, or diet supplement (DS) BioResponse-3,3"-Diindolylmethane (BR-DIM) can induce AMP-activated protein kinase (AMPK)-dependent potency loss in cultured embryos and whether metformin (Met) + Aspirin (Asa) or BR-DIM causes an AMPK-dependent decrease in embryonic development.	Metformin	61-70	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	302-306
27230877-1	2016	PURPOSE: The purpose of the present study is to test whether metformin, aspirin, or diet supplement (DS) BioResponse-3,3"-Diindolylmethane (BR-DIM) can induce AMP-activated protein kinase (AMPK)-dependent potency loss in cultured embryos and whether metformin (Met) + Aspirin (Asa) or BR-DIM causes an AMPK-dependent decrease in embryonic development.	Metformin	250-259	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	159-187
27454290-6	2016	Treatment of pregnant p53d/d mice with either the antidiabetic drug metformin or the antioxidant resveratrol activated AMPK signaling and inhibited mTORC1 signaling in decidual cells.	Metformin	68-77	CREB regulated transcription coactivator 1	Mus musculus	148-154
27454290-10	2016	Together, these results reveal that p53-dependent coordination of AMPK and mTORC1 signaling controls parturition timing and suggest that metformin and resveratrol have therapeutic potential to prevent PTB.	Metformin	137-146	CREB regulated transcription coactivator 1	Mus musculus	75-81
27217019-0	2016	Metformin attenuates fluctuating glucose-induced endothelial dysfunction through enhancing GTPCH1-mediated eNOS recoupling and inhibiting NADPH oxidase.	Metformin	0-9	GTP cyclohydrolase 1	Homo sapiens	91-97
24372553-0	2014	Metformin modulates hyperglycaemia-induced endothelial senescence and apoptosis through SIRT1.	Metformin	0-9	sirtuin 1	Mus musculus	88-93
24372553-9	2014	Treatment with metformin attenuated the HG-induced reduction of SIRT1 expression, modulated the SIRT1 downstream targets FoxO-1 and p53/p21, and protected endothelial cells from HG-induced premature senescence.	Metformin	15-24	sirtuin 1	Mus musculus	64-69
24372553-9	2014	Treatment with metformin attenuated the HG-induced reduction of SIRT1 expression, modulated the SIRT1 downstream targets FoxO-1 and p53/p21, and protected endothelial cells from HG-induced premature senescence.	Metformin	15-24	sirtuin 1	Mus musculus	96-101
24372553-9	2014	Treatment with metformin attenuated the HG-induced reduction of SIRT1 expression, modulated the SIRT1 downstream targets FoxO-1 and p53/p21, and protected endothelial cells from HG-induced premature senescence.	Metformin	15-24	forkhead box O1	Mus musculus	121-127
24372553-9	2014	Treatment with metformin attenuated the HG-induced reduction of SIRT1 expression, modulated the SIRT1 downstream targets FoxO-1 and p53/p21, and protected endothelial cells from HG-induced premature senescence.	Metformin	15-24	transformation related protein 53, pseudogene	Mus musculus	132-135
24372553-10	2014	However, following gene knockdown of SIRT1 the effects of metformin were lost.	Metformin	58-67	sirtuin 1	Mus musculus	37-42
24372553-12	2014	Furthermore, the protective effect of metformin against HG-induced endothelial dysfunction was partly due to its effects on SIRT1 expression and/or activity.	Metformin	38-47	sirtuin 1	Mus musculus	124-129
24762600-0	2014	Metformin ameliorates insulin resistance in L6 rat skeletal muscle cells through upregulation of SIRT3.	Metformin	0-9	sirtuin 3	Rattus norvegicus	97-102
24762600-1	2014	BACKGROUND: SIRT3 is an important regulator in cell metabolism, and recent studies have shown that it may be involved in the pharmacological effects of metformin.	Metformin	152-161	sirtuin 3	Rattus norvegicus	12-17
24762600-9	2014	Metformin increased the expression of SIRT3 (1.5-fold) and SOD2 (2-fold) while down regulating NF-kappaB p65 (1.5-fold) and JNK1 (1.5-fold).	Metformin	0-9	sirtuin 3	Rattus norvegicus	38-43
24762600-9	2014	Metformin increased the expression of SIRT3 (1.5-fold) and SOD2 (2-fold) while down regulating NF-kappaB p65 (1.5-fold) and JNK1 (1.5-fold).	Metformin	0-9	mitogen-activated protein kinase 8	Rattus norvegicus	124-128
24762600-10	2014	Knockdown of SIRT3 (P &lt; 0.05) reversed the metformin-induced decreases in NF-kappaB p65 and JNK1 and the metformin-induced increase in SOD2 (P &lt; 0.05).	Metformin	46-55	sirtuin 3	Rattus norvegicus	13-18
24762600-10	2014	Knockdown of SIRT3 (P &lt; 0.05) reversed the metformin-induced decreases in NF-kappaB p65 and JNK1 and the metformin-induced increase in SOD2 (P &lt; 0.05).	Metformin	46-55	mitogen-activated protein kinase 8	Rattus norvegicus	95-99
24762600-10	2014	Knockdown of SIRT3 (P &lt; 0.05) reversed the metformin-induced decreases in NF-kappaB p65 and JNK1 and the metformin-induced increase in SOD2 (P &lt; 0.05).	Metformin	108-117	sirtuin 3	Rattus norvegicus	13-18
24281401-4	2014	Recently, a variant [single-nucleotide polymorphism (SNP); rs11212617] near the gene for ataxia telangiectasia mutated (ATM) has been associated with glycaemic response to metformin.	Metformin	172-181	ATM serine/threonine kinase	Homo sapiens	89-118
24281401-4	2014	Recently, a variant [single-nucleotide polymorphism (SNP); rs11212617] near the gene for ataxia telangiectasia mutated (ATM) has been associated with glycaemic response to metformin.	Metformin	172-181	ATM serine/threonine kinase	Homo sapiens	120-123
24478399-8	2014	Metformin (but not placebo) led to significant changes in circulating miR-192 (49.5%; P = 0.022), miR-140-5p (-15.8%; P = 0.004), and miR-222 (-47.2%; P = 0.03), in parallel to decreased fasting glucose and HbA1c.	Metformin	0-9	microRNA 222	Homo sapiens	134-141
27217019-7	2016	Furthermore, metformin recoupled eNOS through upregulating GTPCH1 and BH4 levels, and attenuated the upregulation of p47-phox in FG-treated HUVECs.	Metformin	13-22	GTP cyclohydrolase 1	Homo sapiens	59-65
27217019-10	2016	The protective effect of metformin may be mediated through activation of GTPCH1-mediated eNOS recoupling and inhibition of NADPH oxidase via an AMPK-dependent pathway.	Metformin	25-34	GTP cyclohydrolase 1	Homo sapiens	73-79
26939902-5	2016	In this study, we used the HepG2 cell line and found that metformin/AICAR downregulated NANOG expression with decreased cell viability and enhanced chemosensitivity to 5-fluorouracil (5-FU).	Metformin	58-67	5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase	Homo sapiens	68-73
26939902-7	2016	The upregulation of NANOG and phospho-JNK by basic fibroblast growth factor (bFGF) was abrogated by metformin/AICAR.	Metformin	100-109	5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase	Homo sapiens	110-115
26939902-8	2016	Additionally, although transient upregulation of NANOG within 2 h of treatment with metformin/AICAR was concordant with both JNK and AMPK activation, increased NANOG expression with activation of JNK was also observed following AMPK inhibition with compound C. Taken together, our data suggest that metformin/AICAR regulate NANOG expression via the JNK MAPK pathway in HepG2 cells independently of AMPK, and that this JNK/NANOG signaling pathway may offer new therapeutic strategies for the treatment of HCC.	Metformin	84-93	5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase	Homo sapiens	94-99
26939902-8	2016	Additionally, although transient upregulation of NANOG within 2 h of treatment with metformin/AICAR was concordant with both JNK and AMPK activation, increased NANOG expression with activation of JNK was also observed following AMPK inhibition with compound C. Taken together, our data suggest that metformin/AICAR regulate NANOG expression via the JNK MAPK pathway in HepG2 cells independently of AMPK, and that this JNK/NANOG signaling pathway may offer new therapeutic strategies for the treatment of HCC.	Metformin	84-93	5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase	Homo sapiens	309-314
26939902-8	2016	Additionally, although transient upregulation of NANOG within 2 h of treatment with metformin/AICAR was concordant with both JNK and AMPK activation, increased NANOG expression with activation of JNK was also observed following AMPK inhibition with compound C. Taken together, our data suggest that metformin/AICAR regulate NANOG expression via the JNK MAPK pathway in HepG2 cells independently of AMPK, and that this JNK/NANOG signaling pathway may offer new therapeutic strategies for the treatment of HCC.	Metformin	299-308	5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase	Homo sapiens	94-99
27467571-6	2016	Chronic Metformin treatment significantly attenuated the MPTP-induced loss of Tyrosine Hydroxylase (TH) neuronal number and volume and TH protein concentration in the nigrostriatal pathway.	Metformin	8-17	tyrosine hydroxylase	Mus musculus	100-102
26849413-6	2016	The FDA approved anti-diabetic drug Metformin, a well-known AMPK activator, induces mitochondrial biogenesis and is documented for its anti-inflammatory role.	Metformin	36-45	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	60-64
26849413-7	2016	We observed a dose-dependent activation of AMPKalpha1 in metformin-treated X-ALD patient-derived fibroblasts.	Metformin	57-66	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	43-53
26849413-13	2016	Taken together, these results provide proof-of-principle for therapeutic potential of metformin as a useful strategy for correcting the metabolic and inflammatory derangements in X-ALD by targeting AMPK.	Metformin	86-95	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	198-202
26849413-15	2016	We document the therapeutic potential of FDA approved drug, Metformin, for X-ALD by targeting AMPK.	Metformin	60-69	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	94-98
26849413-18	2016	Metformin-induced Abcd2 levels were dependent on AMPKalpha1, a metabolic and anti-inflammatory gene, recently documented by our laboratory to play a putative role in X-ALD pathology.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	49-59
27147746-8	2016	Furthermore, a common diabetes drug, metformin, which carries an AMPK-agonistic activity, drastically inhibited the expression of viral lytic genes and the production of infectious virions, suggesting the use of metformin as a therapeutic agent for KSHV infection and replication.	Metformin	37-46	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	65-69
27147746-8	2016	Furthermore, a common diabetes drug, metformin, which carries an AMPK-agonistic activity, drastically inhibited the expression of viral lytic genes and the production of infectious virions, suggesting the use of metformin as a therapeutic agent for KSHV infection and replication.	Metformin	212-221	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	65-69
27147746-14	2016	AICAR and metformin, both of which are AMPK agonists currently used in clinics for the treatment of conditions associated with metabolic disorders, inhibit KSHV lytic replication.	Metformin	10-19	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	39-43
27334428-0	2016	Metformin and gefitinib cooperate to inhibit bladder cancer growth via both AMPK and EGFR pathways joining at Akt and Erk.	Metformin	0-9	Eph receptor B2	Mus musculus	118-121
27304831-4	2016	Metformin, with its role in increasing GLP-1 may aid weight loss among people on clozapine.	Metformin	0-9	glucagon like peptide 1 receptor	Homo sapiens	39-44
27019345-4	2016	The models were used to simulate inhibition of the MATE1, MATE2-K, OCT1 and OCT2 mediated transport of metformin by cimetidine.	Metformin	103-112	solute carrier family 47 member 2	Homo sapiens	58-65
27082123-7	2016	The results also reveal that microRNA (miR)-26a expression was markedly increased by metformin.	Metformin	85-94	microRNA 26a-1	Homo sapiens	29-47
27082123-9	2016	These results suggest that the anti-proliferative effects of metformin in KB cells may result partly from induction of apoptosis by miR-26a-induced downregulation of Mcl-1.	Metformin	61-70	microRNA 26a-1	Homo sapiens	132-139
27109601-5	2016	We found that metformin inhibited UVC-induced upregulation of p53, as well as downregulated the expression of two DNA damage markers: gammaH2AX and p-chk2.	Metformin	14-23	checkpoint kinase 2	Homo sapiens	150-154
25279360-5	2014	35 of these patients were receiving therapy with dipeptidyl peptidase-4 inhibitors (the vast majority, in association to metformin).	Metformin	121-130	dipeptidyl peptidase 4	Homo sapiens	49-71
25279360-7	2014	RESULTS: Patients on dipeptidyl peptidase-4 inhibitors therapy had a mean peak cardiac troponin plasma level of 50.2+-121.3 ng/ml (n=35), the corresponding value for insulin being 39.2+-108.4 ng/ml (n=56), for metformin the value was 45.8+-97.3 ng/ml (n=93) and for sulfonylureas, 42.4+-77.7 ng/ml (n=52).	Metformin	210-219	dipeptidyl peptidase 4	Homo sapiens	21-43
26718214-6	2016	A significant reduction of serum TGF-beta1 was found in mice after treatment with metformin.	Metformin	82-91	transforming growth factor, beta 1	Mus musculus	33-42
27210760-5	2016	Induction of autophagy through metformin treatment following homeostatic proliferation increased lymphocyte numbers through an Atg5-dependent mechanism.	Metformin	31-40	autophagy related 5	Mus musculus	127-131
27002150-4	2016	Recently, we found that therapeutic metformin concentrations suppressed glucose production in primary hepatocytes through AMPK; activation of the cAMP-PKA pathway negatively regulates AMPK activity by phosphorylating AMPKalpha subunit at Ser-485, which in turn reduces AMPK activity.	Metformin	36-45	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	122-126
27002150-4	2016	Recently, we found that therapeutic metformin concentrations suppressed glucose production in primary hepatocytes through AMPK; activation of the cAMP-PKA pathway negatively regulates AMPK activity by phosphorylating AMPKalpha subunit at Ser-485, which in turn reduces AMPK activity.	Metformin	36-45	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	184-188
27002150-4	2016	Recently, we found that therapeutic metformin concentrations suppressed glucose production in primary hepatocytes through AMPK; activation of the cAMP-PKA pathway negatively regulates AMPK activity by phosphorylating AMPKalpha subunit at Ser-485, which in turn reduces AMPK activity.	Metformin	36-45	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	184-188
27002150-6	2016	Expression of the AMPKalpha1(S485A) mutant, which is unable to be phosphorylated by PKA, increased both AMPKalpha activation and the suppression of glucose production in primary hepatocytes treated with metformin.	Metformin	203-212	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	18-28
27002150-7	2016	Intriguingly, salicylate/aspirin prevents the phosphorylation of AMPKalpha at Ser-485, blocks cAMP-PKA negative regulation of AMPK, and improves metformin resistance.	Metformin	145-154	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	65-69
26987032-0	2016	Metformin inhibits prostate cancer cell proliferation, migration, and tumor growth through upregulation of PEDF expression.	Metformin	0-9	serpin family F member 1	Homo sapiens	107-111
26987032-3	2016	We hypothesized that the antitumorigenic effects of metformin are mediated through upregulation of pigment epithelium-derived factor (PEDF) expression in prostate cancer cells.	Metformin	52-61	serpin family F member 1	Homo sapiens	99-132
26987032-3	2016	We hypothesized that the antitumorigenic effects of metformin are mediated through upregulation of pigment epithelium-derived factor (PEDF) expression in prostate cancer cells.	Metformin	52-61	serpin family F member 1	Homo sapiens	134-138
26987032-6	2016	Metformin also reduced PC3 tumor growth in BALB/c nude mice in vivo.	Metformin	0-9	chromobox 8	Mus musculus	23-26
26987032-7	2016	Furthermore, metformin treatment was associated with higher PEDF expression in both prostate cancer cells and tumor tissue.	Metformin	13-22	serpin family F member 1	Homo sapiens	60-64
26987032-8	2016	Taken together, metformin inhibits prostate cancer cell proliferation, migration, invasion and tumor growth, and these activities are mediated by upregulation of PEDF expression.	Metformin	16-25	serpin family F member 1	Homo sapiens	162-166
26993101-3	2016	Prior incubation of PASMC with metformin induced a dramatic AMPK activation and significantly blocked PDGF-induced cell proliferation.	Metformin	31-40	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	60-64
26993101-5	2016	Metformin did not affect Akt activation but blocked mTOR phosphorylation in response to PDGF; these were accompanied by the reversion of Skp2 up-regulation and p27 reduction.	Metformin	0-9	S-phase kinase associated protein 2	Homo sapiens	137-141
26507723-4	2016	This study sought to identify a selective MATE2K inhibitor in vitro and to determine its clinical impact on the pharmacokinetics and pharmacodynamics of metformin in healthy subjects.	Metformin	153-162	solute carrier family 47 member 2	Homo sapiens	42-48
26507723-8	2016	RESULTS: In healthy volunteers, the MATE2K-selective inhibitor nizatidine significantly increased the apparent volume of distribution, half-life, and hypoglycemic activity of metformin.	Metformin	175-184	solute carrier family 47 member 2	Homo sapiens	36-42
26507723-10	2016	CONCLUSION: This study demonstrates that a selective inhibition of MATE2K by nizatidine affected the apparent volume of distribution, tissue concentrations, and peripheral effects of metformin.	Metformin	183-192	solute carrier family 47 member 2	Homo sapiens	67-73
27123784-0	2016	Atorvastatin Plus Metformin Confer Additive Benefits on Subjects with Dyslipidemia and Overweight/Obese via Reducing ROCK2 Concentration.	Metformin	18-27	Rho associated coiled-coil containing protein kinase 2	Homo sapiens	117-122
27123784-13	2016	CONCLUSION: In subjects with dyslipidemia and overweight/obese, atorvastatin plus metformin may confer additive benefits through reducing leukocyte ROCK2 concentration.	Metformin	82-91	Rho associated coiled-coil containing protein kinase 2	Homo sapiens	148-153
27022443-5	2016	In addition, AMPK activation is believed to mediate most clinical effects of the insulin-sensitizer metformin.	Metformin	100-109	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	13-17
25180036-2	2014	The aim of this study is to examine the efficacy of adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to patients with type 2 diabetes inadequately controlled by metformin and sulphonylurea combination treatment.	Metformin	162-171	dipeptidyl peptidase 4	Homo sapiens	61-83
25180036-2	2014	The aim of this study is to examine the efficacy of adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to patients with type 2 diabetes inadequately controlled by metformin and sulphonylurea combination treatment.	Metformin	162-171	dipeptidyl peptidase 4	Homo sapiens	85-90
25180036-13	2014	DPP-4 inhibitor as a third-line add-on therapy can achieve significant glycaemic improvement in patients with type 2 diabetes inadequately controlled on the combination of metformin and sulphonylurea.	Metformin	172-181	dipeptidyl peptidase 4	Homo sapiens	0-5
23981104-6	2014	RESULTS: Metformin significantly reduced levels of vWF, sVCAM-1, t-PA, PAI-1, CRP and sICAM-1, which, except for CRP, remained significant after adjustment for baseline differences in age, sex, smoking and severity of previous cardiovascular (CV) disease.	Metformin	9-18	serpin family E member 1	Homo sapiens	71-76
27009398-6	2016	Notably, activation of IGF-1 receptor (IGF-1R)-dependent signaling by IGF-1 was inhibited by metformin.	Metformin	93-102	insulin-like growth factor 1	Mus musculus	23-28
27009398-7	2016	Finally, when compared to untreated type 2 diabetes patients, the metformin-treated diabetic patients showed increased IGFBP-2 levels with diminished serum IGF-1 levels.	Metformin	66-75	insulin like growth factor binding protein 2	Homo sapiens	119-126
27009398-8	2016	Taken together, these findings indicate that IGFBP-2 might be a new target of metformin action in diabetes and the metformin-AMPK-Sirt1-PPARalpha-IGFBP-2 network may provide a novel pathway that could be applied to ameliorate metabolic syndromes by controlling IGF-1 bioavailability.	Metformin	78-87	insulin-like growth factor 1	Mus musculus	261-266
27009398-8	2016	Taken together, these findings indicate that IGFBP-2 might be a new target of metformin action in diabetes and the metformin-AMPK-Sirt1-PPARalpha-IGFBP-2 network may provide a novel pathway that could be applied to ameliorate metabolic syndromes by controlling IGF-1 bioavailability.	Metformin	115-124	insulin-like growth factor 1	Mus musculus	261-266
27135362-8	2016	These hypotheses were tested in vivo; as a proof-of-principle, we demonstrated that metformin inhibits the p70S6K-rpS6 axis in a PP2A-phosphatase dependent manner.	Metformin	84-93	ribosomal protein S6	Homo sapiens	114-118
23998949-5	2013	Blockade of AMP-dependent kinase (AMPK), and p38 MAPK by either chemical inhibitors or siRNAs antagonized the inhibitory effect of curcumin on EP4 expression, which was reversed by metformin, an activator of AMPK.	Metformin	181-190	prostaglandin E receptor 4	Homo sapiens	143-146
23875783-7	2013	Group 1 showed post-metformin higher adiponectin and AdipoR1 (P = 0.01) and lower HOMA-IR (P = 0.006) and T (P = 0.001) compared to pre-treatment levels.	Metformin	20-29	adiponectin receptor 1	Homo sapiens	53-60
23875783-8	2013	Post-metformin ovulatory patients had higher adiponectin and AdipoR1 and lower HOMA-IR and T compared to anovulatory patients.	Metformin	5-14	adiponectin receptor 1	Homo sapiens	61-68
24077915-0	2013	Another surprise from Metformin: novel mechanism of action via K-Ras influences endometrial cancer response to therapy.	Metformin	22-31	Kirsten rat sarcoma viral oncogene homolog	Mus musculus	63-68
24077915-7	2013	Metformin inhibited cell proliferation, induced apoptosis, and decreased tumor growth in preclinical endometrial cancer models, with the greatest response observed in cells harboring activating mutations in K-Ras.	Metformin	0-9	Kirsten rat sarcoma viral oncogene homolog	Mus musculus	207-212
24077915-8	2013	Furthermore, metformin displaces constitutively active K-Ras from the cell membrane, causing uncoupling of the MAPK signaling pathway.	Metformin	13-22	Kirsten rat sarcoma viral oncogene homolog	Mus musculus	55-60
24077915-9	2013	These studies provide a rationale for clinical trials using metformin in combination with PI3K-targeted agents for tumors harboring activating K-Ras mutations, and reveal a novel mechanism of action for metformin.	Metformin	60-69	Kirsten rat sarcoma viral oncogene homolog	Mus musculus	143-148
24473757-5	2013	CONCLUSIONS: Metformin, due to its independent effects on liver kinase B1, had antiproliferative effects on the NCI-H460 cell line.	Metformin	13-22	serine/threonine kinase 11	Homo sapiens	58-73
24008375-12	2013	Intragastric treatment of the mouse PLC/PRF/5 cell xenograft model with metformin showed that metformin not only blocked tumor progression, but also reduced tumor morbidity.	Metformin	72-81	heparan sulfate proteoglycan 2	Homo sapiens	36-39
24008375-12	2013	Intragastric treatment of the mouse PLC/PRF/5 cell xenograft model with metformin showed that metformin not only blocked tumor progression, but also reduced tumor morbidity.	Metformin	94-103	heparan sulfate proteoglycan 2	Homo sapiens	36-39
23870706-2	2013	We have analyzed the clinical (diabetic treatment adherence, metabolic control, hypoglycemia and macrovascular complications) and economic (resource use and costs) consequences of the combination of metformin with dipeptidyl peptidase inhibitors (DPPIV) in patients with type 2 diabetes.	Metformin	199-208	dipeptidyl peptidase 4	Homo sapiens	247-252
23870706-5	2013	Two groups of patients were established: a) metformin with DPPIV and metformin with other diabetic drugs.	Metformin	44-53	dipeptidyl peptidase 4	Homo sapiens	59-64
23870706-12	2013	CONCLUSIONS: Despite the limitations of the study, patients treated with metformin associated to DPPIV were more likely to show increased adherence, metabolic control and lower rates of hypoglycemia than those treated with metformin associated to other antidiabetics.	Metformin	73-82	dipeptidyl peptidase 4	Homo sapiens	97-102
24007456-14	2013	DISCUSSION: This is the largest study to compare the efficacy and safety of an SGLT2 inhibitor with an SU in patients with T2DM inadequately controlled on metformin to date.	Metformin	155-164	solute carrier family 5 member 2	Homo sapiens	79-84
23891756-6	2013	Our study further revealed that the inhibitory effects of metformin on DNA damage accumulation may be due to the down-regulation of age-related and oxidative stress-induced AKT activity.	Metformin	58-67	Akt1	Drosophila melanogaster	173-176
23707609-0	2013	Metformin inhibits heme oxygenase-1 expression in cancer cells through inactivation of Raf-ERK-Nrf2 signaling and AMPK-independent pathways.	Metformin	0-9	heme oxygenase 1	Homo sapiens	19-35
23707609-4	2013	In this study, we tested the hypothesis that the anti-tumor effects of metformin are mediated by suppression of HO-1 expression in cancer cells.	Metformin	71-80	heme oxygenase 1	Homo sapiens	112-116
23707609-5	2013	Our results indicate that metformin strongly suppresses HO-1 mRNA and protein expression in human hepatic carcinoma HepG2, cervical cancer HeLa, and non-small-cell lung cancer A549 cells.	Metformin	26-35	heme oxygenase 1	Homo sapiens	56-60
23705823-7	2013	Metformin, the most commonly prescribed insulin sensitizer, increases the insulin-induced metabolic rate.	Metformin	0-9	preproinsulin	Danio rerio	40-47
23705823-7	2013	Metformin, the most commonly prescribed insulin sensitizer, increases the insulin-induced metabolic rate.	Metformin	0-9	preproinsulin	Danio rerio	74-81
23526220-1	2013	Metformin has been used as first-line treatment in patients with type 2 diabetes, and is reported to reduce cancer risk and progression by activating the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway.	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	154-169
23526220-1	2013	Metformin has been used as first-line treatment in patients with type 2 diabetes, and is reported to reduce cancer risk and progression by activating the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway.	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	171-175
23526220-11	2013	This is the first study to demonstrate that metformin suppresses STAT3 activation via LKB1-AMPK-mTOR-independent but ROS-related and autocrine IL-6 production-related pathways.	Metformin	44-53	serine/threonine kinase 11	Homo sapiens	86-90
24009539-6	2013	On the other hand, the protein expressions of anti-inflammatory cytokines, IL-4 and IL-10, were enhanced or maintained by metformin.	Metformin	122-131	interleukin 4	Mus musculus	75-79
26997114-3	2016	Metformin is a first-line drug for treating type 2 diabetes associated with AMPK activation.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	76-80
23648338-5	2013	miR-221/222 levels inversely correlated with metformin dose.	Metformin	45-54	microRNA 221	Homo sapiens	0-7
23695170-0	2013	Synergistic effects of metformin treatment in combination with gefitinib, a selective EGFR tyrosine kinase inhibitor, in LKB1 wild-type NSCLC cell lines.	Metformin	23-32	serine/threonine kinase 11	Homo sapiens	121-125
23695170-4	2013	RESULTS: The combination of metformin with gefitinib induced a strong antiproliferative and proapoptotic effect in NSCLC cell lines that harbored wild-type LKB1 gene.	Metformin	28-37	serine/threonine kinase 11	Homo sapiens	156-160
23695170-7	2013	CONCLUSIONS: Metformin and gefitinib are synergistic in LKB1 wild-type NSCLC cells.	Metformin	13-22	serine/threonine kinase 11	Homo sapiens	56-60
23612973-2	2013	In a previous study, we demonstrated that phosphorylation of Ser-428/431 (in LKB1(L)) by protein kinase Czeta (PKCzeta) was essential for LKB1-mediated activation of AMP-activated protein kinase (AMPK) in response to oxidants or metformin.	Metformin	229-238	serine/threonine kinase 11	Homo sapiens	138-142
23612973-8	2013	PKCzeta-dependent phosphorylation of Ser-399 triggered nucleocytoplasmic translocation of LKB1(S) in response to metformin or peroxynitrite treatment.	Metformin	113-122	serine/threonine kinase 11	Homo sapiens	90-94
23582785-4	2013	Metformin has been reported to be mainly excreted into urine by human organic cation transporter 2 (hOCT2).	Metformin	0-9	solute carrier family 22 member 2	Homo sapiens	70-98
23582785-4	2013	Metformin has been reported to be mainly excreted into urine by human organic cation transporter 2 (hOCT2).	Metformin	0-9	solute carrier family 22 member 2	Homo sapiens	100-105
23582785-10	2013	The results suggest that plasma concentration of phenformin in subjects carrying hOCT2 variant may be higher compared to reference subjects, as reported in metformin.	Metformin	156-165	solute carrier family 22 member 2	Homo sapiens	81-86
23611575-2	2013	The administration of metformin reduced pain intensity from 9/10 to 3/10 and favorably affected the profile of inflammatory cytokines (i.e., TNF a, IL-1beta, IL-6, and IL-10), adipokines (i.e., adiponectin, leptin, and resistin), and beta-endorphin.	Metformin	22-31	leptin	Homo sapiens	207-213
28603691-0	2016	Use of cystatin C to inform metformin eligibility among adult veterans with diabetes.	Metformin	28-37	cystatin C	Homo sapiens	7-17
26717043-5	2016	Second, Metformin, a pharmacological AMPK activator and anti-diabetic drug, or ectopic expression of LKB1, diminished expression of Bmi-1 in cancer cells, an event that was reversed by silencing LKB1.	Metformin	8-17	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	37-41
26717043-5	2016	Second, Metformin, a pharmacological AMPK activator and anti-diabetic drug, or ectopic expression of LKB1, diminished expression of Bmi-1 in cancer cells, an event that was reversed by silencing LKB1.	Metformin	8-17	BMI1 proto-oncogene, polycomb ring finger	Homo sapiens	132-137
26717043-7	2016	Fourth, metformin increased the abundance of miR-15a, miR-128, miR-192, and miR-194, which was prevented by knockdown of LITAF.	Metformin	8-17	microRNA 15a	Homo sapiens	45-52
26703273-8	2016	Stratified Cox regression analysis showed significantly lower risk of treatment failure for metformin users (HR [95% CI], 0.62[0.47-0.81]; p&lt;0.001).	Metformin	92-101	cytochrome c oxidase subunit 8A	Homo sapiens	11-14
26373430-6	2016	When AMPK was activated by AICAR, A769662 and metformin, FcepsilonRI-mediated Syk, ERK, JNK and p38 activation, and TNFalpha release were all inhibited.	Metformin	46-55	mitogen activated protein kinase 14	Rattus norvegicus	96-99
26917483-4	2016	Western blot was used to detect the effect of metformin and (or) MPA on the expression of PR-B in the Ishikawa/MPA and Ishikawa cells.	Metformin	46-55	RB transcriptional corepressor 1	Homo sapiens	90-94
26917483-12	2016	Western blot assay showed that for Ishikawa cells, the protein expression levels of PR-B in metformin group and MPA+metformin group were respectively (53.5+-4.0)% and (37.7+-5.2)%, which were higher than that in the control group [(23.4 +- 3.0)%], and there were significant the differences (P&lt;0.01).	Metformin	92-101	RB transcriptional corepressor 1	Homo sapiens	84-88
26917483-12	2016	Western blot assay showed that for Ishikawa cells, the protein expression levels of PR-B in metformin group and MPA+metformin group were respectively (53.5+-4.0)% and (37.7+-5.2)%, which were higher than that in the control group [(23.4 +- 3.0)%], and there were significant the differences (P&lt;0.01).	Metformin	116-125	RB transcriptional corepressor 1	Homo sapiens	84-88
26917483-13	2016	For Ishikawa/MPA cells, the protein expression levels of PR-B in metformin group and MPA+metformin group were respectively (38.6+-1.7)%, (36.3+-2.5)%, which were higher than those in the control group [(6.4+-1.6)%], and there were also significant differences (P&lt;0.01).	Metformin	65-74	RB transcriptional corepressor 1	Homo sapiens	57-61
23539735-6	2013	Serum CD26/DPP4 levels and enzymatic activities were also higher in patients with T2DM than in the control group only when metformin and/or thiazolidinedione-treated T2DM patients were excluded; metformin and/or thiazolidinedione-treated T2DM patients had lower values compared with other T2DM patients.	Metformin	123-132	dipeptidyl peptidase 4	Homo sapiens	6-10
23539735-6	2013	Serum CD26/DPP4 levels and enzymatic activities were also higher in patients with T2DM than in the control group only when metformin and/or thiazolidinedione-treated T2DM patients were excluded; metformin and/or thiazolidinedione-treated T2DM patients had lower values compared with other T2DM patients.	Metformin	123-132	dipeptidyl peptidase 4	Homo sapiens	11-15
23539735-6	2013	Serum CD26/DPP4 levels and enzymatic activities were also higher in patients with T2DM than in the control group only when metformin and/or thiazolidinedione-treated T2DM patients were excluded; metformin and/or thiazolidinedione-treated T2DM patients had lower values compared with other T2DM patients.	Metformin	195-204	dipeptidyl peptidase 4	Homo sapiens	6-10
26917483-13	2016	For Ishikawa/MPA cells, the protein expression levels of PR-B in metformin group and MPA+metformin group were respectively (38.6+-1.7)%, (36.3+-2.5)%, which were higher than those in the control group [(6.4+-1.6)%], and there were also significant differences (P&lt;0.01).	Metformin	89-98	RB transcriptional corepressor 1	Homo sapiens	57-61
26917483-14	2016	CONCLUSION: Metformin may regulate the progestin-resistance in endometrial carcinoma by increasing the expression of PR-B.	Metformin	12-21	RB transcriptional corepressor 1	Homo sapiens	117-121
26673006-3	2016	In these models, metformin as single agent induced an activation and phosphorylation of mitogen-activated-protein-kinase (MAPK) through an increased C-RAF/B-RAF heterodimerization.	Metformin	17-26	Raf-1 proto-oncogene, serine/threonine kinase	Homo sapiens	149-154
26673006-4	2016	EXPERIMENTAL DESIGN: Since single agent metformin enhances proliferating signals through the RAS/RAF/MAPK pathway, and several MEK inhibitors (MEK-I) demonstrated clinical efficacy in combination with other agents in NSCLC, we tested the effects of metformin plus MEK-I (selumetinib or pimasertib) on proliferation, invasiveness, migration abilities in vitro and in vivo in LKB1 positive NSCLC models harboring KRAS wild type and mutated gene.	Metformin	40-49	zinc fingers and homeoboxes 2	Homo sapiens	97-100
26673006-7	2016	Metformin and MEK-Is combinations also decreased the production and activity of MMP-2 and MMP-9 by reducing the NF-jB (p65) binding to MMP-2 and MMP-9 promoters.	Metformin	0-9	matrix metallopeptidase 2	Homo sapiens	80-85
26673006-7	2016	Metformin and MEK-Is combinations also decreased the production and activity of MMP-2 and MMP-9 by reducing the NF-jB (p65) binding to MMP-2 and MMP-9 promoters.	Metformin	0-9	RELA proto-oncogene, NF-kB subunit	Homo sapiens	119-122
26673006-7	2016	Metformin and MEK-Is combinations also decreased the production and activity of MMP-2 and MMP-9 by reducing the NF-jB (p65) binding to MMP-2 and MMP-9 promoters.	Metformin	0-9	matrix metallopeptidase 2	Homo sapiens	135-140
26673006-8	2016	CONCLUSIONS: Metformin potentiates the antitumor activity of MEK-Is in human LKB1-wild-type NSCLC cell lines, independently from the KRAS mutational status, through GLI1 downregulation and by reducing the NF-jB (p65)-mediated transcription of MMP-2 and MMP-9.	Metformin	13-22	RELA proto-oncogene, NF-kB subunit	Homo sapiens	212-215
26673006-8	2016	CONCLUSIONS: Metformin potentiates the antitumor activity of MEK-Is in human LKB1-wild-type NSCLC cell lines, independently from the KRAS mutational status, through GLI1 downregulation and by reducing the NF-jB (p65)-mediated transcription of MMP-2 and MMP-9.	Metformin	13-22	matrix metallopeptidase 2	Homo sapiens	243-248
26132721-4	2016	This effect was rescued by increasing AMPK phosphorylation via metformin treatment (p&lt;0.001), caloric restriction diet (p&lt;0.001), or NLRP3 inflammasome genetic inactivation using NLRP3 knockout (nlrp3(-/-)) mice (p&lt;0.001).	Metformin	63-72	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	38-42
24991150-0	2013	Effect of combined treatment with clozapine and metformin on fasting blood glucose, insulin level, and expression of the glucose transporter-2 (GLUT2) in Sprague-Dawley rats.	Metformin	48-57	solute carrier family 2 member 2	Rattus norvegicus	121-142
24991150-0	2013	Effect of combined treatment with clozapine and metformin on fasting blood glucose, insulin level, and expression of the glucose transporter-2 (GLUT2) in Sprague-Dawley rats.	Metformin	48-57	solute carrier family 2 member 2	Rattus norvegicus	144-149
24991150-10	2013	There were statistically significant differences in the expression of GLUT2 mRNA (clozapine+metformin group &lt; clozapine group &lt; saline group) and in the expression of GLUT2 protein (clozapine+metformin group, clozapine group &lt; saline group).	Metformin	92-101	solute carrier family 2 member 2	Rattus norvegicus	70-75
24991150-10	2013	There were statistically significant differences in the expression of GLUT2 mRNA (clozapine+metformin group &lt; clozapine group &lt; saline group) and in the expression of GLUT2 protein (clozapine+metformin group, clozapine group &lt; saline group).	Metformin	198-207	solute carrier family 2 member 2	Rattus norvegicus	173-178
26132721-6	2016	In addition, metformin treatment (200 mg/daily), which increased AMPK activation, restored all biochemical alterations examined by us in blood cells and significantly improved clinical symptoms, such as, pain, fatigue, depression, disturbed sleep, and tender points, in patients with FM.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	65-69
26695692-0	2016	Metformin Restrains Pancreatic Duodenal Homeobox-1 (PDX-1) Function by Inhibiting ERK Signaling in Pancreatic Ductal Adenocarcinoma.	Metformin	0-9	pancreatic and duodenal homeobox 1	Homo sapiens	20-50
26695692-0	2016	Metformin Restrains Pancreatic Duodenal Homeobox-1 (PDX-1) Function by Inhibiting ERK Signaling in Pancreatic Ductal Adenocarcinoma.	Metformin	0-9	pancreatic and duodenal homeobox 1	Homo sapiens	52-57
26695692-3	2016	Metformin exerts its anticancer action via a variety of adenosine monophosphate (AMP)-activated protein kinase (AMPK)- dependent and/or AMPK-independent mechanisms.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	112-116
26695692-3	2016	Metformin exerts its anticancer action via a variety of adenosine monophosphate (AMP)-activated protein kinase (AMPK)- dependent and/or AMPK-independent mechanisms.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	136-140
26695692-4	2016	We present data here showing that metformin downregulated pancreatic transcription factor pancreatic duodenal homeobox-1 (PDX-1), suggesting a potential novel mechanism by which metformin exerts its anticancer action.	Metformin	34-43	pancreatic and duodenal homeobox 1	Homo sapiens	90-120
26695692-4	2016	We present data here showing that metformin downregulated pancreatic transcription factor pancreatic duodenal homeobox-1 (PDX-1), suggesting a potential novel mechanism by which metformin exerts its anticancer action.	Metformin	34-43	pancreatic and duodenal homeobox 1	Homo sapiens	122-127
26695692-4	2016	We present data here showing that metformin downregulated pancreatic transcription factor pancreatic duodenal homeobox-1 (PDX-1), suggesting a potential novel mechanism by which metformin exerts its anticancer action.	Metformin	178-187	pancreatic and duodenal homeobox 1	Homo sapiens	90-120
26695692-4	2016	We present data here showing that metformin downregulated pancreatic transcription factor pancreatic duodenal homeobox-1 (PDX-1), suggesting a potential novel mechanism by which metformin exerts its anticancer action.	Metformin	178-187	pancreatic and duodenal homeobox 1	Homo sapiens	122-127
26695692-5	2016	Metformin inhibited PDX-1 expression at both protein and mRNA levels and PDX-1 transactivity as well in PDAC cells.	Metformin	0-9	pancreatic and duodenal homeobox 1	Homo sapiens	20-25
26695692-5	2016	Metformin inhibited PDX-1 expression at both protein and mRNA levels and PDX-1 transactivity as well in PDAC cells.	Metformin	0-9	pancreatic and duodenal homeobox 1	Homo sapiens	73-78
26695692-10	2016	Metformin inhibited EGF-stimulated PDX-1 expression with an accompanied inhibition of ERK kinase activation in PANC- 1 cells.	Metformin	0-9	pancreatic and duodenal homeobox 1	Homo sapiens	35-40
26695692-11	2016	Taken together, our studies show that PDX-1 is a potential novel target for metformin in PDAC cells and that metformin may exert its anticancer action in PDAC by down-regulating PDX-1 via a mechanism involving inhibition of ERK signaling.	Metformin	76-85	pancreatic and duodenal homeobox 1	Homo sapiens	38-43
26695692-11	2016	Taken together, our studies show that PDX-1 is a potential novel target for metformin in PDAC cells and that metformin may exert its anticancer action in PDAC by down-regulating PDX-1 via a mechanism involving inhibition of ERK signaling.	Metformin	109-118	pancreatic and duodenal homeobox 1	Homo sapiens	178-183
26714411-9	2016	Furthermore, the change in BMI after acarbose or metformin treatment is also a factor influencing HbA1c normalization.	Metformin	49-58	hemoglobin subunit alpha 1	Homo sapiens	98-102
27514712-9	2016	Oral administration of metformin (insulin sensitizer) to PCOS-patients increases GLUT4 endometrial levels, improving fertility of those patients.	Metformin	23-32	solute carrier family 2 member 4	Homo sapiens	81-86
27057099-0	2016	Metformin Prevents Fatty Liver and Improves Balance of White/Brown Adipose in an Obesity Mouse Model by Inducing FGF21.	Metformin	0-9	fibroblast growth factor 21	Mus musculus	113-118
27057099-8	2016	In obese mice, metformin also induced the expression of BAT-related markers and increased fibroblast growth factor (FGF) 21 expression in the liver and in white adipocyte.	Metformin	15-24	fibroblast growth factor 21	Mus musculus	90-123
27057099-9	2016	Metformin suppressed white adipocyte differentiation via induction of FGF21.	Metformin	0-9	fibroblast growth factor 21	Mus musculus	70-75
25926238-2	2016	The goal of these studies was to examine the effects of metformin on mTORC1 signaling in aged skeletal muscle in an attempt to normalize growth signaling.	Metformin	56-65	CREB regulated transcription coactivator 1	Mus musculus	69-75
26528626-0	2015	Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3).	Metformin	0-9	solute carrier family 19 member 3	Homo sapiens	74-80
26528626-0	2015	Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3).	Metformin	0-9	solute carrier family 19 member 3	Homo sapiens	82-89
26528626-4	2015	In this study, we tested the reverse, i.e., that metformin is a substrate of thiamine transporters (THTR-1, SLC19A2, and THTR-2, SLC19A3).	Metformin	49-58	solute carrier family 19 member 2	Homo sapiens	100-106
26528626-4	2015	In this study, we tested the reverse, i.e., that metformin is a substrate of thiamine transporters (THTR-1, SLC19A2, and THTR-2, SLC19A3).	Metformin	49-58	solute carrier family 19 member 2	Homo sapiens	108-115
26528626-4	2015	In this study, we tested the reverse, i.e., that metformin is a substrate of thiamine transporters (THTR-1, SLC19A2, and THTR-2, SLC19A3).	Metformin	49-58	solute carrier family 19 member 3	Homo sapiens	121-127
26528626-4	2015	In this study, we tested the reverse, i.e., that metformin is a substrate of thiamine transporters (THTR-1, SLC19A2, and THTR-2, SLC19A3).	Metformin	49-58	solute carrier family 19 member 3	Homo sapiens	129-136
26528626-5	2015	Our study demonstrated that human THTR-2 (hTHTR-2), SLC19A3, which is highly expressed in the small intestine, but not hTHTR-1, transports metformin (Km = 1.15 +- 0.2 mM) and other cationic compounds (MPP(+) and famotidine).	Metformin	139-148	solute carrier family 19 member 3	Homo sapiens	34-40
26528626-5	2015	Our study demonstrated that human THTR-2 (hTHTR-2), SLC19A3, which is highly expressed in the small intestine, but not hTHTR-1, transports metformin (Km = 1.15 +- 0.2 mM) and other cationic compounds (MPP(+) and famotidine).	Metformin	139-148	solute carrier family 19 member 3	Homo sapiens	42-49
26528626-5	2015	Our study demonstrated that human THTR-2 (hTHTR-2), SLC19A3, which is highly expressed in the small intestine, but not hTHTR-1, transports metformin (Km = 1.15 +- 0.2 mM) and other cationic compounds (MPP(+) and famotidine).	Metformin	139-148	solute carrier family 19 member 3	Homo sapiens	52-59
26528626-7	2015	Furthermore, metformin as well as other drugs including phenformin, chloroquine, verapamil, famotidine, and amprolium inhibited hTHTR-2 mediated uptake of both thiamine and metformin.	Metformin	13-22	solute carrier family 19 member 3	Homo sapiens	128-135
26528626-7	2015	Furthermore, metformin as well as other drugs including phenformin, chloroquine, verapamil, famotidine, and amprolium inhibited hTHTR-2 mediated uptake of both thiamine and metformin.	Metformin	173-182	solute carrier family 19 member 3	Homo sapiens	128-135
26528626-9	2015	Taken together, our data suggest that hTHTR-2 may play a role in the intestinal absorption and tissue distribution of metformin and other organic cations and that the transporter may be a target for drug-drug and drug-nutrient interactions.	Metformin	118-127	solute carrier family 19 member 3	Homo sapiens	38-45
26629991-0	2015	Metformin and Resveratrol Inhibited High Glucose-Induced Metabolic Memory of Endothelial Senescence through SIRT1/p300/p53/p21 Pathway.	Metformin	0-9	E1A binding protein p300	Homo sapiens	114-118
26253730-2	2015	RESEARCH DESIGN AND METHODS: Subjects with T2D with HbA1c levels &gt;=7.5% (58.5 mmol/mol) and &lt;=10.0% (86.0 mmol/mol) on metformin alone or two or more OADs were randomized to add-on prandial TI (n = 177) or prandial Technosphere inhaled placebo (TP) (n = 176) to their OAD regimen in this double-blind, placebo-controlled trial.	Metformin	125-134	hemoglobin subunit alpha 1	Homo sapiens	52-56
26537182-0	2015	HbA1c After a Short Period of Monotherapy With Metformin Identifies Durable Glycemic Control Among Adolescents With Type 2 Diabetes.	Metformin	47-56	hemoglobin subunit alpha 1	Homo sapiens	0-4
26706918-6	2015	Pro-apoptotic events (nuclear condensation, hydrolysis of intact poly ADP ribose polymerase and caspase-3) were stimulated by metformin and then suppressed by compound C. Interestingly, the formation of acidic intracellular vesicles, a marker of autophagy, was stimulated by compound C. Although the deprivation of amino acids in culture media also induced apoptosis, neither metformin nor compound C affected cell viability.	Metformin	126-135	caspase 3	Rattus norvegicus	96-105
23717642-1	2013	The precise role of AMP-activated protein kinase (AMPK), a target of metformin, in pancreatic beta cells remains controversial, even though metformin was recently shown to enhance the expression of incretin receptors (GLP-1 and GIP receptors) in pancreatic beta cells.	Metformin	140-149	zinc finger, GATA-like protein 1	Mus musculus	218-223
23561047-11	2013	Increased expression of JNK and NFKB was suppressed following metformin treatment.	Metformin	62-71	mitogen-activated protein kinase 8	Rattus norvegicus	24-27
23561047-11	2013	Increased expression of JNK and NFKB was suppressed following metformin treatment.	Metformin	62-71	RELA proto-oncogene, NF-kB subunit	Rattus norvegicus	32-36
23651102-10	2013	Area above the blood glucose levels-time curve (AAC), maximum hypoglycemic response and time of maximum response (T(max)) were significantly higher (p &lt; 0.001) when MH was administered in niosomal form compared to free drug solution.	Metformin	168-170	glycine-N-acyltransferase	Rattus norvegicus	48-51
23680741-9	2013	In addition to the expected benefits associated with limiting insulin dose and regimen complexity, the specific advantages the DPP-4 inhibitor drug class on hypoglycemia and weight gain could justify combining DPP-4 inhibitors with insulin; additionally, a DPP-4 inhibitor may be of special value to decrease glycemic excursions that are not properly addressed by basal insulin therapy and metformin use, even after optimizing titration of the basal insulin.	Metformin	390-399	dipeptidyl peptidase 4	Homo sapiens	127-132
23324179-9	2013	Metformin (the best known clinical activator of AMPK) suppressed EMT induction through inhibition of ROS via induction of heme oxygenase-1 and endogenous antioxidant thioredoxin.	Metformin	0-9	heme oxygenase 1	Homo sapiens	122-138
23324179-9	2013	Metformin (the best known clinical activator of AMPK) suppressed EMT induction through inhibition of ROS via induction of heme oxygenase-1 and endogenous antioxidant thioredoxin.	Metformin	0-9	thioredoxin	Homo sapiens	166-177
23328000-1	2013	AIMS: To assess the effects of two commonly used oral hypoglycemic medications metformin and pioglitazone on serum concentrations of omentin and leptin in patients with newly diagnosed type 2 diabetes.	Metformin	79-88	intelectin 1	Homo sapiens	133-140
23228696-7	2013	Furthermore, metformin was able to not only decrease the paclitaxel-induced p38 MAPK-mediated ERCC1 expression, but also augment the cytotoxic effect induced by paclitaxel.	Metformin	13-22	ERCC excision repair 1, endonuclease non-catalytic subunit	Homo sapiens	94-99
23395946-6	2013	Furthermore, gene expression arrays revealed that metformin caused expression of stress markers DDIT3, CYP1A1,and GDF-15 and a concomitant reduction in PTGS1 expression.	Metformin	50-59	cytochrome P450 family 1 subfamily A member 1	Homo sapiens	103-109
23613388-0	2013	Metformin inhibits proliferation and promotes apoptosis of HER2 positive breast cancer cells by downregulating HSP90.	Metformin	0-9	heat shock protein 90 alpha family class A member 1	Homo sapiens	111-116
23613388-8	2013	The expression level of HSP90 in the metformin group was significantly lower than that in the control group.	Metformin	37-46	heat shock protein 90 alpha family class A member 1	Homo sapiens	24-29
23613388-9	2013	CONCLUSION: Metformin can inhibit the proliferation and promote apoptosis of HER2 positive breast cancer cells,which is maybe related to inhibition of HSP90.	Metformin	12-21	heat shock protein 90 alpha family class A member 1	Homo sapiens	151-156
23879009-13	2013	Metformin has antiproliferative properties; reduces the VEGF levels, causing a reduction in tumor vasculature; causes an increase in progesterone receptor, which increases the response to hormonal therapy; inhibits the expression of glyoxalase I, mediating resistance to chemotherapy; decreases in the concentration of human telomerase; reduces the activity of Akt and Erk kinases, key regulators of metabolism and progression of tumors and also inhibits the formation of metastases.	Metformin	0-9	glyoxalase I	Homo sapiens	233-245
24137964-9	2013	CONCLUSION: The glucose-lowering efficiency of combination therapy with metformin + vildagliptin, a DPP-4 inhibitor, was comparable with that of a metformin + SU combination, but safer with respect to the risk of developing hypoglycemia.	Metformin	72-81	dipeptidyl peptidase 4	Homo sapiens	100-105
26424816-1	2015	AMP-activated protein kinase (AMPK), an important downstream effector of the tumor suppressor liver kinase 1 (LKB1) and pharmacologic target of metformin, is well known to exert a preventive and inhibitory effect on tumorigenesis; however, its role in cancer progression and metastasis has not been well characterized.	Metformin	144-153	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-28
26424816-1	2015	AMP-activated protein kinase (AMPK), an important downstream effector of the tumor suppressor liver kinase 1 (LKB1) and pharmacologic target of metformin, is well known to exert a preventive and inhibitory effect on tumorigenesis; however, its role in cancer progression and metastasis has not been well characterized.	Metformin	144-153	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	30-34
26424816-3	2015	Our results showed that activation of AMPK by metformin inhibited TGF-beta-induced Smad2/3 phosphorylation in cancer cells in a dose-dependent manner.	Metformin	46-55	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	38-42
26424816-3	2015	Our results showed that activation of AMPK by metformin inhibited TGF-beta-induced Smad2/3 phosphorylation in cancer cells in a dose-dependent manner.	Metformin	46-55	SMAD family member 2	Homo sapiens	83-88
26424816-6	2015	As a consequence, expression of genes downstream of Smad2/3, including plasminogen activator inhibitor-1, fibronectin, and connective tissue growth factor, was suppressed by metformin in a LKB1-dependent fashion.	Metformin	174-183	SMAD family member 2	Homo sapiens	52-59
26395850-9	2015	CONCLUSIONS: Given their dosing scheme and overall efficacy and safety profile, once-weekly GLP-1 RAs are a convenient therapeutic option for use as add-on to metformin.	Metformin	159-168	glucagon like peptide 1 receptor	Homo sapiens	92-97
26359363-7	2015	In contrast to the cells that express N-cadherin, in N-cadherin deficient cells, metformin plays an anti-tumor role via activation of AMPK.	Metformin	81-90	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	134-138
26439622-12	2015	Furthermore, metformin, but not Exendin-4, activated AMPK and induced apoptosis in LNCaP cells.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	53-57
24640684-3	2013	The priority effective therapy tactics for T2DM is to manage the latter without any risk of HG, which can be implemented by the wide clinical application of incretins, dipeptidyl peptidase-4 inhibitors in particular, which have the glucose-lowering activity comparable with that shown by metformin and sulfonylurea drugs, are practically safe when used as monotherapy and significantly enhance the efficiency of therapy without substantially increasing the risk of severe HG when co-administered with other medications.	Metformin	288-297	dipeptidyl peptidase 4	Homo sapiens	168-190
23135276-0	2012	Metformin regulates glucose transporter 4 (GLUT4) translocation through AMP-activated protein kinase (AMPK)-mediated Cbl/CAP signaling in 3T3-L1 preadipocyte cells.	Metformin	0-9	Casitas B-lineage lymphoma	Mus musculus	117-120
23135276-3	2012	Here, we showed that short time treatment with metformin rapidly increased phosphorylation of Cbl in an AMP-activated protein kinase (AMPK)-dependent fashion in 3T3-L1 preadipocytes.	Metformin	47-56	Casitas B-lineage lymphoma	Mus musculus	94-97
23135276-4	2012	Metformin also increased phosphorylation of Src in an AMPK-dependent manner.	Metformin	0-9	Rous sarcoma oncogene	Mus musculus	44-47
23135276-5	2012	Src inhibition blocked metformin-mediated Cbl phosphorylation, suggesting that metformin stimulates AMPK-Src-Cbl axis pathway.	Metformin	23-32	Rous sarcoma oncogene	Mus musculus	0-3
23135276-5	2012	Src inhibition blocked metformin-mediated Cbl phosphorylation, suggesting that metformin stimulates AMPK-Src-Cbl axis pathway.	Metformin	23-32	Casitas B-lineage lymphoma	Mus musculus	42-45
23135276-5	2012	Src inhibition blocked metformin-mediated Cbl phosphorylation, suggesting that metformin stimulates AMPK-Src-Cbl axis pathway.	Metformin	23-32	Rous sarcoma oncogene	Mus musculus	105-108
23135276-5	2012	Src inhibition blocked metformin-mediated Cbl phosphorylation, suggesting that metformin stimulates AMPK-Src-Cbl axis pathway.	Metformin	23-32	Casitas B-lineage lymphoma	Mus musculus	109-112
23135276-5	2012	Src inhibition blocked metformin-mediated Cbl phosphorylation, suggesting that metformin stimulates AMPK-Src-Cbl axis pathway.	Metformin	79-88	Rous sarcoma oncogene	Mus musculus	0-3
23135276-5	2012	Src inhibition blocked metformin-mediated Cbl phosphorylation, suggesting that metformin stimulates AMPK-Src-Cbl axis pathway.	Metformin	79-88	Casitas B-lineage lymphoma	Mus musculus	42-45
23135276-5	2012	Src inhibition blocked metformin-mediated Cbl phosphorylation, suggesting that metformin stimulates AMPK-Src-Cbl axis pathway.	Metformin	79-88	Rous sarcoma oncogene	Mus musculus	105-108
23135276-5	2012	Src inhibition blocked metformin-mediated Cbl phosphorylation, suggesting that metformin stimulates AMPK-Src-Cbl axis pathway.	Metformin	79-88	Casitas B-lineage lymphoma	Mus musculus	109-112
23135276-6	2012	In addition, long term treatment with metformin stimulated the expression of Cbl-associated protein (CAP) mRNA and protein.	Metformin	38-47	Casitas B-lineage lymphoma	Mus musculus	77-80
23122726-8	2012	Further, metformin reduced TLR-dependent inflammatory cytokines as indexed by reduced myocardial levels of TNFalpha (maximum 68%; P&lt;0.001) and IL6 (maximum 84%; P&lt;0.001) as well as by reduced myocardial MPO activity (25%; P&lt;0.01).	Metformin	9-18	myeloperoxidase	Rattus norvegicus	209-212
23162655-0	2012	Metformin inhibits leptin-induced growth and migration of glioblastoma cells.	Metformin	0-9	leptin	Homo sapiens	19-25
23162655-4	2012	Here, we analyzed the effects of metformin on the growth and migration of LN18 and LN229 GBM cells cultured under basal conditions or exposed to leptin, a cytokine that has recently been implicated in GBM development.	Metformin	33-42	leptin	Homo sapiens	145-151
23162655-5	2012	We found that 2-16 mM metformin reduced basal and leptin-stimulated growth of GBM cells in a dose-dependent manner.	Metformin	22-31	leptin	Homo sapiens	50-56
23162655-9	2012	Our results suggest that metformin or similar AMPK-targeting agents with optimized blood-brain-barrier penetrability could be developed as potential treatments of GBM and could be used in conjunction with other target drugs such as leptin receptor antagonists.	Metformin	25-34	leptin	Homo sapiens	232-238
22982676-6	2012	METHODS: We have studied molecular mechanisms mediating lipotoxicity and metformin-induced lipoprotection in GLP-1-secreting L-cells in vitro, using the murine GLUTag cell line as a model.	Metformin	73-82	zinc finger, GATA-like protein 1	Mus musculus	109-114
22698918-8	2012	In primary hepatocytes, dominant-negative mutant-AMPK and SHP knockdown prevented the inhibitory effect of metformin on GH-stimulated PDK4 expression.	Metformin	107-116	growth hormone	Mus musculus	120-122
22698918-10	2012	Metformin inhibits GH-induced PDK4 expression and metabolites via an AMPK-SHP-dependent pathway.	Metformin	0-9	growth hormone	Mus musculus	19-21
22698918-11	2012	The metformin-AMPK-SHP network may provide a novel therapeutic approach for the treatment of hepatic metabolic disorders induced by the GH-mediated pathway.	Metformin	4-13	growth hormone	Mus musculus	136-138
22735790-0	2012	Metformin impairs the growth of liver kinase B1-intact cervical cancer cells.	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	32-47
22735790-3	2012	The present study aimed to determine the role of liver kinase B1 (LKB1) in the response of cervical cancer cells to metformin.	Metformin	116-125	serine/threonine kinase 11	Homo sapiens	49-64
22735790-3	2012	The present study aimed to determine the role of liver kinase B1 (LKB1) in the response of cervical cancer cells to metformin.	Metformin	116-125	serine/threonine kinase 11	Homo sapiens	66-70
22735790-7	2012	Analyzing the expression status and the integrity of LKB1-AMPK-mTOR signaling, we found that cervical cancer cells sensitive to metformin were LKB1 intact and exerted an integral AMPK-mTOR signaling response after the treatment.	Metformin	128-137	serine/threonine kinase 11	Homo sapiens	53-57
22735790-7	2012	Analyzing the expression status and the integrity of LKB1-AMPK-mTOR signaling, we found that cervical cancer cells sensitive to metformin were LKB1 intact and exerted an integral AMPK-mTOR signaling response after the treatment.	Metformin	128-137	serine/threonine kinase 11	Homo sapiens	143-147
22735790-8	2012	Ectopic expression of LKB1 with stable transduction system or inducible expression construct in endogenous LKB1 deficient cells improved the activation of AMPK, promoted the inhibition of mTOR, and prompted the sensitivity of cells to metformin.	Metformin	235-244	serine/threonine kinase 11	Homo sapiens	22-26
22735790-8	2012	Ectopic expression of LKB1 with stable transduction system or inducible expression construct in endogenous LKB1 deficient cells improved the activation of AMPK, promoted the inhibition of mTOR, and prompted the sensitivity of cells to metformin.	Metformin	235-244	serine/threonine kinase 11	Homo sapiens	107-111
22735790-9	2012	In contrast, knock-down of LKB1 compromised cellular response to metformin.	Metformin	65-74	serine/threonine kinase 11	Homo sapiens	27-31
22735790-10	2012	Our further investigation demonstrated that metformin could induce both apoptosis and autophagy in cervical cancer cells when LKB1 is expressed.	Metformin	44-53	serine/threonine kinase 11	Homo sapiens	126-130
22735790-11	2012	CONCLUSIONS: Metformin is a potential drug for the treatment of cervical cancers, in particular to those with intact LKB1 expression.	Metformin	13-22	serine/threonine kinase 11	Homo sapiens	117-121
22898050-0	2012	Metformin inhibits inflammatory response via AMPK-PTEN pathway in vascular smooth muscle cells.	Metformin	0-9	phosphatase and tensin homolog	Homo sapiens	50-54
22898050-7	2012	We treated with the well-known AMPK activator metformin to induce PTEN expression.	Metformin	46-55	phosphatase and tensin homolog	Homo sapiens	66-70
22898050-8	2012	PTEN was induced by metformin (2mM) and inhibited by compound C (10 muM) and AMPK siRNA.	Metformin	20-29	phosphatase and tensin homolog	Homo sapiens	0-4
22898050-13	2012	NF-kappaB activation decreased in response to metformin and was restored by inhibiting AMPK and PTEN.	Metformin	46-55	phosphatase and tensin homolog	Homo sapiens	96-100
22561086-6	2012	The binding of Mondo:MLX to the Txnip gene promoter is reduced, suggesting that the transcription of the Txnip gene is repressed by metformin.	Metformin	132-141	MAX dimerization protein MLX	Homo sapiens	21-24
22329512-9	2012	The mRNA expressions of Bcl-2 and PDX-1 in pancreas were up-regulated, but Bax, iNOS and Casp-3 down-regulated in Gl- PS and metformin groups compared to diabetic control group.	Metformin	125-134	BCL2 associated X, apoptosis regulator	Rattus norvegicus	75-78
22688336-10	2012	TNFRI combined with the antidiabetic agent, metformin, improved DBD beyond that achieved with metformin alone, suggesting that therapies targeting TNF-alpha may have utility in reversing the secondary urologic complications of type 2 diabetes.	Metformin	94-103	TNF receptor superfamily member 1A	Homo sapiens	0-5
22540333-9	2012	RESULTS: The addition of metformin enhanced the sensitivity of endometrial cells to cisplatin and paclitaxel, which was associated with reduced levels of GloI expression.	Metformin	25-34	glyoxalase I	Homo sapiens	154-158
22540333-10	2012	Moreover, low-dose chemotherapeutic drugs alone could not significantly reduce GloI expression, whereas the addition of metformin potently downregulated GloI protein levels.	Metformin	120-129	glyoxalase I	Homo sapiens	153-157
22540333-12	2012	However, the overexpression of GloI abolished the effect of metformin-enhanced cell sensitivity to chemotherapeutic drugs.	Metformin	60-69	glyoxalase I	Homo sapiens	31-35
22540333-13	2012	CONCLUSION: Metformin enhances the rate of cell-killing induced by chemotherapeutic agents by repressing GloI expression.	Metformin	12-21	glyoxalase I	Homo sapiens	105-109
22453232-0	2012	A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetes: a replication and meta-analysis of five cohorts.	Metformin	57-66	ATM serine/threonine kinase	Homo sapiens	20-23
22453232-1	2012	AIMS/HYPOTHESIS: In this study we aimed to replicate the previously reported association between the glycaemic response to metformin and the SNP rs11212617 at a locus that includes the ataxia telangiectasia mutated (ATM) gene in multiple additional populations.	Metformin	123-132	ATM serine/threonine kinase	Homo sapiens	185-214
22453232-1	2012	AIMS/HYPOTHESIS: In this study we aimed to replicate the previously reported association between the glycaemic response to metformin and the SNP rs11212617 at a locus that includes the ataxia telangiectasia mutated (ATM) gene in multiple additional populations.	Metformin	123-132	ATM serine/threonine kinase	Homo sapiens	216-219
22453232-6	2012	CONCLUSIONS/INTERPRETATION: A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetic patients from the Netherlands and the UK.	Metformin	85-94	ATM serine/threonine kinase	Homo sapiens	48-51
22608319-9	2012	Treatment with metformin inhibited insulin-induced activation of Erk1/2 and S6K1.	Metformin	15-24	ribosomal protein S6 kinase B1	Rattus norvegicus	76-80
22686561-4	2012	A critical point is that the LKB1/AMPK network remains functional in a wide range of cancers and could be stimulated by drugs, such as N,N-dimethylimidodicarbonimidic diamide (metformin) or 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR).	Metformin	135-174	serine/threonine kinase 11	Homo sapiens	29-33
22686561-4	2012	A critical point is that the LKB1/AMPK network remains functional in a wide range of cancers and could be stimulated by drugs, such as N,N-dimethylimidodicarbonimidic diamide (metformin) or 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR).	Metformin	176-185	serine/threonine kinase 11	Homo sapiens	29-33
22562515-10	2012	Moreover, metformin prevented the expression of Cox-2, iNOS, and activation of NF-kB in the HNPECs and decreased the levels of NO and PGE2 in cell culture media.	Metformin	10-19	RELA proto-oncogene, NF-kB subunit	Rattus norvegicus	79-84
22425595-0	2012	Metformin attenuates Alzheimer"s disease-like neuropathology in obese, leptin-resistant mice.	Metformin	0-9	leptin	Mus musculus	71-77
22425595-12	2012	Metformin attenuated the reduction of synaptophysin, a synaptic protein, in the db/db mouse hippocampus.	Metformin	0-9	synaptophysin	Mus musculus	38-51
22643892-0	2012	Metformin elicits anticancer effects through the sequential modulation of DICER and c-MYC.	Metformin	0-9	dicer 1, ribonuclease III	Homo sapiens	74-79
22643892-0	2012	Metformin elicits anticancer effects through the sequential modulation of DICER and c-MYC.	Metformin	0-9	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	84-89
22643892-5	2012	In fact, metformin induces DICER expression and its effects are severely impaired in DICER knocked down cells.	Metformin	9-18	dicer 1, ribonuclease III	Homo sapiens	27-32
22643892-5	2012	In fact, metformin induces DICER expression and its effects are severely impaired in DICER knocked down cells.	Metformin	9-18	dicer 1, ribonuclease III	Homo sapiens	85-90
22643892-6	2012	Conversely, ectopic expression of DICER recapitulates the effects of metformin                 in vivo and in vitro.	Metformin	69-78	dicer 1, ribonuclease III	Homo sapiens	34-39
22643892-8	2012	Among the messenger RNAs downregulated by metformin, we found c-MYC, IRS-2 and HIF1alpha.	Metformin	42-51	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	62-67
22643892-8	2012	Among the messenger RNAs downregulated by metformin, we found c-MYC, IRS-2 and HIF1alpha.	Metformin	42-51	insulin receptor substrate 2	Homo sapiens	69-74
22394605-1	2012	Members of the human SLC superfamily such as organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, and organic cation transporter 1 (OCT1) are drug uptake transporters that are localised on the basolateral membrane of hepatocytes mediating the uptake of drugs such as atorvastatin and metformin into hepatocytes.	Metformin	294-303	solute carrier organic anion transporter family member 1B1	Homo sapiens	45-87
22394605-1	2012	Members of the human SLC superfamily such as organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, and organic cation transporter 1 (OCT1) are drug uptake transporters that are localised on the basolateral membrane of hepatocytes mediating the uptake of drugs such as atorvastatin and metformin into hepatocytes.	Metformin	294-303	solute carrier organic anion transporter family member 1B1	Homo sapiens	89-96
22245693-7	2012	Metformin up-regulated the expression of miR-26a, miR-192 and let-7c in a dose-dependent manner.	Metformin	0-9	microRNA let-7c	Homo sapiens	62-68
22245693-10	2012	Nude mice xenograft models confirmed that metformin up-regulated the level of miR-26a and surpressed the expression of HMGA1 in vivo.	Metformin	42-51	microRNA 26a-1	Mus musculus	78-85
22467080-10	2012	In addition, restoring lipogenic gene expression by ectopic expression of the lipogenic transcription factor SREBP1c rescues metformin-mediated growth inhibition.	Metformin	125-134	sterol regulatory element binding transcription factor 1	Homo sapiens	109-116
22421144-8	2012	Mechanistically, metformin caused G 1 arrest, which coincided with a decrease in the protein levels of CDKs (2, 4 and 6), cyclins (D1 and E) and CDK inhibitors (p15, p16, p18 and p27), but no change in p19 and p21.	Metformin	17-26	interferon alpha inducible protein 27	Homo sapiens	179-182
22421144-8	2012	Mechanistically, metformin caused G 1 arrest, which coincided with a decrease in the protein levels of CDKs (2, 4 and 6), cyclins (D1 and E) and CDK inhibitors (p15, p16, p18 and p27), but no change in p19 and p21.	Metformin	17-26	H3 histone pseudogene 16	Homo sapiens	210-213
22421144-9	2012	Metformin also decreased the levels of oncogenic proteins Skp2 and beta-Trcp.	Metformin	0-9	beta-transducin repeat containing E3 ubiquitin protein ligase	Homo sapiens	67-76
22421144-10	2012	In other studies, metformin decreased the phosphorylation of 4E-BP1 at Ser65, Thr37/46 and Thr70 sites, but drastically increased the phosphorylation of EF2 at Thr56 and AMPK at Thr172, which results in global translational inhibition.	Metformin	18-27	eukaryotic translation initiation factor 4E binding protein 1	Homo sapiens	61-67
22421144-10	2012	In other studies, metformin decreased the phosphorylation of 4E-BP1 at Ser65, Thr37/46 and Thr70 sites, but drastically increased the phosphorylation of EF2 at Thr56 and AMPK at Thr172, which results in global translational inhibition.	Metformin	18-27	eukaryotic translation elongation factor 2	Homo sapiens	153-156
22197148-4	2012	DPP-4 inhibitors also exert clinically relevant glucose-lowering effects compared with a placebo in patients treated with SU or TZD (of potential interest when metformin is either not tolerated or contraindicated), and as oral triple therapy with a good tolerability profile when added to a metformin-SU or pioglitazone-SU combination.	Metformin	160-169	dipeptidyl peptidase 4	Homo sapiens	0-5
22325091-5	2012	Expression of orexigenic peptides neuropeptide Y (NPY) and agouti-related protein (AgRP) decreased in the hypothalamus of metformin-treated diabetic rats, though anorexigenic peptides pro-opiomelanocortin (POMC) did not change significantly.	Metformin	122-131	agouti related neuropeptide	Rattus norvegicus	59-81
22325091-5	2012	Expression of orexigenic peptides neuropeptide Y (NPY) and agouti-related protein (AgRP) decreased in the hypothalamus of metformin-treated diabetic rats, though anorexigenic peptides pro-opiomelanocortin (POMC) did not change significantly.	Metformin	122-131	agouti related neuropeptide	Rattus norvegicus	83-87
22325091-8	2012	The anorexic effect of metformin may be mediated by inhibition of NPY and AgRP gene expression through the STAT3 signaling pathway.	Metformin	23-32	agouti related neuropeptide	Rattus norvegicus	74-78
22325091-8	2012	The anorexic effect of metformin may be mediated by inhibition of NPY and AgRP gene expression through the STAT3 signaling pathway.	Metformin	23-32	signal transducer and activator of transcription 3	Rattus norvegicus	107-112
22356767-7	2012	Metformin-induced SIS in BJ-1 fibroblasts was accompanied by the striking activation of several microRNAs belonging to the miR-200s family (miR-200a, miR-141 and miR429) and miR-205, thus mimicking a recently described ability of ROS to chemosensitize cancer cells by specifically upregulating anti-EMT (epithelial-to-mesenchymal transition) miR-200s.	Metformin	0-9	IL2 inducible T cell kinase	Homo sapiens	299-302
26439622-13	2015	The anti-proliferative effect of metformin was abolished by inhibition or knock down of AMPK.	Metformin	33-42	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	88-92
26439622-15	2015	Immunohistochemistry on tumors revealed that the P504S and Ki67 expression decreased by Exendin-4 and/or metformin, and that metformin increased phospho-AMPK expression and the apoptotic cell number.	Metformin	125-134	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	153-157
26186064-2	2015	Our current studies have shown that metformin suppresses cell viability, induces apoptosis, and downregulates the mTORC1 signaling pathway both in the Ph+ALL cell line and primary blasts from Ph+ ALL patients, as well as the CML cell lines K562 (imatinib-sensitive) and K562R (imatinib-resistance).	Metformin	36-45	CREB regulated transcription coactivator 1	Mus musculus	114-120
26372847-8	2015	Although in both treatment groups, metformin decreased plasma levels of fasting and post-challenge plasma glucose and improved insulin receptor sensitivity, this effect was more prominent in patients receiving cabergoline.	Metformin	35-44	insulin receptor	Homo sapiens	127-143
26086617-6	2015	Our results showed that the administration of metformin significantly attenuated TBI-induced increases in ROS production and DNA damage and upregulation of NADPH oxidase 4 expression in BM hematopoietic stem cells (HSCs).	Metformin	46-55	NADPH oxidase 4	Mus musculus	156-171
26263223-7	2015	In the metformin group, TMEM18 minor allele carriers had a greater reduction in insulin levels (P = 0.04).	Metformin	7-16	transmembrane protein 18	Homo sapiens	24-30
26263223-8	2015	A significantly higher proportion of TMEM18 and GNPDA2 minor allele carriers (60% and 40%) lost more than 7% of their body weight after metformin treatment as compared with their homozygous counterparts (21.7% and 15.4%, P = 0.02 and 0.004, respectively).There were trends toward favorable metabolic changes in minor allele carrier groups.	Metformin	136-145	transmembrane protein 18	Homo sapiens	37-43
26335661-5	2015	A chemoinformatics-based method known as Similarity Ensemble Approach predicted diamine oxidase (DAO) as an additional intestinal target of metformin, with an E-value of 7.4 x 10(-5).	Metformin	140-149	amine oxidase copper containing 1	Homo sapiens	80-95
26335661-5	2015	A chemoinformatics-based method known as Similarity Ensemble Approach predicted diamine oxidase (DAO) as an additional intestinal target of metformin, with an E-value of 7.4 x 10(-5).	Metformin	140-149	amine oxidase copper containing 1	Homo sapiens	97-100
26335661-7	2015	The Ki of metformin for DAO was measured to be 8.6 +- 3.1 mM.	Metformin	10-19	amine oxidase copper containing 1	Homo sapiens	24-27
26335661-8	2015	In this study, we found that metformin inhibited intestinal amine transporters and DAO at concentrations that may be achieved in the intestine after therapeutic doses.	Metformin	29-38	amine oxidase copper containing 1	Homo sapiens	83-86
26317792-0	2015	Specificity protein (Sp) transcription factors and metformin regulate expression of the long non-coding RNA HULC.	Metformin	51-60	hepatocellular carcinoma up-regulated long non-coding RNA	Homo sapiens	108-112
26317792-7	2015	The antidiabetic drug metformin down-regulates Sp proteins in pancreatic cancer, and similar results including decreased HULC expression were observed in HepG2, SNU-449 and SK-Hep-1 cells treated with metformin, indicating that metformin and other antineoplastic agents that target Sp proteins may have clinical applications for HCC chemotherapy.	Metformin	22-31	hepatocellular carcinoma up-regulated long non-coding RNA	Homo sapiens	121-125
26317792-7	2015	The antidiabetic drug metformin down-regulates Sp proteins in pancreatic cancer, and similar results including decreased HULC expression were observed in HepG2, SNU-449 and SK-Hep-1 cells treated with metformin, indicating that metformin and other antineoplastic agents that target Sp proteins may have clinical applications for HCC chemotherapy.	Metformin	201-210	hepatocellular carcinoma up-regulated long non-coding RNA	Homo sapiens	121-125
26317792-7	2015	The antidiabetic drug metformin down-regulates Sp proteins in pancreatic cancer, and similar results including decreased HULC expression were observed in HepG2, SNU-449 and SK-Hep-1 cells treated with metformin, indicating that metformin and other antineoplastic agents that target Sp proteins may have clinical applications for HCC chemotherapy.	Metformin	201-210	hepatocellular carcinoma up-regulated long non-coding RNA	Homo sapiens	121-125
26391180-0	2015	Metformin Increases Sensitivity of Pancreatic Cancer Cells to Gemcitabine by Reducing CD133+ Cell Populations and Suppressing ERK/P70S6K Signaling.	Metformin	0-9	prominin 1	Homo sapiens	86-91
26254406-6	2015	The adjusted Cox proportional hazards model revealed that metformin usage was a significant factor for mortality (adjusted hazard ratio=0.361; 95% confidence interval=0.139-0.935).	Metformin	58-67	cytochrome c oxidase subunit 8A	Homo sapiens	13-16
26016715-3	2015	Metformin is almost exclusively eliminated through the kidney primarily through active secretion mediated by Oct1, Oct2, and Mate1.	Metformin	0-9	solute carrier family 47, member 1	Mus musculus	125-130
26294325-5	2015	Of the top 10 genes (fold-change &gt; 10, P &lt; 10(-10)) regulated by metformin plus aspirin, PCDH18, CCL2, RASL11A, FAM111B and BMP5 were down-regulated &gt;= 20-fold, while NGFR, NPTX1, C7orf57, MRPL23AS1 and UNC5B were up-regulated &gt;= 10-fold.	Metformin	71-80	bone morphogenetic protein 5	Homo sapiens	130-134
26294325-5	2015	Of the top 10 genes (fold-change &gt; 10, P &lt; 10(-10)) regulated by metformin plus aspirin, PCDH18, CCL2, RASL11A, FAM111B and BMP5 were down-regulated &gt;= 20-fold, while NGFR, NPTX1, C7orf57, MRPL23AS1 and UNC5B were up-regulated &gt;= 10-fold.	Metformin	71-80	MRPL23 antisense RNA 1	Homo sapiens	198-207
25687657-9	2015	Higher concentrations of metformin lead to a significant (p &lt; 0.05) dose-dependent attenuation of the progesterone effect with regard to IGFBP-1, -3, -5, -6, as well as IGF I receptor, while it did not change the expression of IGFBP-2 and -4, IGF I and II and the IGF II receptor.	Metformin	25-34	insulin like growth factor binding protein 2	Homo sapiens	230-244
25846811-4	2015	Several studies have revealed that the activation of AMPK by chemical stimulators, such as metformin, induces apoptosis in a variety of hematologic malignant cells.	Metformin	91-100	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	53-57
25846811-9	2015	We found an inverse correlation between the intensity of ERK activity and the degree of AMPK activation after stimulation with either glucose deprivation or metformin.	Metformin	157-166	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	88-92
25846811-10	2015	We also found that the inhibition of ERK activity by U0126 restored AMPK activation after metformin treatment.	Metformin	90-99	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	68-72
25846811-12	2015	Importantly, metformin induced ERK activation by suppressing the protein levels of dual specificity phosphatase 6, a negative regulator of ERK.	Metformin	13-22	dual specificity phosphatase 6	Homo sapiens	83-113
25846811-13	2015	This crosstalk between AMPK and ERK could diminish the antileukemic activity of metformin.	Metformin	80-89	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	23-27
22340932-12	2012	Combined patient and insurer spending for patients who were initiated on alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, or dipeptidyl peptidase-4 inhibitors was $677 over a 6-month period compared with $116 and $118 for patients initiated on metformin or a sulfonylurea, respectively, a cost difference of approximately $1120 annually per patient.	Metformin	259-268	sucrase-isomaltase	Homo sapiens	73-90
22340932-12	2012	Combined patient and insurer spending for patients who were initiated on alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, or dipeptidyl peptidase-4 inhibitors was $677 over a 6-month period compared with $116 and $118 for patients initiated on metformin or a sulfonylurea, respectively, a cost difference of approximately $1120 annually per patient.	Metformin	259-268	dipeptidyl peptidase 4	Homo sapiens	140-162
22086681-5	2012	Metformin also decreased the expression of CSC markers,CD44, EpCAM,EZH2, Notch-1, Nanog and Oct4, and caused reexpression of miRNAs (let-7a,let-7b, miR-26a, miR-101, miR-200b, and miR-200c) that are typically lost in pancreatic cancer and especially in pancreatospheres.	Metformin	0-9	POU class 5 homeobox 1	Homo sapiens	92-96
22100460-6	2012	Compared with AGEs-modified BSA prepared without metformin (AGEs-MF0), those prepared in the presence of 30 mM or 100 mM metformin (AGEs-MF30 or AGEs-MF100) significantly reduced RAGE mRNA level, reactive oxygen species (ROS) generation, apoptosis, monocyte chemoattractant protein-1 and transforming growth factor-beta mRNA level in tubular cells.	Metformin	121-130	C-C motif chemokine ligand 2	Homo sapiens	249-319
22129484-0	2012	Metformin may antagonize Lin28 and/or Lin28B activity, thereby boosting let-7 levels and antagonizing cancer progression.	Metformin	0-9	lin-28 homolog A	Mus musculus	25-30
22129484-5	2012	It is proposed that this latter effect of metformin may reflect AMPK-mediated inhibition of the expression or activity of Lin28/Lin28A, proteins which act post-transcriptionally to decrease the levels of all let-7 family members.	Metformin	42-51	lin-28 homolog A	Mus musculus	122-127
22129484-5	2012	It is proposed that this latter effect of metformin may reflect AMPK-mediated inhibition of the expression or activity of Lin28/Lin28A, proteins which act post-transcriptionally to decrease the levels of all let-7 family members.	Metformin	42-51	lin-28 homolog A	Mus musculus	128-134
22124463-6	2012	Of importance, this study also demonstrated that metformin suppressed the "memory" of hyperglycemia stress in the diabetic retinas, which may be involved in the SIRT1/LKB1/AMPK pathway.	Metformin	49-58	serine/threonine kinase 11	Rattus norvegicus	167-171
21968881-4	2012	Here, we have explored the therapeutic potential of the anti-diabetic drug, metformin (an LKB1/AMPK activator), against both T-cell acute lymphoblastic leukemia (T-ALL) cell lines and primary samples from T-ALL patients displaying mTORC1 activation.	Metformin	76-85	serine/threonine kinase 11	Homo sapiens	90-94
21968881-10	2012	In conclusion, metformin displayed a remarkable anti-leukemic activity, which emphasizes future development of LKB1/AMPK activators as clinical candidates for therapy in T-ALL.	Metformin	15-24	serine/threonine kinase 11	Homo sapiens	111-115
23166782-0	2012	Metformin reduces hepatic expression of SIRT3, the mitochondrial deacetylase controlling energy metabolism.	Metformin	0-9	sirtuin 3	Mus musculus	40-45
23166782-3	2012	We hypothesized that metformin treatment could diminish mitochondrial ATP production through downregulation of SIRT3 expression.	Metformin	21-30	sirtuin 3	Mus musculus	111-116
23166782-5	2012	Metformin prevented SIRT3 induction by glucagon.	Metformin	0-9	sirtuin 3	Mus musculus	20-25
23166782-6	2012	Moreover, metformin downregulated constitutive expression of SIRT3 in primary hepatocytes and in the liver in vivo.	Metformin	10-19	sirtuin 3	Mus musculus	61-66
23166782-8	2012	ERRalpha mRNA expression was regulated in a similar manner as SIRT3 mRNA by glucagon, cAMP and metformin.	Metformin	95-104	sirtuin 3	Mus musculus	62-67
23133528-7	2012	Moreover, metformin treatment increased gene expression of PI3K, IRS1, MAP3K, AKT and PTEN more than &gt;1.5 fold.	Metformin	10-19	insulin receptor substrate 1	Homo sapiens	65-69
23133528-7	2012	Moreover, metformin treatment increased gene expression of PI3K, IRS1, MAP3K, AKT and PTEN more than &gt;1.5 fold.	Metformin	10-19	phosphatase and tensin homolog	Homo sapiens	86-90
26252266-3	2015	METHODS: In a user base of 390.000 people we reviewed all the cases of metformin-associated lactic acidosis treated at the First Aid in a 15 months period; we considered the patients characteristics, their risk factors and the outcome.	Metformin	71-80	activation induced cytidine deaminase	Homo sapiens	129-132
25760137-0	2015	Metformin alleviates high glucose-mediated oxidative stress in rat glomerular mesangial cells by modulation of p38 mitogen-activated protein kinase expression in vitro.	Metformin	0-9	mitogen activated protein kinase 14	Rattus norvegicus	111-147
25760137-1	2015	The aim of the current study was to investigate the effects and mechanism of metformin in oxidative stress and p38 mitogen-activated protein kinase (p38MAPK) expression in rat glomerular mesangial cells (MCs) cultured in a high glucose medium.	Metformin	77-86	mitogen activated protein kinase 14	Rattus norvegicus	111-147
25760137-8	2015	When metformin was added to the high glucose medium, the activity of SOD in supernatant fluid was increased significantly, whereas a significant reduction (P&lt;0.05) was observed in the levels of MDA in the supernatant, intracellular p22phox mRNA and protein, p-p38MAPK protein in addition to ROS production in rat glomerular MCs.	Metformin	5-14	mitogen activated protein kinase 14	Rattus norvegicus	263-270
25760137-10	2015	In conclusion, metformin was suggested to alleviate high glucose-induced oxidative stress and p-p38MAPK protein expression in rat glomerular MCs, which may contribute to its reno-protective abilities in diabetes.	Metformin	15-24	mitogen activated protein kinase 14	Rattus norvegicus	96-103
26075749-0	2015	Metformin induces ER stress-dependent apoptosis through miR-708-5p/NNAT pathway in prostate cancer.	Metformin	0-9	microRNA 708	Homo sapiens	56-63
26075749-3	2015	Metformin promotes increased expression of miR-708-5p, leading to suppression of endoplasmic reticulum (ER) membrane protein neuronatin (NNAT) expression and subsequently induces apoptosis of prostate cancer cells through the ER stress pathway.	Metformin	0-9	microRNA 708	Homo sapiens	43-50
26075749-6	2015	Taken together, our findings clearly demonstrate that metformin stimulates increased expression of miR-708-5p to target the NNAT-mediated response to ER stress and apoptosis.	Metformin	54-63	microRNA 708	Homo sapiens	99-106
26075749-7	2015	This novel regulatory mechanism of metformin in prostate cancer cells not only advances our knowledge on the molecular mechanism of metformin but also provides a promising therapeutic strategy by targeting miR-708-5p and NNAT for prostate cancer treatment.	Metformin	35-44	microRNA 708	Homo sapiens	206-213
26065921-2	2015	Here, we identified microRNA-27b (miR-27b) as a key regulator for the generation of a side-population in breast cancer cells that showed CSC properties, and also found that the anti-type II diabetes (T2D) drug metformin reduced this side-population via miR-27b-mediated repression of ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1), which is involved in T2D development.	Metformin	210-219	microRNA 27b	Homo sapiens	20-32
26065921-2	2015	Here, we identified microRNA-27b (miR-27b) as a key regulator for the generation of a side-population in breast cancer cells that showed CSC properties, and also found that the anti-type II diabetes (T2D) drug metformin reduced this side-population via miR-27b-mediated repression of ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1), which is involved in T2D development.	Metformin	210-219	microRNA 27b	Homo sapiens	34-41
26065921-2	2015	Here, we identified microRNA-27b (miR-27b) as a key regulator for the generation of a side-population in breast cancer cells that showed CSC properties, and also found that the anti-type II diabetes (T2D) drug metformin reduced this side-population via miR-27b-mediated repression of ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1), which is involved in T2D development.	Metformin	210-219	microRNA 27b	Homo sapiens	253-260
25847249-6	2015	GLUT4 inhibition also caused sensitization to metformin in multiple myeloma and chronic lymphocytic leukemia and a number of solid tumors suggesting the broader therapeutic utility of targeting GLUT4.	Metformin	46-55	solute carrier family 2 member 4	Homo sapiens	0-5
25370454-7	2015	These observations were further supported by the fact that metformin treatment inhibited CD3/CD28-induced IFN-gamma and IL-17A expression along with the transcription factors that drive their expression (T-bet [Th1] and ROR-gammat [Th17], respectively).	Metformin	59-68	CD3 antigen, epsilon polypeptide	Mus musculus	89-92
25891779-0	2015	Metformin attenuates palmitic acid-induced insulin resistance in L6 cells through the AMP-activated protein kinase/sterol regulatory element-binding protein-1c pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	86-114
25891779-1	2015	AMP-activated protein kinase (AMPK) is an important effector of metformin action on glucose uptake in skeletal muscle cells.	Metformin	64-73	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-28
25891779-1	2015	AMP-activated protein kinase (AMPK) is an important effector of metformin action on glucose uptake in skeletal muscle cells.	Metformin	64-73	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	30-34
26126434-5	2015	Notably, several recent studies demonstrated that the antitumorigenic effects of many indirect AMPK activators, such as metformin, do not depend on AMPK.	Metformin	120-129	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	95-99
26117007-4	2015	After treated with 20 mmol/L metformin for 24 h, the expressions of CD14 and CD11b in THP-1 cells didn"t change much (P&gt;0.05), the early apoptosis rates in exprimental and control groups were (2.02+-0.85)% and (4.46+-1.33)% respectively, the late apoptosis rates in experimental and control groups were (1.43+-0.83)% and (3.31+-0.59)% respectively.	Metformin	29-38	CD14 molecule	Homo sapiens	68-72
25607338-8	2015	A decreasing, but non-significant trend in log-OPG levels was observed in women of the metformin arm (p=0.063).	Metformin	87-96	TNF receptor superfamily member 11b	Homo sapiens	47-50
26081514-8	2015	In metformin-treated cells, the expressions of Arg1 (P = 0.009), IL-10 (P = 0.015) and IL-4 (P = 0.001) mRNA increased while the expressions of IL-1beta (P = 0.001) and IL-6 (P = 0.032) mRNA decreased.	Metformin	3-12	arginase 1	Homo sapiens	47-51
25662275-6	2015	Rosiglitazone (5 micromol/l) and metformin (5 mmol/l) led to increased PRDM16 mRNA and protein levels in isolated human adipocytes and in whole adipose tissue.	Metformin	33-42	PR/SET domain 16	Homo sapiens	71-77
25744403-0	2015	Activation of AMPK by metformin inhibits TGF-beta-induced collagen production in mouse renal fibroblasts.	Metformin	22-31	transforming growth factor, beta 1	Mus musculus	41-49
25744403-1	2015	AIMS: To clarify whether activation of adenosine monophosphate-activated protein kinase (AMPK) by metformin inhibits transforming growth factor beta (TGF-beta)-induced collagen production in primary cultured mouse renal fibroblasts and further to address the molecular mechanisms.	Metformin	98-107	transforming growth factor, beta 1	Mus musculus	150-158
25744403-5	2015	Activation of AMPK by metformin reduced TGF-beta1-induced collagen type I production by suppression of Smad3-driven CTGF expression.	Metformin	22-31	transforming growth factor, beta 1	Mus musculus	40-49
25744403-5	2015	Activation of AMPK by metformin reduced TGF-beta1-induced collagen type I production by suppression of Smad3-driven CTGF expression.	Metformin	22-31	SMAD family member 3	Mus musculus	103-108
25744403-5	2015	Activation of AMPK by metformin reduced TGF-beta1-induced collagen type I production by suppression of Smad3-driven CTGF expression.	Metformin	22-31	cellular communication network factor 2	Mus musculus	116-120
25697376-0	2015	Metformin inhibits 7,12-dimethylbenz[a]anthracene-induced breast carcinogenesis and adduct formation in human breast cells by inhibiting the cytochrome P4501A1/aryl hydrocarbon receptor signaling pathway.	Metformin	0-9	aryl hydrocarbon receptor	Homo sapiens	160-185
25867026-7	2015	We show that metformin induces decreased proliferation, cell cycle arrest, autophagy, apoptosis and cell death in vitro with a concomitant activation of AMPK, Redd1 and inhibition of the mTOR pathway.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	153-157
25867026-9	2015	Interestingly, knockdown of AMPK and Redd1 with siRNA partially, but incompletely, abrogates the induction of apoptosis by metformin suggesting both AMPK/Redd1-dependent and -independent effects.	Metformin	123-132	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	28-32
25867026-9	2015	Interestingly, knockdown of AMPK and Redd1 with siRNA partially, but incompletely, abrogates the induction of apoptosis by metformin suggesting both AMPK/Redd1-dependent and -independent effects.	Metformin	123-132	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	149-153
26405648-7	2015	In addition to the anticancer effect of metformin mediated through the AMPK pathway, additional mechanisms of action that directly target tissues have been identified including effects on stem cells, apoptosis, STAT3 and HER2.	Metformin	40-49	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	71-75
23029387-8	2012	In LKB1 deficient (A549, HeLa) and expressing (SCC9, SCC25) cell lines, metformin enhanced gefitinib cytotoxicity only in LKB1 expressing cell lines while both groups showed synergistic cytotoxic effects with lovastatin treatments.	Metformin	72-81	serine/threonine kinase 11	Homo sapiens	3-7
23029387-8	2012	In LKB1 deficient (A549, HeLa) and expressing (SCC9, SCC25) cell lines, metformin enhanced gefitinib cytotoxicity only in LKB1 expressing cell lines while both groups showed synergistic cytotoxic effects with lovastatin treatments.	Metformin	72-81	serine/threonine kinase 11	Homo sapiens	122-126
22590580-0	2012	Pharmacogenetics meets metabolomics: discovery of tryptophan as a new endogenous OCT2 substrate related to metformin disposition.	Metformin	107-116	solute carrier family 22 member 2	Homo sapiens	81-85
22590580-1	2012	Genetic polymorphisms of the organic cation transporter 2 (OCT2), encoded by SLC22A2, have been investigated in association with metformin disposition.	Metformin	129-138	solute carrier family 22 member 2	Homo sapiens	29-57
22590580-1	2012	Genetic polymorphisms of the organic cation transporter 2 (OCT2), encoded by SLC22A2, have been investigated in association with metformin disposition.	Metformin	129-138	solute carrier family 22 member 2	Homo sapiens	59-63
22590580-1	2012	Genetic polymorphisms of the organic cation transporter 2 (OCT2), encoded by SLC22A2, have been investigated in association with metformin disposition.	Metformin	129-138	solute carrier family 22 member 2	Homo sapiens	77-84
22500211-5	2012	Both metformin and ionizing radiation activated AMPK leading to inactivation of mTOR and suppression of its downstream effectors such as S6K1 and 4EBP1, a crucial signaling pathway for proliferation and survival of cancer cells, in vitro as well as in the in vivo tumors.	Metformin	5-14	ribosomal protein S6 kinase B1	Homo sapiens	137-151
26148594-8	2015	CONCLUSIONS: Metformin inhibited the expression of MMP-2, cisplatin and the combined treatment inhibited the expression of survivin, MMP-2, VEGF-C, and VEGFR-3, and the combined treatment of metformin with cisplatin resulted in enhanced anti-tumor efficacy.	Metformin	13-22	baculoviral IAP repeat-containing 5	Mus musculus	123-131
26148594-8	2015	CONCLUSIONS: Metformin inhibited the expression of MMP-2, cisplatin and the combined treatment inhibited the expression of survivin, MMP-2, VEGF-C, and VEGFR-3, and the combined treatment of metformin with cisplatin resulted in enhanced anti-tumor efficacy.	Metformin	191-200	baculoviral IAP repeat-containing 5	Mus musculus	123-131
25812520-2	2015	This finding may help to explain why the antidiabetic drug metformin, for which AMPK is a key effector, is linked to cancer-protective activity.	Metformin	59-68	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	80-84
25785990-0	2015	Anti-angiogenic effect of metformin in mouse oxygen-induced retinopathy is mediated by reducing levels of the vascular endothelial growth factor receptor Flk-1.	Metformin	26-35	kinase insert domain protein receptor	Mus musculus	154-159
25785990-5	2015	The effects of metformin on the levels of Flk1 (VEGF receptor-2) and phosphorylated Flk1 (pFlk1) were measured by Western blotting (HUVECs) and immunohistochemistry (retinal tissue).	Metformin	15-24	kinase insert domain protein receptor	Mus musculus	42-46
25785990-5	2015	The effects of metformin on the levels of Flk1 (VEGF receptor-2) and phosphorylated Flk1 (pFlk1) were measured by Western blotting (HUVECs) and immunohistochemistry (retinal tissue).	Metformin	15-24	kinase insert domain protein receptor	Mus musculus	48-63
25785990-5	2015	The effects of metformin on the levels of Flk1 (VEGF receptor-2) and phosphorylated Flk1 (pFlk1) were measured by Western blotting (HUVECs) and immunohistochemistry (retinal tissue).	Metformin	15-24	kinase insert domain protein receptor	Mus musculus	84-88
26045896-0	2015	Reversing the reduced level of endometrial GLUT4 expression in polycystic ovary syndrome: a mechanistic study of metformin action.	Metformin	113-122	solute carrier family 2 member 4	Homo sapiens	43-48
26045896-8	2015	Using a human tissue culture system, we investigated the molecular basis by which GLUT4 regulation in endometrial hyperplasia tissues is affected by metformin in PCOS patients.	Metformin	149-158	solute carrier family 2 member 4	Homo sapiens	82-87
26045896-10	2015	Moreover, we demonstrate that metformin induces GLUT4 expression and inhibits AR expression and blocks insulin receptor/PI3K/Akt/mTOR signaling in the same hyperplasia human tissues.	Metformin	30-39	solute carrier family 2 member 4	Homo sapiens	48-53
26045896-10	2015	Moreover, we demonstrate that metformin induces GLUT4 expression and inhibits AR expression and blocks insulin receptor/PI3K/Akt/mTOR signaling in the same hyperplasia human tissues.	Metformin	30-39	insulin receptor	Homo sapiens	103-119
26101707-8	2015	Metformin induced apoptosis and cell cycle arrest in part through inhibiting PARP expression.	Metformin	0-9	collagen type XI alpha 2 chain	Homo sapiens	77-81
26101707-9	2015	Metformin downregulated PI3K, Akt, HIF1alpha, PARP, PKM2 and COX expression.	Metformin	0-9	collagen type XI alpha 2 chain	Homo sapiens	46-50
26101707-9	2015	Metformin downregulated PI3K, Akt, HIF1alpha, PARP, PKM2 and COX expression.	Metformin	0-9	cytochrome c oxidase subunit 8A	Homo sapiens	61-64
25080865-0	2015	Sorafenib synergizes with metformin in NSCLC through AMPK pathway activation.	Metformin	26-35	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	53-57
25849721-0	2015	Changes in insulin receptor signaling underlie neoadjuvant metformin administration in breast cancer: a prospective window of opportunity neoadjuvant study.	Metformin	59-68	insulin receptor	Homo sapiens	11-27
25592197-2	2015	RESEARCH DESIGN AND METHODS: Patients with HbA1c of 7.0% (53 mmol/mol) to 10.5% (91 mmol/mol) receiving sulfonylurea and metformin were randomized to receive dapagliflozin 10 mg/day (n = 109) or placebo (n = 109) for 24 weeks.	Metformin	121-130	hemoglobin subunit alpha 1	Homo sapiens	43-47
25416412-7	2015	In addition, enhancement of vitamin D3"s chemopreventive effects by metformin was associated with inhibition of the protein expressions of c-Myc and Cyclin D1, via the vitamin D receptor/beta-catenin pathway.	Metformin	68-77	MYC proto-oncogene, bHLH transcription factor	Rattus norvegicus	139-144
25417601-7	2015	Metformin decreased expression of phosphorylated (p)-AMPK (P = 0.00001), p-Akt (P = 0.0002), p-S6 (51.2%, P = 0.0002), p-4E-BP-1 (P = 0.001), and ER (P = 0.0002) but not PR expression.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	53-57
25417601-7	2015	Metformin decreased expression of phosphorylated (p)-AMPK (P = 0.00001), p-Akt (P = 0.0002), p-S6 (51.2%, P = 0.0002), p-4E-BP-1 (P = 0.001), and ER (P = 0.0002) but not PR expression.	Metformin	0-9	progesterone receptor	Homo sapiens	170-172
25497710-0	2015	Metformin reduces the Walker-256 tumor development in obese-MSG rats via AMPK and FOXO3a.	Metformin	0-9	forkhead box O3	Rattus norvegicus	82-88
25497710-10	2015	The effect of metformin reducing the tumor development in obese rats might involve increased mRNA expression of pRb and p27, increased activity of AMPK and FOXO3a and decreased expression of p-ERK1/2 (Thr202/Tyr204) in Walker-256 tumor.	Metformin	14-23	forkhead box O3	Rattus norvegicus	156-162
25179820-6	2015	Metformin inhibited mammalian target of rapamycin complex 1 (mTORC1) activity by phosphorylating the mTORC1 component raptor.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	61-67
25179820-6	2015	Metformin inhibited mammalian target of rapamycin complex 1 (mTORC1) activity by phosphorylating the mTORC1 component raptor.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	101-107
25179820-7	2015	This study revealed the anti-angiogenic activity of metformin in ELT-3 cells by suppressing the expression of VEGF via the mTORC1/HIF-1alpha pathway.	Metformin	52-61	CREB regulated transcription coactivator 1	Mus musculus	123-129
25462562-0	2015	Metformin enhances the anti-adipogenic effects of atorvastatin via modulation of STAT3 and TGF-beta/Smad3 signaling.	Metformin	0-9	SMAD family member 3	Homo sapiens	100-105
25790097-7	2015	Metformin inhibited HK2, GLUT1, HIF-1alpha expression and glucose consumption.	Metformin	0-9	hexokinase 2	Homo sapiens	20-23
26496168-6	2015	Metformin, an inhibitor of mitochondrial respiratory chain was able to reconvert oxidative metabolism and abrogate TGFbeta expression in LpH-MSC.	Metformin	0-9	lactase	Homo sapiens	137-140
26496168-8	2015	Both agents, metformin and esomeprazole, inhibited EMT profile in melanoma cells grown in LpH-MSC medium, and reduced glycolytic markers.	Metformin	13-22	lactase	Homo sapiens	90-93
26411966-1	2015	Increasing epidemiologic evidence suggests that metformin, a well-established AMPK activator and the most favorable first-line anti-diabetic drug, reduces stroke incidence and severity.	Metformin	48-57	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	78-82
22153807-0	2012	Serum level of soluble CD26/dipeptidyl peptidase-4 (DPP-4) predicts the response to sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes controlled inadequately by metformin and/or sulfonylurea.	Metformin	176-185	dipeptidyl peptidase 4	Homo sapiens	23-50
22153807-0	2012	Serum level of soluble CD26/dipeptidyl peptidase-4 (DPP-4) predicts the response to sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes controlled inadequately by metformin and/or sulfonylurea.	Metformin	176-185	dipeptidyl peptidase 4	Homo sapiens	52-57
22153807-2	2012	We investigated the relationship between the baseline serum level of soluble CD 26/DPP-4 and the response to treatment with sitagliptin, a DPP-4 inhibitor, over 24 weeks in patients who had type 2 diabetes inadequately controlled by metformin and/or sulfonylurea therapy.	Metformin	233-242	dipeptidyl peptidase 4	Homo sapiens	77-82
21733059-0	2011	Metformin opposes impaired AMPK and SIRT1 function and deleterious changes in core clock protein expression in white adipose tissue of genetically-obese db/db mice.	Metformin	0-9	sirtuin 1	Mus musculus	36-41
21733059-7	2011	3T3-L1 adipocytes were incubated with metformin, EX527 or FK866, inhibitors of SIRT1 and NAMPT, respectively.	Metformin	38-47	sirtuin 1	Mus musculus	79-84
21733059-11	2011	Metformin increased AMPK activity in WAT of db/db mice and in metformin-treated adipocytes, with increased NAMPT, SIRT1 and circadian component expression.	Metformin	0-9	sirtuin 1	Mus musculus	114-119
21907790-2	2011	Metformin exerts cardioprotective actions via AMP-activated protein kinase (AMPK) and increases the expression of adiponectin and its receptors (adipoR1 and adipoR2) in skeletal muscle and adipose tissue, but its effect on cardiac tissue is still unknown.	Metformin	0-9	adiponectin receptor 1	Homo sapiens	145-152
21907790-8	2011	In addition, metformin up-regulated the expression of adiponectin and its receptors, adipoR1 and adipoR2, in cardiomyocytes.	Metformin	13-22	adiponectin receptor 1	Homo sapiens	85-92
21907790-9	2011	In contrast, silencing either adipoR1 or adipoR2 with siRNA inhibited the AMPK activation and the protective effects of metformin.	Metformin	120-129	adiponectin receptor 1	Homo sapiens	30-37
22170748-1	2011	By activating the ataxia telangiectasia mutated (ATM)-mediated DNA Damage Response (DDR), the AMPK agonist metformin might sensitize cells against further damage, thus mimicking the precancerous stimulus that induces an intrinsic barrier against carcinogenesis.	Metformin	107-116	ATM serine/threonine kinase	Homo sapiens	18-47
22170748-1	2011	By activating the ataxia telangiectasia mutated (ATM)-mediated DNA Damage Response (DDR), the AMPK agonist metformin might sensitize cells against further damage, thus mimicking the precancerous stimulus that induces an intrinsic barrier against carcinogenesis.	Metformin	107-116	ATM serine/threonine kinase	Homo sapiens	49-52
22170748-4	2011	The bioenergetic crisis imposed by metformin, which may involve enhanced mitochondrial biogenesis and oxidative stress, can lower the threshold for cellular senescence by pre-activating an ATM-dependent pseudo-DDR.	Metformin	35-44	ATM serine/threonine kinase	Homo sapiens	189-192
22340218-9	2011	However, IKKalpha expression was increased after metformin treatment in both tissues.	Metformin	49-58	conserved helix-loop-helix ubiquitous kinase	Mus musculus	9-17
21872612-7	2011	SIGNIFICANCE: The present study demonstrated that the coadministration of TS-021 and metformin synergistically improved the islet morphology by increasing the circulating level of biologically active GLP-1, which is thought to result from two different mechanisms (namely, an increase in GLP-1 secretion and DPP-IV inhibition).	Metformin	85-94	dipeptidylpeptidase 4	Mus musculus	308-314
21806981-10	2011	These data suggest that anti-melanoma effects of metformin are mediated through p21- and AMPK-independent cell cycle arrest, apoptosis and autophagy associated with p53/Bcl-2 modulation, mitochondrial damage and oxidative stress.	Metformin	49-58	transformation related protein 53, pseudogene	Mus musculus	165-168
21664031-6	2011	This was further augmented in metformin pretreated cells, while IGF II-receptor gene expression changed particularly after pretreatment with metformin.	Metformin	141-150	insulin like growth factor 2 receptor	Homo sapiens	64-79
21618594-0	2011	Metformin stimulates osteoprotegerin and reduces RANKL expression in osteoblasts and ovariectomized rats.	Metformin	0-9	TNF receptor superfamily member 11B	Rattus norvegicus	21-36
21618594-4	2011	In this study, we demonstrated that metformin dose-dependently stimulated OPG and reduced RANKL mRNA and protein expression in mouse calvarial osteoblasts and osteoblastic cell line MC3T3-E1.	Metformin	36-45	tumor necrosis factor (ligand) superfamily, member 11	Mus musculus	90-95
21618594-5	2011	Inhibition of AMP-activated protein kinase (AMPK) and CaM kinase kinase (CaMKK), two targets of metformin, suppressed endogenous and metformin-induced OPG secretion in osteoblasts.	Metformin	96-105	TNF receptor superfamily member 11B	Rattus norvegicus	151-154
21618594-5	2011	Inhibition of AMP-activated protein kinase (AMPK) and CaM kinase kinase (CaMKK), two targets of metformin, suppressed endogenous and metformin-induced OPG secretion in osteoblasts.	Metformin	133-142	TNF receptor superfamily member 11B	Rattus norvegicus	151-154
21618594-7	2011	Most importantly, metformin significantly increased total body bone mineral density, prevented bone loss and decreased TRAP-positive cells in OVX rats proximal tibiae, accompanied with an increase of OPG and decrease of RANKL expression.	Metformin	18-27	TNF receptor superfamily member 11B	Rattus norvegicus	200-203
21618594-8	2011	These in vivo and in vitro studies suggest that metformin reduces RANKL and stimulates OPG expression in osteoblasts, further inhibits osteoclast differentiation and prevents bone loss in OVX rats.	Metformin	48-57	TNF receptor superfamily member 11B	Rattus norvegicus	87-90
21697722-5	2011	Michaelis-Menten kinetics of OCT3-mediated uptake of prototypical OCT substrates 1-methyl-4-phenylpyridinium and metformin were studied in human embryonic kidney 293 cells stably overexpressing OCT3.	Metformin	113-122	plexin A2	Homo sapiens	29-32
21757781-5	2011	OA-induced SREBP-1 transcriptional activity was suppressed by cotreatment with aminoimidazole carboxamide ribonucleotide (AICAR) or metformin, or by overexpression of constitutively active AMPK (CA-AMPK) in the human hepatoma cell line.	Metformin	132-141	sterol regulatory element binding transcription factor 1	Homo sapiens	11-18
21717584-6	2011	Mammalian target of rapamycin complex 1 (mTORC1), which is negatively regulated by AMPK and plays a central role in cell growth and proliferation, was inhibited by metformin, as manifested by dephosphorylation of its downstream targets 40S ribosomal S6 kinase 1 (S6K1) (T389), the eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) (T37/46) and S6 (S235/236) in C666-1 cells.	Metformin	164-173	ribosomal protein S6 kinase A1	Homo sapiens	240-261
21717584-6	2011	Mammalian target of rapamycin complex 1 (mTORC1), which is negatively regulated by AMPK and plays a central role in cell growth and proliferation, was inhibited by metformin, as manifested by dephosphorylation of its downstream targets 40S ribosomal S6 kinase 1 (S6K1) (T389), the eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) (T37/46) and S6 (S235/236) in C666-1 cells.	Metformin	164-173	ribosomal protein S6 kinase B1	Homo sapiens	263-267
21717584-6	2011	Mammalian target of rapamycin complex 1 (mTORC1), which is negatively regulated by AMPK and plays a central role in cell growth and proliferation, was inhibited by metformin, as manifested by dephosphorylation of its downstream targets 40S ribosomal S6 kinase 1 (S6K1) (T389), the eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) (T37/46) and S6 (S235/236) in C666-1 cells.	Metformin	164-173	eukaryotic translation initiation factor 4E binding protein 1	Homo sapiens	326-350
21717584-6	2011	Mammalian target of rapamycin complex 1 (mTORC1), which is negatively regulated by AMPK and plays a central role in cell growth and proliferation, was inhibited by metformin, as manifested by dephosphorylation of its downstream targets 40S ribosomal S6 kinase 1 (S6K1) (T389), the eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) (T37/46) and S6 (S235/236) in C666-1 cells.	Metformin	164-173	eukaryotic translation initiation factor 4E binding protein 1	Homo sapiens	352-358
21727749-4	2011	The incritin memetics are potentially safe during Ramadan; the DPP4 inhibitors vildagliptin and sitagliptin provide an effective and safe therapeutic option, administered either alone or in combination with metformin or sulfonylureas.	Metformin	207-216	dipeptidyl peptidase 4	Homo sapiens	63-67
21307134-3	2011	OBJECTIVE: The aim of the study was to investigate the effects of metformin administration on AMH levels in relation with the clinical and endocrine-metabolic parameters in obese women with PCOS.	Metformin	66-75	anti-Mullerian hormone	Homo sapiens	94-97
21307134-12	2011	Data were further analyzed after dividing patients on the basis of pretreatment insulinemic response to the oral glucose tolerance test; metformin was effective in reducing insulin secretion, AMH levels, and, interestingly, ovarian volume exclusively in PCOS patients with hyperinsulinism; none of these changes occurred in the normoinsulinemic group.	Metformin	137-146	anti-Mullerian hormone	Homo sapiens	192-195
21147283-0	2011	Metformin induces osteoblast differentiation via orphan nuclear receptor SHP-mediated transactivation of Runx2.	Metformin	0-9	runt related transcription factor 2	Mus musculus	105-110
21147283-4	2011	Metformin increased significantly the expression of the key osteogenic genes, such as alkaline phosphatase (ALP), osteocalcin (OC) and bone sialoprotein (BSP) as well as SHP.	Metformin	0-9	bone gamma-carboxyglutamate protein 2	Mus musculus	114-125
21147283-4	2011	Metformin increased significantly the expression of the key osteogenic genes, such as alkaline phosphatase (ALP), osteocalcin (OC) and bone sialoprotein (BSP) as well as SHP.	Metformin	0-9	bone gamma-carboxyglutamate protein 2	Mus musculus	127-129
21147283-5	2011	Transient transfection assays were performed in MC3T3E1 cells to confirm the effects of metformin on SHP, OC and Runx2 promoter activities.	Metformin	88-97	runt related transcription factor 2	Mus musculus	113-118
21147283-6	2011	Metformin increased the transcription of the SHP and OC genes, and the metformin effect was inhibited by dominant negative form of AMPK (DN-AMPK) or compound C (an inhibitor of AMPK).	Metformin	0-9	bone gamma-carboxyglutamate protein 2	Mus musculus	53-55
21147283-10	2011	In addition, metformin-induced AMPK activation increased the level of Runx2 mRNA and protein.	Metformin	13-22	runt related transcription factor 2	Mus musculus	70-75
21147283-12	2011	Transient transfection and chromatin immunoprecipitation assays confirmed that metformin-induced SHP interacts physically and forms a complex with Runx2 on the osteocalcin gene promoter in MC3T3E1 cells.	Metformin	79-88	runt related transcription factor 2	Mus musculus	147-152
21147283-12	2011	Transient transfection and chromatin immunoprecipitation assays confirmed that metformin-induced SHP interacts physically and forms a complex with Runx2 on the osteocalcin gene promoter in MC3T3E1 cells.	Metformin	79-88	bone gamma-carboxyglutamate protein 2	Mus musculus	160-171
21147283-13	2011	These results suggest that metformin may stimulate osteoblast differentiation through the transactivation of Runx2 via AMPK/USF-1/SHP regulatory cascade in mouse calvaria-derived cells.	Metformin	27-36	runt related transcription factor 2	Mus musculus	109-114
21491251-11	2011	At 0 5 h-1 h after metformin administration, the enzyme activities and mRNA expression levels of G6Pase and PEPCK reached their lowest point in the kidney and their highest point in the liver.	Metformin	19-28	phosphoenolpyruvate carboxykinase 1	Gallus gallus	108-113
21368581-9	2011	Metformin"s molecular functioning to prevent invasive breast cancer can be explained in terms of its previously unrecognized ability to efficiently up-regulate the tumor-suppressive miRNAs let-7a &amp; miRNA-96 and inhibit the oncogenic miRNA-181a, thus epigenetically preserving the differentiated phenotype of mammary epithelium while preventing EMT-related cancer-initiating cell self-renewal.	Metformin	0-9	IL2 inducible T cell kinase	Homo sapiens	348-351
26411966-4	2015	However, recent studies have consistently suggested that AMPK-mediated microglia/macrophage polarization and angioneurogenesis may play essential roles in metformin-promoted, long-term functional recovery following stroke.	Metformin	155-164	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	57-61
26411966-5	2015	The present review summarizes the neuropharmacological actions of metformin in experimental stroke with an emphasis on the recent findings that the cell-specific effects and duration of AMPK activation are critical to the effects of metformin on stroke outcomes.	Metformin	233-242	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	186-190
26064989-0	2015	In Vitro and In Vivo Effects of Metformin on Osteopontin Expression in Mice Adipose-Derived Multipotent Stromal Cells and Adipose Tissue.	Metformin	32-41	secreted phosphoprotein 1	Mus musculus	45-56
20500102-9	2011	AMH level was significantly reduced during OC treatment, and there was a trend for AMH decrease during metformin therapy.	Metformin	103-112	anti-Mullerian hormone	Homo sapiens	83-86
21316309-0	2011	Metformin modulates IL-8, IL-1beta, ICAM and IGFBP-1 expression in human endometrial stromal cells.	Metformin	0-9	insulin like growth factor binding protein 1	Homo sapiens	45-52
21316309-6	2011	IGFBP-1 gene expression was reduced after long-term metformin exposure (7.7 fold, P&lt;0.05).	Metformin	52-61	insulin like growth factor binding protein 1	Homo sapiens	0-7
21430707-7	2011	We first reported that metformin and cyclosporin A (CsA) prevented Ca2+-induced PTP opening in permeabilized and intact INS-1 cells.	Metformin	23-32	insulin 1	Rattus norvegicus	120-125
21205107-1	2011	Several new oral antidiabetic agents, known as "gliptins" or "enzyme dipeptidyl peptidase-IV (DPP-4) inhibitors", have been developed for the treatment of type 2 diabetes and a key clinical use of the gliptins is in combination with metformin.	Metformin	233-242	dipeptidyl peptidase 4	Homo sapiens	69-92
21205107-1	2011	Several new oral antidiabetic agents, known as "gliptins" or "enzyme dipeptidyl peptidase-IV (DPP-4) inhibitors", have been developed for the treatment of type 2 diabetes and a key clinical use of the gliptins is in combination with metformin.	Metformin	233-242	dipeptidyl peptidase 4	Homo sapiens	94-99
20303124-0	2011	The anorexigenic effects of metformin involve increases in hypothalamic leptin receptor expression.	Metformin	28-37	leptin receptor	Rattus norvegicus	72-87
20980683-5	2011	Here, we investigated the effects of metformin on gonadotropin secretion in response to activin and GnRH in primary rat pituitary cells (PRP), and studied PRKA in rat pituitary.	Metformin	37-46	gonadotropin releasing hormone 1	Rattus norvegicus	100-104
20980683-6	2011	In PRP, metformin (10 mM) reduced LH and follicle-stimulating hormone (FSH) secretion induced by GnRH (10(-8) M, 3 h), FSH secretion, and mRNA FSHbeta subunit expression induced by activin (10(-8) M, 12 or 24 h).	Metformin	8-17	gonadotropin releasing hormone 1	Rattus norvegicus	97-101
20980683-10	2011	Metformin decreased activin-induced SMAD2 phosphorylation and GnRH-induced mitogen-activated protein kinase (MAPK) 3/1 (ERK1/2) phosphorylation.	Metformin	0-9	SMAD family member 2	Rattus norvegicus	36-41
20980683-10	2011	Metformin decreased activin-induced SMAD2 phosphorylation and GnRH-induced mitogen-activated protein kinase (MAPK) 3/1 (ERK1/2) phosphorylation.	Metformin	0-9	gonadotropin releasing hormone 1	Rattus norvegicus	62-66
20980683-11	2011	The PRKA inhibitor compound C abolished the effects of metformin on gonadotropin release induced by GnRH and on FSH secretion and Fshb mRNA induced by activin.	Metformin	55-64	gonadotropin releasing hormone 1	Rattus norvegicus	100-104
20980683-12	2011	The adenovirus-mediated production of dominant negative PRKA abolished the effects of metformin on the FSHbeta subunit mRNA and SMAD2 phosphorylation induced by activin and on the MAPK3/1 phosphorylation induced by GnRH.	Metformin	86-95	SMAD family member 2	Rattus norvegicus	128-133
20980683-12	2011	The adenovirus-mediated production of dominant negative PRKA abolished the effects of metformin on the FSHbeta subunit mRNA and SMAD2 phosphorylation induced by activin and on the MAPK3/1 phosphorylation induced by GnRH.	Metformin	86-95	gonadotropin releasing hormone 1	Rattus norvegicus	215-219
20980683-13	2011	Thus, in rat pituitary cells, metformin decreases gonadotropin secretion and MAPK3/1 phosphorylation induced by GnRH and FSH release, FSHbeta subunit expression, and SMAD2 phosphorylation induced by activin through PRKA activation.	Metformin	30-39	gonadotropin releasing hormone 1	Rattus norvegicus	112-116
20980683-13	2011	Thus, in rat pituitary cells, metformin decreases gonadotropin secretion and MAPK3/1 phosphorylation induced by GnRH and FSH release, FSHbeta subunit expression, and SMAD2 phosphorylation induced by activin through PRKA activation.	Metformin	30-39	SMAD family member 2	Rattus norvegicus	166-171
21159854-0	2011	Prenatal androgenization of female mice programs an increase in firing activity of gonadotropin-releasing hormone (GnRH) neurons that is reversed by metformin treatment in adulthood.	Metformin	149-158	gonadotropin releasing hormone 1	Mus musculus	83-113
21159854-0	2011	Prenatal androgenization of female mice programs an increase in firing activity of gonadotropin-releasing hormone (GnRH) neurons that is reversed by metformin treatment in adulthood.	Metformin	149-158	gonadotropin releasing hormone 1	Mus musculus	115-119
21159854-8	2011	To assess whether AMPK activation contributed to the metformin-induced reduction in GnRH neuron activity, the AMPK antagonist compound C was acutely applied to cells.	Metformin	53-62	gonadotropin releasing hormone 1	Mus musculus	84-88
21159854-10	2011	GnRH neurons from metformin-treated mice also showed a reduced inhibitory response to low glucose.	Metformin	18-27	gonadotropin releasing hormone 1	Mus musculus	0-4
21187071-3	2011	In addition, metformin induced the phosphorylation of Smad1/5/8 and expression of Dlx5 and Runx2, whereas compound C or dominant negative AMPK inhibited these effects.	Metformin	13-22	SMAD family member 1	Mus musculus	54-63
21187071-3	2011	In addition, metformin induced the phosphorylation of Smad1/5/8 and expression of Dlx5 and Runx2, whereas compound C or dominant negative AMPK inhibited these effects.	Metformin	13-22	runt related transcription factor 2	Mus musculus	91-96
21187071-4	2011	Transient transfection studies also showed that metformin increased the BRE-Luc and Runx2-Luc activities, which were inhibited by DN-AMPK or compound C. Down-regulation of Dlx5 expression by siRNA suppressed metformin-induced Runx2 expression.	Metformin	48-57	runt related transcription factor 2	Mus musculus	84-89
21187071-4	2011	Transient transfection studies also showed that metformin increased the BRE-Luc and Runx2-Luc activities, which were inhibited by DN-AMPK or compound C. Down-regulation of Dlx5 expression by siRNA suppressed metformin-induced Runx2 expression.	Metformin	48-57	runt related transcription factor 2	Mus musculus	226-231
21340016-5	2011	CAT, glutathione reductase (GR), TAS, and GSH remained significantly reduced in the diabetic rats treated with metformin and/or glibenclamide.	Metformin	111-120	glutathione-disulfide reductase	Rattus norvegicus	5-26
21340016-5	2011	CAT, glutathione reductase (GR), TAS, and GSH remained significantly reduced in the diabetic rats treated with metformin and/or glibenclamide.	Metformin	111-120	glutathione-disulfide reductase	Rattus norvegicus	28-30
21340016-6	2011	In contrast, metformin or glibenclamide combined with honey significantly increased CAT, GR, TAS, and GSH.	Metformin	13-22	glutathione-disulfide reductase	Rattus norvegicus	89-91
20956498-10	2011	Furthermore, metformin decreased IL-6 and MCP-1 gene expression in comparison with differentiated adipocytes.	Metformin	13-22	C-C motif chemokine ligand 2	Homo sapiens	42-47
21349801-6	2011	Concomitantly, metformin induces activation of LKB1 (serine/threonine kinase 11), a tumor suppressor gene, which is required for the phosphorylation and activation of AMPK.	Metformin	15-24	serine/threonine kinase 11	Homo sapiens	47-51
21349801-6	2011	Concomitantly, metformin induces activation of LKB1 (serine/threonine kinase 11), a tumor suppressor gene, which is required for the phosphorylation and activation of AMPK.	Metformin	15-24	serine/threonine kinase 11	Homo sapiens	53-79
21799661-10	2011	Poor in vivo and in vitro response to metformin may be the result of pharmacokinetic (OCT-1 expression was low in rat mammary cells; OCT-3 was downregulated in mammary carcinoma) and pharmacodynamic (complex I transcripts were higher in mammary epithelial cells from carcinomas versus uninvolved gland) effects.	Metformin	38-47	solute carrier family 22 member 8	Rattus norvegicus	133-138
20152998-3	2011	Metformin has been reported to inhibit DPP-4.	Metformin	0-9	dipeptidyl peptidase 4	Homo sapiens	39-44
20152998-10	2011	Mean AUC for plasma DPP-4 activity was lower after Metformin + GLP-1 (1505 +- 2 mumol/[mL min], P &lt; .001) and Metformin (1508 +- 2 mumol/[mL min], P &lt; .002) compared with GLP-1 (1587 +- 3 mumol/[mL min]).	Metformin	51-60	dipeptidyl peptidase 4	Homo sapiens	20-25
20152998-10	2011	Mean AUC for plasma DPP-4 activity was lower after Metformin + GLP-1 (1505 +- 2 mumol/[mL min], P &lt; .001) and Metformin (1508 +- 2 mumol/[mL min], P &lt; .002) compared with GLP-1 (1587 +- 3 mumol/[mL min]).	Metformin	113-122	dipeptidyl peptidase 4	Homo sapiens	20-25
20152998-12	2011	In patients with type 2 diabetes mellitus, metformin inhibits DPP-4 activity and thus increases active GLP-1 concentrations after subcutaneous injection.	Metformin	43-52	dipeptidyl peptidase 4	Homo sapiens	62-67
21776823-5	2011	Metformin induced apoptosis by arresting cells in G1 phase and reducing cyclin D level and increasing the expression of p21 and cyclin E. Molecular and cellular studies indicated that metformin significantly elevated p53 and Bax levels and reduced STAT3 and Bcl-2.	Metformin	0-9	H3 histone pseudogene 16	Homo sapiens	120-123
21776823-5	2011	Metformin induced apoptosis by arresting cells in G1 phase and reducing cyclin D level and increasing the expression of p21 and cyclin E. Molecular and cellular studies indicated that metformin significantly elevated p53 and Bax levels and reduced STAT3 and Bcl-2.	Metformin	184-193	H3 histone pseudogene 16	Homo sapiens	120-123
21931813-8	2011	The decrease in RLIP76 protein expression by rosiglitazone and metformin is associated with an up-regulation of PPARgamma and AMPK.	Metformin	63-72	ralA binding protein 1	Mus musculus	16-22
21779389-0	2011	Proton pump inhibitors inhibit metformin uptake by organic cation transporters (OCTs).	Metformin	31-40	ATPase H+/K+ transporting non-gastric alpha2 subunit	Homo sapiens	0-11
21779389-1	2011	Metformin, an oral insulin-sensitizing drug, is actively transported into cells by organic cation transporters (OCT) 1, 2, and 3 (encoded by SLC22A1, SLC22A2, or SLC22A3), which are tissue specifically expressed at significant levels in various organs such as liver, muscle, and kidney.	Metformin	0-9	solute carrier family 22 member 2	Homo sapiens	150-157
21779389-6	2011	All tested PPIs significantly inhibited metformin uptake by OCT1, OCT2, and OCT3 in a concentration-dependent manner.	Metformin	40-49	solute carrier family 22 member 2	Homo sapiens	66-70
21098287-0	2010	Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling.	Metformin	10-19	protein phosphatase 2 catalytic subunit alpha	Homo sapiens	81-85
21098287-3	2010	Using murine primary neurons from wild-type and human tau transgenic mice, we show that the antidiabetic drug metformin induces PP2A activity and reduces tau phosphorylation at PP2A-dependent epitopes in vitro and in vivo.	Metformin	110-119	microtubule associated protein tau	Homo sapiens	54-57
21098287-3	2010	Using murine primary neurons from wild-type and human tau transgenic mice, we show that the antidiabetic drug metformin induces PP2A activity and reduces tau phosphorylation at PP2A-dependent epitopes in vitro and in vivo.	Metformin	110-119	microtubule associated protein tau	Homo sapiens	154-157
21098287-5	2010	Surprisingly, metformin effects on PP2A activity and tau phosphorylation seem to be independent of AMPK activation, because in our experiments (i) metformin induces PP2A activity before and at lower levels than AMPK activity and (ii) the AMPK activator AICAR does not influence the phosphorylation of tau at the sites analyzed.	Metformin	14-23	microtubule associated protein tau	Homo sapiens	53-56
21098287-5	2010	Surprisingly, metformin effects on PP2A activity and tau phosphorylation seem to be independent of AMPK activation, because in our experiments (i) metformin induces PP2A activity before and at lower levels than AMPK activity and (ii) the AMPK activator AICAR does not influence the phosphorylation of tau at the sites analyzed.	Metformin	14-23	microtubule associated protein tau	Homo sapiens	301-304
21098287-6	2010	Affinity chromatography and immunoprecipitation experiments together with PP2A activity assays indicate that metformin interferes with the association of the catalytic subunit of PP2A (PP2Ac) to the so-called MID1-alpha4 protein complex, which regulates the degradation of PP2Ac and thereby influences PP2A activity.	Metformin	109-118	protein phosphatase 2 catalytic subunit alpha	Homo sapiens	185-190
21098287-6	2010	Affinity chromatography and immunoprecipitation experiments together with PP2A activity assays indicate that metformin interferes with the association of the catalytic subunit of PP2A (PP2Ac) to the so-called MID1-alpha4 protein complex, which regulates the degradation of PP2Ac and thereby influences PP2A activity.	Metformin	109-118	protein phosphatase 2 catalytic subunit alpha	Homo sapiens	273-278
20861072-8	2010	Treatment with the AMPK activators AICAR (2 mM) or metformin (1 mM) reduced basolateral KCNQ1 currents in apically permeabilized polarized mpkCCD(c14) cells.	Metformin	51-60	potassium voltage-gated channel, subfamily Q, member 1	Mus musculus	88-93
26064989-7	2015	The reduced level of OPN in the adipose tissue of metformin-treated animals strongly correlated with the lower expression of Ki67 and CD105 and increased caspase-3.	Metformin	50-59	secreted phosphoprotein 1	Mus musculus	21-24
26064989-8	2015	The metformin influenced also circulating levels of OPN, which is what was found with systemic and local action of metformin.	Metformin	4-13	secreted phosphoprotein 1	Mus musculus	52-55
26064989-8	2015	The metformin influenced also circulating levels of OPN, which is what was found with systemic and local action of metformin.	Metformin	115-124	secreted phosphoprotein 1	Mus musculus	52-55
26576433-2	2015	We evaluated the use of Plantago ovata husk-metformin association in diabetic rabbits by determining its effects on glucose and insulin concentrations.	Metformin	44-53	insulin	Oryctolagus cuniculus	128-135
26576433-8	2015	Insulin pharmacokinetics parameters after treatment with oral metformin showed an important increase in Cmax, AUC, and t(max) in animals fed with fiber.	Metformin	62-71	insulin	Oryctolagus cuniculus	0-7
25131770-11	2015	Metformin, an AMPK activator, more strongly suppressed cell growth in p53-mutant cell lines with inactive SIRT1 than in p53-mutant cell lines with active SIRT1.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	14-18
25131770-13	2015	Metformin could be a therapeutic drug for HCC in patients with mutated p53, inactivated SIRT1, and AMPK expression.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	99-103
26119401-3	2015	For example, metformin (an activator of AMPK) is a first-line diabetes drug that protects against cancers.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	40-44
26880912-6	2015	Results of our study revealed that pretreatment with metformin or sitagliptin produced significant (P &lt; 0.05) cardiac protection manifested by a significant decrease in serum levels of LDH and CK-MB enzymes and cardiac MDA and total nitrites and nitrates levels, a significant increase in cardiac SOD activity, and remarkable improvement in the histopathological features as well as a significant reduction in the immunohistochemical expression of COX-2, iNOS, and caspase-3 enzymes as compared to DOX group.	Metformin	53-62	cytochrome c oxidase II, mitochondrial	Rattus norvegicus	451-456
26880912-6	2015	Results of our study revealed that pretreatment with metformin or sitagliptin produced significant (P &lt; 0.05) cardiac protection manifested by a significant decrease in serum levels of LDH and CK-MB enzymes and cardiac MDA and total nitrites and nitrates levels, a significant increase in cardiac SOD activity, and remarkable improvement in the histopathological features as well as a significant reduction in the immunohistochemical expression of COX-2, iNOS, and caspase-3 enzymes as compared to DOX group.	Metformin	53-62	caspase 3	Rattus norvegicus	468-477
26688757-4	2015	In all sensitive cells, metformin decreased the Deltapsi m and it modified the expression of enzymes involved in energy metabolism: PKCepsilon (PKCepsilon) and PKCdelta (PKCdelta).	Metformin	24-33	protein kinase C delta	Homo sapiens	160-168
26688757-4	2015	In all sensitive cells, metformin decreased the Deltapsi m and it modified the expression of enzymes involved in energy metabolism: PKCepsilon (PKCepsilon) and PKCdelta (PKCdelta).	Metformin	24-33	protein kinase C delta	Homo sapiens	170-178
26688757-5	2015	In sensitive cells, metformin altered PKCepsilon and PKCdelta expression leading to a predominance of PKCepsilon over PKCdelta which implies a more glycolytic state.	Metformin	20-29	protein kinase C delta	Homo sapiens	53-61
26688757-5	2015	In sensitive cells, metformin altered PKCepsilon and PKCdelta expression leading to a predominance of PKCepsilon over PKCdelta which implies a more glycolytic state.	Metformin	20-29	protein kinase C delta	Homo sapiens	118-126
26021280-5	2015	A direct or indirect role of adenosine monophosphate (AMP)-activated protein kinase (AMPK), the fuel gauge of the cell, has been inferred in many studies, with evidence that activation of AMPK may result from a mild inhibitory effect of metformin on mitochondrial complex 1, which in turn would raise AMP and activate AMPK.	Metformin	237-246	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	85-89
26021280-5	2015	A direct or indirect role of adenosine monophosphate (AMP)-activated protein kinase (AMPK), the fuel gauge of the cell, has been inferred in many studies, with evidence that activation of AMPK may result from a mild inhibitory effect of metformin on mitochondrial complex 1, which in turn would raise AMP and activate AMPK.	Metformin	237-246	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	188-192
26021280-5	2015	A direct or indirect role of adenosine monophosphate (AMP)-activated protein kinase (AMPK), the fuel gauge of the cell, has been inferred in many studies, with evidence that activation of AMPK may result from a mild inhibitory effect of metformin on mitochondrial complex 1, which in turn would raise AMP and activate AMPK.	Metformin	237-246	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	188-192
25422142-4	2015	In fact, AMPK is a target of some pharmacological agents implemented in the treatment of diabetes (metformin and thiazolidinediones) as well as other naturally derived products, such as berberine, which is used in traditional medicine.	Metformin	99-108	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	9-13
26973866-2	2015	Intriguingly, our new studies reveal that metabolic stressors, such as metformin, inactivate HSF1 and provoke proteomic chaos, thereby impeding tumorigenesis.	Metformin	71-80	heat shock transcription factor 1	Homo sapiens	93-97
20859243-5	2010	Both the OCT inhibitor, cimetidine, and OCT3-specific short hairpin RNA significantly reduced the activating effect of metformin on AMP-activated protein kinase.	Metformin	119-128	plexin A2	Homo sapiens	9-12
20688914-8	2010	In addition, metformin or overexpression of a constitutively active form of AMPK (Ad-CA-AMPK) inhibited S171A-mediated PEPCK and G6Pase gene expression, and hepatic glucose production and knockdown of SHP partially relieved the metformin- and Ad-CA-AMPK-mediated repression of hepatic gluconeogenic enzyme gene expression in primary rat hepatocytes.	Metformin	13-22	glucose-6-phosphatase catalytic subunit 1	Rattus norvegicus	129-135
20688914-8	2010	In addition, metformin or overexpression of a constitutively active form of AMPK (Ad-CA-AMPK) inhibited S171A-mediated PEPCK and G6Pase gene expression, and hepatic glucose production and knockdown of SHP partially relieved the metformin- and Ad-CA-AMPK-mediated repression of hepatic gluconeogenic enzyme gene expression in primary rat hepatocytes.	Metformin	13-22	nuclear receptor subfamily 0, group B, member 2	Rattus norvegicus	201-204
20688914-9	2010	In conclusion, our results suggest that a delayed effect of metformin-mediated induction of SHP gene expression inhibits CREB-dependent hepatic gluconeogenesis.	Metformin	60-69	nuclear receptor subfamily 0, group B, member 2	Rattus norvegicus	92-95
20688914-9	2010	In conclusion, our results suggest that a delayed effect of metformin-mediated induction of SHP gene expression inhibits CREB-dependent hepatic gluconeogenesis.	Metformin	60-69	cAMP responsive element binding protein 1	Rattus norvegicus	121-125
21335294-6	2010	These publications described studies of DPP-4 inhibitors administered as monotherapy or in combination with metformin, a thiazolidinedione, glimepiride, glibenclamide, or insulin.	Metformin	108-117	dipeptidyl peptidase 4	Homo sapiens	40-45
21437102-7	2010	Professional organizations have updated their guidelines for T2D to include a DPP-4 inhibitor as an early treatment option-either as initial therapy in combination with metformin, or as add-on therapy for patients whose glycemia is inadequately controlled by a single oral antidiabetic drug.	Metformin	169-178	dipeptidyl peptidase 4	Homo sapiens	78-83
29699342-10	2010	Treatment with an insulin-sensitizing agent (metformin) improves the levels of glycodelin, insulin-like growth factor binding protein 1, and blood flow in spiral arteries during the peri-implantation period.	Metformin	45-54	progestagen associated endometrial protein	Homo sapiens	79-89
29699342-10	2010	Treatment with an insulin-sensitizing agent (metformin) improves the levels of glycodelin, insulin-like growth factor binding protein 1, and blood flow in spiral arteries during the peri-implantation period.	Metformin	45-54	insulin like growth factor binding protein 1	Homo sapiens	91-135
20810672-2	2010	The biguanide metformin, which is widely prescribed for the treatment of type II diabetes, might be a good candidate for lung cancer chemoprevention because it activates AMP-activated protein kinase (AMPK), which can inhibit the mTOR pathway.	Metformin	14-23	mechanistic target of rapamycin kinase	Mus musculus	229-233
20810672-6	2010	To test whether intraperitoneal administration of metformin might improve mTOR inhibition, we injected mice and assessed biomarkers in liver and lung tissues.	Metformin	50-59	mechanistic target of rapamycin kinase	Mus musculus	74-78
20810672-8	2010	In liver tissue, metformin activated AMPK and inhibited mTOR.	Metformin	17-26	mechanistic target of rapamycin kinase	Mus musculus	56-60
20810672-9	2010	In lung tissue, metformin did not activate AMPK but inhibited phosphorylation of insulin-like growth factor-I receptor/insulin receptor (IGF-1R/IR), Akt, extracellular signal-regulated kinase (ERK), and mTOR.	Metformin	16-25	mechanistic target of rapamycin kinase	Mus musculus	203-207
20810672-10	2010	This suggested that metformin indirectly inhibited mTOR in lung tissue by decreasing activation of insulin-like growth factor-I receptor/insulin receptor and Akt upstream of mTOR.	Metformin	20-29	mechanistic target of rapamycin kinase	Mus musculus	51-55
20810672-10	2010	This suggested that metformin indirectly inhibited mTOR in lung tissue by decreasing activation of insulin-like growth factor-I receptor/insulin receptor and Akt upstream of mTOR.	Metformin	20-29	mechanistic target of rapamycin kinase	Mus musculus	174-178
20810672-12	2010	Metformin decreased tumor burden by 72%, which correlated with decreased cellular proliferation and marked inhibition of mTOR in tumors.	Metformin	0-9	mechanistic target of rapamycin kinase	Mus musculus	121-125
25709223-6	2015	In addition, AMPK activation by two known activators (5-aminoimidazole-4-carboxamide-1-beta-ribofuranoside and metformin) decreased cell viability and induced apoptosis.	Metformin	111-120	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	13-17
26401715-0	2015	IL-1B rs1143623 and EEF1A1P11-RPL7P9 rs10783050 polymorphisms affect the glucose-lowing efficacy of metformin in Chinese overweight or obese Type 2 diabetes mellitus patients.	Metformin	100-109	ribosomal protein L7 pseudogene 9	Homo sapiens	30-36
26401715-7	2015	CONCLUSION: IL1B rs1143623 and EEF1A1P11-RPL7P9 rs10783050 polymorphisms may contribute to metformin"s glucose-lowing efficacy in overweight or obese Chinese T2DM patients.	Metformin	91-100	ribosomal protein L7 pseudogene 9	Homo sapiens	41-47
25734181-5	2015	Metformin, an antidiabetic drug, is effective for endometrial cancer through inhibition of the PI3K-Akt-mTOR pathway by activating LKB1-AMPK and reduction of insulin and insulin-like growth factor-1 due to AMPK activation.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	136-140
25734181-5	2015	Metformin, an antidiabetic drug, is effective for endometrial cancer through inhibition of the PI3K-Akt-mTOR pathway by activating LKB1-AMPK and reduction of insulin and insulin-like growth factor-1 due to AMPK activation.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	206-210
25249235-8	2014	RESULTS: In vitro metformin treatment led to an increase in the proliferation and number of pancreatic duodenal homeobox 1-positive (PDX1(+)) progenitors.	Metformin	18-27	pancreatic and duodenal homeobox 1	Mus musculus	133-137
25249235-10	2014	Similarly, metformin administration to pregnant dams induced an increase in both PDX1(+) and neurogenin 3-positive progenitors in the embryonic pancreas at E14.0 and these changes resulted in an increased beta cell fraction in neonates.	Metformin	11-20	pancreatic and duodenal homeobox 1	Mus musculus	81-88
25502227-8	2014	Placebo-adjusted treatment effect of dapagliflozin plus metformin vs. metformin alone for change in HbA1c from baseline was -0.65% at the average baseline FPG of 192.3 mg/dL (10.7 mmol/L).	Metformin	56-65	hemoglobin subunit alpha 1	Homo sapiens	100-104
25502227-8	2014	Placebo-adjusted treatment effect of dapagliflozin plus metformin vs. metformin alone for change in HbA1c from baseline was -0.65% at the average baseline FPG of 192.3 mg/dL (10.7 mmol/L).	Metformin	70-79	hemoglobin subunit alpha 1	Homo sapiens	100-104
23915261-8	2014	They are amplified by metformin, an AMPK stimulator, and attenuated by resistin, an AMPK inhibitor.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	36-40
20690781-4	2010	Dipeptidylpeptidase-4 (DPP-4) inhibitors are novel oral glucose-lowering agents, which may be used as monotherapy or in combination with other antidiabetic compounds, metformin, thiazolidinediones or even sulfonylureas.	Metformin	167-176	dipeptidyl peptidase 4	Homo sapiens	0-21
20690781-4	2010	Dipeptidylpeptidase-4 (DPP-4) inhibitors are novel oral glucose-lowering agents, which may be used as monotherapy or in combination with other antidiabetic compounds, metformin, thiazolidinediones or even sulfonylureas.	Metformin	167-176	dipeptidyl peptidase 4	Homo sapiens	23-28
20876838-10	2010	Based on the glucose-dependent action of incretins, DPP-4 inhibitors demonstrate a low propensity for hypoglycemia, are generally weight neutral, and have a low risk of interactions with other drugs, which makes them appropriate candidates for combination therapy, particularly with other oral antidiabetic drugs including metformin, thiazolidinediones, and sulfonylureas.	Metformin	323-332	dipeptidyl peptidase 4	Homo sapiens	52-57
19628413-10	2010	Metformin not only significantly decreased intracellular ROS and apoptosis, but also had a direct osteogenic effect on osteoblasts at all glucose concentrations, which could be partially mediated via promotion of Runx2 and IGF-1 expression.	Metformin	0-9	insulin-like growth factor 1	Rattus norvegicus	223-228
20135346-5	2010	We show that metformin (but not rapamycin) exposure leads to increased phosphorylation of IRS-1 at Ser(789), a site previously reported to inhibit downstream signaling and to be an AMPK substrate phosphorylated under conditions of cellular energy depletion.	Metformin	13-22	insulin receptor substrate 1	Homo sapiens	90-95
24903160-4	2014	Metformin enhanced basal and insulin-stimulated glucose uptake and GLUT4 translocation, reduced IRS-1 and Akt phosphorylation and ROS levels, and affected the expression of regulators of mitochondrial biogenesis in LYRM1-over-expressing adipocytes.	Metformin	0-9	solute carrier family 2 member 4	Homo sapiens	67-72
25534180-10	2014	In multivariate Cox regression, metformin usage was a predictive factor that decreased the risk for breast cancer mortality.	Metformin	32-41	cytochrome c oxidase subunit 8A	Homo sapiens	16-19
24824502-6	2014	AMPK-activating drugs reverse many of the metabolic defects associated with insulin resistance, and recent findings suggest that the insulin-sensitizing effects of the widely used antidiabetic drug metformin are mediated by AMPK.	Metformin	198-207	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-4
24824502-6	2014	AMPK-activating drugs reverse many of the metabolic defects associated with insulin resistance, and recent findings suggest that the insulin-sensitizing effects of the widely used antidiabetic drug metformin are mediated by AMPK.	Metformin	198-207	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	224-228
25951664-8	2014	Metformin improved metabolic disorders, upregulated activity of renal AMPK, diminished the expression of renal SREBP-1c, TNF-alpha, NOX4 mRNA, decreased accumulation of renal lipids, and prevened renal injury.	Metformin	0-9	NADPH oxidase 4	Mus musculus	132-136
25365944-6	2014	In tumors, the activation of Rac1 (GTP-Rac1) and Cdc42 (GTP-Cdc42) was increased while RhoA activation (GTP-RhoA) was decreased by metformin.	Metformin	131-140	Rac family small GTPase 1	Mus musculus	29-33
25127677-11	2014	These effects were markedly attenuated in K-Ras(+/LSL-G12D);Trp53(+/LSLR172H);Pdx-1-Cre mice given metformin.	Metformin	99-108	pancreatic and duodenal homeobox 1	Mus musculus	78-83
20573602-0	2010	Protective effect of metformin in CD1 mice placed on a high carbohydrate-high fat diet.	Metformin	21-30	CD1 antigen complex	Mus musculus	34-37
20566445-13	2010	Only metformin increased hepatic glycogen, and normalized glucose-6-phosphatase activity.	Metformin	5-14	glucose-6-phosphatase catalytic subunit 1	Rattus norvegicus	58-79
20038265-5	2010	Metformin also blocked the induction of ER stress proteins (GRP78, Chop, Cleaved ATF-6, p-eIF2 alpha and XBP-1) and regulated serine phosphorylation of IRS-1.	Metformin	0-9	activating transcription factor 6	Homo sapiens	81-86
20462426-1	2010	Sitagliptin is a dipeptidyl peptidase-4 (DPP IV, CD26) inhibitor indicated for treatment of Type II diabetes as a second line therapy after metformin.	Metformin	140-149	dipeptidyl peptidase 4	Homo sapiens	17-39
20462426-1	2010	Sitagliptin is a dipeptidyl peptidase-4 (DPP IV, CD26) inhibitor indicated for treatment of Type II diabetes as a second line therapy after metformin.	Metformin	140-149	dipeptidyl peptidase 4	Homo sapiens	41-47
9802752-7	1998	RESULTS: Plasminogen activator inhibitor 1 (PAI-1) activity and antigen decreased significantly but similarly by 30 and 40%, respectively, in both the placebo and the metformin groups.	Metformin	167-176	serpin family E member 1	Homo sapiens	9-42
9802752-7	1998	RESULTS: Plasminogen activator inhibitor 1 (PAI-1) activity and antigen decreased significantly but similarly by 30 and 40%, respectively, in both the placebo and the metformin groups.	Metformin	167-176	serpin family E member 1	Homo sapiens	44-49
9109854-0	1997	Metformin therapy is associated with a decrease in plasma plasminogen activator inhibitor-1, lipoprotein(a), and immunoreactive insulin levels in patients with the polycystic ovary syndrome.	Metformin	0-9	serpin family E member 1	Homo sapiens	58-91
9109854-4	1997	On metformin, absolute and percent reductions in Izero correlated with absolute and percent reductions in PAI-1 (r = .60, P = .015 and r = .64, P = .008).	Metformin	3-12	serpin family E member 1	Homo sapiens	106-111
8770923-2	1996	To study its mechanism, we examined metformin stimulation of insulin action on the Xenopus oocyte.	Metformin	36-45	insulin S homeolog	Xenopus laevis	61-68
8770923-3	1996	Similar to therapeutic concentrations, maximal stimulation of insulin-induced meiotic cell division was achieved at about 1-10 microg/ml (or 7.7-77 /microM) metformin.	Metformin	157-166	insulin S homeolog	Xenopus laevis	62-69
8770923-5	1996	With whole cells, the preincubation time for metformin stimulation of insulin action (approximately 1 h) was equivalent to the time required for metformin to maximize tyrosine phosphorylation and raise IP3, levels.	Metformin	45-54	insulin S homeolog	Xenopus laevis	70-77
8770923-8	1996	Both the chelator and heparin blocked metformin stimulation of insulin action on whole cells.	Metformin	38-47	insulin S homeolog	Xenopus laevis	63-70
8770923-9	1996	Since microinjection of IP3, also stimulates insulin action, metformin may stimulate insulin action by elevation of intracellular calcium in addition to activation of the receptor tyrosine kinase.	Metformin	61-70	insulin S homeolog	Xenopus laevis	45-52
8770923-9	1996	Since microinjection of IP3, also stimulates insulin action, metformin may stimulate insulin action by elevation of intracellular calcium in addition to activation of the receptor tyrosine kinase.	Metformin	61-70	insulin S homeolog	Xenopus laevis	85-92
8536601-5	1996	Therefore, the purpose of this study was to determine whether metformin evokes alterations in VSMC insulin and IGF-I receptors, glucose transport, and/or [Ca]i.	Metformin	62-71	insulin-like growth factor 1	Rattus norvegicus	111-116
8536601-8	1996	Metformin exposure for 24 h 1) increased basal TK activity (metformin, 3.49 +/- 0.39; control, 1.77 +/- 0.39 pmol 32P incorporated/mg protein; P &lt; 0.01) without changes in insulin-or IGF-I stimulated TK activity, 2) increased 2-deoxyglucose transport in a dose-dependent manner, 3) decreased thrombin-induced elevation in [Ca]i (metformin, 10.3%; control, 35.3% over basal; P &lt; 0.05), These insulin/IGF-I-like effects of metformin may help explain some of its vascular actions.	Metformin	0-9	insulin-like growth factor 1	Rattus norvegicus	186-191
8536601-8	1996	Metformin exposure for 24 h 1) increased basal TK activity (metformin, 3.49 +/- 0.39; control, 1.77 +/- 0.39 pmol 32P incorporated/mg protein; P &lt; 0.01) without changes in insulin-or IGF-I stimulated TK activity, 2) increased 2-deoxyglucose transport in a dose-dependent manner, 3) decreased thrombin-induced elevation in [Ca]i (metformin, 10.3%; control, 35.3% over basal; P &lt; 0.05), These insulin/IGF-I-like effects of metformin may help explain some of its vascular actions.	Metformin	0-9	insulin-like growth factor 1	Rattus norvegicus	405-410
7582542-12	1995	After acute insulin exposure the content of GLUT4 in the intracellular membrane fraction declined significantly in the metformin-treated group, while no significant effect was seen in the plasma membrane fraction.	Metformin	119-128	solute carrier family 2 member 4	Rattus norvegicus	44-49
30740845-12	2019	CONCLUSIONS & INFERENCES: Metformin may block mast cell activation to reduce PAR-2 expression and subsequently inhibit ERK activation and clau-4 phosphorylation at serine sites to normalize the interaction of clau-4 and ZO-1 and clau-4 distribution.	Metformin	26-35	F2R like trypsin receptor 1	Rattus norvegicus	77-82
30740845-12	2019	CONCLUSIONS & INFERENCES: Metformin may block mast cell activation to reduce PAR-2 expression and subsequently inhibit ERK activation and clau-4 phosphorylation at serine sites to normalize the interaction of clau-4 and ZO-1 and clau-4 distribution.	Metformin	26-35	tight junction protein 1	Rattus norvegicus	209-224
34920124-8	2022	When treated with metformin/LKB1, both SLCO1B3 expression and intracellular PTX concentration have increased.	Metformin	18-27	serine/threonine kinase 11	Homo sapiens	28-32
34510471-8	2022	The combination of metformin and dipeptidyl peptidase-4 inhibitors decreased with the hazard ratio of 0.42(95%CI:0.18-0.99), compared to metformin alone.	Metformin	137-146	dipeptidyl peptidase 4	Homo sapiens	33-55
34806449-2	2022	Previous work showed that metformin reduces cyst growth in rapid ADPKD mouse models via inhibition of CFTR-mediated fluid secretion, mTOR, and cAMP pathways.	Metformin	26-35	mechanistic target of rapamycin kinase	Mus musculus	133-137
34943889-7	2021	Moreover, metformin, a deactivator of PXR, dramatically suppressed PB-mediated induction of hepatic SLC13A5 as well as its activation of the SLC13A5 luciferase reporter activity via PXR.	Metformin	10-19	solute carrier family 13 member 5	Homo sapiens	100-107
34943889-7	2021	Moreover, metformin, a deactivator of PXR, dramatically suppressed PB-mediated induction of hepatic SLC13A5 as well as its activation of the SLC13A5 luciferase reporter activity via PXR.	Metformin	10-19	solute carrier family 13 member 5	Homo sapiens	141-148
34432352-0	2021	Pretreatment with metformin prevents microcystin-LR-induced tau hyperphosphorylation via mTOR-dependent PP2A and GSK-3beta activation.	Metformin	18-27	microtubule associated protein tau	Homo sapiens	60-63
34432352-0	2021	Pretreatment with metformin prevents microcystin-LR-induced tau hyperphosphorylation via mTOR-dependent PP2A and GSK-3beta activation.	Metformin	18-27	protein phosphatase 2 phosphatase activator	Homo sapiens	104-108
34432352-4	2021	The results showed that metformin effectively prevented tau hyperphosphorylation at Ser202 caused by MC-LR through PP2A and GSK-3b activity.	Metformin	24-33	microtubule associated protein tau	Homo sapiens	56-59
34432352-4	2021	The results showed that metformin effectively prevented tau hyperphosphorylation at Ser202 caused by MC-LR through PP2A and GSK-3b activity.	Metformin	24-33	protein phosphatase 2 phosphatase activator	Homo sapiens	115-119
34432352-5	2021	The effect of metformin on PP2A activity was dependent on the inhibition of mTOR in MC-LR-treated SH-SY5Y cells.	Metformin	14-23	protein phosphatase 2 phosphatase activator	Homo sapiens	27-31
34432352-7	2021	In sum, the results suggested that metformin can ameliorate the MC-LR-induced AD-like phenotype by preventing tau phosphorylation at Ser202, which was mainly mediated by mTOR-dependent PP2A and GSK-3beta activation.	Metformin	35-44	microtubule associated protein tau	Homo sapiens	110-113
34432352-7	2021	In sum, the results suggested that metformin can ameliorate the MC-LR-induced AD-like phenotype by preventing tau phosphorylation at Ser202, which was mainly mediated by mTOR-dependent PP2A and GSK-3beta activation.	Metformin	35-44	protein phosphatase 2 phosphatase activator	Homo sapiens	185-189
34887262-11	2021	SN-38 or metformin sensitized unresponsive tumors responding to anti-PD-1 therapy by engaging NK or CD8+ T cells to infiltrate the tumor microenvironment (TME) and secret interferon-gamma and granzyme B to kill tumors.	Metformin	9-18	granzyme B	Homo sapiens	192-202
34887262-15	2021	CONCLUSION: We show that SN-38 or metformin can boost antitumor immunity in the TME by inhibiting c-Myc and STAT3 through FOXO3 activation.	Metformin	34-43	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	98-103
34688695-8	2021	On the other hand, metformin exerted a more robust stimulatory action on the AMPKalpha that was accompanied by a notable decrease in the NF-kappaB nuclear binding activity and a decline in the p-mTOR levels.	Metformin	19-28	mechanistic target of rapamycin kinase	Mus musculus	195-199
34884312-10	2021	Metformin treatment impaired the phosphorylation of NF-kappaB induced by IL-36gamma stimulation with the subsequent downregulation of Nfkbiz, resulting in the inhibition of IL-23 production in BMDCs.	Metformin	0-9	nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, zeta	Mus musculus	134-140
34884730-5	2021	By contrast, only 4/15 substrates, i.e., acetylcholine, agmatine, choline and metformin, trans-stimulated DiASP uptake, with a full suppression of the trans-stimulating effect of metformin by the reference OCT2 inhibitor amitriptyline.	Metformin	179-188	solute carrier family 22 member 2	Homo sapiens	206-210
34837101-0	2021	Metformin inhibits human non-small cell lung cancer by regulating AMPK-CEBPB-PDL1 signaling pathway.	Metformin	0-9	CD274 molecule	Homo sapiens	77-81
34837101-4	2021	RNA transcriptome sequencing revealed that PDL1 was significantly downregulated in both cell types following treatment with metformin (P < 0.001).	Metformin	124-133	CD274 molecule	Homo sapiens	43-47
34837101-10	2021	Western blotting showed that metformin could regulate the function of NSCLC cells via AMPK-CEBPB-PDL1 signaling.	Metformin	29-38	CD274 molecule	Homo sapiens	97-101
34837101-14	2021	In conclusion, metformin inhibited the proliferation of NSCLC cells and played an anti-tumor role in an AMPK-CEBPB-PDL1 signaling-dependent manner.	Metformin	15-24	CD274 molecule	Homo sapiens	115-119
34956455-8	2021	Metformin significantly suppressed the deposition of collagen and elastic fibers in the fibrotic pleura and decreased the expression of extracellular matrix (ECM)-related genes, including Col1a1, Col3a1, Fn1, and Eln, in pleural CD90-positive myofibroblasts.	Metformin	0-9	collagen type III alpha 1 chain	Homo sapiens	196-202
34779689-0	2022	Effect of metformin intervention on circulating irisin levels in polycystic ovary syndrome: a systematic review and collaborative meta-analysis.	Metformin	10-19	fibronectin type III domain containing 5	Homo sapiens	48-54
34779689-3	2022	AIM: The aim of this meta-analysis was to compare the circulatory (serum/plasma) irisin levels before and after metformin intervention in subjects with PCOS.	Metformin	112-121	fibronectin type III domain containing 5	Homo sapiens	81-87
25127677-12	2014	Metformin prevented nicotine-induced pancreatic carcinogenesis and tumor growth by up-regulating GATA6 and promoting differentiation toward an acinar cell program.	Metformin	0-9	GATA binding protein 6	Mus musculus	97-102
25172519-0	2014	Mechanism of increase in plasma intact GLP-1 by metformin in type 2 diabetes: stimulation of GLP-1 secretion or reduction in plasma DPP-4 activity?	Metformin	48-57	glucagon like peptide 1 receptor	Homo sapiens	39-44
25172519-1	2014	Metformin was reported to increase plasma intact glucagon-like peptide-1 (GLP-1) concentrations in type 2 diabetes.	Metformin	0-9	glucagon like peptide 1 receptor	Homo sapiens	74-79
25568561-9	2014	CONCLUSION: There was a significant lowering of HbA1c, fasting blood glucose levels, postprandial glucose levels and better blood pressure control by which we have proved that GLP1 analogues in combination with basal insulin and metformin provide a good glycaemic control with a cardio protective effect, and reduce the risk of late complications.	Metformin	229-238	glucagon like peptide 1 receptor	Homo sapiens	176-180
34779689-8	2022	The results based on random effects meta-analysis indicated that irisin levels were significantly decreased after metformin intervention as compared to the baseline pretreatment levels in PCOS (SMD: -1.00, 95% CI: -1.60 to -0.41, Z: 3.29, p = .001).	Metformin	114-123	fibronectin type III domain containing 5	Homo sapiens	65-71
34779689-9	2022	The sensitivity analysis leaving-out a particular observation at a time and repeating the meta-analysis validated the robustness of the overall finding suggesting the significant effect of metformin treatment on irisin levels in PCOS.	Metformin	189-198	fibronectin type III domain containing 5	Homo sapiens	212-218
34779689-10	2022	CONCLUSION: Circulating irisin levels were significantly decreased upon metformin intervention in PCOS patients.	Metformin	72-81	fibronectin type III domain containing 5	Homo sapiens	24-30
34779689-11	2022	The higher pretreatment irisin levels in PCOS may recede once the altered metabolic state is restored upon metformin intervention.	Metformin	107-116	fibronectin type III domain containing 5	Homo sapiens	24-30
34464747-15	2021	CONCLUSION AND IMPLICATIONS: Metformin protects hepatocytes against DF-induced toxicity via cAMP-dependent EPAC-2.	Metformin	29-38	Rap guanine nucleotide exchange factor 4	Rattus norvegicus	107-113
34649197-6	2021	The selective glucose deprivation would not only disrupt tumor energy metabolism, but also upregulate the PP2A regulatory subunit B56delta and sensitize tumor cells to the metformin-induced CIP2A inhibition, leading to efficient apoptosis induction via PP2A-GSK3beta-MCL-1 axis with negligible side effects.	Metformin	172-181	protein phosphatase 2 phosphatase activator	Homo sapiens	253-257
34649197-6	2021	The selective glucose deprivation would not only disrupt tumor energy metabolism, but also upregulate the PP2A regulatory subunit B56delta and sensitize tumor cells to the metformin-induced CIP2A inhibition, leading to efficient apoptosis induction via PP2A-GSK3beta-MCL-1 axis with negligible side effects.	Metformin	172-181	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	267-272
34475030-11	2021	Comparison with diet-treated control subjects with diabetes (to eliminate confounding by hyperglycemia) continued to show raised butyrylcarnitine (C4), isovalerylcarnitine (C5), and glutarylcarnitine (C5D) in the metformin-exposed group.	Metformin	213-222	complement C5	Homo sapiens	201-204
34490702-1	2021	AIMS: To investigate the association between the use of alpha-glucosidase inhibitors (AGIs) and the risk of psoriatic disease (i.e., psoriasis and psoriatic arthritis) in patients with type 2 diabetes mellitus (T2DM) treated with metformin.	Metformin	230-239	sucrase-isomaltase	Homo sapiens	56-73
34478829-0	2021	Metformin and exenatide upregulate hepatocyte nuclear factor-4alpha, sex hormone binding globulin levels and improve hepatic triglyceride deposition in polycystic ovary syndrome with insulin resistance rats.	Metformin	0-9	hepatocyte nuclear factor 4, alpha	Rattus norvegicus	35-67
34697262-5	2021	qPCR analysis demonstrated that that pro-apoptotic genes Bax/Caspase-3 were upregulated in DM group and metformin treatment suppressed their upregulation (DMM group).	Metformin	104-113	BCL2 associated X, apoptosis regulator	Rattus norvegicus	57-60
34716862-7	2021	Our study demonstrates that combination of vemurufenib with metformin has synergistic anti-cancer effects which was evaluated through MTT assay (cytotoxicity), colony formation assay (antiproliferation evaluation) and suppressed the progression of ATC cells growth by inducing significant apoptosis, proven by Annexin V-FITC assay (Early Apoptosis Detection).	Metformin	60-69	annexin A5	Homo sapiens	310-319
34452975-4	2021	These endothelium-protective effects of metformin were absent in orphan-nuclear-receptor Nr4a1-null murine aorta tissues, in accord with our observing a direct metformin-Nr4a1 interaction.	Metformin	40-49	nuclear receptor subfamily 4, group A, member 1	Mus musculus	170-175
34452975-4	2021	These endothelium-protective effects of metformin were absent in orphan-nuclear-receptor Nr4a1-null murine aorta tissues, in accord with our observing a direct metformin-Nr4a1 interaction.	Metformin	160-169	nuclear receptor subfamily 4, group A, member 1	Mus musculus	170-175
34479029-2	2021	The anti-diabetic agent metformin (MET) and the aspirin metabolite salicylate (SAL) are shown to activate AMP-activated protein kinase (AMPK), suppress de novo lipogenesis (DNL), the mammalian target of rapamycin (mTOR) pathway and reduce PrCa proliferation in-vitro.	Metformin	24-33	SAFB like transcription modulator	Homo sapiens	35-38
34745769-6	2021	Mechanistically, metformin induced activation of the JAK1/2/3/STAT5 and AKT/mTOR pathways in a p38 MAPK-dependent manner rather than an AMPK-dependent manner.	Metformin	17-26	signal transducer and activator of transcription 5A	Homo sapiens	62-67
34769067-0	2021	Increased Post-Hypoxic Oxidative Stress and Activation of the PERK Branch of the UPR in Trap1-Deficient Drosophila melanogaster Is Abrogated by Metformin.	Metformin	144-153	Trap1	Drosophila melanogaster	88-93
34689705-5	2022	Treatment of OZ rats with metformin, an activator of AMPK that blocks JNK activity, augments ZO-2 and claudin-1 expression in the liver, reduces the paracellular permeability of hepatocytes, and serum bile acid content.	Metformin	26-35	mitogen-activated protein kinase 8	Rattus norvegicus	70-73
34745014-12	2021	In conclusion, while foetal metformin exposure did not dramatically alter gonad development, these results suggest that metabolic modification by metformin during the foetal period could change the expression of epigenetic regulators such as Tet1 and perturb the genomic DNA in germ cells, changes that might contribute to a reduced fertility.	Metformin	146-155	tet methylcytosine dioxygenase 1	Homo sapiens	242-246
34429755-0	2021	Metformin mitigates PLCepsilon gene expression and modulates the Notch1/Hes and androgen receptor signaling pathways in castration-resistant prostate cancer xenograft models.	Metformin	0-9	ribosome binding protein 1	Homo sapiens	72-75
34291435-4	2021	We delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKalpha/beta signaling that leads to phosphorylation of Ser85 of the key mediator of CMA, Hsc70, and its activation.	Metformin	47-56	conserved helix-loop-helix ubiquitous kinase	Mus musculus	86-99
34291435-7	2021	Importantly, we find that in the APP/PS1 mouse model of Alzheimer"s disease (AD), activation of CMA by Hsc70 overexpression or Metformin potently reduces the accumulated brain Abeta plaque levels and reverses the molecular and behavioral AD phenotypes.	Metformin	127-136	presenilin 1	Mus musculus	37-40
34291435-7	2021	Importantly, we find that in the APP/PS1 mouse model of Alzheimer"s disease (AD), activation of CMA by Hsc70 overexpression or Metformin potently reduces the accumulated brain Abeta plaque levels and reverses the molecular and behavioral AD phenotypes.	Metformin	127-136	amyloid beta (A4) precursor protein	Mus musculus	176-181
34291435-8	2021	Our study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKalpha/beta-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases, such as AD, where such therapeutic intervention could be beneficial.	Metformin	61-70	conserved helix-loop-helix ubiquitous kinase	Mus musculus	76-89
34680477-8	2021	Our results show that treatment with liraglutide, metformin or their combination ameliorates DKD by rectifying renal function tests and protecting against fibrosis paralleled by restored mRNA levels of nephrin, DUOX1 and 2, and reduced ROS production.	Metformin	50-59	NPHS1 adhesion molecule, nephrin	Rattus norvegicus	202-209
34564891-5	2022	Our results showed that topical application of metformin can effectively suppress the PDL-induced early stage of angiogenesis via inhibition of the AKT/mTOR/P70S6K pathway in animal models.	Metformin	47-56	ribosomal protein S6 kinase B1	Rattus norvegicus	157-163
34311050-9	2021	Compared with controls, metformin-treated APP23-ob/ob mice had significantly reduced Abeta levels in the cerebral cortex (p < .05) and hippocampus (p < .05) and increased levels of IDE in the hippocampus (p < .01).	Metformin	24-33	amyloid beta (A4) precursor protein	Mus musculus	85-90
34311050-10	2021	Our results indicate that metformin attenuates the severity of CAA by enhancing Abeta-cleaving IDE expression.	Metformin	26-35	amyloid beta (A4) precursor protein	Mus musculus	80-85
25181053-1	2014	The anti-diabetic drug metformin regulates T-cell responses to immune activation and is proposed to function by regulating the energy-stress-sensing adenosine-monophosphate-activated protein kinase (AMPK).	Metformin	23-32	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	149-197
25181053-1	2014	The anti-diabetic drug metformin regulates T-cell responses to immune activation and is proposed to function by regulating the energy-stress-sensing adenosine-monophosphate-activated protein kinase (AMPK).	Metformin	23-32	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	199-203
25181053-2	2014	However, the molecular details of how metformin controls T cell immune responses have not been studied nor is there any direct evidence that metformin acts on T cells via AMPK.	Metformin	141-150	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	171-175
24970682-12	2014	Our results demonstrated that metformin induces miR-34a to suppress the Sirt1/Pgc-1alpha/Nrf2 pathway and increases susceptibility of wild-type p53 cancer cells to oxidative stress and TRAIL-induced apoptosis.	Metformin	30-39	microRNA 34a	Homo sapiens	48-55
24973221-0	2014	Metformin suppresses lipopolysaccharide (LPS)-induced inflammatory response in murine macrophages via activating transcription factor-3 (ATF-3) induction.	Metformin	0-9	activating transcription factor 3	Mus musculus	102-135
24973221-0	2014	Metformin suppresses lipopolysaccharide (LPS)-induced inflammatory response in murine macrophages via activating transcription factor-3 (ATF-3) induction.	Metformin	0-9	activating transcription factor 3	Mus musculus	137-142
24973221-3	2014	Metformin inhibited LPS-induced production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in a concentration-dependent manner and in parallel induction of activating transcription factor-3 (ATF-3), a transcription factor and member of the cAMP-responsive element-binding protein family.	Metformin	0-9	activating transcription factor 3	Mus musculus	176-209
24973221-3	2014	Metformin inhibited LPS-induced production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in a concentration-dependent manner and in parallel induction of activating transcription factor-3 (ATF-3), a transcription factor and member of the cAMP-responsive element-binding protein family.	Metformin	0-9	activating transcription factor 3	Mus musculus	211-216
24973221-4	2014	ATF-3 knockdown abolished the inhibitory effects of metformin on LPS-induced proinflammatory cytokine production accompanied with reversal of metformin-induced suppression of mitogen-activated protein kinase (MAPK) phosphorylation.	Metformin	52-61	activating transcription factor 3	Mus musculus	0-5
24973221-4	2014	ATF-3 knockdown abolished the inhibitory effects of metformin on LPS-induced proinflammatory cytokine production accompanied with reversal of metformin-induced suppression of mitogen-activated protein kinase (MAPK) phosphorylation.	Metformin	142-151	activating transcription factor 3	Mus musculus	0-5
24973221-6	2014	ChIP-PCR analysis revealed that LPS-induced NF-kappaB enrichments on the promoters of IL-6 and TNF-alpha were replaced by ATF-3 upon metformin treatment.	Metformin	133-142	activating transcription factor 3	Mus musculus	122-127
24973221-7	2014	AMPK knockdown blunted all the effects of metformin (ATF-3 induction, proinflammatory cytokine inhibition, and MAPK inactivation), suggesting that AMPK activation by metformin is required for and precedes ATF-3 induction.	Metformin	166-175	activating transcription factor 3	Mus musculus	205-210
24973221-8	2014	Oral administration of metformin to either mice with LPS-induced endotoxemia or ob/ob mice lowered the plasma and tissue levels of TNF-alpha and IL-6 and increased ATF-3 expression in spleen and lungs.	Metformin	23-32	activating transcription factor 3	Mus musculus	164-169
24973221-9	2014	These results suggest that metformin exhibits anti-inflammatory action in macrophages at least in part via pathways involving AMPK activation and ATF-3 induction.	Metformin	27-36	activating transcription factor 3	Mus musculus	146-151
25089625-1	2014	BACKGROUND: Incretin-based therapies which include glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are recommended by several practice guidelines as second-line agents for add-on therapy to metformin in patients with type 2 diabetes (T2DM) who do not achieve glycemic control with metformin plus lifestyle interventions alone.	Metformin	238-247	glucagon like peptide 1 receptor	Homo sapiens	76-91
24627035-1	2014	OBJECTIVE: To assess the effect of metformin on gene and protein expression of insulin receptor (IR) and IGF-1 (IGF-1R) receptor in human endometrial stromal cells after stimulation with androgen and insulin.	Metformin	35-44	insulin receptor	Homo sapiens	79-95
24627035-1	2014	OBJECTIVE: To assess the effect of metformin on gene and protein expression of insulin receptor (IR) and IGF-1 (IGF-1R) receptor in human endometrial stromal cells after stimulation with androgen and insulin.	Metformin	35-44	insulin receptor	Homo sapiens	97-99
24627035-3	2014	RESULTS: IR gene expression was increased after treatment with insulin (2.9-fold change, p = 0.027) and further after metformin treatment (4.7-fold change, p &lt; 0.001), and in IGF-1R, the group treated with insulin (1.83-fold change) and metformin (1.78-fold change) showed more expression, than control group (p &lt; 0.001).	Metformin	118-127	insulin receptor	Homo sapiens	9-11
24627035-3	2014	RESULTS: IR gene expression was increased after treatment with insulin (2.9-fold change, p = 0.027) and further after metformin treatment (4.7-fold change, p &lt; 0.001), and in IGF-1R, the group treated with insulin (1.83-fold change) and metformin (1.78-fold change) showed more expression, than control group (p &lt; 0.001).	Metformin	240-249	insulin receptor	Homo sapiens	9-11
24627035-4	2014	Similarly, IR protein expression was increased after addition of metformin and insulin (249,869 +- 15,878) in relation to the other groups (p &lt; 0.001).	Metformin	65-74	insulin receptor	Homo sapiens	11-13
24627035-7	2014	CONCLUSION: Metformin in combination with insulin increased IR protein and gene expressions, while it had no influence on the protein expression of IGF-1R in endometrial stromal cells.	Metformin	12-21	insulin receptor	Homo sapiens	60-62
24496803-5	2014	Cox regression-generated hazard ratios (HRs) compared metformin use with SU use, adjusted for age, sex, smoking, obesity, and HbA1c level.	Metformin	54-63	cytochrome c oxidase subunit 8A	Homo sapiens	0-3
24874591-9	2014	Resistin, RBP-4, vaspin and visfatin were decreased by vildagliptin + metformin, but in group to group comparison, only vaspin reduction resulted statistically significant.	Metformin	70-79	nicotinamide phosphoribosyltransferase	Homo sapiens	28-36
24889636-0	2014	Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2.	Metformin	0-9	Peroxiredoxin prdx-2	Caenorhabditis elegans	71-77
24671882-5	2014	In cultured bovine granulosa cells, INSULIN, IGF1, and two insulin sensitizers-metformin and rosiglitazone-increased rarres2 mRNA expression whereas they decreased cmklr1, gpr1, and cclr2 mRNA expression.	Metformin	79-88	insulin	Bos taurus	36-43
34631714-7	2021	Importantly, we found that double treatment with nicotinamide riboside (NR) and metformin rescued mitophagy defects and mitochondrial dysfunction in POLG-mutant astrocytes.	Metformin	80-89	DNA polymerase gamma, catalytic subunit	Homo sapiens	149-153
34551672-8	2021	Hence, this study concludes that SLC29A4 M108V (rs149798710), N86H (rs151039853), and V79E (rs17854505) polymorphisms were associated with the increased risk of T2DM as well as with the increased risk towards the failure of metformin therapeutic response in T2DM patients of Pakistan.	Metformin	224-233	solute carrier family 29 member 4	Homo sapiens	33-40
34548527-3	2021	In particular, metformin treatment has been shown to reduce expression of interleukin (IL-) 1beta during long-term exposure to the pro-inflammatory stimulus lipopolysaccharide (LPS) through a reduction in reactive oxygen species (ROS), which decreases the levels of the hypoxia-inducible factor (HIF) 1-alpha, and through enhanced expression of IL-10.	Metformin	15-24	interleukin 1 alpha	Homo sapiens	74-97
34368808-11	2021	Secondary objective was to evaluate the effects of metformin on the expression of CSC markers by measuring relative mRNA levels of CD133, OCT4 and NANOG by RT-PCR and immunohistochemistry.	Metformin	51-60	POU class 5 homeobox 1	Homo sapiens	138-142
34368808-16	2021	Comparison of markers of CCSC results showed that expression of CD133, OCT4 and NANOG expression were decreased following metformin.	Metformin	122-131	POU class 5 homeobox 1	Homo sapiens	71-75
34428740-7	2021	We found significant differences in fold change of PSA levels in metformin groups in comparison with non-metformin groups.	Metformin	65-74	aminopeptidase puromycin sensitive	Homo sapiens	51-54
34428740-7	2021	We found significant differences in fold change of PSA levels in metformin groups in comparison with non-metformin groups.	Metformin	105-114	aminopeptidase puromycin sensitive	Homo sapiens	51-54
34428740-11	2021	Moreover, Metformin could enhance the tumour-suppressive effect of ADT and decrease the PSA relapse rate.	Metformin	10-19	aminopeptidase puromycin sensitive	Homo sapiens	88-91
34247911-1	2021	AIMS: This study aimed to compare cardiovascular benefits associated with the use of GLP-1RA versus SGLT2i as add-on therapies to metformin among adults with type 2 diabetes (T2D) with and without a history of cardiovascular complications, using real-world data.	Metformin	130-139	solute carrier family 5 member 2	Homo sapiens	100-105
34247911-2	2021	METHODS: Using data from the IBM  MarketScan  Commercial Claims Databases, metformin users above 18years with T2D who initiated GLP-1RA or SGLT2i were identified.	Metformin	75-84	solute carrier family 5 member 2	Homo sapiens	139-144
34531248-1	2021	BACKGROUND: Metformin (Met) is the first-line treatment for type 2 diabetes mellitus and plays an effective role in treating various diseases, such as cardiovascular disease, neurodegenerative disease, cancer, and aging.	Metformin	12-21	SAFB like transcription modulator	Homo sapiens	23-26
34233436-3	2021	Herein, we investigated the expression pattern of urinary exosome-derived microRNA (miRNA) in patients taking a combination of DPP-4 inhibitor and metformin (DPP-4 inhibitor group) and compared them with patients taking a combination of sulfonylurea and metformin (sulfonylurea group).	Metformin	147-156	dipeptidyl peptidase 4	Homo sapiens	158-163
34197898-7	2021	We demonstrated that the drug exerted its cytoprotective effects by activating nuclear factor erythroid 2-related factor 2 (Nrf2)/heme-oxygenase (HO)-1 pathway, which in turn, is dependent on AKT activation by metformin.	Metformin	210-219	heme oxygenase 1	Homo sapiens	130-151
34502314-8	2021	Moreover, metformin resulted in reduced expression of COL3A1, alphaSMA and CD68 after 14 days of reperfusion.	Metformin	10-19	collagen, type III, alpha 1	Mus musculus	54-60
34429434-5	2021	Interestingly, distinct from its reported function as an activator of AMPK in tumor cells, the type 2 diabetes drug metformin enhances the membrane dissociation of PD-L1-CD by disrupting the electrostatic interaction, thereby decreasing the cellular abundance of PD-L1.	Metformin	116-125	CD274 molecule	Homo sapiens	164-172
34429434-5	2021	Interestingly, distinct from its reported function as an activator of AMPK in tumor cells, the type 2 diabetes drug metformin enhances the membrane dissociation of PD-L1-CD by disrupting the electrostatic interaction, thereby decreasing the cellular abundance of PD-L1.	Metformin	116-125	CD274 molecule	Homo sapiens	263-268
34514098-8	2021	We concluded that anti-proliferative effects of metformin in gastric cancer may be partially caused by suppression of the Loc100506691-miR-26a-5p/miR-330-5p-CHAC1 axis.	Metformin	48-57	microRNA 330	Homo sapiens	146-153
34483906-0	2021	Metformin Alleviates Steatohepatitis in Diet-Induced Obese Mice in a SIRT1-Dependent Way.	Metformin	0-9	sirtuin 1	Mus musculus	69-74
34483906-10	2021	In summary, we demonstrated that metformin alleviates steatohepatitis in a SIRT1-dependent manner, and modulation of M1 polarization and cholesterol metabolism may be the underlying mechanism.	Metformin	33-42	sirtuin 1	Mus musculus	75-80
34381133-5	2021	Metformin markedly improved renal function and histological restoration of renal tissues, especially in the early stages of DN, with a significant increase in autophagy and a decrease in the expression of fibrotic biomarkers (fibronectin and collagen I) in renal tissue.	Metformin	0-9	fibronectin 1	Rattus norvegicus	226-237
34415985-8	2021	Treatment of lens epithelial cells with metformin reduced the level of the EMT markers  -SMA and pERK induced by TGF-beta2.	Metformin	40-49	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	97-101
34415985-9	2021	Similarly, metformin treatment reduced  -SMA expression in lens epithelial cells following extracapsular lens extraction in a mouse model.	Metformin	11-20	immunoglobulin mu binding protein 2	Mus musculus	41-44
34303707-8	2021	In addition, metformin upregulated AQP7 expression as well as inhibited activation of p38 and JNK MAPKs both in vivo and in vitro.	Metformin	13-22	mitogen-activated protein kinase 8	Rattus norvegicus	94-97
34303707-10	2021	Our findings demonstrate a new mechanism by which metformin suppresses the p38 and JNK pathways, thereby upregulating pancreatic AQP7 expression, and promoting glycerol influx into pancreatic beta-cells and subsequent insulin secretion in T2DM.	Metformin	50-59	mitogen-activated protein kinase 8	Rattus norvegicus	83-86
34164906-0	2021	lncRNA MALAT1 participates in metformin inhibiting the proliferation of breast cancer cell.	Metformin	30-39	metastasis associated lung adenocarcinoma transcript 1	Homo sapiens	7-13
34164906-5	2021	The expression of lncRNA MALAT1, HOTAIR, DICER1-AS1, LINC01121 and TUG1 was up-regulated by metformin treatment.	Metformin	92-101	metastasis associated lung adenocarcinoma transcript 1	Homo sapiens	25-31
34164906-5	2021	The expression of lncRNA MALAT1, HOTAIR, DICER1-AS1, LINC01121 and TUG1 was up-regulated by metformin treatment.	Metformin	92-101	HOX transcript antisense RNA	Homo sapiens	33-39
34164906-5	2021	The expression of lncRNA MALAT1, HOTAIR, DICER1-AS1, LINC01121 and TUG1 was up-regulated by metformin treatment.	Metformin	92-101	dicer 1, ribonuclease III	Homo sapiens	41-47
34164906-6	2021	In metformin-treated cells, MALAT1 knock-down increased the Bax/Bcl2 ratio and enhanced p21 but decreased cyclin B1 expression.	Metformin	3-12	metastasis associated lung adenocarcinoma transcript 1	Homo sapiens	28-34
34164906-6	2021	In metformin-treated cells, MALAT1 knock-down increased the Bax/Bcl2 ratio and enhanced p21 but decreased cyclin B1 expression.	Metformin	3-12	H3 histone pseudogene 16	Homo sapiens	88-91
34164906-8	2021	The reduced phosphorylation of c-Myc was further decreased in the metformin-treated cells in combination with MALAT1 knock-down than metformin treatment alone.	Metformin	66-75	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	31-36
34164906-8	2021	The reduced phosphorylation of c-Myc was further decreased in the metformin-treated cells in combination with MALAT1 knock-down than metformin treatment alone.	Metformin	133-142	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	31-36
34164906-8	2021	The reduced phosphorylation of c-Myc was further decreased in the metformin-treated cells in combination with MALAT1 knock-down than metformin treatment alone.	Metformin	133-142	metastasis associated lung adenocarcinoma transcript 1	Homo sapiens	110-116
34368369-9	2021	Conclusions: These results provided the first evidence that metformin can activate PP2A in human skeletal muscle cells derived from lean healthy insulin-sensitive participants and may help to understand metformin"s action in skeletal muscle in humans.	Metformin	60-69	protein phosphatase 2 phosphatase activator	Homo sapiens	83-87
34368369-9	2021	Conclusions: These results provided the first evidence that metformin can activate PP2A in human skeletal muscle cells derived from lean healthy insulin-sensitive participants and may help to understand metformin"s action in skeletal muscle in humans.	Metformin	203-212	protein phosphatase 2 phosphatase activator	Homo sapiens	83-87
34284806-12	2021	Metformin promoted SFRP5 and decreased leptin, IL-6 and TNFalpha secretion in PCOS women with metabolic abnormality in a time dependent manner and with improved ovulation rate and pregnancy rate.	Metformin	0-9	leptin	Homo sapiens	39-45
34299301-9	2021	Increased CYP2c gene expression and beneficial effects on CYP-derived arachidonic acid metabolites in the myocardium can also be involved in cardioprotective effect of metformin.	Metformin	168-177	cytochrome P450, subfamily 2, polypeptide 11	Rattus norvegicus	10-15
34115964-3	2021	We show that metformin inhibited NLRP3 inflammasome activation and interleukin (IL)-1beta production in cultured and alveolar macrophages along with inflammasome-independent IL-6 secretion, thus attenuating lipopolysaccharide (LPS)- and SARS-CoV-2-induced ARDS.	Metformin	13-22	interleukin 1 alpha	Homo sapiens	67-89
34102842-0	2021	mPEG2k-PCLx Polymeric Micelles Influence Pharmacokinetics and Hypoglycemic Efficacy of Metformin through Inhibition of Organic Cation Transporters in Rats.	Metformin	87-96	insulin-like growth factor 2	Mus musculus	0-5
34197485-3	2021	GWAS identified SNPs associated with metformin treatment success at a locus containing the NPAT (nuclear protein, ataxia-telangiectasia locus) and ATM (ataxia-telangiectasia mutated) genes.	Metformin	37-46	nuclear protein, coactivator of histone transcription	Homo sapiens	91-95
34335967-11	2021	Furthermore, metformin, an anti-diabetic drug, could upregulate miR-185-5p expression to suppress G6Pase, leading to hepatic gluconeogenesis inhibition.	Metformin	13-22	microRNA 185	Mus musculus	64-71
34235153-9	2021	The in vitro results showed that the combination of metformin and pemetrexed exhibited an antiproliferative effect in reducing cell viability and colony formation, the downregulation of cyclin D1 and A2 and the upregulation of CDKN1B, which are involved in the G1/S phase.	Metformin	52-61	cyclin dependent kinase inhibitor 1B	Homo sapiens	227-233
34130731-3	2021	The VERIFY study in patients with newly diagnosed T2DM (across 34 countries), assessed the normoglycemic durability (5 years), with early combination (EC) therapy approach versus the traditional stepwise approach of initiating treatment with metformin monotherapy (MET).	Metformin	242-251	SAFB like transcription modulator	Homo sapiens	265-268
34078517-2	2021	Low concentration of metformin inhibited osteoclast differentiation and downregulated the expression of TRAP, RANK, Cathepsink, NFATC-1, MMP-9 and TRAF-6.	Metformin	21-30	TNF receptor associated factor 6	Homo sapiens	147-153
34064886-7	2021	Individual contributions of transporters to metformin disposition are renal OCT2   renal MATEs > intestinal OCT3 > hepatic OCT1 > intestinal PMAT.	Metformin	44-53	solute carrier family 29 member 4	Homo sapiens	141-145
34277985-10	2021	Two proteins were significantly affected by metformin treatment, peptidoglycan recognition protein 2 (PGRP2; +23.4%, p = .0058) and alpha-2-macroglobulin (A2MG; +29.8%, p = .049).	Metformin	44-53	alpha-2-macroglobulin	Homo sapiens	132-153
34141868-6	2021	Metformin-upregulated TRAIL was secreted into conditioned medium (CM) and found to be functional, since the CM promoted TNBC cells undergoing apoptosis, which was abrogated by a recombinant TRAIL-R2-Fc chimera.	Metformin	0-9	TNF receptor superfamily member 10b	Homo sapiens	190-198
34141868-7	2021	Moreover, blockade of TRAIL binding to DR4/DR5 or specific knockdown of TRAIL expression significantly attenuated metformin-induced apoptosis.	Metformin	114-123	TNF receptor superfamily member 10b	Homo sapiens	43-46
34277866-12	2021	Results: Photobiomodulation at 1, 2, and 3 J/cm2 combined with metformin significantly promoted diabetic cell lines of HPDLSCs viability (in MTT assay and ELISA reader of ROS, TNF-alpha, IL-10 results) and gene expression of Nrf2, Keap1, PIK3, and HO-1 levels (p< 0.05).	Metformin	63-72	heme oxygenase 1	Homo sapiens	248-252
34124601-5	2021	This is the first report demonstrating that combining AMPK agonist (Metformin) and SHH pathway inhibitor (Vismodegib) confers synergy for MB treatment and provides an effective chemotherapeutic regimen that can be used to overcome resistance to Vismodegib in SHH-driven cancers.	Metformin	68-77	sonic hedgehog signaling molecule	Homo sapiens	259-262
34617056-10	2021	Metformin reduced total cholesterol and mRNA expression of SPP1 (encoding osteopontin), MMP12, and the glycoprotein genes Gpnmb and Clec7a.	Metformin	0-9	glycoprotein (transmembrane) nmb	Mus musculus	122-127
34725288-7	2021	The women, who received the course of the preventive therapy with metformin, vitamin D3 and corvitin, showed a decrease in the concentration of pro-inflammatory cytokines and an increase in anti-inflammatory cytokine IL-10, normalization of the balance between iNOS and arginase activity, and the normalization of the M1 / M2 macrophages ratio.	Metformin	66-75	inositol-3-phosphate synthase 1	Homo sapiens	261-265
35550195-8	2022	Metformin-induced inhibition of ALDH1+ cells, which are enriched with cancer stem cells, was also abrogated in 468/Met cells as compared to 468/C cells.	Metformin	0-9	aldehyde dehydrogenase 1 family member A1	Homo sapiens	32-37
35275438-6	2022	Our results suggest that metformin affects not only the PPAR signaling pathway, as well as glucose and lipid metabolism, but also protein folding, endoplasmic reticulum stress, negative regulation of appetite, and one-carbon folate metabolism in adipocytes.	Metformin	25-34	peroxisome proliferator activated receptor alpha	Homo sapiens	56-60
35568679-1	2022	BACKGROUND: The associations of metformin and statins with overall survival (OS) and prostate specific antigen response rate (PSA-RR) in trials in metastatic castration-resistant prostate cancer remain unclear.	Metformin	32-41	kallikrein related peptidase 3	Homo sapiens	85-110
35481401-0	2022	Metformin combats obesity by targeting FTO in an m6A-YTHDF2-dependent manner.	Metformin	0-9	fat mass and obesity associated	Mus musculus	39-42
35481401-4	2022	Mechanically, we revealed that metformin could inhibit protein expression of FTO, leading to increased m6A methylation levels of cyclin D1 (Ccnd1) and cyclin dependent kinase 2 (Cdk2), two crucial regulators in cell cycle.	Metformin	31-40	fat mass and obesity associated	Mus musculus	77-80
35501295-1	2022	We aimed to investigating the effects of metformin (MET) in combination with alpha lipoic acid (ALA) on hormonal and biochemical parameters, in polycystic ovary syndrome (PCOS) women undergoing intracytoplasmic sperm injection (ICSI).	Metformin	41-50	SAFB like transcription modulator	Homo sapiens	52-55
35603556-0	2022	Metformin suppresses lung adenocarcinoma by downregulating long non-coding RNA (lncRNA) AFAP1-AS1 and secreted phosphoprotein 1 (SPP1) while upregulating miR-3163.	Metformin	0-9	AFAP1 antisense RNA 1	Homo sapiens	88-97
35603556-0	2022	Metformin suppresses lung adenocarcinoma by downregulating long non-coding RNA (lncRNA) AFAP1-AS1 and secreted phosphoprotein 1 (SPP1) while upregulating miR-3163.	Metformin	0-9	secreted phosphoprotein 1	Homo sapiens	102-127
35603556-0	2022	Metformin suppresses lung adenocarcinoma by downregulating long non-coding RNA (lncRNA) AFAP1-AS1 and secreted phosphoprotein 1 (SPP1) while upregulating miR-3163.	Metformin	0-9	secreted phosphoprotein 1	Homo sapiens	129-133
35405526-11	2022	The results indicated that metformin decreased the protein levels of GOLPH3, LDHA, HK2, MCT-4 and improved p-AMPK expression.	Metformin	27-36	solute carrier family 16 member 3	Homo sapiens	88-93
35497918-5	2022	After 12 weeks of treatment, metformin plus alpha-glucosidase inhibitors were associated with significantly lower levels of 2 hPG, FPG, HbA1c, and HOMA-IR versus metformin alone (P < 0.05).	Metformin	162-171	sucrase-isomaltase	Homo sapiens	44-61
35445705-0	2022	Correction to: Metformin induces lactate accumulation and accelerates renal cyst progression in Pkd1-deficient mice.	Metformin	15-24	polycystin 1, transient receptor potential channel interacting	Mus musculus	96-100
35625692-4	2022	Flow cytometry analysis revealed that metformin combined with FuOx induced late apoptosis (p < 0.05) by mediating mitochondria-related Mcl-1 and Bim protein expression.	Metformin	38-47	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	135-140
35625692-4	2022	Flow cytometry analysis revealed that metformin combined with FuOx induced late apoptosis (p < 0.05) by mediating mitochondria-related Mcl-1 and Bim protein expression.	Metformin	38-47	BCL2 like 11	Homo sapiens	145-148
35444236-7	2022	However, different from normal CD34+ cells, the abundance and activity of OXPHOS protein were both unexpectedly elevated with endoplasmic reticulum stress induced by metformin in CML CD34+ cells.	Metformin	166-175	CD34 antigen	Mus musculus	183-187
35444236-8	2022	The four major aberrantly expressed protein sets, in contrast, were downregulated by metformin in CML CD34+ cells.	Metformin	85-94	CD34 antigen	Mus musculus	102-106
35427214-8	2022	The FCM detection displayed that metformin induced apoptosis in H929, RPMI8226 and MM.1s cells, while for U266 cells, it induced necrosis with Annexin V-/Propidium iodide+.	Metformin	33-42	annexin A5	Homo sapiens	143-152
35427214-10	2022	Western blotting analyses demonstrated that the apoptosis-related protein of cleaved caspase 3 was activated; the expressions of Mcl-1, IGF-1R, PI3K, pAKT, and pmTOR proteins were inhibited by metformin in H929, RPMI8226, and MM.1s cells.	Metformin	193-202	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	129-134
35427214-11	2022	The necrosis-related protein of iNOS increased in U266 cells while metformin treated.	Metformin	67-76	inositol-3-phosphate synthase 1	Homo sapiens	32-36
35449816-9	2022	TSJ or metformin markedly upregulated the level of nephrin and podocin, accompanied by evident enhancement of podocyte autophagy and activation of p-AMPK/p-ULK1 signaling in the diabetic nephropathy.	Metformin	7-16	NPHS1 adhesion molecule, nephrin	Rattus norvegicus	51-58
35396719-5	2022	Treating diabetic rats with metformin and forskolin resulted in significant improvement in sperm quality parameters, increased testosterone levels, reduced oxidative stress in blood and testicular tissue, and decreased blood sugar, and Bax to Bcl-2 ratio level.	Metformin	28-37	BCL2 associated X, apoptosis regulator	Rattus norvegicus	236-239
35388027-2	2022	Metformin hydrochloride (MET) is a highly soluble oral antidiabetic drug of small size and high cationic charge.	Metformin	0-23	SAFB like transcription modulator	Homo sapiens	25-28
35379885-0	2022	Metformin Ameliorates Hepatic Steatosis induced by olanzapine through inhibiting LXRalpha/PCSK9 pathway.	Metformin	0-9	proprotein convertase subtilisin/kexin type 9	Mus musculus	90-95
35379885-3	2022	Proprotein convertase subtilisin kexin type 9 (PCSK9) is involved in NAFLD pathogenesis, and metformin can significantly decrease circulating PCSK9.	Metformin	93-102	proprotein convertase subtilisin/kexin type 9	Mus musculus	0-45
35379885-3	2022	Proprotein convertase subtilisin kexin type 9 (PCSK9) is involved in NAFLD pathogenesis, and metformin can significantly decrease circulating PCSK9.	Metformin	93-102	proprotein convertase subtilisin/kexin type 9	Mus musculus	47-52
35379885-3	2022	Proprotein convertase subtilisin kexin type 9 (PCSK9) is involved in NAFLD pathogenesis, and metformin can significantly decrease circulating PCSK9.	Metformin	93-102	proprotein convertase subtilisin/kexin type 9	Mus musculus	142-147
35379885-9	2022	Hepatic lipogenesis-associated genes FAS and SCD1 were significantly upregulated in olanzapine-induced NAFLD mice and HepG2 cells overexpressing PCSK9, and genes related to lipid beta-oxidation (SCAD and PPARalpha) were downregulated, while metformin reversed these changes.	Metformin	241-250	proprotein convertase subtilisin/kexin type 9	Homo sapiens	145-150
35503619-4	2022	Metformin (Met) is one of the most common drugs affecting the most relevant genes involved in PCOS development but with unwanted side effects.	Metformin	0-9	SAFB like transcription modulator	Homo sapiens	11-14
35183887-0	2022	Tamsulosin alters the pharmacokinetics of metformin via inhibition of renal multidrug and toxin extrusion protein 1 and organic cation transporter 2 in rats.	Metformin	42-51	solute carrier family 22 member 2	Rattus norvegicus	120-148
35183887-11	2022	Altogether, our data suggest that tamsulosin could increase systemic exposure and reduce excretion of metformin via inhibiting Oct2 and Mate1-mediated transport cooperatively.	Metformin	102-111	solute carrier family 22 member 2	Homo sapiens	127-131
35414608-12	2022	In addition, metformin alleviated the necroptosis of HK-2 cells stimulated by LPS and TNF-alpha, evidencing by a decrease in the expression of necroptosis markers p-RIPK1, p-RIPK3 and p-MLKL, and the inflammasome-related markers NLRP3 (NLR family pyrin domain containing 3), ASC (apoptosis-associated speck-like protein containing a CARD), caspase-1.	Metformin	13-22	NLR family, pyrin domain containing 3	Mus musculus	229-234
35414608-12	2022	In addition, metformin alleviated the necroptosis of HK-2 cells stimulated by LPS and TNF-alpha, evidencing by a decrease in the expression of necroptosis markers p-RIPK1, p-RIPK3 and p-MLKL, and the inflammasome-related markers NLRP3 (NLR family pyrin domain containing 3), ASC (apoptosis-associated speck-like protein containing a CARD), caspase-1.	Metformin	13-22	NLR family, pyrin domain containing 3	Mus musculus	236-272
35077762-10	2022	Metformin may work through mechanisms involving homeostasis of glucose metabolism, decrease of amyloid plaque deposition, normalization of tau protein phosphorylation and enhancement of autophagy.	Metformin	0-9	microtubule associated protein tau	Homo sapiens	139-142
35115253-9	2022	Metformin-dipeptidyl peptidase-4 inhibitor (e.g., metformin-sitagliptin) combination was the most popular metformin-based single pill drug combination.	Metformin	50-59	dipeptidyl peptidase 4	Homo sapiens	10-32
35387349-0	2022	Metformin Promotes Differentiation and Attenuates H2O2-Induced Oxidative Damage of Osteoblasts via the PI3K/AKT/Nrf2/HO-1 Pathway.	Metformin	0-9	heme oxygenase 1	Homo sapiens	117-121
35387349-9	2022	Antioxidative Nrf2/HO-1 pathway, regarded as the downstream of PI3K/AKT pathway, was modulated by metformin in the protective process.	Metformin	98-107	heme oxygenase 1	Homo sapiens	19-23
35387349-11	2022	In conclusion, our study revealed that metformin promoted osteogenic differentiation and H2O2-induced oxidative damage of osteoblasts via the PI3K/AKT/Nrf2/HO-1 pathway.	Metformin	39-48	heme oxygenase 1	Homo sapiens	156-160
35426808-12	2022	CONCLUSION: pGL3-NFATc2-promoter can be transcribed and activated in 293F cells, and LPS and metformin can activate the transcription of pGL3- NFATc2-promoter in a RUNX2-dependent manner.	Metformin	93-102	nuclear factor of activated T cells 2	Homo sapiens	17-23
35426808-12	2022	CONCLUSION: pGL3-NFATc2-promoter can be transcribed and activated in 293F cells, and LPS and metformin can activate the transcription of pGL3- NFATc2-promoter in a RUNX2-dependent manner.	Metformin	93-102	nuclear factor of activated T cells 2	Homo sapiens	143-149
35328696-7	2022	Proteomics was used to construct protein profiles in neural differentiation, and the results showed that chitosan hydrogels containing metformin promoted the upregulation of neural regeneration-related proteins, including ATP5F1, ATP5J, NADH dehydrogenase (ubiquinone) Fe-S protein 3 (NDUFS3), and Glutamate Dehydrogenase 1 (GLUD1).	Metformin	135-144	NADH:ubiquinone oxidoreductase core subunit S3	Homo sapiens	285-291
35328696-7	2022	Proteomics was used to construct protein profiles in neural differentiation, and the results showed that chitosan hydrogels containing metformin promoted the upregulation of neural regeneration-related proteins, including ATP5F1, ATP5J, NADH dehydrogenase (ubiquinone) Fe-S protein 3 (NDUFS3), and Glutamate Dehydrogenase 1 (GLUD1).	Metformin	135-144	glutamate dehydrogenase 1	Homo sapiens	298-323
35328696-7	2022	Proteomics was used to construct protein profiles in neural differentiation, and the results showed that chitosan hydrogels containing metformin promoted the upregulation of neural regeneration-related proteins, including ATP5F1, ATP5J, NADH dehydrogenase (ubiquinone) Fe-S protein 3 (NDUFS3), and Glutamate Dehydrogenase 1 (GLUD1).	Metformin	135-144	glutamate dehydrogenase 1	Homo sapiens	325-330
35241643-6	2022	Additionally, miR-146a overexpression weakened the metformin-mediated upregulation of NAMPT expression, NAD+ synthesis, SIRT activity, and senescence protection, whereas treatment with the miR-146a inhibitor reversed this effect.	Metformin	51-60	microRNA 146a	Homo sapiens	14-22
35241643-6	2022	Additionally, miR-146a overexpression weakened the metformin-mediated upregulation of NAMPT expression, NAD+ synthesis, SIRT activity, and senescence protection, whereas treatment with the miR-146a inhibitor reversed this effect.	Metformin	51-60	microRNA 146a	Homo sapiens	189-197
35241643-9	2022	AMPK activators metformin and 5-aminoimidazole-4-carboxamide (AICAR) hindered miR-146a expression at the transcriptional level by promoting IkappaB kinase (IKK) phosphorylation to attenuate nuclear factor-kappaB (NF-kappaB) activity.	Metformin	16-25	microRNA 146a	Homo sapiens	78-86
35134385-4	2022	Metformin is a biguanide and the most commonly prescribed medication for type 2 diabetes Due to its pleiotropic properties, metformin"s potential disease-modifying effects are widely studied on different pathophysiological plyers of AD such as amyloid-beta (Abeta) production and clearance, tau phosphorylation, and neuroinflammation, in relevant in vitro and in vivo models.	Metformin	0-9	microtubule associated protein tau	Homo sapiens	291-294
35134385-4	2022	Metformin is a biguanide and the most commonly prescribed medication for type 2 diabetes Due to its pleiotropic properties, metformin"s potential disease-modifying effects are widely studied on different pathophysiological plyers of AD such as amyloid-beta (Abeta) production and clearance, tau phosphorylation, and neuroinflammation, in relevant in vitro and in vivo models.	Metformin	124-133	microtubule associated protein tau	Homo sapiens	291-294
35147740-5	2022	The validated model was used to simulate DDIs of dasatinib and known substrates for OCT2 and MATEs (metformin) and OATP1B1/1B3 (pravastatin and rosuvastatin).	Metformin	100-109	solute carrier family 22 member 2	Homo sapiens	84-88
35147740-7	2022	Sensitivity analysis showed metformin exposure increased < 30% in both AUC and Cmax when dasatinib Ki was reduced by tenfold for OCT2 and MATEs simultaneously, and < 40% with a 20-fold Ki reduction.	Metformin	28-37	solute carrier family 22 member 2	Homo sapiens	129-133
35222699-0	2022	Metformin reduces chondrocyte pyroptosis in an osteoarthritis mouse model by inhibiting NLRP3 inflammasome activation.	Metformin	0-9	NLR family, pyrin domain containing 3	Mus musculus	88-93
35222699-11	2022	Regarding the mechanism, in cartilage, metformin increased the expression of Col II and decreased the expression of MMP-13, NLRP3, caspase-1, GSDMD and IL-1beta.	Metformin	39-48	NLR family, pyrin domain containing 3	Mus musculus	124-129
35222699-11	2022	Regarding the mechanism, in cartilage, metformin increased the expression of Col II and decreased the expression of MMP-13, NLRP3, caspase-1, GSDMD and IL-1beta.	Metformin	39-48	interleukin 1 alpha	Mus musculus	152-160
35222699-13	2022	Overall, metformin inhibited the activation of NLRP3 inflammasome, decreased cartilage degradation, reversed subchondral bone remodelling and inhibited chondrocyte pyroptosis.	Metformin	9-18	NLR family, pyrin domain containing 3	Mus musculus	47-52
35114355-4	2022	We further showed that metformin enhanced expression of lgg-1, daf-16, skn-1 and other genes known to regulate autophagy, longevity and oxidative stress in hSOD1 transgenic worms.	Metformin	23-32	Fork-head domain-containing protein;Forkhead box protein O	Caenorhabditis elegans	63-69
35114355-4	2022	We further showed that metformin enhanced expression of lgg-1, daf-16, skn-1 and other genes known to regulate autophagy, longevity and oxidative stress in hSOD1 transgenic worms.	Metformin	23-32	BZIP domain-containing protein;Protein skinhead-1	Caenorhabditis elegans	71-76
35114355-5	2022	Accordingly, overexpression of lgg-1 or daf-16 attenuated the aging and pathological abnormalities of mutant human SOD1 worms, while genetic deletion of lgg-1 or daf-16 abolished the beneficial effects of metformin.	Metformin	205-214	Fork-head domain-containing protein;Forkhead box protein O	Caenorhabditis elegans	162-168
35114355-6	2022	Collectively, we demonstrate that metformin protects against mutant SOD1-induced cytotoxicity in part through enhancement of autophagy and extends lifespan through daf-16 pathway.	Metformin	34-43	Fork-head domain-containing protein;Forkhead box protein O	Caenorhabditis elegans	164-170
35121287-10	2022	PAI-1 expression can be decreased by physical exercise and medical treatments, including metformin.	Metformin	89-98	serpin family E member 1	Homo sapiens	0-5
35217236-7	2022	The serum and the FF levels of leptin also decreased significantly in the sitaformin group when compared to the metformin and sitagliptin groups.	Metformin	112-121	leptin	Homo sapiens	31-37
35203060-0	2022	Metformin alleviates chronic obstructive pulmonary disease and cigarette smoke extract-induced glucocorticoid resistance by activating the nuclear factor E2-related factor 2/heme oxygenase-1 signaling pathway.	Metformin	0-9	heme oxygenase 1	Homo sapiens	174-190
35203060-3	2022	As a classic hypoglycemic drug, metformin (MET) can be used as a treatment strategy for COPD due to its anti-inflammatory and antioxidant effects, but its specific mechanism of action is not known.	Metformin	32-41	SAFB like transcription modulator	Homo sapiens	43-46
35348721-4	2022	OBJECTIVE: Three simple, accurate, and sensitive methods have been developed and validated for the determination of canagliflozin (CANA); one is a stability-indicating method for CANA and metformin (MET) determination.	Metformin	188-197	SAFB like transcription modulator	Homo sapiens	199-202
35217990-0	2022	Genome-wide CRISPR screen identifies synthetic lethality between DOCK1 inhibition and metformin in liver cancer.	Metformin	86-95	dedicator of cytokinesis 1	Homo sapiens	65-70
35217990-4	2022	Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC.	Metformin	125-134	dedicator of cytokinesis 1	Homo sapiens	76-81
35217990-4	2022	Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC.	Metformin	182-191	dedicator of cytokinesis 1	Homo sapiens	144-149
35217990-5	2022	Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance.	Metformin	17-26	dedicator of cytokinesis 1	Homo sapiens	36-41
35217990-5	2022	Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance.	Metformin	120-129	dedicator of cytokinesis 1	Homo sapiens	36-41
35217990-6	2022	The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models.	Metformin	73-82	dedicator of cytokinesis 1	Homo sapiens	4-9
35217990-7	2022	Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression.	Metformin	9-18	dedicator of cytokinesis 1	Homo sapiens	70-75
35217990-8	2022	This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.	Metformin	22-31	dedicator of cytokinesis 1	Homo sapiens	57-62
35217990-8	2022	This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.	Metformin	22-31	dedicator of cytokinesis 1	Homo sapiens	104-109
35217990-8	2022	This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.	Metformin	89-98	dedicator of cytokinesis 1	Homo sapiens	57-62
35217990-8	2022	This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.	Metformin	183-192	dedicator of cytokinesis 1	Homo sapiens	104-109
35200139-8	2022	Metformin reduced TNFalpha+ wound macrophages, made intracellular redox state more reduced and improved tissue repair.	Metformin	0-9	tumor necrosis factor a (TNF superfamily, member 2)	Danio rerio	18-26
35196199-8	2022	Treatment of APOE-mice with metformin or trehalose ameliorated the loss of retinal function and reduced Bruch"s membrane thickening, enhancing LC3 and LAMP1 labeling in the ocular tissues and restoring LC3-II:LC3-I ratio to WT levels.	Metformin	28-37	microtubule-associated protein 1 light chain 3 alpha	Mus musculus	143-146
35196199-8	2022	Treatment of APOE-mice with metformin or trehalose ameliorated the loss of retinal function and reduced Bruch"s membrane thickening, enhancing LC3 and LAMP1 labeling in the ocular tissues and restoring LC3-II:LC3-I ratio to WT levels.	Metformin	28-37	microtubule-associated protein 1 light chain 3 alpha	Mus musculus	202-205
35196199-8	2022	Treatment of APOE-mice with metformin or trehalose ameliorated the loss of retinal function and reduced Bruch"s membrane thickening, enhancing LC3 and LAMP1 labeling in the ocular tissues and restoring LC3-II:LC3-I ratio to WT levels.	Metformin	28-37	microtubule-associated protein 1 light chain 3 alpha	Mus musculus	209-212
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	eukaryotic translation initiation factor 4E binding protein 1	Homo sapiens	926-934
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	eukaryotic translation initiation factor 4E binding protein 1	Homo sapiens	951-1012
35281267-0	2022	Metformin Combining PD-1 Inhibitor Enhanced Anti-Tumor Efficacy in STK11 Mutant Lung Cancer Through AXIN-1-Dependent Inhibition of STING Ubiquitination.	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	67-72
35281267-2	2022	The glucose-lowering drug metformin exerted anti-cancer effect and enhanced efficacy of chemotherapy in NSCLC with KRAS/STK11 co-mutation, yet it is unknown whether metformin may enhance ICI efficacy in STK11 mutant NSCLC.	Metformin	26-35	serine/threonine kinase 11	Homo sapiens	120-125
35281267-13	2022	Conclusion: Metformin combining PD-1 inhibitor enhanced anti-tumor efficacy in STK11 mutant lung cancer through inhibition of RNF5-mediated K48-linked ubiquitination of STING, which was dependent on AXIN-1.	Metformin	12-21	serine/threonine kinase 11	Homo sapiens	79-84
35007850-0	2022	Metformin and MiR-365 synergistically promote the apoptosis of gastric cancer cells via MiR-365-PTEN-AMPK axis.	Metformin	0-9	phosphatase and tensin homolog	Homo sapiens	96-100
35007850-5	2022	Furthermore, Metformin and miR-365 synergistically promote the apoptosis of gastric cancer cells by miR-365-PTEN-AMPK axis.	Metformin	13-22	phosphatase and tensin homolog	Homo sapiens	108-112
34545025-0	2022	Association of SLC22A1 rs622342 and ATM rs11212617 polymorphisms with metformin efficacy in patients with type 2 diabetes.	Metformin	70-79	ATM serine/threonine kinase	Homo sapiens	36-39
34545025-2	2022	There are controversies about the association of SLC22A1 rs622342, which was not reported in the Chinese population, and ataxia-telangiectasia mutated (ATM) rs11212617 polymorphisms with metformin efficacy in T2DM.	Metformin	187-196	ATM serine/threonine kinase	Homo sapiens	121-150
34545025-2	2022	There are controversies about the association of SLC22A1 rs622342, which was not reported in the Chinese population, and ataxia-telangiectasia mutated (ATM) rs11212617 polymorphisms with metformin efficacy in T2DM.	Metformin	187-196	ATM serine/threonine kinase	Homo sapiens	152-155
34545025-9	2022	Our results indicated that common variants of SLC22A1 rs622342 and ATM rs11212617 were associated with the efficacy of metformin in T2DM of Han nationality in Chaoshan China.	Metformin	119-128	ATM serine/threonine kinase	Homo sapiens	67-70
35153733-5	2021	Previous mechanistic studies have gradually unveiled the effects of metformin on AD pathology and pathophysiology, including neuronal loss, neural dysfunction, amyloid-beta (Abeta) depositions, tau phosphorylation, chronic neuroinflammation, insulin resistance, impaired glucose metabolism and mitochondrial dysfunction.	Metformin	68-77	microtubule associated protein tau	Homo sapiens	194-197
35163393-7	2022	Dividing these values into the different Jmax values for transport of MPP, metformin, and atenolol mediated by MATE1 and OCT2 resulted in calculated TOR values (+-SE, n = 4) of 84.0 +- 22.0 s-1 and 2.9 +- 0.6 s-1; metformin, 461.0 +- 121.0 s-1 and 12.6 +- 2.4 s-1; atenolol, 118.0 +- 31.0 s-1, respectively.	Metformin	75-84	solute carrier family 22 member 2	Homo sapiens	121-125
35163393-7	2022	Dividing these values into the different Jmax values for transport of MPP, metformin, and atenolol mediated by MATE1 and OCT2 resulted in calculated TOR values (+-SE, n = 4) of 84.0 +- 22.0 s-1 and 2.9 +- 0.6 s-1; metformin, 461.0 +- 121.0 s-1 and 12.6 +- 2.4 s-1; atenolol, 118.0 +- 31.0 s-1, respectively.	Metformin	214-223	solute carrier family 22 member 2	Homo sapiens	121-125
35079096-4	2022	We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1).	Metformin	18-27	killer cell lectin like receptor C1	Homo sapiens	87-93
35079115-12	2022	Metformin monotherapy reduced PD-1+ NK cells, and increased NKG2D+ NK cells.	Metformin	0-9	killer cell lectin like receptor K1	Sus scrofa	60-65
35103058-9	2022	Metformin decreased ATF6 content vs. T2DM.	Metformin	0-9	activating transcription factor 6	Rattus norvegicus	20-24
35103058-12	2022	The Iba1 level was upregulated in T2DM (5.44-fold) and metformin groups (6.88-fold).	Metformin	55-64	allograft inflammatory factor 1	Rattus norvegicus	4-8
35103058-13	2022	Despite PA treatment leading to a further 8.9-fold Iba1 elevation, PA+metformin caused the Iba1 decline vs. metformin and PA treatment.	Metformin	70-79	allograft inflammatory factor 1	Rattus norvegicus	51-55
35103058-13	2022	Despite PA treatment leading to a further 8.9-fold Iba1 elevation, PA+metformin caused the Iba1 decline vs. metformin and PA treatment.	Metformin	70-79	allograft inflammatory factor 1	Rattus norvegicus	91-95
35103058-15	2022	PA+metformin administration diminished GFAP vs. PA. T2DM-induced changes were associated with dramatically decreased ZO-1 levels, while PA treatment increased it almost to control values.	Metformin	3-12	tight junction protein 1	Rattus norvegicus	117-121
35013152-4	2022	This study aimed to assess the underlying mechanism of the formation of ARC and investigate the potential anti-ageing effect of metformin (MET) on ARC.	Metformin	128-137	SAFB like transcription modulator	Homo sapiens	139-142
35013155-8	2022	PGC-1alpha induction with the plasmid and metformin improved mitochondrial dynamics and morphology and attenuated the NLRP3 inflammasome and cell injury.	Metformin	42-51	NLR family, pyrin domain containing 3	Mus musculus	118-123
35134807-7	2022	RESULTS: Metformin upregulated mRNA expression of the many genes, including HSPA6, a cancer immune related gene, and inhibited mRNA expression of the other many genes.	Metformin	9-18	heat shock protein family A (Hsp70) member 6	Homo sapiens	76-81
35596630-13	2022	An improvement in glycemic control was established in patients with type 2 DM among carriers of the T allele rs7903146 of the TCF7L2 gene during metformin therapy in combination with a low-calorie standard diet.	Metformin	145-154	transcription factor 7 like 2	Homo sapiens	126-132
35059248-10	2022	Adding DPP-4-inhibitor to the lower dose of metformin is an alternative approach to the stable GV in MDI compared to additional high-dose metformin.	Metformin	44-53	dipeptidyl peptidase 4	Homo sapiens	7-12
35178358-0	2021	Metformin is a Novel Suppressor for Vimentin in Human Gastric Cancer Cell Line.	Metformin	0-9	vimentin	Homo sapiens	36-44
35178358-3	2021	In this study, AGS gastric cancer cells were treated with metformin and vimentin-specific siRNA (vim-siRNA) for 48 h. The impact of metformin and vim-siRNA on vimentin downregulation in AGS cells were analyzed by quantitative PCR and Western blot.	Metformin	58-67	vimentin	Homo sapiens	159-167
35178358-3	2021	In this study, AGS gastric cancer cells were treated with metformin and vimentin-specific siRNA (vim-siRNA) for 48 h. The impact of metformin and vim-siRNA on vimentin downregulation in AGS cells were analyzed by quantitative PCR and Western blot.	Metformin	132-141	vimentin	Homo sapiens	159-167
35178358-5	2021	The results showed that inhibition of vimentin due to metformin was comparable with the vim-siRNA.	Metformin	54-63	vimentin	Homo sapiens	38-46
35178358-7	2021	Our finding for the first time indicated that metformin can be an alternative to specific siRNA for inhibition of vimentin expression and migration of AGS cell line.	Metformin	46-55	vimentin	Homo sapiens	114-122
35316895-0	2022	The UCA1 and microRNA-18a signaling pathway mediates the irisin-lowering effect of metformin in the management of polycystic ovary syndrome.	Metformin	83-92	microRNA 18a	Homo sapiens	13-25
35316895-0	2022	The UCA1 and microRNA-18a signaling pathway mediates the irisin-lowering effect of metformin in the management of polycystic ovary syndrome.	Metformin	83-92	fibronectin type III domain containing 5	Homo sapiens	57-63
1179037-1	1975	Phenformin and metformin have a stimulating effect on lipolysis as determined by the action of mouse pancreas lipase on the dilauric (dido-decanoic) acid ester of fluorescein.	Metformin	15-24	lipase, endothelial	Mus musculus	110-116
33850550-8	2021	Furthermore, metformin treatment significantly inhibited the generation of inflammatory cytokines, including TNF-alpha and IL-1beta in db/db mice.	Metformin	13-22	interleukin 1 alpha	Mus musculus	123-131
33850553-0	2021	Metformin prevents PFKFB3-related aerobic glycolysis from enhancing collagen synthesis in lung fibroblasts by regulating AMPK/mTOR pathway.	Metformin	0-9	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3	Homo sapiens	19-25
33850553-10	2021	Furthermore, the aerobic glycolysis mediated by PFKFB3 and collagen synthesis in LPS-treated MRC-5 cells was gradually inhibited with increasing concentrations of metformin.	Metformin	163-172	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3	Homo sapiens	48-54
33850553-11	2021	However, this inhibitory role of metformin on PFKFB3-meditaed aerobic glycolysis and collagen synthesis was prevented by treatments with 3BDO and compound C, which are specific mTOR activator and AMPK inhibitor, respectively.	Metformin	33-42	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3	Homo sapiens	46-52
33850553-12	2021	Taken together, the findings from this study suggested that metformin may prevent PFKFB3-associated aerobic glycolysis from enhancing collagen synthesis in lung fibroblasts via regulating the AMPK/mTOR pathway.	Metformin	60-69	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3	Homo sapiens	82-88
34057870-5	2021	Metformin also declines the adherence of Sars-cov2 to DPP4 (the other receptor of the virus) on T cells.	Metformin	0-9	dipeptidyl peptidase 4	Homo sapiens	54-58
34004440-0	2021	Metformin prevents BAFF activation of Erk1/2 from B-cell proliferation and survival by impeding mTOR-PTEN/Akt signaling pathway.	Metformin	0-9	phosphatase and tensin homolog	Homo sapiens	101-105
34004440-5	2021	Pretreatment with U0126, knockdown of Erk1/2, or expression of dominant negative MKK1 strengthened metformin"s inhibition of hsBAFF-activated Erk1/2 and B-cell proliferation/viability, whereas expression of constitutively active MKK1 rendered high resistance to metformin.	Metformin	99-108	mitogen-activated protein kinase kinase 1	Homo sapiens	81-85
34004440-5	2021	Pretreatment with U0126, knockdown of Erk1/2, or expression of dominant negative MKK1 strengthened metformin"s inhibition of hsBAFF-activated Erk1/2 and B-cell proliferation/viability, whereas expression of constitutively active MKK1 rendered high resistance to metformin.	Metformin	99-108	mitogen-activated protein kinase kinase 1	Homo sapiens	229-233
34004440-5	2021	Pretreatment with U0126, knockdown of Erk1/2, or expression of dominant negative MKK1 strengthened metformin"s inhibition of hsBAFF-activated Erk1/2 and B-cell proliferation/viability, whereas expression of constitutively active MKK1 rendered high resistance to metformin.	Metformin	262-271	mitogen-activated protein kinase kinase 1	Homo sapiens	81-85
34004440-6	2021	Further investigation found that overexpression of wild type PTEN or ectopic expression of dominant negative Akt potentiated metformin"s suppression of hsBAFF-induced Erk1/2 activation and proliferation/viability in Raji cells, implying a PTEN/Akt-dependent mechanism involved.	Metformin	125-134	phosphatase and tensin homolog	Homo sapiens	61-65
34004440-6	2021	Further investigation found that overexpression of wild type PTEN or ectopic expression of dominant negative Akt potentiated metformin"s suppression of hsBAFF-induced Erk1/2 activation and proliferation/viability in Raji cells, implying a PTEN/Akt-dependent mechanism involved.	Metformin	125-134	phosphatase and tensin homolog	Homo sapiens	239-243
34004440-8	2021	Inhibition of mTOR with rapamycin or knockdown of mTOR enhanced metformin"s suppression of hsBAFF-induced phosphorylation of S6K1, PTEN, Akt, and Erk1/2, as well as B-cell proliferation/viability.	Metformin	64-73	ribosomal protein S6 kinase B1	Homo sapiens	125-129
34004440-8	2021	Inhibition of mTOR with rapamycin or knockdown of mTOR enhanced metformin"s suppression of hsBAFF-induced phosphorylation of S6K1, PTEN, Akt, and Erk1/2, as well as B-cell proliferation/viability.	Metformin	64-73	phosphatase and tensin homolog	Homo sapiens	131-135
34004440-9	2021	These results indicate that metformin prevents BAFF activation of Erk1/2 from cell proliferation and survival by impeding mTOR-PTEN/Akt signaling pathway in normal and neoplastic B-lymphoid cells.	Metformin	28-37	phosphatase and tensin homolog	Homo sapiens	127-131
33982074-10	2021	Along with the upregulation of phosphorylated AMPKalpha and ACCalpha, metformin at 1.5 and 3 mM inactivated NF-kappaB signalling components (p65 and IkappaBalpha) and the inflammatory genes (TNFA, IL6, IL1B and COX-2) which were activated by BHBA.	Metformin	70-79	acetyl-CoA carboxylase alpha	Bos taurus	60-68
33947424-0	2021	Metformin ameliorates scleroderma via inhibiting Th17 cells and reducing mTOR-STAT3 signaling in skin fibroblasts.	Metformin	0-9	mechanistic target of rapamycin kinase	Mus musculus	73-77
33947424-9	2021	These results suggest that metformin treatment has anti-inflammatory effects on lymphocytes via the inhibition of IL-17 and cytokines related to Th17 differentiation, such as IL-1beta, IL-6, and TNF-alpha.	Metformin	27-36	interleukin 1 alpha	Mus musculus	175-183
33947424-10	2021	To investigate how metformin modulates the inflammatory process in skin fibroblasts, we measured mTOR-STAT3 signaling in skin fibroblasts and found that phosphorylated mTOR and phosphorylated STAT3 protein expression were decreased by metformin treatment.	Metformin	19-28	mechanistic target of rapamycin kinase	Mus musculus	97-101
33947424-10	2021	To investigate how metformin modulates the inflammatory process in skin fibroblasts, we measured mTOR-STAT3 signaling in skin fibroblasts and found that phosphorylated mTOR and phosphorylated STAT3 protein expression were decreased by metformin treatment.	Metformin	19-28	mechanistic target of rapamycin kinase	Mus musculus	168-172
33947424-10	2021	To investigate how metformin modulates the inflammatory process in skin fibroblasts, we measured mTOR-STAT3 signaling in skin fibroblasts and found that phosphorylated mTOR and phosphorylated STAT3 protein expression were decreased by metformin treatment.	Metformin	235-244	mechanistic target of rapamycin kinase	Mus musculus	168-172
33947424-11	2021	These results suggest that metformin has potential to treat scleroderma by inhibiting pro-inflammatory cytokines and anti-inflammatory activity mediated by mTOR-STAT3 signaling.	Metformin	27-36	mechanistic target of rapamycin kinase	Mus musculus	156-160
33760349-0	2021	Metformin attenuates synergic effect of diabetes mellitus and Helicobacter pylori infection on gastric cancer cells proliferation by suppressing PTEN expression.	Metformin	0-9	phosphatase and tensin homolog	Homo sapiens	145-149
33760349-3	2021	It is intriguing to explore whether DM may strengthen the tumorigenic effect of H pylori (HP) by promoting the methylation of PTEN promoter and whether the administration of metformin may reduce the risk of GC by suppressing the methylation of PTEN promoter.	Metformin	174-183	phosphatase and tensin homolog	Homo sapiens	244-248
33760349-9	2021	Metformin showed an apparent effect on restoring CagA-induced elevation of PTEN promoter methylation, thus attenuating the PTEN expression.	Metformin	0-9	phosphatase and tensin homolog	Homo sapiens	75-79
33760349-9	2021	Metformin showed an apparent effect on restoring CagA-induced elevation of PTEN promoter methylation, thus attenuating the PTEN expression.	Metformin	0-9	phosphatase and tensin homolog	Homo sapiens	123-127
33760349-11	2021	In this study, we collected GC tumour tissues from GC patients with or without DM/HP to compare their PTEN methylation and expression while testing the effect of metformin on the methylation of PTEN promoter.	Metformin	162-171	phosphatase and tensin homolog	Homo sapiens	194-198
33760349-12	2021	In summary, our study suggested that DM could strengthen the tumorigenic effect of HP by promoting the PTEN promoter methylation, while metformin reduces GC risk by suppressing PTEN promoter methylation.	Metformin	136-145	phosphatase and tensin homolog	Homo sapiens	177-181
33634460-10	2021	Metformin normalized the alterations in the expression of glucose metabolism-related genes (PGC-1alpha, G6pc, Pepck, Gck, PYGL, Gys2, PKLR, GLUT4) and insulin resistance-related genes (AdipoR1, AdipoR2) in the muscles and livers of rats induced by CORT.	Metformin	0-9	glucose-6-phosphatase catalytic subunit 1	Rattus norvegicus	104-108
33634460-10	2021	Metformin normalized the alterations in the expression of glucose metabolism-related genes (PGC-1alpha, G6pc, Pepck, Gck, PYGL, Gys2, PKLR, GLUT4) and insulin resistance-related genes (AdipoR1, AdipoR2) in the muscles and livers of rats induced by CORT.	Metformin	0-9	glycogen phosphorylase L	Rattus norvegicus	122-126
33634460-10	2021	Metformin normalized the alterations in the expression of glucose metabolism-related genes (PGC-1alpha, G6pc, Pepck, Gck, PYGL, Gys2, PKLR, GLUT4) and insulin resistance-related genes (AdipoR1, AdipoR2) in the muscles and livers of rats induced by CORT.	Metformin	0-9	pyruvate kinase L/R	Rattus norvegicus	134-138
33634460-10	2021	Metformin normalized the alterations in the expression of glucose metabolism-related genes (PGC-1alpha, G6pc, Pepck, Gck, PYGL, Gys2, PKLR, GLUT4) and insulin resistance-related genes (AdipoR1, AdipoR2) in the muscles and livers of rats induced by CORT.	Metformin	0-9	solute carrier family 2 member 4	Rattus norvegicus	140-145
33634460-10	2021	Metformin normalized the alterations in the expression of glucose metabolism-related genes (PGC-1alpha, G6pc, Pepck, Gck, PYGL, Gys2, PKLR, GLUT4) and insulin resistance-related genes (AdipoR1, AdipoR2) in the muscles and livers of rats induced by CORT.	Metformin	0-9	adiponectin receptor 2	Rattus norvegicus	194-201
33893356-7	2021	In addition, co-treatment with metformin and UPA was associated with significant increase in the Bax and significant reduction in Bcl-2, PCNA, Cyclin-D1and ER-alpha as compared to treatment with UPA alone.	Metformin	31-40	BCL2 associated X, apoptosis regulator	Rattus norvegicus	97-100
33893356-7	2021	In addition, co-treatment with metformin and UPA was associated with significant increase in the Bax and significant reduction in Bcl-2, PCNA, Cyclin-D1and ER-alpha as compared to treatment with UPA alone.	Metformin	31-40	estrogen receptor 1	Rattus norvegicus	156-164
33886150-7	2021	We found that cotreatment with metformin (30 mM) and pitavastatin (10 muM) significantly reduced cell viability; caused G0/G1 cell cycle arrest; upregulated the expression levels of Bax, PCNA, cleaved PARP-1, cleaved caspase-3, LC3 II, and p27 Kip1 /p21Cip1 ; and inhibited cell migration.	Metformin	31-40	proliferating cell nuclear antigen	Homo sapiens	187-191
33886150-7	2021	We found that cotreatment with metformin (30 mM) and pitavastatin (10 muM) significantly reduced cell viability; caused G0/G1 cell cycle arrest; upregulated the expression levels of Bax, PCNA, cleaved PARP-1, cleaved caspase-3, LC3 II, and p27 Kip1 /p21Cip1 ; and inhibited cell migration.	Metformin	31-40	cyclin dependent kinase inhibitor 1B	Homo sapiens	240-248
33884414-10	2021	Compared to the self-directed group, participants in metformin had significant decreases on IGF-1 (mean difference in change: -5.50 ng/ml, p=0.02) and IGF1:IGFBP3 molar ratio (mean difference in change: -0.0119, p=0.011) at 3 months.	Metformin	53-62	insulin like growth factor binding protein 3	Homo sapiens	156-162
33888740-4	2021	In this sense, Metformin (MET), an FDA-approved drug used for the treatment of type 2 diabetes, has shown an anti-DENV effect in vitro by activating AMPK and reducing HMGCR activity.	Metformin	15-24	SAFB like transcription modulator	Homo sapiens	26-29
33888740-4	2021	In this sense, Metformin (MET), an FDA-approved drug used for the treatment of type 2 diabetes, has shown an anti-DENV effect in vitro by activating AMPK and reducing HMGCR activity.	Metformin	15-24	3-hydroxy-3-methylglutaryl-CoA reductase	Homo sapiens	167-172
33881795-7	2021	Among treatment visits where a single drug was prescribed, use of metformin declined from 57.0% of monotherapy in 2015 to 46.0% of monotherapy in 2019, while during the same period the share of monotherapy accounted for by Glucagon-like peptide -1 (GLP-1) agonists increased from 4.3% to 8.5% and the share accounted for by sodium-glucose cotransporter-2 (SGLT-2) inhibitors increased from 7.3% to 19.5%.	Metformin	66-75	solute carrier family 5 member 2	Homo sapiens	324-354
33881795-7	2021	Among treatment visits where a single drug was prescribed, use of metformin declined from 57.0% of monotherapy in 2015 to 46.0% of monotherapy in 2019, while during the same period the share of monotherapy accounted for by Glucagon-like peptide -1 (GLP-1) agonists increased from 4.3% to 8.5% and the share accounted for by sodium-glucose cotransporter-2 (SGLT-2) inhibitors increased from 7.3% to 19.5%.	Metformin	66-75	solute carrier family 5 member 2	Homo sapiens	356-362
33881795-8	2021	Among treatment visits where metformin plus another drug was prescribed, the share of second line therapy accounted for by dipeptidyl peptidase-4 (DPP-4) inhibitors decreased from 21.9% of treatment visits in 2015 to 20.8% of treatment visits in 2019; sulfonylurea use declined from 45.2% to 32.7%, use of SGLT-2 inhibitors increased from 14.5% to 21.2% and use of GLP-1 agonists increased from 9.8% to 18.2%.	Metformin	29-38	dipeptidyl peptidase 4	Homo sapiens	123-145
33881795-8	2021	Among treatment visits where metformin plus another drug was prescribed, the share of second line therapy accounted for by dipeptidyl peptidase-4 (DPP-4) inhibitors decreased from 21.9% of treatment visits in 2015 to 20.8% of treatment visits in 2019; sulfonylurea use declined from 45.2% to 32.7%, use of SGLT-2 inhibitors increased from 14.5% to 21.2% and use of GLP-1 agonists increased from 9.8% to 18.2%.	Metformin	29-38	dipeptidyl peptidase 4	Homo sapiens	147-152
33881795-8	2021	Among treatment visits where metformin plus another drug was prescribed, the share of second line therapy accounted for by dipeptidyl peptidase-4 (DPP-4) inhibitors decreased from 21.9% of treatment visits in 2015 to 20.8% of treatment visits in 2019; sulfonylurea use declined from 45.2% to 32.7%, use of SGLT-2 inhibitors increased from 14.5% to 21.2% and use of GLP-1 agonists increased from 9.8% to 18.2%.	Metformin	29-38	solute carrier family 5 member 2	Homo sapiens	306-312
33535788-3	2021	In human hepatocytes, metformin treatment suppressed the PCSK9 transcription.	Metformin	22-31	proprotein convertase subtilisin/kexin type 9	Homo sapiens	57-62
24671882-5	2014	In cultured bovine granulosa cells, INSULIN, IGF1, and two insulin sensitizers-metformin and rosiglitazone-increased rarres2 mRNA expression whereas they decreased cmklr1, gpr1, and cclr2 mRNA expression.	Metformin	79-88	insulin	Bos taurus	59-66
24517395-0	2014	Adding a DPP-4 inhibitor to metformin therapy may be safer than you think.	Metformin	28-37	dipeptidyl peptidase 4	Homo sapiens	9-14
24699248-15	2014	The gut hormone effects of this GPR119 agonist were modulated when co-dosed with metformin and sitagliptin.	Metformin	81-90	G protein-coupled receptor 119	Homo sapiens	32-38
33535788-7	2021	Moreover, metformin treatment significantly decreased serum low-density lipoprotein cholesterol and PCSK9 levels in nondiabetic individuals.	Metformin	10-19	proprotein convertase subtilisin/kexin type 9	Homo sapiens	100-105
33535788-8	2021	CONCLUSIONS: Collectively, we revealed a new mechanism of action of metformin in cholesterol-lowering and identified a novel crosstalk signal between glucose and cholesterol homeostasis via ChREBP-mediated PCSK9 regulation.	Metformin	68-77	proprotein convertase subtilisin/kexin type 9	Homo sapiens	206-211
33650651-0	2021	Metformin inhibits mTOR and c-Myc by decreasing YAP protein expression in OSCC cells.	Metformin	0-9	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	28-33
33650651-9	2021	In addition, compared to the control treatment, metformin treatment decreased the protein levels of YAP, mTOR, p-mTOR and c-Myc.	Metformin	48-57	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	122-127
33650651-10	2021	The overexpression of YAP alleviated the inhibitory effect of metformin on the protein expression of mTOR, p-mTOR and c-Myc.	Metformin	62-71	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	118-123
33650651-11	2021	The combination of metformin and verteporfin markedly enhanced the effects of metformin on the protein expression of mTOR, p-mTOR and c-Myc.	Metformin	19-28	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	134-139
33650651-11	2021	The combination of metformin and verteporfin markedly enhanced the effects of metformin on the protein expression of mTOR, p-mTOR and c-Myc.	Metformin	78-87	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	134-139
33650651-12	2021	Therefore, the results of the present study suggest that metformin suppresses OSCC by inhibiting YAP protein expression and by suppressing the YAP-mediated effects of metformin on the protein expression of mTOR and c-Myc.	Metformin	57-66	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	215-220
33650651-12	2021	Therefore, the results of the present study suggest that metformin suppresses OSCC by inhibiting YAP protein expression and by suppressing the YAP-mediated effects of metformin on the protein expression of mTOR and c-Myc.	Metformin	167-176	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	215-220
33649289-0	2021	Metformin targets Clusterin to control lipogenesis and inhibit the growth of bladder cancer cells through SREBP-1c/FASN axis.	Metformin	0-9	sterol regulatory element binding transcription factor 1	Homo sapiens	106-114
33476677-0	2021	Metformin relieves H/R-induced cardiomyocyte injury through miR-19a/ACSL axis - possible therapeutic target for myocardial I/R injury.	Metformin	0-9	microRNA 19a	Homo sapiens	60-67
33476677-1	2021	This study proposed to investigate the function of miR-19a/ACSL axis in hypoxia/reoxygenation (H/R)-induced myocardial injury and determine whether metformin exerts its protective effect via miR-19a/ACSL axis.	Metformin	148-157	microRNA 19a	Homo sapiens	191-198
33476677-9	2021	Furthermore, overexpression of miR-19a significantly strengthened the beneficial effect of metformin on H/R-induced AC16 cells injury, which can be reversed by upregulation of ACSL1.	Metformin	91-100	microRNA 19a	Homo sapiens	31-38
33476677-10	2021	In conclusion, metformin can alleviate H/R-induced cells injury via regulating miR-19a/ACSL axis, which lays a foundation for identifying novel targets for myocardial I/R injury therapy.	Metformin	15-24	microRNA 19a	Homo sapiens	79-86
33517853-0	2021	Metformin attenuates ischemia/reperfusion-induced apoptosis of cardiac cells by downregulation of p53/microRNA-34a via activation SIRT1.	Metformin	0-9	Wistar clone pR53P1 p53 pseudogene	Rattus norvegicus	98-101
33517853-0	2021	Metformin attenuates ischemia/reperfusion-induced apoptosis of cardiac cells by downregulation of p53/microRNA-34a via activation SIRT1.	Metformin	0-9	microRNA 34a	Rattus norvegicus	102-114
33517853-1	2021	Metformin has been demonstrated to be beneficial for the treatment of an impaired myocardium as a result of ischemia reperfusion (I/R) injury and miR-34a may be involved in this process.	Metformin	0-9	microRNA 34a	Rattus norvegicus	146-153
33517853-4	2021	Metformin also reduced apoptosis, the expression of apoptosis associated proteins and miR-34a, which resulted in corresponding changes of Bcl-2 expression.	Metformin	0-9	microRNA 34a	Rattus norvegicus	86-93
33517853-7	2021	Metformin decreased the deacetylation activity of SIRT 1 resulting in reduced Ac-p53 levels, which reduced the levels of pri-miR-34a.	Metformin	0-9	Wistar clone pR53P1 p53 pseudogene	Rattus norvegicus	81-84
33517853-7	2021	Metformin decreased the deacetylation activity of SIRT 1 resulting in reduced Ac-p53 levels, which reduced the levels of pri-miR-34a.	Metformin	0-9	microRNA 34a	Rattus norvegicus	125-132
33485367-15	2021	Moreover, metformin was found to increase the expression of KLF10 and enhance the radiosensitivity of OSCC.	Metformin	10-19	Kruppel like factor 10	Homo sapiens	60-65
33485367-18	2021	Metformin can increase KLF10 expression, which ameliorates the radioresistance induced by exo-miR-340-5p transfer.	Metformin	0-9	Kruppel like factor 10	Homo sapiens	23-28
33520106-20	2021	In addition, metformin treatment may relive the processes of inflammation and fibrosis in individuals with DKD by reducing the levels of the TNC, p-NF-kappaB p65, CTGF, and FN proteins.	Metformin	13-22	cellular communication network factor 2	Rattus norvegicus	163-167
33520106-20	2021	In addition, metformin treatment may relive the processes of inflammation and fibrosis in individuals with DKD by reducing the levels of the TNC, p-NF-kappaB p65, CTGF, and FN proteins.	Metformin	13-22	fibronectin 1	Rattus norvegicus	173-175
33439743-0	2021	Metformin ameliorates ROS-p53-collagen axis of fibrosis and dyslipidemia in type 2 diabetes mellitus-induced left ventricular injury.	Metformin	0-9	Wistar clone pR53P1 p53 pseudogene	Rattus norvegicus	26-29
33439743-4	2021	RESULTS: Diabetes significantly induced blood levels of ROS and left ventricular p53 and collagen expression that was inhibited by metformin.	Metformin	131-140	Wistar clone pR53P1 p53 pseudogene	Rattus norvegicus	81-84
33439743-7	2021	CONCLUSIONS: These findings show that metformin provides substantial protection against diabetic cardiomyopathy-induced ROS-p53 mediated fibrosis and dyslipidemia.	Metformin	38-47	Wistar clone pR53P1 p53 pseudogene	Rattus norvegicus	124-127
33347290-3	2021	In this study, a novel GBR membrane with polycaprolactone (PCL) and poly(vinyl alcohol) (PVA) containing different concentrations of metformin (Met) for improving osteogenic properties was developed.	Metformin	133-142	SAFB like transcription modulator	Homo sapiens	144-147
24692708-0	2014	Metformin suppresses sonic hedgehog expression in pancreatic cancer cells.	Metformin	0-9	sonic hedgehog signaling molecule	Homo sapiens	21-35
24692708-5	2014	The effect of metformin on Shh levels was also examined in three other cancer cell lines.	Metformin	14-23	sonic hedgehog signaling molecule	Homo sapiens	27-30
24692708-6	2014	RESULTS: Shh protein and mRNA expression was suppressed by metformin in BxPC3 cells.	Metformin	59-68	sonic hedgehog signaling molecule	Homo sapiens	9-12
24692708-8	2014	Shh mRNA expression was inhibited by metformin in a concentration-dependent manner in two cancer cell lines.	Metformin	37-46	sonic hedgehog signaling molecule	Homo sapiens	0-3
24692708-9	2014	CONCLUSION: Metformin reduces the expression of Shh in several cancer cell lines including pancreatic cancer cell.	Metformin	12-21	sonic hedgehog signaling molecule	Homo sapiens	48-51
24444314-2	2014	In this study, we elucidated the anti-hypertrophic action of metformin, specifically, the role of the AMPK/eNOS/p53 pathway.	Metformin	61-70	Wistar clone pR53P1 p53 pseudogene	Rattus norvegicus	112-115
24931021-6	2014	RESULTS: Metformin inhibited the proliferation of Fadu cells in a dose-and time-dependent manner.Flow cytometry showed that cell cycle arrest in G1 phase was induced by metformin in Fadu cells.Immunocytochemistry showed the expressions of both AMPK and P21 in cells treated with metformin were higher than those in cells untreated with metformin.	Metformin	9-18	H3 histone pseudogene 16	Homo sapiens	253-256
24931021-6	2014	RESULTS: Metformin inhibited the proliferation of Fadu cells in a dose-and time-dependent manner.Flow cytometry showed that cell cycle arrest in G1 phase was induced by metformin in Fadu cells.Immunocytochemistry showed the expressions of both AMPK and P21 in cells treated with metformin were higher than those in cells untreated with metformin.	Metformin	169-178	H3 histone pseudogene 16	Homo sapiens	253-256
25286600-2	2014	Of drugs prescribed to patients with diabetes mellitus type 2, have the greatest effect receptor agonists that activate the peroxisome proliferator (PPAR], activators of incretine and metformin.	Metformin	184-193	peroxisome proliferator activated receptor alpha	Homo sapiens	149-153
24668601-13	2014	Metformin, a biguanide, targets additional mechanisms of hyperglycemia by inhibiting hepatic glucose production and enhancing peripheral glucose uptake and thereby reducing insulin resistance; acarbose reversibly bind to pancreatic alpha-amylase and membrane-bound intestinal alpha-glucoside hydrolases.	Metformin	0-9	amylase alpha 2A	Homo sapiens	221-245
24505341-10	2014	Furthermore, hyperthermia potentiated the effect of metformin to activate AMPK and inactivate mTOR and S6K.	Metformin	52-61	ribosomal protein S6 kinase B1	Homo sapiens	103-106
24322659-4	2014	Previous studies demonstrated that metformin is a potent inhibitor of ErbB2-overexpressing breast cancer cells; metformin treatment extends the life span and impedes mammary tumor development in ErbB2 transgenic mice in vivo.	Metformin	35-44	erb-b2 receptor tyrosine kinase 2	Mus musculus	70-75
33420333-4	2021	We aimed to systematically synthesize the evidence on the comparative cardiovascular safety and efficacy of combination therapy with metformin-sodium-glucose cotransporter-2 inhibitors versus metformin-sulfonylureas in patients with type 2 diabetes.	Metformin	133-142	solute carrier family 5 member 2	Homo sapiens	143-173
33420333-6	2021	We included randomized controlled trials of patients with type 2 diabetes who were on metformin-sodium-glucose cotransporter-2 inhibitors or metformin-sulphonylureas combination therapy at least for a year.	Metformin	86-95	solute carrier family 5 member 2	Homo sapiens	96-126
32944923-0	2021	Investigation of plasma asprosin and saliva levels in newly diagnosed type 2 diabetes mellitus patients treated with metformin.	Metformin	117-126	fibrillin 1	Homo sapiens	24-32
32944923-4	2021	There is no literature information available in humans to demonstrate how blood and saliva asprosin levels of patients with newly diagnosed T2DM changed after metformin treatment.	Metformin	159-168	fibrillin 1	Homo sapiens	91-99
32994182-0	2021	Metformin mitigates DPP-4 inhibitor-induced breast cancer metastasis via suppression of mTOR signaling.	Metformin	0-9	dipeptidylpeptidase 4	Mus musculus	20-25
32994182-0	2021	Metformin mitigates DPP-4 inhibitor-induced breast cancer metastasis via suppression of mTOR signaling.	Metformin	0-9	mechanistic target of rapamycin kinase	Mus musculus	88-92
32994182-4	2021	In this study, we investigated whether metformin mitigates breast cancer metastasis induced by a DPP-4 inhibitor via suppression of mTOR signaling.	Metformin	39-48	dipeptidyl peptidase 4	Homo sapiens	97-102
32994182-5	2021	In cultured mouse mammary and human breast cancer cells, metformin suppressed DPP-4 inhibitor KR62436 (KR)-induced EMT and cell migration via suppression of the mTOR pathway associated with AMPK activation.	Metformin	57-66	dipeptidyl peptidase 4	Homo sapiens	78-83
33262823-0	2021	Metformin inhibits epithelial-mesenchymal transition of oral squamous cell carcinoma via the mTOR/HIF-1alpha/PKM2/STAT3 pathway.	Metformin	0-9	pyruvate kinase M1/2	Homo sapiens	109-113
33262823-9	2021	Moreover, metformin reversed EMT in OSCC by inhibiting the mTOR-associated HIF-1alpha/PKM2/STAT3 signaling pathway.	Metformin	10-19	pyruvate kinase M1/2	Homo sapiens	86-90
32674107-8	2021	RESULTS: Combination treatment with LMT-28 and metformin diminished proliferation of MH7A cells and IL-6-mediated gp130, STAT3, and ERK signaling more than in individual treatments.	Metformin	47-56	interleukin 6 cytokine family signal transducer	Homo sapiens	114-119
32777157-0	2020	Metformin andbetter survival in Type 2 Diabetes patients with NSCLC during EGFR-TKI Treatment: implications of miR-146a?	Metformin	0-9	microRNA 146a	Homo sapiens	111-119
33169942-5	2020	The present study examines the inhibitory effect of metformin on BMP signalling, osteogenic differentiation and trauma-induced heterotopic ossification.	Metformin	52-61	bone morphogenetic protein 6	Mus musculus	65-68
33169942-6	2020	Our results showed that metformin inhibited Smad1/5 phosphorylation induced by BMP6 in osteoblast MC3T3-E1 cells, concurrent with up-regulation of Smad6, and this effect was attenuated by knockdown of Smad6.	Metformin	24-33	SMAD family member 1	Mus musculus	44-51
33169942-6	2020	Our results showed that metformin inhibited Smad1/5 phosphorylation induced by BMP6 in osteoblast MC3T3-E1 cells, concurrent with up-regulation of Smad6, and this effect was attenuated by knockdown of Smad6.	Metformin	24-33	bone morphogenetic protein 6	Mus musculus	79-83
33169942-6	2020	Our results showed that metformin inhibited Smad1/5 phosphorylation induced by BMP6 in osteoblast MC3T3-E1 cells, concurrent with up-regulation of Smad6, and this effect was attenuated by knockdown of Smad6.	Metformin	24-33	SMAD family member 6	Mus musculus	147-152
33169942-6	2020	Our results showed that metformin inhibited Smad1/5 phosphorylation induced by BMP6 in osteoblast MC3T3-E1 cells, concurrent with up-regulation of Smad6, and this effect was attenuated by knockdown of Smad6.	Metformin	24-33	SMAD family member 6	Mus musculus	201-206
33169942-9	2020	In conjuncture, AMPK activity and Smad6 and Smurf1 expression were enhanced by metformin treatment in the muscle of injured area, concurrently with the reduction of ALK2.	Metformin	79-88	SMAD family member 6	Mus musculus	34-39
33169942-9	2020	In conjuncture, AMPK activity and Smad6 and Smurf1 expression were enhanced by metformin treatment in the muscle of injured area, concurrently with the reduction of ALK2.	Metformin	79-88	SMAD specific E3 ubiquitin protein ligase 1	Mus musculus	44-50
33169942-10	2020	Collectively, our study suggests that metformin prevents heterotopic ossification via activation of AMPK and subsequent up-regulation of Smad6.	Metformin	38-47	SMAD family member 6	Mus musculus	137-142
24322659-4	2014	Previous studies demonstrated that metformin is a potent inhibitor of ErbB2-overexpressing breast cancer cells; metformin treatment extends the life span and impedes mammary tumor development in ErbB2 transgenic mice in vivo.	Metformin	35-44	erb-b2 receptor tyrosine kinase 2	Mus musculus	195-200
24322659-4	2014	Previous studies demonstrated that metformin is a potent inhibitor of ErbB2-overexpressing breast cancer cells; metformin treatment extends the life span and impedes mammary tumor development in ErbB2 transgenic mice in vivo.	Metformin	112-121	erb-b2 receptor tyrosine kinase 2	Mus musculus	70-75
24322659-4	2014	Previous studies demonstrated that metformin is a potent inhibitor of ErbB2-overexpressing breast cancer cells; metformin treatment extends the life span and impedes mammary tumor development in ErbB2 transgenic mice in vivo.	Metformin	112-121	erb-b2 receptor tyrosine kinase 2	Mus musculus	195-200
23668534-5	2014	Moreover, recent studies have suggested that metformin enhances the biological effect of GLP-1 by increasing GLP-1 secretion, suppressing activity of DPP-4 and upregulating the expression of GLP-1 receptor in pancreatic beta-cells.	Metformin	45-54	dipeptidyl peptidase 4	Homo sapiens	150-155
24533710-6	2014	Metformin bad responders or nonresponders based on OCT genotypes might be relevant in clinical practice - their modulation of metformin pharmacokinetics and pharmacodynamics and metformin-independent glucose effects remain to be elucidated.	Metformin	0-9	plexin A2	Homo sapiens	51-54
24533710-6	2014	Metformin bad responders or nonresponders based on OCT genotypes might be relevant in clinical practice - their modulation of metformin pharmacokinetics and pharmacodynamics and metformin-independent glucose effects remain to be elucidated.	Metformin	126-135	plexin A2	Homo sapiens	51-54
24533710-6	2014	Metformin bad responders or nonresponders based on OCT genotypes might be relevant in clinical practice - their modulation of metformin pharmacokinetics and pharmacodynamics and metformin-independent glucose effects remain to be elucidated.	Metformin	178-187	plexin A2	Homo sapiens	51-54
24791887-3	2014	The aim of this study was to observe the effects of metformin on expression of nuclear factor-kappaB (NF-kappaB), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and transforming growth factor-beta 1 (TGF-beta1) induced by high glucose (HG) in cultured rat glomerular mesangial cells (MCs).	Metformin	52-61	C-C motif chemokine ligand 2	Rattus norvegicus	114-148
24791887-9	2014	Both genes and protein expression of NF-kappaB, MCP-1, ICAM-1, TGF-beta1 of MCs induced by high glucose were markedly reduced after metformin treatment in a dose-dependent manner (P &lt; 0.05).	Metformin	132-141	C-C motif chemokine ligand 2	Rattus norvegicus	48-53
25329671-4	2014	Activation of LKB1/AMPK pathway and cancer stem cell destruction along with cell cycle arrest and apoptosis induction are the proposed mechanisms of anticancer potential of metformin.	Metformin	173-182	serine/threonine kinase 11	Homo sapiens	14-18
24601227-5	2014	Furthermore, western blot analysis showed that metformin suppressed the overexpression of the endoplasmic reticulum stress (ERS) markers cleaved caspase-12 and CEBP-homologous protein induced by ISO and increased the phosphorylation of AMP-activated protein kinase (AMPK).	Metformin	47-56	CCAAT/enhancer binding protein gamma	Rattus norvegicus	160-164
24351837-4	2013	Metformin significantly inhibited the proliferation and colony formation of 5637 and T24 cells in vitro; specifically, metformin induced an apparent cell cycle arrest in G0/G1 phases, accompanied by a strong decrease of cyclin D1, cyclin-dependent kinase 4 (CDK4), E2F1 and an increase of p21waf-1.	Metformin	0-9	E2F transcription factor 1	Homo sapiens	265-269
24351837-4	2013	Metformin significantly inhibited the proliferation and colony formation of 5637 and T24 cells in vitro; specifically, metformin induced an apparent cell cycle arrest in G0/G1 phases, accompanied by a strong decrease of cyclin D1, cyclin-dependent kinase 4 (CDK4), E2F1 and an increase of p21waf-1.	Metformin	119-128	E2F transcription factor 1	Homo sapiens	265-269
24351837-6	2013	Moreover, daily treatment of metformin led to a substantial inhibition of tumor growth in a xenograft model with concomitant decrease in the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and p-mTOR.	Metformin	29-38	proliferating cell nuclear antigen	Homo sapiens	155-189
24351837-6	2013	Moreover, daily treatment of metformin led to a substantial inhibition of tumor growth in a xenograft model with concomitant decrease in the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and p-mTOR.	Metformin	29-38	proliferating cell nuclear antigen	Homo sapiens	191-195
24329113-4	2013	The pharmacokinetics of metformin is primarily determined by membrane transporters, including the plasma membrane monoamine transporter (PMAT), the organic cation transporters (OCTs), the multidrug and toxin extrusion (MATE) transporters, and the critical protein kinase AMPactivated protein kinase (AMPK).	Metformin	24-33	solute carrier family 29 member 4	Homo sapiens	98-135
24329113-4	2013	The pharmacokinetics of metformin is primarily determined by membrane transporters, including the plasma membrane monoamine transporter (PMAT), the organic cation transporters (OCTs), the multidrug and toxin extrusion (MATE) transporters, and the critical protein kinase AMPactivated protein kinase (AMPK).	Metformin	24-33	solute carrier family 29 member 4	Homo sapiens	137-141
24329113-5	2013	PMAT may play a role in the uptake of metformin from the gastrointestinal tract, while OCTs mediate the intestinal absorption, hepatic uptake, and renal excretion of metformin.	Metformin	38-47	solute carrier family 29 member 4	Homo sapiens	0-4
24329113-10	2013	In this review, we will discuss the genetic variants of major transporters that purportedly determine the pharmacokinetics of metformin in terms of drug bioavailability, distribution, and excretion, such as PMAT, OCTs, and MATEs.	Metformin	126-135	solute carrier family 29 member 4	Homo sapiens	207-211
24026623-2	2013	Although no inhibition of OAT1 and OAT3 was observed, inhibition of OCT2-mediated uptake of 1-methyl-4-phenylpyridinium (MPP(+)) and metformin was evident (IC(50) of 73.4 +- 14.8 and 8.8 +- 1.9 microM, respectively).	Metformin	133-142	solute carrier family 22 member 2	Homo sapiens	68-72
24185692-0	2013	Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin.	Metformin	112-121	acetyl-Coenzyme A carboxylase alpha	Mus musculus	32-36
24466367-9	2013	These results suggest that biologic effects of metformin are mediated through decreased CSC markers cluster of differentiation 44 (CD44 and CD133), aldehyde dehydrogenase isoform 1 (ALDH1), and epithelial cell adhesion molecule (EPCAM) and modulation of the mTOR signaling pathway.	Metformin	47-56	mechanistic target of rapamycin kinase	Mus musculus	258-262
23987517-0	2013	Metformin reduces the expression of corticotropin-releasing hormone and urocortin in the endometrium of healthy women.	Metformin	0-9	corticotropin releasing hormone	Homo sapiens	36-67
33080281-4	2020	The present study shows new approaches of metformin (MET) as an antioxidant agent.	Metformin	42-51	SAFB like transcription modulator	Homo sapiens	53-56
33174032-10	2020	In addition, metformin stimulated mitochondrial biogenesis, as indicated by increased expression levels of mitochondrial genes (NDUFA1, NDUFA2, NDUFA13 and manganese superoxide dismutase) and mitochondrial biogenesis-related transcription factors [peroxisome proliferator-activated receptor-gamma coactivator-1alpha, nuclear respiratory factor (NRF)-1, and NRF-2] in the metformin + HG group compared with the HG group.	Metformin	13-22	NADH:ubiquinone oxidoreductase subunit A1	Rattus norvegicus	128-134
23987517-0	2013	Metformin reduces the expression of corticotropin-releasing hormone and urocortin in the endometrium of healthy women.	Metformin	0-9	urocortin	Homo sapiens	72-81
23987517-1	2013	OBJECTIVE: To investigate the effect of metformin administration on the expression of endometrial corticotrophin-releasing hormone (CRH) and urocortin (UCN) in the midluteal phase of the cycle.	Metformin	40-49	corticotropin releasing hormone	Homo sapiens	132-135
23987517-1	2013	OBJECTIVE: To investigate the effect of metformin administration on the expression of endometrial corticotrophin-releasing hormone (CRH) and urocortin (UCN) in the midluteal phase of the cycle.	Metformin	40-49	urocortin	Homo sapiens	141-150
23987517-1	2013	OBJECTIVE: To investigate the effect of metformin administration on the expression of endometrial corticotrophin-releasing hormone (CRH) and urocortin (UCN) in the midluteal phase of the cycle.	Metformin	40-49	urocortin	Homo sapiens	152-155
23987517-9	2013	RESULT(S): Compared with samples from control cycles, CRH and UCN were significantly reduced in endometrial samples obtained during metformin treatment.	Metformin	132-141	corticotropin releasing hormone	Homo sapiens	54-57
23987517-9	2013	RESULT(S): Compared with samples from control cycles, CRH and UCN were significantly reduced in endometrial samples obtained during metformin treatment.	Metformin	132-141	urocortin	Homo sapiens	62-65
23987517-11	2013	CONCLUSION(S): This is the first study showing that during the midluteal phase of the cycle, metformin may decrease the production of CRH and UCN in the endometrium.	Metformin	93-102	corticotropin releasing hormone	Homo sapiens	134-137
23987517-11	2013	CONCLUSION(S): This is the first study showing that during the midluteal phase of the cycle, metformin may decrease the production of CRH and UCN in the endometrium.	Metformin	93-102	urocortin	Homo sapiens	142-145
23987517-12	2013	Metformin interference to decidualization could happen by CRH/UCN modification.	Metformin	0-9	corticotropin releasing hormone	Homo sapiens	58-61
23987517-12	2013	Metformin interference to decidualization could happen by CRH/UCN modification.	Metformin	0-9	urocortin	Homo sapiens	62-65
24041694-6	2013	Importantly, inhibition of mitochondrial complex I activity by metformin resulted in FGF21 induction through PKR-like ER kinase (PERK)-eukaryotic translation factor 2alpha (eIF2alpha)-activating transcription factor 4 (ATF4).	Metformin	63-72	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	109-127
24041694-6	2013	Importantly, inhibition of mitochondrial complex I activity by metformin resulted in FGF21 induction through PKR-like ER kinase (PERK)-eukaryotic translation factor 2alpha (eIF2alpha)-activating transcription factor 4 (ATF4).	Metformin	63-72	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	129-133
24457404-2	2013	We aimed to assess the changes in PAI-1 levels in PCOS during treatment with metformin and during weight loss.	Metformin	77-86	serpin family E member 1	Homo sapiens	34-39
33132177-0	2020	Therapeutic effect of metformin on inflammation and apoptosis after spinal cord injury in rats through the Wnt/beta-catenin signaling pathway.	Metformin	22-31	catenin beta 1	Rattus norvegicus	111-123
33132177-1	2020	OBJECTIVE: To verify the effect of metformin on spinal cord injury (SCI) through Wnt/beta-catenin signaling pathway.	Metformin	35-44	catenin beta 1	Rattus norvegicus	85-97
33132177-5	2020	Whether metformin could improve SCI through Wnt/beta-catenin signaling pathway remains unclear.	Metformin	8-17	catenin beta 1	Rattus norvegicus	48-60
33132177-9	2020	RESULTS: Metformin(50 mg/kg) promoted motor functional recovery in rats after SCI, increased the expressions of beta-catenin and brain derived neurotrophic factor (BDNF), inhibited neuron apoptosis and inflammatory response, and improved the recovery of pathological morphology at the injury site by activating the Wnt/beta-catenin signaling pathway.	Metformin	9-18	catenin beta 1	Rattus norvegicus	112-124
33132177-9	2020	RESULTS: Metformin(50 mg/kg) promoted motor functional recovery in rats after SCI, increased the expressions of beta-catenin and brain derived neurotrophic factor (BDNF), inhibited neuron apoptosis and inflammatory response, and improved the recovery of pathological morphology at the injury site by activating the Wnt/beta-catenin signaling pathway.	Metformin	9-18	catenin beta 1	Rattus norvegicus	319-331
33132177-10	2020	CONCLUSION: We found a possible mechanism that metformin could reduce inflammation and apoptosis, and promote functional recovery of SCI rats through activating Wnt/beta-catenin signaling pathway.	Metformin	47-56	catenin beta 1	Rattus norvegicus	165-177
33575476-6	2021	Furthermore, our xenograft murine model confirmed that metformin enhanced cisplatin"s anti-cancer effect by upregulation of AMPK and downregulation of mTOR signaling pathways.	Metformin	55-64	mechanistic target of rapamycin kinase	Mus musculus	151-155
33191271-10	2021	The ability of metformin and increased intracellular free Ca2+ concentrations to activate AMPK is reduced in cells lacking IQGAP1.	Metformin	15-24	IQ motif containing GTPase activating protein 1	Mus musculus	123-129
24457404-5	2013	RESULTS: In normal weight women, treatment with metformin reduced the body mass index (BMI) and circulating androgens, improved markers of IR and lowered PAI-1 levels.	Metformin	48-57	serpin family E member 1	Homo sapiens	154-159
24457404-9	2013	CONCLUSIONS: Metformin and sibutramine, but not orlistat, reduce PAI-1 levels in PCOS.	Metformin	13-22	serpin family E member 1	Homo sapiens	65-70
24227948-0	2013	The Effect of Metformin Treatment on CRBP-I Level and Cancer Development in the Liver of HBx Transgenic Mice.	Metformin	14-23	retinol binding protein 1, cellular	Mus musculus	37-43
23579178-0	2013	Mechanisms of glucose lowering of dipeptidyl peptidase-4 inhibitor sitagliptin when used alone or with metformin in type 2 diabetes: a double-tracer study.	Metformin	103-112	dipeptidyl peptidase 4	Homo sapiens	34-56
33177546-4	2020	Metformin alone slightly deteriorated the aspartate and alanine aminotransferase (AST/ALT) values, whereas co-treatment with GW7647 and metformin greatly suppressed liver injury and fibrosis via activation of the AMP-activated protein kinase (AMPK) pathway.	Metformin	0-9	solute carrier family 17 (anion/sugar transporter), member 5	Mus musculus	82-85
33177546-4	2020	Metformin alone slightly deteriorated the aspartate and alanine aminotransferase (AST/ALT) values, whereas co-treatment with GW7647 and metformin greatly suppressed liver injury and fibrosis via activation of the AMP-activated protein kinase (AMPK) pathway.	Metformin	0-9	glutamic pyruvic transaminase, soluble	Mus musculus	86-89
33177546-4	2020	Metformin alone slightly deteriorated the aspartate and alanine aminotransferase (AST/ALT) values, whereas co-treatment with GW7647 and metformin greatly suppressed liver injury and fibrosis via activation of the AMP-activated protein kinase (AMPK) pathway.	Metformin	136-145	glutamic pyruvic transaminase, soluble	Mus musculus	86-89
33152427-0	2021	Huangkui capsule in combination with metformin ameliorates diabetic nephropathy via the Klotho/TGF-beta1/p38MAPK signaling pathway.	Metformin	37-46	Klotho	Rattus norvegicus	88-94
33152427-4	2021	AIM OF THE STUDY: This study was designed to investigate the efficacy and underlying mechanisms of HKC combined with metformin (MET), the first-line medication for treating type 2 diabetes, in the treatment of renal interstitial fibrosis.	Metformin	117-126	SAFB like transcription modulator	Homo sapiens	128-131
32934682-13	2020	In conclusion, the present results suggested that metformin attenuated RIF of UUO rats, and the mechanism of action was found to be associated with the increase in Deptor expression and inhibition of the mTOR/p70S6K pathway in the kidneys of UUO rats.	Metformin	50-59	ribosomal protein S6 kinase B1	Rattus norvegicus	209-215
33120439-0	2021	Cardiovascular Safety of Sodium Glucose Cotransporter 2 Inhibitors as Add-on to Metformin Monotherapy in Patients with Type 2 Diabetes Mellitus.	Metformin	80-89	solute carrier family 5 member 2	Homo sapiens	25-55
33120439-1	2021	Background: Using real-world data, cardiovascular safety was investigated in metformin users newly starting sodium glucose cotransporter 2 (SGLT2) inhibitors compared with other glucose-lowering drugs in Korea.	Metformin	77-86	solute carrier family 5 member 2	Homo sapiens	108-138
33120439-1	2021	Background: Using real-world data, cardiovascular safety was investigated in metformin users newly starting sodium glucose cotransporter 2 (SGLT2) inhibitors compared with other glucose-lowering drugs in Korea.	Metformin	77-86	solute carrier family 5 member 2	Homo sapiens	140-145
33120439-9	2021	In addition, use of SGLT2 inhibitors versus sulfonylurea as add-on therapy to metformin was associated with decreased risks of HHF, all-cause mortality, HHF plus all-cause mortality, MI, stroke, and modified MACEs.	Metformin	78-87	solute carrier family 5 member 2	Homo sapiens	20-25
33067434-3	2020	Here, we use mass cytometry to show that metformin treatment expands a population of memory-like antigen-inexperienced CD8+CXCR3+ T cells in naive mice, and in healthy individuals and patients with T2D.	Metformin	41-50	chemokine (C-X-C motif) receptor 3	Mus musculus	123-128
33081077-6	2020	Metformin decreased the NGF-induced transcriptional activity of MYC and beta-catenin/T-cell factor/lymphoid enhancer-binding factor (TCF-Lef), as well as the expression of c-MYC, survivin and VEGF in EOC cells, while it increased miR-23b and miR-145 levels.	Metformin	0-9	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	64-67
33081077-6	2020	Metformin decreased the NGF-induced transcriptional activity of MYC and beta-catenin/T-cell factor/lymphoid enhancer-binding factor (TCF-Lef), as well as the expression of c-MYC, survivin and VEGF in EOC cells, while it increased miR-23b and miR-145 levels.	Metformin	0-9	catenin beta 1	Homo sapiens	72-84
33081077-6	2020	Metformin decreased the NGF-induced transcriptional activity of MYC and beta-catenin/T-cell factor/lymphoid enhancer-binding factor (TCF-Lef), as well as the expression of c-MYC, survivin and VEGF in EOC cells, while it increased miR-23b and miR-145 levels.	Metformin	0-9	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	172-177
33081077-6	2020	Metformin decreased the NGF-induced transcriptional activity of MYC and beta-catenin/T-cell factor/lymphoid enhancer-binding factor (TCF-Lef), as well as the expression of c-MYC, survivin and VEGF in EOC cells, while it increased miR-23b and miR-145 levels.	Metformin	0-9	microRNA 145	Homo sapiens	242-249
32556267-0	2020	Combining a high dose of metformin with the SIRT1 activator, SRT1720, reduces lifespan in aged mice fed a high-fat diet.	Metformin	25-34	sirtuin 1	Mus musculus	44-49
33058005-4	2021	By influencing IRS1 phosphorylation pattern, metformin may sensitize TSHR to TSH, thus explaining the findings of clinical studies.	Metformin	45-54	insulin receptor substrate 1	Homo sapiens	15-19
33162888-2	2020	Nowadays, metformin (MET) has been discovered to improve endothelial function, but studies regarding the mechanism of MET improving endothelial cell function and alleviating endothelial function under hyperglycemia are still extremely limited.	Metformin	10-19	SAFB like transcription modulator	Homo sapiens	21-24
33282484-7	2020	The PD-L1 levels were significantly up-regulated by IFN-gamma and inhibited by metformin in human lung cancer cells from the A549 cell line.	Metformin	79-88	CD274 molecule	Homo sapiens	4-9
33025801-11	2021	Metformin slightly reduced expression in ADAMTS5 (beta = 0.34, P = 0.04), HIF-1a (beta = 0.39, P = 0.04), IL4 (beta = 0.30, P = 0.02), MMP1 (beta = 0.47, P < 0.01), and SOX9 (beta = 0.37, P = 0.03).	Metformin	0-9	matrix metallopeptidase 1	Homo sapiens	135-139
33025801-15	2021	Metformin reduced the expression of catabolic genes ADAMTS5 and MMP1 and might play a role in disease prevention.	Metformin	0-9	matrix metallopeptidase 1	Homo sapiens	64-68
33116701-0	2020	Add-On Therapy with DPP-4 Inhibitors May Improve Renal Function Decline in alpha-Glucosidase Inhibitor and Metformin Users: A Retrospective Observational Study.	Metformin	107-116	dipeptidyl peptidase 4	Homo sapiens	20-25
33116701-12	2020	These results suggest that the beneficial effects of DPP-4 inhibitors on kidney function may have occurred in the presence of an alpha-glucosidase inhibitor and/or metformin.	Metformin	164-173	dipeptidyl peptidase 4	Homo sapiens	53-58
32365398-0	2020	Effects of Short Term Metformin Treatment on Brown Adipose Tissue Activity and Plasma Irisin Levels in Women with Polycystic Ovary Syndrome: A Randomized Controlled Trial.	Metformin	22-31	fibronectin type III domain containing 5	Homo sapiens	86-92
32365398-3	2020	The aim of this randomized controlled trial was to evaluate whether a short term treatment with metformin alters BAT activity and plasma irisin levels in women with PCOS.	Metformin	96-105	fibronectin type III domain containing 5	Homo sapiens	137-143
23707609-9	2013	The inactivation of AMPK by siRNA, DN-AMPK or the pharmacological AMPK inhibitor compound C, revealed that metformin reduced HO-1 expression in an AMPK-independent manner.	Metformin	107-116	heme oxygenase 1	Homo sapiens	125-129
23827952-1	2013	Metformin has been reported to increase the expression of the glucagon-like peptide-1 (GLP-1) receptor in pancreatic beta cells in a peroxisome proliferator-activated receptor (PPAR)-alpha-dependent manner.	Metformin	0-9	peroxisome proliferator activated receptor alpha	Rattus norvegicus	133-188
33841532-0	2020	Comparison the Effect of Metformin and Clomiphene Citrate on Sirtuin3 gene Expression in the Oocytes of Mice with Polycystic Ovary Syndrome.	Metformin	25-34	sirtuin 3	Mus musculus	61-69
33841532-3	2020	In the current study, we compared the effects of metformin and clomiphene citrate on the expression of the Sirt3 gene in oocytes obtained from the mice, induced by PCOS.	Metformin	49-58	sirtuin 3	Mus musculus	107-112
33841532-11	2020	Also, no significant difference was found in the expression of Sirt3 between clomiphene and PCOS group, whereas, in the metformin group, Sirt3 expression had the higher rate of expression in comparison with the PCOS group (P < 0.05).	Metformin	120-129	sirtuin 3	Mus musculus	137-142
33841532-12	2020	The administration of metformin and clomiphene showed that metformin is capable of preventing the downregulation of the Sirt3 gene in oocytes, collected from PCOS mice.	Metformin	22-31	sirtuin 3	Mus musculus	120-125
33841532-12	2020	The administration of metformin and clomiphene showed that metformin is capable of preventing the downregulation of the Sirt3 gene in oocytes, collected from PCOS mice.	Metformin	59-68	sirtuin 3	Mus musculus	120-125
32384961-7	2020	RT-qPCR and immunoblotting were used to detect the effects of metformin on the expression of TXNIP and autophagy associated genes-BECN1 and LC3B in the sciatic nerves of pain model mice.	Metformin	62-71	beclin 1, autophagy related	Mus musculus	130-135
32988397-8	2020	Metformin improves IR by reducing the expression of ANGPTL2, thus improving the endocrine environment of PCOS and might change the disease outcome.	Metformin	0-9	angiopoietin-like 2	Rattus norvegicus	52-59
32967076-5	2020	Patients treated with metformin showed decreased levels of all analyzed serum pro-inflammatory markers (TNFalpha, IL6, IL1beta and MCP1) and a downwards trend in IL18 levels associated with a lower production of oxidative stress markers in leukocytes (mitochondrial ROS and myeloperoxidase (MPO)).	Metformin	22-31	interleukin 1 alpha	Homo sapiens	119-126
32967076-5	2020	Patients treated with metformin showed decreased levels of all analyzed serum pro-inflammatory markers (TNFalpha, IL6, IL1beta and MCP1) and a downwards trend in IL18 levels associated with a lower production of oxidative stress markers in leukocytes (mitochondrial ROS and myeloperoxidase (MPO)).	Metformin	22-31	C-C motif chemokine ligand 2	Homo sapiens	131-135
32940892-7	2021	In vitro, metformin dose-dependently reduced lipopolysaccharide (LPS)-induced TF expression in THP-1 cells.	Metformin	10-19	coagulation factor III, tissue factor	Homo sapiens	78-80
32940892-8	2021	The AMPK activator AICAR alone lowered TF expression in THP-1, while the AMPK inhibitor compound C abrogated the metformin-dependent reduction in TF expression.	Metformin	113-122	coagulation factor III, tissue factor	Homo sapiens	146-148
32940892-9	2021	CONCLUSIONS: Our data are the first to report that metformin is associated with reduced plasma TF procoagulant activity possibly explaining-at least in part-the vasculoprotective properties of metformin.	Metformin	51-60	coagulation factor III, tissue factor	Homo sapiens	95-97
32940892-9	2021	CONCLUSIONS: Our data are the first to report that metformin is associated with reduced plasma TF procoagulant activity possibly explaining-at least in part-the vasculoprotective properties of metformin.	Metformin	193-202	coagulation factor III, tissue factor	Homo sapiens	95-97
32497590-9	2020	The activation of AMPK and BDNF signaling pathways was induced by metformin treatment on the 6-OHDA-lesioned side of the striatum.	Metformin	66-75	brain derived neurotrophic factor	Mus musculus	27-31
32905620-11	2021	These findings suggest that Metformin potentiate the antitumor efficacy of doxorubicin and had beneficial effects on PhIP-induced mammary carcinogenesis through the prevention of cellular proliferation and mRNA expression of ERalpha and EGF.	Metformin	28-37	estrogen receptor 1	Rattus norvegicus	225-232
32905620-11	2021	These findings suggest that Metformin potentiate the antitumor efficacy of doxorubicin and had beneficial effects on PhIP-induced mammary carcinogenesis through the prevention of cellular proliferation and mRNA expression of ERalpha and EGF.	Metformin	28-37	epidermal growth factor	Rattus norvegicus	237-240
32590170-12	2020	Local administration of metformin-HCl substantially down-regulated the expression of fibrosis-involved genes: transforming growth factor (TGF-beta1), collagen type 1 (Col-I), fibronectin, collagen type 3 (Col-III), and alpha-smooth muscle actin (alpha-SMA).	Metformin	24-37	fibronectin 1	Rattus norvegicus	175-186
32590170-12	2020	Local administration of metformin-HCl substantially down-regulated the expression of fibrosis-involved genes: transforming growth factor (TGF-beta1), collagen type 1 (Col-I), fibronectin, collagen type 3 (Col-III), and alpha-smooth muscle actin (alpha-SMA).	Metformin	24-37	actin gamma 2, smooth muscle	Rattus norvegicus	219-244
33747526-11	2021	Regulation of the CD39/CD73/adenosine pathway using metformin may represent a therapeutic option to reverse HBV-induced immune pathogenesis.	Metformin	52-61	ectonucleoside triphosphate diphosphohydrolase 1	Homo sapiens	18-22
32821142-0	2020	SGLT2 Inhibitors as Add-On Therapy to Metformin for People with Type 2 Diabetes: A Review of Placebo-Controlled Trials in Asian versus Non-Asian Patients.	Metformin	38-47	solute carrier family 5 member 2	Homo sapiens	0-5
32480011-6	2020	GSDMD positive cells and NLRP3 inflammasome expression were augmented in gingival tissue, which were partly reversed by metformin.	Metformin	120-129	NLR family, pyrin domain containing 3	Mus musculus	25-30
32953746-16	2020	The combination of curcumol and metformin also suppressed tumor growth, EMT marker expression, and the activation of Wnt2/beta-Catenin signaling during in vivo experiments.	Metformin	32-41	catenin beta 1	Homo sapiens	122-134
32470468-0	2020	Metformin protects against ischaemic myocardial injury by alleviating autophagy-ROS-NLRP3-mediated inflammatory response in macrophages.	Metformin	0-9	NLR family, pyrin domain containing 3	Mus musculus	84-89
32274915-5	2020	Metformin seems to be safe and presents evident positive effects on insulin sensitivity, but long-term and consistent data are still missing to establish its role in the paediatric population and the possible effectiveness of other emergent treatments such as glucagon-like peptide-1 (GLP-1) analogues, dipeptidylpeptidase-4 (DPP-4) inhibitors, dual inhibitors of SGLT1 and SGLT2 and weight loss drugs.	Metformin	0-9	dipeptidyl peptidase 4	Homo sapiens	303-324
32274915-5	2020	Metformin seems to be safe and presents evident positive effects on insulin sensitivity, but long-term and consistent data are still missing to establish its role in the paediatric population and the possible effectiveness of other emergent treatments such as glucagon-like peptide-1 (GLP-1) analogues, dipeptidylpeptidase-4 (DPP-4) inhibitors, dual inhibitors of SGLT1 and SGLT2 and weight loss drugs.	Metformin	0-9	dipeptidyl peptidase 4	Homo sapiens	326-331
32274915-5	2020	Metformin seems to be safe and presents evident positive effects on insulin sensitivity, but long-term and consistent data are still missing to establish its role in the paediatric population and the possible effectiveness of other emergent treatments such as glucagon-like peptide-1 (GLP-1) analogues, dipeptidylpeptidase-4 (DPP-4) inhibitors, dual inhibitors of SGLT1 and SGLT2 and weight loss drugs.	Metformin	0-9	solute carrier family 5 member 2	Homo sapiens	374-379
32748391-0	2020	The Influences of Metformin on Prostate in Terms of PSA Level and Prostate Volume.	Metformin	18-27	kallikrein related peptidase 3	Homo sapiens	52-55
32748391-12	2020	CONCLUSION: Metformin appears to cause a decrease in PSA levels.	Metformin	12-21	kallikrein related peptidase 3	Homo sapiens	53-56
32792951-0	2020	Metformin Mitigates Cartilage Degradation by Activating AMPK/SIRT1-Mediated Autophagy in a Mouse Osteoarthritis Model.	Metformin	0-9	sirtuin 1	Mus musculus	61-66
32792951-11	2020	In the presence of IL-1beta, metformin increased phosphorylated levels of AMPKalpha and upregulated SIRT1 protein expression, leading to an increase in autophagy as well as a decrease in catabolism and apoptosis.	Metformin	29-38	interleukin 1 alpha	Mus musculus	19-27
32792951-11	2020	In the presence of IL-1beta, metformin increased phosphorylated levels of AMPKalpha and upregulated SIRT1 protein expression, leading to an increase in autophagy as well as a decrease in catabolism and apoptosis.	Metformin	29-38	sirtuin 1	Mus musculus	100-105
32792951-12	2020	Inactivating AMPKalpha or inhibiting SIRT1 prevented the augmented autophagy in the presence of metformin.	Metformin	96-105	sirtuin 1	Mus musculus	37-42
32792951-14	2020	Metformin protects against IL-1beta-induced extracellular matrix (ECM) degradation in cultured chondrocytes and in mouse osteoarthritis model through activating AMPKalpha/SIRT1 signaling.	Metformin	0-9	interleukin 1 alpha	Mus musculus	27-35
32792951-14	2020	Metformin protects against IL-1beta-induced extracellular matrix (ECM) degradation in cultured chondrocytes and in mouse osteoarthritis model through activating AMPKalpha/SIRT1 signaling.	Metformin	0-9	sirtuin 1	Mus musculus	171-176
32779431-10	2020	Metformin decreased the expression of S100b, neuron specific enolase (Nse), and glial fibrillary acidic protein (Gfap).	Metformin	0-9	enolase 2	Rattus norvegicus	45-68
32779431-10	2020	Metformin decreased the expression of S100b, neuron specific enolase (Nse), and glial fibrillary acidic protein (Gfap).	Metformin	0-9	enolase 2	Rattus norvegicus	70-73
32441464-0	2020	Metformin regulates adiponectin signalling in epicardial adipose tissue and reduces atrial fibrillation vulnerability.	Metformin	0-9	adiponectin, C1Q and collagen domain containing	Canis lupus familiaris	20-31
32460059-0	2020	Metformin suppresses the growth of leukemia cells partly through downregulation of AXL receptor tyrosine kinase.	Metformin	0-9	AXL receptor tyrosine kinase	Homo sapiens	83-86
32460059-2	2020	In this study, we examined the effects of metformin on the activity of receptor tyrosine kinases of the TAM (TYRO3, AXL, and MERTK) family, which have important roles in leukemia cell growth.	Metformin	42-51	AXL receptor tyrosine kinase	Homo sapiens	116-119
32460059-2	2020	In this study, we examined the effects of metformin on the activity of receptor tyrosine kinases of the TAM (TYRO3, AXL, and MERTK) family, which have important roles in leukemia cell growth.	Metformin	42-51	MER proto-oncogene, tyrosine kinase	Homo sapiens	125-130
32460059-3	2020	The results indicated that metformin suppressed the in vitro growth of four leukemia cell lines, OCI/AML2, OCI/AML3, THP-1, and K562, in a dose-dependent manner, which corresponded to the downregulation of the expression and phosphorylation of AXL and inhibition of its downstream targets such as phosphorylation of STAT3.	Metformin	27-36	RUNX family transcription factor 3	Homo sapiens	101-105
32460059-3	2020	The results indicated that metformin suppressed the in vitro growth of four leukemia cell lines, OCI/AML2, OCI/AML3, THP-1, and K562, in a dose-dependent manner, which corresponded to the downregulation of the expression and phosphorylation of AXL and inhibition of its downstream targets such as phosphorylation of STAT3.	Metformin	27-36	AXL receptor tyrosine kinase	Homo sapiens	244-247
32460059-4	2020	Furthermore, metformin augmented the suppressive effects of a small-molecule AXL inhibitor TP-0903 on the growth of OCI/AML3 and K562 cells and prevented doxorubicin-induced AXL activation in K562 cells, which induces chemoresistance in leukemia cells, thus potentiating doxorubicin anti-proliferative effects.	Metformin	13-22	AXL receptor tyrosine kinase	Homo sapiens	77-80
32460059-4	2020	Furthermore, metformin augmented the suppressive effects of a small-molecule AXL inhibitor TP-0903 on the growth of OCI/AML3 and K562 cells and prevented doxorubicin-induced AXL activation in K562 cells, which induces chemoresistance in leukemia cells, thus potentiating doxorubicin anti-proliferative effects.	Metformin	13-22	AXL receptor tyrosine kinase	Homo sapiens	174-177
32460059-5	2020	Given that metformin also downregulated expression of TYRO3 and phosphorylation of MERTK, these findings indicate that anti-leukemic effects exerted by metformin could be partly due to the inhibition of TAM kinases.	Metformin	11-20	MER proto-oncogene, tyrosine kinase	Homo sapiens	83-88
32460059-5	2020	Given that metformin also downregulated expression of TYRO3 and phosphorylation of MERTK, these findings indicate that anti-leukemic effects exerted by metformin could be partly due to the inhibition of TAM kinases.	Metformin	152-161	MER proto-oncogene, tyrosine kinase	Homo sapiens	83-88
32460059-6	2020	Thus, metformin has a clinical potential for patients with leukemia cells positive for AXL and the other TAM proteins as well as activated mTOR.	Metformin	6-15	AXL receptor tyrosine kinase	Homo sapiens	87-90
23500454-9	2013	Treatment with the insulin-sensitizing drug metformin attenuated estrogen-dependent proliferative expression of c-myc and c-fos in the obese rat endometrium compared to untreated controls and was accompanied by inhibition of phosphorylation of the insulin and IGF1 receptors (IRbeta/IGF1R) and ERK1/2.	Metformin	44-53	insulin-like growth factor 1	Rattus norvegicus	260-264
23612973-2	2013	In a previous study, we demonstrated that phosphorylation of Ser-428/431 (in LKB1(L)) by protein kinase Czeta (PKCzeta) was essential for LKB1-mediated activation of AMP-activated protein kinase (AMPK) in response to oxidants or metformin.	Metformin	229-238	serine/threonine kinase 11	Homo sapiens	77-81
23620395-6	2013	In addition, we treated Ins2(+/Akita) mice with metformin, which activates AMP-activated protein kinase (AMPK) and thereby slows the degradation of GTPCH I; despite blood glucose levels that were similar to untreated mice, those treated with metformin had significantly less albuminuria.	Metformin	48-57	GTP cyclohydrolase 1	Mus musculus	148-155
23620395-6	2013	In addition, we treated Ins2(+/Akita) mice with metformin, which activates AMP-activated protein kinase (AMPK) and thereby slows the degradation of GTPCH I; despite blood glucose levels that were similar to untreated mice, those treated with metformin had significantly less albuminuria.	Metformin	242-251	GTP cyclohydrolase 1	Mus musculus	148-155
23730503-1	2013	Dipeptidyl-peptidase-IV (DPP-4) inhibitors have become an important orally active drug class for the treatment of type 2 diabetes as second-line therapy after metformin failure or as monotherapy or combination therapy with other drugs when metformin is not tolerated or contraindicated.	Metformin	159-168	dipeptidyl peptidase 4	Homo sapiens	0-23
23730503-1	2013	Dipeptidyl-peptidase-IV (DPP-4) inhibitors have become an important orally active drug class for the treatment of type 2 diabetes as second-line therapy after metformin failure or as monotherapy or combination therapy with other drugs when metformin is not tolerated or contraindicated.	Metformin	159-168	dipeptidyl peptidase 4	Homo sapiens	25-30
23730503-1	2013	Dipeptidyl-peptidase-IV (DPP-4) inhibitors have become an important orally active drug class for the treatment of type 2 diabetes as second-line therapy after metformin failure or as monotherapy or combination therapy with other drugs when metformin is not tolerated or contraindicated.	Metformin	240-249	dipeptidyl peptidase 4	Homo sapiens	0-23
23730503-1	2013	Dipeptidyl-peptidase-IV (DPP-4) inhibitors have become an important orally active drug class for the treatment of type 2 diabetes as second-line therapy after metformin failure or as monotherapy or combination therapy with other drugs when metformin is not tolerated or contraindicated.	Metformin	240-249	dipeptidyl peptidase 4	Homo sapiens	25-30
23632475-0	2013	Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK.	Metformin	0-9	ATM serine/threonine kinase	Homo sapiens	104-107
23632475-4	2013	Metformin (i) activated the ataxia telengiectasia-mutated (ATM)-AMPK-p53/p21(cip1) and inhibited the Akt-mammalian target of rapamycin (mTOR)-eIF4E-binding protein 1 (4EBP1) pathways, (ii) induced G1 cycle arrest and (iii) enhanced apoptosis.	Metformin	0-9	ATM serine/threonine kinase	Homo sapiens	59-62
23632475-4	2013	Metformin (i) activated the ataxia telengiectasia-mutated (ATM)-AMPK-p53/p21(cip1) and inhibited the Akt-mammalian target of rapamycin (mTOR)-eIF4E-binding protein 1 (4EBP1) pathways, (ii) induced G1 cycle arrest and (iii) enhanced apoptosis.	Metformin	0-9	eukaryotic translation initiation factor 4E binding protein 1	Homo sapiens	142-165
23632475-4	2013	Metformin (i) activated the ataxia telengiectasia-mutated (ATM)-AMPK-p53/p21(cip1) and inhibited the Akt-mammalian target of rapamycin (mTOR)-eIF4E-binding protein 1 (4EBP1) pathways, (ii) induced G1 cycle arrest and (iii) enhanced apoptosis.	Metformin	0-9	eukaryotic translation initiation factor 4E binding protein 1	Homo sapiens	167-172
23632475-10	2013	Metformin and IR mediate their action through an ATM-AMPK-dependent pathway.	Metformin	0-9	ATM serine/threonine kinase	Homo sapiens	49-52
23228442-2	2013	Recent studies suggest that metformin attenuates mTORC1 signalling by the activation of 5" adenosine monophosphate-activated protein kinase (AMPK) in the presence or absence of a functional hamartin/tuberin (TSC1/TSC2) complex.	Metformin	28-37	TSC complex subunit 2	Mus musculus	213-217
23228442-3	2013	Metformin has also been reported to inhibit mTORC1 independent of AMPK through p53-dependent regulated in development and DNA damage responses 1 (REDD1) or by inhibiting Rag GTPases.	Metformin	0-9	transformation related protein 53, pseudogene	Mus musculus	79-82
23228442-8	2013	Surprisingly, the expression of the organic cation transporters Slc22a1, Slc22a2 and Slc22a3 essential for the cellular uptake of metformin was highly suppressed in renal tumours.	Metformin	130-139	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	85-92
22773548-9	2013	Cell line studies showed that metformin inhibits hepatocyte proliferation and induces cell cycle arrest at G0/G1 phase via AMP-activated protein kinase and its upstream kinase LKB1 to upregulate p21/Cip1 and p27/Kip1 and downregulate cyclin D1 in a dose-dependent manner, but independent of p53.	Metformin	30-39	serine/threonine kinase 11	Homo sapiens	176-180
22773548-9	2013	Cell line studies showed that metformin inhibits hepatocyte proliferation and induces cell cycle arrest at G0/G1 phase via AMP-activated protein kinase and its upstream kinase LKB1 to upregulate p21/Cip1 and p27/Kip1 and downregulate cyclin D1 in a dose-dependent manner, but independent of p53.	Metformin	30-39	H3 histone pseudogene 16	Homo sapiens	195-198
22773548-9	2013	Cell line studies showed that metformin inhibits hepatocyte proliferation and induces cell cycle arrest at G0/G1 phase via AMP-activated protein kinase and its upstream kinase LKB1 to upregulate p21/Cip1 and p27/Kip1 and downregulate cyclin D1 in a dose-dependent manner, but independent of p53.	Metformin	30-39	interferon alpha inducible protein 27	Homo sapiens	208-211
22773548-9	2013	Cell line studies showed that metformin inhibits hepatocyte proliferation and induces cell cycle arrest at G0/G1 phase via AMP-activated protein kinase and its upstream kinase LKB1 to upregulate p21/Cip1 and p27/Kip1 and downregulate cyclin D1 in a dose-dependent manner, but independent of p53.	Metformin	30-39	cyclin dependent kinase inhibitor 1B	Homo sapiens	212-216
23111552-0	2013	Gemfibrozil and its combination with metformin on pleiotropic effect on IL-10 and adiponectin and anti-atherogenic treatment in insulin resistant type 2 diabetes mellitus rats.	Metformin	37-46	interleukin 10	Rattus norvegicus	72-77
23111552-8	2013	OVERALL CONCLUSIONS: Gemfibrozil plus metformin decrease MMP-9, increase IL-10 and adiponectin acting as anti-atherogenic, anti-inflammatory and immunomodulatory in IR type 2 DM.	Metformin	38-47	interleukin 10	Rattus norvegicus	73-78
23379278-0	2013	Comment on "Metformin sensitizes endometrial cancer cells to chemotherapy by repressing glyoxalase I expression".	Metformin	12-21	glyoxalase I	Homo sapiens	88-100
23379985-0	2013	Response to "Comment on Metformin sensitizes endometrial cancer cells to chemotherapy by repressing glyoxalase I expression".	Metformin	24-33	glyoxalase I	Homo sapiens	100-112
23497197-12	2013	Metformin-treated ZDF rats showed a reduced expression of adiponectin receptor 2.	Metformin	0-9	adiponectin receptor 2	Rattus norvegicus	58-80
23328000-1	2013	AIMS: To assess the effects of two commonly used oral hypoglycemic medications metformin and pioglitazone on serum concentrations of omentin and leptin in patients with newly diagnosed type 2 diabetes.	Metformin	79-88	leptin	Homo sapiens	145-151
23328000-6	2013	After three months, metformin decreased both omentin and leptin concentrations in women, and leptin concentrations only in men.	Metformin	20-29	intelectin 1	Homo sapiens	45-52
23328000-6	2013	After three months, metformin decreased both omentin and leptin concentrations in women, and leptin concentrations only in men.	Metformin	20-29	leptin	Homo sapiens	57-63
23328000-10	2013	CONCLUSIONS: Metformin and pioglitazone at pharmacologic doses are equally effective in alteration of serum omentin and leptin concentrations in patients with diabetes, albeit sex differences in response to medications exist.	Metformin	13-22	intelectin 1	Homo sapiens	108-115
23328000-10	2013	CONCLUSIONS: Metformin and pioglitazone at pharmacologic doses are equally effective in alteration of serum omentin and leptin concentrations in patients with diabetes, albeit sex differences in response to medications exist.	Metformin	13-22	leptin	Homo sapiens	120-126
23449430-0	2013	Metformin impairs vascular endothelial recovery after stent placement in the setting of locally eluted mammalian target of rapamycin inhibitors via S6 kinase-dependent inhibition of cell proliferation.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	148-157
23241069-5	2013	Of the recently introduced oral hypoglycemic/antihyperglycemic agents, the DPP-4 inhibitors are moderately efficacious compared with mainstay treatment with metformin with a low side-effect profile and have good efficacy in combination with other oral agents and insulin.	Metformin	157-166	dipeptidyl peptidase 4	Homo sapiens	75-80
23373842-3	2013	Dipeptidyl peptidase-4 (DPP-4) inhibitors, commonly referred to as gliptins, offer new options for combined therapy with metformin.	Metformin	121-130	dipeptidyl peptidase 4	Homo sapiens	0-22
31694774-10	2020	SGLT2 inhibitors induced a higher risk for diabetic ketoacidosis (DKA) than metformin/placebo.	Metformin	76-85	solute carrier family 5 member 2	Homo sapiens	0-5
31607509-9	2020	DISCUSSION - CONCLUSION: Based on this study, the drug combination metformin+DPP-4 inhibitor would be the better therapy in elderly diabetic patient.	Metformin	67-76	dipeptidyl peptidase 4	Homo sapiens	77-82
31283677-8	2020	KRAS, GRB2, PCK2, BCL2L1, INSL3, DOK3, and PTPN1 were among the most significantly upregulated genes in both immunosuppression and diabetes subsets and were appropriately reverted by metformin as confirmed in vitro.	Metformin	183-192	insulin like 3	Homo sapiens	26-31
31907158-14	2019	Metformin alone did not obviously affect CD4+ cells or CD8+ cells but significantly decreased the percentage of CD4+Foxp3+ (P < 0.05); the vaccine alone significantly increased CD4+ cells and CD8+ cells (P < 0.001) and also the percentage of CD4+Foxp3+ cells (P < 0.05).	Metformin	0-9	forkhead box P3	Mus musculus	116-121
31907158-14	2019	Metformin alone did not obviously affect CD4+ cells or CD8+ cells but significantly decreased the percentage of CD4+Foxp3+ (P < 0.05); the vaccine alone significantly increased CD4+ cells and CD8+ cells (P < 0.001) and also the percentage of CD4+Foxp3+ cells (P < 0.05).	Metformin	0-9	forkhead box P3	Mus musculus	246-251
31920356-7	2019	Metformin treatment reverted hNAA40, NAMPT, and SIRT-1 expression levels to normal levels.	Metformin	0-9	N-alpha-acetyltransferase 40, NatD catalytic subunit	Homo sapiens	29-35
31620963-0	2019	Metformin-induced AMPK activation stimulates remyelination through induction of neurotrophic factors, downregulation of NogoA and recruitment of Olig2+ precursor cells in the cuprizone murine model of multiple sclerosis.	Metformin	0-9	reticulon 4	Mus musculus	120-125
31620963-7	2019	RESULTS: Our finding indicated that consumption of metformin during the recovery period potentially induced an active form of AMPK (p-AMPK) and promoted repopulation of mature OLGs (MOG+ cells, MBP+ cells) in CC through up-regulation of BDNF, CNTF, and NGF as well as down-regulation of NogoA and recruitment of Olig2+ precursor cells.	Metformin	51-60	myelin oligodendrocyte glycoprotein	Mus musculus	182-185
31620963-7	2019	RESULTS: Our finding indicated that consumption of metformin during the recovery period potentially induced an active form of AMPK (p-AMPK) and promoted repopulation of mature OLGs (MOG+ cells, MBP+ cells) in CC through up-regulation of BDNF, CNTF, and NGF as well as down-regulation of NogoA and recruitment of Olig2+ precursor cells.	Metformin	51-60	brain derived neurotrophic factor	Mus musculus	237-241
31620963-7	2019	RESULTS: Our finding indicated that consumption of metformin during the recovery period potentially induced an active form of AMPK (p-AMPK) and promoted repopulation of mature OLGs (MOG+ cells, MBP+ cells) in CC through up-regulation of BDNF, CNTF, and NGF as well as down-regulation of NogoA and recruitment of Olig2+ precursor cells.	Metformin	51-60	reticulon 4	Mus musculus	287-292
31657647-2	2019	We found that metformin treatment down-regulated integrin beta1 concomitant with the loss of inositol polyphosphate multikinase (IPMK) in murine myocytes, adipocytes, and hepatocytes.	Metformin	14-23	integrin beta 1 (fibronectin receptor beta)	Mus musculus	49-63
31657647-2	2019	We found that metformin treatment down-regulated integrin beta1 concomitant with the loss of inositol polyphosphate multikinase (IPMK) in murine myocytes, adipocytes, and hepatocytes.	Metformin	14-23	inositol polyphosphate multikinase	Mus musculus	93-127
31657647-2	2019	We found that metformin treatment down-regulated integrin beta1 concomitant with the loss of inositol polyphosphate multikinase (IPMK) in murine myocytes, adipocytes, and hepatocytes.	Metformin	14-23	inositol polyphosphate multikinase	Mus musculus	129-133
31657647-6	2019	Together our data indicate that IPMK participates in the regulation of cell migration and provides a potential link between metformin and wound healing impairment.-Tu-Sekine, B., Padhi, A., Jin, S., Kalyan, S., Singh, K., Apperson, M., Kapania, R., Hur, S. C., Nain, A., Kim, S. F. Inositol polyphosphate multikinase is a metformin target that regulates cell migration.	Metformin	124-133	inositol polyphosphate multikinase	Mus musculus	32-36
23373842-3	2013	Dipeptidyl peptidase-4 (DPP-4) inhibitors, commonly referred to as gliptins, offer new options for combined therapy with metformin.	Metformin	121-130	dipeptidyl peptidase 4	Homo sapiens	24-29
23421949-3	2013	Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for combined therapy with metformin.	Metformin	86-95	dipeptidyl peptidase 4	Homo sapiens	0-22
23421949-3	2013	Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for combined therapy with metformin.	Metformin	86-95	dipeptidyl peptidase 4	Homo sapiens	24-29
23194004-9	2013	Maybe, the dose, and possibly the time of use, of metformin are factors associated with the reduction of AMH levels.	Metformin	50-59	anti-Mullerian hormone	Homo sapiens	105-108
22861817-3	2013	As organic cation transporters (OCT) belonging to the solute carrier 22A gene family, including OCT-1, OCT-2, and OCT-3, mediate metformin uptake and activity, it is critical to define what role they play in the antineoplastic activity of metformin.	Metformin	129-138	solute carrier family 22 member 2	Homo sapiens	103-108
23280877-5	2013	In vivo kidney uptake clearances of benzylpenicillin and metformin, which are typical substrates for renal organic anion transporters Oat1 and Oat3 and organic cation transporters Oct1 and Oct2, respectively, were evaluated.	Metformin	57-66	solute carrier family 22 member 8	Rattus norvegicus	143-147
23228696-8	2013	Finally, expression of constitutive activate MKK6 or HA-p38 MAPK vectors in lung cancer cells was able to abrogate ERCC1 downregulation by metformin and paclitaxel as well as cell viability and DNA repair capacity.	Metformin	139-148	ERCC excision repair 1, endonuclease non-catalytic subunit	Homo sapiens	115-120
23391573-0	2013	Metformin decreases meal size and number and increases c-Fos expression in the nucleus tractus solitarius of obese mice.	Metformin	0-9	FBJ osteosarcoma oncogene	Mus musculus	55-60
31633875-4	2019	Furosemide (FUR) and metformin (MET) were added to 99m Tc-DTPA solution (weight ratios 1/1 vol:vol) followed by the quantification of 99m Tc-DTPA binding rates to HSA (40 g/L) using equilibrium dialysis and the qualification of this binding using Molecular Modeling methods.	Metformin	21-30	SAFB like transcription modulator	Homo sapiens	32-35
31744691-8	2019	Metformin promoted the expression of p-AMPK, P53, P21CIP1 and P27KIP1, while inhibited the expression of CDK4 and CyclinD1.	Metformin	0-9	cyclin dependent kinase inhibitor 1B	Homo sapiens	62-69
32694673-6	2019	In primary mouse hepatocytes, metformin stimulates the secretion of GDF15 by increasing the expression of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP; also known as DDIT3).	Metformin	30-39	DNA-damage inducible transcript 3	Mus musculus	151-175
32694673-6	2019	In primary mouse hepatocytes, metformin stimulates the secretion of GDF15 by increasing the expression of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP; also known as DDIT3).	Metformin	30-39	DNA-damage inducible transcript 3	Mus musculus	177-181
32694673-6	2019	In primary mouse hepatocytes, metformin stimulates the secretion of GDF15 by increasing the expression of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP; also known as DDIT3).	Metformin	30-39	DNA-damage inducible transcript 3	Mus musculus	197-202
32694673-7	2019	In wild-type mice fed a high-fat diet, oral administration of metformin increases serum GDF15 and reduces food intake, body mass, fasting insulin and glucose intolerance; these effects are eliminated in GDF15 null mice.	Metformin	62-71	growth differentiation factor 15	Mus musculus	88-93
32694673-7	2019	In wild-type mice fed a high-fat diet, oral administration of metformin increases serum GDF15 and reduces food intake, body mass, fasting insulin and glucose intolerance; these effects are eliminated in GDF15 null mice.	Metformin	62-71	growth differentiation factor 15	Mus musculus	203-208
31582211-5	2019	Met evidently inhibited the migration of HUVEC and HPASMC cells, and UCA1 and MMP9 levels showed a stepwise decline, while miR-204 level displayed a gradual increase as the concentration of Met increased when compared with the negative controls.	Metformin	190-193	microRNA 204	Homo sapiens	123-130
31582211-9	2019	Taken together, we found that administration of metformin prevents pre-eclampsia by suppressing migration of trophoblast cells via modulating the signaling pathway of UCA1/miR-204/MMP-9.	Metformin	48-57	microRNA 204	Homo sapiens	172-179
31849810-6	2019	Clinically, evidence for involvement of insulin signaling pathways in DM1 is based on the increased incidence of insulin resistance seen in clinical practice and recent trial evidence of beneficial effects of metformin on muscle function.	Metformin	209-218	immunoglobulin heavy diversity 1-7	Homo sapiens	70-73
31703101-5	2019	Significantly elevated faecal sIgA levels during administration of metformin, and its correlation with the expression of genes associated with immune response (CXCR4, HLA-DQA1, MAP3K14, TNFRSF21, CCL4, ACVR1B, PF4, EPOR, CXCL8) supports a novel hypothesis of strong association between metformin and intestinal immune system, and for the first time provide evidence for altered RNA expression as a contributing mechanism of metformin"s action.	Metformin	67-76	mitogen-activated protein kinase kinase kinase 14	Homo sapiens	177-184
31703101-5	2019	Significantly elevated faecal sIgA levels during administration of metformin, and its correlation with the expression of genes associated with immune response (CXCR4, HLA-DQA1, MAP3K14, TNFRSF21, CCL4, ACVR1B, PF4, EPOR, CXCL8) supports a novel hypothesis of strong association between metformin and intestinal immune system, and for the first time provide evidence for altered RNA expression as a contributing mechanism of metformin"s action.	Metformin	67-76	TNF receptor superfamily member 21	Homo sapiens	186-194
31703101-5	2019	Significantly elevated faecal sIgA levels during administration of metformin, and its correlation with the expression of genes associated with immune response (CXCR4, HLA-DQA1, MAP3K14, TNFRSF21, CCL4, ACVR1B, PF4, EPOR, CXCL8) supports a novel hypothesis of strong association between metformin and intestinal immune system, and for the first time provide evidence for altered RNA expression as a contributing mechanism of metformin"s action.	Metformin	67-76	C-C motif chemokine ligand 4	Homo sapiens	196-200
31703101-5	2019	Significantly elevated faecal sIgA levels during administration of metformin, and its correlation with the expression of genes associated with immune response (CXCR4, HLA-DQA1, MAP3K14, TNFRSF21, CCL4, ACVR1B, PF4, EPOR, CXCL8) supports a novel hypothesis of strong association between metformin and intestinal immune system, and for the first time provide evidence for altered RNA expression as a contributing mechanism of metformin"s action.	Metformin	67-76	erythropoietin receptor	Homo sapiens	215-219
31698699-7	2019	Additionally, treatment with metformin and 2DG (5 mM) inhibited the Akt/mTOR pathway and down-regulated the cell-cycle-related proteins such as p-cyclin B1 (S147) and cyclins D1 and D2 when compared to cells that were treated with either 2DG or metformin alone.	Metformin	29-38	mechanistic target of rapamycin kinase	Mus musculus	72-76
31695754-9	2019	DPP-4 inhibitors were prescribed over metformin in patients with renal disease (odds ratio [OR]: 4.20; p < 0.0001), coronary heart disease and stroke (OR: 2.22; p < 0.0001).	Metformin	38-47	dipeptidyl peptidase 4	Homo sapiens	0-5
31511257-6	2019	In vivo inhibition of OCT2/MATE2-K by a single dose of DX-619 in cynomolgus monkeys resulted in the elevation of the area under the curve of m1A (1.72-fold) as well as metformin (2.18-fold).	Metformin	168-177	solute carrier family 47, member 2	Mus musculus	27-32
31668383-6	2019	RESULTS: Treatment with the biguanide metformin lowers lipolysis in beige fat by inducing protein phosphatase 2A (PP2A) independently of adenosine monophosphate kinase (AMPK) activation.	Metformin	28-47	protein phosphatase 2 phosphatase activator	Homo sapiens	98-112
31668383-6	2019	RESULTS: Treatment with the biguanide metformin lowers lipolysis in beige fat by inducing protein phosphatase 2A (PP2A) independently of adenosine monophosphate kinase (AMPK) activation.	Metformin	28-47	protein phosphatase 2 phosphatase activator	Homo sapiens	114-118
31668383-8	2019	Moreover, co-incubation of metformin with the PP2A inhibitor okadaic acid countered the anti-lipolytic effects of this biguanide in human adipose.	Metformin	27-36	protein phosphatase 2 phosphatase activator	Homo sapiens	46-50
31442575-7	2019	Metformin and Liraglutide were shown to elicit significantly greater release of TNFa, IL-6, and GM-CSF, while Sitagliptin had a lesser effect on pro-inflammatory cytokine production.	Metformin	0-9	colony stimulating factor 2	Homo sapiens	96-102
31203154-0	2019	Metformin exhibits its therapeutic effect in the treatment of pre-eclampsia via modulating the Met/H19/miR-148a-5p/P28 and Met/H19/miR-216-3p/EBI3 signaling pathways.	Metformin	0-9	microRNA 148a	Rattus norvegicus	103-111
31203154-0	2019	Metformin exhibits its therapeutic effect in the treatment of pre-eclampsia via modulating the Met/H19/miR-148a-5p/P28 and Met/H19/miR-216-3p/EBI3 signaling pathways.	Metformin	0-9	golgi SNAP receptor complex member 1	Rattus norvegicus	115-118
31120617-0	2019	RasGRP1 is a target for VEGF to induce angiogenesis and involved in the endothelial-protective effects of metformin under high glucose in HUVECs.	Metformin	106-115	RAS guanyl releasing protein 1	Homo sapiens	0-7
31120617-4	2019	Furthermore, we investigate whether RasGRP1-dependent VEGF signaling was downregulated under high glucose conditions mimicking diabetes and required for the endothelial protective action of metformin in human umbilical vein endothelial cells (HUVECs).	Metformin	190-199	RAS guanyl releasing protein 1	Homo sapiens	36-43
31120617-8	2019	The expression of VEGF, RasGRP1, and AKT phosphorylation was downregulated in HUVECs exposed to high glucose compared with normal glucose, whereas metformin upregulated the RasGRP1-dependent VEGF signaling and ameliorates the impaired angiogenesis caused by high glucose.	Metformin	147-156	RAS guanyl releasing protein 1	Homo sapiens	173-180
31120617-9	2019	RasGRP1 is involved in the VEGF-induced angiogenesis and the pro-angiogenesis effects of metformin under hyperglycemia.	Metformin	89-98	RAS guanyl releasing protein 1	Homo sapiens	0-7
31375850-9	2019	The use of SGLT-2 inhibitors is recommended in current guidelines and consensus statements as primary combination partners for metformin in patients with type 2 diabetes and established CV disease, high CV risk, heart failure or kidney disease.	Metformin	127-136	solute carrier family 5 member 2	Homo sapiens	11-17
30945296-12	2019	Furthermore, after stimulation with the mTOR inhibitor rapamycin, additional metformin treatment could still downregulate Nek7/NLRP3.	Metformin	77-86	mechanistic target of rapamycin kinase	Mus musculus	40-44
30945296-12	2019	Furthermore, after stimulation with the mTOR inhibitor rapamycin, additional metformin treatment could still downregulate Nek7/NLRP3.	Metformin	77-86	NLR family, pyrin domain containing 3	Mus musculus	127-132
30945296-14	2019	Metformin suppressed the inflammatory state by inhibiting Nek7 expression to decrease NLRP3 inflammasome activity.	Metformin	0-9	NLR family, pyrin domain containing 3	Mus musculus	86-91
31273790-4	2019	We examined metformin"s regulation of angiopoietin-like 3 (ANGPTL3), a liver-derived secretory protein with LPL inhibitory property.	Metformin	12-21	lipoprotein lipase	Homo sapiens	108-111
31273790-12	2019	CONCLUSIONS: Metformin inhibits ANGPTL3 expression in the liver in an AMPK-SIRT1-independent manner as a potential mechanism to regulate LPL and lower plasma lipids.	Metformin	13-22	lipoprotein lipase	Homo sapiens	137-140
31271767-3	2019	A total of 32 db/db mice were randomly divided into four groups (n = 8/group): the DMT1 group, treated with metformin (250 mg/kg/day); the DMT2 group, treated with metformin (250 mg/kg/day) plus empagliflozin (10 mg/kg/day); the DMT3 group, treated with empagliflozin (10 mg/kg/day); the T2DM control group (DM), received 0.5% Natrosol.	Metformin	164-173	rhabdomyosarcoma 2 associated transcript (non-coding RNA)	Mus musculus	139-143
31467666-0	2019	Metformin represses the pathophysiology of AAA by suppressing the activation of PI3K/AKT/mTOR/autophagy pathway in ApoE-/- mice.	Metformin	0-9	mechanistic target of rapamycin kinase	Mus musculus	89-93
31467666-9	2019	In addition, metformin significantly suppressed the activation of the PI3K/AKT/mToR pathway and decreased the mRNA and protein levels of LC3B and Beclin1, which were induced by Ang-II.	Metformin	13-22	mechanistic target of rapamycin kinase	Mus musculus	79-83
31467666-9	2019	In addition, metformin significantly suppressed the activation of the PI3K/AKT/mToR pathway and decreased the mRNA and protein levels of LC3B and Beclin1, which were induced by Ang-II.	Metformin	13-22	beclin 1, autophagy related	Mus musculus	146-153
31467666-13	2019	Conclusions: Metformin represses the pathophysiology of AAA by inhibiting the activation of PI3K/AKT/mTOR/autophagy pathway.	Metformin	13-22	mechanistic target of rapamycin kinase	Mus musculus	101-105
31489272-4	2019	We report a novel complication of hypoglycemia that occurred during the course of treatment of SGLT2 inhibitor-induced DKA in a patient with type 2 diabetes mellitus (T2DM) on the dapagliflozin-metformin combination.	Metformin	194-203	solute carrier family 5 member 2	Homo sapiens	95-100
31501716-4	2019	In this study, fecal microbiota transplantation (FMT) using fecal material from metformin-treated mice was found to upregulate the expression of GLP-1 and pattern-recognition receptors TLR1 and TLR4 for the improvement in hyperglycemia caused by a high-fat diet.	Metformin	80-89	toll-like receptor 1	Mus musculus	185-189
31150647-0	2019	Metformin inhibits PPARdelta agonist-mediated tumor growth by reducing Glut1 and SLC1A5 expressions of cancer cells.	Metformin	0-9	solute carrier family 2 (facilitated glucose transporter), member 1	Mus musculus	71-76
31391459-0	2019	Correction: H19 lncRNA alters methylation and expression of Hnf4alpha in the liver of metformin-exposed fetuses.	Metformin	86-95	H19 imprinted maternally expressed transcript	Homo sapiens	12-15
31132357-5	2019	The results suggested metformin decreased the inflammatory response by reducing the expression of proinflammatory cytokines (TNF-alpha, IL-1beta and IL-6), myeloperoxidase activity, and malondialdehyde levels.	Metformin	22-31	myeloperoxidase	Rattus norvegicus	156-171
31285421-10	2019	Moreover, blocking Drp1 with metformin rescued necroptosis and hepatic injury triggered by CdCl2.	Metformin	29-38	dynamin 1 like	Homo sapiens	19-23
30445633-9	2019	Treatment of metformin led to activation of AMP-activated protein kinase (AMPK) and attenuated signaling of the downstream molecules such as p-mTOR, p-p70S6K and cyclin D1 expression both in vivo and in vitro.	Metformin	13-22	ribosomal protein S6 kinase B1	Rattus norvegicus	151-157
31273547-3	2019	In this study, the application of DMBG partially alleviates the pathological changes in the kidneys of db/db mice, increases the level of the klotho protein in the blood, urine and kidney tissues of the mice, and reduces the levels of the mTOR and p-mTOR proteins.	Metformin	34-38	mechanistic target of rapamycin kinase	Mus musculus	239-243
31273547-3	2019	In this study, the application of DMBG partially alleviates the pathological changes in the kidneys of db/db mice, increases the level of the klotho protein in the blood, urine and kidney tissues of the mice, and reduces the levels of the mTOR and p-mTOR proteins.	Metformin	34-38	mechanistic target of rapamycin kinase	Mus musculus	250-254
31082618-0	2019	Metformin inhibits beta-catenin phosphorylation on Ser-552 through an AMPK/PI3K/Akt pathway in colorectal cancer cells.	Metformin	0-9	catenin beta 1	Homo sapiens	19-31
31082618-4	2019	Here we report that a non-canonical Ser552 phosphorylation in beta-catenin, which promotes its nuclear accumulation and transcriptional activity, is blocked by metformin via AMPK-mediated PI3K/Akt signaling inhibition.	Metformin	160-169	catenin beta 1	Homo sapiens	62-74
31559762-6	2019	In metformin uncontrolled patients, 56.8% responders chose to start a DPP4 inhibitor.	Metformin	3-12	dipeptidyl peptidase 4	Homo sapiens	70-74
31142603-7	2019	Our data show that metformin increased IL-10 and IDO expression in Ad-hMSCs and decreased high-mobility group box 1 protein, IL-1beta, and IL-6 expression.	Metformin	19-28	interleukin 10	Rattus norvegicus	39-44
31142603-9	2019	In cocultures, metformin-stimulated Ad-hMSCs inhibited the mRNA expression of RUNX2, COL X, VEGF, MMP1, MMP3, and MMP13 in IL-1beta-stimulated OA chondrocytes and increased the expression of TIMP1 and TIMP3.	Metformin	15-24	vascular endothelial growth factor A	Rattus norvegicus	92-96
31142603-9	2019	In cocultures, metformin-stimulated Ad-hMSCs inhibited the mRNA expression of RUNX2, COL X, VEGF, MMP1, MMP3, and MMP13 in IL-1beta-stimulated OA chondrocytes and increased the expression of TIMP1 and TIMP3.	Metformin	15-24	matrix metallopeptidase 1	Rattus norvegicus	98-102
31316549-3	2019	After demonstrating the efficacy of the biguanide metformin (a PGC-1alpha activator) in a cell model of DS, we extended the study to other molecules that regulate the PGC-1alpha pathway acting on PPAR genes.	Metformin	50-59	PPARG coactivator 1 alpha	Sus scrofa	63-73
31316549-3	2019	After demonstrating the efficacy of the biguanide metformin (a PGC-1alpha activator) in a cell model of DS, we extended the study to other molecules that regulate the PGC-1alpha pathway acting on PPAR genes.	Metformin	50-59	PPARG coactivator 1 alpha	Sus scrofa	167-177
31271575-0	2019	Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes mellitus with inadequate glycemic control on metformin: a meta-analysis.	Metformin	129-138	solute carrier family 5 member 2	Homo sapiens	23-53
31275243-6	2019	This action was seen when DPP-4 inhibitors were used both as monotherapy and as add-on to other therapies, i.e., metformin, sulfonylureas, tiazolidinediones or exogenous insulin.	Metformin	113-122	dipeptidyl peptidase 4	Homo sapiens	26-31
23391573-6	2013	Furthermore, metformin significantly increased c-Fos immunoreactivity within the NTS of obese mice compared to that in controls and pair-fed group, and induced a CTA at doses of 150 or 300 mg/kg.	Metformin	13-22	FBJ osteosarcoma oncogene	Mus musculus	47-52
23264620-8	2013	Furthermore, PGC-1beta is up-regulated by metformin, and metformin-associated anti-proliferative activity in VSMCs is at least partially dependent on PGC-1beta.	Metformin	42-51	PPARG coactivator 1 beta	Rattus norvegicus	13-22
23264620-8	2013	Furthermore, PGC-1beta is up-regulated by metformin, and metformin-associated anti-proliferative activity in VSMCs is at least partially dependent on PGC-1beta.	Metformin	57-66	PPARG coactivator 1 beta	Rattus norvegicus	150-159
24335168-4	2013	Treatment with metformin was also associated with activation of AMP kinase and inhibition of mTOR/p70S6K/pS6 signaling in both cells.	Metformin	15-24	ribosomal protein S6 kinase B1	Homo sapiens	98-104
23430507-4	2013	RESULTS: The combination of metformin-resveratrol-HMB significantly increased fat oxidation, AMP-activated protein kinase, and Sirt1 activity in muscle cells compared with metformin or resveratrol-HMB alone.	Metformin	28-37	sirtuin 1	Mus musculus	127-132
24324494-5	2013	SLC22A1, SLC47A1, and ATM gene variants were repeatedly associated with the response to metformin.	Metformin	88-97	ATM serine/threonine kinase	Homo sapiens	22-25
24088749-7	2013	Regarding inflammatory biomarkers, sitagliptin + metformin more effectively reduced the levels of resistin, vaspin and omentin-1 than placebo + metformin.	Metformin	49-58	resistin	Homo sapiens	98-106
25098041-0	2013	Effect of metformin hydrochloride in correcting hyperinsulinemia and high leptin levels in treatment of infertile polycystic patients.	Metformin	10-33	leptin	Homo sapiens	74-80
25098041-10	2013	RESULTS: After 3 and 6 months of Metformin therapy, significant reduction in biochemical parameters was observed such as fasting glucose, insulin and leptin.	Metformin	33-42	leptin	Homo sapiens	150-156
23662021-1	2013	OBJECTIVE: To compare and study the dipeptidy1 peptidase-4 (DPP-4) inhibitors in combination with metformin against established combination therapies.	Metformin	98-107	dipeptidyl peptidase 4	Homo sapiens	36-58
23662021-1	2013	OBJECTIVE: To compare and study the dipeptidy1 peptidase-4 (DPP-4) inhibitors in combination with metformin against established combination therapies.	Metformin	98-107	dipeptidyl peptidase 4	Homo sapiens	60-65
23563040-3	2013	RESULTS: Twelve-week treatment with fenofibrate and metformin reduced plasma levels of fibrinogen and PAI-1 and tended to change the other hemostatic markers measured, as well as improved insulin sensitivity.	Metformin	52-61	serpin family E member 1	Homo sapiens	102-107
23437362-0	2013	Different patterns of Akt and ERK feedback activation in response to rapamycin, active-site mTOR inhibitors and metformin in pancreatic cancer cells.	Metformin	112-121	EPH receptor B2	Homo sapiens	30-33
23437362-8	2013	In contrast, metformin abolished mTORC1 activation without over-stimulating Akt phosphorylation on Ser(473) and prevented mitogen-stimulated ERK activation in PDAC cells.	Metformin	13-22	EPH receptor B2	Homo sapiens	141-144
23437362-10	2013	Thus, the effects of metformin on Akt and ERK activation are strikingly different from allosteric or active-site mTOR inhibitors in PDAC cells, though all these agents potently inhibited the mTORC1/S6K axis.	Metformin	21-30	EPH receptor B2	Homo sapiens	42-45
31165723-8	2019	Moreover, metformin intake reduces the number of nuclear aggregates of mutant huntingtin in the striatum.	Metformin	10-19	huntingtin	Mus musculus	78-88
31165723-9	2019	The expression of brain-derived neurotrophic factor, which is reduced in mutant animals, is partially restored in metformin-treated mice, and glial activation in mutant mice is reduced in metformin-treated animals.	Metformin	114-123	brain derived neurotrophic factor	Mus musculus	18-51
31165723-9	2019	The expression of brain-derived neurotrophic factor, which is reduced in mutant animals, is partially restored in metformin-treated mice, and glial activation in mutant mice is reduced in metformin-treated animals.	Metformin	188-197	brain derived neurotrophic factor	Mus musculus	18-51
30753544-3	2019	RESULTS: Metformin added to peripheral blood mononuclear cells from healthy volunteers enhanced in vitro cellular metabolism while inhibiting the mammalian target of rapamycin targets p70S6K and 4EBP1, with decreased cytokine production and cellular proliferation and increased phagocytosis activity.	Metformin	9-18	ribosomal protein S6 kinase B1	Homo sapiens	184-200
31002870-5	2019	The results showed that metformin pretreatment increased the phosphorylation of HDAC5 at serine 498, leading to the upregulation of KLF2, and eliminated lipopolysaccharide (LPS) and tumor necrosis factor   (TNF )-induced upregulation of vascular cell adhesion molecule 1 (VCAM1).	Metformin	24-33	vascular cell adhesion molecule 1	Mus musculus	237-270
31002870-5	2019	The results showed that metformin pretreatment increased the phosphorylation of HDAC5 at serine 498, leading to the upregulation of KLF2, and eliminated lipopolysaccharide (LPS) and tumor necrosis factor   (TNF )-induced upregulation of vascular cell adhesion molecule 1 (VCAM1).	Metformin	24-33	vascular cell adhesion molecule 1	Mus musculus	272-277
30604594-1	2019	BACKGROUND: Combination of metformin to reduce the fasting plasma glucose level and an alpha-glucosidase inhibitor to decrease the postprandial glucose level is expected to generate a complementary effect.	Metformin	27-36	sucrase-isomaltase	Homo sapiens	87-104
23041647-11	2012	Fibronectin and collagen expression was diminished by metformin through AMPKalpha1 activation in cultured fibroblasts.	Metformin	54-63	fibronectin 1	Mus musculus	0-11
23141431-6	2012	Metformin with insulin significantly increased mRNA expressions of INSR, IGF-1R, and IRS-1, while metformin alone had no significant effect.	Metformin	0-9	insulin receptor substrate 1	Homo sapiens	85-90
23041548-0	2012	Carbon source and myc expression influence the antiproliferative actions of metformin.	Metformin	76-85	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	18-21
23041548-5	2012	Overexpression of myc was associated with sensitization to the antiproliferative effects of metformin, consistent with myc involvement in "glutamine addiction".	Metformin	92-101	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	18-21
22968630-0	2012	NYGGF4 (PID1) effects on insulin resistance are reversed by metformin in 3T3-L1 adipocytes.	Metformin	60-69	phosphotyrosine interaction domain containing 1	Homo sapiens	0-6
22968630-0	2012	NYGGF4 (PID1) effects on insulin resistance are reversed by metformin in 3T3-L1 adipocytes.	Metformin	60-69	phosphotyrosine interaction domain containing 1	Homo sapiens	8-12
22968630-2	2012	We aimed in the present study to further elucidate the effects of NYGGF4 on IR and the underlying mechanisms through using metformin treatment in 3T3-L1 adipocytes.	Metformin	123-132	phosphotyrosine interaction domain containing 1	Homo sapiens	66-72
22968630-3	2012	Our data showed that the metformin pretreatment strikingly enhanced insulin-stimulated glucose uptake through increasing GLUT4 translocation to the PM in NYGGF4 overexpression adipocytes.	Metformin	25-34	phosphotyrosine interaction domain containing 1	Homo sapiens	154-160
22968630-4	2012	NYGGF4 overexpression resulted in significant inhibition of tyrosine phosphorylation of IRS-1 and serine phosphorylation of Akt, whereas incubation with metformin strongly activated IRS-1 and Akt phosphorylation in NYGGF4 overexpression adipocytes.	Metformin	153-162	insulin receptor substrate 1	Homo sapiens	182-187
22968630-4	2012	NYGGF4 overexpression resulted in significant inhibition of tyrosine phosphorylation of IRS-1 and serine phosphorylation of Akt, whereas incubation with metformin strongly activated IRS-1 and Akt phosphorylation in NYGGF4 overexpression adipocytes.	Metformin	153-162	phosphotyrosine interaction domain containing 1	Homo sapiens	215-221
22736406-2	2012	This work, therefore, aimed to assess the impact of such factors on the efficacy of the DPP-4 inhibitor, vildagliptin, in add-on therapy to metformin.	Metformin	140-149	dipeptidyl peptidase 4	Homo sapiens	88-93
31137785-0	2019	Heme Oxygenase-1 Inhibition Sensitizes Human Prostate Cancer Cells towards Glucose Deprivation and Metformin-Mediated Cell Death.	Metformin	99-108	heme oxygenase 1	Homo sapiens	0-16
31123716-4	2019	We demonstrate metformin intake at a clinically relevant dose impacts the hormone receptor positive (HR+) luminal cells in the normal murine mammary gland.	Metformin	15-24	nuclear receptor subfamily 4, group A, member 1	Mus musculus	74-90
31031016-0	2019	Combination of Hypoglycemia and Metformin Impairs Tumor Metabolic Plasticity and Growth by Modulating the PP2A-GSK3beta-MCL-1 Axis.	Metformin	32-41	protein phosphatase 2 phosphatase activator	Homo sapiens	106-110
31031016-0	2019	Combination of Hypoglycemia and Metformin Impairs Tumor Metabolic Plasticity and Growth by Modulating the PP2A-GSK3beta-MCL-1 Axis.	Metformin	32-41	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	120-125
31031016-4	2019	Synergistic anti-neoplastic effects of the metformin/hypoglycemia combination were mediated by glycogen synthase kinase 3beta (GSK3beta) activation downstream of PP2A, leading to a decline in the pro-survival protein MCL-1, and cell death.	Metformin	43-52	protein phosphatase 2 phosphatase activator	Homo sapiens	162-166
31031016-4	2019	Synergistic anti-neoplastic effects of the metformin/hypoglycemia combination were mediated by glycogen synthase kinase 3beta (GSK3beta) activation downstream of PP2A, leading to a decline in the pro-survival protein MCL-1, and cell death.	Metformin	43-52	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	217-222
31031016-5	2019	Mechanistically, specific activation of the PP2A-GSK3beta axis was the sum of metformin-induced inhibition of CIP2A, a PP2A suppressor, and of upregulation of the PP2A regulatory subunit B56delta by low glucose, leading to an active PP2A-B56delta complex with high affinity toward GSK3beta.	Metformin	78-87	protein phosphatase 2 phosphatase activator	Homo sapiens	44-48
31031016-5	2019	Mechanistically, specific activation of the PP2A-GSK3beta axis was the sum of metformin-induced inhibition of CIP2A, a PP2A suppressor, and of upregulation of the PP2A regulatory subunit B56delta by low glucose, leading to an active PP2A-B56delta complex with high affinity toward GSK3beta.	Metformin	78-87	protein phosphatase 2 phosphatase activator	Homo sapiens	119-123
31031016-5	2019	Mechanistically, specific activation of the PP2A-GSK3beta axis was the sum of metformin-induced inhibition of CIP2A, a PP2A suppressor, and of upregulation of the PP2A regulatory subunit B56delta by low glucose, leading to an active PP2A-B56delta complex with high affinity toward GSK3beta.	Metformin	78-87	protein phosphatase 2 phosphatase activator	Homo sapiens	119-123
31031016-5	2019	Mechanistically, specific activation of the PP2A-GSK3beta axis was the sum of metformin-induced inhibition of CIP2A, a PP2A suppressor, and of upregulation of the PP2A regulatory subunit B56delta by low glucose, leading to an active PP2A-B56delta complex with high affinity toward GSK3beta.	Metformin	78-87	protein phosphatase 2 phosphatase activator	Homo sapiens	119-123
31077199-0	2019	Metformin regulates lipid metabolism in a canine model of atrial fibrillation through AMPK/PPAR-alpha/VLCAD pathway.	Metformin	0-9	peroxisome proliferator activated receptor alpha	Canis lupus familiaris	91-101
31077199-12	2019	Metformin reduces lipid accumulation and promotes beta-oxidation of FA in AF models partially through AMPK/PPAR-alpha/VLCAD pathway.	Metformin	0-9	peroxisome proliferator activated receptor alpha	Canis lupus familiaris	107-117
30703397-6	2019	At the molecular level, we found that metformin pretreatment not only prevented the changes of FOS, JUNB and BDNF at both mRNA and protein levels, but also increased the expression of the postsynaptic scaffold genes HOMER and PSD95 after exposure to hypobaric hypoxia.	Metformin	38-47	JunB proto-oncogene, AP-1 transcription factor subunit	Rattus norvegicus	100-104
30032440-2	2019	We found that, in ultra-high-molecular-weight polyethylene particle-induced osteolysis mouse models, metformin had bone protect property and reduced the negative regulator of bone formation sclerostin (SOST) and Dickkopf-related protein 1 (DKK1), and increased osteoprotegerin (OPG) secretion and the ratio of OPG/Receptor Activator for Nuclear Factor-kappaB Ligand (RANKL).	Metformin	101-110	tumor necrosis factor (ligand) superfamily, member 11	Mus musculus	367-372
31205529-11	2019	Metformin blocked the inhibitory effect of insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor substrate 1 (IRS-1) pathway on TSC-2, and hyperglycemia impaired metformin-induced inhibition of IGF-1R/IRS-1 pathway and modulated the invasiveness of bile duct cancer cells; however, this effect was impaired by hyperglycemia.	Metformin	0-9	insulin receptor substrate 1	Homo sapiens	90-118
31205529-11	2019	Metformin blocked the inhibitory effect of insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor substrate 1 (IRS-1) pathway on TSC-2, and hyperglycemia impaired metformin-induced inhibition of IGF-1R/IRS-1 pathway and modulated the invasiveness of bile duct cancer cells; however, this effect was impaired by hyperglycemia.	Metformin	0-9	insulin receptor substrate 1	Homo sapiens	120-125
31205529-11	2019	Metformin blocked the inhibitory effect of insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor substrate 1 (IRS-1) pathway on TSC-2, and hyperglycemia impaired metformin-induced inhibition of IGF-1R/IRS-1 pathway and modulated the invasiveness of bile duct cancer cells; however, this effect was impaired by hyperglycemia.	Metformin	0-9	insulin receptor substrate 1	Homo sapiens	211-216
31205529-11	2019	Metformin blocked the inhibitory effect of insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor substrate 1 (IRS-1) pathway on TSC-2, and hyperglycemia impaired metformin-induced inhibition of IGF-1R/IRS-1 pathway and modulated the invasiveness of bile duct cancer cells; however, this effect was impaired by hyperglycemia.	Metformin	172-181	insulin receptor substrate 1	Homo sapiens	90-118
31205529-11	2019	Metformin blocked the inhibitory effect of insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor substrate 1 (IRS-1) pathway on TSC-2, and hyperglycemia impaired metformin-induced inhibition of IGF-1R/IRS-1 pathway and modulated the invasiveness of bile duct cancer cells; however, this effect was impaired by hyperglycemia.	Metformin	172-181	insulin receptor substrate 1	Homo sapiens	120-125
31205529-11	2019	Metformin blocked the inhibitory effect of insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor substrate 1 (IRS-1) pathway on TSC-2, and hyperglycemia impaired metformin-induced inhibition of IGF-1R/IRS-1 pathway and modulated the invasiveness of bile duct cancer cells; however, this effect was impaired by hyperglycemia.	Metformin	172-181	insulin receptor substrate 1	Homo sapiens	211-216
30502742-3	2019	Metformin, in use for 60 years, is the first choice drug for type 2 diabetes and based on pre-clinical and clinical data metformin has proven cardiovascular protective actions; in contrast SGLT2 inhibitors were only introduced in 2013 but show great promise.	Metformin	0-9	solute carrier family 5 member 2	Homo sapiens	189-194
30456843-0	2019	Impact of metformin use on the cardiovascular effects of dipeptidyl peptidase-4 inhibitors: An analysis of Medicare claims data from 2007 to 2015.	Metformin	10-19	dipeptidyl peptidase 4	Homo sapiens	57-79
30456843-5	2019	RESULTS: For the DPP-4 inhibitor (n = 13 391) versus sulphonylurea (n = 33 206) comparison, rate differences in composite outcome incidence favoured DPP-4 inhibitors: -2.0/100 person-years among metformin users (95% confidence interval [CI] -2.7 to -1.3) and - 1.0/100 person-years (95% CI -1.8 to -0.2) among metformin non-users.	Metformin	195-204	dipeptidyl peptidase 4	Homo sapiens	149-154
30456843-5	2019	RESULTS: For the DPP-4 inhibitor (n = 13 391) versus sulphonylurea (n = 33 206) comparison, rate differences in composite outcome incidence favoured DPP-4 inhibitors: -2.0/100 person-years among metformin users (95% confidence interval [CI] -2.7 to -1.3) and - 1.0/100 person-years (95% CI -1.8 to -0.2) among metformin non-users.	Metformin	310-319	dipeptidyl peptidase 4	Homo sapiens	149-154
30456843-7	2019	The interaction between DPP-4 inhibitor initiation and metformin was statistically significant for non-fatal MI (P = 0.008).	Metformin	55-64	dipeptidyl peptidase 4	Homo sapiens	24-29
30456843-8	2019	For the DPP-4 inhibitor (n = 22 210) versus thiazolidinedione (n = 9517) comparison, rate differences in composite outcome incidence for DPP-4 inhibitor initiation were -0.6/100 person-years (95% CI -1.5 to 0.2) among metformin users and 1.0 (95% CI 0.0 to 2.0) among metformin non-users.	Metformin	218-227	dipeptidyl peptidase 4	Homo sapiens	137-142
30456843-8	2019	For the DPP-4 inhibitor (n = 22 210) versus thiazolidinedione (n = 9517) comparison, rate differences in composite outcome incidence for DPP-4 inhibitor initiation were -0.6/100 person-years (95% CI -1.5 to 0.2) among metformin users and 1.0 (95% CI 0.0 to 2.0) among metformin non-users.	Metformin	268-277	dipeptidyl peptidase 4	Homo sapiens	137-142
30456843-10	2019	The interaction between DPP-4 inhibitor initiation and metformin was statistically significant for the composite outcome (P = 0.024) and mortality (P = 0.023).	Metformin	55-64	dipeptidyl peptidase 4	Homo sapiens	24-29
30456843-11	2019	CONCLUSION: Incidence rate differences in multiple CV outcomes appeared more favourable when DPP-4 inhibitor initiation occurred in the presence of metformin, suggesting a possible interaction between DPP-4 inhibitors and metformin.	Metformin	148-157	dipeptidyl peptidase 4	Homo sapiens	93-98
30456843-11	2019	CONCLUSION: Incidence rate differences in multiple CV outcomes appeared more favourable when DPP-4 inhibitor initiation occurred in the presence of metformin, suggesting a possible interaction between DPP-4 inhibitors and metformin.	Metformin	148-157	dipeptidyl peptidase 4	Homo sapiens	201-206
30456843-11	2019	CONCLUSION: Incidence rate differences in multiple CV outcomes appeared more favourable when DPP-4 inhibitor initiation occurred in the presence of metformin, suggesting a possible interaction between DPP-4 inhibitors and metformin.	Metformin	222-231	dipeptidyl peptidase 4	Homo sapiens	93-98
30565386-0	2019	Cost-effectiveness of intensification with sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes on metformin and sitagliptin vs direct intensification with insulin in the United Kingdom.	Metformin	122-131	solute carrier family 5 member 2	Homo sapiens	43-74
30565386-10	2019	CONCLUSIONS: For UK patients with T2D not at goal on metformin and sitagliptin therapy, treatment intensification with SGLT2 inhibitors prior to NPH insulin is cost-neutral or cost-effective compared with immediate NPH insulin intensification.	Metformin	53-62	solute carrier family 5 member 2	Homo sapiens	119-124
22982676-0	2012	Molecular mechanisms of lipoapoptosis and metformin protection in GLP-1 secreting cells.	Metformin	42-51	zinc finger, GATA-like protein 1	Mus musculus	66-71
22982676-2	2012	We recently published data indicating lipotoxic effects of simulated hyperlipidemia also in GLP-1-secreting cells, where the antidiabetic drug metformin conferred protection from lipoapoptosis.	Metformin	143-152	zinc finger, GATA-like protein 1	Mus musculus	92-97
22982676-3	2012	The aim of the present study was to identify mechanisms involved in mediating lipotoxicity and metformin lipoprotection in GLP-1 secreting cells.	Metformin	95-104	zinc finger, GATA-like protein 1	Mus musculus	123-128
22698918-0	2012	Metformin inhibits growth hormone-mediated hepatic PDK4 gene expression through induction of orphan nuclear receptor small heterodimer partner.	Metformin	0-9	growth hormone	Mus musculus	19-33
22698918-5	2012	Metformin inhibited the induction of PDK4 expression by GH via a pathway dependent on AMP-activated protein kinase (AMPK) and SHP induction.	Metformin	0-9	growth hormone	Mus musculus	56-58
22698918-7	2012	Metformin decreased GH-mediated induction of PDK4 expression and metabolites in wild-type but not in SHP-null mice.	Metformin	0-9	growth hormone	Mus musculus	20-22
22520230-3	2012	Metformin enhances LPL in skeletal muscle through adenosine monophosphate-activated protein kinase (AMPK) activation but not in adipocytes.	Metformin	0-9	lipoprotein lipase	Homo sapiens	19-22
22752027-6	2012	In addition, metformin inhibited hepatic,             intestinal and lung metastasis (P&lt;0.05), with no weight loss in vivo, consistent             with decreased expression of vWF and macrophage infiltration.	Metformin	13-22	Von Willebrand factor	Mus musculus	179-182
22735389-0	2012	Association of genetic variation in the organic cation transporters OCT1, OCT2 and multidrug and toxin extrusion 1 transporter protein genes with the gastrointestinal side effects and lower BMI in metformin-treated type 2 diabetes patients.	Metformin	197-206	solute carrier family 22 member 2	Homo sapiens	74-78
22735389-2	2012	So far, the number of polymorphisms in SLC22A1, SLC22A2, and SLC47A1 genes coding for organic cation transporter 1 (OCT1), OCT2, and multidrug and toxin extrusion transporter 1 (MATE1) metformin transporters have been described in association with the efficacy of metformin.	Metformin	185-194	solute carrier family 22 member 2	Homo sapiens	48-55
22735389-2	2012	So far, the number of polymorphisms in SLC22A1, SLC22A2, and SLC47A1 genes coding for organic cation transporter 1 (OCT1), OCT2, and multidrug and toxin extrusion transporter 1 (MATE1) metformin transporters have been described in association with the efficacy of metformin.	Metformin	185-194	solute carrier family 22 member 2	Homo sapiens	123-127
22486277-0	2012	Effects of chronic treatment with metformin on dipeptidyl peptidase-4 activity, glucagon-like peptide 1 and ghrelin in obese patients with Type 2 diabetes mellitus.	Metformin	34-43	dipeptidyl peptidase 4	Homo sapiens	47-69
22540333-0	2012	Metformin sensitizes endometrial cancer cells to chemotherapy by repressing glyoxalase I expression.	Metformin	0-9	glyoxalase I	Homo sapiens	76-88
22540333-7	2012	In addition, plasmid transfection was used to overexpress GloI and determine whether high GloI levels blocked metformin-enhanced cell sensitivity to chemotherapy.	Metformin	110-119	glyoxalase I	Homo sapiens	90-94
22378745-7	2012	The decrease in p53 abundance caused by metformin was abolished by inhibition of murine double minute 2 (MDM2), a ubiquitin ligase that mediates p53 degradation, as well as by overexpression of a dominant-negative AMPK or a shRNA-mediated knockdown of SIRT1.	Metformin	40-49	transformation related protein 53, pseudogene	Mus musculus	16-19
22378745-7	2012	The decrease in p53 abundance caused by metformin was abolished by inhibition of murine double minute 2 (MDM2), a ubiquitin ligase that mediates p53 degradation, as well as by overexpression of a dominant-negative AMPK or a shRNA-mediated knockdown of SIRT1.	Metformin	40-49	transformed mouse 3T3 cell double minute 2	Mus musculus	105-109
22378745-7	2012	The decrease in p53 abundance caused by metformin was abolished by inhibition of murine double minute 2 (MDM2), a ubiquitin ligase that mediates p53 degradation, as well as by overexpression of a dominant-negative AMPK or a shRNA-mediated knockdown of SIRT1.	Metformin	40-49	transformation related protein 53, pseudogene	Mus musculus	145-148
22378745-7	2012	The decrease in p53 abundance caused by metformin was abolished by inhibition of murine double minute 2 (MDM2), a ubiquitin ligase that mediates p53 degradation, as well as by overexpression of a dominant-negative AMPK or a shRNA-mediated knockdown of SIRT1.	Metformin	40-49	sirtuin 1	Mus musculus	252-257
22703658-0	2012	Protective effect of metformin on periapical lesions in rats by decreasing the ratio of receptor activator of nuclear factor kappa B ligand/osteoprotegerin.	Metformin	21-30	TNF receptor superfamily member 11B	Rattus norvegicus	140-155
22703658-7	2012	RESULTS: The number of RANKL-positive and tartrate-resistant acid phosphatase (TRAP)-positive cells in the metformin-treated groups decreased on day 14, whereas the number of OPG-positive cells increased on day 28.	Metformin	107-116	TNF receptor superfamily member 11B	Rattus norvegicus	175-178
22703658-9	2012	CONCLUSIONS: Metformin inhibits the periapical lesions possibly by lowering the RANKL/OPG ratio, subsequently reducing the number of osteoclasts and bone resorption areas.	Metformin	13-22	TNF receptor superfamily member 11B	Rattus norvegicus	86-89
22683131-1	2012	BACKGROUND: In people with type 2 diabetes, a dipeptidyl peptidase-4 (DPP-4) inhibitor is one choice as second-line treatment after metformin, with basal insulin recommended as an alternative.	Metformin	132-141	dipeptidyl peptidase 4	Homo sapiens	46-68
22683131-1	2012	BACKGROUND: In people with type 2 diabetes, a dipeptidyl peptidase-4 (DPP-4) inhibitor is one choice as second-line treatment after metformin, with basal insulin recommended as an alternative.	Metformin	132-141	dipeptidyl peptidase 4	Homo sapiens	70-75
22469973-5	2012	Real-time PCR was used to investigate the effect of metformin on LH induction of VEGF and slit2 expression.	Metformin	52-61	slit guidance ligand 2	Homo sapiens	90-95
22469973-7	2012	However, metformin inhibited the mTOR signaling pathway and further blocked LH-induced VEGF and slit2 expression.	Metformin	9-18	slit guidance ligand 2	Homo sapiens	96-101
22525678-4	2012	In cultured rat VSMCs, AMPK activation through LKB1 by metformin-inhibited phenylephrine-mediated myosin light chain kinase (MLCK) and myosin light chain phosphorylation (p-MLC).	Metformin	55-64	serine/threonine kinase 11	Rattus norvegicus	47-51
22525678-7	2012	Metformin inhibited PE-induced p-MLC and alpha-smooth muscle actin co-localization.	Metformin	0-9	actin gamma 2, smooth muscle	Rattus norvegicus	41-66
22593441-15	2012	The analysis of cell cycle-regulating proteins cyclin D, cyclin E and p27 by western blot indicated that the synergistic inhibition of G1 phase of the cell cycle by the combination treatment of metformin, chemotherapeutic drugs and/or RAD001 contributed to the synergistic inhibition of cell proliferation.	Metformin	194-203	interferon alpha inducible protein 27	Homo sapiens	70-73
22252099-11	2012	Metformin decreased hTERT mRNA expression while paclitaxel alone had no effect on telomerase activity.	Metformin	0-9	telomerase reverse transcriptase	Homo sapiens	20-25
22322462-0	2012	MicroRNA-21-mediated regulation of Sprouty2 protein expression enhances the cytotoxic effect of 5-fluorouracil and metformin in colon cancer cells.	Metformin	115-124	microRNA 21	Homo sapiens	0-11
22324384-5	2012	We concluded that, once metformin fails to maintain glycemic control, addition of DPP-4 inhibitors should be the logical choice: they seems to lower HbA(1c) levels by 0.6-0.9 percentage points and to have a comparable effect on HbA(1c) versus the addition of a sulfonylurea or glitazone.	Metformin	24-33	dipeptidyl peptidase 4	Homo sapiens	82-87
30483391-0	2018	Combination of metformin and phenformin synergistically inhibits proliferation and hTERT expression in human breast cancer cells.	Metformin	15-24	telomerase reverse transcriptase	Homo sapiens	83-88
29319171-10	2018	Two target genes of Metformin were significantly interacted with six hub genes (HADHB, NDUFS3, TAF1, MYC, HNFF4A, and MAX) with significant changes in expression values (P &lt; 0.05, t-test).	Metformin	20-29	NADH:ubiquinone oxidoreductase core subunit S3	Homo sapiens	87-93
29319171-10	2018	Two target genes of Metformin were significantly interacted with six hub genes (HADHB, NDUFS3, TAF1, MYC, HNFF4A, and MAX) with significant changes in expression values (P &lt; 0.05, t-test).	Metformin	20-29	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	101-104
22456732-0	2012	The role of ATM in response to metformin treatment and activation of AMPK.	Metformin	31-40	ATM serine/threonine kinase	Homo sapiens	12-15
22456733-0	2012	The role of ATM in response to metformin treatment and activation of AMPK.	Metformin	31-40	ATM serine/threonine kinase	Homo sapiens	12-15
22456734-0	2012	The role of ATM in response to metformin treatment and activation of AMPK.	Metformin	31-40	ATM serine/threonine kinase	Homo sapiens	12-15
22378068-8	2012	In vivo, metformin induced AMPK activation, mTOR inhibition and remarkably blocked tumor growth in murine lymphoma xenografts.	Metformin	9-18	mechanistic target of rapamycin kinase	Mus musculus	44-48
22107872-5	2012	We found that metformin activates the PERK-ATF4 but not the ATF6 or IRE1-XBP1 branch in ERSS and leads to a strong upregulation of CHOP mRNA and protein.	Metformin	14-23	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	38-42
22068616-8	2012	Treatment with metformin for 4 weeks attenuated the increased levels of Angptl4 mRNA.	Metformin	15-24	angiopoietin-like 4	Mus musculus	72-79
30764006-2	2012	Incretin-based therapies, and especially dipeptidyl peptidase-4 inhibitors, offer new opportunities after failure of metformin.	Metformin	117-126	dipeptidyl peptidase 4	Homo sapiens	41-63
22108913-10	2012	The effect of metformin was linked to a reduction of phosphorylated S6 ribosomal protein (active form) and of phosphorylated 4E-BP1 (inactive form), a translation repressor.	Metformin	14-23	eukaryotic translation initiation factor 4E binding protein 1	Mus musculus	125-131
30149143-0	2018	Metformin Enhances Cisplatin-Induced Apoptosis and Prevents Resistance to Cisplatin in Co-mutated KRAS/LKB1 NSCLC.	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	103-107
30149143-7	2018	In preclinical experiments, metformin produced pro-apoptotic effects and enhanced cisplatin anticancer activity specifically in KRAS/LKB1 co-mutated patient-derived xenografts.	Metformin	28-37	serine/threonine kinase 11	Homo sapiens	133-137
30149143-10	2018	Metformin synergizes with cisplatin against KRAS/LKB1 co-mutated tumors, and may prevent or delay the onset of resistance to cisplatin by targeting CD133+ cancer stem cells.	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	49-53
30149143-11	2018	This study lays the foundations for combining metformin with standard platinum-based chemotherapy in the treatment of KRAS/LKB1 co-mutated NSCLC.	Metformin	46-55	serine/threonine kinase 11	Homo sapiens	123-127
30221473-0	2018	Metformin blocks MYC protein synthesis in colorectal cancer via mTOR-4EBP-eIF4E and MNK1-eIF4G-eIF4E signaling.	Metformin	0-9	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	17-20
30221473-0	2018	Metformin blocks MYC protein synthesis in colorectal cancer via mTOR-4EBP-eIF4E and MNK1-eIF4G-eIF4E signaling.	Metformin	0-9	eukaryotic translation initiation factor 4E	Mus musculus	64-79
30221473-5	2018	We discovered that metformin causes a robust reduction of MYC protein level.	Metformin	19-28	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	58-61
30221473-6	2018	Through the use of luciferase assay and coincubation with either protein synthesis or proteasome inhibitors, we demonstrated that regulation of MYC by metformin is independent of the proteasome and 3" UTR-mediated regulation, but depends on protein synthesis.	Metformin	151-160	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	144-147
30221473-8	2018	Repression of protein synthesis by metformin preferentially affects cell cycle-associated proteins, by altering signaling through the mTOR-4EBP-eIF4E and MNK1-eIF4G-eIF4E axes.	Metformin	35-44	eukaryotic translation initiation factor 4E	Mus musculus	134-149
30221473-9	2018	The inhibition of MYC protein synthesis may underlie metformin"s beneficial effects on CRC risk and prognosis.	Metformin	53-62	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	18-21
30266241-7	2018	Metformin could enhance the cytotoxicity of DOX by increasing DOX cellular uptake and cell cycle arrest at G1/S checkpoint which is associated with the enhancement of p21 protein expression.	Metformin	0-9	H3 histone pseudogene 16	Homo sapiens	167-170
30410867-0	2018	Erratum to: Metformin treatment ameliorates diabetes-associated decline in hippocampal neurogenesis and memory via phosphorylation of insulin receptor substrate 1.	Metformin	12-21	insulin receptor substrate 1	Homo sapiens	134-162
30347712-0	2018	Anti-Angiogenic miR-222, miR-195, and miR-21a Plasma Levels in T1DM Are Improved by Metformin Therapy, Thus Elucidating Its Cardioprotective Effect: The MERIT Study.	Metformin	84-93	microRNA 222	Homo sapiens	16-23
30347712-8	2018	Metformin reduced miR-222, miR-195 and miR-21a levels in TG; p = 0.007, p = 0.002 p = 0.0012, respectively.	Metformin	0-9	microRNA 222	Homo sapiens	18-25
30347712-13	2018	Metformin has cardioprotective effects through downregulating miR-222, miR-195 and miR-21a, beyond improving glycemic control.	Metformin	0-9	microRNA 222	Homo sapiens	62-69
30337733-3	2018	qRT-PCR and Western blot were used to detect the effect of different concentrations of metformin on the changes of adiponectin receptors (AdipoR1 and AdipoR2) of the EC cells both in mRNA and protein level and the role of compound C, an adenosine monophosphate-activated protein kinase (AMPK) inhibitor, on the above effects.	Metformin	87-96	adiponectin receptor 1	Homo sapiens	138-145
30310100-5	2018	Initiators of DPP4 inhibitors were associated with an increased risk of acute kidney injury when compared to metformin initiators (HR [95% CI] for acute kidney injury: 1.85 [1.10-3.12], although this association was attenuated when DPP4 inhibitor monotherapy was compared to metformin monotherapy exposure as a time-dependent variable (HR 1.39 [0.91-2.11]).	Metformin	275-284	dipeptidyl peptidase 4	Homo sapiens	14-18
30356719-10	2018	Metformin treatment in T2DM reverted CD11c, CD169, IL-6, iNOS, TNFalpha, and CD36 to levels comparable to lean subjects.	Metformin	0-9	sialic acid binding Ig like lectin 1	Homo sapiens	44-49
30275441-2	2018	This study investigated whether metformin increases the incidence of cardiac rupture after myocardial infarction through the AMPK-MTOR/PGC-1alpha signaling pathway.	Metformin	32-41	mechanistic target of rapamycin kinase	Mus musculus	130-134
30275441-14	2018	CONCLUSIONS These results suggest that metformin increases cardiac rupture after myocardial infarction through the AMPK-MTOR/PGC-1alpha signaling pathway.	Metformin	39-48	mechanistic target of rapamycin kinase	Mus musculus	120-124
30222970-8	2018	The gene expression of the metabolic regulator glutamic-oxaloacetic transaminase 1 decreased in wild type cells upon metformin treatment whereas there was a trend of increased expression in the siSLC25A10 cells upon metformin treatment.	Metformin	117-126	glutamic-oxaloacetic transaminase 1	Homo sapiens	47-82
30222970-8	2018	The gene expression of the metabolic regulator glutamic-oxaloacetic transaminase 1 decreased in wild type cells upon metformin treatment whereas there was a trend of increased expression in the siSLC25A10 cells upon metformin treatment.	Metformin	216-225	glutamic-oxaloacetic transaminase 1	Homo sapiens	47-82
30119251-0	2018	Involvement of organic cation transporter 2 in the metformin-associated increased lactate levels caused by contrast-induced nephropathy.	Metformin	51-60	solute carrier family 22 member 2	Rattus norvegicus	15-43
30119251-11	2018	These findings highlight that OCT2 deficiency was associated with increased lactate levels during metformin treatment caused by CIN.	Metformin	98-107	solute carrier family 22 member 2	Rattus norvegicus	30-34
22149373-2	2012	Dipeptidyl peptidase-4 (DPP-4) inhibitors, by promoting insulin secretion and reducing glucagon secretion in a glucose-dependent manner, offer new opportunities for oral therapy after failure of metformin.	Metformin	195-204	dipeptidyl peptidase 4	Homo sapiens	0-22
22149373-2	2012	Dipeptidyl peptidase-4 (DPP-4) inhibitors, by promoting insulin secretion and reducing glucagon secretion in a glucose-dependent manner, offer new opportunities for oral therapy after failure of metformin.	Metformin	195-204	dipeptidyl peptidase 4	Homo sapiens	24-29
22837722-0	2012	The role of PPARalpha in metformin-induced attenuation of mitochondrial dysfunction in acute cardiac ischemia/reperfusion in rats.	Metformin	25-34	peroxisome proliferator activated receptor alpha	Rattus norvegicus	12-21
22837722-3	2012	In this study, we examined the role of PPARalpha in mediating cardioprotective effects of metformin on mitochondria.	Metformin	90-99	peroxisome proliferator activated receptor alpha	Rattus norvegicus	39-48
22837722-9	2012	Thus, our results demonstrate that inhibition of PPARalpha attenuates the beneficial effects of metformin on mitochondria in acute IR.	Metformin	96-105	peroxisome proliferator activated receptor alpha	Rattus norvegicus	49-58
21964537-9	2012	Seventy eight different genes were overlapping the exercise and AICAR group at 24 h. Ingenuity identified six overlapping genes between the exercise, AICAR, and metformin groups including NR4A3, TNFRSF12A, HBB, PENK, PAP, and MAP4K4.	Metformin	161-170	hemoglobin subunit beta	Rattus norvegicus	206-209
21964537-9	2012	Seventy eight different genes were overlapping the exercise and AICAR group at 24 h. Ingenuity identified six overlapping genes between the exercise, AICAR, and metformin groups including NR4A3, TNFRSF12A, HBB, PENK, PAP, and MAP4K4.	Metformin	161-170	proenkephalin	Rattus norvegicus	211-215
21964537-9	2012	Seventy eight different genes were overlapping the exercise and AICAR group at 24 h. Ingenuity identified six overlapping genes between the exercise, AICAR, and metformin groups including NR4A3, TNFRSF12A, HBB, PENK, PAP, and MAP4K4.	Metformin	161-170	mitogen-activated protein kinase kinase kinase kinase 4	Rattus norvegicus	226-232
23166782-9	2012	However, a higher metformin concentration was required for downregulation of ERRalpha than SIRT3.	Metformin	18-27	sirtuin 3	Mus musculus	91-96
23166782-11	2012	Overexpression of the constitutively active form of AMP-activated protein kinase (AMPK) induced SIRT3 mRNA, indicating that the SIRT3 downregulation by metformin is not mediated by AMPK.	Metformin	152-161	sirtuin 3	Mus musculus	128-133
23166782-14	2012	Furthermore, metformin decreased mitochondrial SIRT3 protein levels and this was associated with enhanced acetylation of several mitochondrial proteins.	Metformin	13-22	sirtuin 3	Mus musculus	47-52
23166782-16	2012	Altogether, our results indicate that metformin attenuates mitochondrial expression of SIRT3 and suggest that this mechanism is involved in regulation of energy metabolism by metformin in the liver and may contribute to the therapeutic action of metformin.	Metformin	38-47	sirtuin 3	Mus musculus	87-92
23166782-16	2012	Altogether, our results indicate that metformin attenuates mitochondrial expression of SIRT3 and suggest that this mechanism is involved in regulation of energy metabolism by metformin in the liver and may contribute to the therapeutic action of metformin.	Metformin	175-184	sirtuin 3	Mus musculus	87-92
23166782-16	2012	Altogether, our results indicate that metformin attenuates mitochondrial expression of SIRT3 and suggest that this mechanism is involved in regulation of energy metabolism by metformin in the liver and may contribute to the therapeutic action of metformin.	Metformin	175-184	sirtuin 3	Mus musculus	87-92
23077661-0	2012	Activation of AMPK by the putative dietary restriction mimetic metformin is insufficient to extend lifespan in Drosophila.	Metformin	63-72	AMP-activated protein kinase alpha subunit	Drosophila melanogaster	14-18
30249366-1	2018	PURPOSE: The aim of this study was to assess the pharmacokinetic interactions between a newly developed dipeptidyl peptidase (DPP)-4 inhibitor, gemigliptin, and metformin in healthy Mexican male volunteers, and the differences in the pharmacokinetic profile of gemigliptin between Korean and Mexican healthy volunteers.	Metformin	161-170	dipeptidyl peptidase 4	Homo sapiens	104-132
29862627-8	2018	Gene knockdown by RNAi showed that MATE1 and PMAT reduction attenuated the antilipolytic effect of metformin but only PMAT knockdown decreased the effect of all three biguanides.	Metformin	99-108	solute carrier family 29 member 4	Homo sapiens	45-49
23077661-1	2012	The biguanide drug, metformin, commonly used to treat type-2 diabetes, has been shown to extend lifespan and reduce fecundity in C. elegans through a dietary restriction-like mechanism via the AMP-activated protein kinase (AMPK) and the AMPK-activating kinase, LKB1.	Metformin	20-29	AMP-activated protein kinase alpha subunit	Drosophila melanogaster	223-227
23077661-1	2012	The biguanide drug, metformin, commonly used to treat type-2 diabetes, has been shown to extend lifespan and reduce fecundity in C. elegans through a dietary restriction-like mechanism via the AMP-activated protein kinase (AMPK) and the AMPK-activating kinase, LKB1.	Metformin	20-29	AMP-activated protein kinase alpha subunit	Drosophila melanogaster	237-241
23077661-3	2012	We show here that while feeding metformin to adult Drosophila resulted in a robust activation of AMPK and reduced lipid stores, it did not increase lifespan in either male or female flies.	Metformin	32-41	AMP-activated protein kinase alpha subunit	Drosophila melanogaster	97-101
21801267-7	2011	Treatment with metformin significantly reduced IL-6, especially in PCOS patients with IRS-2 homozygous Asp variant.	Metformin	15-24	insulin receptor substrate 2	Homo sapiens	86-91
21733059-12	2011	Metformin-mediated induction of Clock mRNA in adipocytes was blocked by inhibition of NAMPT and SIRT1.	Metformin	0-9	sirtuin 1	Mus musculus	96-101
21733059-14	2011	Metformin mediates a phenotypic shift away from lipid accretion through AMPK-NAMPT-SIRT1 mediated changes in clock components, supporting chronotherapeutic treatment approaches for obesity.	Metformin	0-9	sirtuin 1	Mus musculus	83-88
21631893-6	2011	The major molecular targets of metformin are the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) signaling and mammalian target of rapamycin (mTOR) pathways, which are central in the regulation of cellular energy homeostasis and play a crucial role in the control of cell division and cell proliferation.	Metformin	31-40	serine/threonine kinase 11	Homo sapiens	49-64
21631893-6	2011	The major molecular targets of metformin are the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) signaling and mammalian target of rapamycin (mTOR) pathways, which are central in the regulation of cellular energy homeostasis and play a crucial role in the control of cell division and cell proliferation.	Metformin	31-40	serine/threonine kinase 11	Homo sapiens	66-70
21700905-11	2011	We concluded that the AMPK activators AICAR and metformin inhibited transcriptional activities of PPAR-alpha and PPAR-gamma, whereas inhibition of AMPK with compound C activated both PPARs.	Metformin	48-57	peroxisome proliferator activated receptor alpha	Rattus norvegicus	98-108
21664031-0	2011	Does metformin influence the insulin-, IGF I- and IGF II-receptor gene expression and Akt phosphorylation in human decidualized endometrial stromal cells?	Metformin	5-14	insulin like growth factor 2 receptor	Homo sapiens	50-65
21835890-5	2011	Interestingly, we found that metformin also induces LKB1 cytosolic translocation, but the stimulation is independent of APPL1 and the PP2A-PKCzeta pathway.	Metformin	29-38	serine/threonine kinase 11	Homo sapiens	52-56
21835890-5	2011	Interestingly, we found that metformin also induces LKB1 cytosolic translocation, but the stimulation is independent of APPL1 and the PP2A-PKCzeta pathway.	Metformin	29-38	protein phosphatase 2 phosphatase activator	Homo sapiens	134-138
21824668-4	2011	Preclinical studies suggest that metformin inhibits mitochondrial complex I. TZDs, as peroxisome proliferator-activated receptor (PPAR) gamma-agonists, predominantly reduce the flux of FFA and cytokines from adipose tissue to the liver, but could also directly inhibit mitochondrial complex I.	Metformin	33-42	peroxisome proliferator activated receptor alpha	Homo sapiens	86-128
21824668-4	2011	Preclinical studies suggest that metformin inhibits mitochondrial complex I. TZDs, as peroxisome proliferator-activated receptor (PPAR) gamma-agonists, predominantly reduce the flux of FFA and cytokines from adipose tissue to the liver, but could also directly inhibit mitochondrial complex I.	Metformin	33-42	peroxisome proliferator activated receptor alpha	Homo sapiens	130-134
21646436-8	2011	The IC(50) values were 0.1, 3.8, 14, and 671 muM (hexyl-, butyl-, and ethyl-pyridinium and pyridinium chloride) for rOCT2-mediated metformin transport.	Metformin	131-140	solute carrier family 22 member 2	Rattus norvegicus	116-121
21932178-0	2011	Anti-Mullerian hormone in women with polycystic ovary syndrome before and after therapy with metformin.	Metformin	93-102	anti-Mullerian hormone	Homo sapiens	0-22
21932178-10	2011	In the other 4 patients who did not show satisfactory clinical response to metformin, AMH levels increased from 31.30+-16.52 to 80.77+-12.73 (p=0.021).	Metformin	75-84	anti-Mullerian hormone	Homo sapiens	86-89
21932178-12	2011	AMH levels are significantly elevated in women with PCOS and they may serve as a marker for evaluation of treatment efficacy with metformin.	Metformin	130-139	anti-Mullerian hormone	Homo sapiens	0-3
21813293-0	2011	The beneficial effect of alpha-glucosidase inhibitor on glucose variability compared with sulfonylurea in Taiwanese type 2 diabetic patients inadequately controlled with metformin: preliminary data.	Metformin	170-179	sucrase-isomaltase	Homo sapiens	25-42
21168492-7	2011	In parallel, IGF-II increases phosphorylation of AKT and p70S6K, while metformin increases AMPK phosphorylation and decreases p70S6K phosphorylation.	Metformin	71-80	ribosomal protein S6 kinase B1	Homo sapiens	126-132
21168492-8	2011	The effects of metformin on PR A/B and p70S6K are partially reversed by an AMPK inhibitor.	Metformin	15-24	ribosomal protein S6 kinase B1	Homo sapiens	39-45
21168492-10	2011	Our results demonstrate that metformin promotes PR expression, which can be inhibited by overexpressed IGF-II in EC.	Metformin	29-38	insulin like growth factor 2	Homo sapiens	103-109
21945753-4	2011	RESULTS: Metformin induced apoptosis and caspase 9 activation in 786-O cells in low-serum medium but not in normal-serum medium.	Metformin	9-18	caspase 9	Homo sapiens	41-50
21655990-12	2011	By ingenuity pathway analysis, the tumour necrosis factor receptor 1 (TNFR1) signaling pathway was most affected by metformin: TGFB and MEKK were upregulated and cdc42 downregulated; mTOR and AMPK pathways were also affected.	Metformin	116-125	TNF receptor superfamily member 1A	Homo sapiens	35-68
21655990-12	2011	By ingenuity pathway analysis, the tumour necrosis factor receptor 1 (TNFR1) signaling pathway was most affected by metformin: TGFB and MEKK were upregulated and cdc42 downregulated; mTOR and AMPK pathways were also affected.	Metformin	116-125	TNF receptor superfamily member 1A	Homo sapiens	70-75
21756359-8	2011	On top of metformin, patients with thiazolidine (OR 0.50; 95%CI 0.28-0.89) and DPP-4 inhibitor use (OR 0.34; 95%CI 0.16-0.70) had a decreased risk for hypoglycaemia while it was again increased with sulfonylureas (OR 2.08; 95%CI 1.44-2.99).	Metformin	10-19	dipeptidyl peptidase 4	Homo sapiens	79-84
30095971-1	2018	BACKGROUND: As initial combination therapy of metformin and dipeptidyl peptidase-4 (DPP-4) inhibitor, the efficacy and safety for the use of high dose of metformin or low dose of metformin and the efficacy and safety for the combination use for Asian and Caucasian patients were not clear.	Metformin	154-163	dipeptidyl peptidase 4	Homo sapiens	60-82
30095971-1	2018	BACKGROUND: As initial combination therapy of metformin and dipeptidyl peptidase-4 (DPP-4) inhibitor, the efficacy and safety for the use of high dose of metformin or low dose of metformin and the efficacy and safety for the combination use for Asian and Caucasian patients were not clear.	Metformin	154-163	dipeptidyl peptidase 4	Homo sapiens	84-89
30095971-1	2018	BACKGROUND: As initial combination therapy of metformin and dipeptidyl peptidase-4 (DPP-4) inhibitor, the efficacy and safety for the use of high dose of metformin or low dose of metformin and the efficacy and safety for the combination use for Asian and Caucasian patients were not clear.	Metformin	154-163	dipeptidyl peptidase 4	Homo sapiens	60-82
30095971-1	2018	BACKGROUND: As initial combination therapy of metformin and dipeptidyl peptidase-4 (DPP-4) inhibitor, the efficacy and safety for the use of high dose of metformin or low dose of metformin and the efficacy and safety for the combination use for Asian and Caucasian patients were not clear.	Metformin	154-163	dipeptidyl peptidase 4	Homo sapiens	84-89
30095971-7	2018	CONCLUSION: As an initial treatment, the high dose of metformin in combination with DPP-4 inhibitors not only provided better glycemic control but also had less effect on weight gain compared with the low-dose combination therapy through the correction of metformin monotherapy.	Metformin	256-265	dipeptidyl peptidase 4	Homo sapiens	84-89
30259865-5	2018	Metformin is shown to negatively regulate PI3K through AMPK induced IRS1 phosphorylation and this brings about a reversal of AKT bistablity in codimension-1 bifurcation diagram from S-shaped, related to cell proliferation in the absence of drug metformin, to Z-shaped, related to apoptosis in the presence of drug metformin.	Metformin	0-9	insulin receptor substrate 1	Homo sapiens	68-72
30259865-5	2018	Metformin is shown to negatively regulate PI3K through AMPK induced IRS1 phosphorylation and this brings about a reversal of AKT bistablity in codimension-1 bifurcation diagram from S-shaped, related to cell proliferation in the absence of drug metformin, to Z-shaped, related to apoptosis in the presence of drug metformin.	Metformin	245-254	insulin receptor substrate 1	Homo sapiens	68-72
30259865-5	2018	Metformin is shown to negatively regulate PI3K through AMPK induced IRS1 phosphorylation and this brings about a reversal of AKT bistablity in codimension-1 bifurcation diagram from S-shaped, related to cell proliferation in the absence of drug metformin, to Z-shaped, related to apoptosis in the presence of drug metformin.	Metformin	314-323	insulin receptor substrate 1	Homo sapiens	68-72
30090931-11	2018	The association of DPP-4 inhibitor use with BP was independent of the use of metformin and was stronger among male (OR, 4.46; 95% CI, 2.11-9.40) than female (OR, 1.88; 95%, CI 0.92-3.86) patients and strongest in patients younger than 70 years (OR, 5.59; 95% CI, 1.73-18.01).	Metformin	77-86	dipeptidyl peptidase 4	Homo sapiens	19-24
30012584-0	2018	Organic Cation Transporter 3 Facilitates Fetal Exposure to Metformin during Pregnancy.	Metformin	59-68	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	0-28
30012584-7	2018	After oral dosing of [14C]metformin at gestational day 19, the systemic drug exposure (AUC0- ) in maternal plasma was slightly reduced by ~16% in the Oct3-/- pregnant mice.	Metformin	26-35	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	150-154
30012584-9	2018	Consistent with our previous findings in nonpregnant mice, metformin tissue distribution was respectively reduced by 70% and 52% in the salivary glands and heart in Oct3-/- pregnant mice.	Metformin	59-68	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	165-169
30012584-10	2018	Our in vivo data in mice clearly demonstrated a significant role of Oct3 in facilitating metformin fetal distribution and exposure during pregnancy.	Metformin	89-98	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	68-72
30012584-11	2018	Modulation of placental OCT3 expression or activity by gestational age, genetic polymorphism, or pharmacological inhibitors may alter fetal exposure to metformin or other drugs transported by OCT3.	Metformin	152-161	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	24-28
30012584-11	2018	Modulation of placental OCT3 expression or activity by gestational age, genetic polymorphism, or pharmacological inhibitors may alter fetal exposure to metformin or other drugs transported by OCT3.	Metformin	152-161	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	192-196
29921847-0	2018	Metformin sensitizes endometrial cancer cells to chemotherapy through IDH1-induced Nrf2 expression via an epigenetic mechanism.	Metformin	0-9	isocitrate dehydrogenase (NADP(+)) 1	Homo sapiens	70-74
29921847-4	2018	However, whether IDH1 play a role in metformin-induced endometrial cancer chemosensitivity through epigenetic modification is incompletely understood.	Metformin	37-46	isocitrate dehydrogenase (NADP(+)) 1	Homo sapiens	17-21
29921847-12	2018	Dot blot and HMeDIP assays revealed that metformin blocked IDH1-alpha-KG-TET1-mediated enhancement of Nrf2 hydroxymethylation levels, eliminating chemoresistance.	Metformin	41-50	isocitrate dehydrogenase (NADP(+)) 1	Homo sapiens	59-63
29921847-12	2018	Dot blot and HMeDIP assays revealed that metformin blocked IDH1-alpha-KG-TET1-mediated enhancement of Nrf2 hydroxymethylation levels, eliminating chemoresistance.	Metformin	41-50	tet methylcytosine dioxygenase 1	Homo sapiens	73-77
29921847-14	2018	Our findings highlight a critical role of IDH1-alpha-KG-TET1-Nrf2 signaling in chemoresistance and suggest that rational combination therapy with metformin and chemotherapeutics has the potential to suppress chemoresistance.	Metformin	146-155	isocitrate dehydrogenase (NADP(+)) 1	Homo sapiens	42-46
29921847-14	2018	Our findings highlight a critical role of IDH1-alpha-KG-TET1-Nrf2 signaling in chemoresistance and suggest that rational combination therapy with metformin and chemotherapeutics has the potential to suppress chemoresistance.	Metformin	146-155	tet methylcytosine dioxygenase 1	Homo sapiens	56-60
29877750-8	2018	Our results showed that metformin attenuated ROS generation, downregulated pro-apoptotic BAX expression, and upregulated expression of the Bcl-2 protein in the PC12 cells.	Metformin	24-33	BCL2 associated X, apoptosis regulator	Rattus norvegicus	89-92
30017187-4	2018	Moreover, metformin treatment increased the expression of inhibitory Smad6, but not of that Smad7, in human granulosa cells, while metformin had no significant impact on the expression levels of BMP type-I and -II receptors.	Metformin	10-19	SMAD family member 6	Homo sapiens	69-74
30017187-5	2018	Thus, the mechanism by which metformin suppresses BMP-15-induced Smad1/5/9 phosphorylation is likely, at least in part, to be upregulation of inhibitory Smad6 expression in granulosa cells.	Metformin	29-38	SMAD family member 6	Homo sapiens	153-158
30017190-6	2018	Moreover, alpha-LA lowered the levels of O-linked beta-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells.	Metformin	189-198	O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N-acetylglucosamine:polypeptide-N-acetylglucosaminyl transferase)	Mus musculus	41-86
30017190-6	2018	Moreover, alpha-LA lowered the levels of O-linked beta-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells.	Metformin	189-198	O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N-acetylglucosamine:polypeptide-N-acetylglucosaminyl transferase)	Mus musculus	88-91
30017802-8	2018	The up-regulation of E-cadherin and the down-regulation of vimentin for both SW480 and HCT116 cells revealed the anti-EMT abilities of metformin.	Metformin	135-144	vimentin	Homo sapiens	59-67
21552292-6	2011	Furthermore, metformin suppressed the phosphorylation of Akt/protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in response to pressure overload in wild type mice, but not in AMPKalpha2-/- mice.	Metformin	13-22	protein tyrosine kinase 2 beta	Homo sapiens	61-77
21572254-2	2011	Besides the discovery of somatic mutations in the LKB1 gene in certain type of cancers, a critical emerging point was that the LKB1/AMPK axis remains generally functional and could be stimulated by pharmacological molecules such as metformin in cancer cells.	Metformin	232-241	serine/threonine kinase 11	Homo sapiens	50-54
21572254-2	2011	Besides the discovery of somatic mutations in the LKB1 gene in certain type of cancers, a critical emerging point was that the LKB1/AMPK axis remains generally functional and could be stimulated by pharmacological molecules such as metformin in cancer cells.	Metformin	232-241	serine/threonine kinase 11	Homo sapiens	127-131
21572254-4	2011	Further basic research work should be conducted to elucidate the molecular targets of LKB1/AMPK responsible for its anti-tumor activity in parallel of conducting clinical trials using metformin, AICAR or new AMPK activating agents to explore the potential of the LKB1/AMPK signaling pathway as a new target for anticancer drug development.	Metformin	184-193	serine/threonine kinase 11	Homo sapiens	86-90
21472661-1	2011	The purpose of this phase 2, multicentre, randomized, double-blind, placebo-controlled, 12-week dose-ranging study was to assess the efficacy, safety, and tolerability of the dipeptidyl peptidase-IV (DPP-IV) inhibitor PF-734200 in adult subjects with type 2 diabetes who were on a stable dose of metformin.	Metformin	296-305	dipeptidyl peptidase 4	Homo sapiens	200-206
21709633-8	2011	CONCLUSIONS: Our results suggest that the magnitude of FPG reduction after 6-month sulphonylurea treatment in addition to metformin in patients with type 2 diabetes is related to the variation in KCNQ1.	Metformin	122-131	potassium voltage-gated channel subfamily Q member 1	Homo sapiens	196-201
30179155-5	2018	We furthermore show that the antidiabetic drug metformin diminishes aberrant Huntingtin protein load and fully restores both early network activity patterns and behavioral aberrations.	Metformin	47-56	huntingtin	Mus musculus	77-87
21543517-1	2011	PURPOSE: Metformin is a widely used antidiabetic drug whose anticancer effects, mediated by the activation of AMP-activated protein kinase (AMPK) and reduction of mTOR signaling, have become noteworthy.	Metformin	9-18	mechanistic target of rapamycin kinase	Mus musculus	163-167
21543517-6	2011	RESULTS: The results presented herein show that the addition of metformin to paclitaxel leads to quantitative potentialization of molecular signaling through AMPK and a subsequent potent inhibition of the mTOR signaling pathway.	Metformin	64-73	mechanistic target of rapamycin kinase	Mus musculus	205-209
21501658-8	2011	Metformin increased the phosphorylation of beta-catenin and decreased beta-catenin protein levels leading to suppression of Wnt/beta-catenin signaling.	Metformin	0-9	catenin beta 1	Homo sapiens	43-55
21501658-8	2011	Metformin increased the phosphorylation of beta-catenin and decreased beta-catenin protein levels leading to suppression of Wnt/beta-catenin signaling.	Metformin	0-9	catenin beta 1	Homo sapiens	70-82
21501658-8	2011	Metformin increased the phosphorylation of beta-catenin and decreased beta-catenin protein levels leading to suppression of Wnt/beta-catenin signaling.	Metformin	0-9	catenin beta 1	Homo sapiens	70-82
21458097-11	2011	CONCLUSIONS: In T2DM patients, plasma omentin-1 levels decreased, but significantly increased after the treatment with liraglutide and metformin.	Metformin	135-144	intelectin 1	Homo sapiens	38-45
21677353-8	2011	Although metformin is not metabolized, the latest research has shown that it is actively transported into hepatocytes and renal tubular epithelium, by OCT1 (organic cation transporter 1, encoded by the SLC22A1 gene) and OCT2 (organic cation transporter 2, encoded by the SLC22A2 gene), respectively.	Metformin	9-18	solute carrier family 22 member 2	Homo sapiens	220-224
21677353-8	2011	Although metformin is not metabolized, the latest research has shown that it is actively transported into hepatocytes and renal tubular epithelium, by OCT1 (organic cation transporter 1, encoded by the SLC22A1 gene) and OCT2 (organic cation transporter 2, encoded by the SLC22A2 gene), respectively.	Metformin	9-18	solute carrier family 22 member 2	Homo sapiens	226-254
21677353-8	2011	Although metformin is not metabolized, the latest research has shown that it is actively transported into hepatocytes and renal tubular epithelium, by OCT1 (organic cation transporter 1, encoded by the SLC22A1 gene) and OCT2 (organic cation transporter 2, encoded by the SLC22A2 gene), respectively.	Metformin	9-18	solute carrier family 22 member 2	Homo sapiens	271-278
21250975-7	2011	Metformin treatment significantly improved glycation, oxidative stress, CCL2 levels, NO bioavailability and insulin resistance and normalized endothelial function in aorta.	Metformin	0-9	C-C motif chemokine ligand 2	Rattus norvegicus	72-76
21566461-0	2011	Metformin activates an ataxia telangiectasia mutated (ATM)/Chk2-regulated DNA damage-like response.	Metformin	0-9	ATM serine/threonine kinase	Homo sapiens	23-52
21566461-0	2011	Metformin activates an ataxia telangiectasia mutated (ATM)/Chk2-regulated DNA damage-like response.	Metformin	0-9	ATM serine/threonine kinase	Homo sapiens	54-57
30233191-7	2018	Initiation of therapy with SUs or DPP-4 inhibitors was associated with a significantly higher risk of both treatment addition and switching than with metformin (HR 1.49 versus 1.47 for overall treatment adjustment, respectively).	Metformin	150-159	dipeptidyl peptidase 4	Homo sapiens	34-39
29752759-0	2018	Metformin targets brown adipose tissue in vivo and reduces oxygen consumption in vitro.	Metformin	0-9	WD and tetratricopeptide repeats 1	Mus musculus	24-31
29752759-1	2018	AIMS: To test the hypothesis that brown adipose tissue (BAT) is a metformin target tissue by investigating in vivo uptake of [11 C]-metformin tracer in mice and studying in vitro effects of metformin on cultured human brown adipocytes.	Metformin	66-75	WD and tetratricopeptide repeats 1	Mus musculus	40-47
29752759-1	2018	AIMS: To test the hypothesis that brown adipose tissue (BAT) is a metformin target tissue by investigating in vivo uptake of [11 C]-metformin tracer in mice and studying in vitro effects of metformin on cultured human brown adipocytes.	Metformin	132-141	WD and tetratricopeptide repeats 1	Mus musculus	40-47
29752759-1	2018	AIMS: To test the hypothesis that brown adipose tissue (BAT) is a metformin target tissue by investigating in vivo uptake of [11 C]-metformin tracer in mice and studying in vitro effects of metformin on cultured human brown adipocytes.	Metformin	132-141	WD and tetratricopeptide repeats 1	Mus musculus	40-47
29956804-8	2018	Treatment with metformin also suppressed tumor growth, invasion and EMT in LSL-KrasG12D/+, Trp53fl/+and Pdx1-Cre (KPC) transgenic mice that harbor spontaneous pancreatic cancer.	Metformin	15-24	transformation related protein 53	Mus musculus	91-96
29740925-0	2018	Metformin directly targets the H3K27me3 demethylase KDM6A/UTX.	Metformin	0-9	lysine (K)-specific demethylase 6A	Mus musculus	52-57
29740925-0	2018	Metformin directly targets the H3K27me3 demethylase KDM6A/UTX.	Metformin	0-9	lysine (K)-specific demethylase 6A	Mus musculus	58-61
29740925-3	2018	Using several structure- and ligand-based software tools and reference databases containing 1,300,000 chemical compounds and more than 9,000 binding sites protein cavities, we identified 41 putative metformin targets including several epigenetic modifiers such as the member of the H3K27me3-specific demethylase subfamily, KDM6A/UTX.	Metformin	199-208	lysine (K)-specific demethylase 6A	Mus musculus	323-328
29740925-3	2018	Using several structure- and ligand-based software tools and reference databases containing 1,300,000 chemical compounds and more than 9,000 binding sites protein cavities, we identified 41 putative metformin targets including several epigenetic modifiers such as the member of the H3K27me3-specific demethylase subfamily, KDM6A/UTX.	Metformin	199-208	lysine (K)-specific demethylase 6A	Mus musculus	329-332
29740925-4	2018	AlphaScreen and AlphaLISA assays confirmed the ability of metformin to inhibit the demethylation activity of purified KDM6A/UTX enzyme.	Metformin	58-67	lysine (K)-specific demethylase 6A	Mus musculus	118-123
29740925-4	2018	AlphaScreen and AlphaLISA assays confirmed the ability of metformin to inhibit the demethylation activity of purified KDM6A/UTX enzyme.	Metformin	58-67	lysine (K)-specific demethylase 6A	Mus musculus	124-127
29740925-5	2018	Structural studies revealed that metformin might occupy the same set of residues involved in H3K27me3 binding and demethylation within the catalytic pocket of KDM6A/UTX.	Metformin	33-42	lysine (K)-specific demethylase 6A	Mus musculus	159-164
29740925-5	2018	Structural studies revealed that metformin might occupy the same set of residues involved in H3K27me3 binding and demethylation within the catalytic pocket of KDM6A/UTX.	Metformin	33-42	lysine (K)-specific demethylase 6A	Mus musculus	165-168
21465524-8	2011	Both pharmacologic inhibition and knock-down of AMPK blocked metformin-induced phosphorylation of JNK and mTOR.	Metformin	61-70	mechanistic target of rapamycin kinase	Mus musculus	106-110
21465524-10	2011	PTEN promoter activity was suppressed by metformin and inhibition of mTOR and JNK by pharmacologic inhibitors blocked metformin-induced PTEN promoter activity suppression.	Metformin	118-127	mechanistic target of rapamycin kinase	Mus musculus	69-73
21459323-3	2011	Ser372 phosphorylation of SREBP-1c by AMPK is necessary for inhibition of proteolytic processing and transcriptional activity of SREBP-1c in response to polyphenols and metformin.	Metformin	169-178	sterol regulatory element binding transcription factor 1	Mus musculus	26-34
21459323-3	2011	Ser372 phosphorylation of SREBP-1c by AMPK is necessary for inhibition of proteolytic processing and transcriptional activity of SREBP-1c in response to polyphenols and metformin.	Metformin	169-178	sterol regulatory element binding transcription factor 1	Mus musculus	129-137
21505202-0	2011	Variation in the ATM gene may alter glycemic response to metformin.	Metformin	57-66	ATM serine/threonine kinase	Homo sapiens	17-20
28678551-0	2018	Nano-encapsulated metformin-curcumin in PLGA/PEG inhibits synergistically growth and hTERT gene expression in human breast cancer cells.	Metformin	18-27	telomerase reverse transcriptase	Homo sapiens	85-90
29658305-8	2018	The rise in total antioxidant capacity after melatonin and particularly metformin and melatonin combination might result from the initiation of anaerobic metabolism and increasing SOD, GR, and glutathione peroxidase activity.	Metformin	72-81	glutathione-disulfide reductase	Rattus norvegicus	185-187
29859833-0	2018	Metformin alleviated endotoxemia-induced acute lung injury via restoring AMPK-dependent suppression of mTOR.	Metformin	0-9	mechanistic target of rapamycin kinase	Mus musculus	103-107
30116349-8	2018	Furthermore, secretion of TNF-alpha, IL-1alpha, M-CSF and TCA-3 into the conditioned media was significantly decreased by metformin (5 and 10 mM; P&lt;0.05).	Metformin	122-131	interleukin 1 alpha	Mus musculus	37-46
29678660-2	2018	Our findings showed that metformin in combination with quercetin synergistically inhibited the growth, migration and invasion of both PC-3 and LNCaP cells.	Metformin	25-34	chromobox 8	Homo sapiens	134-138
28962892-7	2018	Finally, metformin was still able to induce AMPK activation and to inhibit cell growth in cells treated with forskolin and in transfected cells overexpressing GHRH-receptor and treated with GHRH.	Metformin	9-18	growth hormone releasing hormone receptor	Rattus norvegicus	159-172
21735693-15	2011	CONCLUSIONS: Metformin administration decreases the circulating PAI-1 concentration and simultaneously improves insulin sensitivity and BMI in PCOS women with hyperinsulinemia.	Metformin	13-22	serpin family E member 1	Homo sapiens	64-69
21209036-5	2011	MAIN OUTCOME MEASURES: The effect of metformin on insulin-receptor substrate proteins 1 and 2 (IRS-1 and -2) mRNA and protein expression was determined.	Metformin	37-46	insulin receptor substrate 1	Homo sapiens	95-107
21319871-1	2011	Sitagliptin/metformin is a single-tablet, fixed-dose combination of the dipeptidyl peptidase-4 inhibitor sitagliptin and the biguanide antihyperglycaemic metformin that achieves greater improvements in glycaemic control than either component alone in patients with type 2 diabetes mellitus.	Metformin	12-21	dipeptidyl peptidase 4	Homo sapiens	72-94
20972533-2	2011	Although it reduces hepatic glucose production, clinical studies show that metformin may reduce plasma dipeptidyl peptidase-4 activity and increase circulating levels of glucagon-like peptide 1 (GLP-1).	Metformin	75-84	dipeptidylpeptidase 4	Mus musculus	103-125
20972533-10	2011	Metformin directly increased Glp1r expression in INS-1 beta cells via a PPAR-alpha-dependent, AMPK-independent mechanism.	Metformin	0-9	peroxisome proliferator activated receptor alpha	Rattus norvegicus	72-82
21199270-0	2011	Phosphoprotein enriched in diabetes gene product (Ped/pea-15) is increased in omental adipose tissue of women with the polycystic ovary syndrome: ex vivo regulation of ped/pea-15 by glucose, insulin and metformin.	Metformin	203-212	proliferation and apoptosis adaptor protein 15	Homo sapiens	0-35
21199270-0	2011	Phosphoprotein enriched in diabetes gene product (Ped/pea-15) is increased in omental adipose tissue of women with the polycystic ovary syndrome: ex vivo regulation of ped/pea-15 by glucose, insulin and metformin.	Metformin	203-212	proliferation and apoptosis adaptor protein 15	Homo sapiens	54-60
21199270-6	2011	Importantly, glucose and insulin increased whereas metformin significantly decreased Ped/pea-15 levels in human omental AT explants.	Metformin	51-60	proliferation and apoptosis adaptor protein 15	Homo sapiens	89-95
21241199-5	2011	AREAS COVERED: This review describes the general properties of OCT and illustrates their importance for the development of important drug toxicities using the examples of metformin and cisplatin.	Metformin	171-180	plexin A2	Homo sapiens	63-66
21270604-0	2011	Metformin reverses progestin resistance in endometrial cancer cells by downregulating GloI expression.	Metformin	0-9	glyoxalase I	Homo sapiens	86-90
21270604-2	2011	So, the aim of this study was to investigate the role of glyoxalase I (GloI), a mediator of chemotherapy resistance, in metformin reversal of progestin resistance in endometrial carcinoma.	Metformin	120-129	glyoxalase I	Homo sapiens	57-69
21270604-2	2011	So, the aim of this study was to investigate the role of glyoxalase I (GloI), a mediator of chemotherapy resistance, in metformin reversal of progestin resistance in endometrial carcinoma.	Metformin	120-129	glyoxalase I	Homo sapiens	71-75
21270604-9	2011	Metformin abolishes mTOR phosphorylation and inhibits GloI expression, attenuating proliferation and inducing apoptosis in progestin-resistant Ishikawa cells.	Metformin	0-9	glyoxalase I	Homo sapiens	54-58
21123367-4	2011	We found that in LKB1-null A549 lung adenocarcinoma cells, an AMPK activator, metformin, failed to block the nuclear export of PTEN, and the reintroduction of functional LKB1 into these cells restored the metformin-mediated inhibition of the nuclear export of PTEN.	Metformin	205-214	serine/threonine kinase 11	Homo sapiens	170-174
21123367-6	2011	Although the nuclear export of PTEN is blocked by metformin in MCF-7 breast cancer cells carrying wild-type LKB1, this inhibition could not be reversed by an AMPK inhibitor, suggesting that LKB1 could regulate the nuclear export of PTEN by bypassing AMPK alpha1/2.	Metformin	50-59	phosphatase and tensin homolog	Homo sapiens	31-35
21123367-6	2011	Although the nuclear export of PTEN is blocked by metformin in MCF-7 breast cancer cells carrying wild-type LKB1, this inhibition could not be reversed by an AMPK inhibitor, suggesting that LKB1 could regulate the nuclear export of PTEN by bypassing AMPK alpha1/2.	Metformin	50-59	serine/threonine kinase 11	Homo sapiens	190-194
21123367-8	2011	However, metformin was still able to induce the LKB1-mediated inhibition of the nuclear export of PTEN in these cells.	Metformin	9-18	serine/threonine kinase 11	Homo sapiens	48-52
21123367-8	2011	However, metformin was still able to induce the LKB1-mediated inhibition of the nuclear export of PTEN in these cells.	Metformin	9-18	phosphatase and tensin homolog	Homo sapiens	98-102
29966520-2	2018	Apart from its hypoglycemic properties, metformin also inhibits the cell cycle by restricting protein synthesis and cell proliferation via regulating the LKB1/AMPL pathway.	Metformin	40-49	serine/threonine kinase 11	Homo sapiens	154-158
29877321-9	2018	Statins and antidiabetic drugs (including sitagliptin, metformin, pioglitazone, liraglutide and empagliflozin) may affect leptin levels.	Metformin	55-64	leptin	Homo sapiens	122-128
29516618-6	2018	In cross-sectional analysis, greater prescribing of metformin and analogue insulin were associated with a higher proportion of patients achieving HbA1c &lt;=58 mmol/mol; the use of SGLT2 inhibitors and metformin was associated with a reduced proportion of patients with HbA1c &gt;86 mol/mol; otherwise associations for sulphonylureas, GLP-1 analogues, SGLT2 inhibitors and DPP-4 inhibitors were neutral or negative.	Metformin	52-61	solute carrier family 5 member 2	Homo sapiens	181-186
29516618-6	2018	In cross-sectional analysis, greater prescribing of metformin and analogue insulin were associated with a higher proportion of patients achieving HbA1c &lt;=58 mmol/mol; the use of SGLT2 inhibitors and metformin was associated with a reduced proportion of patients with HbA1c &gt;86 mol/mol; otherwise associations for sulphonylureas, GLP-1 analogues, SGLT2 inhibitors and DPP-4 inhibitors were neutral or negative.	Metformin	52-61	solute carrier family 5 member 2	Homo sapiens	352-357
29516618-6	2018	In cross-sectional analysis, greater prescribing of metformin and analogue insulin were associated with a higher proportion of patients achieving HbA1c &lt;=58 mmol/mol; the use of SGLT2 inhibitors and metformin was associated with a reduced proportion of patients with HbA1c &gt;86 mol/mol; otherwise associations for sulphonylureas, GLP-1 analogues, SGLT2 inhibitors and DPP-4 inhibitors were neutral or negative.	Metformin	52-61	dipeptidyl peptidase 4	Homo sapiens	373-378
29516618-6	2018	In cross-sectional analysis, greater prescribing of metformin and analogue insulin were associated with a higher proportion of patients achieving HbA1c &lt;=58 mmol/mol; the use of SGLT2 inhibitors and metformin was associated with a reduced proportion of patients with HbA1c &gt;86 mol/mol; otherwise associations for sulphonylureas, GLP-1 analogues, SGLT2 inhibitors and DPP-4 inhibitors were neutral or negative.	Metformin	202-211	solute carrier family 5 member 2	Homo sapiens	352-357
29516618-6	2018	In cross-sectional analysis, greater prescribing of metformin and analogue insulin were associated with a higher proportion of patients achieving HbA1c &lt;=58 mmol/mol; the use of SGLT2 inhibitors and metformin was associated with a reduced proportion of patients with HbA1c &gt;86 mol/mol; otherwise associations for sulphonylureas, GLP-1 analogues, SGLT2 inhibitors and DPP-4 inhibitors were neutral or negative.	Metformin	202-211	dipeptidyl peptidase 4	Homo sapiens	373-378
29536608-2	2018	MATERIALS AND METHODS: From US Centricity Electronic Medical Records, 163 081 patients with type 2 diabetes aged 18 to 80 years, who had initiated metformin, intensified their treatment with dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs), sulphonylureas (SUs), insulin or thiazolidinediones (TZDs), and continued second-line treatment for &gt;=6 months, were selected.	Metformin	147-156	dipeptidyl peptidase 4	Homo sapiens	191-213
29895585-6	2018	Moreover, metformin ameliorated CA-induced neuronal degeneration and glial activation in the hippocampal CA1 region, which was accompanied by augmented AMPK phosphorylation and autophagy activation in affected neuronal tissue.	Metformin	10-19	carbonic anhydrase 1	Rattus norvegicus	105-108
30023463-7	2018	Our study shows that both of the two signaling pathways can be blocked by this combinational strategy: metformin suppressed both pathways by inhibiting the phosphorylation of ERK, 4E-BP1 and S6, and BEZ235 suppressed PI3K/AKT/ mTOR pathway by reducing the phosphorylation of 4E-BP1 and S6.	Metformin	103-112	eukaryotic translation initiation factor 4E binding protein 1	Homo sapiens	180-186
30023463-7	2018	Our study shows that both of the two signaling pathways can be blocked by this combinational strategy: metformin suppressed both pathways by inhibiting the phosphorylation of ERK, 4E-BP1 and S6, and BEZ235 suppressed PI3K/AKT/ mTOR pathway by reducing the phosphorylation of 4E-BP1 and S6.	Metformin	103-112	eukaryotic translation initiation factor 4E binding protein 1	Homo sapiens	275-281
32055553-2	2018	We evaluated the role of PMAT genetic variations on the pharmacokinetic characteristics of metformin in a Korean population.	Metformin	91-100	solute carrier family 29 member 4	Homo sapiens	25-29
32055553-4	2018	Subjects who had more than one allele of c.883-144A>G single nucleotide polymorphism (SNP) in PMAT gene (rs3889348) showed increased renal clearance of metformin compared to wild-type subjects (814.79 +- 391.73 vs. 619.90 +- 195.43 mL/min, p=0.003), whereas no differences in metformin exposure were observed between the PMAT variant subjects and wild-type subjects.	Metformin	152-161	solute carrier family 29 member 4	Homo sapiens	94-98
32055553-4	2018	Subjects who had more than one allele of c.883-144A>G single nucleotide polymorphism (SNP) in PMAT gene (rs3889348) showed increased renal clearance of metformin compared to wild-type subjects (814.79 +- 391.73 vs. 619.90 +- 195.43 mL/min, p=0.003), whereas no differences in metformin exposure were observed between the PMAT variant subjects and wild-type subjects.	Metformin	152-161	solute carrier family 29 member 4	Homo sapiens	321-325
32055553-4	2018	Subjects who had more than one allele of c.883-144A>G single nucleotide polymorphism (SNP) in PMAT gene (rs3889348) showed increased renal clearance of metformin compared to wild-type subjects (814.79 +- 391.73 vs. 619.90 +- 195.43 mL/min, p=0.003), whereas no differences in metformin exposure were observed between the PMAT variant subjects and wild-type subjects.	Metformin	276-285	solute carrier family 29 member 4	Homo sapiens	94-98
32055553-7	2018	In conclusion, the genetic variation of c.883-144A>G SNP in PMAT significantly affects the renal clearance of metformin in healthy Korean male subjects.	Metformin	110-119	solute carrier family 29 member 4	Homo sapiens	60-64
29795113-0	2018	Inhibition of LCMR1 and ATG12 by demethylation-activated miR-570-3p is involved in the anti-metastasis effects of metformin on human osteosarcoma.	Metformin	114-123	microRNA 570	Homo sapiens	57-64
29988567-0	2018	Metformin treatment ameliorates diabetes-associated decline in hippocampal neurogenesis and memory via phosphorylation of insulin receptor substrate 1.	Metformin	0-9	insulin receptor substrate 1	Mus musculus	122-150
29988567-6	2018	Although chronic therapy with metformin fails to achieve recovery from hyperglycemia, a key feature of diabetes in middle-aged diabetic mice, it improves hippocampal-dependent spatial memory functions accompanied by increased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), atypical protein kinase C zeta (aPKC zeta), and insulin receptor substrate 1 (IRS1) at selective serine residues in the hippocampus.	Metformin	30-39	insulin receptor substrate 1	Mus musculus	350-378
29988567-6	2018	Although chronic therapy with metformin fails to achieve recovery from hyperglycemia, a key feature of diabetes in middle-aged diabetic mice, it improves hippocampal-dependent spatial memory functions accompanied by increased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), atypical protein kinase C zeta (aPKC zeta), and insulin receptor substrate 1 (IRS1) at selective serine residues in the hippocampus.	Metformin	30-39	insulin receptor substrate 1	Mus musculus	380-384
29988567-7	2018	Our findings suggest that signaling networks acting through long-term metformin-stimulated phosphorylation of AMPK, aPKC zeta/lambda, and IRS1 serine sites contribute to neuroprotective effects on hippocampal neurogenesis and cognitive function independent of a hypoglycemic effect.	Metformin	70-79	insulin receptor substrate 1	Mus musculus	138-142
29759071-14	2018	Additionally, the phosphorylation of AMPK after metformin treatment was 2-fold higher, and the expression of sterol regulatory element-binding protein-1c (SREBP-1c) after metformin treatment was about 2-fold lower compared to high glucose and high insulin group in HepG2 cells.	Metformin	171-180	sterol regulatory element binding transcription factor 1	Homo sapiens	109-153
29490902-3	2018	The objectives of this study were to use a physiologically based pharmacokinetic modeling platform to 1) assess the impact of alterations in DT expression, toxin-drug interactions (TDIs), and free fraction (fu) on PK predictions for the organic cation transporter 2/multidrug and toxin extrusion protein 1 substrate metformin in RI populations; and 2) use available in vitro data to improve predictions of CLR for two actively secreted substrates, metformin and ranitidine.	Metformin	316-325	solute carrier family 22 member 2	Homo sapiens	237-305
29490902-3	2018	The objectives of this study were to use a physiologically based pharmacokinetic modeling platform to 1) assess the impact of alterations in DT expression, toxin-drug interactions (TDIs), and free fraction (fu) on PK predictions for the organic cation transporter 2/multidrug and toxin extrusion protein 1 substrate metformin in RI populations; and 2) use available in vitro data to improve predictions of CLR for two actively secreted substrates, metformin and ranitidine.	Metformin	448-457	solute carrier family 22 member 2	Homo sapiens	237-305
29635345-0	2018	Bis-Indole-Derived NR4A1 Ligands and Metformin Exhibit NR4A1-Dependent Glucose Metabolism and Uptake in C2C12 Cells.	Metformin	37-46	nuclear receptor subfamily 4, group A, member 1	Mus musculus	55-60
29635345-3	2018	Metformin and the bis-indole substituted analogs also induced expression of several glycolytic genes and Rab4, which has previously been linked to enhancing cell membrane accumulation of Glut4 and overall glucose uptake in C2C12 cells, and these responses were also observed after treatment with metformin and the NR4A1 ligands.	Metformin	0-9	nuclear receptor subfamily 4, group A, member 1	Mus musculus	314-319
29635345-4	2018	The role of NR4A1 in mediating the responses induced by the bis-indoles and metformin was determined by knockdown of NR4A1, and this resulted in attenuating the gene and protein expression and enhanced glucose uptake responses induced by these compounds.	Metformin	76-85	nuclear receptor subfamily 4, group A, member 1	Mus musculus	12-17
29635345-4	2018	The role of NR4A1 in mediating the responses induced by the bis-indoles and metformin was determined by knockdown of NR4A1, and this resulted in attenuating the gene and protein expression and enhanced glucose uptake responses induced by these compounds.	Metformin	76-85	nuclear receptor subfamily 4, group A, member 1	Mus musculus	117-122
29635345-5	2018	Our results demonstrate that the bis-indole-derived NR4A1 ligands represent a class of drugs that enhance glucose uptake in C2C12 muscle cells, and we also show that the effects of metformin in this cell line are NR4A1-dependent.	Metformin	181-190	nuclear receptor subfamily 4, group A, member 1	Mus musculus	52-57
29635345-5	2018	Our results demonstrate that the bis-indole-derived NR4A1 ligands represent a class of drugs that enhance glucose uptake in C2C12 muscle cells, and we also show that the effects of metformin in this cell line are NR4A1-dependent.	Metformin	181-190	nuclear receptor subfamily 4, group A, member 1	Mus musculus	213-218
21426695-13	2011	The liver protective mechanisms of metformin in non-alcoholic fatty liver disease may be contributed to down-regulation of secretory phospholipase A2 mRNA expression, decrease in serum secretory phospholipase A2, lysophosphatidylcholine, lower inflammatory response and protect mitochondrial function.	Metformin	35-44	phospholipase A2 group IB	Rattus norvegicus	133-149
21426695-13	2011	The liver protective mechanisms of metformin in non-alcoholic fatty liver disease may be contributed to down-regulation of secretory phospholipase A2 mRNA expression, decrease in serum secretory phospholipase A2, lysophosphatidylcholine, lower inflammatory response and protect mitochondrial function.	Metformin	35-44	phospholipase A2 group IB	Rattus norvegicus	195-211
21059655-0	2011	Metformin activates AMP kinase through inhibition of AMP deaminase.	Metformin	0-9	adenosine monophosphate deaminase 1	Homo sapiens	53-66
21059655-14	2011	Having ruled out existing proposals, we suggest a new one: metformin might increase AMP through inhibition of AMP deaminase (AMPD).	Metformin	59-68	adenosine monophosphate deaminase 1	Homo sapiens	110-123
21059655-14	2011	Having ruled out existing proposals, we suggest a new one: metformin might increase AMP through inhibition of AMP deaminase (AMPD).	Metformin	59-68	adenosine monophosphate deaminase 1	Homo sapiens	125-129
21059655-15	2011	We found that metformin inhibited purified AMP deaminase activity.	Metformin	14-23	adenosine monophosphate deaminase 1	Homo sapiens	43-56
21059655-18	2011	Knockdown of AMPD obviated metformin stimulation of glucose transport.	Metformin	27-36	adenosine monophosphate deaminase 1	Homo sapiens	13-17
21059655-19	2011	We conclude that AMPD inhibition is the mechanism of metformin action.	Metformin	53-62	adenosine monophosphate deaminase 1	Homo sapiens	17-21
21114608-5	2011	In conclusion, the magnitude of HbA1c and FPG reductions after 6-month sulphonylurea treatment in addition to metformin is related to the TCF7L2 gene polymorphism.	Metformin	110-119	transcription factor 7 like 2	Homo sapiens	138-144
21954641-1	2011	The use of metformin during the first month of treatment of patients with coronary artery disease and diabetes type 2 led to the decrease of insulin resistance and reduced activity of systemic inflammation (significant decrease in the concentrations of IL-1, IL-6, IL-8 and TNF-alpha).	Metformin	11-20	interleukin 1 alpha	Homo sapiens	253-257
22132214-0	2011	Metformin represses self-renewal of the human breast carcinoma stem cells via inhibition of estrogen receptor-mediated OCT4 expression.	Metformin	0-9	POU class 5 homeobox 1	Homo sapiens	119-123
22132214-8	2011	Results also demonstrated the metformin reduced the expression of OCT4 in E2 &amp; TCDD mammospheres but not in the bisphenol A mammospheres, suggesting different mechanisms of action of the bisphenol A on human breast carcinoma cells.	Metformin	30-39	POU class 5 homeobox 1	Homo sapiens	66-70
22005339-0	2011	Metformin restores the correlation between serum-oxidized LDL and leptin levels in type 2 diabetic patients.	Metformin	0-9	leptin	Homo sapiens	66-72
22005339-3	2011	We also studied the effect of metformin therapy  on the correlation between serum ox-LDL and leptin levels in patients with newly diagnosed diabetes.	Metformin	30-39	leptin	Homo sapiens	93-99
22005339-9	2011	Leptin was significantly correlated with ox-LDL/LDL ratio in controls (r=0.78, P&lt;0.01), and in patients with newly diagnosed diabetes (r=0.4,  P&lt;0.05), after metformin therapy.	Metformin	164-173	leptin	Homo sapiens	0-6
22005339-11	2011	DISCUSSION: Metformin restores the positive correlation  between serum ox-LDL and leptin levels in patients with type 2 diabetes.	Metformin	12-21	leptin	Homo sapiens	82-88
21098287-0	2010	Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling.	Metformin	10-19	microtubule associated protein tau	Homo sapiens	28-31
20977583-4	2010	Genotyping of the IRS-1 Arg(972) variant was performed in type 2 diabetes patients treated with either sulphonylurea drugs, glinides or insulin or with metformin, acarbose or glitazones using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.	Metformin	152-161	insulin receptor substrate 1	Homo sapiens	18-23
28704854-6	2018	The DPP-4 inhibitor+-metformin group showed a greater HbA1c reduction than the metformin group (1.3+-1.4% vs. 0.9+-1.0%, p=0.022), with no significant differences between groups in hypoglycemic episodes.	Metformin	21-30	dipeptidyl peptidase 4	Homo sapiens	4-9
29665787-0	2018	Valproic acid sensitizes metformin-resistant human renal cell carcinoma cells by upregulating H3 acetylation and EMT reversal.	Metformin	25-34	IL2 inducible T cell kinase	Homo sapiens	113-116
29654226-0	2018	Metformin Enhances the Effect of Regorafenib and Inhibits Recurrence and Metastasis of Hepatic Carcinoma After Liver Resection via Regulating Expression of Hypoxia Inducible Factors 2alpha (HIF-2alpha) and 30 kDa HIV Tat-Interacting Protein (TIP30).	Metformin	0-9	endothelial PAS domain protein 1	Mus musculus	190-200
29383869-8	2018	While each tissue had a signature reflecting its own function, we identified a cascade of predictive upstream transcriptional regulators, including mTORC1, MYC, TNF, TGFss1, and miRNA-29b that may explain tissue-specific transcriptomic changes in response to metformin treatment.	Metformin	259-268	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	156-159
29366775-3	2018	AMPK activators metformin and AICAR delayed endothelial senescence via SIRT1-mediated upregulation of DOT1L, leading to increased trimethylation of H3K79 (H3K79me3).	Metformin	16-25	sirtuin 1	Mus musculus	71-76
29366775-3	2018	AMPK activators metformin and AICAR delayed endothelial senescence via SIRT1-mediated upregulation of DOT1L, leading to increased trimethylation of H3K79 (H3K79me3).	Metformin	16-25	DOT1-like, histone H3 methyltransferase (S. cerevisiae)	Mus musculus	102-107
29366775-10	2018	Overall, the results of this study show a novel regulation of mitochondrial biogenesis/function, and cellular senescence by H3K79me acting through SIRT3, thus providing a molecular basis for metformin-mediated age-delaying effects.	Metformin	191-200	sirtuin 3	Mus musculus	147-152
29374065-0	2018	Metformin-Induced Reduction of CD39 and CD73 Blocks Myeloid-Derived Suppressor Cell Activity in Patients with Ovarian Cancer.	Metformin	0-9	ectonucleoside triphosphate diphosphohydrolase 1	Homo sapiens	31-35
29374065-2	2018	We show here that metformin treatment blocks the suppressive function of myeloid-derived suppressor cells (MDSC) in patients with ovarian cancer by downregulating the expression and ectoenzymatic activity of CD39 and CD73 on monocytic and polymononuclear MDSC subsets.	Metformin	18-27	ectonucleoside triphosphate diphosphohydrolase 1	Homo sapiens	208-212
29374065-3	2018	Metformin triggered activation of AMP-activated protein kinase alpha and subsequently suppressed hypoxia-inducible factor alpha, which was critical for induction of CD39/CD73 expression in MDSC.	Metformin	0-9	ectonucleoside triphosphate diphosphohydrolase 1	Homo sapiens	165-169
29374065-4	2018	Furthermore, metformin treatment correlated with longer overall survival in diabetic patients with ovarian cancer, which was accompanied by a metformin-induced reduction in the frequency of circulating CD39+CD73+ MDSC and a concomitant increase in the antitumor activities of circulating CD8+ T cells.	Metformin	13-22	ectonucleoside triphosphate diphosphohydrolase 1	Homo sapiens	202-206
29374065-4	2018	Furthermore, metformin treatment correlated with longer overall survival in diabetic patients with ovarian cancer, which was accompanied by a metformin-induced reduction in the frequency of circulating CD39+CD73+ MDSC and a concomitant increase in the antitumor activities of circulating CD8+ T cells.	Metformin	142-151	ectonucleoside triphosphate diphosphohydrolase 1	Homo sapiens	202-206
29374065-5	2018	Our results highlight a direct effect of metformin on MDSC and suggest that metformin may yield clinical benefit through improvement of antitumor T-cell immunity by dampening CD39/CD73-dependent MDSC immunosuppression in ovarian cancer patients.Significance: The antitumor activity of an antidiabetes drug is attributable to reduced immunosuppressive activity of myeloid-derived tumor suppressor cells.	Metformin	76-85	ectonucleoside triphosphate diphosphohydrolase 1	Homo sapiens	175-179
29552226-1	2018	Metformin, a widely used antidiabetic drug, exhibits anticancer effects which are mediated by the phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (AKT) signaling pathway.	Metformin	0-9	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta	Homo sapiens	98-127
29554968-13	2018	The xenograft mouse model further confirmed that metformin inhibited tumor growth by upregulation of AMPK and downregulation of mTOR.	Metformin	49-58	mechanistic target of rapamycin kinase	Mus musculus	128-132
29513760-6	2018	Several inflammatory molecules upregulated by tumor necrosis factor-alpha in human retinal vascular endothelial cells were markedly reduced by metformin, including nuclear factor kappa B p65 (NFkappaB p65), intercellular adhesion molecule-1 (ICAM-1), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8).	Metformin	143-152	C-C motif chemokine ligand 2	Homo sapiens	251-281
29513760-6	2018	Several inflammatory molecules upregulated by tumor necrosis factor-alpha in human retinal vascular endothelial cells were markedly reduced by metformin, including nuclear factor kappa B p65 (NFkappaB p65), intercellular adhesion molecule-1 (ICAM-1), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8).	Metformin	143-152	C-C motif chemokine ligand 2	Homo sapiens	283-288
29513760-8	2018	Activation of AMP-activated protein kinase was found to play a partial role in the suppression of ICAM-1 and MCP-1 by metformin, but not in those of NFkappaB p65 and IL-8.	Metformin	118-127	C-C motif chemokine ligand 2	Homo sapiens	109-114
29253574-0	2018	Metformin treatment prevents amyloid plaque deposition and memory impairment in APP/PS1 mice.	Metformin	0-9	presenilin 1	Mus musculus	84-87
29253574-4	2018	However, whether metformin is responsible for the anti-neuroinflammationand neuroprotection on APPswe/PS1DeltaE9 (APP/PS1) mice remains unclear.	Metformin	17-26	presenilin 1	Mus musculus	102-105
29253574-5	2018	Here we showed that metformin attenuated spatial memory deficit, neuron loss in the hippocampus and enhanced neurogenesis in APP/PS1 mice.	Metformin	20-29	presenilin 1	Mus musculus	129-132
29326107-0	2018	TCF7L2 Genetic Variation Augments Incretin Resistance and Influences Response to a Sulfonylurea and Metformin: The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH).	Metformin	100-109	transcription factor 7 like 2	Homo sapiens	0-6
29326107-0	2018	TCF7L2 Genetic Variation Augments Incretin Resistance and Influences Response to a Sulfonylurea and Metformin: The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH).	Metformin	173-182	transcription factor 7 like 2	Homo sapiens	0-6
29326107-8	2018	CONCLUSIONS: Our findings demonstrate that common variation at TCF7L2 influences acute responses to both glipizide and metformin in people without diabetes and highlight altered incretin signaling as a potential mechanism by which TCF7L2 variation increases T2D risk.	Metformin	119-128	transcription factor 7 like 2	Homo sapiens	63-69
29326107-8	2018	CONCLUSIONS: Our findings demonstrate that common variation at TCF7L2 influences acute responses to both glipizide and metformin in people without diabetes and highlight altered incretin signaling as a potential mechanism by which TCF7L2 variation increases T2D risk.	Metformin	119-128	transcription factor 7 like 2	Homo sapiens	231-237
29138876-6	2018	RESULTS: Individuals aged &gt;=65 years on metformin + pioglitazone had a significantly lower risk of dementia compared with those on metformin + sulfonylurea (HR 0.56; 95% CI 0.34, 0.93), and a lower, but insignificant, risk of dementia compared with those on other metformin-based dual regimens (i.e. metformin + acarbose, metformin + meglitinide, metformin + insulin or metformin + dipeptidyl peptidase 4 inhibitors).	Metformin	43-52	dipeptidyl peptidase 4	Homo sapiens	385-407
29456653-8	2018	Expression of scavenger receptors, including scavenger receptor A, cluster of differentiation 36 and lectin-type oxidized LDL receptor 1 was examined in the presence or absence of metformin with ox-LDL treatment.	Metformin	180-189	CD36 molecule	Homo sapiens	14-96
29286158-0	2018	Metformin inhibits HaCaT cell viability via the miR-21/PTEN/Akt signaling pathway.	Metformin	0-9	microRNA 21	Homo sapiens	48-54
29286158-0	2018	Metformin inhibits HaCaT cell viability via the miR-21/PTEN/Akt signaling pathway.	Metformin	0-9	phosphatase and tensin homolog	Homo sapiens	55-59
29286158-7	2018	Metformin treatment downregulated miR-21 expression (t=-8.903, P&lt;0.05).	Metformin	0-9	microRNA 21	Homo sapiens	34-40
29286158-10	2018	Metformin was, therefore, concluded to inhibit HaCaT cell growth in a time-and dose-dependent manner, and the miR-21/PTEN/Akt signaling pathway may serve a crucial role in the molecular mechanism of metformin"s effect on HaCaT cells.	Metformin	199-208	microRNA 21	Homo sapiens	110-116
29286158-10	2018	Metformin was, therefore, concluded to inhibit HaCaT cell growth in a time-and dose-dependent manner, and the miR-21/PTEN/Akt signaling pathway may serve a crucial role in the molecular mechanism of metformin"s effect on HaCaT cells.	Metformin	199-208	phosphatase and tensin homolog	Homo sapiens	117-121
29472557-6	2018	Metformin reduced cyclin D1 expression and RB, STAT3, STAT5, ERK1/2 and p70S6K phosphorylation.	Metformin	0-9	signal transducer and activator of transcription 5A	Homo sapiens	54-59
29472557-6	2018	Metformin reduced cyclin D1 expression and RB, STAT3, STAT5, ERK1/2 and p70S6K phosphorylation.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	72-78
29472557-8	2018	Notably, metformin reduced Ba/F3 JAK2V617F tumor burden and splenomegaly in Jak2V617F knock-in-induced MPN mice and spontaneous erythroid colony formation in primary cells from polycythemia vera patients.	Metformin	9-18	Janus kinase 2	Mus musculus	76-80
20977583-7	2010	CONCLUSIONS: Thus, we were able to replicate the earlier findings of an association between the IRS-1 Arg(972) variant and secondary failure to sulphonylurea drugs, and further observed a general association between HbA1c and this polymorphism in type 2 diabetes patients treated with insulinotropic hypoglycaemic drugs but not with metformin.	Metformin	333-342	insulin receptor substrate 1	Homo sapiens	96-101
21189532-4	2010	Janumet is a fixed-dose combination of sitagliptin, a specific inhibitor of dipeptidylpeptidase-4 that blocks the rapid degradation of so-called incretin hormones (resulting in a potentiation of insulin secretion and reduction of glucagon secretion in a glucose-dependent manner), and of metformin, a biguanide compound that reduces glucose hepatic production and slightly improves insulin sensitivity.	Metformin	288-297	dipeptidyl peptidase 4	Homo sapiens	76-97
20824678-1	2010	BACKGROUND: Dipeptidyl peptidase-4 inhibitors improve glycaemic control in patients with type 2 diabetes mellitus when used as monotherapy or in combination with other anti-diabetic drugs (metformin, sulphonylurea, or thiazolidinedione).	Metformin	189-198	dipeptidyl peptidase 4	Homo sapiens	12-34
20707611-4	2010	AREAS COVERED IN THIS REVIEW: An extensive literature search was performed to analyze the potential pharmacokinetic (PK) and pharmacodynamic (PD) interactions between metformin (first-line drug for the management of type 2 diabetes) and sitagliptin (first commercialized DPP IV inhibitor).	Metformin	167-176	dipeptidyl peptidase 4	Homo sapiens	271-277
20300828-6	2010	Interestingly, metformin also causes a significant increase in LKB1 protein expression and promoter activity, thereby providing for the first time an additional mechanism by which metformin activates AMPK.	Metformin	15-24	serine/threonine kinase 11	Homo sapiens	63-67
20300828-6	2010	Interestingly, metformin also causes a significant increase in LKB1 protein expression and promoter activity, thereby providing for the first time an additional mechanism by which metformin activates AMPK.	Metformin	180-189	serine/threonine kinase 11	Homo sapiens	63-67
19937362-8	2010	Similarly, serum leptin levels decreased in both sibutramine (P = 0.04, P = 0.01) and sibutramine plus metformin groups (P = 0.023, P = 0.025) after 3 and 12 months, respectively.	Metformin	103-112	leptin	Homo sapiens	17-23
20615625-12	2010	AMPK appears to (1) participate in an ATM-AMPK-p21(waf/cip) pathway, (2) be involved in regulation of the IR-induced G2/M checkpoint, and (3) may be targeted by metformin to enhance IR responses.	Metformin	161-170	ATM serine/threonine kinase	Homo sapiens	38-41
19628413-8	2010	Metformin stimulated the expression of Runx2 and IGF-1 in three glucose groups, but it did not affect IGF-1R.	Metformin	0-9	insulin-like growth factor 1	Rattus norvegicus	49-54
20180027-9	2010	In contrast, GnRH-induced FSHbeta promoter activity was significantly potentiated in the presence of metformin.	Metformin	101-110	follicle stimulating hormone subunit beta	Homo sapiens	26-33
20214894-0	2010	Metformin induces reductions in plasma cobalamin and haptocorrin bound cobalamin levels in elderly diabetic patients.	Metformin	0-9	transcobalamin 1	Homo sapiens	53-64
20214894-4	2010	RESULTS: As compared to baseline measures, there was a metformin therapy specific significant decrease in plasma levels of total cobalamin, total haptocorrin and haptocorrin bound cobalamin.	Metformin	55-64	transcobalamin 1	Homo sapiens	146-157
20214894-4	2010	RESULTS: As compared to baseline measures, there was a metformin therapy specific significant decrease in plasma levels of total cobalamin, total haptocorrin and haptocorrin bound cobalamin.	Metformin	55-64	transcobalamin 1	Homo sapiens	162-173
20214894-5	2010	CONCLUSIONS: Plasma total cobalamin and haptocorrin bound cobalamin levels are reduced by short term metformin therapy in an elderly diabetic population.	Metformin	101-110	transcobalamin 1	Homo sapiens	40-51
20038265-5	2010	Metformin also blocked the induction of ER stress proteins (GRP78, Chop, Cleaved ATF-6, p-eIF2 alpha and XBP-1) and regulated serine phosphorylation of IRS-1.	Metformin	0-9	X-box binding protein 1	Homo sapiens	105-110
20038265-5	2010	Metformin also blocked the induction of ER stress proteins (GRP78, Chop, Cleaved ATF-6, p-eIF2 alpha and XBP-1) and regulated serine phosphorylation of IRS-1.	Metformin	0-9	insulin receptor substrate 1	Homo sapiens	152-157
20363874-3	2010	The AMPK activator metformin stimulated AMPK Thr172 phosphorylation and inhibited IGF-I-stimulated phosphorylation of Akt/tuberous sclerosis 2 (TSC2)/mammalian target of rapamycin (mTOR)/p70S6 kinase (p70S6K).	Metformin	19-28	ribosomal protein S6 kinase B1	Homo sapiens	201-207
29391064-10	2018	RESULTS: The discounted incremental cost of metformin+DPP-4i compared to metformin+SU was $11,849 and the incremental life-years gained were 0.61, resulting in an ICER of $19,420 per life-year gained for patients in the metformin+DPP-4i treatment pathway.	Metformin	44-53	dipeptidyl peptidase 4	Homo sapiens	54-59
29204687-9	2018	Specific DDI simulations using PBPK models of simvastatin (OATP1B3 substrate) and metformin (OCT2 substrate) predict no significant changes of the plasma concentrations of these two victim drugs during co-administration.	Metformin	82-91	solute carrier family 22 member 2	Homo sapiens	93-97
29385181-0	2018	Simvastatin and metformin inhibit cell growth in hepatitis C virus infected cells via mTOR increasing PTEN and autophagy.	Metformin	16-25	phosphatase and tensin homolog	Homo sapiens	102-106
29385181-7	2018	Simvastatin and metformin co-administered down-regulated mTOR and TCTP, while PTEN was increased.	Metformin	16-25	tumor protein, translationally-controlled 1	Homo sapiens	66-70
29385181-10	2018	In human primary hepatocytes, metformin treatment inhibited mTOR and PTEN, but up-regulated p62, LC3BII and Caspase 3.	Metformin	30-39	phosphatase and tensin homolog	Homo sapiens	69-73
29531801-6	2018	Based on this, we used one compound that we discovered previously to interfere with the MID1 complex, metformin, for in vivo experiments.	Metformin	102-111	midline 1	Mus musculus	88-92
29531801-9	2018	These findings together with our previous observation, showing that inhibition of the MID1 complex by metformin also decreases tau phosphorylation, make the MID1 complex a particularly interesting drug target for treating AD.	Metformin	102-111	midline 1	Mus musculus	86-90
29531801-9	2018	These findings together with our previous observation, showing that inhibition of the MID1 complex by metformin also decreases tau phosphorylation, make the MID1 complex a particularly interesting drug target for treating AD.	Metformin	102-111	midline 1	Mus musculus	157-161
29368615-0	2018	Glitazones and alpha-glucosidase inhibitors as the second-line oral anti-diabetic agents added to metformin reduce cardiovascular risk in Type 2 diabetes patients: a nationwide cohort observational study.	Metformin	98-107	sucrase-isomaltase	Homo sapiens	15-32
29351188-8	2018	Metformin promoted HUVEC migration and inhibited apoptosis via upregulation of vascular endothelial growth factor (VEGF) receptors (VEGFR1/R2), fatty acid binding protein 4 (FABP4), ERK/mitogen-activated protein kinase signaling, chemokine ligand 8, lymphocyte antigen 96, Rho kinase 1 (ROCK1), matrix metalloproteinase 16 (MMP16) and tissue factor inhibitor-2 under hyperglycemia-chemical hypoxia.	Metformin	0-9	fatty acid binding protein 4	Homo sapiens	144-172
29351188-8	2018	Metformin promoted HUVEC migration and inhibited apoptosis via upregulation of vascular endothelial growth factor (VEGF) receptors (VEGFR1/R2), fatty acid binding protein 4 (FABP4), ERK/mitogen-activated protein kinase signaling, chemokine ligand 8, lymphocyte antigen 96, Rho kinase 1 (ROCK1), matrix metalloproteinase 16 (MMP16) and tissue factor inhibitor-2 under hyperglycemia-chemical hypoxia.	Metformin	0-9	fatty acid binding protein 4	Homo sapiens	174-179
29351188-8	2018	Metformin promoted HUVEC migration and inhibited apoptosis via upregulation of vascular endothelial growth factor (VEGF) receptors (VEGFR1/R2), fatty acid binding protein 4 (FABP4), ERK/mitogen-activated protein kinase signaling, chemokine ligand 8, lymphocyte antigen 96, Rho kinase 1 (ROCK1), matrix metalloproteinase 16 (MMP16) and tissue factor inhibitor-2 under hyperglycemia-chemical hypoxia.	Metformin	0-9	matrix metallopeptidase 16	Homo sapiens	295-322
29351188-8	2018	Metformin promoted HUVEC migration and inhibited apoptosis via upregulation of vascular endothelial growth factor (VEGF) receptors (VEGFR1/R2), fatty acid binding protein 4 (FABP4), ERK/mitogen-activated protein kinase signaling, chemokine ligand 8, lymphocyte antigen 96, Rho kinase 1 (ROCK1), matrix metalloproteinase 16 (MMP16) and tissue factor inhibitor-2 under hyperglycemia-chemical hypoxia.	Metformin	0-9	matrix metallopeptidase 16	Homo sapiens	324-329
29351188-9	2018	Therefore, metformin"s dual effect in hyperglycemia-chemical hypoxia is mediated by direct effect on VEGFR1/R2 leading to activation of cell migration through MMP16 and ROCK1 upregulation, and inhibition of apoptosis by increase in phospho-ERK1/2 and FABP4, components of VEGF signaling cascades.	Metformin	11-20	matrix metallopeptidase 16	Homo sapiens	159-164
29351188-9	2018	Therefore, metformin"s dual effect in hyperglycemia-chemical hypoxia is mediated by direct effect on VEGFR1/R2 leading to activation of cell migration through MMP16 and ROCK1 upregulation, and inhibition of apoptosis by increase in phospho-ERK1/2 and FABP4, components of VEGF signaling cascades.	Metformin	11-20	fatty acid binding protein 4	Homo sapiens	251-256
29303184-6	2018	By screening chemicals that could help the endosomal/lysosomal escape of chemicals related to LDLR-mediated transcytosis, it was shown that hemagglutinin-2 (HA2) and metformin had higher abilities to enhance the exocytosis of P22NPs.	Metformin	166-175	low density lipoprotein receptor	Homo sapiens	94-98
28689771-8	2018	Therapeutic interventions with tacrolimus or metformin normalized the expression of decidual IFNgamma, PGR and FKBP52, increased co-localization of protein inhibitor of activated STATy (PIASy) to PGR and resulted in the upregulation of uterine IL11and LIF.	Metformin	45-54	protein inhibitor of activated STAT 4	Mus musculus	186-191
28689771-8	2018	Therapeutic interventions with tacrolimus or metformin normalized the expression of decidual IFNgamma, PGR and FKBP52, increased co-localization of protein inhibitor of activated STATy (PIASy) to PGR and resulted in the upregulation of uterine IL11and LIF.	Metformin	45-54	leukemia inhibitory factor	Mus musculus	252-255
29323154-8	2018	Knockdown of glutaminase 1, ASCT2, and c-Myc induced significant CSC-suppression and enhanced CSC-suppressing effect of metformin and compound 968.	Metformin	120-129	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	39-44
29151256-6	2018	Metformin caused a decrease in oxidative stress in the heart, accompanied by a decrease in diene conjugates, the elimination of ROS (stable total antioxidant status), and the activation of catalase and glutathione reductase.	Metformin	0-9	glutathione-disulfide reductase	Rattus norvegicus	202-223
29412124-3	2018	The newest antidiabetic drugs, possibly with the most pleiotropic actions after metformin are the sodium-glucose cotransporter 2 (SGLT-2) inhibitors (SGLT-2i).	Metformin	80-89	solute carrier family 5 member 2	Homo sapiens	98-128
29412124-3	2018	The newest antidiabetic drugs, possibly with the most pleiotropic actions after metformin are the sodium-glucose cotransporter 2 (SGLT-2) inhibitors (SGLT-2i).	Metformin	80-89	solute carrier family 5 member 2	Homo sapiens	130-136
30036874-11	2018	CONCLUSIONS: The results indicated that metformin suppresses radiation-induced skin injuries by modulating the expression of FOXO3 through PIK3r1.	Metformin	40-49	phosphoinositide-3-kinase regulatory subunit 1	Mus musculus	139-145
28782285-0	2018	Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P-gp-overexpressing MCF-7 cells.	Metformin	0-9	phosphoglycolate phosphatase	Homo sapiens	83-87
28782285-5	2018	The P-gp mRNA/protein expression levels following treatment with metformin were determined using real-time polymerase chain reaction and Western blot analysis, respectively.	Metformin	65-74	phosphoglycolate phosphatase	Homo sapiens	4-8
28782285-8	2018	The effect of metformin on DOX-induced apoptosis was evaluated by annexin V/FITC assay.	Metformin	14-23	annexin A5	Homo sapiens	66-75
28782285-10	2018	Metformin had no substantial effect on P-gp expression, while the activity of P-gp and intracellular ATP content decreased with metformin treatment in a dose-dependent manner.	Metformin	128-137	phosphoglycolate phosphatase	Homo sapiens	78-82
28782285-12	2018	These results indicate that metformin could reverse MDR in breast cancer cells by reducing P-gp activity.	Metformin	28-37	phosphoglycolate phosphatase	Homo sapiens	91-95
29399562-5	2018	In addition, mRNA expression of pro-apoptotic genes, p21 and Bax, was decreased and of anti-apoptotic genes, Bcl-2 and Bcl-xl, was increased with metformin treatment compared to QUIN-induced cells.	Metformin	146-155	H3 histone pseudogene 16	Homo sapiens	53-56
28467723-5	2017	Furthermore, increases in leukocyte-endothelial interactions and intercellular adhesion molecule-1 and P-selectin levels were found in T2D and were also restored in metformin-treated patients.	Metformin	165-174	selectin P	Homo sapiens	103-113
29215608-0	2017	H19 lncRNA alters methylation and expression of Hnf4alpha in the liver of metformin-exposed fetuses.	Metformin	74-83	H19 imprinted maternally expressed transcript	Homo sapiens	0-3
29215608-7	2017	We also provide evidence that altered H19 expression is a direct effect of metformin in the fetal liver.	Metformin	75-84	H19 imprinted maternally expressed transcript	Homo sapiens	38-41
29215608-8	2017	Our results suggest that metformin from the mother can directly act upon the fetal liver to modify Hnf4alpha expression, a key factor for both liver development and function, and that perturbation of this H19/Hnf4alpha-mediated pathway may contribute to the fetal origin of adult metabolic abnormalities.	Metformin	25-34	H19 imprinted maternally expressed transcript	Homo sapiens	205-208
29187435-4	2017	MATERIALS AND METHODS: MTS assays were used to determine the effect of metformin-docetaxel treatment on PC3 and DU145 cell viability.	Metformin	71-80	chromobox 8	Homo sapiens	104-107
29187435-7	2017	RESULTS: Metformin-docetaxel treatment significantly reduced PC3 cell viability.	Metformin	9-18	chromobox 8	Homo sapiens	61-64
28847510-6	2017	In contrast, knockdown of Smad6 or Smurf1 prevented metformin-induced reduction of ALK2.	Metformin	52-61	SMAD family member 6	Homo sapiens	26-31
29174215-11	2017	IMPLICATIONS: Although both DPP-4i and SGLT2i are effective add-on antihyperglycemic therapies to metformin monotherapy, baseline characteristics, such as HbA1C, renal function, and age, should be considered when choosing between the 2 classes to allow for optimal and timely diabetes management.	Metformin	98-107	solute carrier family 5 member 2	Homo sapiens	39-44
28701284-12	2017	CONCLUSION: The most cost-effective DPP-4 Inhibitor was sitagliptin with metformin.	Metformin	73-82	dipeptidyl peptidase 4	Homo sapiens	36-41
29051159-0	2017	Metformin Use May Moderate the Effect of DPP-4 Inhibitors on Cardiovascular Outcomes.	Metformin	0-9	dipeptidyl peptidase 4	Homo sapiens	41-46
29051159-1	2017	OBJECTIVE: To explore prevalent metformin use as a potential moderator of the cardiovascular effects of dipeptidyl peptidase 4 inhibitors (DPP-4i).	Metformin	32-41	dipeptidyl peptidase 4	Homo sapiens	104-126
28988825-6	2017	Indeed, biguanides fail to mitigate the PGC-1alpha-dependent lung metastatic phenotype and PGC-1alpha confers resistance to stepwise increases in metformin concentration.	Metformin	146-155	PPARG coactivator 1 alpha	Sus scrofa	91-101
29188065-8	2017	Conclusion: Non-obese Asian Indian patients with T2DM and on metformin therapy have significantly higher circulating plasma DPP4 levels as compared to non-obese non-diabetic controls, and these levels correlate with fasting insulin and LDL-C levels, upper limb subcutaneous adipose tissue, intra-abdominal adiposity and presence of diabetes.	Metformin	61-70	dipeptidyl peptidase 4	Homo sapiens	124-128
29122080-9	2017	Metformin also significantly decreased contractile activity, with a concomitant reduction in the production of MMP-1 and MMP-2 but not of MMP-9.	Metformin	0-9	matrix metallopeptidase 1	Homo sapiens	111-116
28323503-2	2017	The aim of the study was to evaluate whether dipeptidyl peptidase-4 (DPP-4) inhibitor alogliptin (ALO) alone or in combination with pioglitazone (PIO) improves beta-cell function along with insulin resistance (IR) in metformin (MET) treated obese women with PCOS with persistent IR.	Metformin	217-226	dipeptidyl peptidase 4	Homo sapiens	45-67
29066174-2	2017	We found that metformin (Met) reduced tumor-infiltrating Treg (Ti-Treg), particularly the terminally-differentiated CD103+KLRG1+ population, and also decreased effector molecules such as CTLA4 and IL-10.	Metformin	14-23	cytotoxic T-lymphocyte associated protein 4	Homo sapiens	187-192
28843855-8	2017	Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-kappaB; and reduced interaction between OGT and ChREBP or NF-kappaB.	Metformin	9-18	O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N-acetylglucosamine:polypeptide-N-acetylglucosaminyl transferase)	Mus musculus	124-127
28843855-8	2017	Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-kappaB; and reduced interaction between OGT and ChREBP or NF-kappaB.	Metformin	9-18	O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N-acetylglucosamine:polypeptide-N-acetylglucosaminyl transferase)	Mus musculus	190-193
28843855-9	2017	Our results indicate that OGT inhibition might be one of the mechanisms by which metformin decreases retinal cell death.	Metformin	81-90	O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N-acetylglucosamine:polypeptide-N-acetylglucosaminyl transferase)	Mus musculus	26-29
28821394-8	2017	Furthermore, hNSCs exposed to AGEs had significantly lower mRNA levels among other components of normal cellular oxidative defenses (GSH, Catalase and HO-1), which were all rescued by co-treatment with metformin.	Metformin	202-211	heme oxygenase 1	Homo sapiens	151-155
29254204-7	2017	Peritendinous tissue from metformin-treated rats also showed decreased expression of fibrotic genes including col1a1, col3a1, and alpha-smooth muscle actin (alpha-SMA), and inhibition of transforming growth factor (TGF)-beta1 signaling.	Metformin	26-35	collagen type III alpha 1 chain	Rattus norvegicus	118-124
29254204-7	2017	Peritendinous tissue from metformin-treated rats also showed decreased expression of fibrotic genes including col1a1, col3a1, and alpha-smooth muscle actin (alpha-SMA), and inhibition of transforming growth factor (TGF)-beta1 signaling.	Metformin	26-35	actin gamma 2, smooth muscle	Rattus norvegicus	130-155
29254204-7	2017	Peritendinous tissue from metformin-treated rats also showed decreased expression of fibrotic genes including col1a1, col3a1, and alpha-smooth muscle actin (alpha-SMA), and inhibition of transforming growth factor (TGF)-beta1 signaling.	Metformin	26-35	actin gamma 2, smooth muscle	Rattus norvegicus	157-166
29254204-9	2017	Metformin treatment also inhibited the expression of fibrotic genes and decreased the phosphorylation of smad2/3 and extracellular signal-regulated kinase (ERK) 1/2.	Metformin	0-9	SMAD family member 2	Rattus norvegicus	105-112
20363874-6	2010	Both metformin and constitutively activated AMPK enhanced phosphorylation of IRS-1 Ser794, which led to decreased IRS-1 tyrosine phosphorylation and recruitment of the p85 subunit of PI3K.	Metformin	5-14	insulin receptor substrate 1	Homo sapiens	77-82
20363874-6	2010	Both metformin and constitutively activated AMPK enhanced phosphorylation of IRS-1 Ser794, which led to decreased IRS-1 tyrosine phosphorylation and recruitment of the p85 subunit of PI3K.	Metformin	5-14	insulin receptor substrate 1	Homo sapiens	114-119
20363874-10	2010	These findings are relevant to whole animal physiology because administration of metformin to mice resulted in inhibition of IGF-I-stimulated phosphorylation of Akt/mTOR/p70S6K.	Metformin	81-90	mechanistic target of rapamycin kinase	Mus musculus	165-169
20398632-0	2010	Metformin reduces intracellular reactive oxygen species levels by upregulating expression of the antioxidant thioredoxin via the AMPK-FOXO3 pathway.	Metformin	0-9	thioredoxin	Homo sapiens	109-120
20398632-6	2010	Additionally, metformin increased the expression of the antioxidant thioredoxin (Trx), which mediated metformin"s effects on ROS reduction.	Metformin	14-23	thioredoxin	Homo sapiens	68-79
20398632-6	2010	Additionally, metformin increased the expression of the antioxidant thioredoxin (Trx), which mediated metformin"s effects on ROS reduction.	Metformin	14-23	thioredoxin	Homo sapiens	81-84
20398632-6	2010	Additionally, metformin increased the expression of the antioxidant thioredoxin (Trx), which mediated metformin"s effects on ROS reduction.	Metformin	102-111	thioredoxin	Homo sapiens	68-79
20398632-6	2010	Additionally, metformin increased the expression of the antioxidant thioredoxin (Trx), which mediated metformin"s effects on ROS reduction.	Metformin	102-111	thioredoxin	Homo sapiens	81-84
20398632-7	2010	Metformin increased Trx expression through the AMP-activated protein kinase (AMPK) pathway.	Metformin	0-9	thioredoxin	Homo sapiens	20-23
20398632-8	2010	Metformin-regulated Trx at the transcriptional level and forkhead transcription factor 3 (FOXO3) was involved in this process.	Metformin	0-9	thioredoxin	Homo sapiens	20-23
20398632-9	2010	CONCLUSION: These results suggest that metformin reduces ROS levels by inducing Trx expression through activation of the AMPK-FOXO3 pathway.	Metformin	39-48	thioredoxin	Homo sapiens	80-83
20097509-8	2010	Treatment with metformin (10mM), an activator of AMPK, increased AMPK phosphorylation (P&lt;0.05) and reduced progesterone secretion by 50% (P&lt;0.05) in the basal state and in response to IGF-1 or FSH in goat granulosa cells.	Metformin	15-24	insulin-like growth factor I	Capra hircus	190-195
20093281-0	2010	Metformin suppresses hepatic gluconeogenesis through induction of SIRT1 and GCN5.	Metformin	0-9	sirtuin 1	Mus musculus	66-71
20093281-4	2010	We report that in db/db mice, metformin (250 mg/kg per day; 7 days) increases hepatic levels of GCN5 protein and mRNA compared with the untreated db/db mice, as well as increases levels of SIRT1 protein and activity relative to controls and untreated db/db mice.	Metformin	30-39	sirtuin 1	Mus musculus	189-194
20093281-6	2010	Inhibition of SIRT1 partially blocked the effects of metformin on gluconeogenesis.	Metformin	53-62	sirtuin 1	Mus musculus	14-19
20093281-10	2010	In conclusion, induction of GCN5 and SIRT1 potentially represents a critical mechanism of action of metformin.	Metformin	100-109	sirtuin 1	Mus musculus	37-42
19906888-0	2010	Metformin decreases IGF1-induced cell proliferation and protein synthesis through AMP-activated protein kinase in cultured bovine granulosa cells.	Metformin	0-9	insulin like growth factor 1	Bos taurus	20-24
19906888-4	2010	Here, we investigated the effects and the molecular mechanisms of metformin in IGF1-induced proliferation and protein synthesis in cultured bovine granulosa cells.	Metformin	66-75	insulin like growth factor 1	Bos taurus	79-83
19906888-5	2010	Treatment with metformin (10 mM) for 24 h reduced cell proliferation and the levels of cyclin D2 and E, and increased the associations cyclin D2/p21 and cyclin D2/p27 without affecting cell viability in response to IGF1 (10(-8) M).	Metformin	15-24	insulin like growth factor 1	Bos taurus	215-219
19906888-7	2010	Interestingly, metformin treatment for 1 h decreased MAPK3/1 (ERK1/2) and P90RSK phosphorylation without affecting AKT phosphorylation in response to IGF1.	Metformin	15-24	insulin like growth factor 1	Bos taurus	150-154
19906888-8	2010	Adenovirus-mediated expression of dominant-negative AMPK totally abolished the effects of metformin on cell proliferation and phosphorylation of P70S6K in response to IGF1.	Metformin	90-99	insulin like growth factor 1	Bos taurus	167-171
19906888-10	2010	Taken together, our results strongly suggest that metformin reduces cell growth, protein synthesis, MAPK3/1, and P90RSK phosphorylation in response to IGF1 through an AMPK-dependent mechanism in cultured bovine granulosa cells.	Metformin	50-59	insulin like growth factor 1	Bos taurus	151-155
19454315-1	2010	It has been reported that metformin was primarily metabolized via hepatic CYP2C11, 2D1, and 3A1/2 in rats.	Metformin	26-35	cytochrome P450, subfamily 2, polypeptide 11	Rattus norvegicus	74-81
28923291-13	2017	IMPLICATIONS: The use of prohibited metformin in a trial of a dipeptidyl peptidase-4 inhibitor, omarigliptin, introduced a confounding factor that invalidated the results of the trial.	Metformin	36-45	dipeptidyl peptidase 4	Homo sapiens	62-84
28547998-2	2017	dipeptidyl peptidase-4 inhibitor, omarigliptin, in patients with type 2 diabetes (T2DM) and inadequate glycemic control on metformin monotherapy.	Metformin	123-132	dipeptidyl peptidase 4	Homo sapiens	0-22
28797524-0	2017	Systematic review of metformin monotherapy and dual therapy with sodium glucose co-transporter 2 inhibitor (SGLT-2) in treatment of type 2 diabetes mellitus.	Metformin	21-30	solute carrier family 5 member 2	Homo sapiens	108-114
28797524-2	2017	Addition of sodium glucose cotransporter 2 inhibitor (SGLT2) will improve the glycemic control in patients on metformin alone.	Metformin	110-119	solute carrier family 5 member 2	Homo sapiens	12-52
28797524-2	2017	Addition of sodium glucose cotransporter 2 inhibitor (SGLT2) will improve the glycemic control in patients on metformin alone.	Metformin	110-119	solute carrier family 5 member 2	Homo sapiens	54-59
28797524-9	2017	CONCLUSION: The combined therapy of SGLT2 inhibitor along with metformin is more effective in HbA1c reduction and weight reduction as compared to monotherapy using metformin alone.	Metformin	164-173	solute carrier family 5 member 2	Homo sapiens	36-41
19900541-9	2010	Although the existence of other active transporting systems cannot be ruled out, the influence of OCT-dependent active transport system on the placental pharmacokinetics of metformin is unlikely significant.	Metformin	173-182	plexin A2	Homo sapiens	98-101
19822355-11	2010	Treatment with metformin resulted in G1 arrest, induction of apoptosis and decreased hTERT expression.	Metformin	15-24	telomerase reverse transcriptase	Homo sapiens	85-90
19854668-5	2009	We also determined whether fenofibrate and metformin, agents with TG-lowering activities, have an effect on LMF1 expression in ZDF rats.	Metformin	43-52	lipase maturation factor 1	Rattus norvegicus	108-112
19854668-8	2009	Although fenofibrate and metformin both decreased plasma TG levels, fenofibrate had no effect on LMF1 expression, whereas metformin increased LMF1 mRNA in heart tissue (14- and 21-week-old ZDF rats; P&lt;0.01), and induced a trend towards increases in adipose tissue (14-week-old ZDF rats) and muscle (14- and 21-week-old ZDF rats).	Metformin	122-131	lipase maturation factor 1	Rattus norvegicus	142-146
19854668-10	2009	However, metformin increased LMF1 expression in the heart, suggesting that stimulation of LMF1 may play a part in its TG-lowering action.	Metformin	9-18	lipase maturation factor 1	Rattus norvegicus	29-33
19854668-10	2009	However, metformin increased LMF1 expression in the heart, suggesting that stimulation of LMF1 may play a part in its TG-lowering action.	Metformin	9-18	lipase maturation factor 1	Rattus norvegicus	90-94
19943222-1	2009	Dapagliflozin (BMS-512148), a specific inhibitor of the sodium-glucose cotransporter SGLT2, is under development by AstraZeneca plc and Bristol-Myers Squibb Co for the potential oral treatment of type 2 diabetes mellitus (T2DM); a fixed-dose combination of dapagliflozin and metformin is also being developed by the companies for the potential treatment of diabetes mellitus.	Metformin	275-284	solute carrier family 5 member 2	Homo sapiens	85-90
19725053-9	2009	Metformin significantly inhibited gene expression of Runx2 along with osteoblast differentiation markers including osteocalcin (Ocn), bone sialo protein (Bsp), and osteopontin (Opn).	Metformin	0-9	runt related transcription factor 2	Mus musculus	53-58
19725053-9	2009	Metformin significantly inhibited gene expression of Runx2 along with osteoblast differentiation markers including osteocalcin (Ocn), bone sialo protein (Bsp), and osteopontin (Opn).	Metformin	0-9	bone gamma-carboxyglutamate protein 2	Mus musculus	115-126
19725053-9	2009	Metformin significantly inhibited gene expression of Runx2 along with osteoblast differentiation markers including osteocalcin (Ocn), bone sialo protein (Bsp), and osteopontin (Opn).	Metformin	0-9	bone gamma-carboxyglutamate protein 2	Mus musculus	128-131
19858366-0	2009	LKB1 and mammalian target of rapamycin as predictive factors for the anticancer efficacy of metformin.	Metformin	92-101	serine/threonine kinase 11	Homo sapiens	0-4
19925384-4	2009	The greater (slower) intravenous AUCs (CL(NR)s) of metformin in 24-h and 96-h ECLPS rats were due to the slower hepatic intrinsic clearance (CL(int)) because of a decrease in the protein expression of hepatic cytochrome P450 (CYP) 2C11 and/or CYP3A subfamily than controls.	Metformin	51-60	cytochrome P450, subfamily 2, polypeptide 11	Rattus norvegicus	209-235
19900194-6	2009	The DPP-4 inhibitors are orally administered and demonstrate modest A1c reductions (0.6%-0.8%); the best results occur when combined with metformin.	Metformin	138-147	dipeptidyl peptidase 4	Homo sapiens	4-9
19664596-0	2009	Metformin suppresses glucose-6-phosphatase expression by a complex I inhibition and AMPK activation-independent mechanism.	Metformin	0-9	glucose-6-phosphatase catalytic subunit 1	Rattus norvegicus	21-42
19664596-2	2009	Both metformin and rotenone, an inhibitor of respiratory chain complex I, suppressed glucose-6-phosphatase (G6pc), a rate limiting enzyme of liver glucose production, mRNA expression in a rat hepatoma cell line accompanied by a reduction of intracellular ATP concentration and an activation of AMP-activated protein kinase (AMPK).	Metformin	5-14	glucose-6-phosphatase catalytic subunit 1	Rattus norvegicus	85-106
19664596-2	2009	Both metformin and rotenone, an inhibitor of respiratory chain complex I, suppressed glucose-6-phosphatase (G6pc), a rate limiting enzyme of liver glucose production, mRNA expression in a rat hepatoma cell line accompanied by a reduction of intracellular ATP concentration and an activation of AMP-activated protein kinase (AMPK).	Metformin	5-14	glucose-6-phosphatase catalytic subunit 1	Rattus norvegicus	108-112
19664596-4	2009	Interestingly, in contrast to rotenone treatment, G6pc mRNA down-regulation was observed in the NDI1 expressing cells after metformin treatment.	Metformin	124-133	glucose-6-phosphatase catalytic subunit 1	Rattus norvegicus	50-54
19664596-5	2009	Since NDI1 can functionally complement the complex I under the presence of metformin or rotenone, our results indicate that metformin induces down-regulation of G6pc expression through an inhibition of complex I and an activation of AMPK-independent mechanism.	Metformin	124-133	glucose-6-phosphatase catalytic subunit 1	Rattus norvegicus	161-165
19570550-13	2009	These results suggest that metformin increases LPL activity, LPL protein expression, and LPL mRNA expression through activation of AMPK in skeletal muscle cells but not in adipocytes.	Metformin	27-36	lipoprotein lipase	Homo sapiens	47-50
19570550-13	2009	These results suggest that metformin increases LPL activity, LPL protein expression, and LPL mRNA expression through activation of AMPK in skeletal muscle cells but not in adipocytes.	Metformin	27-36	lipoprotein lipase	Homo sapiens	61-64
19570550-13	2009	These results suggest that metformin increases LPL activity, LPL protein expression, and LPL mRNA expression through activation of AMPK in skeletal muscle cells but not in adipocytes.	Metformin	27-36	lipoprotein lipase	Homo sapiens	61-64
19414528-0	2009	Metformin decreases angiogenesis via NF-kappaB and Erk1/2/Erk5 pathways by increasing the antiangiogenic thrombospondin-1.	Metformin	0-9	mitogen-activated protein kinase 7	Homo sapiens	58-62
19414528-7	2009	After 6 months of metformin treatment, there was a significant increase in serum TSP-1 (P &lt; 0.05) and a corresponding decrease in PAI-1 and PAI-1 activity (P &lt; 0.01).	Metformin	18-27	serpin family E member 1	Homo sapiens	133-138
19414528-7	2009	After 6 months of metformin treatment, there was a significant increase in serum TSP-1 (P &lt; 0.05) and a corresponding decrease in PAI-1 and PAI-1 activity (P &lt; 0.01).	Metformin	18-27	serpin family E member 1	Homo sapiens	143-148
19414528-8	2009	In vitro migration and angiogenesis were significantly increased in serum from PCOS women (P &lt; 0.01); these effects were significantly attenuated by metformin treatment (P &lt; 0.01) through the regulation of TSP-1 levels via nuclear factor-kappaB (NF-kappaB), extracellular regulated-signal kinase 1/2 (Erk1/2) and Erk5 pathways.	Metformin	152-161	mitogen-activated protein kinase 7	Homo sapiens	319-323
19501448-11	2009	CONCLUSION: Metformin seems to have possible antiproliferative effects on the endometrium of estradiol or tamoxifen treated mice via inhibiting the mTOR mediated S6K1 activation.	Metformin	12-21	mechanistic target of rapamycin kinase	Mus musculus	148-152
19440038-7	2009	At the molecular level, metformin increases P-AMPK, reduces P-EGFR, EGFR, P-MAPK, P-Src, cyclin D1 and cyclin E (but not cyclin A or B, p27 or p21), and induces PARP cleavage in a dose- and time-dependent manner.	Metformin	24-33	interferon alpha inducible protein 27	Homo sapiens	136-139
18839053-3	2009	The aim of this study is to determine the effect of metformin on plasma leptin levels in obese patients with type 2 diabetes mellitus and NAFLD compared with lifestyle interventions.	Metformin	52-61	leptin	Homo sapiens	72-78
18839053-12	2009	The data demonstrate that, metformin and lifestyle interventions equally affected the plasma leptin levels, BMI and degree of NAFLD in obese patients with type 2 diabetes mellitus.	Metformin	27-36	leptin	Homo sapiens	93-99
19131464-5	2009	RESULTS: Elevated ACR levels (&gt;or=30 mg/g creatinine) were present at baseline in 198 (6.2%) of 3,188 participants: placebo 5.3%, metformin 6.5%, and intensive lifestyle (ILS) 6.8%.	Metformin	133-142	acrosin	Homo sapiens	18-21
18256928-6	2009	Systemic therapy with metformin was tested for efficacy in an orthotopic model of ERalpha negative breast cancer performed in athymic nude mice.	Metformin	22-31	estrogen receptor 1 (alpha)	Mus musculus	82-89
18972094-4	2009	METHODS: Type 2 diabetic patients were examined before and 5 to 6 weeks after combined thiazolidinedione-metformin therapy for activation of muscle aPKC and PKBbeta and their upstream activators, the insulin receptor (IR) and IRS-1-associated phosphatidylinositol 3-kinase (PI3K), during euglycaemic-hyperinsulinaemic clamp studies conducted with sub-maximal (400-500 pmol/l) and maximal (1400 pmol/l) insulin concentrations.	Metformin	105-114	AKT serine/threonine kinase 2	Homo sapiens	157-164
28822889-7	2017	This effect was confirmed by the study of the expression of CSC markers (CD44 and Sox2) and differentiation markers (Kruppel-like factor 4 and MUC5AC), which were decreased or increased in response to metformin, respectively.	Metformin	201-210	mucin 5AC, oligomeric mucus/gel-forming	Homo sapiens	143-149
27876536-16	2017	Our results showed a protective effect of 1alpha,25(OH)2D3 and metformin on liver in diabetic rats as indicated by an improvement of the level of the liver enzymes, decreased apoptosis and increased proliferation and this was confirmed histologically, with modulating NFkB and PPAR-alpha.	Metformin	63-72	RELA proto-oncogene, NF-kB subunit	Rattus norvegicus	268-272
27876536-16	2017	Our results showed a protective effect of 1alpha,25(OH)2D3 and metformin on liver in diabetic rats as indicated by an improvement of the level of the liver enzymes, decreased apoptosis and increased proliferation and this was confirmed histologically, with modulating NFkB and PPAR-alpha.	Metformin	63-72	peroxisome proliferator activated receptor alpha	Rattus norvegicus	277-287
29340030-5	2017	In the K18-gT121+/-; p53fl/fl; Brca1fl/fl (KpB) mouse model, metformin inhibited tumor growth in both lean and obese mice.	Metformin	61-70	transformation related protein 53, pseudogene	Mus musculus	21-24
18972094-5	2009	RESULTS: Following combined thiazolidinedione-metformin therapy, increases in glucose disposal and increases in sub-maximal and maximal insulin-induced activities of all four muscle signalling factors, IR, IRS-1-dependent PI3K (IRS-1/PI3K), aPKC and PKBbeta, were observed.	Metformin	46-55	insulin receptor substrate 1	Homo sapiens	206-211
18972094-5	2009	RESULTS: Following combined thiazolidinedione-metformin therapy, increases in glucose disposal and increases in sub-maximal and maximal insulin-induced activities of all four muscle signalling factors, IR, IRS-1-dependent PI3K (IRS-1/PI3K), aPKC and PKBbeta, were observed.	Metformin	46-55	insulin receptor substrate 1	Homo sapiens	228-233
18972094-5	2009	RESULTS: Following combined thiazolidinedione-metformin therapy, increases in glucose disposal and increases in sub-maximal and maximal insulin-induced activities of all four muscle signalling factors, IR, IRS-1-dependent PI3K (IRS-1/PI3K), aPKC and PKBbeta, were observed.	Metformin	46-55	AKT serine/threonine kinase 2	Homo sapiens	250-257
19995720-0	2009	Leptin concentrations in patients with polycystic ovary syndrome before and after met-formin treatment depending on insulin resistance, body mass index and androgen con-centrations--introductory report.	Metformin	82-92	leptin	Homo sapiens	0-6
19995720-9	2009	Metformin treatment considerably reduces leptin concentration, if it is employed in non-obese PCOS patients, patients with normal an-drogen concentrations and those who not have an impaired glucose tolerance.	Metformin	0-9	leptin	Homo sapiens	41-47
18955435-8	2009	To elucidate the basis for this antilipolytic action, we showed that metformin decreased cellular cAMP production, reduced the activities of PKA and MAPK1/3, and attenuated the phosphorylation of perilipin during isoproterenol-stimulated lipolysis.	Metformin	69-78	mitogen activated protein kinase 13	Rattus norvegicus	149-156
18771725-7	2008	In contrast to data reported for the full-length AS160 protein, over expression and activation of transcript variant 2 in this cell line increased GLUT4 translocation and glucose-uptake rates in response to insulin and IGF-1 but not in response to AICAR or metformin.	Metformin	257-266	solute carrier family 2 member 4	Rattus norvegicus	147-152
18839134-11	2008	CONCLUSIONS/INTERPRETATION: Within the DPP study population, common variants in FTO and INSIG2 are nominally associated with quantitative measures of obesity, directly and possibly by interacting with metformin or lifestyle intervention.	Metformin	201-210	FTO alpha-ketoglutarate dependent dioxygenase	Homo sapiens	80-83
18393297-1	2008	It has been reported that metformin was primarily metabolized via hepatic CYP2C11, 2D1, and 3A1/2 in rats, and the expression and mRNA levels of hepatic CYP2C11 and 3A1 decreased and increased, respectively, whereas the expression of CYP2D1 was not changed in rat model of diabetes induced by streptozotocin (DMIS).	Metformin	26-35	cytochrome P450, subfamily 2, polypeptide 11	Rattus norvegicus	74-81
18393297-1	2008	It has been reported that metformin was primarily metabolized via hepatic CYP2C11, 2D1, and 3A1/2 in rats, and the expression and mRNA levels of hepatic CYP2C11 and 3A1 decreased and increased, respectively, whereas the expression of CYP2D1 was not changed in rat model of diabetes induced by streptozotocin (DMIS).	Metformin	26-35	cytochrome P450, subfamily 2, polypeptide 11	Rattus norvegicus	153-160
18393297-4	2008	After intravenous administration of metformin (100 mg/kg) to rat model of DMIS, the CL(R) became significantly faster (46.9% and 77.8% increase for the 7th and the 29th days, respectively; due to urine flow rate-dependent timed-interval renal clearance of the drug) and CL(NR) became significantly slower (28.0% and 34.3% decrease, respectively; due to decreased hepatic CYP2C11) than in their respective controls.	Metformin	36-45	cytochrome P450, subfamily 2, polypeptide 11	Rattus norvegicus	371-378
18401339-0	2008	Genetic variants of the organic cation transporter 2 influence the disposition of metformin.	Metformin	82-91	solute carrier family 22 member 2	Homo sapiens	24-52
18401339-1	2008	Genetic variants of the organic cation transporter 2 (protein, OCT2; gene, SLC22A2) were evaluated for their contribution to the variations in the pharmacokinetics of metformin, especially to its renal elimination.	Metformin	167-176	solute carrier family 22 member 2	Homo sapiens	24-52
18401339-1	2008	Genetic variants of the organic cation transporter 2 (protein, OCT2; gene, SLC22A2) were evaluated for their contribution to the variations in the pharmacokinetics of metformin, especially to its renal elimination.	Metformin	167-176	solute carrier family 22 member 2	Homo sapiens	63-67
18401339-1	2008	Genetic variants of the organic cation transporter 2 (protein, OCT2; gene, SLC22A2) were evaluated for their contribution to the variations in the pharmacokinetics of metformin, especially to its renal elimination.	Metformin	167-176	solute carrier family 22 member 2	Homo sapiens	75-82
18681789-1	2008	Metformin, ovulation and polymorphism of the STK11 gene in polycystic ovary syndrome.	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	45-50
18681789-17	2008	The C allele of a SNP in the STK11 gene was associated with a significantly decreased chance of ovulation in polycystic ovary syndrome women treated with metformin.	Metformin	154-163	serine/threonine kinase 11	Homo sapiens	29-34
18358555-7	2008	Our results indicated that, metformin addition had beneficial effect on VEGF and PAI-1 levels in obese type 2 diabetic patients under MNT+REP, independent from its" favourable effects on BMI and glycemic control.	Metformin	28-37	serpin family E member 1	Homo sapiens	81-86
18551044-0	2008	OCT2 polymorphisms and in-vivo renal functional consequence: studies with metformin and cimetidine.	Metformin	74-83	solute carrier family 22 member 2	Homo sapiens	0-4
18551044-8	2008	CONCLUSION: Our study results demonstrated for the first time the existence of genetic polymorphisms of OCT2 in the Chinese population, and further showed that the 808G&gt;T polymorphism is associated with a reduced metformin renal or tubular clearance.	Metformin	216-225	solute carrier family 22 member 2	Homo sapiens	104-108
18212742-4	2008	Metformin inhibited the proliferation of DU145, PC-3 and LNCaP cancer cells with a 50% decrease of cell viability and had a modest effect on normal prostate epithelial cell line P69.	Metformin	0-9	islet cell autoantigen 1	Homo sapiens	178-181
18333888-9	2008	CONCLUSIONS: Addition of the DPP4 inhibitor PHX1149 to a stable regimen of metformin or metformin plus a glitazone in patients with type 2 diabetes was well tolerated and improved blood glucose control.	Metformin	75-84	dipeptidyl peptidase 4	Homo sapiens	29-33
28483424-4	2017	We first screened 72 uremic solutes as inhibitors of [14C]-labeled metformin uptake by OCT2.	Metformin	67-76	solute carrier family 22 member 2	Homo sapiens	87-91
28927780-9	2017	The combination of specific inhibitors of ERK1/2, JNK or PI3K/Akt pathway and metformin further promoted cell apoptosis and the up-regulation of p21, Bax, Bad, cleaved caspase-3 and -9 as well as the down-regulation of Bcl-2 mediated by metformin alone, but inhibition of p38 pathway exhibited the opposite results.	Metformin	78-87	H3 histone pseudogene 16	Homo sapiens	145-148
18333888-9	2008	CONCLUSIONS: Addition of the DPP4 inhibitor PHX1149 to a stable regimen of metformin or metformin plus a glitazone in patients with type 2 diabetes was well tolerated and improved blood glucose control.	Metformin	88-97	dipeptidyl peptidase 4	Homo sapiens	29-33
18446452-3	2008	Here, we investigate the relationship between human resistin and insulin resistance in hepatocytes and the effect of Metformin on resistin.	Metformin	117-126	resistin	Homo sapiens	130-138
18446452-9	2008	We also concluded that Metformin reversed the effect of resistin and downregulated the expression of resistin in hepatocytes.	Metformin	23-32	resistin	Homo sapiens	56-64
18446452-9	2008	We also concluded that Metformin reversed the effect of resistin and downregulated the expression of resistin in hepatocytes.	Metformin	23-32	resistin	Homo sapiens	101-109
18303133-17	2008	Drugs that interfere with elimination-that is, other drugs utilizing the organic cation transporter-2 in the tubule, such as trimethoprim, metformin, or imipramine-may lead to drug accumulation.	Metformin	139-148	solute carrier family 22 member 2	Homo sapiens	73-101
18000088-7	2008	RESULTS: We found that the C allele of a single nucleotide polymorphism in the STK11 gene (expressed in liver; also known as LKB1) was associated with a significantly decreased chance of ovulation in PCOS women treated with metformin.	Metformin	224-233	serine/threonine kinase 11	Homo sapiens	79-84
29109662-4	2017	Dipeptidyl-peptidase-IV (DPP-4) inhibitors like linagliptin are usually add-on therapy to metformin in order to achieve glycemic control.	Metformin	90-99	dipeptidyl peptidase 4	Homo sapiens	0-23
29109662-4	2017	Dipeptidyl-peptidase-IV (DPP-4) inhibitors like linagliptin are usually add-on therapy to metformin in order to achieve glycemic control.	Metformin	90-99	dipeptidyl peptidase 4	Homo sapiens	25-30
28859673-13	2017	CONCLUSION: Finally, we conclude on eNOS-metformin-HSp90 signaling and its remedial effect for controlling the EPC to improve the diabetic condition for delaying diabetes-related complication.	Metformin	41-50	heat shock protein 90 alpha family class A member 1	Homo sapiens	51-56
28859084-9	2017	Although the details of the molecular mechanisms underlying the effect of the drug on myoblasts still need to be clarified, we propose that metformin negatively affects myogenic differentiation by inhibiting irreversible exit from the cell cycle through reduction of MyoD and p21cip1 levels.	Metformin	140-149	myogenic differentiation 1	Mus musculus	267-271
28837141-0	2017	Metformin reverses prostate cancer resistance to enzalutamide by targeting TGF-beta1/STAT3 axis-regulated EMT.	Metformin	0-9	IL2 inducible T cell kinase	Homo sapiens	106-109
28837141-5	2017	We showed that metformin alleviated resistance to enzalutamide by inhibiting EMT.	Metformin	15-24	IL2 inducible T cell kinase	Homo sapiens	77-80
29088816-6	2017	More importantly, we investigated the anti-angiogenic effect of metformin, and found that metformin abrogated the ESCC microenvironment-induced transition of NECs toward TECs by inhibiting JAK/STAT3/c-MYC signaling pathway.	Metformin	90-99	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	199-204
28769124-2	2017	Metformin reduces cyst growth in mouse models of PKD1.	Metformin	0-9	polycystin 1, transient receptor potential channel interacting	Mus musculus	49-53
28109184-8	2017	RESULTS: DPP4is as a second-line add-on to metformin had a significantly lower stroke risk [hazard ratio (HR) 0.817 (95% confidence interval 0.687, 0.971)] and all-cause mortality [HR 0.825 (0.687, 0.992)] than those for sulphonylurea.	Metformin	43-52	dipeptidyl peptidase 4	Homo sapiens	9-13
27857021-9	2017	Further study revealed that metformin could suppress the expression of insulin-like growth factor 1 receptor and its downstream proteins, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT/PKB), phosphorylation of AKT (pAKT), mammalian target of rapamycin (mTOR), p70S6K, and PKM2.	Metformin	28-37	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta	Homo sapiens	138-163
27857021-9	2017	Further study revealed that metformin could suppress the expression of insulin-like growth factor 1 receptor and its downstream proteins, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT/PKB), phosphorylation of AKT (pAKT), mammalian target of rapamycin (mTOR), p70S6K, and PKM2.	Metformin	28-37	protein tyrosine kinase 2 beta	Homo sapiens	172-188
27857021-9	2017	Further study revealed that metformin could suppress the expression of insulin-like growth factor 1 receptor and its downstream proteins, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT/PKB), phosphorylation of AKT (pAKT), mammalian target of rapamycin (mTOR), p70S6K, and PKM2.	Metformin	28-37	ribosomal protein S6 kinase B1	Homo sapiens	269-275
27857021-9	2017	Further study revealed that metformin could suppress the expression of insulin-like growth factor 1 receptor and its downstream proteins, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT/PKB), phosphorylation of AKT (pAKT), mammalian target of rapamycin (mTOR), p70S6K, and PKM2.	Metformin	28-37	pyruvate kinase M1/2	Homo sapiens	281-285
27857021-13	2017	Furthermore, we found that metformin treatment increased the rate of apoptosis, down-regulation of PKM2, and up-regulation of Bim in tumor tissues.	Metformin	27-36	pyruvate kinase M1/2	Homo sapiens	99-103
27857021-13	2017	Furthermore, we found that metformin treatment increased the rate of apoptosis, down-regulation of PKM2, and up-regulation of Bim in tumor tissues.	Metformin	27-36	BCL2 like 11	Homo sapiens	126-129
28330386-9	2017	CONCLUSION: In routine clinical practice, intensification of metformin + sulfonylurea therapy by adding insulin is associated with increased risk of cardiovascular events and death compared with adding a dipeptidylpeptidase-4 inhibitor.	Metformin	61-70	dipeptidyl peptidase 4	Homo sapiens	204-225
28332871-6	2017	Recent clinical evidence shows that SGLT2 inhibitor/DPP-4 inhibitor therapy is an effective combination for T2DM treatment, providing glycated hemoglobin (HbA1c) reductions of 1.1 to 1.5%, and weight reductions of approximately 2 kg when added to metformin, which is its primary place in therapy.	Metformin	247-256	solute carrier family 5 member 2	Homo sapiens	36-41
28332871-6	2017	Recent clinical evidence shows that SGLT2 inhibitor/DPP-4 inhibitor therapy is an effective combination for T2DM treatment, providing glycated hemoglobin (HbA1c) reductions of 1.1 to 1.5%, and weight reductions of approximately 2 kg when added to metformin, which is its primary place in therapy.	Metformin	247-256	dipeptidyl peptidase 4	Homo sapiens	52-57
28332871-7	2017	CONCLUSION: The combination of an SGLT2 inhibitor/DPP-4 inhibitor is a safe and effective treatment choice for patients with T2DM who are unable to obtain adequate glycemic control with metformin therapy, cannot use metformin, or have a higher baseline HbA1c.	Metformin	186-195	solute carrier family 5 member 2	Homo sapiens	34-39
28332871-7	2017	CONCLUSION: The combination of an SGLT2 inhibitor/DPP-4 inhibitor is a safe and effective treatment choice for patients with T2DM who are unable to obtain adequate glycemic control with metformin therapy, cannot use metformin, or have a higher baseline HbA1c.	Metformin	186-195	dipeptidyl peptidase 4	Homo sapiens	50-55
28332871-7	2017	CONCLUSION: The combination of an SGLT2 inhibitor/DPP-4 inhibitor is a safe and effective treatment choice for patients with T2DM who are unable to obtain adequate glycemic control with metformin therapy, cannot use metformin, or have a higher baseline HbA1c.	Metformin	216-225	solute carrier family 5 member 2	Homo sapiens	34-39
28332871-7	2017	CONCLUSION: The combination of an SGLT2 inhibitor/DPP-4 inhibitor is a safe and effective treatment choice for patients with T2DM who are unable to obtain adequate glycemic control with metformin therapy, cannot use metformin, or have a higher baseline HbA1c.	Metformin	216-225	dipeptidyl peptidase 4	Homo sapiens	50-55
28281393-7	2017	CONCLUSION: Metformin effects on tumor cells measured under in vitro conditions may differ from those determined in vivo due to p53 and heterogeneous environmental factors.	Metformin	12-21	transformation related protein 53, pseudogene	Mus musculus	128-131
28682870-8	2017	SGLT2 inhibitors as add-on to metformin treatment reduced % HbA1c significantly more than non-SGLT2 combinations after 52 weeks (P = .002) as well as after 104 weeks (P &lt; .00001).	Metformin	30-39	solute carrier family 5 member 2	Homo sapiens	0-5
28682870-11	2017	CONCLUSION: As add-on to metformin treatment, SGLT2 inhibitors are found significantly more efficacious than non-SGLT2 inhibitor combinations in the management of type 2 diabetes mellitus, although, SGLT2 inhibitor therapy is associated with significantly higher incidence of suspected or confirmed genital tract infections.	Metformin	25-34	solute carrier family 5 member 2	Homo sapiens	46-51
28407669-10	2017	Furthermore, metformin reduced serum insulin as well as IGF-1, and also suppressed expression of insulin receptor, IGF-1, IGF-1 receptor and several pro-inflammatory cytokines mRNAs in stomach of db/db mice, but did not significantly influence IGF-2 and IGF-2 receptor expressions.	Metformin	13-22	insulin-like growth factor 2	Mus musculus	244-249
28407669-10	2017	Furthermore, metformin reduced serum insulin as well as IGF-1, and also suppressed expression of insulin receptor, IGF-1, IGF-1 receptor and several pro-inflammatory cytokines mRNAs in stomach of db/db mice, but did not significantly influence IGF-2 and IGF-2 receptor expressions.	Metformin	13-22	insulin-like growth factor 2	Mus musculus	254-259
27957796-3	2017	Mechanistically, we demonstrated that activation of AMPK with its activators such as AICAR and metformin decreased the expression of MAD2B, indicating a role of AMPK in regulating the expression of MAD2B.	Metformin	95-104	mitotic arrest deficient 2 like 2	Homo sapiens	133-138
27957796-3	2017	Mechanistically, we demonstrated that activation of AMPK with its activators such as AICAR and metformin decreased the expression of MAD2B, indicating a role of AMPK in regulating the expression of MAD2B.	Metformin	95-104	mitotic arrest deficient 2 like 2	Homo sapiens	198-203
28504725-3	2017	Here we show that metformin, the most widely used drug for type 2 diabetes, rescues core phenotypes in Fmr1-/y mice and selectively normalizes ERK signaling, eIF4E phosphorylation and the expression of MMP-9.	Metformin	18-27	eukaryotic translation initiation factor 4E	Mus musculus	158-163
27897089-8	2017	In contrast, metformin treated groups exhibited significant reduction in MDA, PCO, ROS, and NO levels and a significant increase in AChE activity in induced aging rats.	Metformin	13-22	acetylcholinesterase	Rattus norvegicus	132-136
28532406-0	2017	The addition of vildagliptin to metformin prevents the elevation of interleukin 1ss in patients with type 2 diabetes and coronary artery disease: a prospective, randomized, open-label study.	Metformin	32-41	interleukin 1 alpha	Homo sapiens	68-81
28532406-11	2017	CONCLUSION: The addition of vildagliptin to metformin treatment in patients with type 2 diabetes and CAD led to a significant suppression of the IL-1ss elevation during follow up.	Metformin	44-53	interleukin 1 alpha	Homo sapiens	145-149
28526827-10	2017	Metformin significantly inhibited in vivo progression of heat-exposed residual HCC via suppressing POSTN secretion and decreasing cancer stem cell marker expression.	Metformin	0-9	periostin	Homo sapiens	99-104
28274614-7	2017	Treatment with metformin reduced phosphorylation of Akt and mTOR and inhibited downstream targets of mTOR.	Metformin	15-24	mechanistic target of rapamycin kinase	Mus musculus	60-64
28274614-7	2017	Treatment with metformin reduced phosphorylation of Akt and mTOR and inhibited downstream targets of mTOR.	Metformin	15-24	mechanistic target of rapamycin kinase	Mus musculus	101-105
18000088-7	2008	RESULTS: We found that the C allele of a single nucleotide polymorphism in the STK11 gene (expressed in liver; also known as LKB1) was associated with a significantly decreased chance of ovulation in PCOS women treated with metformin.	Metformin	224-233	serine/threonine kinase 11	Homo sapiens	125-129
18000088-11	2008	CONCLUSIONS: We have demonstrated that a polymorphism in STK11, a kinase gene expressed in liver and implicated in metformin action, is associated with ovulatory response to treatment with metformin alone in a prospective randomized trial.	Metformin	115-124	serine/threonine kinase 11	Homo sapiens	57-62
18000088-11	2008	CONCLUSIONS: We have demonstrated that a polymorphism in STK11, a kinase gene expressed in liver and implicated in metformin action, is associated with ovulatory response to treatment with metformin alone in a prospective randomized trial.	Metformin	189-198	serine/threonine kinase 11	Homo sapiens	57-62
18250273-0	2008	Phosphorylation of LKB1 at serine 428 by protein kinase C-zeta is required for metformin-enhanced activation of the AMP-activated protein kinase in endothelial cells.	Metformin	79-88	serine/threonine kinase 11	Homo sapiens	19-23
17687118-11	2008	Roscovitine, U0126, and metformin inhibited meiotic divisions; they all induced a decrease of CCNB1 and phospho-MAPK3/1 levels and prevented CPEB degradation.	Metformin	24-33	cytoplasmic polyadenylation element binding protein 1	Mus musculus	141-145
17909097-8	2008	Furthermore, oral administration of metformin increased SHP mRNA levels in B6-Lep(ob/ob) mice.	Metformin	36-45	leptin	Mus musculus	78-81
18237462-1	2008	Metformin is metabolized primarily via hepatic microsomal cytochrome P450 (CYP)2C11, CYP2D1 and CYP3A1/2 in rats.	Metformin	0-9	cytochrome P450, subfamily 2, polypeptide 11	Rattus norvegicus	58-83
19079687-5	2008	In contrast to the in vivo data, FoxO1, 3 and 4 mRNA content was decreased dose-dependently, with the decrement in FoxO1 being the largest, in C(2)C1(2) myotubes incubated with the AMPK agonists AICAR or metformin.	Metformin	204-213	forkhead box O1	Mus musculus	33-38
28026911-6	2017	In multivariate adjusted analyses, total event rates for MACE with metformin + dipeptidyl peptidase-4 (DPP-4) inhibitor were significantly lower than with metformin + SU (0.61, 95% confidence interval [CI] 0.39-0.98), driven by a lower MI rate in the metformin + DPP-4 inhibitor group (0.52, 95% CI 0.27-0.99).	Metformin	67-76	dipeptidyl peptidase 4	Homo sapiens	79-101
28026911-6	2017	In multivariate adjusted analyses, total event rates for MACE with metformin + dipeptidyl peptidase-4 (DPP-4) inhibitor were significantly lower than with metformin + SU (0.61, 95% confidence interval [CI] 0.39-0.98), driven by a lower MI rate in the metformin + DPP-4 inhibitor group (0.52, 95% CI 0.27-0.99).	Metformin	67-76	dipeptidyl peptidase 4	Homo sapiens	103-108
28026911-6	2017	In multivariate adjusted analyses, total event rates for MACE with metformin + dipeptidyl peptidase-4 (DPP-4) inhibitor were significantly lower than with metformin + SU (0.61, 95% confidence interval [CI] 0.39-0.98), driven by a lower MI rate in the metformin + DPP-4 inhibitor group (0.52, 95% CI 0.27-0.99).	Metformin	67-76	dipeptidyl peptidase 4	Homo sapiens	263-268
28459206-8	2017	The anti-tumorigenic effect of metformin was mediated by enhancement of adenosine monophosphate protein kinase activity and elevation of P53 protein as well as the suppression of nuclear factor-kappa B, DNA contents, and cyclin D1 gene expression.	Metformin	31-40	transformation related protein 53, pseudogene	Mus musculus	137-140
28302481-10	2017	Myocardial mitochondrial respiratory function and membrane potential were decreased after myocardial infarction, and metformin treatment significantly improved the mitochondrial respiratory function and mitochondrial membrane potential; Metformin up-regulated the expression of Sirt3 and the activity of PGC-1alpha in myocardial tissue of heart failure after myocardial infarction.	Metformin	117-126	sirtuin 3	Mus musculus	278-283
28302481-10	2017	Myocardial mitochondrial respiratory function and membrane potential were decreased after myocardial infarction, and metformin treatment significantly improved the mitochondrial respiratory function and mitochondrial membrane potential; Metformin up-regulated the expression of Sirt3 and the activity of PGC-1alpha in myocardial tissue of heart failure after myocardial infarction.	Metformin	237-246	sirtuin 3	Mus musculus	278-283
28302481-11	2017	Metformin decreases the acetylation level of PGC-1alpha through up-regulating Sirt3, mitigates the damage to mitochondrial membrane potential of model of heart failure after myocardial infarction and improves the respiratory function of mitochondria, thus improving the cardiac function of mice.	Metformin	0-9	sirtuin 3	Mus musculus	78-83
27775072-2	2017	Here we report that metformin induces genome-wide alterations in DNA methylation by modulating the activity of S-adenosylhomocysteine hydrolase (SAHH).	Metformin	20-29	adenosylhomocysteinase	Homo sapiens	111-143
27775072-2	2017	Here we report that metformin induces genome-wide alterations in DNA methylation by modulating the activity of S-adenosylhomocysteine hydrolase (SAHH).	Metformin	20-29	adenosylhomocysteinase	Homo sapiens	145-149
27775072-4	2017	Metformin acts by upregulating microRNA let-7 through AMPK activation, leading to degradation of H19 long noncoding RNA, which normally binds to and inactivates SAHH.	Metformin	0-9	H19 imprinted maternally expressed transcript	Homo sapiens	97-100
27775072-4	2017	Metformin acts by upregulating microRNA let-7 through AMPK activation, leading to degradation of H19 long noncoding RNA, which normally binds to and inactivates SAHH.	Metformin	0-9	adenosylhomocysteinase	Homo sapiens	161-165
27775072-6	2017	This metformin-induced H19 repression and alteration of gene methylation are recapitulated in endometrial cancer tissue samples obtained from patients treated with antidiabetic doses of metformin.	Metformin	5-14	H19 imprinted maternally expressed transcript	Homo sapiens	23-26
27775072-6	2017	This metformin-induced H19 repression and alteration of gene methylation are recapitulated in endometrial cancer tissue samples obtained from patients treated with antidiabetic doses of metformin.	Metformin	186-195	H19 imprinted maternally expressed transcript	Homo sapiens	23-26
28450808-7	2017	Metformin deregulated the expression of p-Akt in HepG2 and SMMC7721 cells after insufficient RFA through AMPK/PTEN pathway.	Metformin	0-9	phosphatase and tensin homolog	Homo sapiens	110-114
28425952-0	2017	Antioxidant and Anti-Senescence Effect of Metformin on Mouse Olfactory Ensheathing Cells (mOECs) May Be Associated with Increased Brain-Derived Neurotrophic Factor Levels-An Ex Vivo Study.	Metformin	42-51	brain derived neurotrophic factor	Mus musculus	130-163
28480051-4	2017	In this study, we demonstrated that metformin decreased the percentage of TNBC stem cells partially through the downregulation of the expression of the stem cell transcription factor Kruppel-like factor 5 (KLF5) and its downstream target genes, such as Nanog and FGF-BP1, in TNBC cell lines.	Metformin	36-45	fibroblast growth factor binding protein 1	Homo sapiens	263-270
18429758-13	2008	Practical lack of positive influence of metformin on glycemia at its initially not high level was accompanied with improvement of FC CHF, parameters of central hemodynamics, augmentation of functional capacities of patients, improvement of quality of life, lowering of number of decompensations of CHF and diminishment of degree of activation of SAS.	Metformin	40-49	tetraspanin 31	Homo sapiens	346-349
18054733-10	2007	DPP-4 inhibition is suggested to be a first-line treatment of type-2 diabetes, particularly in its early stages in combination with metformin.	Metformin	132-141	dipeptidyl peptidase 4	Homo sapiens	0-5
18217246-3	2007	When used in combination with metformin, sulfonylureas, or TZDs, GLP-1 analogs such as exenatide and DPP-IV inhibitors such as sitagliptin reduce A1C, fasting glucose levels, and postprandial glucose levels with few additional adverse events.	Metformin	30-39	dipeptidyl peptidase 4	Homo sapiens	101-107
18006825-8	2007	The decrease in translation caused by metformin was associated with mammalian target of rapamycin (mTOR) inhibition, and a decrease in the phosphorylation of S6 kinase, ribosomal protein S6, and eIF4E-binding protein 1.	Metformin	38-47	eukaryotic translation initiation factor 4E binding protein 1	Homo sapiens	195-218
17936664-12	2007	If confirmed on more patients, early use of pioglitazone in association with metformin could be proposed in FPLD2.	Metformin	77-86	lamin A/C	Homo sapiens	108-113
28406985-8	2017	To further explore the underlying mechanism, we found that metformin treatment could significantly damp the expression of 4EBP1 and S6K1 in KYSE 450 cells in vitro and in vivo, furthermore, the p-4EBP1 and p-S6K1 expression in KYSE 450 cells were also inhibited greatly in vitro and in vivo.	Metformin	59-68	eukaryotic translation initiation factor 4E binding protein 1	Homo sapiens	122-127
28406985-8	2017	To further explore the underlying mechanism, we found that metformin treatment could significantly damp the expression of 4EBP1 and S6K1 in KYSE 450 cells in vitro and in vivo, furthermore, the p-4EBP1 and p-S6K1 expression in KYSE 450 cells were also inhibited greatly in vitro and in vivo.	Metformin	59-68	ribosomal protein S6 kinase B1	Homo sapiens	132-136
28406985-8	2017	To further explore the underlying mechanism, we found that metformin treatment could significantly damp the expression of 4EBP1 and S6K1 in KYSE 450 cells in vitro and in vivo, furthermore, the p-4EBP1 and p-S6K1 expression in KYSE 450 cells were also inhibited greatly in vitro and in vivo.	Metformin	59-68	eukaryotic translation initiation factor 4E binding protein 1	Homo sapiens	196-201
28406985-8	2017	To further explore the underlying mechanism, we found that metformin treatment could significantly damp the expression of 4EBP1 and S6K1 in KYSE 450 cells in vitro and in vivo, furthermore, the p-4EBP1 and p-S6K1 expression in KYSE 450 cells were also inhibited greatly in vitro and in vivo.	Metformin	59-68	ribosomal protein S6 kinase B1	Homo sapiens	208-212
28383051-5	2017	Next, we combined Akti-1/2 with metformin, a widely-prescribed drug for treating type 2 diabetes, which was reported to down-regulate OCT4 expression.	Metformin	32-41	POU class 5 homeobox 1	Homo sapiens	134-138
28156052-10	2017	Moreover, activation of AMPK with metformin significantly inhibited LPS-induced gp91phox upregualtion in endothelial cells.	Metformin	34-43	paired Ig-like receptor B	Mus musculus	80-84
28153413-2	2017	Results indicate that Metformin (27 ton/y), Paracetamol (6.9 ton/y) and Ibuprofen (2.33 ton/y) were the drugs with higher amounts reaching the Baltic Sea in 2011.	Metformin	22-31	S13 erythroblastosis (avian) oncogene homolog	Homo sapiens	150-153
28276972-6	2017	Insulin basal therapy (+- metformin) may be optimized by the addition of a SGLT2 inhibitor or a glucagon-like peptide-1 (GLP-1) receptor agonist.	Metformin	23-35	solute carrier family 5 member 2	Homo sapiens	75-80
27981392-5	2017	Metformin administration resulted in normalization of osteoclast numbers, cathepsin K immunostaining, and of tooth movement as well as partly recovery of alkaline phosphatase expression in diabetic rats.	Metformin	0-9	cathepsin K	Rattus norvegicus	74-85
28253329-9	2017	RESULTS: Metformin (0.5-10mM, 6-48h) significantly inhibited the proliferation of BPH-1 and P69 cells in a dose-dependent and time-dependent manner.	Metformin	9-18	islet cell autoantigen 1	Homo sapiens	92-95
28253329-10	2017	Treatment with metformin for 24 hours lowered the G2/M cell population by 43.24% in P69 cells and 24.22% in BPH-1 cells.	Metformin	15-24	islet cell autoantigen 1	Homo sapiens	84-87
28154203-0	2017	Metformin Accumulation Correlates with Organic Cation Transporter 2 Protein Expression and Predicts Mammary Tumor Regression In Vivo.	Metformin	0-9	solute carrier family 22 member 2	Rattus norvegicus	39-67
28154203-7	2017	Highly responsive tumors accumulated 3-fold greater metformin amounts (P &lt; 0.05) that were positively correlated with organic cation transporter-2 (OCT2) protein expression (r = 0.57; P = 0.038).	Metformin	52-61	solute carrier family 22 member 2	Rattus norvegicus	121-149
28154203-7	2017	Highly responsive tumors accumulated 3-fold greater metformin amounts (P &lt; 0.05) that were positively correlated with organic cation transporter-2 (OCT2) protein expression (r = 0.57; P = 0.038).	Metformin	52-61	solute carrier family 22 member 2	Rattus norvegicus	151-155
28154203-10	2017	Collectively, these preclinical data provide evidence for a direct effect of metformin in vivo and suggest that OCT2 expression may predict metformin uptake and tumor response.	Metformin	140-149	solute carrier family 22 member 2	Rattus norvegicus	112-116
28161619-7	2017	In contrast, suppression of HIF-1, p-gp and MRP1 protein expression is its main mechanism when metformin combines with anti-metabolites.	Metformin	95-104	phosphoglycolate phosphatase	Homo sapiens	35-39
28253084-2	2017	Many pharmacologically significant compounds are transported by SLC22A2, including the antidiabetic drug metformin, anticancer agent cisplatin, and antiretroviral lamivudine.	Metformin	105-114	solute carrier family 22 member 2	Homo sapiens	64-71
28234914-7	2017	Finally, we have assessed the mechanisms(s) whereby addition of metformin as an augmenting chemotherapeutic agent in CD200-/- animals given EMT6 tumors and treated with a previously established immunotherapy regime can increase host resistance.	Metformin	64-73	CD200 antigen	Mus musculus	117-122
28230206-0	2017	MiRNA-21 mediates the antiangiogenic activity of metformin through targeting PTEN and SMAD7 expression and PI3K/AKT pathway.	Metformin	49-58	microRNA 21	Homo sapiens	0-8
28230206-0	2017	MiRNA-21 mediates the antiangiogenic activity of metformin through targeting PTEN and SMAD7 expression and PI3K/AKT pathway.	Metformin	49-58	phosphatase and tensin homolog	Homo sapiens	77-81
28230206-3	2017	However, the precise regulatory mechanisms by which the metformin-induced endothelial suppression and its effects on miR-21-dependent pathways are still unclear.	Metformin	56-65	microRNA 21	Homo sapiens	117-123
28230206-4	2017	Bioinformatic analysis and identification of miR-21 and its targets and their effects on metformin-induced antiangiogenic activity were assessed using luciferase assays, quantitative real-time PCR, western blots, scratch assays, CCK-8 assays and tubule formation assays.	Metformin	89-98	microRNA 21	Homo sapiens	45-51
28230206-5	2017	In this study, miR-21 was strikingly downregulated by metformin in a time- and dose-dependent manner.	Metformin	54-63	microRNA 21	Homo sapiens	15-21
28230206-7	2017	Overexpression of miR-21 abrogated the metformin-mediated inhibition of endothelial cells proliferation, migration, tubule formation and the TGF-beta-induced AKT, SMAD- and ERK-dependent phosphorylations, and conversely, down-regulation of miR-21 aggravated metformin"s action and revealed significant promotion effects.	Metformin	39-48	microRNA 21	Homo sapiens	18-24
28230206-7	2017	Overexpression of miR-21 abrogated the metformin-mediated inhibition of endothelial cells proliferation, migration, tubule formation and the TGF-beta-induced AKT, SMAD- and ERK-dependent phosphorylations, and conversely, down-regulation of miR-21 aggravated metformin"s action and revealed significant promotion effects.	Metformin	39-48	microRNA 21	Homo sapiens	240-246
28230206-7	2017	Overexpression of miR-21 abrogated the metformin-mediated inhibition of endothelial cells proliferation, migration, tubule formation and the TGF-beta-induced AKT, SMAD- and ERK-dependent phosphorylations, and conversely, down-regulation of miR-21 aggravated metformin"s action and revealed significant promotion effects.	Metformin	258-267	microRNA 21	Homo sapiens	18-24
28230206-8	2017	Our study broadens our understanding of the regulatory mechanism of miR-21 mediating metformin-induced anti-angiogenic effects, providing important implications regarding the design of novel miRNA-based therapeutic strategies against angiogenesis.	Metformin	85-94	microRNA 21	Homo sapiens	68-74
17698034-8	2007	Metformin treatment of the hepatocytes resulted in activation of the AMP-activated kinase, attenuation of the mTOR/S6K1 pathway, reduction of IRS-1 phosphorylation, and a leftward shift in the insulin dose-response curve for PKB activation.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	115-119
17698034-8	2007	Metformin treatment of the hepatocytes resulted in activation of the AMP-activated kinase, attenuation of the mTOR/S6K1 pathway, reduction of IRS-1 phosphorylation, and a leftward shift in the insulin dose-response curve for PKB activation.	Metformin	0-9	insulin receptor substrate 1	Homo sapiens	142-147
17374417-0	2007	Effect of metformin on serum lipoprotein lipase mass levels and LDL particle size in type 2 diabetes mellitus patients.	Metformin	10-19	lipoprotein lipase	Homo sapiens	29-47
17374417-2	2007	The aim of this study was to clarify the effects of metformin on serum lipoprotein lipase mass levels (preheparin LPL mass), adiponectin and lipid metabolism in patients with type 2 diabetes mellitus.	Metformin	52-61	lipoprotein lipase	Homo sapiens	71-89
17374417-8	2007	These results suggest that metformin may increase LPL production, thereby increasing LDL particle size.	Metformin	27-36	lipoprotein lipase	Homo sapiens	50-53
17573070-3	2007	Recent reports indicate that other antidiabetic drugs, such as metformin, may also have inhibitory effects on DPP IV activity.	Metformin	63-72	dipeptidylpeptidase 4	Mus musculus	110-116
17559747-8	2007	Initial clinical trial experience with the new oral DPP-4 inhibitors such as sitagliptin and vildagliptin suggests that these agents are weight-neutral, while providing improved glycaemic control when added to metformin.	Metformin	210-219	dipeptidyl peptidase 4	Homo sapiens	52-57
17559747-10	2007	Initial clinical trial experience with oral DPP-4 inhibitors such as sitagliptin and vildagliptin suggest that these agents may represent an important oral treatment option for weight-neutral, glycaemic control when added to metformin.	Metformin	225-234	dipeptidyl peptidase 4	Homo sapiens	44-49
17391159-11	2007	Reductions in PAI-1 and leptin levels indicate that the early effects of metformin involve also the adipose tissue.	Metformin	73-82	serpin family E member 1	Homo sapiens	14-19
17525501-0	2007	Effect of metformin therapy on plasma adiponectin and leptin levels in obese and insulin resistant postmenopausal females with type 2 diabetes.	Metformin	10-19	leptin	Homo sapiens	54-60
17525501-9	2007	In summary, our data suggest that hypoadiponectinemia in PM may be explained by only IR because the amelioration of whole-body insulin action by 6-month Metformin therapy leads to increase of plasma adiponectin levels; leptin levels did not significantly change after 6-month Metformin therapy.	Metformin	153-162	leptin	Homo sapiens	219-225
17525501-9	2007	In summary, our data suggest that hypoadiponectinemia in PM may be explained by only IR because the amelioration of whole-body insulin action by 6-month Metformin therapy leads to increase of plasma adiponectin levels; leptin levels did not significantly change after 6-month Metformin therapy.	Metformin	276-285	leptin	Homo sapiens	219-225
17123942-6	2007	In granulosa cells from small follicles, metformin (10 mM) reduced production of both progesterone and estradiol and decreased the abundance of HSD3B, CYP11A1, and STAR proteins in presence or absence of FSH (10(-8) M) and IGF1 (10(-8) M).	Metformin	41-50	insulin like growth factor 1	Bos taurus	223-227
17123942-8	2007	In bovine granulosa cells from small follicles, metformin, like AICAR (1 mM) a pharmaceutical activator of AMPK, increased phosphorylation of both Thr172 of AMPK alpha and Ser 79 of ACACA (Acetyl-CoA Carboxylase).	Metformin	48-57	acetyl-CoA carboxylase alpha	Bos taurus	182-187
17123942-8	2007	In bovine granulosa cells from small follicles, metformin, like AICAR (1 mM) a pharmaceutical activator of AMPK, increased phosphorylation of both Thr172 of AMPK alpha and Ser 79 of ACACA (Acetyl-CoA Carboxylase).	Metformin	48-57	acetyl-CoA carboxylase alpha	Bos taurus	189-211
17135357-4	2007	We report that when S122 on NDPK-A is phosphorylated by AMPK alpha1 in vivo, (i.e., stimulation of AMPK using either metformin or phenformin) initiating the substrate channeling mechanism, the catalytic subunit of CK2 (CK2alpha) is expelled from the complex and translocates to bind NDPK-B, a closely related but independent isoform of NDPK.	Metformin	117-126	NME/NM23 nucleoside diphosphate kinase 2	Homo sapiens	283-289
16902066-2	2006	The purposes of the present study were 1) to confirm whether acute metformin administration induced AMPK phosphorylation and 2) to determine whether chronic metformin treatment increased the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) protein expression, glycolytic and oxidative enzyme activities, and cytochrome c and glucose transporter-4 (GLUT4) protein expressions in the rat soleus and red and white gastrocnemius muscles.	Metformin	157-166	solute carrier family 2 member 4	Rattus norvegicus	357-378
16902066-2	2006	The purposes of the present study were 1) to confirm whether acute metformin administration induced AMPK phosphorylation and 2) to determine whether chronic metformin treatment increased the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) protein expression, glycolytic and oxidative enzyme activities, and cytochrome c and glucose transporter-4 (GLUT4) protein expressions in the rat soleus and red and white gastrocnemius muscles.	Metformin	157-166	solute carrier family 2 member 4	Rattus norvegicus	380-385
16957566-6	2006	Addition of rosiglitazone to metformin also reduced levels of plasminogen activator inhibitor-1 antigen and activity, C-reactive protein, von Willebrand factor and fibrinogen compared with addition of glyburide.	Metformin	29-38	serpin family E member 1	Homo sapiens	62-95
16492692-9	2006	Metformin was also associated with lower insulin resistance and leptin and IGF-I levels and higher SHBG and IGF-binding protein-1 levels and with a more favorable lipid profile.	Metformin	0-9	leptin	Homo sapiens	64-70
16492692-9	2006	Metformin was also associated with lower insulin resistance and leptin and IGF-I levels and higher SHBG and IGF-binding protein-1 levels and with a more favorable lipid profile.	Metformin	0-9	insulin like growth factor binding protein 1	Homo sapiens	108-129
16564524-6	2006	Metformin induced activation and redistribution of phosphorylated extracellular signal-regulated kinase (P-ERK) in a transient manner, and dose-dependently stimulated the expression of endothelial and inducible nitric oxide synthases (e/iNOS).	Metformin	0-9	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	105-110
16321138-5	2006	The AMPK activators AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) and metformin also stimulated Bax translocation.	Metformin	78-87	BCL2 associated X, apoptosis regulator	Rattus norvegicus	104-107
28158227-10	2017	Metformin treatment brought about a significant reduction of visceral fat mass compared to controls accompanied by an up-regulation of fat oxidation-related enzyme in the liver, UCP-1 in the brown adipose tissue and UCP-3 in the skeletal muscle.	Metformin	0-9	uncoupling protein 1	Homo sapiens	178-183
28345832-9	2017	Furthermore, metformin exposure resultedin decreased STAT3 activation and down-regulation of anti-apoptotic protein Bcl-2 and Mcl-1 expression.	Metformin	13-22	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	126-131
27305912-9	2017	RESULTS: After adjusting for multiple comparisons in the 32 tumors from metformin-treated patients vs. 34 untreated historical controls, 11 proteins were significantly different between cases vs. CONTROLS: increases in Raptor, C-Raf, Cyclin B1, Cyclin D1, TRFC, and Syk; and reductions in pMAPKpT202,Y204, JNKpT183,pT185, BadpS112, PKC.alphapS657, and SrcpY416.	Metformin	72-81	cyclin B1	Homo sapiens	234-243
28056431-1	2017	AIMS: The objective of this nationwide study was to compare the risk of all-cause mortality, fatal and nonfatal cardiovascular disease (CVD), and severe hypoglycemia in patients with type 2 diabetes (T2D) on metformin monotherapy treatment starting second-line treatment with either insulin or dipeptidyl peptidase-4 inhibitor (DPP-4i).	Metformin	208-217	dipeptidyl peptidase 4	Homo sapiens	294-316
28744307-1	2017	OBJECTIVES: We aimed to explore the association between metformin treatment and epithelial-mesenchymal transition (EMT) phenotype and further appraise the prognostic values of metformin and EMT markers E-cadherin and vimentin for colorectal cancer (CRC) in clinical practice.	Metformin	56-65	vimentin	Homo sapiens	217-225
27705028-8	2017	Taking the effect of drugs into consideration, the effect on adiponectin and resistin levels was found to be highly significant in Group 2 before and after treatment (11 +- 5 versus 19.2 +- 4.5 mug/ml) (13.6 +- 2.5 versus 7.3 +- 2.9 pg/ml), while more effect was observed in leptin among Group 1 (metformin)-treated cases (27 +- 15 ng/ml versus 15 +- 15 ng/ml).	Metformin	297-306	resistin	Homo sapiens	77-85
16530014-4	2006	Importantly, the absence of LKB1 in the liver abolishes the effect of lowering glucose level caused by metformin, a drug that is widely used for the treatment of type 2 diabetes.	Metformin	103-112	serine/threonine kinase 11	Homo sapiens	28-32
28105986-5	2017	This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium-glucose co-transporter 2 (SGLT2) inhibitors.	Metformin	78-87	solute carrier family 5 member 2	Homo sapiens	108-139
28105986-5	2017	This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium-glucose co-transporter 2 (SGLT2) inhibitors.	Metformin	78-87	solute carrier family 5 member 2	Homo sapiens	141-146
28188318-2	2017	Sulfonylureas have been the preferred add-on therapy to metformin for T2DM, but a study finds that DPP-4s have lower risks of death, CV events, and hypoglycemia.	Metformin	56-65	dipeptidyl peptidase 4	Homo sapiens	99-104
28479753-4	2017	AIM: To determine the effect of metformin and DLBS3233 on serum AMH level.	Metformin	32-41	anti-Mullerian hormone	Homo sapiens	64-67
28479753-11	2017	After 6 months of therapy, we found that the decrease in AMH level was higher in the metformin group compared to the DLBS3233 group (DeltaAMH = 1.83 ng/mL, P = 0.003 and DeltaAMH = 1.15 ng/mL, P = 0.077, respectively).	Metformin	85-94	anti-Mullerian hormone	Homo sapiens	57-60
28479753-14	2017	CONCLUSION: There was a significant decrease in the serum AMH level after administration of either metformin or DLBS3233.	Metformin	99-108	anti-Mullerian hormone	Homo sapiens	58-61
29147073-0	2017	Metformin Suppressed CXCL8 Expression and Cell Migration in HEK293/TLR4 Cell Line.	Metformin	0-9	toll like receptor 4	Homo sapiens	67-71
27931017-11	2017	While metformin significantly altered circulating adiponectin levels in obese and lean animals, it had no effect on EH.	Metformin	6-15	adiponectin, C1Q and collagen domain containing	Mus musculus	50-61
28770024-0	2017	Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity.	Metformin	0-9	butyrylcholinesterase	Homo sapiens	53-67
27871888-7	2017	Cd2+ could inhibit the uptake of metformin, a substrate of MATE transporters, with the half maximal inhibitory concentration (IC50) of 97.5+-6.0muM, 20.2+-2.6muM, and 49.9+-6.9muM in HEK-hMATE1, HEK-hMATE2-K, and HEK-mMate1 cells, respectively.	Metformin	33-42	CD2 molecule	Homo sapiens	0-3
28025449-8	2017	Treatment for seven days with metformin increased the expression levels of osteogenic protein mRNAs, including alkaline phosphatase, runt-related transcription factor 2, and osteopontin.	Metformin	30-39	secreted phosphoprotein 1	Homo sapiens	174-185
27756748-9	2016	In tumor-prone Fancd2-/-Trp53+/- mice, metformin delayed the onset of tumors and significantly extended the tumor-free survival time.	Metformin	39-48	transformation related protein 53	Mus musculus	24-29
16322356-8	2006	Increases in biomarkers of inflammation (e.g., interleukin 6, interferon gamma, and neutrophil number) were also blunted by metformin treatment.	Metformin	124-133	interferon gamma	Rattus norvegicus	62-78
16443786-3	2006	Exposure of cultured bovine aortic endothelial cells (BAECs) to clinically relevant concentrations of metformin (50-500 micromol/l) dose-dependently increased serine-1179 (Ser1179) phosphorylation (equal to human Ser1179) of endothelial nitric oxide (NO) synthase (eNOS) as well as its association with heat shock protein (hsp)-90, resulting in increased activation of eNOS and NO bioactivity (cyclic GMP).	Metformin	102-111	heat shock protein 90 alpha family class A member 1	Homo sapiens	303-330
16443786-5	2006	Furthermore, administration of metformin as well as 5-aminoimidazole-4-carboxamide ribonucleoside, an AMPK agonist, significantly increased eNOS Ser1179 phosphorylation, NO bioactivity, and coimmunoprecipitation of eNOS with hsp90 in wild-type C57BL6 mice but not in AMPK-alpha1 knockout mice, suggesting that AMPK is required for metformin-enhanced eNOS activation in vivo.	Metformin	31-40	nitric oxide synthase 3, endothelial cell	Mus musculus	140-144
16443786-5	2006	Furthermore, administration of metformin as well as 5-aminoimidazole-4-carboxamide ribonucleoside, an AMPK agonist, significantly increased eNOS Ser1179 phosphorylation, NO bioactivity, and coimmunoprecipitation of eNOS with hsp90 in wild-type C57BL6 mice but not in AMPK-alpha1 knockout mice, suggesting that AMPK is required for metformin-enhanced eNOS activation in vivo.	Metformin	31-40	nitric oxide synthase 3, endothelial cell	Mus musculus	215-219
16242377-5	2006	In recent studies of 3-12 months duration in patients with type 2 diabetes, dipeptidyl peptidase IV inhibitors have proved efficacious, both as monotherapy and when given in combination with metformin.	Metformin	191-200	dipeptidyl peptidase 4	Homo sapiens	76-99
16272756-5	2005	A kinetic analysis of metformin transport demonstrated that the amount of plasmid cDNA for transfection was also important parameter to the quantitative elucidation of functional characteristics of transporters, and both human and rat OCT2 had about a 10- and 100-fold greater capacity to transport metformin than did OCT1, respectively.	Metformin	22-31	solute carrier family 22 member 2	Rattus norvegicus	235-239
16272756-5	2005	A kinetic analysis of metformin transport demonstrated that the amount of plasmid cDNA for transfection was also important parameter to the quantitative elucidation of functional characteristics of transporters, and both human and rat OCT2 had about a 10- and 100-fold greater capacity to transport metformin than did OCT1, respectively.	Metformin	299-308	solute carrier family 22 member 2	Rattus norvegicus	235-239
16272756-7	2005	The in vivo distribution of metformin in rats revealed that the expression level of renal OCT2 was a key factor in the control of the concentrative accumulation of metformin in the kidney.	Metformin	28-37	solute carrier family 22 member 2	Rattus norvegicus	90-94
16272756-7	2005	The in vivo distribution of metformin in rats revealed that the expression level of renal OCT2 was a key factor in the control of the concentrative accumulation of metformin in the kidney.	Metformin	164-173	solute carrier family 22 member 2	Rattus norvegicus	90-94
15665022-0	2005	The importance of IRS-1 Gly972Arg polymorphism in evaluating the response to metformin treatment in polycystic ovary syndrome.	Metformin	77-86	insulin receptor substrate 1	Homo sapiens	18-23
15665022-2	2005	With this in mind, we supposed that the G972A variant of insulin receptor substrate-1 (IRS-1) may modulate the response to metformin treatment in women with polycystic ovary syndrome (PCOS).	Metformin	123-132	insulin receptor substrate 1	Homo sapiens	57-85
15665022-2	2005	With this in mind, we supposed that the G972A variant of insulin receptor substrate-1 (IRS-1) may modulate the response to metformin treatment in women with polycystic ovary syndrome (PCOS).	Metformin	123-132	insulin receptor substrate 1	Homo sapiens	87-92
15671098-6	2005	MCP-1 is stimulated by IL-1beta, TNF-alpha, IL-8, IL-4, and IL-6 + IL-6-soluble receptor and is decreased by dexamethasone, IL-10, metformin, and thiazolidinediones.	Metformin	131-140	C-C motif chemokine ligand 2	Homo sapiens	0-5
27828777-3	2016	Additionally, further studies have reported that SLC22A2 is responsible for 80% of the total metformin clearance.	Metformin	93-102	solute carrier family 22 member 2	Homo sapiens	49-56
27828777-4	2016	Therefore, loss-of-function variants of SLC22A2 could affect the pharmacokinetic and pharmacodynamic characteristics of metformin.	Metformin	120-129	solute carrier family 22 member 2	Homo sapiens	40-47
27609360-0	2016	Single nucleotide polymorphisms in the intergenic region between metformin transporter OCT2 and OCT3 coding genes are associated with short-term response to metformin monotherapy in type 2 diabetes mellitus patients.	Metformin	65-74	solute carrier family 22 member 2	Homo sapiens	87-91
27609360-9	2016	CONCLUSIONS: For the first time, we have identified an association between the lack of metformin response and SNPs rs3119309 and rs7757336 located in the 5" flanking region of the genes coding for Organic cation transporter 2 and rs2481030 located in the 5" flanking region of Organic cation transporter 3 that was supported by the results of a pharmacokinetic study on 25 healthy volunteers.	Metformin	87-96	solute carrier family 22 member 2	Homo sapiens	197-225
27576133-0	2016	Metformin inhibits JAK2V617F activity in MPN cells by activating AMPK and PP2A complexes containing the B56alpha subunit.	Metformin	0-9	protein phosphatase 2 phosphatase activator	Homo sapiens	74-78
27576133-7	2016	Second, metformin activates protein tyrosine phosphatase PP2A, a negative regulator of JAK2V617F.	Metformin	8-17	protein phosphatase 2 phosphatase activator	Homo sapiens	57-61
27745917-11	2016	After metformin, there were significant decreases in serum IGF-1 (p=0.046), omentin (p=0.007), insulin (p=0.012), C-peptide (p=0.018), and leptin (p=0.0035).	Metformin	6-15	intelectin 1	Homo sapiens	76-83
28129682-10	2016	Histological examinations revealed that metformin remarkably attenuated congestion and inflammatory cellular infiltration into the alveolar walls and also decreased MPO activity by 37% (p&lt;0.05).	Metformin	40-49	myeloperoxidase	Rattus norvegicus	165-168
27225841-0	2016	Metformin Protects Cells from Mutant Huntingtin Toxicity Through Activation of AMPK and Modulation of Mitochondrial Dynamics.	Metformin	0-9	huntingtin	Mus musculus	37-47
27225841-6	2016	In this study, we showed that metformin rescued cells from mutant huntingtin (HTT)-induced toxicity, as indicated by reduced lactate dehydrogenase (LDH) release from cells and preserved ATP levels in cells expressing mutant HTT.	Metformin	30-39	huntingtin	Mus musculus	66-76
27225841-6	2016	In this study, we showed that metformin rescued cells from mutant huntingtin (HTT)-induced toxicity, as indicated by reduced lactate dehydrogenase (LDH) release from cells and preserved ATP levels in cells expressing mutant HTT.	Metformin	30-39	huntingtin	Mus musculus	78-81
27225841-6	2016	In this study, we showed that metformin rescued cells from mutant huntingtin (HTT)-induced toxicity, as indicated by reduced lactate dehydrogenase (LDH) release from cells and preserved ATP levels in cells expressing mutant HTT.	Metformin	30-39	huntingtin	Mus musculus	224-227
27225841-7	2016	Further mechanistic study indicated that metformin activated AMP-activated protein kinase (AMPK) and that inhibition of AMPK activation reduced its protective effects on mutant HTT toxicity, suggesting that AMPK mediates the protection of metformin in HD cells.	Metformin	239-248	huntingtin	Mus musculus	177-180
27779693-5	2016	Metformin upregulated the expression of p21Waf1 and p27kip1, and downregulated the expression of cyclin D1, a key protein required for cell cycle progression.	Metformin	0-9	cyclin dependent kinase inhibitor 1B	Homo sapiens	52-59
27252117-12	2016	Metformin (200 mg/kg/d) significantly normalized MDA, SOD and GSH levels (p &lt; 0.001), and exerted a hepatoprotective effect by significant decreasing ALT, AST and ALP concentrations (p &lt; 0.001).	Metformin	0-9	glutamic pyruvic transaminase, soluble	Mus musculus	153-156
27252117-12	2016	Metformin (200 mg/kg/d) significantly normalized MDA, SOD and GSH levels (p &lt; 0.001), and exerted a hepatoprotective effect by significant decreasing ALT, AST and ALP concentrations (p &lt; 0.001).	Metformin	0-9	solute carrier family 17 (anion/sugar transporter), member 5	Mus musculus	158-161
27645247-0	2016	Moxifloxacin Is a Potent In Vitro Inhibitor of OCT- and MATE-Mediated Transport of Metformin and Ethambutol.	Metformin	83-92	plexin A2	Homo sapiens	47-50
27600020-3	2016	Pre-incubation of cells with metformin, an AMPK activator, blocked PDGF-induced activation of mTOR and its downstream targets changes of Skp2 and p27 without changing Akt phosphorylation and inhibited ASMCs proliferation.	Metformin	29-38	interferon alpha inducible protein 27	Homo sapiens	146-149
27600020-4	2016	Transfection of ASMCs with AMPK alpha2-specific small interfering RNA (siRNA) reversed the effect of metformin on mTOR phosphorylation, Skp2 and p27 protein expression and cell proliferation.	Metformin	101-110	interferon alpha inducible protein 27	Homo sapiens	145-148
27813479-5	2016	Expression of an oncogenic mutant of GIV (cataloged in TCGA) that cannot be phosphorylated by AMPK increased anchorage-independent growth of tumor cells and helped these cells to evade the tumor-suppressive action of Metformin.	Metformin	217-226	coiled-coil domain containing 88A	Homo sapiens	37-40
27813479-6	2016	This work defines a fundamental homeostatic mechanism by which the AMPK-GIV axis reinforces cell junctions against stress-induced collapse and also provides mechanistic insight into the tumor-suppressive action of Metformin.	Metformin	214-223	coiled-coil domain containing 88A	Homo sapiens	72-75
15671098-8	2005	Despite this, MCP-1 may be involved in obesity-related health complications, and the decrease of MCP-1 by metformin and thiazolidinediones suggests that these antidiabetic compounds have antiinflammatory properties improving the low-grade inflammatory state observed in obesity.	Metformin	106-115	C-C motif chemokine ligand 2	Homo sapiens	97-102
15736108-0	2005	The effects of rosiglitazone and metformin on the plasma concentrations of resistin in patients with type 2 diabetes mellitus.	Metformin	33-42	resistin	Homo sapiens	75-83
27764050-10	2016	Interestingly, 3 months after treatment discontinuation, leptin levels showed a reduction in both metformin (baseline, 25.3 +- 14.7, week 7: 5.7 +- 3.7 ng/mL) and topiramate (baseline: 28.4 +- 16.1, week 7: 9.2 +- 15.5 ng/mL) groups.	Metformin	98-107	leptin	Homo sapiens	57-63
27551045-12	2016	In kidney, metformin increased the activation of AMP-activated protein kinase (AMPK) and decreased inflammatory markers (COX-2 and IL-1beta) and apoptotic markers (poly(ADP-ribose) polymerase (PARP) and caspase 3).	Metformin	11-20	poly (ADP-ribose) polymerase 1	Rattus norvegicus	164-191
27551045-12	2016	In kidney, metformin increased the activation of AMP-activated protein kinase (AMPK) and decreased inflammatory markers (COX-2 and IL-1beta) and apoptotic markers (poly(ADP-ribose) polymerase (PARP) and caspase 3).	Metformin	11-20	poly (ADP-ribose) polymerase 1	Rattus norvegicus	193-197
27282621-10	2016	CONCLUSIONS: This nationwide observational study showed that second-line treatment with TZD and DPP-4 inhibitor as add-on medication to metformin were associated with significantly lower risks of mortality and cardiovascular events compared with SU, whereas basal insulin was associated with a higher risk of mortality.	Metformin	136-145	dipeptidyl peptidase 4	Homo sapiens	96-101
27569291-0	2016	Involvement of organic cation transporter 3 (Oct3/Slc22a3) in the bioavailability and pharmacokinetics of antidiabetic metformin in mice.	Metformin	119-128	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	15-43
27569291-0	2016	Involvement of organic cation transporter 3 (Oct3/Slc22a3) in the bioavailability and pharmacokinetics of antidiabetic metformin in mice.	Metformin	119-128	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	45-49
27569291-0	2016	Involvement of organic cation transporter 3 (Oct3/Slc22a3) in the bioavailability and pharmacokinetics of antidiabetic metformin in mice.	Metformin	119-128	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	50-57
27569291-3	2016	However, the role of OCT3/Oct3 in the intestinal absorption process of metformin remains obscure.	Metformin	71-80	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	21-25
27569291-3	2016	However, the role of OCT3/Oct3 in the intestinal absorption process of metformin remains obscure.	Metformin	71-80	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	26-30
27569291-4	2016	In the present study, we aimed to clarify the impact of Oct3 on the oral bioavailability and pharmacokinetics of metformin in mice, by means of in vivo pharmacokinetic study using wild-type (Oct3+/+) and Oct3-knockout (Oct3-/-) mice.	Metformin	113-122	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	56-60
27569291-5	2016	When metformin (8.0 mg/kg) was intravenously administered to male Oct3+/+ and Oct3-/- mice, AUC0-  of metformin was evaluated to be 659 +- 133 mug h/mL and 734 +- 213 mug h/mL, respectively.	Metformin	5-14	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	66-70
27569291-5	2016	When metformin (8.0 mg/kg) was intravenously administered to male Oct3+/+ and Oct3-/- mice, AUC0-  of metformin was evaluated to be 659 +- 133 mug h/mL and 734 +- 213 mug h/mL, respectively.	Metformin	5-14	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	78-82
27569291-6	2016	In the case of orally administered metformin (15 mg/kg), AUC0-  was 578 +- 158 mug h/mL and 449 +- 101 mug h/mL in Oct3+/+ and Oct3-/- mice, respectively.	Metformin	35-44	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	115-119
27569291-6	2016	In the case of orally administered metformin (15 mg/kg), AUC0-  was 578 +- 158 mug h/mL and 449 +- 101 mug h/mL in Oct3+/+ and Oct3-/- mice, respectively.	Metformin	35-44	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	127-131
27569291-7	2016	Based on these pharmacokinetic parameters, absolute bioavailability (F) of metformin in Oct3+/+ mice was evaluated as 46.8%, and it was significantly decreased to 32.6% in Oct3-/- mice.	Metformin	75-84	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	88-92
27569291-8	2016	Taking into account the fact that metformin undergoes negligible metabolism, these results imply that intestinal absorption of metformin is mediated at least in part by Oct3 in mice.	Metformin	127-136	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	169-173
25876759-0	2016	Gender-Related Differences in the Expression of Organic Cation Transporter 2 and its Role in Urinary Excretion of Metformin in Rats.	Metformin	114-123	solute carrier family 22 member 2	Rattus norvegicus	48-76
25876759-1	2016	Organic cation transporter 2 (rOCT2) and multidrug and toxin extrusion protein 1 (rMATE1) are mainly expressed in rat renal proximal tubules and mediate urinary excretion of cationic drugs, such as metformin.	Metformin	198-207	solute carrier family 22 member 2	Rattus norvegicus	0-28
25876759-1	2016	Organic cation transporter 2 (rOCT2) and multidrug and toxin extrusion protein 1 (rMATE1) are mainly expressed in rat renal proximal tubules and mediate urinary excretion of cationic drugs, such as metformin.	Metformin	198-207	solute carrier family 22 member 2	Rattus norvegicus	30-35
25876759-3	2016	However, it is unclear whether the gender-related differences in rOCT2 expression between male and female rats can affect the urinary excretion of metformin.	Metformin	147-156	solute carrier family 22 member 2	Rattus norvegicus	65-70
25876759-4	2016	The aim of this study was to investigate the effect of gender on the pharmacokinetics of metformin and to clarify the effect of gender-related differences on renal rOCT2 expression and its role in urinary excretion of metformin.	Metformin	218-227	solute carrier family 22 member 2	Rattus norvegicus	164-169
25876759-7	2016	These results indicated that effect of gender-related differences on renal rOCT2 expression indeed contributes to the decreased urinary excretion of metformin in female rats when metformin was administered at relatively high doses.	Metformin	149-158	solute carrier family 22 member 2	Rattus norvegicus	75-80
25876759-7	2016	These results indicated that effect of gender-related differences on renal rOCT2 expression indeed contributes to the decreased urinary excretion of metformin in female rats when metformin was administered at relatively high doses.	Metformin	179-188	solute carrier family 22 member 2	Rattus norvegicus	75-80
27569287-4	2016	Unexpectedly, DR5 is upregulated in the cells treated with DCA/metformin, and sustained under hypoxia.	Metformin	63-72	TNF receptor superfamily member 10b	Homo sapiens	14-17
27569287-5	2016	Blocking DR5 by siRNA inhibited DCA/metformin/TRAIL-induced cell death, indicating that DR5 upregulation plays an important role in sensitizing cancer cells to TRAIL-induced cell death.	Metformin	36-45	TNF receptor superfamily member 10b	Homo sapiens	9-12
27569287-5	2016	Blocking DR5 by siRNA inhibited DCA/metformin/TRAIL-induced cell death, indicating that DR5 upregulation plays an important role in sensitizing cancer cells to TRAIL-induced cell death.	Metformin	36-45	TNF receptor superfamily member 10b	Homo sapiens	88-91
27569287-6	2016	Furthermore, we found that activation of JNK and c-Jun is responsible for upregulation of DR5 induced by DCA/metformin.	Metformin	109-118	TNF receptor superfamily member 10b	Homo sapiens	90-93
27564915-1	2016	Ion transfer voltammetry is used to estimate the acid dissociation constants Ka1 and Ka2 of the mono- and diprotonated forms of the biguanide drugs metformin (MF), phenformin (PF), and 1-phenylbiguanide (PB) in an aqueous solution.	Metformin	148-157	glutamate ionotropic receptor kainate type subunit 4	Homo sapiens	77-80
27564915-1	2016	Ion transfer voltammetry is used to estimate the acid dissociation constants Ka1 and Ka2 of the mono- and diprotonated forms of the biguanide drugs metformin (MF), phenformin (PF), and 1-phenylbiguanide (PB) in an aqueous solution.	Metformin	159-161	glutamate ionotropic receptor kainate type subunit 4	Homo sapiens	77-80
27542265-7	2016	Consequently, targeting mitochondrial complex I by metformin administration, impairs proliferation and invasiveness of PC3-DR cells without effects on parental cells.	Metformin	51-60	chromobox 8	Homo sapiens	119-122
27640062-26	2016	Alpha-glucosidase CT compared to IM showed a MD of -0.5 kg (95% CI -1.2 to 0.3); P = 0.26; 241 participants; 2 trials; low-quality evidence.Users of metformin CT (range 7% to 67% versus 5% to 16%), and alpha-glucosidase inhibitors CT (14% to 75% versus 4% to 35%) experienced more gastro-intestinal adverse effects compared to participants on IM.	Metformin	149-158	sucrase-isomaltase	Homo sapiens	0-17
27517746-0	2016	Metformin enhances TRAIL-induced apoptosis by Mcl-1 degradation via Mule in colorectal cancer cells.	Metformin	0-9	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	46-51
27517746-5	2016	We attempted to elucidate the underlying mechanism, and found that metformin significantly reduced the protein levels of myeloid cell leukemia 1 (Mcl-1) in CRC cells and, the overexpression of Mcl-1 inhibited cell death induced by metformin and/or TRAIL.	Metformin	67-76	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	121-144
27517746-5	2016	We attempted to elucidate the underlying mechanism, and found that metformin significantly reduced the protein levels of myeloid cell leukemia 1 (Mcl-1) in CRC cells and, the overexpression of Mcl-1 inhibited cell death induced by metformin and/or TRAIL.	Metformin	67-76	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	146-151
27517746-5	2016	We attempted to elucidate the underlying mechanism, and found that metformin significantly reduced the protein levels of myeloid cell leukemia 1 (Mcl-1) in CRC cells and, the overexpression of Mcl-1 inhibited cell death induced by metformin and/or TRAIL.	Metformin	67-76	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	193-198
27517746-5	2016	We attempted to elucidate the underlying mechanism, and found that metformin significantly reduced the protein levels of myeloid cell leukemia 1 (Mcl-1) in CRC cells and, the overexpression of Mcl-1 inhibited cell death induced by metformin and/or TRAIL.	Metformin	231-240	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	121-144
27517746-5	2016	We attempted to elucidate the underlying mechanism, and found that metformin significantly reduced the protein levels of myeloid cell leukemia 1 (Mcl-1) in CRC cells and, the overexpression of Mcl-1 inhibited cell death induced by metformin and/or TRAIL.	Metformin	231-240	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	146-151
27517746-5	2016	We attempted to elucidate the underlying mechanism, and found that metformin significantly reduced the protein levels of myeloid cell leukemia 1 (Mcl-1) in CRC cells and, the overexpression of Mcl-1 inhibited cell death induced by metformin and/or TRAIL.	Metformin	231-240	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	193-198
27517746-6	2016	Further experiments revealed that metformin did not affect mRNA levels, but increased proteasomal degradation and protein stability of Mcl-1.	Metformin	34-43	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	135-140
27517746-8	2016	Metformin caused the dissociation of Noxa from Mcl-1, which allowed the binding of the BH3-containing ubiquitin ligase Mule followed by Mcl-1ubiquitination and degradation.	Metformin	0-9	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	47-52
27517746-9	2016	The metformin-induced degradation of Mcl-1 required E3 ligase Mule, which is responsible for the polyubiquitination of Mcl-1.	Metformin	4-13	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	37-42
27517746-9	2016	The metformin-induced degradation of Mcl-1 required E3 ligase Mule, which is responsible for the polyubiquitination of Mcl-1.	Metformin	4-13	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	119-124
27517746-10	2016	Our study is the first report indicating that metformin enhances TRAIL-induced apoptosis through Noxa and favors the interaction between Mcl-1 and Mule, which consequently affects Mcl-1 ubiquitination.	Metformin	46-55	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	137-142
27517746-10	2016	Our study is the first report indicating that metformin enhances TRAIL-induced apoptosis through Noxa and favors the interaction between Mcl-1 and Mule, which consequently affects Mcl-1 ubiquitination.	Metformin	46-55	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	180-185
15736108-2	2005	We examined the effects of rosiglitazone and metformin on the plasma resistin levels in individuals with type 2 diabetes mellitus.	Metformin	45-54	resistin	Homo sapiens	69-77
15736108-9	2005	The plasma resistin levels decreased in the rosiglitazone group (2.49 +/- 1.93 vs 1.95 +/- 1.59 ng/ml; P &lt; .05) but increased in the metformin group (2.61 +/- 1.69 vs 5.13 +/- 2.81 ng/ml; P &lt; .05).	Metformin	136-145	resistin	Homo sapiens	11-19
15652898-0	2005	Metformin reduces serum mullerian-inhibiting substance levels in women with polycystic ovary syndrome after protracted treatment.	Metformin	0-9	anti-Mullerian hormone	Homo sapiens	24-54
15823767-13	2004	CONCLUSION: In this study population, Mix 75/25 plus metformin was associated with lower HbA(1c) than insulin glargine plus metformin, smaller rise in ppBG after breakfast and dinner, and higher proportion of patients achieving HbA(1c) &lt; or =7.0%, with a slight increase in overall (but not nocturnal) hypoglycemia.	Metformin	53-62	Mix paired-like homeobox	Homo sapiens	38-41
15823767-13	2004	CONCLUSION: In this study population, Mix 75/25 plus metformin was associated with lower HbA(1c) than insulin glargine plus metformin, smaller rise in ppBG after breakfast and dinner, and higher proportion of patients achieving HbA(1c) &lt; or =7.0%, with a slight increase in overall (but not nocturnal) hypoglycemia.	Metformin	124-133	Mix paired-like homeobox	Homo sapiens	38-41
15561958-8	2004	Metformin also increased hepatic basal IkappaBalpha levels (by 260%; P &lt; 0.001) but had no effect on tyrosine phosphorylation or expression of insulin receptor substrate-1 (IRS-1).	Metformin	0-9	NFKB inhibitor alpha	Rattus norvegicus	39-51
27524482-7	2016	Metformin, a drug that stimulates glucose uptake in cells, mimicked these effects, with a concomitant reduction in Grp78 levels and rescue of the shortened lifespan and climbing defects of Abeta-expressing flies.	Metformin	0-9	Heat shock 70-kDa protein cognate 3	Drosophila melanogaster	115-120
27524482-7	2016	Metformin, a drug that stimulates glucose uptake in cells, mimicked these effects, with a concomitant reduction in Grp78 levels and rescue of the shortened lifespan and climbing defects of Abeta-expressing flies.	Metformin	0-9	beta amyloid protein precursor-like	Drosophila melanogaster	189-194
27246734-6	2016	Western blot revealed that the expression of Beclin-1 and LC3B-II was enhanced, and the phosphorylation levels of the mammalian target of rapamycin (mTOR) protein and p70S6K were reduced by metformin after SCI.	Metformin	190-199	ribosomal protein S6 kinase B1	Homo sapiens	167-173
27246734-9	2016	Hence, metformin attenuated SCI by inhibiting apoptosis and inflammation and enhancing the autophagy via the mTOR/p70S6K signalling pathway.	Metformin	7-16	ribosomal protein S6 kinase B1	Homo sapiens	114-120
27343375-5	2016	Metformin and resveratrol attenuated adipose hypoxia, inhibited HIF-1alpha expression and inflammation in the adipose tissue of HFD-fed mice.	Metformin	0-9	hypoxia inducible factor 1, alpha subunit	Mus musculus	64-74
15562200-0	2004	Twelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes.	Metformin	80-89	dipeptidyl peptidase 4	Homo sapiens	36-59
15562200-1	2004	OBJECTIVE: To assess the 12- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 versus placebo in patients with type 2 diabetes continuing metformin treatment.	Metformin	157-166	dipeptidyl peptidase 4	Homo sapiens	57-80
15063962-10	2004	CONCLUSIONS: The present study shows that metformin therapy not only restores normal levels of insulin and testosterone, but also decreases the pool of free-bioactive IGF-I by increasing the levels of circulating IGFBP-1.	Metformin	42-51	insulin like growth factor binding protein 1	Homo sapiens	213-220
12629126-0	2003	Metformin rapidly increases insulin receptor activation in human liver and signals preferentially through insulin-receptor substrate-2.	Metformin	0-9	insulin receptor substrate 2	Homo sapiens	106-134
12629126-7	2003	Metformin (1 micro g/ml) increased IR tyrosine phosphorylation by 78% (P = 0.0007) in 30 min in human hepatocytes and Huh7 cells and increased IRS-2 but not IRS-1 activation, and the downstream increase in deoxyglucose uptake was mediated via increased translocation of GLUT-1 to the plasma membrane.	Metformin	0-9	insulin receptor substrate 2	Homo sapiens	143-148
12629126-7	2003	Metformin (1 micro g/ml) increased IR tyrosine phosphorylation by 78% (P = 0.0007) in 30 min in human hepatocytes and Huh7 cells and increased IRS-2 but not IRS-1 activation, and the downstream increase in deoxyglucose uptake was mediated via increased translocation of GLUT-1 to the plasma membrane.	Metformin	0-9	insulin receptor substrate 1	Homo sapiens	157-162
12629126-11	2003	This study demonstrates that the mechanism of action of metformin in liver involves IR activation, followed by selective IRS-2 activation, and increased glucose uptake via increased GLUT-1 translocation.	Metformin	56-65	insulin receptor substrate 2	Homo sapiens	121-126
12604391-3	2003	The present observation reports on a type 2 diabete mellitus patient presenting with a coma while the patient was on metformin and glibenclamide treatment.	Metformin	117-126	COMA	Homo sapiens	87-91
27500523-6	2016	This was about half the effect seen with the addition of a DPP-4 inhibitor, and equated to a dose difference of 550 mg of metformin, suggesting rs8192675 as a potential biomarker for stratified medicine.	Metformin	122-131	dipeptidyl peptidase 4	Homo sapiens	59-64
27578220-2	2016	OBJECTIVES    The aim of the study was to determine the influence of metformin on the metabolism of atherogenic lipid fractions in relation to Lp-PLA2 and CEL levels, as well as assess consequent improvement in the intima-media thickness (IMT) of the common carotid artery in young type 1 diabetes patients with excess body fat.	Metformin	69-78	carboxyl ester lipase	Homo sapiens	155-158
27555877-12	2016	Prenatal obesogenic diet exposure significantly increased fetal liver IFNgamma levels (p &lt; 0.05), which was reversed by maternal metformin treatment (p &lt; 0.05).	Metformin	132-141	interferon gamma	Rattus norvegicus	70-78
27570447-0	2016	Pharmacokinetic and pharmacodynamic interactions between metformin and a novel dipeptidyl peptidase-4 inhibitor, evogliptin, in healthy subjects.	Metformin	57-66	dipeptidyl peptidase 4	Homo sapiens	79-101
27570447-1	2016	Evogliptin is a newly developed dipeptidyl peptidase-4 (DPP-4) inhibitor, which is expected to be combined with metformin for treating type 2 diabetes mellitus.	Metformin	112-121	dipeptidyl peptidase 4	Homo sapiens	32-54
27570447-1	2016	Evogliptin is a newly developed dipeptidyl peptidase-4 (DPP-4) inhibitor, which is expected to be combined with metformin for treating type 2 diabetes mellitus.	Metformin	112-121	dipeptidyl peptidase 4	Homo sapiens	56-61
27555891-7	2016	Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters (SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin.	Metformin	310-319	solute carrier family 22 member 2	Homo sapiens	217-224
27570448-0	2016	Treatment progression in sulfonylurea and dipeptidyl peptidase-4 inhibitor cohorts of type 2 diabetes patients on metformin.	Metformin	114-123	dipeptidyl peptidase 4	Homo sapiens	42-64
27495291-13	2016	TRIAL REGISTRATION: Clinical trial registry name: CANagliflozin Treatment And Trial Analysis-Sulfonylurea (CANTATA-SU) SGLT2 Add-on to Metformin Versus Glimepiride.	Metformin	135-144	solute carrier family 5 member 2	Homo sapiens	119-124
27432282-9	2016	Hypothalamic FNDC5 expression did not change for any of the tested diets but increased with leptin, insulin and metformin treatments suggesting that the regulation of central and peripheral FNDC5/irisin expression and functions are different.	Metformin	112-121	fibronectin type III domain containing 5	Rattus norvegicus	13-18
27432282-9	2016	Hypothalamic FNDC5 expression did not change for any of the tested diets but increased with leptin, insulin and metformin treatments suggesting that the regulation of central and peripheral FNDC5/irisin expression and functions are different.	Metformin	112-121	fibronectin type III domain containing 5	Rattus norvegicus	190-195
12669266-0	2003	Metformin, but not thiazolidinediones, inhibits plasminogen activator inhibitor-1 production in human adipose tissue in vitro.	Metformin	0-9	serpin family E member 1	Homo sapiens	48-81
12669266-5	2003	Metformin (0.1 - 10 mM) dose-dependently decreased PAI-1 production (and PAI-1 mRNA) under both basal (43 % inhibition at 10 mM, p &lt; 0.05) and interleukin-1beta (IL-1beta)-stimulated conditions where the levels were inhibited by 47.8 % at 1 mM metformin (p &lt; 0.05) and by 100 % at 10 mM (p &lt; 0.01).	Metformin	0-9	serpin family E member 1	Homo sapiens	51-56
12669266-5	2003	Metformin (0.1 - 10 mM) dose-dependently decreased PAI-1 production (and PAI-1 mRNA) under both basal (43 % inhibition at 10 mM, p &lt; 0.05) and interleukin-1beta (IL-1beta)-stimulated conditions where the levels were inhibited by 47.8 % at 1 mM metformin (p &lt; 0.05) and by 100 % at 10 mM (p &lt; 0.01).	Metformin	0-9	serpin family E member 1	Homo sapiens	73-78
12669266-8	2003	Our findings indicate no direct effects of TZDs on PAI-1 secretion, whereas metformin was able to directly inhibit PAI-1 production in human adipose tissue.	Metformin	76-85	serpin family E member 1	Homo sapiens	115-120
12453948-8	2002	PAI-1 concentrations were extraordinarily high (5- to 10-fold more than normal) at baseline (202 +/- 12 ng/ml glipizide GITS; 201 +/- 13 ng/ml metformin) but declined comparably, and significantly, after treatment with either agent as monotherapy and decreased further with combination therapy.	Metformin	143-152	serpin family E member 1	Homo sapiens	0-5
12453948-10	2002	Control of hyperglycemia with either glipizide GITS, an insulin secretagogue, or metformin as monotherapy comparably ameliorates elevated PAI-1.	Metformin	81-90	serpin family E member 1	Homo sapiens	138-143
12237252-6	2002	Treatment with metformin was able to increase the tyrosine phosphorylation of IR and IRS-1 by 100 and 90% respectively.	Metformin	15-24	insulin receptor substrate 1	Homo sapiens	85-90
12202407-5	2002	Metformin also appears to induce cardioprotective effects on serum lipids as well as plasminogen activator inhibitor (PAI)-1 and may decrease the risk of development of type 2 diabetes.	Metformin	0-9	serpin family E member 1	Homo sapiens	85-124
11811898-10	2001	Hepatic glucose-6-phosphatase activity was significantly lower (P&lt;0.05) in AF- and metformin-treated groups, but not in BuF-treated groups, compared to that in vehicle-treated group.	Metformin	86-95	glucose-6-phosphatase catalytic subunit 1	Rattus norvegicus	8-29
11529255-2	2001	Metformin is the only currently marketed anti-hyperglycaemic drug whose action is attributed largely to its having inhibitory effects on hepatic glucose production, but its molecular site and mechanism(s) of action remain unknown, whereas the liver acting PPAR alpha agonists have their effects primarily on lipid metabolism.	Metformin	0-9	peroxisome proliferator activated receptor alpha	Homo sapiens	256-266
11436194-22	2001	Metformin safely and effectively reduces CHD risk factors (weight, fasting insulin, leptin, LDL cholesterol, centripetal obesity) in morbidly obese, nondiabetic subjects with BMI &gt; 30, probably by virtue of its insulin-sensitizing action.	Metformin	0-9	leptin	Homo sapiens	84-90
11331217-8	2001	After metformin therapy a significant reduction in BMI, % of body fat and leptin concentration were observed in both groups of obese patients.	Metformin	6-15	leptin	Homo sapiens	74-80
11762694-8	2001	The results of the present study show that in hyperoxia-exposed rats, metformin treatment reverses the abolished vascular relaxation to AChe.	Metformin	70-79	acetylcholinesterase	Rattus norvegicus	136-140
11603293-11	2000	The activity of hepatic glucose-6-phosphatase (G-6-Pase) was significantly reduced by the extract as well as by metformin (both P &lt; 0.05).	Metformin	112-121	glucose-6-phosphatase catalytic subunit 1	Rattus norvegicus	24-45
28881582-0	2017	Metformin requires 4E-BPs to induce apoptosis and repress translation of Mcl-1 in hepatocellular carcinoma cells.	Metformin	0-9	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	73-78
28881582-5	2017	A genetic HCC mouse model was employed to assess the ability of metformin to reduce tumor formation, induce apoptosis, and control 4E-BP1 activation and Mcl-1 protein expression.	Metformin	64-73	eukaryotic translation initiation factor 4E binding protein 1	Mus musculus	131-137
28881582-8	2017	We found that metformin decreased HCC tumor burden, and tumor tissues showed elevated apoptosis with reduced Mcl-1 and phosphorylated 4E-BP1 protein levels.	Metformin	14-23	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	109-114
28881582-8	2017	We found that metformin decreased HCC tumor burden, and tumor tissues showed elevated apoptosis with reduced Mcl-1 and phosphorylated 4E-BP1 protein levels.	Metformin	14-23	eukaryotic translation initiation factor 4E binding protein 1	Homo sapiens	134-140
28881582-9	2017	In control but not 4E-BP KD Huh7 cells, metformin induced apoptosis and repressed Mcl-1 mRNA translation and protein levels.	Metformin	40-49	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	82-87
11603293-11	2000	The activity of hepatic glucose-6-phosphatase (G-6-Pase) was significantly reduced by the extract as well as by metformin (both P &lt; 0.05).	Metformin	112-121	glucose-6-phosphatase catalytic subunit 1	Rattus norvegicus	47-55
11225659-3	2000	We studied the effect of metformin treatment on the activities of Cu, Zn-superoxide dismutase (EC 1.	Metformin	25-34	Susceptibility to lysis by alloreactive natural killer cells	Homo sapiens	95-99
10794717-0	2000	Chronic insulin effects on insulin signalling and GLUT4 endocytosis are reversed by metformin.	Metformin	84-93	solute carrier family 2 member 4	Rattus norvegicus	50-55
26433129-7	2016	Metformin use appeared to strengthen the association between the index single nucleotide polymorphism at PPP1R3B/LOC157273 and plasma lactate in European-American subjects (P for interaction=0.01).	Metformin	0-9	protein phosphatase 1 regulatory subunit 3B	Homo sapiens	105-112
26305116-10	2016	Metformin at 50 mM significantly reduced the phosphorylation of mTOR and p70S6K, by 49.0 and 62.1%, respectively.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	73-79
27223262-3	2016	Compared to metformin-HCl, it more potently activates AMPK, inhibits mTOR, and impairs cell cycle progression at S and G2/M phases.	Metformin	12-25	mechanistic target of rapamycin kinase	Mus musculus	69-73
27076180-7	2016	Conversely, DPP-4 inhibitors and GLP-1 receptor agonists gained market shares due to their efficacy in glycemic control as an add-on treatment to metformin.	Metformin	146-155	dipeptidyl peptidase 4	Homo sapiens	12-17
26979520-2	2016	The gastrointestinal uptake of metformin is mediated by the human equilibrative nucleoside transporter 4 (ENT4), which is inhibited by dipyridamole in preclinical studies.	Metformin	31-40	solute carrier family 29 member 4	Homo sapiens	66-104
26979520-2	2016	The gastrointestinal uptake of metformin is mediated by the human equilibrative nucleoside transporter 4 (ENT4), which is inhibited by dipyridamole in preclinical studies.	Metformin	31-40	solute carrier family 29 member 4	Homo sapiens	106-110
26979520-10	2016	CONCLUSIONS: Previous in vitro studies report that dipyridamole inhibits the ENT4 transporter that mediates gastrointestinal uptake of metformin.	Metformin	135-144	solute carrier family 29 member 4	Homo sapiens	77-81
27262901-0	2016	Metformin enhances anti-tumor effect of L-type amino acid transporter 1 (LAT1) inhibitor.	Metformin	0-9	solute carrier family 7 member 5	Homo sapiens	40-71
27262901-0	2016	Metformin enhances anti-tumor effect of L-type amino acid transporter 1 (LAT1) inhibitor.	Metformin	0-9	solute carrier family 7 member 5	Homo sapiens	73-77
27262901-10	2016	A combination of anti-LAT1 drug with metformin may be an effective anti-proliferative therapy for certain subsets of cancers.	Metformin	37-46	solute carrier family 7 member 5	Homo sapiens	22-26
27109601-7	2016	Treatment with metformin also induced cell cycle arrest in UVC-induced cells, in correlation with a reduction in the levels of cyclin E/cdk2/Rb and cyclin B1/cdk1.	Metformin	15-24	cyclin B1	Homo sapiens	148-157
27109601-7	2016	Treatment with metformin also induced cell cycle arrest in UVC-induced cells, in correlation with a reduction in the levels of cyclin E/cdk2/Rb and cyclin B1/cdk1.	Metformin	15-24	cyclin dependent kinase 1	Homo sapiens	158-162
26962099-7	2016	Metformin, an AMPK activator, increased phosphorylation of both AQP2 and UT-A1 in rat inner medullary collecting ducts (IMCDs).	Metformin	0-9	aquaporin 2	Rattus norvegicus	64-68
26962099-8	2016	Metformin increased the apical plasma membrane accumulation of AQP2, but not UT-A1, in rat IM.	Metformin	0-9	aquaporin 2	Rattus norvegicus	63-67
26962099-10	2016	These findings suggest that metformin increases osmotic water permeability by increasing AQP2 accumulation in the apical plasma membrane but increases urea permeability by activating UT-A1 already present in the membrane.	Metformin	28-37	aquaporin 2	Rattus norvegicus	89-93
27274280-0	2016	Metformin induces apoptosis of human hepatocellular carcinoma HepG2 cells by activating an AMPK/p53/miR-23a/FOXA1 pathway.	Metformin	0-9	forkhead box A1	Homo sapiens	108-113
27274280-4	2016	We next established forkhead box protein A1 (FOXA1) as the functional target of miR-23a, and silencing FOXA1 mimicked the effect of metformin.	Metformin	132-141	forkhead box A1	Homo sapiens	45-50
27274280-4	2016	We next established forkhead box protein A1 (FOXA1) as the functional target of miR-23a, and silencing FOXA1 mimicked the effect of metformin.	Metformin	132-141	forkhead box A1	Homo sapiens	103-108
27274280-6	2016	In summary, we unraveled a novel AMPK/p53/miR-23a/FOXA1 axis in the regulation of apoptosis in HCC, and the application of metformin could, therefore, be effective in the treatment of HCC.	Metformin	123-132	forkhead box A1	Homo sapiens	50-55
27036040-8	2016	In Sawano cells and normal HEEs, a decrease of LSR induced by leptin and an increase of LSR induced by adiponectin and the drugs for type 2 diabetes metformin and berberine were observed via distinct signaling pathways including JAK2/STAT.	Metformin	149-158	lipolysis stimulated lipoprotein receptor	Homo sapiens	88-91
27036040-9	2016	In Sawano cells, metformin and berberine prevented cell migration and invasion induced by downregulation of LSR by the siRNA and leptin treatment.	Metformin	17-26	lipolysis stimulated lipoprotein receptor	Homo sapiens	108-111
27058422-0	2016	Metformin represses bladder cancer progression by inhibiting stem cell repopulation via COX2/PGE2/STAT3 axis.	Metformin	0-9	signal transducer and activator of transcription 3	Rattus norvegicus	98-103
27058422-5	2016	And also metformin represses bladder cancer CSC repopulation evidenced by reducing cytokeratin 14 (CK14+) and octamer-binding transcription factor 3/4 (OCT3/4+) cells in both animal and cellular models.	Metformin	9-18	solute carrier family 22 member 8	Rattus norvegicus	152-158
27058422-6	2016	More importantly, we found that metformin exerts these anticancer effects by inhibiting COX2, subsequently PGE2 as well as the activation of STAT3.	Metformin	32-41	signal transducer and activator of transcription 3	Rattus norvegicus	141-146
27058422-7	2016	In conclusion, we are the first to systemically demonstrate in both animal and cell models that metformin inhibits bladder cancer progression by inhibiting stem cell repopulation through the COX2/PGE2/STAT3 axis.	Metformin	96-105	signal transducer and activator of transcription 3	Rattus norvegicus	201-206
26854518-2	2016	SGLT-2 inhibitors may be prescribed alone or as add-on treatment in patients receiving metformin, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, and/or insulin across the natural history of the disease.	Metformin	87-96	solute carrier family 5 member 2	Homo sapiens	0-6
26258801-6	2016	Results of cellular and mitochondrial uptake showed that the metformin-SLNs were easier to uptake in cells and mitochondria than the pure drug group (that was the control group without SLN structure modification).	Metformin	61-70	sarcolipin	Homo sapiens	71-74
26669511-9	2016	In vitro data were corroborated by in vivo observations of significantly greater antitumor efficacy of metformin in xenograft mice bearing OCT3-overexpressing tumors versus low transporter-expressing wildtype tumors.	Metformin	103-112	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	139-143
26669511-10	2016	Collectively, these findings establish a clear relationship between cation-selective transporter expression, the AMPK-mTOR-pS6K signaling cascade, and the antiproliferative activity of metformin in breast cancer.	Metformin	185-194	ribosomal protein S6 kinase B1	Homo sapiens	123-127
26986571-6	2016	Metformin repressed E2-inducible estrogen response element (ERE) luciferase activity, protein levels and mRNA levels of E2/ERalpha-regulated genes [including c-Myc, cyclin D1, progesterone receptor (PR) and pS2] to a greater degree than tamoxifen, resulting in inhibition of cell proliferation of MCF-7, TR MCF-7 and MDA-MB-361 cells.	Metformin	0-9	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	158-163
26959881-0	2016	Metformin combined with sodium dichloroacetate promotes B leukemic cell death by suppressing anti-apoptotic protein Mcl-1.	Metformin	0-9	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	116-121
27040861-0	2016	Safety and efficacy of dipeptidyl peptidase-4 inhibitors vs sulfonylurea in metformin-based combination therapy for type 2 diabetes mellitus: Systematic review and meta-analysis.	Metformin	76-85	dipeptidyl peptidase 4	Homo sapiens	23-45
27040861-1	2016	PURPOSE: The purpose of this study was to compare the safety and efficacy of DPP-4 inhibitors versus sulfonylurea as adjunctive second-line therapy in patients with type 2 diabetes mellitus, inadequately controlled with metformin mono-therapy.	Metformin	220-229	dipeptidyl peptidase 4	Homo sapiens	77-82
26972495-13	2016	Treatment of cultured skeletal muscle cells with rutaecarpine (20-180 mumol/L) or metformin (20 mumol/L) promoted the phosphorylation of AMPK and ACC2, and increased glucose uptake.	Metformin	82-91	acetyl-CoA carboxylase beta	Rattus norvegicus	146-150
27079349-4	2016	We investigated improved survival, lower risks of recurrences, and lower, more stable levels of prostate-specific antigen (PSA) in patients with DM2 along with prostate cancer on metformin.	Metformin	179-188	kallikrein related peptidase 3	Homo sapiens	96-127
27079349-8	2016	The final PSA value was lower in the metformin-treated group with a result approaching significance (P = 0.067).	Metformin	37-46	kallikrein related peptidase 3	Homo sapiens	10-13
27079349-11	2016	Not only are PSA levels controlled for several years but also there are significantly fewer cancer recurrences in metformin-treated patients.	Metformin	114-123	kallikrein related peptidase 3	Homo sapiens	13-16
26752068-0	2016	Metformin inhibits the prometastatic effect of sorafenib in hepatocellular carcinoma by upregulating the expression of TIP30.	Metformin	0-9	HIV-1 Tat interactive protein 2	Homo sapiens	119-124
26752068-3	2016	This study evaluated whether the combination of sorafenib and metformin is sufficient to revert the expression of TIP30, thereby simultaneously reducing lung metastasis and improving survival.	Metformin	62-71	HIV-1 Tat interactive protein 2	Homo sapiens	114-119
26902691-7	2016	Metformin resulted in a significant reduction of IGF-1, IGF-1: IGFBP-3 molar ratio, insulin, FBG and HOMA-IR.	Metformin	0-9	insulin like growth factor binding protein 3	Homo sapiens	63-70
26902691-8	2016	On the other hand, metformin caused a significant increase of IGFBP-3.	Metformin	19-28	insulin like growth factor binding protein 3	Homo sapiens	62-69
25663310-0	2016	Autophagy and protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 alpha kinase (eIF2alpha) pathway protect ovarian cancer cells from metformin-induced apoptosis.	Metformin	172-181	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	14-66
25663310-0	2016	Autophagy and protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 alpha kinase (eIF2alpha) pathway protect ovarian cancer cells from metformin-induced apoptosis.	Metformin	172-181	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	68-72
25663310-4	2016	In this study, we observed that metformin-induced apoptosis was relieved by autophagy and the PERK/eIF2alpha pathway in ovarian cancer cells, but not in peripheral blood mononuclear cells (PBMC) or "normal" ovarian surface epithelial cells (OSE).	Metformin	32-41	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	94-98
25663310-7	2016	Interestingly, metformin induced interdependent activation between autophagy and the UPR, especially the PERK/eIF2alpha pathway.	Metformin	15-24	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	105-109
25663310-9	2016	Moreover, autophagy and PERK activation protected ovarian cancer cells against metformin-induced apoptosis.	Metformin	79-88	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	24-28
25663310-10	2016	Metformin treatment in the presence of inhibitors of PERK and autophagy, however, had no cytotoxic effects on OSE or PBMC.	Metformin	0-9	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	53-57
25663310-11	2016	In conclusion, these results suggest that inhibition of autophagy and PERK can enhance the selective anticancer effects of metformin on ovarian cancer cells.	Metformin	123-132	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	70-74
10794717-3	2000	The effects of chronic insulin treatment on glucose transport and GLUT4 trafficking were ameliorated by inclusion of metformin in the culture medium.	Metformin	117-126	solute carrier family 2 member 4	Rattus norvegicus	66-71
10513991-0	1999	Cellular and molecular mechanisms involved in insulin"s potentiation of glycogen synthase activity by metformin.	Metformin	102-111	insulin S homeolog	Xenopus laevis	46-53
27042132-0	2016	Sodium-glucose cotransporter-2 inhibitor combination therapy to optimize glycemic control and tolerability in patients with type 2 diabetes: focus on dapagliflozin-metformin.	Metformin	164-173	solute carrier family 5 member 2	Homo sapiens	0-30
27042132-3	2016	This review focuses on the combination of metformin with dapagliflozin, a member of the SGLT-2 inhibitor class of antidiabetes agents.	Metformin	42-51	solute carrier family 5 member 2	Homo sapiens	88-94
26681807-6	2016	Similarly, AMPK activation using genetic manipulation and low-dose metformin treatment protects mouse striatal cells expressing full-length mutant Htt (mHtt), counteracting their vulnerability to stress, with reduction of soluble mHtt levels by metformin and compensation of cytotoxicity by AMPKalpha1.	Metformin	67-76	huntingtin	Mus musculus	147-150
26681807-6	2016	Similarly, AMPK activation using genetic manipulation and low-dose metformin treatment protects mouse striatal cells expressing full-length mutant Htt (mHtt), counteracting their vulnerability to stress, with reduction of soluble mHtt levels by metformin and compensation of cytotoxicity by AMPKalpha1.	Metformin	67-76	huntingtin	Mus musculus	152-156
26681807-6	2016	Similarly, AMPK activation using genetic manipulation and low-dose metformin treatment protects mouse striatal cells expressing full-length mutant Htt (mHtt), counteracting their vulnerability to stress, with reduction of soluble mHtt levels by metformin and compensation of cytotoxicity by AMPKalpha1.	Metformin	67-76	huntingtin	Mus musculus	230-234
26681807-6	2016	Similarly, AMPK activation using genetic manipulation and low-dose metformin treatment protects mouse striatal cells expressing full-length mutant Htt (mHtt), counteracting their vulnerability to stress, with reduction of soluble mHtt levels by metformin and compensation of cytotoxicity by AMPKalpha1.	Metformin	245-254	huntingtin	Mus musculus	230-234
26943960-5	2016	Suppressed activation of mTOR and its downstream target, HIF-1alpha, likely mediated the protective effects of metformin.	Metformin	111-120	mechanistic target of rapamycin kinase	Mus musculus	25-29
26943960-5	2016	Suppressed activation of mTOR and its downstream target, HIF-1alpha, likely mediated the protective effects of metformin.	Metformin	111-120	hypoxia inducible factor 1, alpha subunit	Mus musculus	57-67
26963617-12	2016	In the SHR-CRP transgenic strain, we found that metformin treatment decreased circulating levels of inflammatory response marker IL-6, TNFalpha and MCP-1 while levels of human CRP remained unchanged.	Metformin	48-57	C-C motif chemokine ligand 2	Homo sapiens	148-153
26957312-11	2016	RESULTS: Our study demonstrated that metformin synergized with sorafenib reduced HIF-2alpha expression as examined by Western blot.	Metformin	37-46	endothelial PAS domain protein 1	Mus musculus	81-91
26957312-17	2016	CONCLUSIONS: Metformin may potentially enhance the effect of sorafenib to inhibit HCC recurrence and metastasis after liver resection by regulating the expression of HIF-2alpha and TIP30.	Metformin	13-22	endothelial PAS domain protein 1	Mus musculus	166-176
10513991-1	1999	By taking advantage of the Xenopus oocyte model, we recently confirmed the in vitro enhancing effect of metformin (MET) on glycogen synthase (GS) activity when induced by insulin (INS).	Metformin	104-113	insulin S homeolog	Xenopus laevis	171-178
10448935-0	1999	Metformin interaction with insulin-regulated glucose uptake, using the Xenopus laevis oocyte model expressing the mammalian transporter GLUT4.	Metformin	0-9	insulin S homeolog	Xenopus laevis	27-34
8879966-7	1996	A group of 30 diabetic patients were treated for 3 months with metformin, an antidiabetic biguanide compound which has been reported to reduce PAI-1 levels both in diabetic and in non-diabetic patients.	Metformin	63-72	serpin family E member 1	Homo sapiens	143-148
8879966-8	1996	Metformin significantly reduced PAI-1 AG and PAI-1 AT but did not influence plasma Lp(a) levels.	Metformin	0-9	serpin family E member 1	Homo sapiens	32-37
8879966-8	1996	Metformin significantly reduced PAI-1 AG and PAI-1 AT but did not influence plasma Lp(a) levels.	Metformin	0-9	serpin family E member 1	Homo sapiens	45-50
7846898-4	1994	Since plasma lipid values and plasminogen-activator-inhibitor (PAI-1) concentrations are also lowered under metformin therapy, it currently represents the treatment of choice for the obese group of type-2 diabetic patients.	Metformin	108-117	serpin family E member 1	Homo sapiens	63-68
1285699-7	1992	The preventive effect of low-dose vitamin K antagonists which reduce factor VII activity and the effect of metformin which counteracts insulin resistance and reduces PAI-1 concentrations, are at present under trial.	Metformin	107-116	serpin family E member 1	Homo sapiens	166-171
26761944-2	2016	To assess the impact of metformin and oral contraceptives (OC) on serum AMH levels in a cohort of adolescents with PCOS.	Metformin	24-33	anti-Mullerian hormone	Homo sapiens	72-75
26998043-5	2016	Therefore, the aim of the present study was to investigate the in vitro impact of metformin on cell viability and the expression levels of nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase (p22phox), a major enzyme in reactive oxygen species generation, and the three antioxidative enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) in monocytes/macrophages derived from 10 healthy volunteers.	Metformin	82-91	cytochrome b-245 alpha chain	Homo sapiens	200-207
26998043-10	2016	The results indicated that metformin, predominantly in LPS-pretreated monocytes/macrophages, reduced the expression levels of p22phox and increased those of SOD and GPx, but had only a minor effect on CAT levels.	Metformin	27-36	calcineurin like EF-hand protein 1	Homo sapiens	126-129
1916049-4	1991	Attempts to decrease insulin resistance such as fasting, diet, or administration of an oral anti-diabetic drug such as Metformin induced a parallel decrease in plasma insulin and plasminogen activator inhibitor 1 levels.	Metformin	119-128	serpin family E member 1	Homo sapiens	179-212
1713132-0	1991	Metformin causes a reduction in basal and post-venous occlusion plasminogen activator inhibitor-1 in type 2 diabetic patients.	Metformin	0-9	serpin family E member 1	Homo sapiens	64-97
1713132-3	1991	In the metformin-treated patients basal plasminogen activator inhibitor-1 antigen (PAI-1Ag) fell from 57.4 micrograms l-1 before treatment to 36.1 (p less than 0.05) and 41.0 micrograms l-1 (p less than 0.01) after 3 and 6 weeks therapy.	Metformin	7-16	serpin family E member 1	Homo sapiens	40-73
1936468-5	1991	Microinjection of pp60c-src kinase or treatment with metformin potentiates both the rate and the level of insulin-induced oocyte maturation.	Metformin	53-62	insulin S homeolog	Xenopus laevis	106-113
1936468-7	1991	It is concluded that annexins are substrates of the phosphorylation cascade initiated by insulin which is synergistic to the action of pp60c-src kinase and that this early phosphorylation events correlate well with the enhanced biological effect of insulin during metformin treatment.	Metformin	264-273	insulin S homeolog	Xenopus laevis	89-96
1936468-7	1991	It is concluded that annexins are substrates of the phosphorylation cascade initiated by insulin which is synergistic to the action of pp60c-src kinase and that this early phosphorylation events correlate well with the enhanced biological effect of insulin during metformin treatment.	Metformin	264-273	insulin S homeolog	Xenopus laevis	249-256
1936471-6	1991	Recent studies using assays specific for the components of the fibrinolytic system have shown that the effects of metformin are to cause a fall in plasma levels of the fibrinolytic inhibitor, plasminogen activator inhibitor-1 (PAI-1).	Metformin	114-123	serpin family E member 1	Homo sapiens	227-232
33773207-1	2021	BACKGROUND: Metformin (MET) may exert anti-rheumatic effects and reduce cartilage degradation through its immunomodulatory and anti-inflammatory actions.	Metformin	12-21	SAFB like transcription modulator	Homo sapiens	23-26
33973870-0	2021	The different hypoglycemic effects between East Asian and non-Asian type 2 diabetes patients when treated with SGLT-2 inhibitors as an add-on treatment for metformin: a systematic review and meta-analysis of randomized controlled trials.	Metformin	156-165	solute carrier family 5 member 2	Homo sapiens	111-117
33973870-1	2021	AIMS: To investigate the efficacy and safety of SGLT-2 inhibitors as an add-on treatment for metformin between Asian and non-Asian T2DM.	Metformin	93-102	solute carrier family 5 member 2	Homo sapiens	48-54
33973870-10	2021	CONCLUSION: SGLT-2 inhibitors as an add-on treatment for metformin are more efficacious in East Asian T2DM patients than in non-Asian T2DM patients without an additional risk of severe adverse events.	Metformin	57-66	solute carrier family 5 member 2	Homo sapiens	12-18
33779213-8	2021	Future studies of aspirin, statins, and metformin may better inform our recommendations for pharmacotherapy in primary CVD prevention among women who have had an APO.	Metformin	40-49	aminopeptidase O (putative)	Homo sapiens	162-165
33762564-0	2021	Retracted: Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway.	Metformin	34-43	cellular communication network factor 1	Homo sapiens	119-135
33762564-0	2021	Retracted: Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway.	Metformin	34-43	cellular communication network factor 1	Homo sapiens	137-142
33762564-2	2021	Reference: Fengli Zhang, Huixiao Chen, Jing Du, Bin Wang, Lixiao Yang: Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway.	Metformin	94-103	cellular communication network factor 1	Homo sapiens	179-195
33762564-2	2021	Reference: Fengli Zhang, Huixiao Chen, Jing Du, Bin Wang, Lixiao Yang: Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway.	Metformin	94-103	cellular communication network factor 1	Homo sapiens	197-202
34890997-11	2022	Metformin and fluoxetine also reduced IBA-1 and GFAP positive cells in the hippocampus.	Metformin	0-9	induction of brown adipocytes 1	Mus musculus	38-43
34890997-11	2022	Metformin and fluoxetine also reduced IBA-1 and GFAP positive cells in the hippocampus.	Metformin	0-9	glial fibrillary acidic protein	Mus musculus	48-52
34890997-12	2022	Moreover, metformin reduced the phospho-NF-kB, IL-1beta in the prefrontal cortex and iNOS levels in the hippocampus.	Metformin	10-19	interleukin 1 alpha	Mus musculus	47-55
34890997-15	2022	Lastly, metformin potentiated the effect of fluoxetine on neuroplasticity by increasing BDNF positive cells.	Metformin	8-17	brain derived neurotrophic factor	Mus musculus	88-92
34713937-0	2022	Metformin functionalized dendritic fibrous nanosilica (KCC-1-nPr-Met) as an innovative and green nanocatalyst for the efficient synthesis of tetrahydro-4H-chromene derivatives.	Metformin	0-9	solute carrier family 12 member 4	Homo sapiens	55-60
34713937-1	2022	An innovative nanocatalyst (KCC-1-nPr-Met) has been prepared from the covalent attachment of metformin on the channels and the pores of n-propyl amine functionalized dendritic fibrous nanosilica (DFNS) and used towards efficient, green, and high yield synthesis of tetrahydro-4H-chromenes derivatives by one-pot three-component reaction of aromatic aldehydes, malononitrile, and dimedone in H2 O-EtOH at room temperature.	Metformin	93-102	solute carrier family 12 member 4	Homo sapiens	28-33
34780856-9	2022	Circulating adiponectin and insulin levels were altered by metformin treatment in a sex-specific manner.	Metformin	59-68	adiponectin, C1Q and collagen domain containing	Mus musculus	12-23
34964193-2	2022	Metformin (MET) is a commonly used antidiabetic drug with multiple properties including antiproliferative activity, antioxidant potency, and is used in polycystic ovarian syndrome treatment.	Metformin	11-14	SAFB like transcription modulator	Homo sapiens	0-9
34955900-9	2021	Several other agents, including metformin and statins, have been found to induce antidiuresis and AQP2 upregulation through various V2R-independent pathways in animal experiments but are not associated with hyponatremia despite being frequently used clinically.	Metformin	32-41	aquaporin 2	Homo sapiens	98-102
34865304-14	2022	Metformin reduces the risk for eGWG and improves leptin sensitivity in pregnant women with PCOS.	Metformin	0-9	leptin	Homo sapiens	49-55
34629300-2	2021	Several retrospective studies suggested a decrease in Prostate Cancer incidence and mortality with metformin (MET).	Metformin	99-108	SAFB like transcription modulator	Homo sapiens	110-113
34569406-2	2021	In this investigation, the combination of cisplatin (CPT) and metformin (MET) to kill the HepG2 and caco-2 cells was developed into a new pH-responding magnetic nanocomposite based on reduced graphene oxide.	Metformin	62-71	SAFB like transcription modulator	Homo sapiens	73-76
34866061-4	2021	This case illustrates the in vivo effect of an SGLT2 inhibitor in a 30-year-old woman with MODY3 with poor glycaemic control despite the treatment with supramaximal doses of sulfonylurea and metformin.	Metformin	191-200	solute carrier family 5 member 2	Homo sapiens	47-52
34551339-8	2021	Metformin treated hUC-MSCs up-regulated the expression of osteogenic marker ALP, OCN and RUNX2, but down-regulated the expression of adipogenic markers PPARgamma and LPL.	Metformin	0-9	lipoprotein lipase	Homo sapiens	166-169
34432321-0	2021	Metformin suppresses IL-22 induced hepatocellular carcinoma by upregulating Hippo signaling pathway.	Metformin	0-9	interleukin 22	Mus musculus	21-26
34432321-6	2021	As expected, the expression of IL-22, an important factor involved in HCC progression, was markedly reduced by metformin.	Metformin	111-120	interleukin 22	Mus musculus	31-36
34432321-12	2021	CONCLUSIONS: Collectively, our findings illuminate a new regulatory mechanism, metformin activates Hippo signaling pathway to regulate IL-22 mediated HCC progression and provide new insights into its tumor-suppressive roles.	Metformin	79-88	interleukin 22	Mus musculus	135-140
34662551-10	2021	SIGNIFICANCE: Propranolol and L-D-ISOPROT like metformin can reduce insulin-resistance and cardiac remodeling in HFrHFD-fed mice, possibly by upregulating beta-arrestin2 signaling activity.	Metformin	47-56	arrestin, beta 2	Mus musculus	155-169
34570348-6	2021	In addition, metformin therapy significantly alleviated reactive microgliosis and astrogliosis in the corpus callosum, as measured by Iba-1 and GFAP staining.	Metformin	13-22	induction of brown adipocytes 1	Mus musculus	134-139
34881181-0	2021	Metformin Downregulates PD-L1 Expression in Esophageal Squamous Cell Catrcinoma by Inhibiting IL-6 Signaling Pathway.	Metformin	0-9	CD274 molecule	Homo sapiens	24-29
34881181-1	2021	Purpose: To characterize the mechanism by which metformin inhibits PD-L1 expression in esophageal squamous cell carcinoma (ESCC) and to evaluate the effect of metformin on the antitumor immune response.	Metformin	48-57	CD274 molecule	Homo sapiens	67-72
34881181-1	2021	Purpose: To characterize the mechanism by which metformin inhibits PD-L1 expression in esophageal squamous cell carcinoma (ESCC) and to evaluate the effect of metformin on the antitumor immune response.	Metformin	159-168	CD274 molecule	Homo sapiens	67-72
34881181-3	2021	Reverse transcription-quantitative polymerase chain reaction (RT-PCR), Western blotting and immunofluorescence were used to study the mechanism by which metformin affects PD-L1 expression.	Metformin	153-162	CD274 molecule	Homo sapiens	171-176
34881181-7	2021	PD-L1 expression in ESCC cell lines was significantly inhibited by metformin via the IL-6/JAK2/STAT3 signaling pathway but was not correlated with the canonical AMPK pathway.	Metformin	67-76	CD274 molecule	Homo sapiens	0-5
34825068-10	2021	Metformin treatment also found to modulate the expression of fat metabolizing and anti-inflammatory genes including PPAR--gamma, C/EBP-alpha, SREBP1c, FAS, AMPK and GLUT-4.	Metformin	0-9	CCAAT/enhancer binding protein alpha	Rattus norvegicus	129-140
34825068-10	2021	Metformin treatment also found to modulate the expression of fat metabolizing and anti-inflammatory genes including PPAR--gamma, C/EBP-alpha, SREBP1c, FAS, AMPK and GLUT-4.	Metformin	0-9	solute carrier family 2 member 4	Rattus norvegicus	165-171
34834341-1	2021	The mechanochemical synthesis of drug-drug solid forms containing metformin hydrochloride (MET HCl) and thiazide diuretics hydrochlorothiazide (HTZ) or chlorothiazide (CTZ) is reported.	Metformin	66-89	SAFB like transcription modulator	Homo sapiens	91-94
34738906-6	2021	The AMPK activators metformin or AICAR-two compounds that mimic fasting-elevate hepatic gluconeogenic gene expression dependent on in turn activation of the AMPK-TET1-SIRT1 axis.	Metformin	20-29	sirtuin 1	Mus musculus	167-172
34725961-0	2022	Metformin induces muscle atrophy by transcriptional regulation of myostatin via HDAC6 and FoxO3a.	Metformin	0-9	myostatin	Mus musculus	66-75
34725961-5	2022	METHODS: Myostatin expression was investigated at the protein and transcript levels after metformin administration.	Metformin	90-99	myostatin	Mus musculus	9-18
34725961-8	2022	RESULTS: Metformin induced the expression of myostatin, a key molecule that regulates muscle volume and triggers the phosphorylation of AMPK.	Metformin	9-18	myostatin	Mus musculus	45-54
34725961-9	2022	AMPK alpha2 knockdown in the background of metformin treatment reduced the myostatin expression of C2C12 myotubes (-49.86 +- 12.03%, P < 0.01) and resulted in increased myotube diameter compared with metformin (+46.62 +- 0.88%, P < 0.001).	Metformin	43-52	myostatin	Mus musculus	75-84
34725961-10	2022	Metformin induced the interaction between AMPK and FoxO3a, a key transcription factor of myostatin.	Metformin	0-9	myostatin	Mus musculus	89-98
34725961-14	2022	Chromatin immunoprecipitation revealed that metformin induced the binding of FoxO3a to the myostatin promoter.	Metformin	44-53	myostatin	Mus musculus	91-100
34725961-15	2022	The transcript-level expression of myostatin was higher in the gastrocnemius (GC) muscles of metformin-treated wild-type (WT) (+68.9 +- 10.01%, P < 0.001) and db/db mice (+55.84 +- 6.62%, P < 0.001) than that in the GC of controls (n = 4 per group).	Metformin	93-102	myostatin	Mus musculus	35-44
34725961-18	2022	CONCLUSIONS: Our results demonstrate that metformin treatment impairs muscle function through the regulation of myostatin in skeletal muscle cells via AMPK-FoxO3a-HDAC6 axis.	Metformin	42-51	myostatin	Mus musculus	112-121
34927008-7	2021	Metformin activates the LKB1/AMPK pathway to interact with several intracellular signaling pathways and molecular mechanisms.	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	24-28
34607979-6	2021	Accordingly, the p27 and p21 promoter activities were enhanced while Bcl-2 and IL-6 activities were significantly reduced by metformin treatment.	Metformin	125-134	H3 histone pseudogene 16	Homo sapiens	25-28
34607979-7	2021	Metformin diminished the phosphorylation of mTOR, p70S6K and 4E-BP1 by accelerating adenosine monophosphateactivated kinase (AMPK) in HeLa cancer cells, but it did not affect other cell lines.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	50-56
34607979-9	2021	Consistently, the overexpression of LKB1 in HeLa cancer cells prevented metformin-triggered apoptosis while LKB1 knockdown significantly increased apoptosis in HEC-1-A and KLE cancer cells.	Metformin	72-81	serine/threonine kinase 11	Homo sapiens	36-40
34607979-10	2021	Taken together, these findings indicate an underlying biological/physiological molecular function specifically for metformin-triggered apoptosis dependent on the presence of the LKB1 gene in tumorigenesis.	Metformin	115-124	serine/threonine kinase 11	Homo sapiens	178-182
34727651-11	2021	After metformin intervention, the expression of E-Cad was significantly increased, the expression levels of Vimentin and alpha-SMA were significantly decreased (P<0.05) .	Metformin	6-15	cadherin 1	Rattus norvegicus	48-53
34628484-9	2021	In addition, Metformin reversed mitophagy dysfunction and the over-expression of NLRP3.	Metformin	13-22	NLR family, pyrin domain containing 3	Mus musculus	81-86
34628484-10	2021	In vitro pretreatment of HK-2 cells with AMPK inhibitor compound C or Pink1 siRNA negated the beneficial effects of metformin.	Metformin	116-125	PTEN induced putative kinase 1	Mus musculus	70-75
34628484-11	2021	Furthermore, we noted that metformin activated p-AMPK and promoted the translocation of Pink1 from the cytoplasm to mitochondria, then promoted the occurrence of mitophagy in HK-2 cells under HG/HFA ambience.	Metformin	27-36	PTEN induced putative kinase 1	Mus musculus	88-93
34628484-12	2021	Our results suggested for the first time that AMPK agonist metformin ameliorated renal oxidative stress and tubulointerstitial fibrosis in HFD/STZ-induced diabetic mice via activating mitophagy through a p-AMPK-Pink1-Parkin pathway.	Metformin	59-68	PTEN induced putative kinase 1	Mus musculus	211-216
34676202-11	2021	In metformin-treated samples, the CEBPA, TP53 and USF1 transcription factors appeared to be involved in the regulation of several factors (SOD1, SOD2, CAT, GLRX, GSTP1) blocking ROS.	Metformin	3-12	upstream transcription factor 1	Homo sapiens	50-54
34676202-11	2021	In metformin-treated samples, the CEBPA, TP53 and USF1 transcription factors appeared to be involved in the regulation of several factors (SOD1, SOD2, CAT, GLRX, GSTP1) blocking ROS.	Metformin	3-12	glutathione S-transferase pi 1	Homo sapiens	162-167
34601503-0	2021	Metformin sensitises hepatocarcinoma cells to methotrexate by targeting dihydrofolate reductase.	Metformin	0-9	dihydrofolate reductase	Homo sapiens	72-95
34601503-3	2021	Herein, we report that metformin treatment increases the sensitivity of hepatocarcinoma cells to methotrexate (MTX) by suppressing the expression of the one-carbon metabolism enzyme DHFR.	Metformin	23-32	dihydrofolate reductase	Homo sapiens	182-186
34601503-5	2021	Mechanistically, metformin not only transcriptionally represses DHFR via E2F4 but also promotes lysosomal degradation of the DHFR protein.	Metformin	17-26	dihydrofolate reductase	Homo sapiens	64-68
34601503-5	2021	Mechanistically, metformin not only transcriptionally represses DHFR via E2F4 but also promotes lysosomal degradation of the DHFR protein.	Metformin	17-26	dihydrofolate reductase	Homo sapiens	125-129
34601503-7	2021	Taken together, our findings identify an important role for DHFR in the suppressive effects of metformin on therapeutic resistance, thus revealing a therapeutically targetable potential vulnerability in hepatocarcinoma.	Metformin	95-104	dihydrofolate reductase	Homo sapiens	60-64
34664819-7	2021	Treatment of the BC mice with metformin alone and in combination with cimetidine and/or ibuprofen enhanced the frequency of Th1 cells, and IFN-gamma concentration, while it resulted in a decrease in the frequency of Treg cells, serum TGF-beta concentration, and the expression of FOXP3 and TGF-beta compared with un-treated BC mice.	Metformin	30-39	transforming growth factor alpha	Mus musculus	234-242
34664819-7	2021	Treatment of the BC mice with metformin alone and in combination with cimetidine and/or ibuprofen enhanced the frequency of Th1 cells, and IFN-gamma concentration, while it resulted in a decrease in the frequency of Treg cells, serum TGF-beta concentration, and the expression of FOXP3 and TGF-beta compared with un-treated BC mice.	Metformin	30-39	forkhead box P3	Mus musculus	280-285
34664819-7	2021	Treatment of the BC mice with metformin alone and in combination with cimetidine and/or ibuprofen enhanced the frequency of Th1 cells, and IFN-gamma concentration, while it resulted in a decrease in the frequency of Treg cells, serum TGF-beta concentration, and the expression of FOXP3 and TGF-beta compared with un-treated BC mice.	Metformin	30-39	transforming growth factor alpha	Mus musculus	290-298
34664819-8	2021	FOXP3 expression in the metformin-treated group was lower in mice who received combination therapy.	Metformin	24-33	forkhead box P3	Mus musculus	0-5
34684418-7	2021	Maternal metformin increased MyoD expression but decreased Ppargc1a, Drp1 and Mfn2 expression in SM of adult male and female offspring.	Metformin	9-18	collapsin response mediator protein 1	Rattus norvegicus	69-73
34280460-0	2021	Metformin reduces oxandrolone- induced depression-like behavior in rats via modulating the expression of IL-1beta, IL-6, IL-10 and TNF-alpha.	Metformin	0-9	interleukin 10	Rattus norvegicus	121-126
34572149-8	2021	In addition, metformin, a potential inhibitor of TLR4, also decreased expression of COX-2 and IL-6 induced by co-incubation with IL-26 and palmitate.	Metformin	13-22	toll like receptor 4	Homo sapiens	49-53
34572586-0	2021	Dual Blockade of Lactate/GPR81 and PD-1/PD-L1 Pathways Enhances the Anti-Tumor Effects of Metformin.	Metformin	90-99	CD274 molecule	Homo sapiens	40-45
34572586-6	2021	In addition, considering that 3-OBA could recover the inhibitory effects of metformin on PD-1 expression, we further determined the dual blockade effects of PD-1/PD-L1 and lactate/GPR81 on the antitumor activity of metformin.	Metformin	76-85	CD274 molecule	Homo sapiens	162-167
34572586-6	2021	In addition, considering that 3-OBA could recover the inhibitory effects of metformin on PD-1 expression, we further determined the dual blockade effects of PD-1/PD-L1 and lactate/GPR81 on the antitumor activity of metformin.	Metformin	215-224	CD274 molecule	Homo sapiens	162-167
34116042-9	2021	High-dextrose and TM increased IRE1alpha and PERK phosphorylation and ATF6 and GRP78 expression, while treatment with metformin, liraglutide (a GLP-1 receptor agonist) and dapagliflozin (a SGLT-2 inhibitor), suppressed IRE1alpha and PERK phosphorylation as well as ATF6 and GRP78 expression.	Metformin	118-127	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	45-49
34116042-9	2021	High-dextrose and TM increased IRE1alpha and PERK phosphorylation and ATF6 and GRP78 expression, while treatment with metformin, liraglutide (a GLP-1 receptor agonist) and dapagliflozin (a SGLT-2 inhibitor), suppressed IRE1alpha and PERK phosphorylation as well as ATF6 and GRP78 expression.	Metformin	118-127	activating transcription factor 6	Homo sapiens	70-74
34116042-9	2021	High-dextrose and TM increased IRE1alpha and PERK phosphorylation and ATF6 and GRP78 expression, while treatment with metformin, liraglutide (a GLP-1 receptor agonist) and dapagliflozin (a SGLT-2 inhibitor), suppressed IRE1alpha and PERK phosphorylation as well as ATF6 and GRP78 expression.	Metformin	118-127	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	233-237
34116042-9	2021	High-dextrose and TM increased IRE1alpha and PERK phosphorylation and ATF6 and GRP78 expression, while treatment with metformin, liraglutide (a GLP-1 receptor agonist) and dapagliflozin (a SGLT-2 inhibitor), suppressed IRE1alpha and PERK phosphorylation as well as ATF6 and GRP78 expression.	Metformin	118-127	activating transcription factor 6	Homo sapiens	265-269
34572545-2	2021	In this study, using cellulose acetate (CA) as a biomacromolecular matrix, core-sheath nanofibers were developed for providing a sustained release of a model drug-metformin hydrochloride (MET).	Metformin	163-186	SAFB like transcription modulator	Homo sapiens	188-191
34540601-11	2021	In the multivariate analysis, independent risk factors for metformin-associated VitB12 deficiency in patients with tbl2DM include high daily dose of metformin >2000 mg, male gender, high BMI, smoking, sulfonylurea, dipeptidyl peptidase-4 inhibitor, H2 blockers/PPI, low fasting blood glucose, and low hemoglobin.	Metformin	59-68	dipeptidyl peptidase 4	Homo sapiens	215-237
34502566-6	2021	ASP+ uptake was inhibited by tetraethylammonium (TEA+), tetrapentylammonium (TPA+), metformin and baricitinib both in the hOCT2-HEK cells and the hOCT2- MDCK cysts, even though the apparent affinities of TEA+ and baricitinib were dependent on the expression system.	Metformin	84-93	solute carrier family 22 member 2	Homo sapiens	122-127
34298100-1	2021	The objective of this work was to investigate the effect of microfluidics on the quality attributes of metformin hydrochloride-loaded poly lactic-co-glycolic acid polymeric particles (MFH-PLGA PPs) when compared to a traditional double emulsion batch method.	Metformin	103-126	forkhead box P1	Homo sapiens	184-187
27042415-0	2016	Effects of gliclazide add on metformin on serum omentin-1 levels in patients with type 2 diabetes mellitus.	Metformin	29-38	intelectin 1	Homo sapiens	48-55
27042415-3	2016	AIM OF THE STUDY: To investigate the influence of metformin alone or in combination with gliclazide on the level of serum omentin among patients with type 2 diabetes mellitus (T2DM).	Metformin	50-59	intelectin 1	Homo sapiens	122-129
26847819-0	2016	Metformin inhibits growth of human non-small cell lung cancer cells via liver kinase B-1-independent activation of adenosine monophosphate-activated protein kinase.	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	72-88
26847819-1	2016	Metformin, the most widely administered oral anti-diabetic therapeutic agent, exerts its glucose-lowering effect predominantly via liver kinase B1 (LKB1)-dependent activation of adenosine monophosphate-activated protein kinase (AMPK).	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	131-146
26847819-1	2016	Metformin, the most widely administered oral anti-diabetic therapeutic agent, exerts its glucose-lowering effect predominantly via liver kinase B1 (LKB1)-dependent activation of adenosine monophosphate-activated protein kinase (AMPK).	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	148-152
26847819-3	2016	However, whether the antitumor effect of metformin is via the LKB1/AMPK signaling pathway remains to be determined.	Metformin	41-50	serine/threonine kinase 11	Homo sapiens	62-66
26847819-11	2016	These results provide evidence that the growth inhibition of metformin in NSCLC cells is mediated by LKB1-independent activation of AMPK, indicating that metformin may be a potential therapeutic agent for the treatment of human NSCLC.	Metformin	61-70	serine/threonine kinase 11	Homo sapiens	101-105
26847819-11	2016	These results provide evidence that the growth inhibition of metformin in NSCLC cells is mediated by LKB1-independent activation of AMPK, indicating that metformin may be a potential therapeutic agent for the treatment of human NSCLC.	Metformin	154-163	serine/threonine kinase 11	Homo sapiens	101-105
26921394-4	2016	Metformin significantly improved survival, reduced urinary tract obstruction, reduced bladder weight (a surrogate for tumor volume), and led to clear activation of AMP alpha kinase and inhibition of mTOR signaling in neoplastic tissue.	Metformin	0-9	mechanistic target of rapamycin kinase	Mus musculus	199-203
26911584-4	2016	ELIGIBILITY CRITERIA: Randomised controlled trials assessing the efficacy of SGLT-2 inhibitors in patients with type 2 diabetes inadequately controlled with diet and exercise alone or metformin monotherapy.	Metformin	184-193	solute carrier family 5 member 2	Homo sapiens	77-83
26896068-9	2016	Moreover, metformin enhanced the anti-inflammatory effect of 5-ASA by decreasing the gene expression of IL-1beta, IL-6, COX-2 and TNF-alpha and its receptors; TNF-R1 and TNF-R2.	Metformin	10-19	TNF receptor superfamily member 1A	Homo sapiens	159-165
26858121-0	2016	Metformin promotes tau aggregation and exacerbates abnormal behavior in a mouse model of tauopathy.	Metformin	0-9	microtubule associated protein tau	Homo sapiens	19-22
26858121-6	2016	RESULTS: Here, we report that in the P301S mutant human tau (P301S) transgenic mouse model of tauopathy, chronic administration of metformin exerts paradoxical effects on tau pathology.	Metformin	131-140	microtubule associated protein tau	Homo sapiens	56-59
26858121-6	2016	RESULTS: Here, we report that in the P301S mutant human tau (P301S) transgenic mouse model of tauopathy, chronic administration of metformin exerts paradoxical effects on tau pathology.	Metformin	131-140	microtubule associated protein tau	Homo sapiens	94-97
26858121-7	2016	Despite reducing tau phosphorylation in the cortex and hippocampus via AMPK/mTOR and PP2A, metformin increases insoluble tau species (including tau oligomers) and the number of inclusions with beta-sheet aggregates in the brain of P301S mice.	Metformin	91-100	microtubule associated protein tau	Homo sapiens	121-124
26858121-7	2016	Despite reducing tau phosphorylation in the cortex and hippocampus via AMPK/mTOR and PP2A, metformin increases insoluble tau species (including tau oligomers) and the number of inclusions with beta-sheet aggregates in the brain of P301S mice.	Metformin	91-100	microtubule associated protein tau	Homo sapiens	121-124
26858121-8	2016	In addition, metformin exacerbates hindlimb atrophy, increases P301S hyperactive behavior, induces tau cleavage by caspase 3 and disrupts synaptic structures.	Metformin	13-22	microtubule associated protein tau	Homo sapiens	99-102
29931872-3	2016	RESULTS: Compared with that in the model group, SOD and GPX activities were significantly increased and levels of BNP cTnI cardiac weight index (CWI) apoptosis index (AI) were decreased in TTM and metformin (Met) group.	Metformin	197-206	troponin I3, cardiac type	Rattus norvegicus	118-122
26956973-7	2016	We observed that metformin decreased c-Myc levels, and ectopic expression of c-Myc blocked the effect of metformin on TTP expression and cell proliferation.	Metformin	17-26	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	37-42
26956973-7	2016	We observed that metformin decreased c-Myc levels, and ectopic expression of c-Myc blocked the effect of metformin on TTP expression and cell proliferation.	Metformin	105-114	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	77-82
26956973-8	2016	Our data indicate that metformin induces TTP expression by reducing the expression of c-Myc, suggesting a new model whereby TTP acts as a mediator of metformin"s anti-proliferative activity in cancer cells.	Metformin	23-32	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	86-91
26956973-8	2016	Our data indicate that metformin induces TTP expression by reducing the expression of c-Myc, suggesting a new model whereby TTP acts as a mediator of metformin"s anti-proliferative activity in cancer cells.	Metformin	150-159	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	86-91
26740120-5	2016	Metformin influences various cellular pathways, including activation of the LKB1/AMPK pathway, inhibition of cell division, promotion of apoptosis and autophagy, down-regulation of circulating insulin, and activation of the immune system.	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	76-80
26631545-5	2016	FOS expression levels increased in the paraventricular nucleus, area postrema, and central amygdala of mice administered an acute single dose of metformin (SM group) compared to the control mice.	Metformin	145-154	FBJ osteosarcoma oncogene	Mus musculus	0-3
26631545-8	2016	The FOS expression levels decreased in the ventromedial hypothalamic nucleus in the PF group, but not the RM group, compared to the control group, suggesting a potential hypothalamic area involvement for metformin-induced anorexia.	Metformin	204-213	FBJ osteosarcoma oncogene	Mus musculus	4-7
26529121-6	2016	We then revealed that metformin impedes Wnt axis, a major signaling pathway active during NC formation via DVL-3 inhibition and impairment in nuclear translocation of beta-catenin.	Metformin	22-31	catenin beta 1	Homo sapiens	167-179
26529121-8	2016	Further studies involving loss and gain of function confirmed that NCC specifiers like Sox-1 and Sox-9 are direct targets of miR-200 and miR-145, respectively and that they are essentially modulated by metformin.	Metformin	202-211	microRNA 145	Homo sapiens	137-144
26529121-10	2016	Given that metformin is a widely used drug, for the first time we demonstrate that it can induce a delayed onset of developmental EMT during NC formation by interfering with canonical Wnt signaling and mysregulation of miR-145 and miR-200.	Metformin	11-20	microRNA 145	Homo sapiens	219-226
25913633-5	2016	In contrast, metformin has a positive effect on osteoblast differentiation due to increased activity of Runx2 via the AMPK/USF-1/SHP regulatory cascade resulting in a neutral or potentially protective effect on bone.	Metformin	13-22	upstream transcription factor 1	Homo sapiens	123-128
27889750-0	2016	Metformin Protects Neurons against Oxygen-Glucose Deprivation/Reoxygenation -Induced Injury by Down-Regulating MAD2B.	Metformin	0-9	mitotic arrest deficient 2 like 2	Homo sapiens	111-116
27889750-4	2016	The present study investigated whether metformin modifies the expression of MAD2B and to exert its neuroprotective effects in primary cultured cortical neurons during oxygen-glucose deprivation/reoxygenation (OGD/R), a widely used in vitro model of ischemia/reperfusion.	Metformin	39-48	mitotic arrest deficient 2 like 2	Homo sapiens	76-81
27889750-12	2016	Metformin further decreased the expression of MAD2B, cyclin B1 and phosphorylation levels of histone 3.	Metformin	0-9	mitotic arrest deficient 2 like 2	Homo sapiens	46-51
27889750-12	2016	Metformin further decreased the expression of MAD2B, cyclin B1 and phosphorylation levels of histone 3.	Metformin	0-9	cyclin B1	Homo sapiens	53-62
27889750-13	2016	CONCLUSION: Metformin exerts its neuroprotective effect through regulating the expression of MAD2B in neurons under OGD/R.	Metformin	12-21	mitotic arrest deficient 2 like 2	Homo sapiens	93-98
27633039-0	2016	Relationships Between Metformin, Paraoxonase-1 and the Chemokine (C-C Motif) Ligand 2.	Metformin	22-31	C-C motif chemokine ligand 2	Homo sapiens	55-85
26288997-6	2016	Results of cellular and mitochondrial uptake showed that the metformin-SLNs were easier to uptake in cells and mitochondria than the pure drug group (that was the control group without SLN structure modification).	Metformin	61-70	sarcolipin	Homo sapiens	71-74
27386433-0	2016	Impact of ATM and SLC22A1 Polymorphisms on Therapeutic Response to Metformin in Iranian Diabetic Patients.	Metformin	67-76	ATM serine/threonine kinase	Homo sapiens	10-13
34480113-8	2021	Using co-immunofluorescence of IBa-1 and MBP, and luxol fasting blue (LFB) staining, we demonstrated that metformin promoted the transformation of M1 to M2 phenotype polarization of microglial cells, then greatly facilitated myelin debris clearance and protected the myelin in SCI rats.	Metformin	106-115	allograft inflammatory factor 1	Rattus norvegicus	31-36
34557403-11	2021	Finally, we showed that metformin can induce cell death in BL cells by stressing cellular metabolism through the induction of GLUT1, PKM2, and LDHA.	Metformin	24-33	pyruvate kinase M1/2	Homo sapiens	133-137
34398301-8	2022	Flow cytometric analysis demonstrated that the balance of M1/M2-polarized or phospho-Stat3-positive macrophages, regulatory T, cytotoxic T, natural killer (NK), NK T cells, and Th17 T cells was dynamically changed at each stage of the disease and were resolved by metformin treatment.	Metformin	264-273	signal transducer and activator of transcription 3	Rattus norvegicus	85-90
27294149-0	2016	Metformin Protects H9C2 Cardiomyocytes from High-Glucose and Hypoxia/Reoxygenation Injury via Inhibition of Reactive Oxygen Species Generation and Inflammatory Responses: Role of AMPK and JNK.	Metformin	0-9	mitogen-activated protein kinase 8	Rattus norvegicus	188-191
27294149-5	2016	We further elucidated molecular mechanisms underlying metformin-induced cytoprotection, especially the possible involvement of AMP-activated protein kinase (AMPK) and Jun NH(2)-terminal kinase (JNK).	Metformin	54-63	mitogen-activated protein kinase 8	Rattus norvegicus	167-192
27294149-5	2016	We further elucidated molecular mechanisms underlying metformin-induced cytoprotection, especially the possible involvement of AMP-activated protein kinase (AMPK) and Jun NH(2)-terminal kinase (JNK).	Metformin	54-63	mitogen-activated protein kinase 8	Rattus norvegicus	194-197
27294149-8	2016	Metformin enhanced phosphorylation level of AMPK and suppressed HG + H/R induced JNK activation.	Metformin	0-9	mitogen-activated protein kinase 8	Rattus norvegicus	81-84
27294149-9	2016	Inhibitor of AMPK (compound C) or activator of JNK (anisomycin) abolished the cytoprotective effects of metformin.	Metformin	104-113	mitogen-activated protein kinase 8	Rattus norvegicus	47-50
27294149-10	2016	In conclusion, our study demonstrated for the first time that metformin possessed direct cytoprotective effects against HG and H/R injury in cardiac cells via signaling mechanisms involving activation of AMPK and concomitant inhibition of JNK.	Metformin	62-71	mitogen-activated protein kinase 8	Rattus norvegicus	239-242
27882332-2	2016	Our aim was to define the conditions that affect therapeutic success when dipeptidyl peptidase-4 (DPP-4) inhibitor is added to metformin monotherapy.	Metformin	127-136	dipeptidyl peptidase 4	Homo sapiens	74-96
27882332-2	2016	Our aim was to define the conditions that affect therapeutic success when dipeptidyl peptidase-4 (DPP-4) inhibitor is added to metformin monotherapy.	Metformin	127-136	dipeptidyl peptidase 4	Homo sapiens	98-103
27882332-7	2016	Patients who added DPP-4 inhibitor to metformin monotherapy had significant weight loss (P = 0.004) and FBG and HbA1c levels were significantly lowered during the first 6 months (both P &lt; 0.001).	Metformin	38-47	dipeptidyl peptidase 4	Homo sapiens	19-24
27882332-11	2016	Our study demonstrates that in patients having inadequate glycemic control, the addition of a DPP-4 inhibitor as a second oral agent to metformin monotherapy provides better glycemic control, protects beta-cell reserves, and does not cause weight gain.	Metformin	136-145	dipeptidyl peptidase 4	Homo sapiens	94-99
26467186-8	2015	The 3-h exposure of MMECs to metformin significantly (P&lt;0.05) reversed the HG-induced reduction in phosphorylation of both eNOS and Akt; however, no changes were detected for phosphorylation of AMPK or the expression of SIRT1.	Metformin	29-38	nitric oxide synthase 3, endothelial cell	Mus musculus	126-130
26467186-8	2015	The 3-h exposure of MMECs to metformin significantly (P&lt;0.05) reversed the HG-induced reduction in phosphorylation of both eNOS and Akt; however, no changes were detected for phosphorylation of AMPK or the expression of SIRT1.	Metformin	29-38	sirtuin 1	Mus musculus	223-228
26467186-9	2015	Our data indicate that a 3-h exposure to metformin can reverse/reduce the impact of HG on endothelial function, via mechanisms linked to increased phosphorylation of eNOS and Akt.	Metformin	41-50	nitric oxide synthase 3, endothelial cell	Mus musculus	166-170
26304716-4	2015	Mechanistically, metformin caused abrogation of the G2 checkpoint and increase of mitotic catastrophe, associated with suppression of Wee1 kinase and in turn CDK1 Tyr15 phosphorylation.	Metformin	17-26	cyclin dependent kinase 1	Homo sapiens	158-162
26304716-6	2015	Finally, metformin-mediated AMPK/mTOR/p70S6K was identified as a possible upstream pathway controlling translational regulation of Wee1 and Rad51.	Metformin	9-18	ribosomal protein S6 kinase B1	Homo sapiens	38-44
26867302-2	2015	Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are more and more prominent medications in the management of type 2 diabetes (T2D), with five molecules commercialized and as many fixed-dose combinations with metformin.	Metformin	213-222	dipeptidyl peptidase 4	Homo sapiens	0-22
26867302-2	2015	Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are more and more prominent medications in the management of type 2 diabetes (T2D), with five molecules commercialized and as many fixed-dose combinations with metformin.	Metformin	213-222	dipeptidyl peptidase 4	Homo sapiens	24-29
26164004-7	2015	Consistent with this, the positive rates of CD90, CD133, and stage-specific embryonic antigen-4 (SSEA-4) were all observed with reductions in response to metformin exposure.	Metformin	154-163	Thy-1 cell surface antigen	Homo sapiens	44-48
26885449-4	2015	We found that metformin suppressed HSY cell growth in vitro in a time and dose dependent manner associated with a reduced expression of MYC onco-protein, and the same inhibitory effect of metformin was also confirmed in HSG cells.	Metformin	14-23	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	136-139
26885449-5	2015	In association with the reduction of MYC onco-protein, metformin significantly restored p53 tumor suppressor gene expression.	Metformin	55-64	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	37-40
26885449-6	2015	The distinctive effects of metformin and PP242 on MYC reduction and P53 restoration suggested that metformin inhibited cell growth through a different pathway from PP242 in salivary carcinoma cells.	Metformin	99-108	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	50-53
26576639-8	2015	Treatment with metformin markedly suppressed PKM2 and SDC2 expression at both the transcriptional and posttranscriptional levels and inhibited HC cell proliferation and tumor growth.	Metformin	15-24	pyruvate kinase M1/2	Homo sapiens	45-49
26576639-10	2015	Inhibition of PKM2 and SDC2 expression contributes to the therapeutic effect of metformin on HC.	Metformin	80-89	pyruvate kinase M1/2	Homo sapiens	14-18
26548416-8	2015	By suppressing SRC-2 at the transcriptional level, metformin impeded recruitment of SRC-2 and RNA polymerase II to the G6Pc promoter and to SREs of mutual SRC-2/SREBP-1 target gene promoters.	Metformin	51-60	glucose-6-phosphatase catalytic subunit 1	Rattus norvegicus	119-123
34489707-9	2021	Interestingly, empagliflozin/metformin combination significantly enhanced AMPK phosphorylation and depressed mTOR and NLRP3 expression leading to a subsequent reduction in caspase-1 cleavage and inhibition of several inflammatory cytokines, including IL-1beta, and IL-18.	Metformin	29-38	interleukin 18	Rattus norvegicus	265-270
34440221-9	2021	Treatment with metformin, alendronate, or their combination inhibited the expression of RANK and RANKL on osteoblasts and osteoclasts obtained by ex vivo cultivation of bone marrow cells in mineralization or osteoclastogenic media.	Metformin	15-24	tumor necrosis factor (ligand) superfamily, member 11	Mus musculus	97-102
26457538-0	2015	Effects on Clinical Outcomes of Adding Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas to Metformin Therapy in Patients With Type 2 Diabetes Mellitus.	Metformin	97-106	dipeptidyl peptidase 4	Homo sapiens	39-61
26457538-13	2015	CONCLUSION: Compared with sulfonylureas, DPP-4 inhibitors were associated with lower risks for all-cause death, MACEs, ischemic stroke, and hypoglycemia when used as add-ons to metformin therapy.	Metformin	177-186	dipeptidyl peptidase 4	Homo sapiens	41-46
25990477-5	2015	RESULTS: Vascular permeability, VEGF and COX-2 expressions were reduced in animals treated with MI and/or metformin.	Metformin	106-115	vascular endothelial growth factor A	Rattus norvegicus	32-36
26344902-9	2015	To understand this more, we show activation of AMPK by metformin also prevented palmitate-induced changes in the phosphorylations of raptor and p70S6K, confirming that the mTORC1/p70S6K signaling pathway is responsive to AMPK activity.	Metformin	55-64	ribosomal protein S6 kinase B1	Homo sapiens	144-150
26344902-9	2015	To understand this more, we show activation of AMPK by metformin also prevented palmitate-induced changes in the phosphorylations of raptor and p70S6K, confirming that the mTORC1/p70S6K signaling pathway is responsive to AMPK activity.	Metformin	55-64	ribosomal protein S6 kinase B1	Homo sapiens	179-185
26492952-5	2015	Mechanistically, metformin significantly protected against testosterone-induced elevation of estrogen receptor-alpha (ER-alpha) and decrease of estrogen receptor-beta (ER-beta) expression, with no significant effect of androgen receptor (AR) and 5alpha-reductase expression.	Metformin	17-26	estrogen receptor 1	Rattus norvegicus	118-126
26492952-5	2015	Mechanistically, metformin significantly protected against testosterone-induced elevation of estrogen receptor-alpha (ER-alpha) and decrease of estrogen receptor-beta (ER-beta) expression, with no significant effect of androgen receptor (AR) and 5alpha-reductase expression.	Metformin	17-26	estrogen receptor 2	Rattus norvegicus	144-166
26492952-5	2015	Mechanistically, metformin significantly protected against testosterone-induced elevation of estrogen receptor-alpha (ER-alpha) and decrease of estrogen receptor-beta (ER-beta) expression, with no significant effect of androgen receptor (AR) and 5alpha-reductase expression.	Metformin	17-26	estrogen receptor 2	Rattus norvegicus	168-175
26473366-7	2015	Metformin treatment was associated with significantly elevated serum adiponectin concentrations (standard mean differences [95% confidence interval], -0.43 [-0.75 to -0.11]) and decreased serum leptin concentrations (0.65 [0.26 to 1.04]), whereas no significant difference in resistin level (-0.01 [-0.49 to 0.45]) or visfatin level (-0.04 [-1.55 to 1.46]) was found.	Metformin	0-9	resistin	Homo sapiens	276-284
34440221-12	2021	Treatment with metformin, alendronate, and their combination decreased serum concentrations of leptin and resistin in the chronic phase of arthritis.	Metformin	15-24	leptin	Mus musculus	95-101
34484112-2	2021	This study assessed the economic outcomes of different DPP-4 inhibitors in patients with T2DM inadequately controlled with metformin in the Chinese context.	Metformin	123-132	dipeptidyl peptidase 4	Homo sapiens	55-60
34484117-7	2021	Decreased FSHR expression and increased LHCGR expression were observed in F1 female rats of the PCOS-IR and PCOS-IR+Metformin groups, suggesting that FSHR and LHCGR dysfunction might promote the development of PCOS.	Metformin	116-125	follicle stimulating hormone receptor	Rattus norvegicus	10-14
34484117-7	2021	Decreased FSHR expression and increased LHCGR expression were observed in F1 female rats of the PCOS-IR and PCOS-IR+Metformin groups, suggesting that FSHR and LHCGR dysfunction might promote the development of PCOS.	Metformin	116-125	follicle stimulating hormone receptor	Rattus norvegicus	150-154
34434111-7	2021	Besides, metformin increased the expression levels of phosphorylated adenosine 5"-monophosphate (AMP)-activated protein kinase (p-AMPK), microtubule-associated protein (MAP) light chain 3B (LC3B) and Beclin1 proteins, and reduced levels of phosphorylated mammalian target of rapamycin (p-mTOR) and p62 proteins in vivo and in vitro.	Metformin	9-18	regulator of microtubule dynamics 1	Homo sapiens	137-167
34434111-7	2021	Besides, metformin increased the expression levels of phosphorylated adenosine 5"-monophosphate (AMP)-activated protein kinase (p-AMPK), microtubule-associated protein (MAP) light chain 3B (LC3B) and Beclin1 proteins, and reduced levels of phosphorylated mammalian target of rapamycin (p-mTOR) and p62 proteins in vivo and in vitro.	Metformin	9-18	regulator of microtubule dynamics 1	Homo sapiens	169-172
34439169-3	2021	In vitro competitive binding assays with human recombinant SHMT1 and SHMT2 isoforms revealed that metformin preferentially inhibits SHMT2 activity by a non-catalytic mechanism.	Metformin	98-107	serine hydroxymethyltransferase 1	Homo sapiens	59-64
34439169-6	2021	CRISPR/Cas9-based disruption of SHMT2, but not of SHMT1, prevented metformin from inhibiting total SHMT activity in cancer cell lines.	Metformin	67-76	serine hydroxymethyltransferase 1	Homo sapiens	99-103
34441802-10	2021	Diabetes patients given metformin had a significantly reduced risk of mortality (RR, 0.65; 95% CI: 0.54-0.80, p < 0.001, heterogeneity I2 = 75.88, Q = 62.20, and tau2 = 0.06, p < 0.001) compared with those who were not given metformin.	Metformin	24-33	microtubule associated protein tau	Homo sapiens	162-165
34129225-8	2021	The expression of COL3A1 and RELA/p65 were upregulated (P < 0.01 for COL3A1), and percentage of late apoptotic cells increased significantly by HG without metformin (P < 0.001) while it decreased in two concentrations of metformin dramatically compared with 5.5 mM glucose (P < 0.01 for expressions and < 0.001 for apoptosis).	Metformin	155-164	collagen type III alpha 1 chain	Homo sapiens	18-24
34129225-8	2021	The expression of COL3A1 and RELA/p65 were upregulated (P < 0.01 for COL3A1), and percentage of late apoptotic cells increased significantly by HG without metformin (P < 0.001) while it decreased in two concentrations of metformin dramatically compared with 5.5 mM glucose (P < 0.01 for expressions and < 0.001 for apoptosis).	Metformin	221-230	collagen type III alpha 1 chain	Homo sapiens	18-24
34129225-8	2021	The expression of COL3A1 and RELA/p65 were upregulated (P < 0.01 for COL3A1), and percentage of late apoptotic cells increased significantly by HG without metformin (P < 0.001) while it decreased in two concentrations of metformin dramatically compared with 5.5 mM glucose (P < 0.01 for expressions and < 0.001 for apoptosis).	Metformin	221-230	collagen type III alpha 1 chain	Homo sapiens	69-75
34129225-9	2021	Metformin not only significantly downregulated RELA/p65 expression, but also inhibited the apoptosis of HDFs from aged human skin at toxic glucose concentrations which could be inversely mediated via COL1A1 and COL3A1 expression.	Metformin	0-9	collagen type III alpha 1 chain	Homo sapiens	211-217
34180939-2	2021	Objective: To evaluate the comparative effectiveness of SGLT2 inhibitors and sulfonylureas associated with the risk of all-cause mortality among patients with type 2 diabetes using metformin.	Metformin	181-190	solute carrier family 5 member 2	Homo sapiens	56-61
34180939-14	2021	In additional per-protocol analyses, continued use of SGLT2 inhibitors with metformin was associated with a reduced risk of death compared with SGLT2 inhibitor treatment without metformin (HR, 0.70; 95% CI, 0.50-0.97; event rate difference, -7.62; 95% CI, -17.12 to -0.48 deaths per 1000 person-years).	Metformin	76-85	solute carrier family 5 member 2	Homo sapiens	54-59
34180939-15	2021	Conclusions and Relevance: In this comparative effectiveness study analyzing data from the US Department of Veterans Affairs, among patients with type 2 diabetes receiving metformin therapy, SGLT2 inhibitor treatment was associated with a reduced risk of all-cause mortality compared with sulfonylureas.	Metformin	172-181	solute carrier family 5 member 2	Homo sapiens	191-196
34302119-0	2021	Correction: Repurposing dextromethorphan and metformin for treating nicotine-induced cancer by directly targeting CHRNA7 to inhibit JAK2/STAT3/SOX2 signaling.	Metformin	45-54	cholinergic receptor nicotinic alpha 7 subunit	Homo sapiens	114-120
34230443-0	2021	Metformin, valproic acid, and starvation induce seizures in a patient with partial SLC13A5 deficiency: A case of pharmaco-synergistic heterozygosity: Erratum.	Metformin	0-9	solute carrier family 13 member 5	Homo sapiens	83-90
34354368-14	2021	Notably, six hub genes (STAT1, IFIT3, RSAD2, ISG15, IFI44, IFI6) were down-regulated in cells exposed to both metformin and Mycobacterium tuberculosis antigens.	Metformin	110-119	interferon induced protein with tetratricopeptide repeats 3	Homo sapiens	31-36
34354368-14	2021	Notably, six hub genes (STAT1, IFIT3, RSAD2, ISG15, IFI44, IFI6) were down-regulated in cells exposed to both metformin and Mycobacterium tuberculosis antigens.	Metformin	110-119	interferon alpha inducible protein 6	Homo sapiens	59-63
34440108-0	2021	Metformin Therapy Effects on the Expression of Sodium-Glucose Cotransporter 2, Leptin, and SIRT6 Levels in Pericoronary Fat Excised from Pre-Diabetic Patients with Acute Myocardial Infarction.	Metformin	0-9	solute carrier family 5 member 2	Homo sapiens	47-77
34440108-0	2021	Metformin Therapy Effects on the Expression of Sodium-Glucose Cotransporter 2, Leptin, and SIRT6 Levels in Pericoronary Fat Excised from Pre-Diabetic Patients with Acute Myocardial Infarction.	Metformin	0-9	leptin	Homo sapiens	79-85
34440108-11	2021	PDM never-metformin-users showed higher SGLT2 and leptin levels in pericoronary fat than current-metformin-users (p < 0.05).	Metformin	10-19	solute carrier family 5 member 2	Homo sapiens	40-45
34440108-11	2021	PDM never-metformin-users showed higher SGLT2 and leptin levels in pericoronary fat than current-metformin-users (p < 0.05).	Metformin	10-19	leptin	Homo sapiens	50-56
34440108-12	2021	CONCLUSIONS: metformin therapy might ameliorate cardiovascular outcomes by reducing inflammatory parameters, SGLT2, and leptin levels, and finally improving SIRT6 levels in AMI-PDM patients treated with CABG.	Metformin	13-22	solute carrier family 5 member 2	Homo sapiens	109-114
34440108-12	2021	CONCLUSIONS: metformin therapy might ameliorate cardiovascular outcomes by reducing inflammatory parameters, SGLT2, and leptin levels, and finally improving SIRT6 levels in AMI-PDM patients treated with CABG.	Metformin	13-22	leptin	Homo sapiens	120-126
34360870-4	2021	Half the obese dams were treated orally with 300 mg/kg/d of metformin (Ob-Met) during pregnancy.	Metformin	60-69	leptin	Mus musculus	71-73
34368369-1	2021	Objective: To investigate if PP2A plays a role in metformin-induced insulin sensitivity improvement in human skeletal muscle cells.	Metformin	50-59	protein phosphatase 2 phosphatase activator	Homo sapiens	29-33
34368369-8	2021	Results: The results indicated that metformin significantly increased the activity of PP2A in the myotubes for all 8 lean insulin-sensitive nondiabetic participants, and the average fold increase is 1.54 +- 0.11 (P < 0.001).	Metformin	36-45	protein phosphatase 2 phosphatase activator	Homo sapiens	86-90
34436421-0	2021	Metformin Decreases 2-HG Production through the MYC-PHGDH Pathway in Suppressing Breast Cancer Cell Proliferation.	Metformin	0-9	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	48-51
34436421-7	2021	We also showed that metformin"s inhibitory effect on the PHGDH-2HG axis may occur through the regulation of the AMPK-MYC pathway.	Metformin	20-29	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	117-120
34335983-0	2021	CCDC65 as a new potential tumor suppressor induced by metformin inhibits activation of AKT1 via ubiquitination of ENO1 in gastric cancer.	Metformin	54-63	enolase 1	Homo sapiens	114-118
34335983-10	2021	Finally, we observed that metformin, a new anti-cancer drug, can significantly induce CCDC65 to suppress ENO1-AKT1 complex-mediated cell proliferation and EMT signals and finally suppresses the malignant phenotypes of gastric cancer cells.	Metformin	26-35	enolase 1	Homo sapiens	105-109
34335983-11	2021	Conclusion: These results firstly highlight a critical role of CCDC65 in suppressing ENO1-AKT1 pathway to reduce the progression of gastric cancer and reveals a new molecular mechanism for metformin in suppressing gastric cancer.	Metformin	189-198	enolase 1	Homo sapiens	85-89
34105824-0	2021	A novel imidazolinone metformin-methylglyoxal metabolite promotes endothelial cell angiogenesis via the eNOS/HIF-1alpha pathway.	Metformin	22-31	nitric oxide synthase 3, endothelial cell	Mus musculus	104-108
26474470-7	2015	In T2DM subjects, sCD26/DPP-IV levels were associated with significantly higher A1c levels, but were significantly lower in patients using monotherapy with metformin.	Metformin	156-165	dipeptidyl peptidase 4	Homo sapiens	24-30
26474470-14	2015	Moreover, metformin monotherapy was associated with reduced sCD26/DPP-IV levels.	Metformin	10-19	dipeptidyl peptidase 4	Homo sapiens	66-72
26692929-7	2015	RESULTS: Metformin elevated FNDC5 mRNA/protein expression of skeletal muscle and plasma irisin concentration in ob/ob mice.	Metformin	9-18	fibronectin type III domain containing 5	Mus musculus	28-33
26365176-6	2015	Intriguingly, no resistance was observed for the mitochondrial ROS inducer menadione and resistance could also be prevented/reversed for metformin by genetic/pharmacological inhibition of MYC.	Metformin	137-146	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	188-191
34105824-0	2021	A novel imidazolinone metformin-methylglyoxal metabolite promotes endothelial cell angiogenesis via the eNOS/HIF-1alpha pathway.	Metformin	22-31	hypoxia inducible factor 1, alpha subunit	Mus musculus	109-119
34564972-5	2021	RESULTS: At 72 h after treatment with either 25 microM metformin, 150 nM iRNA-PFK-1, or the combined treatment, the transcriptional levels of these biomarkers were decreased by ~73% (p 0.05), ~99.9%, (p 0.01), and ~76% (p 0.05), respectively.	Metformin	55-64	phosphofructokinase, muscle	Homo sapiens	78-83
34220516-9	2021	This study found obvious changes in the pharmacokinetics of acetaminophen and metformin hydrochloride in rats after exposure to simulated high altitude hypoxia, and they might be due to significant decreases in the expressions of UGT1A1 and OCT2.	Metformin	78-101	solute carrier family 22 member 2	Rattus norvegicus	241-245
34900765-2	2021	Metformin, the most used anti-diabetic medication, is found to reduce body weight via growth differentiation factor 15 (GDF-15) signalling pathways.	Metformin	0-9	growth differentiation factor 15	Mus musculus	120-126
34139918-4	2022	Areas of ongoing investigation focus on metformin"s ability to activate adenosine monophosphate kinase (AMPK), in addition to its effect on Myc mRNA, monocarboxylate transporter 1 (MCT1), hypoxia-inducible factor 1 (HIF1), mammalian target of rapamycin (mTOR), and human epidermal growth factor receptor 2 (HER2).	Metformin	40-49	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	140-143
34211461-0	2021	Metformin-Inducible Small Heterodimer Partner Interacting Leucine Zipper Protein Ameliorates Intestinal Inflammation.	Metformin	0-9	CREB/ATF bZIP transcription factor	Mus musculus	20-80
34194474-9	2021	Carriers of reduced-function alleles of organic cation transporter 1 (OCT 1, encoded by SLC22A1) or reduced expression alleles of plasma membrane monoamine transporter (PMAT, encoded by SLC29A4) or serotonin transporter (SERT, encoded by SLC6A4) were associated with increased incidence of metformin-related gastrointestinal (GI) adverse effects.	Metformin	290-299	solute carrier family 29 member 4	Homo sapiens	130-167
34194474-9	2021	Carriers of reduced-function alleles of organic cation transporter 1 (OCT 1, encoded by SLC22A1) or reduced expression alleles of plasma membrane monoamine transporter (PMAT, encoded by SLC29A4) or serotonin transporter (SERT, encoded by SLC6A4) were associated with increased incidence of metformin-related gastrointestinal (GI) adverse effects.	Metformin	290-299	solute carrier family 29 member 4	Homo sapiens	169-173
34194474-9	2021	Carriers of reduced-function alleles of organic cation transporter 1 (OCT 1, encoded by SLC22A1) or reduced expression alleles of plasma membrane monoamine transporter (PMAT, encoded by SLC29A4) or serotonin transporter (SERT, encoded by SLC6A4) were associated with increased incidence of metformin-related gastrointestinal (GI) adverse effects.	Metformin	290-299	solute carrier family 29 member 4	Homo sapiens	186-193
34208360-0	2021	Metformin Targets Foxo1 to Control Glucose Homeostasis.	Metformin	0-9	forkhead box O1	Mus musculus	18-23
34208360-5	2021	We showed that metformin inhibits HGP and blood glucose in a Foxo1-dependent manner.	Metformin	15-24	forkhead box O1	Mus musculus	61-66
34208360-6	2021	Furthermore, we identified that metformin suppresses glucagon-induced HGP through inhibiting the PKA Foxo1 signaling pathway.	Metformin	32-41	forkhead box O1	Mus musculus	101-106
34208360-7	2021	In both cells and mice, Foxo1-S273D or A mutation abolished the suppressive effect of metformin on glucagon or fasting-induced HGP.	Metformin	86-95	forkhead box O1	Mus musculus	24-29
34208360-8	2021	We further showed that metformin attenuates PKA activity, decreases Foxo1-S273 phosphorylation, and improves glucose homeostasis in diet-induced obese mice.	Metformin	23-32	forkhead box O1	Mus musculus	68-73
34208360-10	2021	Our study demonstrates that metformin inhibits HGP through PKA-regulated transcription factor Foxo1 and its S273 phosphorylation.	Metformin	28-37	forkhead box O1	Mus musculus	94-99
34135572-0	2021	Metformin Decreases Insulin Resistance in Type 1 Diabetes Through Regulating P53 and RAP2A in vitro and in vivo (Retraction).	Metformin	0-9	RAP2A, member of RAS oncogene family	Homo sapiens	85-90
34163481-3	2021	The mechanisms by which metformin regulates the function of macrophages include AMPK, AMPK independent targets, NF-kappaB, ABCG5/8, Sirt1, FOXO1/FABP4 and HMGB1.	Metformin	24-33	fatty acid binding protein 4	Homo sapiens	145-150
34163481-6	2021	In addition, the combination of metformin with other drugs that improve the function of macrophages (such as SGLT2 inhibitors, statins and IL-1beta inhibitors/monoclonal antibodies) may further enhance the pleiotropic therapeutic potential of metformin in conditions such as atherosclerosis, obesity, cancer, dementia and aging.	Metformin	32-41	solute carrier family 5 member 2	Homo sapiens	109-114
34163481-6	2021	In addition, the combination of metformin with other drugs that improve the function of macrophages (such as SGLT2 inhibitors, statins and IL-1beta inhibitors/monoclonal antibodies) may further enhance the pleiotropic therapeutic potential of metformin in conditions such as atherosclerosis, obesity, cancer, dementia and aging.	Metformin	32-41	interleukin 1 alpha	Homo sapiens	139-147
34163481-6	2021	In addition, the combination of metformin with other drugs that improve the function of macrophages (such as SGLT2 inhibitors, statins and IL-1beta inhibitors/monoclonal antibodies) may further enhance the pleiotropic therapeutic potential of metformin in conditions such as atherosclerosis, obesity, cancer, dementia and aging.	Metformin	243-252	solute carrier family 5 member 2	Homo sapiens	109-114
34163481-6	2021	In addition, the combination of metformin with other drugs that improve the function of macrophages (such as SGLT2 inhibitors, statins and IL-1beta inhibitors/monoclonal antibodies) may further enhance the pleiotropic therapeutic potential of metformin in conditions such as atherosclerosis, obesity, cancer, dementia and aging.	Metformin	243-252	interleukin 1 alpha	Homo sapiens	139-147
34087084-4	2021	However, the effect of metformin administration on hsa-miR-21-5p and MMP9 has not been evaluated in T2DM and DN patients.	Metformin	23-32	microRNA 21	Homo sapiens	51-61
26025384-10	2015	CONCLUSIONS: The glucose-lowering effect and increased insulin sensitivity associated with EA-metformin administration is governed, at least in part, by its ability to stimulate the activation of GLUT4 via upregulation of MAPK expression.	Metformin	94-103	solute carrier family 2 member 4	Rattus norvegicus	196-201
34087084-10	2021	However, in metformin-treated group, a downregulation of hsa-miR-21-5p and upregulation of MMP9 was observed.	Metformin	12-21	microRNA 21	Homo sapiens	57-67
34087084-12	2021	Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.	Metformin	0-9	microRNA 21	Homo sapiens	27-33
34087084-12	2021	Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.	Metformin	0-9	phosphatase and tensin homolog	Homo sapiens	399-403
26173919-3	2015	DPP-4 inhibitors may be used as monotherapy or in double or triple combination with other oral glucose-lowering agents such as metformin, thiazolidinediones, or sulfonylureas.	Metformin	127-136	dipeptidyl peptidase 4	Homo sapiens	0-5
26116230-0	2015	Metformin regulates stromal-epithelial cells communication via Wnt2/beta-catenin signaling in endometriosis.	Metformin	0-9	catenin beta 1	Homo sapiens	68-80
26172303-5	2015	Mechanistically, maintenance of c-Myc expression under conditions of hyperglycemia or via gene amplification facilitated metabolic escape from the effects of metformin.	Metformin	158-167	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	32-37
26172303-6	2015	In vivo, treatment of an ovarian cancer mouse model with metformin resulted in greater tumor weight reduction in normoglycemic vs. hyperglycemic mice, with increased c-Myc expression observed in metformin-treated hyperglycemic mice.	Metformin	57-66	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	166-171
26172303-6	2015	In vivo, treatment of an ovarian cancer mouse model with metformin resulted in greater tumor weight reduction in normoglycemic vs. hyperglycemic mice, with increased c-Myc expression observed in metformin-treated hyperglycemic mice.	Metformin	195-204	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	166-171
26225749-5	2015	Treatment of MCF-7 cells with metformin or phenformin induced increase in p53 protein levels and the transcription of its downstream target genes, Bax and p21, in a dose-dependent manner.	Metformin	30-39	H3 histone pseudogene 16	Homo sapiens	155-158
34087084-12	2021	Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.	Metformin	0-9	microRNA 21	Homo sapiens	421-431
34087084-12	2021	Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.	Metformin	0-9	microRNA 21	Homo sapiens	514-524
34087084-12	2021	Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.	Metformin	280-289	microRNA 21	Homo sapiens	27-33
34087084-12	2021	Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.	Metformin	280-289	microRNA 21	Homo sapiens	137-147
34087084-12	2021	Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.	Metformin	280-289	microRNA 21	Homo sapiens	315-325
34087084-12	2021	Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.	Metformin	280-289	phosphatase and tensin homolog	Homo sapiens	399-403
34087084-12	2021	Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.	Metformin	280-289	microRNA 21	Homo sapiens	421-431
34087084-12	2021	Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.	Metformin	280-289	microRNA 21	Homo sapiens	514-524
34386644-9	2021	Metformin, on the contrary, suppressed the expression of sparc, integrin alphaV, fibronectin and N-cadherin with the reduced cell motility.	Metformin	0-9	secreted protein acidic and cysteine rich	Homo sapiens	57-62
34124444-0	2021	Proteomic Analysis Reveals That Metformin Suppresses PSMD2, STIP1, and CAP1 for Preventing Gastric Cancer AGS Cell Proliferation and Migration.	Metformin	32-41	stress induced phosphoprotein 1	Homo sapiens	60-65
34124444-6	2021	Using small-scale quantitative proteomics, we identified 177 differentially expressed proteins upon metformin treatment; among these, nine proteins such as 26S proteasome non-ATPase regulatory subunit 2 (PSMD2), stress-induced phosphoprotein 1 (STIP1), and adenylyl cyclase-associated protein 1 (CAP1) were significantly altered.	Metformin	100-109	stress induced phosphoprotein 1	Homo sapiens	212-243
34124444-6	2021	Using small-scale quantitative proteomics, we identified 177 differentially expressed proteins upon metformin treatment; among these, nine proteins such as 26S proteasome non-ATPase regulatory subunit 2 (PSMD2), stress-induced phosphoprotein 1 (STIP1), and adenylyl cyclase-associated protein 1 (CAP1) were significantly altered.	Metformin	100-109	stress induced phosphoprotein 1	Homo sapiens	245-250
34073245-2	2021	Anti-cancer efficacy of metformin depends on its uptake in cancer cells, which is mediated by plasma membrane monoamine transporters (PMAT) and organic cation transporters (OCTs).	Metformin	24-33	solute carrier family 29 member 4	Homo sapiens	134-138
24981592-3	2015	Knowing that both metformin and atenolol are eliminated by organic cation transporter 2 (OCT2/SLC22A2) expressed in the renal basolateral membrane, it is not clear whether there is a competitive effect on the renal excretion of metformin and/or atenolol when metformin and atenolol were co-administered, and whether age was involved in this drug-drug interaction.	Metformin	18-27	solute carrier family 22 member 2	Rattus norvegicus	59-87
24981592-3	2015	Knowing that both metformin and atenolol are eliminated by organic cation transporter 2 (OCT2/SLC22A2) expressed in the renal basolateral membrane, it is not clear whether there is a competitive effect on the renal excretion of metformin and/or atenolol when metformin and atenolol were co-administered, and whether age was involved in this drug-drug interaction.	Metformin	18-27	solute carrier family 22 member 2	Rattus norvegicus	89-93
24981592-3	2015	Knowing that both metformin and atenolol are eliminated by organic cation transporter 2 (OCT2/SLC22A2) expressed in the renal basolateral membrane, it is not clear whether there is a competitive effect on the renal excretion of metformin and/or atenolol when metformin and atenolol were co-administered, and whether age was involved in this drug-drug interaction.	Metformin	18-27	solute carrier family 22 member 2	Rattus norvegicus	94-101
24981592-3	2015	Knowing that both metformin and atenolol are eliminated by organic cation transporter 2 (OCT2/SLC22A2) expressed in the renal basolateral membrane, it is not clear whether there is a competitive effect on the renal excretion of metformin and/or atenolol when metformin and atenolol were co-administered, and whether age was involved in this drug-drug interaction.	Metformin	228-237	solute carrier family 22 member 2	Rattus norvegicus	89-93
24981592-3	2015	Knowing that both metformin and atenolol are eliminated by organic cation transporter 2 (OCT2/SLC22A2) expressed in the renal basolateral membrane, it is not clear whether there is a competitive effect on the renal excretion of metformin and/or atenolol when metformin and atenolol were co-administered, and whether age was involved in this drug-drug interaction.	Metformin	228-237	solute carrier family 22 member 2	Rattus norvegicus	89-93
24981592-9	2015	Moreover, a significant age-related decrease in rOCT2 protein expression was observed in the aged rats (P &lt; 0.01), which may be responsible for the effect of atenolol on the renal excretion of metformin in the aged rats.	Metformin	196-205	solute carrier family 22 member 2	Rattus norvegicus	48-53
25971328-9	2015	The GEO analysis revealed downregulation of a series of pro-tumorigenic micro-RNAs following metformin treatment, which was in part restored by DICER knockdown.	Metformin	93-102	dicer 1, ribonuclease III	Homo sapiens	144-149
25971328-11	2015	BrCa patients with DM could possibly benefit from metformin treatment via DICER mediation.	Metformin	50-59	dicer 1, ribonuclease III	Homo sapiens	74-79
25993908-11	2015	Moreover, treatment of megakaryocytes with metformin enhanced mitochondrial content and in the same cells metformin enhanced the phosphorylation of the Drp-1 on Ser637 via an AMPKalpha1-dependent mechanism.	Metformin	43-52	dynamin 1 like	Homo sapiens	152-157
25993908-11	2015	Moreover, treatment of megakaryocytes with metformin enhanced mitochondrial content and in the same cells metformin enhanced the phosphorylation of the Drp-1 on Ser637 via an AMPKalpha1-dependent mechanism.	Metformin	106-115	dynamin 1 like	Homo sapiens	152-157
26056043-0	2015	Metformin combined with aspirin significantly inhibit pancreatic cancer cell growth in vitro and in vivo by suppressing anti-apoptotic proteins Mcl-1 and Bcl-2.	Metformin	0-9	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	144-149
26056043-5	2015	Compared to the untreated control or individual drug, the combination of metformin and aspirin significantly inhibited cell migration and colony formation of both PANC-1 and BxPC-3 cells.	Metformin	73-82	pancreas protein 1	Mus musculus	163-169
26056043-9	2015	In a PANC-1 xenograft mouse model, we demonstrated that the combination of metformin and aspirin significantly inhibited tumor growth and downregulated the protein expression of Mcl-1 and Bcl-2 in tumors.	Metformin	75-84	pancreas protein 1	Mus musculus	5-11
25871950-3	2015	In this study, the effect of metformin on senescence and antisenescence mediators (SirT1-7, p53, and p16(INK4a)) mRNA expression in white blood cells (WBCs) following lipopolysaccharides (LPS)-induced inflammation in mice was examined.	Metformin	29-38	sirtuin 1	Mus musculus	83-88
25871950-9	2015	Metformin inhibited SirT2 expression in WBCs significantly (P&lt;0.05) and did not induce any significant changes in other SirT forms and p53, whereas it induced p16(INK4a) mRNA expression in WBCs (P&lt;0.05) at the basal levels.	Metformin	0-9	sirtuin 2	Mus musculus	20-25
25871950-10	2015	Additionally, metformin treatment significantly inhibited SirT7, SirT1, and p16(INK4a) mRNA expression in WBCs at 1, 2, and 3 hr, whereas p53 was inhibited significantly at 2 hr after LPS injection.	Metformin	14-23	sirtuin 1	Mus musculus	65-70
25871950-12	2015	The data suggest that metformin may exert its potential antisenescence and anti-inflammatory effects by targeting SirT7 and SirT1 pathways.	Metformin	22-31	sirtuin 1	Mus musculus	124-129
25962562-9	2015	Following treatment with bisperoxopicolinatooxovanadate (BPV) or metformin in the insulin-resistant skeletal muscle cells, there was an increase in the rate of glucose uptake, an increase in GLUT4 expression and its translocation, a reduction in the expression of PTEN and p-PTEN, and a decrease in cell apoptosis compared with untreated insulin-resistant cells.	Metformin	65-74	phosphatase and tensin homolog	Homo sapiens	264-268
25962562-9	2015	Following treatment with bisperoxopicolinatooxovanadate (BPV) or metformin in the insulin-resistant skeletal muscle cells, there was an increase in the rate of glucose uptake, an increase in GLUT4 expression and its translocation, a reduction in the expression of PTEN and p-PTEN, and a decrease in cell apoptosis compared with untreated insulin-resistant cells.	Metformin	65-74	phosphatase and tensin homolog	Homo sapiens	275-279
25854169-5	2015	Cyclin D1 and c-Myc are important regulators of cancer cell growth, and we observed that treatment of thyroid cancer cells with metformin reduced c-Myc and cyclin D1 expression through suppression of mTOR and subsequent inhibition of P70S6K1 and 4E-BP1 phosphorylation.	Metformin	128-137	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	14-19
25854169-5	2015	Cyclin D1 and c-Myc are important regulators of cancer cell growth, and we observed that treatment of thyroid cancer cells with metformin reduced c-Myc and cyclin D1 expression through suppression of mTOR and subsequent inhibition of P70S6K1 and 4E-BP1 phosphorylation.	Metformin	128-137	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	146-151
25854169-5	2015	Cyclin D1 and c-Myc are important regulators of cancer cell growth, and we observed that treatment of thyroid cancer cells with metformin reduced c-Myc and cyclin D1 expression through suppression of mTOR and subsequent inhibition of P70S6K1 and 4E-BP1 phosphorylation.	Metformin	128-137	eukaryotic translation initiation factor 4E binding protein 1	Homo sapiens	234-252
26196392-5	2015	Moreover, we observed that metformin induced G0/G1 phase arrest accompanied by the up-regulation of p21CIP1 and p27KIP1.	Metformin	27-36	cyclin dependent kinase inhibitor 1B	Homo sapiens	112-119
26196392-7	2015	Most importantly, the up-regulation of AMPK, p53, p21CIP1, p27KIP1 and the down-regulation of cyclinD1 are involved in the anti-tumor action of metformin in vivo.	Metformin	144-153	cyclin dependent kinase inhibitor 1B	Homo sapiens	59-66
26196392-9	2015	AMPK, p53, p21CIP1, p27KIP1 and cyclinD1 are involved in the inhibition of tumor growth that is induced by metformin and cell cycle arrest in ESCC.	Metformin	107-116	cyclin dependent kinase inhibitor 1B	Homo sapiens	20-27
25999130-0	2015	Metformin exerts anticancer effects through the inhibition of the Sonic hedgehog signaling pathway in breast cancer.	Metformin	0-9	sonic hedgehog signaling molecule	Homo sapiens	66-80
25999130-4	2015	The aim of the present study was to elucidate the role of the Shh pathway in mediating the anticancer effects of metformin and the correlation between AMPK and the Shh pathway.	Metformin	113-122	sonic hedgehog signaling molecule	Homo sapiens	62-65
25999130-7	2015	The results revealed that the treatment of breast cancer cells with metformin led to the inhibition of the Shh signaling pathway.	Metformin	68-77	sonic hedgehog signaling molecule	Homo sapiens	107-110
25999130-8	2015	Importantly, metformin inhibited recombinant human Shh (rhShh)-induced cell migration, invasion, and stemness, and impaired cell proliferation both in vitro and in vivo.	Metformin	13-22	sonic hedgehog signaling molecule	Homo sapiens	51-54
25999130-10	2015	Our findings identified a role of the Shh signaling pathway in the anticancer effects of metformin in breast cancer.	Metformin	89-98	sonic hedgehog signaling molecule	Homo sapiens	38-41
25999130-11	2015	Furthermore, we revealed that the metformin-mediated inhibition of the Shh signaling pathway may be dependent on AMPK.	Metformin	34-43	sonic hedgehog signaling molecule	Homo sapiens	71-74
34069550-0	2021	A Phase Ib Clinical Trial of Metformin and Chloroquine in Patients with IDH1-Mutated Solid Tumors.	Metformin	29-38	isocitrate dehydrogenase (NADP(+)) 1	Homo sapiens	72-76
34069550-12	2021	CONCLUSION: Treatment of advanced IDH1-mutated solid tumors with metformin and chloroquine was well tolerated but did not induce a clinical response in this phase Ib clinical trial.	Metformin	65-74	isocitrate dehydrogenase (NADP(+)) 1	Homo sapiens	34-38
34064886-1	2021	Transmembrane transport of metformin is highly controlled by transporters including organic cation transporters (OCTs), plasma membrane monoamine transporter (PMAT), and multidrug/toxin extrusions (MATEs).	Metformin	27-36	solute carrier family 29 member 4	Homo sapiens	120-157
34064886-1	2021	Transmembrane transport of metformin is highly controlled by transporters including organic cation transporters (OCTs), plasma membrane monoamine transporter (PMAT), and multidrug/toxin extrusions (MATEs).	Metformin	27-36	solute carrier family 29 member 4	Homo sapiens	159-163
34064886-2	2021	Hepatic OCT1, intestinal OCT3, renal OCT2 on tubule basolateral membrane, and MATE1/2-K on tubule apical membrane coordinately work to control metformin disposition.	Metformin	143-152	solute carrier family 22 member 2	Homo sapiens	37-41
34064886-7	2021	Individual contributions of transporters to metformin disposition are renal OCT2   renal MATEs > intestinal OCT3 > hepatic OCT1 > intestinal PMAT.	Metformin	44-53	solute carrier family 22 member 2	Homo sapiens	76-80
34113829-5	2021	In addition, similar to the antidiabetic drug metformin, we observed that in db/db mice, DHODH inhibitors elevate levels of circulating GDF15 and reduce food intake.	Metformin	46-55	growth differentiation factor 15	Mus musculus	136-141
34095013-3	2021	Methods: After searching for trials using combination therapy of metformin with DPP4 inhibitor or SU in PubMed, Cochrane Library, and Embase, one prospective observation study and 15 randomized controlled studies were selected.	Metformin	65-74	dipeptidyl peptidase 4	Homo sapiens	80-84
34277866-0	2021	Efficacy of Photobiomodulation and Metformin on Diabetic Cell Line of Human Periodontal Ligament Stem Cells through Keap1/Nrf2/Ho-1 Pathway.	Metformin	35-44	heme oxygenase 1	Homo sapiens	127-131
34277866-12	2021	Results: Photobiomodulation at 1, 2, and 3 J/cm2 combined with metformin significantly promoted diabetic cell lines of HPDLSCs viability (in MTT assay and ELISA reader of ROS, TNF-alpha, IL-10 results) and gene expression of Nrf2, Keap1, PIK3, and HO-1 levels (p< 0.05).	Metformin	63-72	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma	Homo sapiens	238-242
35568294-5	2022	Metformin deregulated the expression of BUBR1 and MAD2, two core genes of spindle assembly checkpoint (SAC) that surveillances chromosome segregation.	Metformin	0-9	BUB1 mitotic checkpoint serine/threonine kinase B	Homo sapiens	40-45
35568294-5	2022	Metformin deregulated the expression of BUBR1 and MAD2, two core genes of spindle assembly checkpoint (SAC) that surveillances chromosome segregation.	Metformin	0-9	mitotic arrest deficient 2 like 1	Homo sapiens	50-54
35430208-0	2022	The lactate receptor GPR81 mediates hepatic lipid metabolism and the therapeutic effect of metformin on experimental NAFLDs.	Metformin	91-100	hydrocarboxylic acid receptor 1	Mus musculus	21-26
35430208-6	2022	Importantly, metformin improved experimental nonalcoholic fatty liver disease (NAFLDs) in a GPR81-dependent manner.	Metformin	13-22	hydrocarboxylic acid receptor 1	Mus musculus	92-97
35460908-2	2022	Metformin (Met) is a promising drug for tumor treatment that targets hexokinase 2 (HK2) to block the glycolytic process, thereby further disrupting the metabolism of cancer cells.	Metformin	0-9	SAFB like transcription modulator	Homo sapiens	11-14
35237909-0	2022	Metformin enhances LDL-cholesterol uptake by suppressing the expression of the pro-protein convertase subtilisin/kexin type 9 (PCSK9) in liver cells.	Metformin	0-9	proprotein convertase subtilisin/kexin type 9	Homo sapiens	79-125
25920679-0	2015	Targeted disruption of organic cation transporter 3 attenuates the pharmacologic response to metformin.	Metformin	93-102	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	23-51
25920679-2	2015	Organic cation transporter 3 (OCT3, SLC22A3), expressed ubiquitously, transports metformin, but its in vivo role in metformin response is not known.	Metformin	81-90	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	0-28
25920679-2	2015	Organic cation transporter 3 (OCT3, SLC22A3), expressed ubiquitously, transports metformin, but its in vivo role in metformin response is not known.	Metformin	81-90	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	30-34
25920679-2	2015	Organic cation transporter 3 (OCT3, SLC22A3), expressed ubiquitously, transports metformin, but its in vivo role in metformin response is not known.	Metformin	81-90	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	36-43
25920679-2	2015	Organic cation transporter 3 (OCT3, SLC22A3), expressed ubiquitously, transports metformin, but its in vivo role in metformin response is not known.	Metformin	116-125	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	0-28
25920679-2	2015	Organic cation transporter 3 (OCT3, SLC22A3), expressed ubiquitously, transports metformin, but its in vivo role in metformin response is not known.	Metformin	116-125	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	30-34
25920679-2	2015	Organic cation transporter 3 (OCT3, SLC22A3), expressed ubiquitously, transports metformin, but its in vivo role in metformin response is not known.	Metformin	116-125	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	36-43
25920679-4	2015	After an intravenous dose of metformin, a 2-fold decrease in the apparent volume of distribution and clearance was observed in knockout compared with wild-type mice (P &lt; 0.001), indicating an important role of OCT3 in tissue distribution and elimination of the drug.	Metformin	29-38	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	213-217
25920679-7	2015	Furthermore, the effect of metformin on phosphorylation of AMP activated protein kinase, and expression of glucose transporter type 4 was absent in the adipose tissue of Oct3(-/-) mice.	Metformin	27-36	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	170-174
25920679-8	2015	Additional analysis revealed that an OCT3 3" untranslated region variant was associated with reduced activity in luciferase assays and reduced response to metformin in 57 healthy volunteers.	Metformin	155-164	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	37-41
25920679-9	2015	These findings suggest that OCT3 plays an important role in the absorption and elimination of metformin and that the transporter is a critical determinant of metformin bioavailability, clearance, and pharmacologic action.	Metformin	94-103	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	28-32
26261558-9	2015	Metformin is also capable of maintaining the biological activities of SCs after hypoxia injury, such as increasing the expression and secretion of BDNF, NGF, GDNF, and N-CAM.	Metformin	0-9	neural cell adhesion molecule 1	Homo sapiens	168-173
25891779-5	2015	The effects of metformin on SREBP-1c gene transcription were determined by a luciferase reporter assay.	Metformin	15-24	sterol regulatory element binding transcription factor 1	Homo sapiens	28-36
25891779-7	2015	In the PA-treated L6 cells, metformin treatment enhanced AMPK phosphorylation, reduced SREBP-1c expression and increased IRS-1 and Akt protein expression, whereas treatment with compound C blocked the effects of metformin on SREBP-1c expression and the IRS-1 and Akt levels.	Metformin	28-37	sterol regulatory element binding transcription factor 1	Homo sapiens	87-95
25891779-7	2015	In the PA-treated L6 cells, metformin treatment enhanced AMPK phosphorylation, reduced SREBP-1c expression and increased IRS-1 and Akt protein expression, whereas treatment with compound C blocked the effects of metformin on SREBP-1c expression and the IRS-1 and Akt levels.	Metformin	28-37	insulin receptor substrate 1	Homo sapiens	121-126
25891779-7	2015	In the PA-treated L6 cells, metformin treatment enhanced AMPK phosphorylation, reduced SREBP-1c expression and increased IRS-1 and Akt protein expression, whereas treatment with compound C blocked the effects of metformin on SREBP-1c expression and the IRS-1 and Akt levels.	Metformin	28-37	sterol regulatory element binding transcription factor 1	Homo sapiens	225-233
25891779-7	2015	In the PA-treated L6 cells, metformin treatment enhanced AMPK phosphorylation, reduced SREBP-1c expression and increased IRS-1 and Akt protein expression, whereas treatment with compound C blocked the effects of metformin on SREBP-1c expression and the IRS-1 and Akt levels.	Metformin	28-37	insulin receptor substrate 1	Homo sapiens	253-258
25891779-7	2015	In the PA-treated L6 cells, metformin treatment enhanced AMPK phosphorylation, reduced SREBP-1c expression and increased IRS-1 and Akt protein expression, whereas treatment with compound C blocked the effects of metformin on SREBP-1c expression and the IRS-1 and Akt levels.	Metformin	212-221	sterol regulatory element binding transcription factor 1	Homo sapiens	225-233
25891779-8	2015	Moreover, metformin suppressed SREBP-1c promoter activity and promoted glucose uptake through AMPK.	Metformin	10-19	sterol regulatory element binding transcription factor 1	Homo sapiens	31-39
25891779-9	2015	The results from this study demonstrate that metformin ameliorates PA-induced insulin resistance through the activation of AMPK and the suppression of SREBP-1c in skeletal muscle cells.	Metformin	45-54	sterol regulatory element binding transcription factor 1	Homo sapiens	151-159
25909163-4	2015	In addition to activation of AMPK and suppression of the mTOR pathway, a series of increased and decreased genes expression were induced by metformin, including PTEN, MMP7, and FN1.	Metformin	140-149	mechanistic target of rapamycin kinase	Mus musculus	57-61
25909163-4	2015	In addition to activation of AMPK and suppression of the mTOR pathway, a series of increased and decreased genes expression were induced by metformin, including PTEN, MMP7, and FN1.	Metformin	140-149	fibronectin 1	Mus musculus	177-180
25980580-0	2015	Oncometabolic mutation IDH1 R132H confers a metformin-hypersensitive phenotype.	Metformin	44-53	isocitrate dehydrogenase (NADP(+)) 1	Homo sapiens	23-27
25980580-6	2015	The mitochondrial biguanide poisons, metformin and phenformin, further impaired the intrinsic weakness of IDH1-mutant cells to use certain carbon-energy sources.	Metformin	37-46	isocitrate dehydrogenase (NADP(+)) 1	Homo sapiens	106-110
25980580-7	2015	Additionally, metabolic reprogramming of IDH1-mutant cells increased their sensitivity to metformin in assays of cell proliferation, clonogenic potential, and mammosphere formation.	Metformin	90-99	isocitrate dehydrogenase (NADP(+)) 1	Homo sapiens	41-45
25980580-8	2015	Targeted metabolomics studies revealed that the ability of metformin to interfere with the anaplerotic entry of glutamine into the tricarboxylic acid cycle could explain the hypersensitivity of IDH1-mutant cells to biguanides.	Metformin	59-68	isocitrate dehydrogenase (NADP(+)) 1	Homo sapiens	194-198
25980580-9	2015	Moreover, synergistic interactions occurred when metformin treatment was combined with the selective R132H-IDH1 inhibitor AGI-5198.	Metformin	49-58	isocitrate dehydrogenase (NADP(+)) 1	Homo sapiens	107-111
26052399-6	2015	Metformin (through 5"-adenosine monophosphate-activated protein kinase pathway activation) and statins (through 3-hydroxy-3-methylglutaryl coenzyme A inhibition) show anti-tumoral properties modifying several steps of RAS/RAF/MEK/ERK, PI3K/AKT/mTOR and Wnt/beta-catenin signaling cascades.	Metformin	0-9	catenin beta 1	Homo sapiens	257-269
25999728-1	2015	Dipeptidyl-peptidase-IV (DPP-4) inhibitors are oral antidiabetic agents that can be administered as monotherapy in patients with contraindications to metformin or metformin intolerance, and in combination with other oral compounds and/or insulin.	Metformin	150-159	dipeptidyl peptidase 4	Homo sapiens	0-23
25999728-1	2015	Dipeptidyl-peptidase-IV (DPP-4) inhibitors are oral antidiabetic agents that can be administered as monotherapy in patients with contraindications to metformin or metformin intolerance, and in combination with other oral compounds and/or insulin.	Metformin	150-159	dipeptidyl peptidase 4	Homo sapiens	25-30
25999728-1	2015	Dipeptidyl-peptidase-IV (DPP-4) inhibitors are oral antidiabetic agents that can be administered as monotherapy in patients with contraindications to metformin or metformin intolerance, and in combination with other oral compounds and/or insulin.	Metformin	163-172	dipeptidyl peptidase 4	Homo sapiens	0-23
25999728-1	2015	Dipeptidyl-peptidase-IV (DPP-4) inhibitors are oral antidiabetic agents that can be administered as monotherapy in patients with contraindications to metformin or metformin intolerance, and in combination with other oral compounds and/or insulin.	Metformin	163-172	dipeptidyl peptidase 4	Homo sapiens	25-30
25895126-6	2015	Metformin resulted in activation of AMPK and SIRT1 and inhibition of pAkt and pmTOR, similar to CR.	Metformin	0-9	sirtuin 1	Mus musculus	45-50
25955843-0	2015	Metformin Causes G1-Phase Arrest via Down-Regulation of MiR-221 and Enhances TRAIL Sensitivity through DR5 Up-Regulation in Pancreatic Cancer Cells.	Metformin	0-9	microRNA 221	Homo sapiens	56-63
25955843-0	2015	Metformin Causes G1-Phase Arrest via Down-Regulation of MiR-221 and Enhances TRAIL Sensitivity through DR5 Up-Regulation in Pancreatic Cancer Cells.	Metformin	0-9	TNF receptor superfamily member 10b	Homo sapiens	103-106
25955843-5	2015	We demonstrated that metformin suppressed the expression of miR-221, one of the most well-known oncogenic microRNAs, in human pancreatic cancer PANC-1 cells.	Metformin	21-30	microRNA 221	Homo sapiens	60-67
25955843-6	2015	Moreover, we showed that the down-regulation of miR-221 by metformin caused G1-phase arrest via the up-regulation of p27, one of the direct targets of miR-221.	Metformin	59-68	microRNA 221	Homo sapiens	48-55
25955843-6	2015	Moreover, we showed that the down-regulation of miR-221 by metformin caused G1-phase arrest via the up-regulation of p27, one of the direct targets of miR-221.	Metformin	59-68	interferon alpha inducible protein 27	Homo sapiens	117-120
25955843-6	2015	Moreover, we showed that the down-regulation of miR-221 by metformin caused G1-phase arrest via the up-regulation of p27, one of the direct targets of miR-221.	Metformin	59-68	microRNA 221	Homo sapiens	151-158
25955843-9	2015	Metformin induced the expressions of death receptor 5 (DR5), a receptor for TRAIL, and Bim with a pro-apoptotic function in the downstream of TRAIL-DR5 pathway.	Metformin	0-9	TNF receptor superfamily member 10b	Homo sapiens	37-53
25955843-9	2015	Metformin induced the expressions of death receptor 5 (DR5), a receptor for TRAIL, and Bim with a pro-apoptotic function in the downstream of TRAIL-DR5 pathway.	Metformin	0-9	TNF receptor superfamily member 10b	Homo sapiens	55-58
25955843-9	2015	Metformin induced the expressions of death receptor 5 (DR5), a receptor for TRAIL, and Bim with a pro-apoptotic function in the downstream of TRAIL-DR5 pathway.	Metformin	0-9	TNF receptor superfamily member 10b	Homo sapiens	148-151
25576058-3	2015	In DIO/prediabetic mice, metformin and rapamycin significantly reduced pancreatic tumor growth and mTOR-related signaling.	Metformin	25-34	mechanistic target of rapamycin kinase	Mus musculus	99-103
26136915-8	2015	Furthermore, metformin upregulated the expression of insulin receptors and genes associated with lipid metabolism, including acyl-CoA oxidase, carnitine palmitoyl transferase-1 and peroxisome proliferator activated receptor-alpha.	Metformin	13-22	peroxisome proliferator activated receptor alpha	Rattus norvegicus	143-229
26136915-9	2015	In addition, treatment with metformin downregulated the expression levels of fetuin-A and retinol binding protein-4 (RBP-4), while normalizing the expression of perilipin that had been reduced in the T2DM rats.	Metformin	28-37	retinol binding protein 4	Rattus norvegicus	90-115
26136915-9	2015	In addition, treatment with metformin downregulated the expression levels of fetuin-A and retinol binding protein-4 (RBP-4), while normalizing the expression of perilipin that had been reduced in the T2DM rats.	Metformin	28-37	retinol binding protein 4	Rattus norvegicus	117-122
26136915-12	2015	In summary, metformin treatment ameliorated a number of the harmful effects associated with T2DM via the modulation of the expression levels of fetuin-A, RBP-4, perilipin and various genes associated with lipid metabolism, resulting in regenerative changes in the liver and pancreatic cells.	Metformin	12-21	retinol binding protein 4	Rattus norvegicus	154-159
30298777-5	2015	Dipeptidyl peptidase (DPP)-4 inhibitors and sodium glucose cotransporter (SGLT) 2 inhibitors are two newer classes of OADs that are efficacious and are less likely to induce adverse effects such as gastrointestinal reactions, hypoglycemia and weight gain when compared with metformin, sulfonylureas, and thiazolidinediones.	Metformin	274-283	dipeptidyl peptidase 4	Homo sapiens	0-28
25791462-10	2015	CONCLUSION: We demonstrated that adding metformin to OCP treatment may have beneficial effect on FMD and CIMT that represent vascular function in patients with PCOS.	Metformin	40-49	CIMT	Homo sapiens	105-109
25935176-5	2015	RESULTS: The mean +- standard error of the mean value of serum AMH levels was significantly decreased in post metformin treatment women (3 months; GII) compared with those before treatment (GI), and those women on prolonged treatment (GIII) (p less than 0.01 for both).	Metformin	110-119	anti-Mullerian hormone	Homo sapiens	63-66
25935176-8	2015	CONCLUSION: This study showed the efficacy of serum AMH measurement as a prognostic biochemical marker in the follow up of metformin treatment of PCOS women.	Metformin	123-132	anti-Mullerian hormone	Homo sapiens	52-55
35237909-0	2022	Metformin enhances LDL-cholesterol uptake by suppressing the expression of the pro-protein convertase subtilisin/kexin type 9 (PCSK9) in liver cells.	Metformin	0-9	proprotein convertase subtilisin/kexin type 9	Homo sapiens	127-132
35237909-5	2022	RESULTS: MF treatment resulted in decreased expression and secretion of PCSK9, increased expression of LDLR and enhanced LDL-C uptake in hepatocytes.	Metformin	9-11	proprotein convertase subtilisin/kexin type 9	Homo sapiens	72-77
35237909-5	2022	RESULTS: MF treatment resulted in decreased expression and secretion of PCSK9, increased expression of LDLR and enhanced LDL-C uptake in hepatocytes.	Metformin	9-11	low density lipoprotein receptor	Homo sapiens	103-107
35341775-0	2022	Metformin alleviates dexamethasone-induced apoptosis by regulating autophagy via AMPK/mTOR/p70S6K in osteoblasts.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	91-97
35341775-12	2022	Treatment with the autophagy inhibitor 3-methyladenine (3-MA) attenuated the effect of metformin on apoptosis, autophagy, and the AMPK/mTOR/p70S6K signaling pathway.	Metformin	87-96	ribosomal protein S6 kinase B1	Homo sapiens	140-146
35341775-15	2022	The AMPK/mTOR/p70S6K signaling pathway plays a role in metformin-mediated apoptosis suppression and autophagy promotion.	Metformin	55-64	ribosomal protein S6 kinase B1	Homo sapiens	14-20
35341775-16	2022	In conclusion, metformin can alleviate Dex-induced osteoblast apoptosis by inducing autophagy via the AMPK/mTOR/p70S6K pathway.	Metformin	15-24	ribosomal protein S6 kinase B1	Homo sapiens	112-118
35015172-2	2022	We and others previously demonstrated that metformin reduced splenomegaly and platelets counts in peripheral blood in JAK2V617F pre-clinical MPN models, which highlighted the antineoplastic potential of biguanides for MPN treatment.	Metformin	43-52	Janus kinase 2	Mus musculus	118-122
35512853-4	2022	We first used ENaC-overexpressing human bronchial epithelial cells (beta/gammaENaC-16HBE14o-) and identified that Metformin significantly reduced ENaC activity.	Metformin	114-123	sodium channel, nonvoltage-gated 1 alpha	Mus musculus	14-18
35512853-4	2022	We first used ENaC-overexpressing human bronchial epithelial cells (beta/gammaENaC-16HBE14o-) and identified that Metformin significantly reduced ENaC activity.	Metformin	114-123	sodium channel, nonvoltage-gated 1 alpha	Mus musculus	146-150
35512853-7	2022	Overall, the present study demonstrates that metformin directly inhibits ENaC activity in vitro and provides the first evidence of therapeutical benefit of Metformin for COPD with higher ENaC activity.	Metformin	45-54	sodium channel, nonvoltage-gated 1 alpha	Mus musculus	73-77
35512853-7	2022	Overall, the present study demonstrates that metformin directly inhibits ENaC activity in vitro and provides the first evidence of therapeutical benefit of Metformin for COPD with higher ENaC activity.	Metformin	156-165	sodium channel, nonvoltage-gated 1 alpha	Mus musculus	73-77
35512853-7	2022	Overall, the present study demonstrates that metformin directly inhibits ENaC activity in vitro and provides the first evidence of therapeutical benefit of Metformin for COPD with higher ENaC activity.	Metformin	156-165	sodium channel, nonvoltage-gated 1 alpha	Mus musculus	187-191
35525887-15	2022	CONCLUSIONS: Shikonin and metformin synergize in inhibiting the tumorigenic activities of MCF-7 cells including their proliferation, invasiveness, and EMT with a potential to inhibit multidrug resistance.	Metformin	26-35	IL2 inducible T cell kinase	Homo sapiens	151-154
35090865-1	2022	The aim of this study was to investigate the contributions of multiple transport mechanisms to the intestinal absorption of metformin, focusing on OCT3, PMAT, THTR2, SERT and OCTN2.	Metformin	124-133	solute carrier family 29 member 4	Homo sapiens	153-157
35090865-3	2022	Uptake studies with MDCKII cells expressing OCT3, PMAT, THTR2 or SERT confirmed that metformin is a substrate of these transporters.	Metformin	85-94	solute carrier family 29 member 4	Homo sapiens	50-54
35090865-6	2022	AG835, thiamine and paroxetine specifically inhibited PMAT-, THTR2- and SERT-mediated uptake of metformin, respectively.	Metformin	96-105	solute carrier family 29 member 4	Homo sapiens	54-58
35090865-7	2022	Using these inhibitors, the relative contributions of OCT3, PMAT, THTR2, SERT, OCTN2 and others to the intestinal permeation of metformin across Caco-2 cells were estimated to be 9.77%, 9.68%, 22.2%, 1.52%, 0% and 0.66%, respectively.	Metformin	128-137	solute carrier family 29 member 4	Homo sapiens	60-64
35098296-12	2022	IL-2 levels were significantly elevated in PCOS mice and significantly reduced after metformin administration.	Metformin	85-94	interleukin 2	Mus musculus	0-4
35454162-1	2022	Dual Blockade of Lactate/GPR81 and PD-1/PD-L1 Pathways Enhances the Anti-Tumor Effects of Metformin.	Metformin	90-99	CD274 molecule	Homo sapiens	40-45
35496297-14	2022	A combination of 1.25 mM metformin and 0.625 microM TQ increased the levels of cleaved poly (ADP-ribose) polymerase (PARP), decreased the levels of proliferation regulatory proteins, and inhibited protein kinase B (Akt) and NF-kappaB signaling in primary CLL cells.	Metformin	25-34	protein tyrosine kinase 2 beta	Homo sapiens	197-213
35379885-10	2022	In addition, we found that LXRalpha overexpression compromised the effect of metformin on PCSK9 levels and intracellular lipid droplet formation.	Metformin	77-86	proprotein convertase subtilisin/kexin type 9	Homo sapiens	90-95
35379885-11	2022	Taken together, our findings suggest that olanzapine enhances hepatic PCSK9 expression by upregulating LXRalpha, thereby increasing FAS and SCD1 expression as well as decreasing SCAD and PPARalpha, and promoting lipid accumulation, and, subsequently, NAFLD, which is ameliorated by metformin.	Metformin	282-291	proprotein convertase subtilisin/kexin type 9	Homo sapiens	70-75
34990285-4	2022	Therefore, the aim of the current study was to investigate the effects of metformin on the biological behavior of HCC and the underlying functional mechanism of metformin on the Shh pathway.	Metformin	74-83	sonic hedgehog signaling molecule	Homo sapiens	178-181
34990285-0	2022	Metformin exerts anti-tumor effects via Sonic hedgehog signaling pathway by targeting AMPK in HepG2 cells.	Metformin	0-9	sonic hedgehog signaling molecule	Homo sapiens	40-54
34990285-4	2022	Therefore, the aim of the current study was to investigate the effects of metformin on the biological behavior of HCC and the underlying functional mechanism of metformin on the Shh pathway.	Metformin	161-170	sonic hedgehog signaling molecule	Homo sapiens	178-181
34990285-9	2022	Furthermore, metformin decreased mRNA and protein expression of components of the Shh pathway including Shh, Ptch, Smo and Gli-1.	Metformin	13-22	sonic hedgehog signaling molecule	Homo sapiens	82-85
34990285-9	2022	Furthermore, metformin decreased mRNA and protein expression of components of the Shh pathway including Shh, Ptch, Smo and Gli-1.	Metformin	13-22	sonic hedgehog signaling molecule	Homo sapiens	104-107
34990285-9	2022	Furthermore, metformin decreased mRNA and protein expression of components of the Shh pathway including Shh, Ptch, Smo and Gli-1.	Metformin	13-22	smoothened, frizzled class receptor	Homo sapiens	115-118
34990285-11	2022	Our findings demonstrate that metformin can suppress the migration and invasion of HepG2 cells via AMPK-mediated inhibition of the Shh pathway.	Metformin	30-39	sonic hedgehog signaling molecule	Homo sapiens	131-134
35286856-1	2022	Here, inspired by the concept of supramolecular inclusion complex, we successfully fabricate metformin (Met)-based supramolecular nanodrugs with the Abeta-responsive on-demand drug release for synergistic Alzheimer"s disease (AD) therapy via enhancing microglial Abeta clearance.	Metformin	93-102	SAFB like transcription modulator	Homo sapiens	104-107
25862846-7	2015	CONCLUSION: Together, these results indicate that metformin indirectly blocks protein phosphorylation, including that of heat shock protein 27 (HSP27).	Metformin	50-59	heat shock protein family B (small) member 1	Homo sapiens	121-142
25862846-7	2015	CONCLUSION: Together, these results indicate that metformin indirectly blocks protein phosphorylation, including that of heat shock protein 27 (HSP27).	Metformin	50-59	heat shock protein family B (small) member 1	Homo sapiens	144-149
35212193-11	2022	Metformin was the most commonly used antidiabetic medication, followed by insulin, sodium-glucose transport protein 2 (SGLT2) inhibitors, and sulfonylurea.	Metformin	0-9	solute carrier family 5 member 2	Homo sapiens	119-124
35050486-0	2022	Metformin exerts an antitumoral effect on papillary thyroid cancer cells through altered cell energy metabolism and sensitized by BACH1 depletion.	Metformin	0-9	BTB and CNC homology 1, basic leucine zipper transcription factor 1	Mus musculus	130-135
35050486-2	2022	Metformin may reduce the risk of cancer, and BACH1 was reported to affect the sensitivity of cancer cells to metformin.	Metformin	109-118	BTB and CNC homology 1, basic leucine zipper transcription factor 1	Mus musculus	45-50
35050486-3	2022	The aims of this study were to investigate whether metformin exerts antitumor effects in PTC cells and explore the role of BACH1 depletion on the sensitivity of PTC cells to metformin.	Metformin	174-183	BTB and CNC homology 1, basic leucine zipper transcription factor 1	Mus musculus	123-128
35050486-7	2022	Furthermore, metformin changed the pattern of cell energy metabolism in PTC cells, which manifested as inhibition of mitochondrial respiration, and the combination of BACH1 depletion with metformin magnified the effect of metformin alone.	Metformin	13-22	BTB and CNC homology 1, basic leucine zipper transcription factor 1	Mus musculus	167-172
35050486-7	2022	Furthermore, metformin changed the pattern of cell energy metabolism in PTC cells, which manifested as inhibition of mitochondrial respiration, and the combination of BACH1 depletion with metformin magnified the effect of metformin alone.	Metformin	188-197	BTB and CNC homology 1, basic leucine zipper transcription factor 1	Mus musculus	167-172
35050486-7	2022	Furthermore, metformin changed the pattern of cell energy metabolism in PTC cells, which manifested as inhibition of mitochondrial respiration, and the combination of BACH1 depletion with metformin magnified the effect of metformin alone.	Metformin	222-231	BTB and CNC homology 1, basic leucine zipper transcription factor 1	Mus musculus	167-172
35050486-10	2022	Knocking down BACH1 caused the switching of energy metabolism and sensitized PTC cells to metformin, which eventually enhanced the anti-tumor effect of metformin.	Metformin	90-99	BTB and CNC homology 1, basic leucine zipper transcription factor 1	Mus musculus	14-19
35050486-10	2022	Knocking down BACH1 caused the switching of energy metabolism and sensitized PTC cells to metformin, which eventually enhanced the anti-tumor effect of metformin.	Metformin	152-161	BTB and CNC homology 1, basic leucine zipper transcription factor 1	Mus musculus	14-19
35104599-1	2022	Metformin hydrochloride (MET-HCl) was applied as a model compound to investigate the nucleation behavior in four hydroxylic solvents based on the experimental and simulated methods.	Metformin	0-23	SAFB like transcription modulator	Homo sapiens	25-28
35306537-4	2022	Levels of phosphorylated IkBalpha and p65 significantly rose in mdx/mTR-/- dystrophic hearts and Wt1 expression declined in the epicardium of mdx/mTR-/- mice when nuclear factor kappaB (NF-kappaB) and inflammation were inhibited by metformin.	Metformin	232-241	v-rel reticuloendotheliosis viral oncogene homolog A (avian)	Mus musculus	38-41
35306537-4	2022	Levels of phosphorylated IkBalpha and p65 significantly rose in mdx/mTR-/- dystrophic hearts and Wt1 expression declined in the epicardium of mdx/mTR-/- mice when nuclear factor kappaB (NF-kappaB) and inflammation were inhibited by metformin.	Metformin	232-241	WT1 transcription factor	Mus musculus	97-100
35306537-7	2022	Our study demonstrates that upregulation of Wt1 in epicardial cells contributes to fibrosis in dystrophic hearts and metformin-mediated inhibition of NF-kappaB can ameliorate the pathology, and thus showing clinical potential for dystrophic cardiomyopathy.	Metformin	117-126	WT1 transcription factor	Mus musculus	44-47
35426808-0	2022	(Metformin and lipopolysaccharide regulate transcription of NFATc2 gene via the transcription factor RUNX2).	Metformin	1-10	nuclear factor of activated T cells 2	Homo sapiens	60-66
35426808-1	2022	OBJECTIVE: To construct a luciferase reporter gene vector carrying human nuclear factor of activated T cells 2 (NFATc2) gene promoter and examine the effects of metformin and lipopolysaccharide (LPS) on the transcriptional activity of NFATc2 gene.	Metformin	161-170	nuclear factor of activated T cells 2	Homo sapiens	73-110
35426808-1	2022	OBJECTIVE: To construct a luciferase reporter gene vector carrying human nuclear factor of activated T cells 2 (NFATc2) gene promoter and examine the effects of metformin and lipopolysaccharide (LPS) on the transcriptional activity of NFATc2 gene.	Metformin	161-170	nuclear factor of activated T cells 2	Homo sapiens	112-118
35426808-1	2022	OBJECTIVE: To construct a luciferase reporter gene vector carrying human nuclear factor of activated T cells 2 (NFATc2) gene promoter and examine the effects of metformin and lipopolysaccharide (LPS) on the transcriptional activity of NFATc2 gene.	Metformin	161-170	nuclear factor of activated T cells 2	Homo sapiens	235-241
35426808-6	2022	The changes in transcription activity of NFATc2 gene were assessed after treatment with different concentrations of metformin and LPS for 24 h. We also examined the effect of mutation in RUNX2-binding site in NFATC2 gene promoter on the regulatory effects of metformin and LPS on NFATc2 transcription.	Metformin	116-125	nuclear factor of activated T cells 2	Homo sapiens	41-47
35426808-6	2022	The changes in transcription activity of NFATc2 gene were assessed after treatment with different concentrations of metformin and LPS for 24 h. We also examined the effect of mutation in RUNX2-binding site in NFATC2 gene promoter on the regulatory effects of metformin and LPS on NFATc2 transcription.	Metformin	259-268	nuclear factor of activated T cells 2	Homo sapiens	41-47
35326689-0	2022	In Vivo and In Vitro Enhanced Tumoricidal Effects of Metformin, Active Vitamin D3, and 5-Fluorouracil Triple Therapy against Colon Cancer by Modulating the PI3K/Akt/PTEN/mTOR Network.	Metformin	53-62	phosphatase and tensin homolog	Homo sapiens	165-169
35370693-0	2022	Metformin Inhibits NLR Family Pyrin Domain Containing 3 (NLRP)-Relevant Neuroinflammation via an Adenosine-5"-Monophosphate-Activated Protein Kinase (AMPK)-Dependent Pathway to Alleviate Early Brain Injury After Subarachnoid Hemorrhage in Mice.	Metformin	0-9	NLR family, pyrin domain containing 3	Mus musculus	19-55
35370693-5	2022	The SAH-induced NLRP3-associated inflammatory response and the activation of microglia are also suppressed by metformin.	Metformin	110-119	NLR family, pyrin domain containing 3	Mus musculus	16-21
35370693-7	2022	Collectively, our findings indicate that metformin exerts its neuroprotective effects by inhibiting neuroinflammation in an AMPK-dependent manner, by modulating the production of NLRP3-associated proinflammatory factors and the activation of microglia.	Metformin	41-50	NLR family, pyrin domain containing 3	Mus musculus	179-184
35301425-7	2022	Interestingly, the antidiabetic drug metformin reversed mTORC1 hyperactivation and alleviated major behavioral and PC deficits in Bmal1 KO mice.	Metformin	37-46	aryl hydrocarbon receptor nuclear translocator-like	Mus musculus	130-135
35267651-0	2022	Dual Effect of Combined Metformin and 2-Deoxy-D-Glucose Treatment on Mitochondrial Biogenesis and PD-L1 Expression in Triple-Negative Breast Cancer Cells.	Metformin	24-33	CD274 molecule	Homo sapiens	98-103
35267651-1	2022	Metformin and 2-deoxy-D-glucose (2DG) exhibit multiple metabolic and immunomodulatory anti-cancer effects, such as suppressed proliferation or PD-L1 expression.	Metformin	0-9	CD274 molecule	Homo sapiens	143-148
35267651-8	2022	Suppressed N-glycosylation by 2DG or metformin + 2DG also caused PD-L1 deglycosylation and reduced surface expression in MDA-MB-231 cells.	Metformin	37-46	CD274 molecule	Homo sapiens	65-70
35131865-0	2022	The anti-diabetic drug metformin regulates voltage-gated sodium channel NaV1.7 via the ubiquitin-ligase NEDD4-2.	Metformin	23-32	neural precursor cell expressed, developmentally down-regulated gene 4-like	Mus musculus	104-111
35131865-8	2022	In addition, metformin induced a significant reduction in NEDD4-2 phosphorylation at the Serine 328 residue in DRG neurons, an inhibitory phosphorylation site of NEDD4-2.	Metformin	13-22	neural precursor cell expressed, developmentally down-regulated gene 4-like	Mus musculus	58-65
35131865-8	2022	In addition, metformin induced a significant reduction in NEDD4-2 phosphorylation at the Serine 328 residue in DRG neurons, an inhibitory phosphorylation site of NEDD4-2.	Metformin	13-22	neural precursor cell expressed, developmentally down-regulated gene 4-like	Mus musculus	162-169
35131865-9	2022	In current clamp recordings, metformin reduced the number of action potentials elicited by DRG neurons from Nedd4Lfl/fl , with a partial decrease also present in SNS-Nedd4L-/- mice, suggesting that metformin can also change neuronal excitability in an NEDD4-2-independent manner.	Metformin	29-38	neural precursor cell expressed, developmentally down-regulated gene 4-like	Mus musculus	252-259
35131865-9	2022	In current clamp recordings, metformin reduced the number of action potentials elicited by DRG neurons from Nedd4Lfl/fl , with a partial decrease also present in SNS-Nedd4L-/- mice, suggesting that metformin can also change neuronal excitability in an NEDD4-2-independent manner.	Metformin	198-207	neural precursor cell expressed, developmentally down-regulated gene 4-like	Mus musculus	166-172
35131865-9	2022	In current clamp recordings, metformin reduced the number of action potentials elicited by DRG neurons from Nedd4Lfl/fl , with a partial decrease also present in SNS-Nedd4L-/- mice, suggesting that metformin can also change neuronal excitability in an NEDD4-2-independent manner.	Metformin	198-207	neural precursor cell expressed, developmentally down-regulated gene 4-like	Mus musculus	252-259
35131865-10	2022	We suggest that NEDD4-2 is a critical player for the effect of metformin on the excitability of nociceptive neurons; this action may contribute to the relief of neuropathic pain.Significance StatementMetformin is a multi-target, anti-diabetic drug that has shown therapeutic potential to reduce neuropathic pain.	Metformin	63-72	neural precursor cell expressed, developmentally down-regulated gene 4-like	Mus musculus	16-23
35131865-12	2022	We found that metformin acts through the activity of the E3-ubiquitin ligase NEDD4-2 to reduce cell surface expression and currents of voltage gated sodium channels (Navs), especially the Nav1.7 isoform.	Metformin	14-23	neural precursor cell expressed, developmentally down-regulated gene 4-like	Mus musculus	77-84
35131865-14	2022	On the other hand, NEDD4-2 is indispensable for the metformin effect on the rheobase and the resting membrane potential of DRG neurons.	Metformin	52-61	neural precursor cell expressed, developmentally down-regulated gene 4-like	Mus musculus	19-26
35309430-0	2022	Determination and Correlation of Solubility of Metformin Hydrochloride in Aqueous Binary Solvents from 283.15 to 323.15 K. Metformin hydrochloride (MET HCl) is one of the most widely used oral hypoglycemic drugs in the world.	Metformin	47-70	SAFB like transcription modulator	Homo sapiens	148-151
35309430-0	2022	Determination and Correlation of Solubility of Metformin Hydrochloride in Aqueous Binary Solvents from 283.15 to 323.15 K. Metformin hydrochloride (MET HCl) is one of the most widely used oral hypoglycemic drugs in the world.	Metformin	123-146	SAFB like transcription modulator	Homo sapiens	148-151
35220243-1	2022	BACKGROUND/AIM: Recent evidence suggests potential synergistic antitumor effects of the combination of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors with the oral hypoglycemic agent metformin.	Metformin	225-234	CD274 molecule	Homo sapiens	156-161
35216470-0	2022	Proline Dehydrogenase/Proline Oxidase (PRODH/POX) Is Involved in the Mechanism of Metformin-Induced Apoptosis in C32 Melanoma Cell Line.	Metformin	82-91	proline dehydrogenase 1	Homo sapiens	39-44
25671589-1	2015	Dapagliflozin (Farxiga), alone, or in the fixed dose combination with metformin (Xigduo), is an orally active, highly selective, reversible inhibitor of sodium-glucose cotransporter type 2 (SGLT2) that is marketed in United States, Europe, and many other countries for the treatment of type 2 diabetes mellitus.	Metformin	70-79	solute carrier family 5 member 2	Homo sapiens	153-188
25671589-1	2015	Dapagliflozin (Farxiga), alone, or in the fixed dose combination with metformin (Xigduo), is an orally active, highly selective, reversible inhibitor of sodium-glucose cotransporter type 2 (SGLT2) that is marketed in United States, Europe, and many other countries for the treatment of type 2 diabetes mellitus.	Metformin	70-79	solute carrier family 5 member 2	Homo sapiens	190-195
25681088-2	2015	Metformin increases levels of activated AMPK (AMP-activated protein kinase) and decreases circulating IGF-1; encouraging its potential use in both cancer prevention and therapeutic settings.	Metformin	0-9	insulin-like growth factor 1	Rattus norvegicus	102-107
25681088-7	2015	In rats bearing small palpable mammary cancers, short-term metformin (150 mg/kg BW/d) treatment increased levels of phospho-AMPK and phospho-p53 (Ser20), but failed to reduce Ki67 labeling or expression of proliferation-related genes.	Metformin	59-68	Wistar clone pR53P1 p53 pseudogene	Rattus norvegicus	141-144
25542900-9	2015	Ritonavir and metformin effectively suppressed AKT and mTORC1 phosphorylation and prosurvival BCL-2 family member MCL-1 expression in multiple myeloma cell lines in vitro and in vivo.	Metformin	14-23	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	114-119
25216510-11	2015	CONCLUSIONS: Dual inhibition of SGLT1/SGLT2 with LX4211 produced significant dose-ranging improvements in glucose control without dose-increasing glucosuria and was associated with reductions in weight and systolic BP in metformin-treated patients with type 2 diabetes.	Metformin	221-230	solute carrier family 5 member 2	Homo sapiens	38-43
26120598-6	2015	Further investigation into the effects of metformin suggest that the drug directly activates AMPK and dose-dependently suppressed the release of TNF-alpha, IL-6, and MCP-1 by macrophages while enhancing the release of IL-10 in vitro.	Metformin	42-51	C-C motif chemokine ligand 2	Homo sapiens	166-171
25673763-6	2015	Metformin also restored the defective interleukin-2 (IL-2) production by TC CD4(+) T cells.	Metformin	0-9	interleukin 2	Mus musculus	38-51
25673763-6	2015	Metformin also restored the defective interleukin-2 (IL-2) production by TC CD4(+) T cells.	Metformin	0-9	interleukin 2	Mus musculus	53-57
35216470-0	2022	Proline Dehydrogenase/Proline Oxidase (PRODH/POX) Is Involved in the Mechanism of Metformin-Induced Apoptosis in C32 Melanoma Cell Line.	Metformin	82-91	proline dehydrogenase 1	Homo sapiens	45-48
35216470-1	2022	The role of proline dehydrogenase/proline oxidase (PRODH/POX) in the mechanism of antineoplastic activity of metformin (MET) was studied in C32 melanoma cells.	Metformin	109-118	proline dehydrogenase 1	Homo sapiens	51-56
35216470-1	2022	The role of proline dehydrogenase/proline oxidase (PRODH/POX) in the mechanism of antineoplastic activity of metformin (MET) was studied in C32 melanoma cells.	Metformin	109-118	proline dehydrogenase 1	Homo sapiens	57-60
35216470-1	2022	The role of proline dehydrogenase/proline oxidase (PRODH/POX) in the mechanism of antineoplastic activity of metformin (MET) was studied in C32 melanoma cells.	Metformin	109-118	SAFB like transcription modulator	Homo sapiens	120-123
35190587-6	2022	Among eight metformin sensitizing miRNAs identified by functional screening, miR-676-3p had both pro-apoptotic and cell cycle arrest activity in combination with metformin, whereas other miRNAs (miR-18b-5p, miR-145-3p miR-376b-5p, and miR-718) resulted primarily in cell cycle arrest when combined with metformin.	Metformin	12-21	microRNA 6763	Homo sapiens	77-87
35190587-6	2022	Among eight metformin sensitizing miRNAs identified by functional screening, miR-676-3p had both pro-apoptotic and cell cycle arrest activity in combination with metformin, whereas other miRNAs (miR-18b-5p, miR-145-3p miR-376b-5p, and miR-718) resulted primarily in cell cycle arrest when combined with metformin.	Metformin	303-312	microRNA 6763	Homo sapiens	77-87
35190587-7	2022	Investigation of the combined effect of miRNAs and metformin on CRC cell metabolism showed that miR-18b-5p, miR-145-3p, miR-376b-5p, miR-676-3p and miR-718 affected glycolysis only, while miR-1181 only regulated CRC respiration.	Metformin	51-60	microRNA 145	Homo sapiens	108-115
35190587-7	2022	Investigation of the combined effect of miRNAs and metformin on CRC cell metabolism showed that miR-18b-5p, miR-145-3p, miR-376b-5p, miR-676-3p and miR-718 affected glycolysis only, while miR-1181 only regulated CRC respiration.	Metformin	51-60	microRNA 6763	Homo sapiens	133-143
35085591-2	2022	Metformin (MET) is considered as the first-line therapy for patients with type 2 diabetes (T2D).	Metformin	0-9	SAFB like transcription modulator	Homo sapiens	11-14
35169250-5	2022	We aimed to investigate the therapeutic efficacy of tofacitinib and metformin on IL-17 and TGF-beta cytokines, skin fibrosis and inflammation in mouse model of systemic sclerosis (SSc).	Metformin	68-77	transforming growth factor alpha	Mus musculus	91-99
25538235-5	2015	In the current study, we find that low concentrations of metformin promote the formation of the AMPK alphabetagamma complex, resulting in an increase in net phosphorylation of the AMPK alpha catalytic subunit at Thr-172 by augmenting phosphorylation by LKB1 and antagonizing dephosphorylation by PP2C.	Metformin	57-66	serine/threonine kinase 11	Homo sapiens	253-257
25534988-9	2015	In turn, major mechanism of metformin action involved increased expression of proteins implicated in mitochondrial biogenesis and metabolism (PGC-1alpha, PPARalpha, COX IV, cytochrome c, HADHSC).	Metformin	28-37	peroxisome proliferator activated receptor alpha	Homo sapiens	154-163
25393640-10	2015	CONCLUSIONS: In a 2-months prospective pilot study, the addition of liraglutide to metformin resulted in improvement in oxidative stress as well as plasma ghrelin and HO-1 concentrations in patients with T2DM.	Metformin	83-92	heme oxygenase 1	Homo sapiens	167-171
25527635-4	2015	As predicted, metformin hampers cell motility in PC3 and DU145 prostate cancer cells and triggers a radical reorganization of the cell cytoskeleton.	Metformin	14-23	proprotein convertase subtilisin/kexin type 1	Homo sapiens	49-52
25527635-6	2015	We report that metformin leads to a major inhibition of Rac1 GTPase activity by interfering with some of its multiple upstream signaling pathways, namely P-Rex1 (a Guanine nucleotide exchange factor and activator of Rac1), cAMP, and CXCL12/CXCR4, resulting in decreased migration of prostate cancer cells.	Metformin	15-24	phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1	Homo sapiens	154-160
25573751-0	2015	Polymorphism of organic cation transporter 2 improves glucose-lowering effect of metformin via influencing its pharmacokinetics in Chinese type 2 diabetic patients.	Metformin	81-90	solute carrier family 22 member 2	Homo sapiens	16-44
25573751-1	2015	BACKGROUND AND OBJECTIVES: This study aimed to investigate how the organic cation transporter 2 nucleotide polymorphism at site 808 (G   T) affects metformin pharmacokinetics and its long-term anti-diabetic effect.	Metformin	148-157	solute carrier family 22 member 2	Homo sapiens	67-95
25573751-8	2015	CONCLUSION: As well as gender, the glucose-lowering efficiency of metformin can be enhanced by SLC22A2 808G &gt; T variants through the delay of its transportation and CLr in Chinese type 2 diabetes populations.	Metformin	66-75	solute carrier family 22 member 2	Homo sapiens	95-102
25305450-6	2015	Western blot showed that metformin activated caspase 3, caspase 9, PARP-1, Bak, and p21 and inactivated Mcl-1, HIAP-1, cyclin D1, CDK4, and CDK6.	Metformin	25-34	caspase 9	Homo sapiens	56-65
25305450-6	2015	Western blot showed that metformin activated caspase 3, caspase 9, PARP-1, Bak, and p21 and inactivated Mcl-1, HIAP-1, cyclin D1, CDK4, and CDK6.	Metformin	25-34	H3 histone pseudogene 16	Homo sapiens	84-87
25305450-6	2015	Western blot showed that metformin activated caspase 3, caspase 9, PARP-1, Bak, and p21 and inactivated Mcl-1, HIAP-1, cyclin D1, CDK4, and CDK6.	Metformin	25-34	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	104-109
25305450-6	2015	Western blot showed that metformin activated caspase 3, caspase 9, PARP-1, Bak, and p21 and inactivated Mcl-1, HIAP-1, cyclin D1, CDK4, and CDK6.	Metformin	25-34	baculoviral IAP repeat containing 3	Homo sapiens	111-117
25305450-7	2015	Metformin inhibited the expression of insulin growth factor-I receptor (IGF-IR), and phosphatidyl inositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and the downstream mammalian target of rapamycin (mTOR).	Metformin	0-9	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta	Homo sapiens	85-115
25305450-7	2015	Metformin inhibited the expression of insulin growth factor-I receptor (IGF-IR), and phosphatidyl inositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and the downstream mammalian target of rapamycin (mTOR).	Metformin	0-9	protein tyrosine kinase 2 beta	Homo sapiens	124-140
25305450-7	2015	Metformin inhibited the expression of insulin growth factor-I receptor (IGF-IR), and phosphatidyl inositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and the downstream mammalian target of rapamycin (mTOR).	Metformin	0-9	protein tyrosine kinase 2 beta	Homo sapiens	142-149
25628514-3	2015	Addition of the dipeptidyl peptidase-4 inhibitor linagliptin, with its proven efficacy, low propensity for hypoglycemia, and weight neutrality, has been shown to improve glycemic control for patients who are not well controlled with metformin.	Metformin	233-242	dipeptidyl peptidase 4	Homo sapiens	16-38
25359200-5	2015	In HEK293 cells, berberine inhibited OCT1- and OCT2-mediated metformin uptake in a concentration dependent manner and IC50 values for OCT1 and OCT2 were 7.28 and 11.3 muM, respectively.	Metformin	61-70	solute carrier family 22 member 2	Homo sapiens	47-51
35135603-2	2022	Metformin exerts antitumor effects in glioblastoma stem cells (GSCs) inhibiting CLIC1 activity, but its low potency hampers its translation in clinical settings.	Metformin	0-9	chloride intracellular channel 1	Danio rerio	80-85
35135603-5	2022	RESULTS: We identified Q48 and Q54 as two novel CLIC1 blockers, characterized by higher antiproliferative potency than metformin in vitro, in both GSC 2D cultures and 3D spheroids.	Metformin	119-128	chloride intracellular channel 1	Danio rerio	48-53
35186762-6	2022	The aim of this study was to investigate the metabolic alterations associated with metformin (MET), an anti-diabetic agent when combined with two antifolate drugs: trimethoprim (TMP) or methotrexate (MTX), and how metabolic changes within the cancer cell may be used to increase cellular death.	Metformin	94-97	SAFB like transcription modulator	Homo sapiens	83-92
35156512-11	2022	Metformin also inhibited PDK1, HIF-1alpha expression, including downstream inflammatory mediators, HMGB1 and TNF-alpha.	Metformin	0-9	hypoxia inducible factor 1, alpha subunit	Mus musculus	31-41
35100024-9	2022	Treatment with metformin activated AMPK, which inhibited salt-induced hepatic inflammatory memory and cardiovascular damage by lowering the H3K27ac level on SIRT3 promoter, and increased NRF2 binding ability to activate SIRT3 expression.	Metformin	15-24	sirtuin 3	Mus musculus	157-162
35100024-9	2022	Treatment with metformin activated AMPK, which inhibited salt-induced hepatic inflammatory memory and cardiovascular damage by lowering the H3K27ac level on SIRT3 promoter, and increased NRF2 binding ability to activate SIRT3 expression.	Metformin	15-24	sirtuin 3	Mus musculus	220-225
35120085-3	2022	Many glucose-lowering treatment options are available, but glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are recommended in recent guidelines as the preferred add-on therapy to metformin to improve glycemic control.	Metformin	239-248	solute carrier family 5 member 2	Homo sapiens	148-154
35014178-10	2022	Metformin and icaritin regulate miR-381 expression and present anticancer properties.	Metformin	0-9	microRNA 381	Homo sapiens	32-39
35005849-8	2022	SGLT-2 inhibitors were associated with a higher risk of genital infections than DPP-4 inhibitors (HR: 2.39, 95% CI: 2.07-2.76), SU (HR: 3.23, 95% CI: 2.73-3.81), and TZD (HR: 3.23, 95% CI: 2.35-4.44), as an add-on therapy to metformin.	Metformin	225-234	solute carrier family 5 member 2	Homo sapiens	0-6
35158846-8	2022	In endometriosis, metformin might modify the stroma-epithelium communication via Wnt2/beta-catenin.	Metformin	18-27	catenin beta 1	Homo sapiens	86-98
35158754-0	2022	High Metabolic Dependence on Oxidative Phosphorylation Drives Sensitivity to Metformin Treatment in MLL/AF9 Acute Myeloid Leukemia.	Metformin	77-86	lysine methyltransferase 2A	Homo sapiens	100-103
35158754-5	2022	Furthermore, we show that metformin repressed the proliferation of MLL/AF9 AML cells by inhibiting mitochondrial respiration.	Metformin	26-35	lysine methyltransferase 2A	Homo sapiens	67-70
35158754-6	2022	Together, this study demonstrates that AML cells with an MLL/AF9 genotype have a high dependency on OXPHOS and could be therapeutically targeted by metformin.	Metformin	148-157	lysine methyltransferase 2A	Homo sapiens	57-60
35096812-11	2021	Metformin inhibited osteoclast formation and accordingly downregulated the genes involved in osteoclastogenesis: RANKL, macrophage colony stimulating factor (M-CSF) and osteoclast fusion gene DC-STAMP.	Metformin	0-9	colony stimulating factor 1	Homo sapiens	120-156
35096812-11	2021	Metformin inhibited osteoclast formation and accordingly downregulated the genes involved in osteoclastogenesis: RANKL, macrophage colony stimulating factor (M-CSF) and osteoclast fusion gene DC-STAMP.	Metformin	0-9	colony stimulating factor 1	Homo sapiens	158-163
35096812-12	2021	Osteoclast formation on both plastic and bone as well as bone resorption was inhibited by metformin in M-CSF and RANKL stimulated monocyte cultures, probably by reduction of RANK expression.	Metformin	90-99	colony stimulating factor 1	Homo sapiens	103-108
34994666-9	2022	Furthermore, the increasing protein levels of LC3-II, BECLIN 1, autophagy related 5 (ATG5) and AMP-activated protein kinase suggested activated autophagy-associated intracellular signalling AMPK and mTOR pathways upon DMBG treated.	Metformin	218-222	microtubule-associated protein 1 light chain 3 alpha	Rattus norvegicus	46-52
34994666-9	2022	Furthermore, the increasing protein levels of LC3-II, BECLIN 1, autophagy related 5 (ATG5) and AMP-activated protein kinase suggested activated autophagy-associated intracellular signalling AMPK and mTOR pathways upon DMBG treated.	Metformin	218-222	autophagy related 5	Rattus norvegicus	64-83
34994666-9	2022	Furthermore, the increasing protein levels of LC3-II, BECLIN 1, autophagy related 5 (ATG5) and AMP-activated protein kinase suggested activated autophagy-associated intracellular signalling AMPK and mTOR pathways upon DMBG treated.	Metformin	218-222	autophagy related 5	Rattus norvegicus	85-89
35056573-3	2022	The antibacterial effect of the combination of Triton X-100 (TX-100) and metformin (Met) on Enterococcus faecalis (E. faecalis) was evaluated by determining the minimum inhibitory concentration (MIC), minimum bactericidal concentration required to kill 99% bacteria (MBC99) and by conducting dynamic time-killing assays.	Metformin	73-82	SAFB like transcription modulator	Homo sapiens	84-87
35070958-6	2021	The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3a/b) to the METTL3 promoter.	Metformin	16-25	DNA methyltransferase 3 alpha	Homo sapiens	80-88
25484077-0	2015	Metformin alleviates hepatosteatosis by restoring SIRT1-mediated autophagy induction via an AMP-activated protein kinase-independent pathway.	Metformin	0-9	sirtuin 1	Mus musculus	50-55
25484077-1	2015	Metformin activates both PRKA and SIRT1.	Metformin	0-9	sirtuin 1	Mus musculus	34-39
25484077-3	2015	We aimed to elucidate the mechanism by which metformin alleviates hepatosteatosis by examining the molecular interplay between SIRT1, PRKA, and autophagy.	Metformin	45-54	sirtuin 1	Mus musculus	127-132
25484077-7	2015	Furthermore, CR and metformin both upregulated SIRT1 expression and also stimulated autophagy induction and flux in vivo.	Metformin	20-29	sirtuin 1	Mus musculus	47-52
25484077-8	2015	Metformin also prevented OA with high glucose-induced suppression of both SIRT1 expression and SIRT1-dependent activation of autophagy machinery, thereby alleviating intracellular lipid accumulation in vitro.	Metformin	0-9	sirtuin 1	Mus musculus	74-79
25484077-8	2015	Metformin also prevented OA with high glucose-induced suppression of both SIRT1 expression and SIRT1-dependent activation of autophagy machinery, thereby alleviating intracellular lipid accumulation in vitro.	Metformin	0-9	sirtuin 1	Mus musculus	95-100
25484077-9	2015	Interestingly, metformin treatment upregulated SIRT1 expression and activated PRKA even after siRNA-mediated knockdown of PRKAA1/2 and SIRT1, respectively.	Metformin	15-24	sirtuin 1	Mus musculus	47-52
25484077-9	2015	Interestingly, metformin treatment upregulated SIRT1 expression and activated PRKA even after siRNA-mediated knockdown of PRKAA1/2 and SIRT1, respectively.	Metformin	15-24	sirtuin 1	Mus musculus	135-140
25484077-10	2015	Taken together, these results suggest that metformin alleviates hepatic steatosis through PRKA-independent, SIRT1-mediated effects on the autophagy machinery.	Metformin	43-52	sirtuin 1	Mus musculus	108-113
25901291-11	2015	Pre-treatment with metformin in comparison to Iso (MI) group reduced peripheral neutrophils (p&lt;0.05, p&lt;0.01, and p&lt;0.001 at 25, 50, and 100 mg/kg; respectively) as well as MPO activity (p&lt;0.05 and p&lt;0.01 at 50 and 100 mg/ kg, respectively).	Metformin	19-28	myeloperoxidase	Rattus norvegicus	181-184
26380295-8	2015	Both PPARA and PPARGC1A regulate transcription of genes commonly regulated by glycolysis, by the antidiabetic agent metformin and by NOX, suggesting their major interplay in the control of HCC progression.	Metformin	116-125	peroxisome proliferator activated receptor alpha	Homo sapiens	5-10
26064951-7	2015	Further, the analysis of IGF2 concentration in cell supernatants showed that it decreased in BMSC cultures after 5 and 10 mM metformin treatments.	Metformin	125-134	insulin-like growth factor 2	Mus musculus	25-29
26064951-8	2015	In case of Balb/3T3 the concentration of IGF2 in culture supernatants decreased after 1 and 5 mM and increased after 10 mM of metformin.	Metformin	126-135	insulin-like growth factor 2	Mus musculus	41-45
25456211-12	2015	Xenograft nude mouse experiment also confirmed that AMPK/mTOR-mediated decrease of suvivin is in vivo implicated in metformin-induced apoptosis.	Metformin	116-125	mechanistic target of rapamycin kinase	Mus musculus	57-61
25607951-14	2015	These findings--albeit limited to a single case--suggest that tumors lacking LKB1 expression and/or endowed with an highly glycolytic phenotype might develop large necrotic areas following combined treatment with metformin plus bevacizumab.	Metformin	213-222	serine/threonine kinase 11	Homo sapiens	77-81
35070958-6	2021	The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3a/b) to the METTL3 promoter.	Metformin	16-25	methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit	Homo sapiens	97-103
35118026-3	2022	Methods: After searching for trials using combination therapy of metformin with an SU or DPP4 inhibitor in PubMed, Cochrane Library, and Embase, 1 prospective observational study and 15 randomized controlled studies were selected.	Metformin	65-74	dipeptidyl peptidase 4	Homo sapiens	89-93
33524789-6	2021	First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3.	Metformin	32-41	melanocyte inducing transcription factor	Homo sapiens	172-176
33524789-6	2021	First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3.	Metformin	32-41	microRNA 221	Homo sapiens	202-209
33524789-6	2021	First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3.	Metformin	32-41	eukaryotic translation initiation factor 2 alpha kinase 2	Homo sapiens	269-272
33524789-7	2021	Secondly, some signaling pathways were involved in the process of metformin inhibiting autophagy, such as AMPK-related signaling pathways (AMPK/NF-kappaB and other undetermined AMPK-related signaling pathways), Hedgehog, miR-570-3p, miR-142-3p, and MiR-3127-5p.	Metformin	66-75	microRNA 570	Homo sapiens	221-228
33609419-12	2021	Moreover, metformin attenuated the mTOR/AKT signaling pathway and altered adipokine profiles.	Metformin	10-19	mechanistic target of rapamycin kinase	Mus musculus	35-39
33404163-0	2021	Roles of Metformin-mediated Girdin expression in metastasis of Epithelial Ovarian Cancer (EOC).	Metformin	9-18	coiled-coil domain containing 88A	Homo sapiens	28-34
33404163-5	2021	In addition, we confirmed that the inhibitory effect of Metformin on Girdin expression.	Metformin	56-65	coiled-coil domain containing 88A	Homo sapiens	69-75
33404163-6	2021	Mechanistically, the oncogenic effects of Girdin could be reversed by LY294002 (an AKT pathway inhibitor) and Metformin.	Metformin	110-119	coiled-coil domain containing 88A	Homo sapiens	42-48
33404163-7	2021	These results suggested that Metformin attenuated EOC metastasis through Girdin and targeting Girdin may be a promising therapeutic strategy for EOC in the future.	Metformin	29-38	coiled-coil domain containing 88A	Homo sapiens	73-79
33404163-7	2021	These results suggested that Metformin attenuated EOC metastasis through Girdin and targeting Girdin may be a promising therapeutic strategy for EOC in the future.	Metformin	29-38	coiled-coil domain containing 88A	Homo sapiens	94-100
33311577-3	2021	Here we found that background treatment with metformin diminished the SGLT2i-induced reductions in eGFR after 3 months of SGLT2i therapy in patients with type 2 diabetes and hypertension (-2.29 +- 0.90 vs -5.85 +- 1.27 mL/min/1.73 m2 for metformin users (n = 126) and nonusers (n = 97), respectively).	Metformin	45-54	solute carrier family 5 member 2	Homo sapiens	70-75
33311577-3	2021	Here we found that background treatment with metformin diminished the SGLT2i-induced reductions in eGFR after 3 months of SGLT2i therapy in patients with type 2 diabetes and hypertension (-2.29 +- 0.90 vs -5.85 +- 1.27 mL/min/1.73 m2 for metformin users (n = 126) and nonusers (n = 97), respectively).	Metformin	238-247	solute carrier family 5 member 2	Homo sapiens	70-75
33311577-6	2021	Next, we evaluated the interaction between metformin and RASis in the eGFR responses to SGLT2is.	Metformin	43-52	solute carrier family 5 member 2	Homo sapiens	88-93
33311577-7	2021	Under no background treatment with RASis, metformin abrogated the eGFR response to SGLT2is, but this response was preserved when RASis had been given along with metformin (decreases of 0.75 +- 1.28 vs. 4.60 +- 1.15 mL/min/1.73 m2 in eGFR, p = 0.028).	Metformin	42-51	solute carrier family 5 member 2	Homo sapiens	83-88
33946426-0	2021	Metformin Dysregulates the Unfolded Protein Response and the WNT/beta-Catenin Pathway in Endometrial Cancer Cells through an AMPK-Independent Mechanism.	Metformin	0-9	catenin beta 1	Homo sapiens	65-77
33946426-4	2021	More importantly, we report that metformin affects two important pro-survival pathways, such as the Unfolded Protein Response (UPR), following endoplasmic reticulum stress, and the WNT/beta-catenin pathway.	Metformin	33-42	catenin beta 1	Homo sapiens	185-197
33946426-6	2021	Furthermore, metformin dramatically inhibited beta-catenin mRNA and protein expression.	Metformin	13-22	catenin beta 1	Homo sapiens	46-58
33946426-7	2021	This was paralleled by a reduction in beta-catenin transcriptional activity, since metformin inhibited the activity of a TCF/LEF-luciferase promoter.	Metformin	83-92	catenin beta 1	Homo sapiens	38-50
34001842-0	2021	ZNF423 modulates the AMP-activated protein kinase pathway and metformin response in a single nucleotide polymorphisms, estrogen and selective estrogen receptor modulator dependent fashion.	Metformin	62-71	estrogen receptor 1 (alpha)	Mus musculus	142-159
34001842-6	2021	Moreover, using clustered regularly interspaced short palindromic repeats/Cas9-engineered ZR75-1 breast cancer cells with different ZNF423 SNP genotypes, striking differences in cellular responses to metformin, either alone or in the combination of tamoxifen, were observed in both cell culture and the mouse xenograft model.	Metformin	200-209	zinc finger protein 423	Homo sapiens	132-138
33350292-9	2021	The high concentration of metformin elevated the number of Annexin V positive apoptotic cells, and the increase in the apoptotic index was statistically significant.	Metformin	26-35	annexin A5	Homo sapiens	59-68
33935082-6	2021	RESULTS: Dual therapy with metformin (Met) + dipeptidyl peptidase-4 inhibitor (DPP-4i), Met + thiazolidinedione (TZD), and sulfonylurea (SU) + thiazolidinediones (TZD) were significantly associated with all-cause dementia (HR = 0.904, 0.804, and 0.962, respectively) and VaD (HR = 0.865, 0.725, and 0.911, respectively), compared with Met + SU.	Metformin	27-36	SAFB like transcription modulator	Homo sapiens	38-41
33915173-9	2021	Importantly, enhancing TET2 stability using Metformin and VitaminC/ascorbic acid (AA) restores 5hmc and GATA6 levels, reverting squamous-like tumor phenotypes and WNT-dependence in vitro and in vivo.	Metformin	44-53	GATA binding protein 6	Homo sapiens	104-109
32667970-7	2021	Metformin at a clinically relevant concentration (10muM) evoked AMPK-dependent and ATF1-dependent increases in Hmox1, Nr1h2 (Lxrb), Abca1, Apoe, Igf1 and Pdgf, increases in several M2-markers and decreases in Nos2, in murine bone marrow macrophages.	Metformin	0-9	nuclear receptor subfamily 1, group H, member 2	Mus musculus	118-123
32667970-7	2021	Metformin at a clinically relevant concentration (10muM) evoked AMPK-dependent and ATF1-dependent increases in Hmox1, Nr1h2 (Lxrb), Abca1, Apoe, Igf1 and Pdgf, increases in several M2-markers and decreases in Nos2, in murine bone marrow macrophages.	Metformin	0-9	nuclear receptor subfamily 1, group H, member 2	Mus musculus	125-129
24824197-1	2014	AIMS: To investigate the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in patients with Type 2 diabetes mellitus inadequately controlled by a combination of metformin and pioglitazone.	Metformin	183-192	dipeptidyl peptidase 4	Homo sapiens	52-74
25310259-7	2014	Metformin targeted the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, suppressed the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and transcriptionally downregulated the expression of multidrug resistance protein 1/P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1).	Metformin	0-9	phosphoglycolate phosphatase	Homo sapiens	280-284
25310259-8	2014	Collectively, these findings suggested that metformin may target the AMPK/mTOR/HIF-1alpha/P-gp and MRP1 pathways to reverse MDR in hepatocellular carcinoma.	Metformin	44-53	phosphoglycolate phosphatase	Homo sapiens	90-94
25333332-10	2014	Our study demonstrated that metformin significantly reduced the cell viability, enhanced radiosensitivity and potentiated radiation-induced caspase-9/-3 cleavage in the NPC cells.	Metformin	28-37	caspase 9	Homo sapiens	140-149
25333332-11	2014	In addition, metformin plus radiation significantly upregulated the expression of p-ATM, p-ATR, gamma-H2AX and downregulated the expression of ATM, ATR, p95/NBS1, Rad50, DNA-PK, Ku70 and Ku80.	Metformin	13-22	ATM serine/threonine kinase	Homo sapiens	84-87
25333332-11	2014	In addition, metformin plus radiation significantly upregulated the expression of p-ATM, p-ATR, gamma-H2AX and downregulated the expression of ATM, ATR, p95/NBS1, Rad50, DNA-PK, Ku70 and Ku80.	Metformin	13-22	ATM serine/threonine kinase	Homo sapiens	143-146
25333332-11	2014	In addition, metformin plus radiation significantly upregulated the expression of p-ATM, p-ATR, gamma-H2AX and downregulated the expression of ATM, ATR, p95/NBS1, Rad50, DNA-PK, Ku70 and Ku80.	Metformin	13-22	nibrin	Homo sapiens	153-156
25333332-11	2014	In addition, metformin plus radiation significantly upregulated the expression of p-ATM, p-ATR, gamma-H2AX and downregulated the expression of ATM, ATR, p95/NBS1, Rad50, DNA-PK, Ku70 and Ku80.	Metformin	13-22	nibrin	Homo sapiens	157-161
25608995-9	2014	By real-time FQ-PCR tested, the expression levels of c-fos and c-myc in both cell lines gradually declined subsequent to metformin treatment at different concentrations (1, 5 and 15 mmol/L).	Metformin	121-130	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	63-68
25608995-10	2014	As compared with the control group, the c-myc and c-fos expressions in both cell lines in metformin groups had significant differences (P &lt; 0.05) except for the c-myc expression of the concentration of 1 mmol/L in HEC-1A cell line (P = 0.074).	Metformin	90-99	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	40-45
32667970-8	2021	Similar effects were seen in human blood-derived macrophages, in which metformin induced protective genes and M2-like genes, suppressible by si-ATF1-mediated knockdown.	Metformin	71-80	activating transcription factor 1	Homo sapiens	144-148
32667970-10	2021	Metformin induced lesional macrophage expression of p-AMPK, p-ATF1 and downstream M2-like protective effects.	Metformin	0-9	activating transcription factor 1	Homo sapiens	62-66
33968030-3	2021	Using an adenovirus (Ad)-induced viral hepatitis mouse model, we found that metformin treatment significantly attenuated liver injury, with reduced serum aspartate transaminase (AST) and alanine transaminase (ALT) levels and liver histological changes, presumably via decreased effector T cell responses.	Metformin	76-85	solute carrier family 17 (anion/sugar transporter), member 5	Mus musculus	154-176
33968030-3	2021	Using an adenovirus (Ad)-induced viral hepatitis mouse model, we found that metformin treatment significantly attenuated liver injury, with reduced serum aspartate transaminase (AST) and alanine transaminase (ALT) levels and liver histological changes, presumably via decreased effector T cell responses.	Metformin	76-85	solute carrier family 17 (anion/sugar transporter), member 5	Mus musculus	178-181
33968030-3	2021	Using an adenovirus (Ad)-induced viral hepatitis mouse model, we found that metformin treatment significantly attenuated liver injury, with reduced serum aspartate transaminase (AST) and alanine transaminase (ALT) levels and liver histological changes, presumably via decreased effector T cell responses.	Metformin	76-85	glutamic pyruvic transaminase, soluble	Mus musculus	187-207
33968030-3	2021	Using an adenovirus (Ad)-induced viral hepatitis mouse model, we found that metformin treatment significantly attenuated liver injury, with reduced serum aspartate transaminase (AST) and alanine transaminase (ALT) levels and liver histological changes, presumably via decreased effector T cell responses.	Metformin	76-85	glutamic pyruvic transaminase, soluble	Mus musculus	209-212
33880815-4	2021	Glucagon like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 (SGLT2) inhibitors improve glycemic control, lower body weight and blood pressure, are recommended after lifestyle and metformin as initial therapy for diabetic patients with cardiovascular or kidney comorbidities regarding their cardiorenal benefits.	Metformin	206-215	solute carrier family 5 member 2	Homo sapiens	56-86
33880815-4	2021	Glucagon like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 (SGLT2) inhibitors improve glycemic control, lower body weight and blood pressure, are recommended after lifestyle and metformin as initial therapy for diabetic patients with cardiovascular or kidney comorbidities regarding their cardiorenal benefits.	Metformin	206-215	solute carrier family 5 member 2	Homo sapiens	88-93
33887464-9	2021	Metformin treatment prompted apoptosis upon miR-17-overexpression only in LKB1WT cell lines, as well as in LWT/miR17H PDXs.	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	74-78
33860456-0	2022	Brain Boron Level, DNA Content, and Myeloperoxidase Activity of Metformin-Treated Rats in Diabetes and Prostate Cancer Model.	Metformin	64-73	myeloperoxidase	Rattus norvegicus	36-51
33860456-9	2022	The administration of metformin with CM and DCM obviously declined MPO activity and increased brain boron levels almost near to control group level.	Metformin	22-31	myeloperoxidase	Rattus norvegicus	67-70
33857309-8	2021	Compared to other calorie restriction mimetics such as metformin, rapamycin, resveratrol and NAD+ precursors, SGLT2 inhibitors appear to be the most promising in the treatment of ageing-related diseases, due to its regulation of multiple longevity pathways that closely resemble that achieved by calorie restriction, and their established efficacy in reduction in cardiovascular events and all-cause mortality.	Metformin	55-64	solute carrier family 5 member 2	Homo sapiens	110-115
33535788-0	2021	New Insight Into Metformin-Induced Cholesterol-Lowering Effect Crosstalk Between Glucose and Cholesterol Homeostasis via ChREBP (Carbohydrate-Responsive Element-Binding Protein)-Mediated PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Regulation.	Metformin	17-26	proprotein convertase subtilisin/kexin type 9	Homo sapiens	187-192
33535788-0	2021	New Insight Into Metformin-Induced Cholesterol-Lowering Effect Crosstalk Between Glucose and Cholesterol Homeostasis via ChREBP (Carbohydrate-Responsive Element-Binding Protein)-Mediated PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Regulation.	Metformin	17-26	proprotein convertase subtilisin/kexin type 9	Homo sapiens	194-239
33535788-2	2021	Approach and Results: In 2 dyslipidemia mouse models, administration of metformin significantly decreased serum cholesterol and PCSK9 (proprotein convertase subtilisin/kexin type 9) levels, accompanied by decreased expression of PCSK9 in both mRNA and protein levels resulting in a 3-fold increase of LDLR (low-density lipoprotein receptor) in the liver.	Metformin	72-81	proprotein convertase subtilisin/kexin type 9	Mus musculus	128-133
33535788-2	2021	Approach and Results: In 2 dyslipidemia mouse models, administration of metformin significantly decreased serum cholesterol and PCSK9 (proprotein convertase subtilisin/kexin type 9) levels, accompanied by decreased expression of PCSK9 in both mRNA and protein levels resulting in a 3-fold increase of LDLR (low-density lipoprotein receptor) in the liver.	Metformin	72-81	proprotein convertase subtilisin/kexin type 9	Mus musculus	135-180
33535788-2	2021	Approach and Results: In 2 dyslipidemia mouse models, administration of metformin significantly decreased serum cholesterol and PCSK9 (proprotein convertase subtilisin/kexin type 9) levels, accompanied by decreased expression of PCSK9 in both mRNA and protein levels resulting in a 3-fold increase of LDLR (low-density lipoprotein receptor) in the liver.	Metformin	72-81	proprotein convertase subtilisin/kexin type 9	Mus musculus	229-234
33577301-0	2021	Metformin Liposome-Mediated PD-L1 Downregulation for Amplifying the Photodynamic Immunotherapy Efficacy.	Metformin	0-9	CD274 molecule	Homo sapiens	28-33
33610593-1	2021	BACKGROUND: Metformin has anti-carcinogenic properties and is also known to inhibit the Sonic hedgehog pathway, but no population-based studies exist analyzing the potential protective effect for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).	Metformin	12-21	sonic hedgehog signaling molecule	Homo sapiens	88-102
33610593-1	2021	BACKGROUND: Metformin has anti-carcinogenic properties and is also known to inhibit the Sonic hedgehog pathway, but no population-based studies exist analyzing the potential protective effect for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).	Metformin	12-21	serpin family B member 3	Homo sapiens	252-255
33610593-2	2021	OBJECTIVES: To delineate the association between metformin use and invasive SCC, SCC in situ (SCCis) and BCC.	Metformin	49-58	serpin family B member 3	Homo sapiens	76-79
33610593-2	2021	OBJECTIVES: To delineate the association between metformin use and invasive SCC, SCC in situ (SCCis) and BCC.	Metformin	49-58	serpin family B member 3	Homo sapiens	81-84
33669354-3	2021	DPP4 inhibitors play an important role in the clinical management of T2DM: if metformin alone is not sufficient enough to control the blood sugar levels, DPP4 inhibitors are often used as second-line therapy; additionally, DPP-4 inhibitors are also used in triple therapies with metformin and sodium-glucose co-transporter-2 (SGLT-2) inhibitors or with metformin and insulin.	Metformin	78-87	dipeptidyl peptidase 4	Homo sapiens	0-4
25394090-3	2014	In vitro, DTG inhibits organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporter 1 (MATE 1) which are known to be involved in the disposition of metformin.	Metformin	169-178	solute carrier family 22 member 2	Homo sapiens	23-51
25394090-3	2014	In vitro, DTG inhibits organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporter 1 (MATE 1) which are known to be involved in the disposition of metformin.	Metformin	169-178	solute carrier family 22 member 2	Homo sapiens	53-57
25253174-5	2014	The ki-67 response to metformin was assessed comparing data obtained from baseline biopsy (ki-67 and tumor subtype) and serum markers (HOMA index, C-peptide, IGF-I, IGFBP-1, IGFBP-3, free IGF-I, hs-CRP, adiponectin) with the same measurements at definitive surgery.	Metformin	22-31	insulin like growth factor binding protein 3	Homo sapiens	174-181
25253174-7	2014	Compared with placebo, metformin significantly decreased ki-67 in women with HOMA &gt; 2.8, those in the lowest IGFBP-1 quintile, those in the highest IGFBP-3 quartile, those with low free IGF-I, those in the top hs-CRP tertile, and those with HER2-positive tumors.	Metformin	23-32	insulin like growth factor binding protein 1	Homo sapiens	112-119
25253174-7	2014	Compared with placebo, metformin significantly decreased ki-67 in women with HOMA &gt; 2.8, those in the lowest IGFBP-1 quintile, those in the highest IGFBP-3 quartile, those with low free IGF-I, those in the top hs-CRP tertile, and those with HER2-positive tumors.	Metformin	23-32	insulin like growth factor binding protein 3	Homo sapiens	151-158
25538335-10	2014	Moreover, TNF-alpha, MPO activity, TGF-beta, and nitrite content were significantly increased in diabetic rats, while treatment with coenzyme Q10 or metformin or their combination ameliorate STZ-nicotinamide induced renal damage due to improvement in renal function, oxidative stress, suppression of TNF-alpha, MPO activity, TGF-beta and nitrite content along with histopathological changes.	Metformin	149-158	myeloperoxidase	Rattus norvegicus	21-24
25538335-10	2014	Moreover, TNF-alpha, MPO activity, TGF-beta, and nitrite content were significantly increased in diabetic rats, while treatment with coenzyme Q10 or metformin or their combination ameliorate STZ-nicotinamide induced renal damage due to improvement in renal function, oxidative stress, suppression of TNF-alpha, MPO activity, TGF-beta and nitrite content along with histopathological changes.	Metformin	149-158	myeloperoxidase	Rattus norvegicus	311-314
25289085-7	2014	Metformin was observed to downregulate IGF-1R and upregulate IGF binding protein-1 (IGFBP-1) mRNA and protein expression, while compound C, an adenosine monophosphate protein kinase inhibitor, reversed this effect.	Metformin	0-9	insulin like growth factor binding protein 1	Homo sapiens	61-82
25289085-7	2014	Metformin was observed to downregulate IGF-1R and upregulate IGF binding protein-1 (IGFBP-1) mRNA and protein expression, while compound C, an adenosine monophosphate protein kinase inhibitor, reversed this effect.	Metformin	0-9	insulin like growth factor binding protein 1	Homo sapiens	84-91
25419360-6	2014	As a result, protein abundance of Bcl-2 and cyclin D1 was decreased and PTEN was increased in cells exposed to metformin.	Metformin	111-120	phosphatase and tensin homolog	Homo sapiens	72-76
25143389-3	2014	Treatment with metformin or down-regulation of Sp TFs by RNAi also inhibits two major pro-oncogenic pathways in pancreatic cancer cells, namely mammalian target of rapamycin (mTOR) signaling and epidermal growth factor (EGFR)-dependent activation of Ras.	Metformin	15-24	epidermal growth factor	Homo sapiens	195-218
25143389-3	2014	Treatment with metformin or down-regulation of Sp TFs by RNAi also inhibits two major pro-oncogenic pathways in pancreatic cancer cells, namely mammalian target of rapamycin (mTOR) signaling and epidermal growth factor (EGFR)-dependent activation of Ras.	Metformin	15-24	epidermal growth factor	Homo sapiens	220-224
25143389-6	2014	Thus, the antineoplastic activities of metformin in pancreatic cancer are due, in part, to down-regulation of Sp TFs and Sp-regulated IGF-1R and EGFR, which in turn results in inhibition of mTOR and Ras signaling, respectively.	Metformin	39-48	epidermal growth factor	Homo sapiens	145-149
24863949-3	2014	Dipeptidyl peptidase-4 inhibitors are good candidates for early use as they are efficacious in combination with metformin, show weight neutrality and a low risk of hypoglycaemia.	Metformin	112-121	dipeptidyl peptidase 4	Homo sapiens	0-22
24827939-1	2014	AIM: Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists are widely used in combinations with metformin in the treatment of type 2 diabetes; however, data on long-term safety compared with conventional combination therapies are limited.	Metformin	129-138	dipeptidyl peptidase 4	Homo sapiens	5-27
24827939-1	2014	AIM: Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists are widely used in combinations with metformin in the treatment of type 2 diabetes; however, data on long-term safety compared with conventional combination therapies are limited.	Metformin	129-138	dipeptidyl peptidase 4	Homo sapiens	29-34
25402373-5	2014	Treatment of human pancreatic BON1, bronchopulmonary NCI-H727, and midgut GOT1 neuroendocrine tumor cells with increasing concentrations of metformin (0.1-10 mM) dose-dependently suppressed cell viability and cell counts.	Metformin	140-149	glutamic-oxaloacetic transaminase 1	Homo sapiens	74-78
25402373-6	2014	Metformin induced AMPK phosphorylation in pancreatic BON1 and midgut GOT1 but suppressed AMPK activity in bronchopulmonary NCI-H727.	Metformin	0-9	glutamic-oxaloacetic transaminase 1	Homo sapiens	69-73
25402373-8	2014	Metformin suppressed mTORC1 signaling in all three tumor cell types, evidenced by suppression of 4EBP1, pP70S6K, and S6 phosphorylation, and was associated with compensatory AKT activity.	Metformin	0-9	eukaryotic translation initiation factor 4E binding protein 1	Homo sapiens	97-102
25110054-0	2014	Metformin suppresses CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating aryl hydrocarbon receptor expression.	Metformin	0-9	cytochrome P450 family 1 subfamily A member 1	Homo sapiens	21-27
25110054-2	2014	Here, we investigated the effects of the anti-diabetes drug metformin on expression of CYP1A1 and CYP1B1 in breast cancer cells under constitutive and inducible conditions.	Metformin	60-69	cytochrome P450 family 1 subfamily A member 1	Homo sapiens	87-93
25110054-3	2014	Our results indicated that metformin down-regulated the expression of CYP1A1 and CYP1B1 in breast cancer cells under constitutive and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced conditions.	Metformin	27-36	cytochrome P450 family 1 subfamily A member 1	Homo sapiens	70-76
25110054-4	2014	Down-regulation of AhR expression was required for metformin-mediated decreases in CYP1A1 and CYP1B1 expression, and the metformin-mediated CYP1A1 and CYP1B1 reduction is irrelevant to estrogen receptor alpha (ERalpha) signaling.	Metformin	51-60	cytochrome P450 family 1 subfamily A member 1	Homo sapiens	83-89
25110054-4	2014	Down-regulation of AhR expression was required for metformin-mediated decreases in CYP1A1 and CYP1B1 expression, and the metformin-mediated CYP1A1 and CYP1B1 reduction is irrelevant to estrogen receptor alpha (ERalpha) signaling.	Metformin	121-130	cytochrome P450 family 1 subfamily A member 1	Homo sapiens	140-146
25110054-7	2014	Metformin inhibited endogenous AhR ligand-induced CYP1A1 and CYP1B1 expression by suppressing tryptophan-2,3-dioxygenase (TDO) expression in MCF-7 cells.	Metformin	0-9	cytochrome P450 family 1 subfamily A member 1	Homo sapiens	50-56
25110054-9	2014	Our findings demonstrate that metformin reduces CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating AhR signaling.	Metformin	30-39	cytochrome P450 family 1 subfamily A member 1	Homo sapiens	48-54
25110054-10	2014	Metformin would be able to act as a potential chemopreventive agent against CYP1A1 and CYP1B1-mediated carcinogenesis and development of cancer.	Metformin	0-9	cytochrome P450 family 1 subfamily A member 1	Homo sapiens	76-82
33669354-3	2021	DPP4 inhibitors play an important role in the clinical management of T2DM: if metformin alone is not sufficient enough to control the blood sugar levels, DPP4 inhibitors are often used as second-line therapy; additionally, DPP-4 inhibitors are also used in triple therapies with metformin and sodium-glucose co-transporter-2 (SGLT-2) inhibitors or with metformin and insulin.	Metformin	279-288	dipeptidyl peptidase 4	Homo sapiens	0-4
33669354-3	2021	DPP4 inhibitors play an important role in the clinical management of T2DM: if metformin alone is not sufficient enough to control the blood sugar levels, DPP4 inhibitors are often used as second-line therapy; additionally, DPP-4 inhibitors are also used in triple therapies with metformin and sodium-glucose co-transporter-2 (SGLT-2) inhibitors or with metformin and insulin.	Metformin	279-288	dipeptidyl peptidase 4	Homo sapiens	0-4
33578894-4	2021	Metformin suppressed the expression of H3K4 methyltransferases MLL1, MLL2, and WDR82.	Metformin	0-9	lysine methyltransferase 2A	Homo sapiens	63-67
33563332-0	2021	Metformin attenuates plaque-associated tau pathology and reduces amyloid-beta burden in APP/PS1 mice.	Metformin	0-9	presenilin 1	Mus musculus	92-95
33563332-15	2021	Metformin ameliorated the microglial autophagy impairment, increased the number of microglia around Abeta plaques, promoted the phagocytosis of NP tau, and reduced Abeta load and NP tau pathology in APP/PS1 mice.	Metformin	0-9	presenilin 1	Mus musculus	203-206
33562646-7	2021	Enhanced annexin V staining occurred in LNCaP cells only with metformin/ARAT combinations, but no caspase 3 recruitment occurred in either cell line.	Metformin	62-71	annexin A5	Homo sapiens	9-18
33562646-8	2021	Finally, metformin and metformin/ARAT combinations increased lysosomal permeability resulting in cathepsin G-mediated PARP-1 cleavage and cell death.	Metformin	9-18	cathepsin G	Homo sapiens	97-108
33562646-8	2021	Finally, metformin and metformin/ARAT combinations increased lysosomal permeability resulting in cathepsin G-mediated PARP-1 cleavage and cell death.	Metformin	23-32	cathepsin G	Homo sapiens	97-108
33614629-0	2020	Metformin-Enhanced Cardiac AMP-Activated Protein Kinase/Atrogin-1 Pathways Inhibit Charged Multivesicular Body Protein 2B Accumulation in Ischemia-Reperfusion Injury.	Metformin	0-9	F-box protein 32	Mus musculus	56-65
33614629-0	2020	Metformin-Enhanced Cardiac AMP-Activated Protein Kinase/Atrogin-1 Pathways Inhibit Charged Multivesicular Body Protein 2B Accumulation in Ischemia-Reperfusion Injury.	Metformin	0-9	charged multivesicular body protein 2B	Mus musculus	83-121
33614629-13	2020	Metformin suppressed CHMP2B accumulation and ameliorated H/R-induced autophagic dysfunction by activating AMPK.	Metformin	0-9	charged multivesicular body protein 2B	Mus musculus	21-27
33614629-16	2020	Finally, this study revealed that metformin-inhibited CHMP2B accumulation induced autophagic impairment and ischemic susceptibility in vivo through the AMPK-regulated CHMP2B degradation by atrogin-1.	Metformin	34-43	charged multivesicular body protein 2B	Mus musculus	54-60
33614629-16	2020	Finally, this study revealed that metformin-inhibited CHMP2B accumulation induced autophagic impairment and ischemic susceptibility in vivo through the AMPK-regulated CHMP2B degradation by atrogin-1.	Metformin	34-43	charged multivesicular body protein 2B	Mus musculus	167-173
33614629-16	2020	Finally, this study revealed that metformin-inhibited CHMP2B accumulation induced autophagic impairment and ischemic susceptibility in vivo through the AMPK-regulated CHMP2B degradation by atrogin-1.	Metformin	34-43	F-box protein 32	Mus musculus	189-198
33614629-18	2020	Metformin treatment degrades CHMP2B through the AMPK-atrogin-1-dependent pathway to maintain the homeostasis of autophagic flux.	Metformin	0-9	charged multivesicular body protein 2B	Mus musculus	29-35
33614629-18	2020	Metformin treatment degrades CHMP2B through the AMPK-atrogin-1-dependent pathway to maintain the homeostasis of autophagic flux.	Metformin	0-9	F-box protein 32	Mus musculus	53-62
33059952-11	2021	RESULTS: Data showed that metformin decreased cell survival and expression of miRNA-21, miRNA-155, and miRNA-182 (p <0.05).	Metformin	26-35	microRNA 21	Homo sapiens	78-86
25249538-0	2014	Activation of EGFR, HER2 and HER3 by neurotensin/neurotensin receptor 1 renders breast tumors aggressive yet highly responsive to lapatinib and metformin in mice.	Metformin	144-153	epidermal growth factor receptor	Mus musculus	14-18
25249538-0	2014	Activation of EGFR, HER2 and HER3 by neurotensin/neurotensin receptor 1 renders breast tumors aggressive yet highly responsive to lapatinib and metformin in mice.	Metformin	144-153	neurotensin receptor 1	Mus musculus	49-71
25249538-8	2014	Accordingly, lapatinib, an EGFR/HER2 tyrosine kinase inhibitor, as well as metformin, reduced the tumor growth of cells overexpressing NTS and NTSR1.	Metformin	75-84	neurotensin receptor 1	Mus musculus	143-148
25201727-7	2014	Metformin could inhibit TGF-beta-induced EMT in Vcap cells, as manifested by inhibition of the increase of N-cadherin (p=0.013), Vimentin (p=0.002) and the decrease of E-cadherin (p=0.0023) and beta-catenin (p=0.034) at mRNA and protein levels.	Metformin	0-9	vimentin	Homo sapiens	129-137
25201727-7	2014	Metformin could inhibit TGF-beta-induced EMT in Vcap cells, as manifested by inhibition of the increase of N-cadherin (p=0.013), Vimentin (p=0.002) and the decrease of E-cadherin (p=0.0023) and beta-catenin (p=0.034) at mRNA and protein levels.	Metformin	0-9	catenin beta 1	Homo sapiens	194-206
25067825-8	2014	Interestingly, phosphorylated alpha-synuclein was significantly decreased by metformin administration.	Metformin	77-86	synuclein, alpha	Mus musculus	30-45
24714080-6	2014	However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway.	Metformin	206-215	ribosomal protein S6 kinase B1	Homo sapiens	142-146
24714080-8	2014	Taken together, our results indicate that metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through downregulation of c-FLIP, which is mediated by the mTOR/S6K1 pathway, but independent of AMPK; furthermore, these findings provide a rationale for the combined application of metformin with TRAIL in the treatment of bladder cancer.	Metformin	42-51	ribosomal protein S6 kinase B1	Homo sapiens	181-185
25309796-13	2014	CONCLUSION: These results demonstrate that Vav3 is involved in the process of metformin-mediated glucose regulation.	Metformin	78-87	vav 3 oncogene	Mus musculus	43-47
25089625-1	2014	BACKGROUND: Incretin-based therapies which include glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are recommended by several practice guidelines as second-line agents for add-on therapy to metformin in patients with type 2 diabetes (T2DM) who do not achieve glycemic control with metformin plus lifestyle interventions alone.	Metformin	238-247	dipeptidyl peptidase 4	Homo sapiens	105-127
25089625-1	2014	BACKGROUND: Incretin-based therapies which include glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are recommended by several practice guidelines as second-line agents for add-on therapy to metformin in patients with type 2 diabetes (T2DM) who do not achieve glycemic control with metformin plus lifestyle interventions alone.	Metformin	238-247	dipeptidyl peptidase 4	Homo sapiens	129-134
25089625-1	2014	BACKGROUND: Incretin-based therapies which include glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are recommended by several practice guidelines as second-line agents for add-on therapy to metformin in patients with type 2 diabetes (T2DM) who do not achieve glycemic control with metformin plus lifestyle interventions alone.	Metformin	329-338	dipeptidyl peptidase 4	Homo sapiens	105-127
25089625-1	2014	BACKGROUND: Incretin-based therapies which include glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are recommended by several practice guidelines as second-line agents for add-on therapy to metformin in patients with type 2 diabetes (T2DM) who do not achieve glycemic control with metformin plus lifestyle interventions alone.	Metformin	329-338	dipeptidyl peptidase 4	Homo sapiens	129-134
24859412-10	2014	Sorted ALDH-1+ cell tumor sphere forming capacity was preferentially reduced by metformin.	Metformin	80-89	aldehyde dehydrogenase 1 family member A1	Homo sapiens	7-13
24193408-0	2014	Polycystin-1 but not polycystin-2 deficiency causes upregulation of the mTOR pathway and can be synergistically targeted with rapamycin and metformin.	Metformin	140-149	polycystin 1, transient receptor potential channel interacting	Homo sapiens	0-12
24193408-8	2014	Interestingly, combining low concentrations of rapamycin and metformin was more effective for inhibiting mTOR complex 1 activity in TRPP1-deficient cells than either drug alone.	Metformin	61-70	polycystin 1, transient receptor potential channel interacting	Homo sapiens	132-137
25025689-4	2014	As we have shown recently, the anti-diabetic drug metformin is capable of dephosphorylating tau at AD-relevant phospho-sites.	Metformin	50-59	microtubule associated protein tau	Homo sapiens	92-95
25118504-11	2014	Cells treated with metformin for 48 hour showed higher expression of OGT than cells treated for 24 hours.	Metformin	19-28	O-linked N-acetylglucosamine (GlcNAc) transferase	Homo sapiens	69-72
25118504-13	2014	However taking into account its impact on the expression of O-GlcNAc transferase, further studies on the molecular mechanism of metformin action are necessary	Metformin	128-137	O-linked N-acetylglucosamine (GlcNAc) transferase	Homo sapiens	60-80
24877601-0	2014	Convergence of IPMK and LKB1-AMPK signaling pathways on metformin action.	Metformin	56-65	inositol polyphosphate multikinase	Mus musculus	15-19
24877601-5	2014	Here we investigated the role of IPMK in metformin-induced AMPK activation.	Metformin	41-50	inositol polyphosphate multikinase	Mus musculus	33-37
24877601-7	2014	Overexpression of wild-type IPMK was sufficient to restore LKB1-AMPK activation by either metformin or AICAR in IPMK(-/-) murine embryonic fibroblast cells, suggesting that IPMK may act as an upstream regulator of LKB1-AMPK signaling in response to metformin.	Metformin	90-99	inositol polyphosphate multikinase	Mus musculus	28-32
24877601-7	2014	Overexpression of wild-type IPMK was sufficient to restore LKB1-AMPK activation by either metformin or AICAR in IPMK(-/-) murine embryonic fibroblast cells, suggesting that IPMK may act as an upstream regulator of LKB1-AMPK signaling in response to metformin.	Metformin	249-258	inositol polyphosphate multikinase	Mus musculus	28-32
24877601-8	2014	Moreover, this regulation was mediated by protein-protein interaction between IPMK and LKB1 as a dominant-negative peptide, which abrogates this interaction, attenuated metformin"s ability to activate AMPK.	Metformin	169-178	inositol polyphosphate multikinase	Mus musculus	78-82
24639059-11	2014	CONCLUSIONS: DPP-IV inhibitors could achieve a long-term effective and safe glycaemic control for use as monotherapy or in combination with metformin.	Metformin	140-149	dipeptidyl peptidase 4	Homo sapiens	13-19
32654569-0	2021	Metformin alleviates experimental colitis in mice by up-regulating TGF-beta signaling.	Metformin	0-9	transforming growth factor alpha	Mus musculus	67-75
32979231-0	2021	Efficacy and safety of a sodium-glucose co-transporter-2 inhibitor vs placebo as an add-on therapy for people with type 2 diabetes inadequately treated with metformin and a dipeptidyl peptidase-4 inhibitor: a systematic review and meta-analysis of randomized controlled trials.	Metformin	157-166	solute carrier family 5 member 2	Homo sapiens	25-56
32979231-8	2021	CONCLUSIONS: In comparison with placebo, add-on therapy with a sodium-glucose co-transporter-2 inhibitor is significantly more efficacious in lowering HbA1c , fasting plasma glucose and weight in people with type 2 diabetes following inadequate glycaemic control with metformin and a dipeptidyl peptidase-4 inhibitor.	Metformin	268-277	solute carrier family 5 member 2	Homo sapiens	63-94
33043620-0	2021	SGLT2 inhibitors with and without metformin: a meta-analysis of cardiovascular, kidney and mortality outcomes.	Metformin	34-43	solute carrier family 5 member 2	Homo sapiens	0-5
33043620-8	2021	SGLT2 inhibitors reduced the risk of MACE, with and without concomitant metformin use (HR 0.93, 95% CI 0.87-1.00 and HR 0.82, 95% CI 0.71-0.86 respectively; P-heterogeneity=0.14).	Metformin	72-81	solute carrier family 5 member 2	Homo sapiens	0-5
33181201-0	2021	Does background metformin therapy influence the cardiovascular outcomes with SGLT-2 inhibitors in type 2 diabetes?	Metformin	16-25	solute carrier family 5 member 2	Homo sapiens	77-83
32594364-6	2021	In addition, metformin/MCC950 augmented the antioxidant defense machinery and attenuated the myeloperoxidase (MPO) activity.	Metformin	13-22	myeloperoxidase	Rattus norvegicus	93-108
32594364-6	2021	In addition, metformin/MCC950 augmented the antioxidant defense machinery and attenuated the myeloperoxidase (MPO) activity.	Metformin	13-22	myeloperoxidase	Rattus norvegicus	110-113
32741295-4	2021	Similar to metformin, the PolyMet-HA nanocomplexs could reduce the catalytic activity of the recombinant SHIP2 phosphatase domain in vitro.	Metformin	11-20	inositol polyphosphate phosphatase like 1	Homo sapiens	105-110
33527807-5	2021	Evogliptin is a recently developed dipeptidyl peptidase-4 (DPP-4) inhibitor, which can to be combined with metformin for treating T2DM.	Metformin	107-116	dipeptidyl peptidase 4	Homo sapiens	35-57
33527807-5	2021	Evogliptin is a recently developed dipeptidyl peptidase-4 (DPP-4) inhibitor, which can to be combined with metformin for treating T2DM.	Metformin	107-116	dipeptidyl peptidase 4	Homo sapiens	59-64
32067559-8	2021	SGLT-2 inhibitors and GLP-1 agonists should be considered when patients" diabetes is no longer well controlled with metformin.	Metformin	116-125	solute carrier family 5 member 2	Homo sapiens	0-6
33352227-8	2021	Furthermore, we use miR-21 as an example to explain the specific molecular mechanism underlying metformin-mediated regulation of the miRNA signaling pathway controlling angiogenesis and vascular protective effects.	Metformin	96-105	microRNA 21	Homo sapiens	20-26
33290383-0	2021	Metformin, valproic acid, and starvation induce seizures in a patient with partial SLC13A5 deficiency: a case of pharmaco-synergistic heterozygosity.	Metformin	0-9	solute carrier family 13 member 5	Homo sapiens	83-90
24980829-7	2014	Additionally, metformin modulated the levels of c-MYC and IRS-2, and this correlated with changes of the microRNA-33a levels.	Metformin	14-23	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	48-53
24980829-7	2014	Additionally, metformin modulated the levels of c-MYC and IRS-2, and this correlated with changes of the microRNA-33a levels.	Metformin	14-23	insulin receptor substrate 2	Homo sapiens	58-63
24797033-11	2014	In addition, metformin also increased the circulating adiponectin and liver adiponectin receptor 2 expression.	Metformin	13-22	adiponectin, C1Q and collagen domain containing	Rattus norvegicus	54-65
24683044-7	2014	Modulation by metformin of 42 of 1281 pulmonary microRNAs in smoke-free mice highlighted a variety of mechanisms, including modulation of AMPK, stress response, inflammation, NFkappaB, Tlr9, Tgf, p53, cell cycle, apoptosis, antioxidant pathways, Ras, Myc, Dicer, angiogenesis, stem cell recruitment, and angiogenesis.	Metformin	14-23	toll-like receptor 9	Mus musculus	185-189
24943970-0	2014	The relationship between anticancer effect of metformin and the transcriptional regulation of certain genes (CHOP, CAV-1, HO-1, SGK-1 and Par-4) on MCF-7 cell line.	Metformin	46-55	serum/glucocorticoid regulated kinase 1	Homo sapiens	128-133
24676803-0	2014	Increased FoxM1 expression is a target for metformin in the suppression of EMT in prostate cancer.	Metformin	43-52	forkhead box M1	Homo sapiens	10-15
24676803-5	2014	We observed that FoxM1 was expressed in the PCa cell lines and that metformin suppressed cell proliferation and the expression of FoxM1.	Metformin	68-77	forkhead box M1	Homo sapiens	130-135
24676803-8	2014	These results indicate that metformin suppresses EMT by inhibiting FoxM1.	Metformin	28-37	forkhead box M1	Homo sapiens	67-72
24676803-9	2014	We demonstrate that the suppression of FoxM1 may be an effective therapeutic strategy for PCa and provide further evidence of the anticancer effects of metformin.	Metformin	152-161	forkhead box M1	Homo sapiens	39-44
24747132-8	2014	AMPK and PTEN activities were modified by metformin, Compound C, siRNA for AMPK isoforms alpha1 and alpha2 and siRNA for PTEN, respectively.	Metformin	42-51	phosphatase and tensin homolog	Rattus norvegicus	9-13
24561578-7	2014	The activators of the AMPK/Akt pathway, adiponectin, AICAR, and metformin, attenuated superoxide generation, TRAF3IP2 expression, and oxLDL/TRAF3IP2-mediated EC death.	Metformin	64-73	TRAF3 interacting protein 2	Homo sapiens	109-117
24561578-7	2014	The activators of the AMPK/Akt pathway, adiponectin, AICAR, and metformin, attenuated superoxide generation, TRAF3IP2 expression, and oxLDL/TRAF3IP2-mediated EC death.	Metformin	64-73	TRAF3 interacting protein 2	Homo sapiens	140-148
24270984-8	2014	Furthermore, therapeutic concentrations of metformin increased AMPK and HSL activities and promoted lipolysis in T37i differentiated brown adipocytes.	Metformin	43-52	lipase, hormone sensitive	Mus musculus	72-75
24261663-7	2014	KEY RESULTS: Metformin (50 muM) decreased mRNA and protein levels of GLUT1, GLUT3, MCT4 and PFK 1 but did not affect LDH mRNA or protein levels.	Metformin	13-22	solute carrier family 2 member 1	Homo sapiens	69-74
24261663-7	2014	KEY RESULTS: Metformin (50 muM) decreased mRNA and protein levels of GLUT1, GLUT3, MCT4 and PFK 1 but did not affect LDH mRNA or protein levels.	Metformin	13-22	solute carrier family 2 member 3	Homo sapiens	76-81
24935589-0	2014	Cisplatin combined with metformin inhibits migration and invasion of human nasopharyngeal carcinoma cells by regulating E-cadherin and MMP-9.	Metformin	24-33	matrix metallopeptidase 9	Homo sapiens	135-140
24935589-9	2014	In the present study, with an increasing concentration of metformin, the expression of MMP-9 was downregulated whereas that of E-cadherin was significantly upregulated.	Metformin	58-67	matrix metallopeptidase 9	Homo sapiens	87-92
24372553-9	2014	Treatment with metformin attenuated the HG-induced reduction of SIRT1 expression, modulated the SIRT1 downstream targets FoxO-1 and p53/p21, and protected endothelial cells from HG-induced premature senescence.	Metformin	15-24	cyclin-dependent kinase inhibitor 1A (P21)	Mus musculus	136-139
24762600-9	2014	Metformin increased the expression of SIRT3 (1.5-fold) and SOD2 (2-fold) while down regulating NF-kappaB p65 (1.5-fold) and JNK1 (1.5-fold).	Metformin	0-9	superoxide dismutase 2	Rattus norvegicus	59-63
33290383-6	2021	Here, we report on a heterozygous SLC13A5-deficient patient who demonstrated evidence of pharmaco-synergistic heterozygosity upon administration of metformin, valproic acid, and starvation.	Metformin	148-157	solute carrier family 13 member 5	Homo sapiens	34-41
33510216-0	2021	Inhibition of mitochondrial function by metformin increases glucose uptake, glycolysis and GDF-15 release from intestinal cells.	Metformin	40-49	growth differentiation factor 15	Mus musculus	91-97
33510216-5	2021	Metformin increased expression of Slc2a1 (GLUT1), decreased expression of Slc2a2 (GLUT2) and Slc5a1 (SGLT1) whilst increasing GLUT-dependent glucose uptake and glycolytic rate as observed by live cell imaging of genetically encoded metabolite sensors and measurement of oxygen consumption and extracellular acidification rates.	Metformin	0-9	solute carrier family 2 (facilitated glucose transporter), member 1	Mus musculus	34-40
33510216-5	2021	Metformin increased expression of Slc2a1 (GLUT1), decreased expression of Slc2a2 (GLUT2) and Slc5a1 (SGLT1) whilst increasing GLUT-dependent glucose uptake and glycolytic rate as observed by live cell imaging of genetically encoded metabolite sensors and measurement of oxygen consumption and extracellular acidification rates.	Metformin	0-9	solute carrier family 2 (facilitated glucose transporter), member 1	Mus musculus	42-47
33510216-6	2021	Metformin caused mitochondrial dysfunction and metformin"s effects on 2D-cultures were phenocopied by treatment with rotenone and antimycin-A, including upregulation of GDF15 expression, previously linked to metformin dependent weight loss.	Metformin	0-9	growth differentiation factor 15	Mus musculus	169-174
33510216-6	2021	Metformin caused mitochondrial dysfunction and metformin"s effects on 2D-cultures were phenocopied by treatment with rotenone and antimycin-A, including upregulation of GDF15 expression, previously linked to metformin dependent weight loss.	Metformin	47-56	growth differentiation factor 15	Mus musculus	169-174
33510216-6	2021	Metformin caused mitochondrial dysfunction and metformin"s effects on 2D-cultures were phenocopied by treatment with rotenone and antimycin-A, including upregulation of GDF15 expression, previously linked to metformin dependent weight loss.	Metformin	208-217	growth differentiation factor 15	Mus musculus	169-174
33510216-8	2021	We conclude that metformin affects glucose uptake, glycolysis and GDF-15 secretion, likely downstream of the observed mitochondrial dysfunction.	Metformin	17-26	growth differentiation factor 15	Mus musculus	66-72
33019813-0	2021	Effects of Brief Adjunctive Metformin Therapy in Virologically Suppressed HIV-Infected Adults on Polyfunctional HIV-Specific CD8 T cell Responses to PD-L1 Blockade.	Metformin	28-37	CD274 molecule	Homo sapiens	149-154
33019813-8	2021	Ex vivo polyfunctional HIV-Gag-specific CD8 T cell responses to anti-PD-L1 mAb significantly improved (p < 0.05) over the 8-week course of metformin therapy.	Metformin	139-148	CD274 molecule	Homo sapiens	69-74
32926865-8	2021	Our optimized, validated bioanalytic method for measuring DPP4 activity in plasma samples was successfully employed to evaluate the effect of evogliptin (DA-1229) tartrate, which irreversibly and dose-dependently inhibits DPP4 enzymatic activity, without the dilution effect of human plasma samples and irrespective of the co-treated metformin.	Metformin	334-343	dipeptidyl peptidase 4	Homo sapiens	58-62
33220581-0	2021	Metformin inhibits proliferation of oral squamous cell carcinoma cells by suppressing proteolysis of nerve growth factor receptor.	Metformin	0-9	nerve growth factor receptor	Homo sapiens	101-129
33220581-5	2021	RESULTS: Metformin inhibited OSCC cell proliferation and blocked NGFR proteolysis, thereby reducing the generation of its intracellular domain and NGFR-N.	Metformin	9-18	nerve growth factor receptor	Homo sapiens	65-69
33220581-5	2021	RESULTS: Metformin inhibited OSCC cell proliferation and blocked NGFR proteolysis, thereby reducing the generation of its intracellular domain and NGFR-N.	Metformin	9-18	nerve growth factor receptor	Homo sapiens	147-151
33220581-7	2021	Furthermore, upregulation of NGFR-N downregulated levels of p53-specific downstream transcripts and proteins, whereas these levels were significantly upregulated in metformin-treated cells overexpressing NGFR.	Metformin	165-174	nerve growth factor receptor	Homo sapiens	204-208
33220581-8	2021	CONCLUSIONS: These results showed that metformin inhibited cell proliferation by suppressing NGFR proteolysis, thereby promoting its antitumor effect in OSCC and offering novel insight into a role for metformin in OSCC treatment.	Metformin	39-48	nerve growth factor receptor	Homo sapiens	93-97
33227290-1	2021	Cell based studies have suggested that the diabetes drug metformin may combine with the anaplastic lymphoma kinase receptor (ALK) inhibitor crizotinib to increase ALK positive lung cancer cell killing and overcome crizotinib resistance.	Metformin	57-66	anaplastic lymphoma kinase	Mus musculus	163-166
32958585-3	2021	A systematic literature search was performed up to March 23, 2020 to identify randomized controlled trials (RCTs) and observational studies of metformin that reported any event of squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma.	Metformin	143-152	serpin family B member 3	Homo sapiens	205-208
32987433-0	2021	Efficacy of Metformin and Chemotherapeutic Agents on the Inhibition of Colony Formation and Shh/Gli1 Pathway: Metformin/Docetaxel Versus Metformin/5-Fluorouracil.	Metformin	12-21	sonic hedgehog signaling molecule	Homo sapiens	92-95
32987433-0	2021	Efficacy of Metformin and Chemotherapeutic Agents on the Inhibition of Colony Formation and Shh/Gli1 Pathway: Metformin/Docetaxel Versus Metformin/5-Fluorouracil.	Metformin	110-119	sonic hedgehog signaling molecule	Homo sapiens	92-95
32987433-0	2021	Efficacy of Metformin and Chemotherapeutic Agents on the Inhibition of Colony Formation and Shh/Gli1 Pathway: Metformin/Docetaxel Versus Metformin/5-Fluorouracil.	Metformin	110-119	sonic hedgehog signaling molecule	Homo sapiens	92-95
32987433-11	2021	The combination of metformin with 5-FU or docetaxel significantly reduced the number of cells expressing the Shh protein compared to the 5-FU alone or docetaxel alone.	Metformin	19-28	sonic hedgehog signaling molecule	Homo sapiens	109-112
33187870-10	2021	Metformin treatment reverted LMNA, LMNC, and p53 expression levels to normal levels.	Metformin	0-9	lamin A/C	Homo sapiens	29-33
33187870-10	2021	Metformin treatment reverted LMNA, LMNC, and p53 expression levels to normal levels.	Metformin	0-9	lamin A/C	Homo sapiens	35-39
33187870-13	2021	Metformin may exert its anti-inflammatory property by modulation of senescence mediator LMNA.	Metformin	0-9	lamin A/C	Homo sapiens	88-92
33545810-3	2021	In this study, a poly(L-lactic acid) (PLLA)/nanoscale hydroxyapatite (nHA)/metformin (MET) nanocomposite scaffold was constructed via selective laser sintering.	Metformin	75-84	SAFB like transcription modulator	Homo sapiens	86-89
33545810-5	2021	The PLLA/nHA/MET scaffolds showed improved cell adhesion, appropriate porosity, good biocompatibility and osteogenic-induced ability in vitro because metformin improves water solubility and promotes the osteogenic differentiation of cells within the scaffold.	Metformin	150-159	SAFB like transcription modulator	Homo sapiens	13-16
32994182-8	2021	Treatment with metformin inhibited the lung metastasis of DPP-4-deficient 4T1 mammary tumor cells generated by either KR administration or DPP-4 knockdown.	Metformin	15-24	dipeptidylpeptidase 4	Mus musculus	58-63
32994182-8	2021	Treatment with metformin inhibited the lung metastasis of DPP-4-deficient 4T1 mammary tumor cells generated by either KR administration or DPP-4 knockdown.	Metformin	15-24	dipeptidylpeptidase 4	Mus musculus	139-144
32994182-9	2021	Immunostaining of primary tumors indicated that DPP-4 suppression promoted the expression of EMT-inducing transcription factor Snail through activation of the CXCR4-mediated mTOR/p70S6K pathway in an allograft breast cancer model; metformin abolished this alteration.	Metformin	231-240	dipeptidylpeptidase 4	Mus musculus	48-53
32994182-11	2021	Our findings suggest that metformin may serve as an antimetastatic agent by mitigating the undesirable effects of DPP-4 inhibitors in patients with certain cancers.	Metformin	26-35	dipeptidyl peptidase 4	Homo sapiens	114-119
32994182-12	2021	Implications: Metformin could combat the detrimental effects of DPP-4 inhibitor on breast cancer metastasis via mTOR suppression, suggesting the potential clinical relevance.	Metformin	14-23	dipeptidyl peptidase 4	Homo sapiens	64-69
32657143-8	2021	In the metformin treated group, the expression of Bax and PUMA genes was enhanced while the expression of Bcl-2, hTERT, mTOR, and p53 genes declined.	Metformin	7-16	telomerase reverse transcriptase	Homo sapiens	113-118
32862004-7	2021	We found that metformin could significantly reduce the levels of liver function enzymes (ALT, AST and GGT) and ameliorate inflammatory cell infiltration and hepatocyte necrosis induced by BPA.	Metformin	14-23	gamma-glutamyltransferase 1	Rattus norvegicus	102-105
33458460-1	2021	An expired metformin drug (MET) was used as a corrosion inhibitor for C1018 carbon steel in a CO2-saturated 3.5 wt % NaCl + 340 ppm acetic acid solution under static conditions.	Metformin	11-20	SAFB like transcription modulator	Homo sapiens	27-30
24253218-0	2014	Metformin prevents hepatic steatosis by regulating the expression of adipose differentiation-related protein.	Metformin	0-9	perilipin 2	Mus musculus	69-108
24253218-6	2014	Therefore, the aim of this study was to determine the role of ADRP in the metformin-mediated regulation of hepatic steatosis.	Metformin	74-83	perilipin 2	Mus musculus	62-66
24253218-11	2014	We found that metformin significantly decreased the expression levels of ADRP.	Metformin	14-23	perilipin 2	Mus musculus	73-77
24253218-13	2014	In the hepatocytes in which ADRP was overexpressed, the reducing effects of metformin on lipid accumulation were diminished.	Metformin	76-85	perilipin 2	Mus musculus	28-32
24253218-15	2014	Taken together, our data demonstrate that metformin prevents hepatic steatosis by regulating the expression of ADRP, which may be a key target in the treatment of NAFLD.	Metformin	42-51	perilipin 2	Mus musculus	111-115
32516360-10	2020	Of note, either nicotine treatment or activation of AMPK by intracerebroventricular infusion of metformin reduced LPS-induced impairment of fear memory reconsolidation, and ameliorated inflammation factor TNF-alpha and IL-1beta as well as the expression of CRTC1.	Metformin	96-105	interleukin 1 alpha	Homo sapiens	219-227
33243251-8	2020	Insulin and the insulin sensitizers rosiglitazone and metformin prevent in part the RD-induced cone loss in vivo, despite the persistence of inflammation CONCLUSION: Our results describe a new mechanism by which inflammation induces cone death in RD, likely through cone starvation due to the downregulation of RdCVF that could be reversed by insulin.	Metformin	54-63	nucleoredoxin like 1	Homo sapiens	311-316
24378856-8	2013	Metformin inhibited the proliferation of Alex, HLE and Huh7 cells in vitro and in vivo.	Metformin	0-9	MIR7-3 host gene	Homo sapiens	55-59
33221742-8	2020	We suspected that metformin may play a neuroprotective role in early AD by increasing NEAT1 expression and through FZD3/GSK3beta/p-tau pathway.	Metformin	18-27	microtubule associated protein tau	Homo sapiens	131-134
33205256-1	2021	A 64-year old man developed alopecia universalis after one month of treatment with metformin and sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor.	Metformin	83-92	dipeptidyl peptidase 4	Homo sapiens	112-134
32207092-5	2020	The neuroprotective effect of metformin on rotenone-induced dopaminergic toxicity was assessed by tyrosine hydroxylase (TH), cleaved caspase-3 and alpha-synuclein immunohistochemistry in substantia nigra (SN).	Metformin	30-39	synuclein, alpha	Mus musculus	147-162
24238901-1	2013	In order to develop a new positron emission tomography (PET) probe to study hepatobiliary transport mediated by the multi-drug and toxin extrusion transporter 1 (MATE1), (11)C-labelled metformin was synthesized and then evaluated as a PET probe.	Metformin	185-194	solute carrier family 47 member 1	Homo sapiens	162-167
23982736-9	2013	Intriguingly, co-expression of SIRT1 and p53 dramatically reduced the levels of Ac-p53, however, low doses of metformin treatment partially reversed the effect of SIRT1 on p53 acetylation and elevated SA-beta-gal activity.	Metformin	110-119	sirtuin 1	Homo sapiens	31-36
23982736-9	2013	Intriguingly, co-expression of SIRT1 and p53 dramatically reduced the levels of Ac-p53, however, low doses of metformin treatment partially reversed the effect of SIRT1 on p53 acetylation and elevated SA-beta-gal activity.	Metformin	110-119	sirtuin 1	Homo sapiens	163-168
24074896-0	2013	Inhibitory effect of metformin on bone metastasis of cancer via OPG/RANKL/RANK system.	Metformin	21-30	basic transcription factor 3 pseudogene 11	Homo sapiens	64-67
24074896-0	2013	Inhibitory effect of metformin on bone metastasis of cancer via OPG/RANKL/RANK system.	Metformin	21-30	TNF superfamily member 11	Homo sapiens	68-73
24074896-5	2013	In addition, metformin as a commonly used medicine for type 2 diabetes is a negative regulator of RANKL and inhibits the differentiation of osteoclasts.	Metformin	13-22	TNF superfamily member 11	Homo sapiens	98-103
24074896-6	2013	We present a hypothesis that metformin serves an inhibitory effect on bone metastasis of cancer via OPG/RANKL/RANK system.	Metformin	29-38	basic transcription factor 3 pseudogene 11	Homo sapiens	100-103
24074896-6	2013	We present a hypothesis that metformin serves an inhibitory effect on bone metastasis of cancer via OPG/RANKL/RANK system.	Metformin	29-38	TNF superfamily member 11	Homo sapiens	104-109
23877793-0	2013	K-ras gene mutation as a predictor of cancer cell responsiveness to metformin.	Metformin	68-77	KRAS proto-oncogene, GTPase	Homo sapiens	0-5
23877793-3	2013	In the current study, metformin was observed to effectively inhibit the growth of the K-ras mutant but not wild-type tumors in vivo.	Metformin	22-31	KRAS proto-oncogene, GTPase	Homo sapiens	86-91
23877793-5	2013	In addition, metformin induced apoptosis in the K-ras mutant tumors, A549 and PANC-1, but not in the K-ras wild-type tumor, A431, in vitro.	Metformin	13-22	KRAS proto-oncogene, GTPase	Homo sapiens	48-53
23877793-6	2013	Similarly, at lower concentrations, metformin inhibited cell proliferation in the K-ras mutant, but not in the K-ras wild-type tumor cells in vitro.	Metformin	36-45	KRAS proto-oncogene, GTPase	Homo sapiens	82-87
23877793-7	2013	These observations indicate that tumors with K-ras mutations are sensitive to metformin therapy.	Metformin	78-87	KRAS proto-oncogene, GTPase	Homo sapiens	45-50
23877793-8	2013	In addition, metformin significantly arrested K-ras mutant and wild-type tumor cells in G1 phase in vitro and metformin downregulated two important downstream effectors of the Ras signaling pathway in K-ras mutant tumors.	Metformin	13-22	KRAS proto-oncogene, GTPase	Homo sapiens	46-51
23877793-8	2013	In addition, metformin significantly arrested K-ras mutant and wild-type tumor cells in G1 phase in vitro and metformin downregulated two important downstream effectors of the Ras signaling pathway in K-ras mutant tumors.	Metformin	110-119	KRAS proto-oncogene, GTPase	Homo sapiens	201-206
23877793-9	2013	Metformin was concluded to function as a potential K-ras-targeting agent that has potential for cancer therapy.	Metformin	0-9	KRAS proto-oncogene, GTPase	Homo sapiens	51-56
23612973-2	2013	In a previous study, we demonstrated that phosphorylation of Ser-428/431 (in LKB1(L)) by protein kinase Czeta (PKCzeta) was essential for LKB1-mediated activation of AMP-activated protein kinase (AMPK) in response to oxidants or metformin.	Metformin	229-238	protein kinase C zeta	Homo sapiens	111-118
23612973-8	2013	PKCzeta-dependent phosphorylation of Ser-399 triggered nucleocytoplasmic translocation of LKB1(S) in response to metformin or peroxynitrite treatment.	Metformin	113-122	protein kinase C zeta	Homo sapiens	0-7
23612973-10	2013	Overexpression of PKCzeta up-regulated metformin-mediated phosphorylation of both AMPK (Thr-172) and ACC (Ser-79), but the effect was ablated in the S399A mutant.	Metformin	39-48	protein kinase C zeta	Homo sapiens	18-25
23521863-4	2013	In agreement, metformin prevented the translocation of NF-kappaB to the nucleus and inhibited the phosphorylation of IkappaB and IKKalpha/beta, events required for activation of the NF-kappaB pathway.	Metformin	14-23	component of inhibitor of nuclear factor kappa B kinase complex	Homo sapiens	129-142
23611575-2	2013	The administration of metformin reduced pain intensity from 9/10 to 3/10 and favorably affected the profile of inflammatory cytokines (i.e., TNF a, IL-1beta, IL-6, and IL-10), adipokines (i.e., adiponectin, leptin, and resistin), and beta-endorphin.	Metformin	22-31	interleukin 10	Homo sapiens	168-173
23620395-6	2013	In addition, we treated Ins2(+/Akita) mice with metformin, which activates AMP-activated protein kinase (AMPK) and thereby slows the degradation of GTPCH I; despite blood glucose levels that were similar to untreated mice, those treated with metformin had significantly less albuminuria.	Metformin	48-57	insulin II	Mus musculus	24-28
23558289-1	2013	Multidrug and toxin extrusion 1 (MATE1, SLC47A1), an organic cation transporter, plays an important role in the renal and biliary elimination of various clinical drugs, including the anti-diabetic drug metformin.	Metformin	202-211	solute carrier family 47 member 1	Homo sapiens	0-31
23558289-1	2013	Multidrug and toxin extrusion 1 (MATE1, SLC47A1), an organic cation transporter, plays an important role in the renal and biliary elimination of various clinical drugs, including the anti-diabetic drug metformin.	Metformin	202-211	solute carrier family 47 member 1	Homo sapiens	33-38
23558289-1	2013	Multidrug and toxin extrusion 1 (MATE1, SLC47A1), an organic cation transporter, plays an important role in the renal and biliary elimination of various clinical drugs, including the anti-diabetic drug metformin.	Metformin	202-211	solute carrier family 47 member 1	Homo sapiens	40-47
23620761-7	2013	Given the cross-talk between the insulin and IGF signaling pathways, the aim of this study was to examine the hypothesis that the anti-proliferative actions of metformin in uterine serous carcinoma (USC) are potentially mediated via suppression of the IGF-I receptor (IGF-IR) pathway.	Metformin	160-169	insulin like growth factor 1 receptor	Homo sapiens	252-266
23620761-7	2013	Given the cross-talk between the insulin and IGF signaling pathways, the aim of this study was to examine the hypothesis that the anti-proliferative actions of metformin in uterine serous carcinoma (USC) are potentially mediated via suppression of the IGF-I receptor (IGF-IR) pathway.	Metformin	160-169	insulin like growth factor 1 receptor	Homo sapiens	268-274
23417334-4	2013	Genetic polymorphisms of OCT2-808 G&gt;T and OCTN1-917C&gt;T had a significant (P&lt;0.05) effect on metformin pharmacokinetics, yielding a higher peak concentration with a larger area under the serum time-concentration curve.	Metformin	101-110	POU class 2 homeobox 2	Homo sapiens	25-29
23417334-4	2013	Genetic polymorphisms of OCT2-808 G&gt;T and OCTN1-917C&gt;T had a significant (P&lt;0.05) effect on metformin pharmacokinetics, yielding a higher peak concentration with a larger area under the serum time-concentration curve.	Metformin	101-110	solute carrier family 22 member 4	Homo sapiens	45-50
23417334-9	2013	Thus, genetic variants of OCTN1-917C&gt;T, along with OCT2-808 G&gt;T genetic polymorphisms, could be useful in titrating the optimal metformin dose.	Metformin	134-143	solute carrier family 22 member 4	Homo sapiens	26-31
23417334-9	2013	Thus, genetic variants of OCTN1-917C&gt;T, along with OCT2-808 G&gt;T genetic polymorphisms, could be useful in titrating the optimal metformin dose.	Metformin	134-143	POU class 2 homeobox 2	Homo sapiens	54-58
23207880-7	2013	Accordingly, metformin led to increased S100A9 mRNA in ex vivo-treated adipose tissue explants (n = 5/treatment).	Metformin	13-22	S100 calcium binding protein A9 (calgranulin B)	Mus musculus	40-46
23267855-4	2013	The renal and secretory clearances of metformin were higher (22% and 26%, respectively) in carriers of variant MATE2 who were also MATE1 reference (P &lt; 0.05).	Metformin	38-47	solute carrier family 47 member 1	Homo sapiens	131-136
23267855-5	2013	Both MATE genotypes were associated with altered post-metformin glucose tolerance, with variant carriers of MATE1 and MATE2 having an enhanced (P &lt; 0.01) and reduced (P &lt; 0.05) response, respectively.	Metformin	54-63	solute carrier family 47 member 1	Homo sapiens	108-113
23267855-6	2013	Consistent with these results, patients with diabetes (n = 145) carrying the MATE1 variant showed enhanced metformin response.	Metformin	107-116	solute carrier family 47 member 1	Homo sapiens	77-82
23267855-7	2013	These findings suggest that promoter variants of MATE1 and MATE2 are important determinants of metformin disposition and response in healthy volunteers and diabetic patients.	Metformin	95-104	solute carrier family 47 member 1	Homo sapiens	49-54
22882994-0	2013	Pharmacogenomic association between a variant in SLC47A1 gene and therapeutic response to metformin in type 2 diabetes.	Metformin	90-99	solute carrier family 47 member 1	Homo sapiens	49-56
22882994-2	2013	The aim of this study was to investigate possible associations of the variants in genes encoding organic cationic transporters-solute carrier family 22, members A1, A2 (SLC22A1, SLC22A2) and solute carrier family 47, member A1 (SLC47A1) with response to metformin in type 2 diabetes.	Metformin	254-263	solute carrier family 47 member 1	Homo sapiens	191-226
22882994-2	2013	The aim of this study was to investigate possible associations of the variants in genes encoding organic cationic transporters-solute carrier family 22, members A1, A2 (SLC22A1, SLC22A2) and solute carrier family 47, member A1 (SLC47A1) with response to metformin in type 2 diabetes.	Metformin	254-263	solute carrier family 47 member 1	Homo sapiens	228-235
23395946-6	2013	Furthermore, gene expression arrays revealed that metformin caused expression of stress markers DDIT3, CYP1A1,and GDF-15 and a concomitant reduction in PTGS1 expression.	Metformin	50-59	growth differentiation factor 15	Homo sapiens	114-120
23034939-5	2013	The "cluster II" inhibitors (which contain known OCT2 substrates) metformin and cimetidine interacted competitively with MPP.	Metformin	66-75	POU class 2 homeobox 2	Homo sapiens	49-53
32207092-9	2020	Additionally, metformin significantly decreased the rotenone-induced increase of cleaved caspase-3 and alpha-synuclein accumulation in the SN; however, there was no difference in motor behaviours between the experimental groups.	Metformin	14-23	synuclein, alpha	Mus musculus	103-118
32715434-7	2020	The apoptosis induction in metformin treated hypoxic and normoxic cells was verified by Annexin V/PI staining followed by FACS analysis.	Metformin	27-36	annexin A5	Homo sapiens	88-97
33061964-1	2020	Introduction: To conduct the first meta-analysis of randomized controlled trials (RCTs) comparing glucagon-like peptide 1 receptor agonists (GLP-1RAs) with sodium-glucose cotransporter 2 inhibitors (SGLT-2is) for obese type 2 diabetes (T2D) patients uncontrolled on metformin.	Metformin	266-275	solute carrier family 5 member 2	Homo sapiens	199-205
33062917-4	2020	Objective: To assess the endometrial expression changes of vascular endothelial growth factor A (VEGFA) and leukemia inhibitory factor (LIF), at the time of implantation in diabetic rats following treatment with Metformin and Pioglitazone.	Metformin	212-221	vascular endothelial growth factor A	Rattus norvegicus	59-95
33062917-4	2020	Objective: To assess the endometrial expression changes of vascular endothelial growth factor A (VEGFA) and leukemia inhibitory factor (LIF), at the time of implantation in diabetic rats following treatment with Metformin and Pioglitazone.	Metformin	212-221	vascular endothelial growth factor A	Rattus norvegicus	97-102
33062917-8	2020	Results: The relative expression of VEGFA transcript was higher in the diabetic (p = 0.02) and Metformin-treated (p = 0.04) rats compared to the control group.	Metformin	95-104	vascular endothelial growth factor A	Rattus norvegicus	36-41
32940892-3	2021	Here, we aimed to assess the effect of metformin on TF activity and markers of vascular inflammation in poorly controlled type 2 diabetes.	Metformin	39-48	coagulation factor III, tissue factor	Homo sapiens	52-54
32940892-6	2021	Moreover, the patients on metformin showed lower levels of vascular cell adhesion molecule (VCAM)1 (26.6 +- 1.4 vs. 35.03 +- 3.1 ng/mL, p = 0.014) and higher expression of miR-126-3p/U6sno (11.39 +- 2.8 vs. 4.26 +- 0.9, p = 0.006), a known post-transcriptional down regulator of TF and VCAM1.	Metformin	26-35	coagulation factor III, tissue factor	Homo sapiens	279-281
32905192-9	2020	Metformin initiators had a significantly greater decrease in HbA1c than MTX, beta - 0.38 (95% CI: - 0.52, - 0.23), p < 0.001.	Metformin	0-9	metaxin 1	Homo sapiens	72-75
32905192-12	2020	Reductions in HbA1c after initiation of a TNFi or MTX are about half (~ 0.4 units) the decrease observed after initiation of metformin.	Metformin	125-134	metaxin 1	Homo sapiens	50-53
32472692-0	2020	Metformin mitigates gastrointestinal radiotoxicity and radiosensitises P53 mutation colorectal tumours via optimising autophagy.	Metformin	0-9	Wistar clone pR53P1 p53 pseudogene	Rattus norvegicus	71-74
32472692-6	2020	In addition, our data indicated that metformin increased the radiosensitivity of colorectal tumours with P53 mutation both in vitro and in vivo.	Metformin	37-46	Wistar clone pR53P1 p53 pseudogene	Rattus norvegicus	105-108
32472692-7	2020	CONCLUSION AND IMPLICATIONS: Metformin may be a radiotherapy adjuvant agent for colorectal cancers especially those carrying P53 mutation.	Metformin	29-38	Wistar clone pR53P1 p53 pseudogene	Rattus norvegicus	125-128
32437914-9	2020	CONCLUSION: Our meta-analysis suggests that GLP-1RAs provide better glycaemic effects than SGLT-2is in patients with T2DM uncontrolled by metformin, albeit while increasing risk for hypoglycaemia and gastrointestinal adverse events.	Metformin	138-147	solute carrier family 5 member 2	Homo sapiens	91-97
32872293-0	2020	Metformin Derivative HL156A Reverses Multidrug Resistance by Inhibiting HOXC6/ERK1/2 Signaling in Multidrug-Resistant Human Cancer Cells.	Metformin	0-9	homeobox C6	Homo sapiens	72-77
32814716-5	2020	Interestingly, T2DM subjects treated with the antidiabetic drug metformin had fewer NPY-ir neurons and microglia than T2DM subjects not treated with metformin.	Metformin	64-73	neuropeptide Y	Homo sapiens	84-87
32780768-4	2020	The longitudinal blood-derived transcriptome analysis revealed metformin-induced differential expression of novel and previously described genes involved in cholesterol homeostasis (SLC46A1 and LRP1), cancer development (CYP1B1, STAB1, CCR2, TMEM176B), and immune responses (CD14, CD163) after administration of metformin for three months.	Metformin	63-72	solute carrier family 46 member 1	Homo sapiens	182-189
32780768-6	2020	Moreover, we found a significant upregulation of IRS2 gene (log2FC 0.89) in responders compared to non-responders before the use of metformin.	Metformin	132-141	insulin receptor substrate 2	Homo sapiens	49-53
32908958-11	2020	Conclusions: The combination of mTOR dual inhibition by Torin 2 and metformin is associated with an altered metabolomic profile and a significant reduction in pancreatic tumor burden compared with single-agent therapy, and it is better tolerated.	Metformin	68-77	mechanistic target of rapamycin kinase	Mus musculus	32-36
32472157-3	2020	Hepatic and renal uptake of metformin is mediated by organic cation transporter 1 (OCT1) and OCT2, respectively, and its renal excretion by multidrug and toxin extrusion 1 (MATE1) and MATE2-K.	Metformin	28-37	solute carrier family 22 member 2	Homo sapiens	93-97
31749144-3	2020	In this study, we aimed to assess the association between T2D, metformin use, and the risk of cancer in DM1 patients.	Metformin	63-72	immunoglobulin heavy diversity 1-7	Homo sapiens	104-107
31749144-8	2020	DM1 patients with T2D, compared with those without T2D, were more likely to develop cancer (hazard ratio [HR]= 3.60, 95% confidence interval [CI]=1.18-10.97; p=0.02), but not if they were treated with metformin (HR=0.43, 95%CI=0.06-3.35; p=0.42).	Metformin	201-210	immunoglobulin heavy diversity 1-7	Homo sapiens	0-3
31749144-10	2020	These results show an association between T2D and cancer risk in DM1 patients and may provide new insights into the possible benefits of Metformin use in DM1.	Metformin	137-146	immunoglobulin heavy diversity 1-7	Homo sapiens	154-157
32652973-0	2020	Metformin and insulin treatment of gestational diabetes: effects on inflammatory markers and IGF-binding protein-1 - secondary analysis of a randomized controlled trial.	Metformin	0-9	insulin like growth factor binding protein 1	Homo sapiens	93-114
32652973-2	2020	We studied whether metformin treatment has favorable or unfavorable effects on inflammatory markers and insulin-like growth factor-binding protein 1 (IGFBP-1) in GDM patients compared with insulin, and whether these markers associate with major maternal or fetal clinical outcomes.	Metformin	19-28	insulin like growth factor binding protein 1	Homo sapiens	104-148
32652973-2	2020	We studied whether metformin treatment has favorable or unfavorable effects on inflammatory markers and insulin-like growth factor-binding protein 1 (IGFBP-1) in GDM patients compared with insulin, and whether these markers associate with major maternal or fetal clinical outcomes.	Metformin	19-28	insulin like growth factor binding protein 1	Homo sapiens	150-157
32652973-7	2020	GlycA (p = 0.02) and non-phosphorylated IGFBP-1 (p = 0.008) increased more in patients treated with metformin than those treated with insulin.	Metformin	100-109	insulin like growth factor binding protein 1	Homo sapiens	40-47
32652973-9	2020	CONCLUSIONS: Metformin had beneficial effects on maternal serum IGFBP-1 concentrations compared to insulin, as increased IGFBP-1 related to lower total and late pregnancy maternal weight gain.	Metformin	13-22	insulin like growth factor binding protein 1	Homo sapiens	64-71
32311500-6	2020	GDF15, for example, extends both lifespan and healthspan when overexpressed in mice and is additionally required for the anti-diabetic drug metformin to exert beneficial effects on body weight and energy balance.	Metformin	140-149	growth differentiation factor 15	Mus musculus	0-5
25033808-4	2013	Here we summarize the biochemistry and biology of three classes of compound identified by this screening method that inhibit K-Ras PM targeting: staurosporine and analogs, fendiline, and metformin.	Metformin	187-196	KRAS proto-oncogene, GTPase	Homo sapiens	125-130
23135276-7	2012	Long term treatment with metformin stimulated phosphorylation of c-Jun N-terminal kinase (JNK) and its downstream molecule c-Jun, which is a critical molecule for CAP transcription.	Metformin	25-34	mitogen-activated protein kinase 8	Mus musculus	65-88
23135276-7	2012	Long term treatment with metformin stimulated phosphorylation of c-Jun N-terminal kinase (JNK) and its downstream molecule c-Jun, which is a critical molecule for CAP transcription.	Metformin	25-34	mitogen-activated protein kinase 8	Mus musculus	90-93
23135276-8	2012	Knockdown of AMPK and JNK blocked metformin-induced expression of CAP, implying that metformin stimulates AMPK-JNK-CAP axis pathway.	Metformin	34-43	mitogen-activated protein kinase 8	Mus musculus	22-25
23135276-8	2012	Knockdown of AMPK and JNK blocked metformin-induced expression of CAP, implying that metformin stimulates AMPK-JNK-CAP axis pathway.	Metformin	34-43	mitogen-activated protein kinase 8	Mus musculus	111-114
23135276-8	2012	Knockdown of AMPK and JNK blocked metformin-induced expression of CAP, implying that metformin stimulates AMPK-JNK-CAP axis pathway.	Metformin	85-94	mitogen-activated protein kinase 8	Mus musculus	22-25
23135276-8	2012	Knockdown of AMPK and JNK blocked metformin-induced expression of CAP, implying that metformin stimulates AMPK-JNK-CAP axis pathway.	Metformin	85-94	mitogen-activated protein kinase 8	Mus musculus	111-114
23121473-6	2012	Vildagliptin + metformin also decreased resistin, RBP-4, and chemerin better.	Metformin	15-24	retinol binding protein 4	Homo sapiens	50-55
23121473-6	2012	Vildagliptin + metformin also decreased resistin, RBP-4, and chemerin better.	Metformin	15-24	retinoic acid receptor responder 2	Homo sapiens	61-69
22977252-10	2012	GH-induced hepatic gluconeogenesis was decreased by either metformin or Ad-SHP, whereas the inhibition by metformin was abolished by SHP knockdown.	Metformin	106-115	nuclear receptor subfamily 0, group B, member 2	Mus musculus	133-136
22698918-8	2012	In primary hepatocytes, dominant-negative mutant-AMPK and SHP knockdown prevented the inhibitory effect of metformin on GH-stimulated PDK4 expression.	Metformin	107-116	nuclear receptor subfamily 0, group B, member 2	Mus musculus	58-61
22698918-10	2012	Metformin inhibits GH-induced PDK4 expression and metabolites via an AMPK-SHP-dependent pathway.	Metformin	0-9	nuclear receptor subfamily 0, group B, member 2	Mus musculus	74-77
22698918-11	2012	The metformin-AMPK-SHP network may provide a novel therapeutic approach for the treatment of hepatic metabolic disorders induced by the GH-mediated pathway.	Metformin	4-13	nuclear receptor subfamily 0, group B, member 2	Mus musculus	19-22
22524458-9	2012	Livin levels decreased in a dose-dependent manner upon metformin treatment.	Metformin	55-64	baculoviral IAP repeat containing 7	Homo sapiens	0-5
22524458-10	2012	Metformin activated 5"-adenosine monophosphate-activated protein kinase, inhibited the mammalian target of rapamycin pathway and downregulated Livin protein expression.	Metformin	0-9	baculoviral IAP repeat containing 7	Homo sapiens	143-148
33099954-0	2020	Metformin induces apoptosis of melanoma B16 cells via PI3K/Akt/mTOR signaling pathways.	Metformin	0-9	mechanistic target of rapamycin kinase	Mus musculus	63-67
33099954-1	2020	PURPOSE: To investigate the influences of metformin on the proliferation and apoptosis of mouse melanoma B16 cells through regulating the phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway.	Metformin	42-51	phosphoinositide-3-kinase regulatory subunit 1	Mus musculus	138-175
33099954-9	2020	CONCLUSIONS: Metformin can inhibit the proliferation of mouse melanoma B16 cells and induce their apoptosis probably through its regulation on the PI3K/AKT/mTOR signaling pathway in cells.	Metformin	13-22	mechanistic target of rapamycin kinase	Mus musculus	156-160
32591547-6	2020	Furthermore, we determined the role of each regulatory cystathionine-beta-synthase (CBS) domain in the gamma1 subunit in metformin action and found that deletion of either CBS1 or CBS4 negated metformin"s effect on AMPKalpha phosphorylation at T172 and suppression of glucose production in hepatocytes.	Metformin	121-130	cystathionine beta-synthase	Mus musculus	55-82
32591547-6	2020	Furthermore, we determined the role of each regulatory cystathionine-beta-synthase (CBS) domain in the gamma1 subunit in metformin action and found that deletion of either CBS1 or CBS4 negated metformin"s effect on AMPKalpha phosphorylation at T172 and suppression of glucose production in hepatocytes.	Metformin	121-130	cystathionine beta-synthase	Mus musculus	84-87
32591547-6	2020	Furthermore, we determined the role of each regulatory cystathionine-beta-synthase (CBS) domain in the gamma1 subunit in metformin action and found that deletion of either CBS1 or CBS4 negated metformin"s effect on AMPKalpha phosphorylation at T172 and suppression of glucose production in hepatocytes.	Metformin	193-202	cystathionine beta-synthase	Mus musculus	55-82
32591547-6	2020	Furthermore, we determined the role of each regulatory cystathionine-beta-synthase (CBS) domain in the gamma1 subunit in metformin action and found that deletion of either CBS1 or CBS4 negated metformin"s effect on AMPKalpha phosphorylation at T172 and suppression of glucose production in hepatocytes.	Metformin	193-202	cystathionine beta-synthase	Mus musculus	84-87
32670025-4	2020	Here in the present study, we showed that metformin, the most widely used drug for type 2 diabetes, suppressed Cdk5 hyper-activation and Cdk5-dependent tau hyper-phosphorylation in the APP/PS1 mouse hippocampus.	Metformin	42-51	presenilin 1	Mus musculus	189-192
32670025-6	2020	Moreover, chronic metformin treatment rescued the core phenotypes in APP/PS1 mice as evidenced by restored spine density, surface GluA1 trafficking, Long-term potentiation (LTP) expression, and spatial memory.	Metformin	18-27	presenilin 1	Mus musculus	73-76
32728616-8	2020	These findings demonstrate that c-Myc activates, whereas AMPK inhibits, TDG-mediated DNA demethylation of the SREBP1 promoter in insulin-promoted and metformin-suppressed cancer progression, respectively.	Metformin	150-159	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	32-37
32728616-8	2020	These findings demonstrate that c-Myc activates, whereas AMPK inhibits, TDG-mediated DNA demethylation of the SREBP1 promoter in insulin-promoted and metformin-suppressed cancer progression, respectively.	Metformin	150-159	sterol regulatory element binding transcription factor 1	Homo sapiens	110-116
32575674-0	2020	rs622342 in SLC22A1, CYP2C9*2 and CYP2C9*3 and Glycemic Response in Individuals with Type 2 Diabetes Mellitus Receiving Metformin/Sulfonylurea Combination Therapy: 6-Month Follow-Up Study.	Metformin	120-129	cytochrome P450 family 2 subfamily C member 9	Homo sapiens	34-40
32575674-11	2020	CONCLUSION: The combination of metformin/sulfonylurea therapy led to the maximum glycemic control in individuals with T2DM carrying AA or AC genotypes in SLC22A1 and *1*3 in CYP2C9.	Metformin	31-40	cytochrome P450 family 2 subfamily C member 9	Homo sapiens	174-180
32399705-14	2020	Furthermore, insulin showed more beneficial effects than metformin in hindering these complications by modifying the expression of VEGF and TGF-beta.	Metformin	57-66	vascular endothelial growth factor A	Rattus norvegicus	131-135
22445233-1	2012	AIMS: To investigate whether metformin regulates chemerin expression in vivo by alleviating ER stress.	Metformin	29-38	retinoic acid receptor responder 2	Rattus norvegicus	49-57
22445233-7	2012	Metformin reduced chemerin expression in the HM group compared with HF.	Metformin	0-9	retinoic acid receptor responder 2	Rattus norvegicus	18-26
22445233-8	2012	Metformin reduced the GRP78 mRNA expression in HM rats.	Metformin	0-9	heat shock protein family A (Hsp70) member 5	Rattus norvegicus	22-27
26097796-0	2012	Metformin- A Promising Agent for Chemoprevention in BRCA1 Carriers.	Metformin	0-9	BRCA1 DNA repair associated	Homo sapiens	52-57
22425595-10	2012	Metformin attenuated the increase of total tau, phospho-tau and activated JNK.	Metformin	0-9	mitogen-activated protein kinase 8	Mus musculus	74-77
22416982-6	2012	After the simultaneous single intravenous administration of both drugs together, the AUCs of each drug were significantly greater than that in each drug alone due to the competitive inhibition for the metabolism of nifedipine by metformin via hepatic CYP3A1/2 and of metformin by nifedipine via hepatic CYP2C6 and 3A1/2.	Metformin	229-238	cytochrome P450, family 2, subfamily C, polypeptide 6, variant 1	Rattus norvegicus	303-309
22415520-6	2012	However, contrary to the case of OCT1, the uptake of MPP+, TEA, metformin and lamivudine in oocytes expressing OCT2-T199I, -T201M and -A270S variants was decreased significantly compared with that in oocytes expressing OCT2-WT.	Metformin	64-73	POU class 2 homeobox 2	Homo sapiens	111-116
22415520-6	2012	However, contrary to the case of OCT1, the uptake of MPP+, TEA, metformin and lamivudine in oocytes expressing OCT2-T199I, -T201M and -A270S variants was decreased significantly compared with that in oocytes expressing OCT2-WT.	Metformin	64-73	POU class 2 homeobox 2	Homo sapiens	111-115
22415520-7	2012	In conclusion, the effect of genetic variations of OCT1 and OCT2 on the uptake of MPP+, TEA, metformin and lamivudine was substrate-dependent.	Metformin	93-102	POU class 2 homeobox 2	Homo sapiens	60-64
22421144-10	2012	In other studies, metformin decreased the phosphorylation of 4E-BP1 at Ser65, Thr37/46 and Thr70 sites, but drastically increased the phosphorylation of EF2 at Thr56 and AMPK at Thr172, which results in global translational inhibition.	Metformin	18-27	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	170-174
22325091-5	2012	Expression of orexigenic peptides neuropeptide Y (NPY) and agouti-related protein (AgRP) decreased in the hypothalamus of metformin-treated diabetic rats, though anorexigenic peptides pro-opiomelanocortin (POMC) did not change significantly.	Metformin	122-131	proopiomelanocortin	Rattus norvegicus	184-204
22325091-5	2012	Expression of orexigenic peptides neuropeptide Y (NPY) and agouti-related protein (AgRP) decreased in the hypothalamus of metformin-treated diabetic rats, though anorexigenic peptides pro-opiomelanocortin (POMC) did not change significantly.	Metformin	122-131	proopiomelanocortin	Rattus norvegicus	206-210
22086681-5	2012	Metformin also decreased the expression of CSC markers,CD44, EpCAM,EZH2, Notch-1, Nanog and Oct4, and caused reexpression of miRNAs (let-7a,let-7b, miR-26a, miR-101, miR-200b, and miR-200c) that are typically lost in pancreatic cancer and especially in pancreatospheres.	Metformin	0-9	CD44 molecule (Indian blood group)	Homo sapiens	55-59
22086681-5	2012	Metformin also decreased the expression of CSC markers,CD44, EpCAM,EZH2, Notch-1, Nanog and Oct4, and caused reexpression of miRNAs (let-7a,let-7b, miR-26a, miR-101, miR-200b, and miR-200c) that are typically lost in pancreatic cancer and especially in pancreatospheres.	Metformin	0-9	Nanog homeobox	Homo sapiens	82-87
22086681-5	2012	Metformin also decreased the expression of CSC markers,CD44, EpCAM,EZH2, Notch-1, Nanog and Oct4, and caused reexpression of miRNAs (let-7a,let-7b, miR-26a, miR-101, miR-200b, and miR-200c) that are typically lost in pancreatic cancer and especially in pancreatospheres.	Metformin	0-9	microRNA let-7b	Homo sapiens	140-146
22100460-0	2012	Beneficial effects of metformin and irbesartan on advanced glycation end products (AGEs)-RAGE-induced proximal tubular cell injury.	Metformin	22-31	long intergenic non-protein coding RNA 914	Homo sapiens	89-93
22100460-3	2012	Further, since a pathophysiological crosstalk between renin-angiotensin system (RAS) and AGEs-RAGE axis is involved in diabetic nephropathy, it is conceivable that metformin and irbesartan additively could protect against the AGEs-RAGE-induced tubular cell injury.	Metformin	164-173	long intergenic non-protein coding RNA 914	Homo sapiens	94-98
22100460-3	2012	Further, since a pathophysiological crosstalk between renin-angiotensin system (RAS) and AGEs-RAGE axis is involved in diabetic nephropathy, it is conceivable that metformin and irbesartan additively could protect against the AGEs-RAGE-induced tubular cell injury.	Metformin	164-173	long intergenic non-protein coding RNA 914	Homo sapiens	231-235
22100460-6	2012	Compared with AGEs-modified BSA prepared without metformin (AGEs-MF0), those prepared in the presence of 30 mM or 100 mM metformin (AGEs-MF30 or AGEs-MF100) significantly reduced RAGE mRNA level, reactive oxygen species (ROS) generation, apoptosis, monocyte chemoattractant protein-1 and transforming growth factor-beta mRNA level in tubular cells.	Metformin	121-130	long intergenic non-protein coding RNA 914	Homo sapiens	179-183
22100460-8	2012	Our present study suggests that combination therapy with metformin and irbesartan may have therapeutic potential in diabetic nephropathy; it could play a protective role against tubular injury in diabetes not only by inhibiting AGEs formation, but also by attenuating the deleterious effects of AGEs via down-regulating RAGE expression and subsequently suppressing ROS generation.	Metformin	57-66	long intergenic non-protein coding RNA 914	Homo sapiens	320-324
22293193-9	2012	However, treatment with an AMPK activator, metformin, improved the changes induced by the AII, suggesting that AII induced sodium retention works by acting on AMPK activity.	Metformin	43-52	arginase type II	Mus musculus	90-93
22293193-9	2012	However, treatment with an AMPK activator, metformin, improved the changes induced by the AII, suggesting that AII induced sodium retention works by acting on AMPK activity.	Metformin	43-52	arginase type II	Mus musculus	111-114
22138650-6	2012	In addition, we showed that exposure of ER stressed-induced NIT-1 cells to metformin decreases the phosphorylation of c-Jun NH(2) terminal kinase (JNK).	Metformin	75-84	mitogen-activated protein kinase 8	Mus musculus	118-145
22138650-6	2012	In addition, we showed that exposure of ER stressed-induced NIT-1 cells to metformin decreases the phosphorylation of c-Jun NH(2) terminal kinase (JNK).	Metformin	75-84	mitogen-activated protein kinase 8	Mus musculus	147-150
22138650-7	2012	These data suggest that metformin is an important determinant of ER stress-induced apoptosis in NIT-1 cells and may have implications for ER stress-mediated pancreatic beta cell destruction via regulation of the AMPK-PI3 kinase-JNK pathway.	Metformin	24-33	mitogen-activated protein kinase 8	Mus musculus	228-231
31904843-8	2020	RESULTS: Metformin enhanced the immunomodulatory functions of Ad-MSCs including IDO, IL-10 and TGF-beta.	Metformin	9-18	indoleamine 2,3-dioxygenase 1	Mus musculus	80-83
31904843-9	2020	Metformin upregulated the expression of p-AMPK, p-STAT1 and inhibited the expression of p-STAT3, p-mTOR in Ad-MSCs.	Metformin	0-9	mechanistic target of rapamycin kinase	Mus musculus	99-103
31904843-10	2020	STAT1 inhibition by siRNA strongly diminished IDO, IL-10, TGF-beta in metformin-treated Ad-MSCs.	Metformin	70-79	indoleamine 2,3-dioxygenase 1	Mus musculus	46-49
31904843-11	2020	As a result, metformin promoted the immunoregulatory effect of Ad-MSCs by enhancing STAT1 expression, which was dependent on the AMPK/mTOR pathway.	Metformin	13-22	mechanistic target of rapamycin kinase	Mus musculus	134-138
32189544-9	2020	Furthermore, 50mg/kg metformin markedly down-regulated the expression of proinflammatory cytokines (TNF-alpha and IL-1beta) and ER stress related genes (ATF4, ATF6, XBP1, Grp78 and CHOP) in rotenone-induced PD mice.	Metformin	21-30	interleukin 1 alpha	Mus musculus	114-122
32189544-9	2020	Furthermore, 50mg/kg metformin markedly down-regulated the expression of proinflammatory cytokines (TNF-alpha and IL-1beta) and ER stress related genes (ATF4, ATF6, XBP1, Grp78 and CHOP) in rotenone-induced PD mice.	Metformin	21-30	DNA-damage inducible transcript 3	Mus musculus	181-185
32897197-8	2020	Activation of AMPK by metformin significantly reduced TGF-beta1-induced collagen I production by suppressing Smad3-driven CTGF expression (P < 0.01), and the application of Compound C reversed such changes in the fibroblasts (P < 0.01).	Metformin	22-31	cellular communication network factor 2	Rattus norvegicus	122-126
32897197-9	2020	CONCLUSIONS: Metformin inhibits TGF-beta1-stimulated collagen I production by activating AMPK and inhibiting Smad3- driven CTGF expression in rat biliary fibroblasts.	Metformin	13-22	cellular communication network factor 2	Rattus norvegicus	123-127
32843973-9	2020	Metformin treatment suppressed the diabetes-induced AKT/mTOR pathway activation and tumor growth.	Metformin	0-9	mechanistic target of rapamycin kinase	Mus musculus	56-60
32456076-9	2020	Also, metformin is an effective therapeutic option in TOM40 overexpressed ovarian cancer than normal ovarian epithelium.	Metformin	6-15	translocase of outer mitochondrial membrane 40	Mus musculus	54-59
32444674-0	2020	The Hepatic Plasma Membrane Citrate Transporter NaCT (SLC13A5) as a Molecular Target for Metformin.	Metformin	89-98	solute carrier family 13 member 5	Homo sapiens	48-52
32444674-0	2020	The Hepatic Plasma Membrane Citrate Transporter NaCT (SLC13A5) as a Molecular Target for Metformin.	Metformin	89-98	solute carrier family 13 member 5	Homo sapiens	54-61
32444674-6	2020	Metformin inhibits the expression of the plasma membrane citrate transporter NaCT in HepG2 cells and decreases cellular levels of citrate.	Metformin	0-9	solute carrier family 13 member 5	Homo sapiens	77-81
32444674-11	2020	The transcription factor downstream of AMPK that is relevant to cAMP signaling is CREB; decreased levels of phospho-CREB seem to mediate the observed effects of metformin on NaCT.	Metformin	161-170	solute carrier family 13 member 5	Homo sapiens	174-178
32455555-0	2020	Pharmacokinetic Interaction between Metformin and Verapamil in Rats: Inhibition of the OCT2-Mediated Renal Excretion of Metformin by Verapamil.	Metformin	36-45	solute carrier family 22 member 2	Rattus norvegicus	87-91
32455555-0	2020	Pharmacokinetic Interaction between Metformin and Verapamil in Rats: Inhibition of the OCT2-Mediated Renal Excretion of Metformin by Verapamil.	Metformin	120-129	solute carrier family 22 member 2	Rattus norvegicus	87-91
32455555-7	2020	In our results, verapamil inhibited the OCT2-mediated renal excretion of metformin, subsequently leading to increase of the systemic exposure of metformin.	Metformin	73-82	solute carrier family 22 member 2	Homo sapiens	40-44
32455555-7	2020	In our results, verapamil inhibited the OCT2-mediated renal excretion of metformin, subsequently leading to increase of the systemic exposure of metformin.	Metformin	145-154	solute carrier family 22 member 2	Homo sapiens	40-44
32455555-9	2020	Although the further clinical investigation is required, our finding suggests a possibility of OCT2-mediated interaction of metformin and verapamil.	Metformin	124-133	solute carrier family 22 member 2	Homo sapiens	95-99
32550202-10	2020	Results: Treatment with metformin/donepezil combination significantly reduced the activities of AchE, BchE as well as levels of malondialdehyde, TNF-alpha and IL-6, while the activities of SOD, GPx and catalase were significantly increased in the brain.	Metformin	24-33	acetylcholinesterase	Rattus norvegicus	96-100
32467714-0	2020	High fat-induced inflammation in vascular endothelium can be improved by Abelmoschus esculentus and metformin via increasing the expressions of miR-146a and miR-155.	Metformin	100-109	microRNA 146a	Rattus norvegicus	144-152
32467714-9	2020	While AE and metformin could ameliorate the endothelial inflammation by increasing miR-146a and miR-155.	Metformin	13-22	microRNA 146a	Rattus norvegicus	83-91
32467714-11	2020	AE and metformin can attenuate endothelial inflammation through regulating miR-146a and miR-155.	Metformin	7-16	microRNA 146a	Rattus norvegicus	75-83
32518807-9	2020	After metformin treatment, expression of interleukin 6 (IL-6), TNF-alpha, and IL-1beta were significantly downregulated in RA-FLSs; however, increased expression of p-AMPK-alpha1, protein kinase A (PKA)-alpha1, and HAPLN1 (hyaluronan and proteoglycan link protein 1) was observed.	Metformin	6-15	interleukin 1 alpha	Homo sapiens	78-86
32454819-2	2020	Organic cation transporter 1 (encoded by SLC22A1) is responsible for the transport of metformin, and ataxia-telangiectasia-mutated (ATM) is a gene relating to the DNA repair and cell cycle control.	Metformin	86-95	ATM serine/threonine kinase	Homo sapiens	132-135
32454819-3	2020	The aim of this study was to evaluate if the genetic variants in SLC22A1 rs622342 and ATM rs11212617 could be effective predictors of islet function improvement in patients with type 2 diabetes mellitus (T2DM) on metformin treatment.	Metformin	213-222	ATM serine/threonine kinase	Homo sapiens	86-89
32382652-4	2020	Metformin and desferrioxamine are drugs that decrease c-myc; and statins increase levels of EGF.	Metformin	0-9	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	54-59
32375255-6	2020	In conditions of either glucose excess or gluconeogenic substrate excess, metformin lowers hexose monophosphates by mechanisms that are independent of AMPK-activation and most likely mediated by allosteric activation of phosphofructokinase-1 and/or inhibition of fructose bisphosphatase-1.	Metformin	74-83	phosphofructokinase, muscle	Homo sapiens	220-241
32208194-3	2020	Here, we attempt to find out the effect of metformin on cancer stem cell marker CD44 and stemness related transcription factors including OCT4, SOX2, NANOG, c-Myc and KLF4.	Metformin	43-52	POU class 5 homeobox 1	Homo sapiens	138-142
32208194-3	2020	Here, we attempt to find out the effect of metformin on cancer stem cell marker CD44 and stemness related transcription factors including OCT4, SOX2, NANOG, c-Myc and KLF4.	Metformin	43-52	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	157-162
21972424-11	2012	Three months" treatment with metformin maintained the reduction of androstenedione and DHEAS concentrations with atorvastatin compared with baseline.	Metformin	29-38	sulfotransferase family 2A member 1	Homo sapiens	87-92
21769504-0	2012	Metformin induced expression of Hsp60 in human THP-1 monocyte cells.	Metformin	0-9	heat shock protein family D (Hsp60) member 1	Homo sapiens	32-37
21769504-4	2012	Since this protein has important immune-modulatory properties, we have investigated the expression of Hsp60 in human THP-1 monocyte cells exposed to metformin.	Metformin	149-158	heat shock protein family D (Hsp60) member 1	Homo sapiens	102-107
23108012-13	2012	Our in vivo animal study showed that metformin reduced the renal cortical expression of ER stress protein (GRP78) in protein-overload proteinuria rats.	Metformin	37-46	heat shock protein family A (Hsp70) member 5	Rattus norvegicus	107-112
23133528-8	2012	PTP1B, encoding a tyrosin phosphatase, was found highly induced (&gt;3 fold) in infected cells treated with metformin.	Metformin	108-117	protein tyrosine phosphatase non-receptor type 1	Homo sapiens	0-5
23133528-9	2012	However, PTP1B protein expression was reduced in metformin treated cells after JFH1 infection.	Metformin	49-58	protein tyrosine phosphatase non-receptor type 1	Homo sapiens	9-14
22021366-3	2011	We report that AMPK activators, such as metformin and 5-aminoimidazole-4-carboxamide ribonucleotide, suppress activation of the mTOR pathway in BCR-ABL-expressing cells.	Metformin	40-49	ABL proto-oncogene 1, non-receptor tyrosine kinase	Homo sapiens	144-151
21920351-7	2011	Consistently, metformin significantly suppressed the up-regulation of Cyp3a11 mRNA in the liver and intestine of wild-type mice, but not in Pxr(-/-) mice.	Metformin	14-23	cytochrome P450, family 3, subfamily a, polypeptide 11	Mus musculus	70-77
25610182-2	2011	Our aim was to examine the effect of metformin treatment either alone or in combination with non-steroidal anti-inflammatory drugs (NSAID) on plasma levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in patients with early stage MS (MS-es) and generalized MS (MS-ge).	Metformin	37-46	brain derived neurotrophic factor	Homo sapiens	189-222
25610182-2	2011	Our aim was to examine the effect of metformin treatment either alone or in combination with non-steroidal anti-inflammatory drugs (NSAID) on plasma levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in patients with early stage MS (MS-es) and generalized MS (MS-ge).	Metformin	37-46	brain derived neurotrophic factor	Homo sapiens	224-228
25610182-12	2011	CONCLUSION: The combination of metformin and NSAID treatment is more effective than metformin alone on NGF and BDNF production as well as on metabolism-related anthropometric and laboratory features.	Metformin	31-40	brain derived neurotrophic factor	Homo sapiens	111-115
21989078-1	2011	OBJECTIVE: The aim of this study was to evaluate the effect of genetic variations in OCT1, OCT2, MATE1, MATE 2, and PMAT on the trough steady-state plasma concentration of metformin and hemoglobin A1c (Hb1Ac).	Metformin	172-181	POU class 2 homeobox 2	Homo sapiens	91-95
21989078-1	2011	OBJECTIVE: The aim of this study was to evaluate the effect of genetic variations in OCT1, OCT2, MATE1, MATE 2, and PMAT on the trough steady-state plasma concentration of metformin and hemoglobin A1c (Hb1Ac).	Metformin	172-181	solute carrier family 47 member 1	Homo sapiens	97-102
22340218-8	2011	NIK expression was significantly lower in the liver and renal tissues of HFD-fed mice that were treated with insulin sensitizers, metformin and sulfasalazine.	Metformin	130-139	mitogen-activated protein kinase kinase kinase 14	Mus musculus	0-3
21806981-10	2011	These data suggest that anti-melanoma effects of metformin are mediated through p21- and AMPK-independent cell cycle arrest, apoptosis and autophagy associated with p53/Bcl-2 modulation, mitochondrial damage and oxidative stress.	Metformin	49-58	cyclin-dependent kinase inhibitor 1A (P21)	Mus musculus	80-83
21338323-6	2011	AMPKalpha1 is involved in metformin-induced HSL phosphorylation at Ser-552.	Metformin	26-35	lipase E, hormone sensitive type	Homo sapiens	44-47
21618594-4	2011	In this study, we demonstrated that metformin dose-dependently stimulated OPG and reduced RANKL mRNA and protein expression in mouse calvarial osteoblasts and osteoblastic cell line MC3T3-E1.	Metformin	36-45	tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)	Mus musculus	74-77
21618594-6	2011	Moreover, supernatant of osteoblasts treated with metformin reduced formation of tartrate resistant acid phosphatase (TRAP)-positive multi-nucleated cells in Raw264.7 cells.	Metformin	50-59	acid phosphatase 5, tartrate resistant	Mus musculus	81-116
21618594-6	2011	Moreover, supernatant of osteoblasts treated with metformin reduced formation of tartrate resistant acid phosphatase (TRAP)-positive multi-nucleated cells in Raw264.7 cells.	Metformin	50-59	acid phosphatase 5, tartrate resistant	Mus musculus	118-122
21618594-7	2011	Most importantly, metformin significantly increased total body bone mineral density, prevented bone loss and decreased TRAP-positive cells in OVX rats proximal tibiae, accompanied with an increase of OPG and decrease of RANKL expression.	Metformin	18-27	acid phosphatase 5, tartrate resistant	Rattus norvegicus	119-123
32208194-7	2020	RESULTS: Metformin showed downregulation in the gene expressions of stemness related transcription factors OCT4, SOX2, NANOG, c-Myc, and KLF4 in a dose-dependent as well as time-dependent manner.	Metformin	9-18	POU class 5 homeobox 1	Homo sapiens	107-111
32208194-7	2020	RESULTS: Metformin showed downregulation in the gene expressions of stemness related transcription factors OCT4, SOX2, NANOG, c-Myc, and KLF4 in a dose-dependent as well as time-dependent manner.	Metformin	9-18	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	126-131
31525254-0	2020	Knockout model reveals the role of Nischarin in mammary gland development, breast tumorigenesis and response to metformin treatment.	Metformin	112-121	nischarin	Homo sapiens	35-44
31525254-10	2020	Here, we show for the first time, metformin activates AMPK signaling and inhibits tumor growth of Nischarin lacking PyMT tumors suggesting a potential use for metformin as a cancer therapeutic, particularly in the case of Nischarin-deficient breast cancers.	Metformin	34-43	nischarin	Homo sapiens	98-107
31525254-10	2020	Here, we show for the first time, metformin activates AMPK signaling and inhibits tumor growth of Nischarin lacking PyMT tumors suggesting a potential use for metformin as a cancer therapeutic, particularly in the case of Nischarin-deficient breast cancers.	Metformin	34-43	nischarin	Homo sapiens	222-231
31525254-10	2020	Here, we show for the first time, metformin activates AMPK signaling and inhibits tumor growth of Nischarin lacking PyMT tumors suggesting a potential use for metformin as a cancer therapeutic, particularly in the case of Nischarin-deficient breast cancers.	Metformin	159-168	nischarin	Homo sapiens	98-107
31525254-10	2020	Here, we show for the first time, metformin activates AMPK signaling and inhibits tumor growth of Nischarin lacking PyMT tumors suggesting a potential use for metformin as a cancer therapeutic, particularly in the case of Nischarin-deficient breast cancers.	Metformin	159-168	nischarin	Homo sapiens	222-231
32092034-7	2020	We observed that dapagliflozin or metformin mitigated the enhanced expression of renal gluconeogenic enzymes, PEPCK, G6Pase and FBPase, as well as improved glucose tolerance and renal function in obese rats.	Metformin	34-43	glucose-6-phosphatase catalytic subunit 1	Rattus norvegicus	117-123
32092034-9	2020	Metformin reduced the expression levels of renal cortical FOXO1 and CREB.	Metformin	0-9	cAMP responsive element binding protein 1	Rattus norvegicus	68-72
32249489-0	2020	Effect of metformin on testicular expression and localization of leptin receptor and levels of leptin in the diabetic mice.	Metformin	10-19	leptin receptor	Mus musculus	65-80
32249489-0	2020	Effect of metformin on testicular expression and localization of leptin receptor and levels of leptin in the diabetic mice.	Metformin	10-19	leptin	Mus musculus	65-71
32249489-5	2020	In the diabetic testes, the plasma and intratesticular leptin levels and plasma testosterone levels were reduced and completely restored by metformin treatment.	Metformin	140-149	leptin	Mus musculus	55-61
32249489-9	2020	Metformin increased the Ob-R expression and immunostaining in the different cell types and improved the PCNA expression.	Metformin	0-9	leptin receptor	Homo sapiens	24-28
32249489-9	2020	Metformin increased the Ob-R expression and immunostaining in the different cell types and improved the PCNA expression.	Metformin	0-9	proliferating cell nuclear antigen	Homo sapiens	104-108
32327628-8	2020	Metformin was significantly superior to placebo with regards to decrease in body weight, body mass index, glycated hemoglobin A1c, fasting insulin, and homeostasis model assessment-insulin resistance (P = 0.002-0.01), but not regarding changes in waist circumference, waist-to-hip rate, leptin, fasting glucose, and blood pressure (P = 0.07-0.33).	Metformin	0-9	leptin	Homo sapiens	287-293
32004509-0	2020	Metformin rescues Parkin protein expression and mitophagy in high glucose-challenged human renal epithelial cells by inhibiting NF-kappaB via PP2A activation.	Metformin	0-9	protein phosphatase 2 phosphatase activator	Homo sapiens	142-146
32004509-8	2020	The data suggested high glucose challenge significantly reduced PRKN gene expression, mitophagy, mitochondria integrity and cell viability in vitro, which was rescued by metformin co-treatment.	Metformin	170-179	parkin RBR E3 ubiquitin protein ligase	Homo sapiens	64-68
32004509-9	2020	The effects of metformin were crippled by PRKN gene knockdown.	Metformin	15-24	parkin RBR E3 ubiquitin protein ligase	Homo sapiens	42-46
32004509-10	2020	Metformin increased PRKN gene transcription while reducednuclear factor kappa B (NF-kappaB) activation but not that of p53 or ATF4.	Metformin	0-9	parkin RBR E3 ubiquitin protein ligase	Homo sapiens	20-24
32004509-11	2020	Inhibiting PP2A weakened NF-kappaB inhibition and PRKN induction by metformin in high glucose-challenged cells, reducing its mitochondrial protective and cytoprotective effect.	Metformin	68-77	protein phosphatase 2 phosphatase activator	Homo sapiens	11-15
32004509-11	2020	Inhibiting PP2A weakened NF-kappaB inhibition and PRKN induction by metformin in high glucose-challenged cells, reducing its mitochondrial protective and cytoprotective effect.	Metformin	68-77	parkin RBR E3 ubiquitin protein ligase	Homo sapiens	50-54
31874168-6	2020	We further indicated that treatment with the FDA-approved drug metformin normalized the hyperactive Akt-mTOR signaling, and attenuated pain-related hypersensitivity in Cntnap2-/- mice.	Metformin	63-72	mechanistic target of rapamycin kinase	Mus musculus	104-108
31977586-10	2020	It was also shown that LPS increased the mRNA expression levels of Lcn-2 and inflammation-related molecules such as IL-1beta in the amygdala tissue, which could be alleviated by metformin.	Metformin	178-187	interleukin 1 alpha	Mus musculus	116-124
31977586-11	2020	Taken together, metformin mitigates LPS-induced depressive-like behavior in mice by regulating the expression level of Lcn-2 and inflammation-related molecules, including IL-1beta, IL-6 and vWF.Video abstract: http://links.lww.com/WNR/A568.	Metformin	16-25	interleukin 1 alpha	Mus musculus	171-179
31977586-11	2020	Taken together, metformin mitigates LPS-induced depressive-like behavior in mice by regulating the expression level of Lcn-2 and inflammation-related molecules, including IL-1beta, IL-6 and vWF.Video abstract: http://links.lww.com/WNR/A568.	Metformin	16-25	Von Willebrand factor	Mus musculus	190-193
32355824-9	2020	All of the 10 hub genes (CCNA2, CCNB1, MAD2L1, BU1B, RACGAP1, CHEK1, BUB1, ASPM, NCAPG and TTK) have a strong association with lower overall survival in liver cancer patients and four genes (CCNA2, CCNB1, CHEK1 and BUB1) have reduced expression in metformin-treated samples.	Metformin	248-257	cyclin B1	Homo sapiens	32-37
32355824-9	2020	All of the 10 hub genes (CCNA2, CCNB1, MAD2L1, BU1B, RACGAP1, CHEK1, BUB1, ASPM, NCAPG and TTK) have a strong association with lower overall survival in liver cancer patients and four genes (CCNA2, CCNB1, CHEK1 and BUB1) have reduced expression in metformin-treated samples.	Metformin	248-257	mitotic arrest deficient 2 like 1	Homo sapiens	39-45
32355824-9	2020	All of the 10 hub genes (CCNA2, CCNB1, MAD2L1, BU1B, RACGAP1, CHEK1, BUB1, ASPM, NCAPG and TTK) have a strong association with lower overall survival in liver cancer patients and four genes (CCNA2, CCNB1, CHEK1 and BUB1) have reduced expression in metformin-treated samples.	Metformin	248-257	assembly factor for spindle microtubules	Homo sapiens	75-79
32355824-9	2020	All of the 10 hub genes (CCNA2, CCNB1, MAD2L1, BU1B, RACGAP1, CHEK1, BUB1, ASPM, NCAPG and TTK) have a strong association with lower overall survival in liver cancer patients and four genes (CCNA2, CCNB1, CHEK1 and BUB1) have reduced expression in metformin-treated samples.	Metformin	248-257	cyclin B1	Homo sapiens	198-203
31926250-0	2020	Inhibition of mTORC1/P70S6K pathway by Metformin synergistically sensitizes Acute Myeloid Leukemia to Ara-C.	Metformin	39-48	ribosomal protein S6 kinase B1	Homo sapiens	21-27
31706881-0	2020	Metformin in colorectal cancer: A match ruled by MiR26b?	Metformin	0-9	microRNA 26b	Homo sapiens	49-55
31740192-0	2020	Response to Letter to the Editor: Metformin in colorectal cancer: A match ruled by MiR26b?	Metformin	34-43	microRNA 26b	Homo sapiens	83-89
31818851-2	2020	The signaling pathway activated by metformin (LKB1/AMPK/mTOR) is implicated in tumor suppression in ApcMin/+ mice via metformin-induced reduction in polyp burden, increased ratio of pAMPK/AMPK, decreased pmTOR/mTOR ratio, and decreased pS6Ser235/S6Ser235 ratio in polyps.	Metformin	35-44	mechanistic target of rapamycin kinase	Mus musculus	56-60
31818851-2	2020	The signaling pathway activated by metformin (LKB1/AMPK/mTOR) is implicated in tumor suppression in ApcMin/+ mice via metformin-induced reduction in polyp burden, increased ratio of pAMPK/AMPK, decreased pmTOR/mTOR ratio, and decreased pS6Ser235/S6Ser235 ratio in polyps.	Metformin	35-44	mechanistic target of rapamycin kinase	Mus musculus	205-209
31818851-2	2020	The signaling pathway activated by metformin (LKB1/AMPK/mTOR) is implicated in tumor suppression in ApcMin/+ mice via metformin-induced reduction in polyp burden, increased ratio of pAMPK/AMPK, decreased pmTOR/mTOR ratio, and decreased pS6Ser235/S6Ser235 ratio in polyps.	Metformin	118-127	mechanistic target of rapamycin kinase	Mus musculus	56-60
31818851-2	2020	The signaling pathway activated by metformin (LKB1/AMPK/mTOR) is implicated in tumor suppression in ApcMin/+ mice via metformin-induced reduction in polyp burden, increased ratio of pAMPK/AMPK, decreased pmTOR/mTOR ratio, and decreased pS6Ser235/S6Ser235 ratio in polyps.	Metformin	118-127	mechanistic target of rapamycin kinase	Mus musculus	205-209
31989218-0	2020	Novel complementary antitumour effects of celastrol and metformin by targeting IkappaBkappaB, apoptosis and NLRP3 inflammasome activation in diethylnitrosamine-induced murine hepatocarcinogenesis.	Metformin	56-65	NLR family, pyrin domain containing 3	Mus musculus	108-113
31989218-11	2020	In conclusion, by inhibiting NLRP3 inflammasome and its prerequisite NFkappaB signalling, simultaneous administration of metformin and celastrol appears to have additive benefits in the treatment of HCC compared to cela monotherapy.	Metformin	121-130	NLR family, pyrin domain containing 3	Mus musculus	29-34
32067218-0	2020	Decreased Circulating MANF in Women with PCOS is Elevated by Metformin Therapy and is Inversely Correlated with Insulin Resistance and Hyperandrogenism.	Metformin	61-70	mesencephalic astrocyte derived neurotrophic factor	Homo sapiens	22-26
21697722-1	2011	The organic cation transporter 3 (OCT3, SLC22A3) contributes to the control of cardiac catecholamine concentrations and is important for the disposition and action of cationic drugs, such as metformin, in the myocardium.	Metformin	191-200	OCTN3	Homo sapiens	4-32
21697722-1	2011	The organic cation transporter 3 (OCT3, SLC22A3) contributes to the control of cardiac catecholamine concentrations and is important for the disposition and action of cationic drugs, such as metformin, in the myocardium.	Metformin	191-200	OCTN3	Homo sapiens	34-38
21697722-1	2011	The organic cation transporter 3 (OCT3, SLC22A3) contributes to the control of cardiac catecholamine concentrations and is important for the disposition and action of cationic drugs, such as metformin, in the myocardium.	Metformin	191-200	solute carrier family 22 member 3	Homo sapiens	40-47
21697722-2	2011	We sought to characterize the regulation of OCT3 in failing human hearts and to study commonly prescribed drugs for their potential to interact with OCT3-dependent uptake of metformin.	Metformin	174-183	OCTN3	Homo sapiens	149-153
21697722-5	2011	Michaelis-Menten kinetics of OCT3-mediated uptake of prototypical OCT substrates 1-methyl-4-phenylpyridinium and metformin were studied in human embryonic kidney 293 cells stably overexpressing OCT3.	Metformin	113-122	OCTN3	Homo sapiens	29-33
21697722-6	2011	The affinity of 1-methyl-4-phenylpyridinium for OCT3 was much higher (Km 157 +- 16 muM) than the affinity of metformin (Km 2.46 +- 0.36 mM; P &lt; 0.01), whereas maximum transport rate of 1-methyl-4-phenylpyridinium was significantly lower than that of metformin.	Metformin	253-262	OCTN3	Homo sapiens	48-52
21697722-7	2011	Verapamil, carvedilol, imipramine, and cimetidine were competitive inhibitors of OCT3-mediated metformin uptake (Ki 3.6-15.8 muM).	Metformin	95-104	OCTN3	Homo sapiens	81-85
21862872-10	2011	Metformin disrupts erbB2/IGF-1R complexes, erbB3 and IGF-1R expression and activity, as well as Src kinase and/or PI-3K/Akt signaling.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	25-31
21862872-10	2011	Metformin disrupts erbB2/IGF-1R complexes, erbB3 and IGF-1R expression and activity, as well as Src kinase and/or PI-3K/Akt signaling.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	53-59
21881601-5	2011	We showed that 24 h metformin treatment induced a cell cycle arrest in G0/G1 phases, while after 72 h, melanoma cells underwent autophagy as demonstrated by electron microscopy, immunochemistry, and by quantification of the autolysosome-associated LC3 and Beclin1 proteins.	Metformin	20-29	microtubule associated protein 1 light chain 3 alpha	Homo sapiens	248-251
21881601-5	2011	We showed that 24 h metformin treatment induced a cell cycle arrest in G0/G1 phases, while after 72 h, melanoma cells underwent autophagy as demonstrated by electron microscopy, immunochemistry, and by quantification of the autolysosome-associated LC3 and Beclin1 proteins.	Metformin	20-29	beclin 1	Homo sapiens	256-263
21881601-7	2011	Interestingly, inhibition of autophagy by knocking down LC3 or ATG5 decreased the extent of apoptosis, and suppressed the antiproliferative effect of metformin on melanoma cells, suggesting that apoptosis is a consequence of autophagy.	Metformin	150-159	microtubule associated protein 1 light chain 3 alpha	Homo sapiens	56-59
21540236-0	2011	Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1.	Metformin	0-9	DNA damage inducible transcript 4	Homo sapiens	86-91
21540236-4	2011	We identified REDD1 (also known as DDIT4 and RTP801), a negative regulator of mTOR, as a new molecular target of metformin.	Metformin	113-122	DNA damage inducible transcript 4	Homo sapiens	14-19
21540236-4	2011	We identified REDD1 (also known as DDIT4 and RTP801), a negative regulator of mTOR, as a new molecular target of metformin.	Metformin	113-122	DNA damage inducible transcript 4	Homo sapiens	35-40
21540236-5	2011	We show that metformin increases REDD1 expression in a p53-dependent manner.	Metformin	13-22	DNA damage inducible transcript 4	Homo sapiens	33-38
21540236-6	2011	REDD1 invalidation, using siRNA or REDD1(-/-) cells, abrogates metformin inhibition of mTOR.	Metformin	63-72	DNA damage inducible transcript 4	Homo sapiens	0-5
21540236-6	2011	REDD1 invalidation, using siRNA or REDD1(-/-) cells, abrogates metformin inhibition of mTOR.	Metformin	63-72	DNA damage inducible transcript 4	Homo sapiens	35-40
21540236-7	2011	Importantly, inhibition of REDD1 reverses metformin-induced cell-cycle arrest and significantly protects from the deleterious effects of metformin on cell transformation.	Metformin	42-51	DNA damage inducible transcript 4	Homo sapiens	27-32
21540236-7	2011	Importantly, inhibition of REDD1 reverses metformin-induced cell-cycle arrest and significantly protects from the deleterious effects of metformin on cell transformation.	Metformin	137-146	DNA damage inducible transcript 4	Homo sapiens	27-32
21540236-9	2011	These results highlight the p53/REDD1 axis as a new molecular target in anticancer therapy in response to metformin treatment.	Metformin	106-115	DNA damage inducible transcript 4	Homo sapiens	32-37
21478464-0	2011	Metformin inhibits nuclear receptor TR4-mediated hepatic stearoyl-CoA desaturase 1 gene expression with altered insulin sensitivity.	Metformin	0-9	stearoyl-Coenzyme A desaturase 1	Mus musculus	57-82
21478464-5	2011	RESULTS: TR4 transactivation is inhibited via phosphorylation by metformin-induced AMP-activated protein kinase (AMPK) at the amino acid serine 351, which results in the suppression of SCD1 gene expression.	Metformin	65-74	stearoyl-Coenzyme A desaturase 1	Mus musculus	185-189
21478464-7	2011	The pathophysiological consequences of the metformin AMPK TR4 SCD1 pathway are examined via TR4 knockout mice and primary hepatocytes with either knockdown or overexpression of TR4.	Metformin	43-52	stearoyl-Coenzyme A desaturase 1	Mus musculus	62-66
21532889-5	2011	A2780 ovarian cancer cells were injected intraperitoneally in nude mice; A2780-induced tumors in nude mice, when treated with metformin in drinking water, resulted in a significant reduction of tumor growth, accompanied by inhibition of tumor cell proliferation (as assessed by immunohistochemical staining of Ki-67, Cyclin D1) as well as decreased live tumor size and mitotic cell count.	Metformin	126-135	antigen identified by monoclonal antibody Ki 67	Mus musculus	310-315
21532889-5	2011	A2780 ovarian cancer cells were injected intraperitoneally in nude mice; A2780-induced tumors in nude mice, when treated with metformin in drinking water, resulted in a significant reduction of tumor growth, accompanied by inhibition of tumor cell proliferation (as assessed by immunohistochemical staining of Ki-67, Cyclin D1) as well as decreased live tumor size and mitotic cell count.	Metformin	126-135	cyclin D1	Mus musculus	317-326
21147283-0	2011	Metformin induces osteoblast differentiation via orphan nuclear receptor SHP-mediated transactivation of Runx2.	Metformin	0-9	nuclear receptor subfamily 0, group B, member 2	Mus musculus	73-76
21147283-3	2011	Metformin-induced mRNA expression of the osteogenic genes and small heterodimer partner (SHP) in MC3T3E1 cells were determined by RT-PCR and real-time PCR.	Metformin	0-9	nuclear receptor subfamily 0, group B, member 2	Mus musculus	89-92
21147283-4	2011	Metformin increased significantly the expression of the key osteogenic genes, such as alkaline phosphatase (ALP), osteocalcin (OC) and bone sialoprotein (BSP) as well as SHP.	Metformin	0-9	nuclear receptor subfamily 0, group B, member 2	Mus musculus	170-173
21147283-5	2011	Transient transfection assays were performed in MC3T3E1 cells to confirm the effects of metformin on SHP, OC and Runx2 promoter activities.	Metformin	88-97	nuclear receptor subfamily 0, group B, member 2	Mus musculus	101-104
21147283-6	2011	Metformin increased the transcription of the SHP and OC genes, and the metformin effect was inhibited by dominant negative form of AMPK (DN-AMPK) or compound C (an inhibitor of AMPK).	Metformin	0-9	nuclear receptor subfamily 0, group B, member 2	Mus musculus	45-48
21147283-9	2011	Moreover, upstream stimulatory factor-1 (USF-1) specifically mediated metformin-induced SHP gene expression.	Metformin	70-79	nuclear receptor subfamily 0, group B, member 2	Mus musculus	88-91
21147283-12	2011	Transient transfection and chromatin immunoprecipitation assays confirmed that metformin-induced SHP interacts physically and forms a complex with Runx2 on the osteocalcin gene promoter in MC3T3E1 cells.	Metformin	79-88	nuclear receptor subfamily 0, group B, member 2	Mus musculus	97-100
21147283-13	2011	These results suggest that metformin may stimulate osteoblast differentiation through the transactivation of Runx2 via AMPK/USF-1/SHP regulatory cascade in mouse calvaria-derived cells.	Metformin	27-36	nuclear receptor subfamily 0, group B, member 2	Mus musculus	130-133
20458531-4	2011	Of note, CD44-overexpressing Tzb-refractory SKBR3 TzbR and JIMT-1 cells retained an exquisite sensitivity to single-agent metformin.	Metformin	122-131	CD44 molecule (Indian blood group)	Homo sapiens	9-13
20857458-0	2011	Metformin induces Rab4 through AMPK and modulates GLUT4 translocation in skeletal muscle cells.	Metformin	0-9	RAB4A, member RAS oncogene family	Mus musculus	18-22
20857458-3	2011	In this study, we found that AICAR, an AMPK activator, and metformin increased the expression of Rab4 mRNA and protein levels in skeletal muscle C2C12 cells.	Metformin	59-68	RAB4A, member RAS oncogene family	Mus musculus	97-101
20857458-4	2011	The promoter activity of Rab4 was increased by metformin in an AMPK-dependent manner.	Metformin	47-56	RAB4A, member RAS oncogene family	Mus musculus	25-29
20857458-11	2011	Together, these results demonstrate that metformin induces Rab4 expression via AMPK-AS160-PKC-zeta and modulates insulin-mediated GLUT4 translocation.	Metformin	41-50	RAB4A, member RAS oncogene family	Mus musculus	59-63
21282369-0	2011	Tubular injury in a rat model of type 2 diabetes is prevented by metformin: a possible role of HIF-1alpha expression and oxygen metabolism.	Metformin	65-74	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	95-105
32067218-3	2020	The aim of our study was to determine the serum MANF levels in women with PCOS and controls, to investigate their relationship to insulin resistance, and to evaluate circulating MANF changes with metformin intervention in PCOS women.	Metformin	196-205	mesencephalic astrocyte derived neurotrophic factor	Homo sapiens	178-182
32067218-10	2020	After six months of metformin treatment, there was a significant increase in serum MANF levels in PCOS women.	Metformin	20-29	mesencephalic astrocyte derived neurotrophic factor	Homo sapiens	83-87
32067218-12	2020	Metformin treatment elevates serum MANF levels and alleviates insulin resistance and hyperandrogenism in PCOS women.	Metformin	0-9	mesencephalic astrocyte derived neurotrophic factor	Homo sapiens	35-39
32405365-3	2020	We aimed to investigate the combination therapeutic effect of these cells with insulin and metformin on neuropeptide Y, melanocortin-4 receptor, and leptin receptor genes expression in TID.	Metformin	91-100	leptin receptor	Rattus norvegicus	149-164
31476446-0	2020	Recuperative effect of metformin loaded Polydopamine Nanoformulation promoting EZH2 mediated proteasomal degradation of phospho-alpha-Synuclein in Parkinson"s disease model.	Metformin	23-32	synuclein alpha	Homo sapiens	128-143
31875646-0	2020	GDF15 mediates the effects of metformin on body weight and energy balance.	Metformin	30-39	growth differentiation factor 15	Mus musculus	0-5
31875646-4	2020	Here we show-in two independent randomized controlled clinical trials-that metformin increases circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15), which has been shown to reduce food intake and lower body weight through a brain-stem-restricted receptor.	Metformin	75-84	growth differentiation factor 15	Mus musculus	137-169
31875646-5	2020	In wild-type mice, oral metformin increased circulating GDF15, with GDF15 expression increasing predominantly in the distal intestine and the kidney.	Metformin	24-33	growth differentiation factor 15	Mus musculus	56-61
31875646-7	2020	In obese mice on a high-fat diet, the effects of metformin to reduce body weight were reversed by a GFRAL-antagonist antibody.	Metformin	49-58	GDNF family receptor alpha like	Mus musculus	100-105
31875646-8	2020	Metformin had effects on both energy intake and energy expenditure that were dependent on GDF15, but retained its ability to lower circulating glucose levels in the absence of GDF15 activity.	Metformin	0-9	growth differentiation factor 15	Mus musculus	90-95
31875646-9	2020	In summary, metformin elevates circulating levels of GDF15, which is necessary to obtain its beneficial effects on energy balance and body weight, major contributors to its action as a chemopreventive agent.	Metformin	12-21	growth differentiation factor 15	Mus musculus	53-58
31843673-7	2020	Regarding the underlying molecular mechanisms, metformin has been shown to inhibit alpha-synuclein (SNCA) phosphorylation and aggregation, prevent mitochondrial dysfunction, attenuate oxidative stress, modulate autophagy mainly via AMP-activated protein kinase (AMPK) activation, as well as prevent neurodegeneration and neuroinflammation.	Metformin	47-56	synuclein alpha	Homo sapiens	83-98
31843673-7	2020	Regarding the underlying molecular mechanisms, metformin has been shown to inhibit alpha-synuclein (SNCA) phosphorylation and aggregation, prevent mitochondrial dysfunction, attenuate oxidative stress, modulate autophagy mainly via AMP-activated protein kinase (AMPK) activation, as well as prevent neurodegeneration and neuroinflammation.	Metformin	47-56	synuclein alpha	Homo sapiens	100-104
32020874-11	2020	Compared with the DM group, Ser577 phosphorylation of SIK1 was obviously reduced in the liver, while T182 phosphorylation of SIK1 and S171 phosphorylation of CRTC2 were evidently increased in the Ad-SIK1, Met and ZQR groups.	Metformin	205-208	salt-inducible kinase 1	Rattus norvegicus	125-129
32020874-11	2020	Compared with the DM group, Ser577 phosphorylation of SIK1 was obviously reduced in the liver, while T182 phosphorylation of SIK1 and S171 phosphorylation of CRTC2 were evidently increased in the Ad-SIK1, Met and ZQR groups.	Metformin	205-208	CREB regulated transcription coactivator 2	Rattus norvegicus	158-163
32020874-11	2020	Compared with the DM group, Ser577 phosphorylation of SIK1 was obviously reduced in the liver, while T182 phosphorylation of SIK1 and S171 phosphorylation of CRTC2 were evidently increased in the Ad-SIK1, Met and ZQR groups.	Metformin	205-208	salt-inducible kinase 1	Rattus norvegicus	125-129
32083006-8	2020	Thus, metformin treatment showed combinatorial therapeutic value, which resulted in greater induction of lung SCC apoptosis in vitro and in vivo.	Metformin	6-15	serpin family B member 3	Homo sapiens	110-113
31198956-6	2020	The effect of metformin on fenestrations was blocked by inhibitors of AMPK, endothelial nitric oxide synthase and myosin light chain kinase phosphorylation.	Metformin	14-23	nitric oxide synthase 3, endothelial cell	Mus musculus	76-109
31198956-7	2020	Metformin led to increased transgelin expression and structural changes in the actin cytoskeleton but had no effect on lactate production.	Metformin	0-9	transgelin	Mus musculus	27-37
31945013-0	2020	Metformin attenuates cartilage degeneration in an experimental osteoarthritis model by regulating AMPK/mTOR.	Metformin	0-9	mechanistic target of rapamycin kinase	Mus musculus	103-107
31945013-7	2020	CONCLUSIONS: Metformin effectively alleviated cartilage degradation and aging through regulation of the AMPK/mTOR signaling pathways, suggesting that it could be an effective treatment for OA.	Metformin	13-22	mechanistic target of rapamycin kinase	Mus musculus	109-113
31342643-0	2020	SHIPping out diabetes-Metformin, an old friend among new SHIP2 inhibitors.	Metformin	22-31	inositol polyphosphate phosphatase like 1	Homo sapiens	57-62
31342643-7	2020	One of the newly identified SHIP2 inhibitors is metformin, the first-line medication prescribed to patients with type 2 diabetes, further boosting the attraction of SHIP2 as a treatment target to ameliorate metabolic disorders.	Metformin	48-57	inositol polyphosphate phosphatase like 1	Homo sapiens	28-33
31342643-7	2020	One of the newly identified SHIP2 inhibitors is metformin, the first-line medication prescribed to patients with type 2 diabetes, further boosting the attraction of SHIP2 as a treatment target to ameliorate metabolic disorders.	Metformin	48-57	inositol polyphosphate phosphatase like 1	Homo sapiens	165-170
31892560-8	2020	Immunohistochemical analysis of tumor tissues revealed down-regulation of cyclin D1 and proliferating cell nuclear antigen in the metformin-treated group.	Metformin	130-139	proliferating cell nuclear antigen	Homo sapiens	88-122
31902918-6	2020	Furthermore, metformin also enhanced autophagic flux, inhibited the phosphorylation of the serine/threonine protein kinase (AKT)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs) related protein levels and the level of miR-221 in LPS-stimulated RAW264.7 cells.	Metformin	13-22	microRNA 221	Homo sapiens	249-256
31995024-13	2020	The subgroup analysis of metformin monotherapy revealed that, in intervention group, there was a significant increase in gastrin levels (39.9+-12.6 vs. 95.5+-52.5, p=0.026), but the HbA1c levels did not change (6.0+-0.4 % vs. 5.9+-0.6 %, p=0.288); and in control group, gastrin levels did not change (37.5 +- 26.7 vs. 36.1 +-23.3, p=0.367), but there was an increase in HbA1c levels (6.1 +- 0.50 vs. 6.4 +- 0.60, p=0.01).	Metformin	25-34	gastrin	Homo sapiens	121-128
21186350-0	2011	Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes.	Metformin	66-75	ATM serine/threonine kinase	Rattus norvegicus	21-24
21186350-4	2011	In a rat hepatoma cell line, inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMP-activated protein kinase in response to metformin.	Metformin	154-163	ATM serine/threonine kinase	Rattus norvegicus	43-46
21186350-5	2011	We conclude that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMP-activated protein kinase, and variation in this gene alters glycemic response to metformin.	Metformin	118-127	ATM serine/threonine kinase	Rattus norvegicus	17-20
21186350-5	2011	We conclude that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMP-activated protein kinase, and variation in this gene alters glycemic response to metformin.	Metformin	225-234	ATM serine/threonine kinase	Rattus norvegicus	17-20
21799661-10	2011	Poor in vivo and in vitro response to metformin may be the result of pharmacokinetic (OCT-1 expression was low in rat mammary cells; OCT-3 was downregulated in mammary carcinoma) and pharmacodynamic (complex I transcripts were higher in mammary epithelial cells from carcinomas versus uninvolved gland) effects.	Metformin	38-47	solute carrier family 22 member 1	Rattus norvegicus	86-91
21779389-1	2011	Metformin, an oral insulin-sensitizing drug, is actively transported into cells by organic cation transporters (OCT) 1, 2, and 3 (encoded by SLC22A1, SLC22A2, or SLC22A3), which are tissue specifically expressed at significant levels in various organs such as liver, muscle, and kidney.	Metformin	0-9	solute carrier family 22 member 3	Homo sapiens	162-169
21779389-6	2011	All tested PPIs significantly inhibited metformin uptake by OCT1, OCT2, and OCT3 in a concentration-dependent manner.	Metformin	40-49	solute carrier family 22 member 3	Homo sapiens	76-80
21628978-2	2011	However, we hypothesized that retinoid X receptor (RXR) agonists, which are researched for the treatment of type 2 diabetes, will also be useful like metformin, which shows insulin-sparing effect in type 1 diabetes.	Metformin	150-159	retinoid X receptor alpha	Homo sapiens	30-49
21628978-2	2011	However, we hypothesized that retinoid X receptor (RXR) agonists, which are researched for the treatment of type 2 diabetes, will also be useful like metformin, which shows insulin-sparing effect in type 1 diabetes.	Metformin	150-159	retinoid X receptor alpha	Homo sapiens	51-54
20869956-9	2010	In the STZ/NA-induced diabetic mice, metformin increased the splenic T-lymphocyte CD4(+) and CD8(+) cell numbers without any change in T-lymphocyte proliferation.	Metformin	37-46	CD4 antigen	Mus musculus	82-85
32293703-0	2020	An Investigation of Saliva and Plasma Levels of Urotensin-2 in Recently Diagnosed Type 2 Diabetes Mellitus Patients on Metformin Treatment.	Metformin	119-128	urotensin 2	Homo sapiens	48-59
32293703-5	2020	OBJECTIVE: This study aims to investigate the plasma and saliva levels of U-II at diagnosis and after 3-month metformin treatment in recently diagnosed Type 2 DM patients and compare these levels to those of healthy volunteers.	Metformin	110-119	urotensin 2	Homo sapiens	74-78
32293703-9	2020	CONCLUSIONS: It is concluded that , the patients with Type 2 DM, have a multifactorial ethiopathogenesis, U-II levels increase after metformin treatment.	Metformin	133-142	urotensin 2	Homo sapiens	106-110
31851935-3	2019	Metformin interrupts bidirectional signaling between tumor and mesothelial cells by blocking OvCa cell TGF-beta signaling and mesothelial cell production of CCL2 and IL-8.	Metformin	0-9	C-C motif chemokine ligand 2	Homo sapiens	157-161
31626790-0	2019	Metformin attenuates hepatoma cell proliferation by decreasing glycolytic flux through the HIF-1alpha/PFKFB3/PFK1 pathway.	Metformin	0-9	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3	Homo sapiens	102-108
31626790-0	2019	Metformin attenuates hepatoma cell proliferation by decreasing glycolytic flux through the HIF-1alpha/PFKFB3/PFK1 pathway.	Metformin	0-9	phosphofructokinase, muscle	Homo sapiens	109-113
31626790-8	2019	KEY FINDINGS: We found that metformin significantly impaired hepatoma cell proliferation by inhibiting the glycolytic flux via PFK1 blockade.	Metformin	28-37	phosphofructokinase, muscle	Homo sapiens	127-131
31626790-9	2019	Interestingly, activation of PFK1 by F2,6BP reverses the inhibitory effect of metformin on hepatoma cell proliferation and glycolysis.	Metformin	78-87	phosphofructokinase, muscle	Homo sapiens	29-33
31626790-10	2019	Mechanistically, PFKFB3,a potent allosteric activator of PFK1, was markedly suppressed through inhibiting hypoxia-induced factor 1 (HIF-1alpha) accumulation mediated by metformin.	Metformin	169-178	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3	Homo sapiens	17-23
31626790-10	2019	Mechanistically, PFKFB3,a potent allosteric activator of PFK1, was markedly suppressed through inhibiting hypoxia-induced factor 1 (HIF-1alpha) accumulation mediated by metformin.	Metformin	169-178	phosphofructokinase, muscle	Homo sapiens	57-61
31626790-11	2019	SIGNIFICANCE: Taken together these data indicate that HIF-1alpha/PFKFB3/PFK1 regulatory axis is a vital determinant of glucose metabolic reprogramming in hepatocellular carcinoma, which gives new insights into the action of metformin in combatting liver cancer.	Metformin	224-233	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3	Homo sapiens	65-71
31628524-8	2019	Metformin effectively inhibited the increase of IGF-1 and maintained the IGFBP-1.	Metformin	0-9	insulin like growth factor binding protein 1	Homo sapiens	73-80
32694673-0	2019	Metformin-induced increases in GDF15 are important for suppressing appetite and promoting weight loss.	Metformin	0-9	growth differentiation factor 15	Mus musculus	31-36
20812964-6	2010	The known agonists of Sirt1, resveratrol and metformin, also significantly inhibited MMP-9 expression and appeared to protect collagen from degradation after UVR.	Metformin	45-54	sirtuin 1	Homo sapiens	22-27
20812964-6	2010	The known agonists of Sirt1, resveratrol and metformin, also significantly inhibited MMP-9 expression and appeared to protect collagen from degradation after UVR.	Metformin	45-54	matrix metallopeptidase 9	Homo sapiens	85-90
21311678-4	2010	Coinfusion of metformin (150 mg/kg/24 h) with isoproterenol partially inhibited cardiac hypertrophy that was followed by reduced IL-6, TGF-beta, ANP, collagen I and III, and MMP-2.	Metformin	14-23	matrix metallopeptidase 2	Mus musculus	174-179
20652679-4	2010	RESULTS: AICAR and metformin markedly blunt the IL-6-stimulated expression of SAA cluster genes as well as of haptoglobin in a dose-dependent manner.	Metformin	19-28	serum amyloid A1 cluster	Homo sapiens	78-81
20652679-5	2010	Moreover, the repression of AMPK activity by siRNA significantly reversed the inhibition of SAA expression by both AICAR and metformin, indicating that the effect of the agonists is dependent on AMPK.	Metformin	125-134	serum amyloid A1 cluster	Homo sapiens	92-95
20859243-0	2010	Role of organic cation transporter 3 (SLC22A3) and its missense variants in the pharmacologic action of metformin.	Metformin	104-113	OCTN3	Homo sapiens	8-36
20859243-0	2010	Role of organic cation transporter 3 (SLC22A3) and its missense variants in the pharmacologic action of metformin.	Metformin	104-113	solute carrier family 22 member 3	Homo sapiens	38-45
20859243-1	2010	OBJECTIVES: The goals of this study were to determine the role of organic cation transporter 3 (OCT3) in the pharmacological action of metformin and to identify and functionally characterize genetic variants of OCT3 with respect to the uptake of metformin and monoamines.	Metformin	135-144	OCTN3	Homo sapiens	66-94
20859243-1	2010	OBJECTIVES: The goals of this study were to determine the role of organic cation transporter 3 (OCT3) in the pharmacological action of metformin and to identify and functionally characterize genetic variants of OCT3 with respect to the uptake of metformin and monoamines.	Metformin	135-144	OCTN3	Homo sapiens	96-100
20859243-1	2010	OBJECTIVES: The goals of this study were to determine the role of organic cation transporter 3 (OCT3) in the pharmacological action of metformin and to identify and functionally characterize genetic variants of OCT3 with respect to the uptake of metformin and monoamines.	Metformin	135-144	OCTN3	Homo sapiens	211-215
20859243-1	2010	OBJECTIVES: The goals of this study were to determine the role of organic cation transporter 3 (OCT3) in the pharmacological action of metformin and to identify and functionally characterize genetic variants of OCT3 with respect to the uptake of metformin and monoamines.	Metformin	246-255	OCTN3	Homo sapiens	211-215
20859243-4	2010	RESULTS: Quantitative PCR and immunostaining showed that OCT3 was expressed high on the plasma membrane of skeletal muscle and liver, target tissues for metformin action.	Metformin	153-162	OCTN3	Homo sapiens	57-61
20859243-5	2010	Both the OCT inhibitor, cimetidine, and OCT3-specific short hairpin RNA significantly reduced the activating effect of metformin on AMP-activated protein kinase.	Metformin	119-128	OCTN3	Homo sapiens	40-44
20859243-11	2010	CONCLUSION: Our study suggests that OCT3 plays a role in the therapeutic action of metformin and that genetic variants of OCT3 may modulate metformin and catecholamine action.	Metformin	83-92	OCTN3	Homo sapiens	36-40
20859243-11	2010	CONCLUSION: Our study suggests that OCT3 plays a role in the therapeutic action of metformin and that genetic variants of OCT3 may modulate metformin and catecholamine action.	Metformin	140-149	OCTN3	Homo sapiens	122-126
20688914-8	2010	In addition, metformin or overexpression of a constitutively active form of AMPK (Ad-CA-AMPK) inhibited S171A-mediated PEPCK and G6Pase gene expression, and hepatic glucose production and knockdown of SHP partially relieved the metformin- and Ad-CA-AMPK-mediated repression of hepatic gluconeogenic enzyme gene expression in primary rat hepatocytes.	Metformin	13-22	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	119-124
20135346-2	2010	Adenosine 5"- monophosphate-activated protein kinase (AMPK) activators such as metformin have similar actions, in keeping with the TSC2/1 pathway linking activation of AMPK to inhibition of mTOR.	Metformin	79-88	TSC complex subunit 2	Homo sapiens	131-135
20590612-0	2010	Metformin blocks migration and invasion of tumour cells by inhibition of matrix metalloproteinase-9 activation through a calcium and protein kinase Calpha-dependent pathway: phorbol-12-myristate-13-acetate-induced/extracellular signal-regulated kinase/activator protein-1.	Metformin	0-9	matrix metallopeptidase 9	Homo sapiens	73-99
20590612-0	2010	Metformin blocks migration and invasion of tumour cells by inhibition of matrix metalloproteinase-9 activation through a calcium and protein kinase Calpha-dependent pathway: phorbol-12-myristate-13-acetate-induced/extracellular signal-regulated kinase/activator protein-1.	Metformin	0-9	Jun proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	252-271
1505458-8	1992	Western blot analysis using antisera reactive with the GLUT1 and GLUT4 isoforms of glucose transporters showed that metformin caused a reduction in GLUT1 content in the IM fraction and a concomitant increase in the PM.	Metformin	116-125	solute carrier family 2 member 1	Homo sapiens	55-60
1505458-8	1992	Western blot analysis using antisera reactive with the GLUT1 and GLUT4 isoforms of glucose transporters showed that metformin caused a reduction in GLUT1 content in the IM fraction and a concomitant increase in the PM.	Metformin	116-125	solute carrier family 2 member 1	Homo sapiens	148-153
1505458-10	1992	We propose that the molecular basis of metformin action in skeletal muscle involves the subcellular redistribution of GLUT1 proteins from an intracellular compartment to the plasma membrane.	Metformin	39-48	solute carrier family 2 member 1	Homo sapiens	118-123
32694673-5	2019	Here we show, using unbiased transcriptomics of mouse hepatocytes and analysis of proteins in human serum, that metformin induces expression and secretion of growth differentiating factor 15 (GDF15).	Metformin	112-121	growth differentiation factor 15	Mus musculus	158-190
32694673-5	2019	Here we show, using unbiased transcriptomics of mouse hepatocytes and analysis of proteins in human serum, that metformin induces expression and secretion of growth differentiating factor 15 (GDF15).	Metformin	112-121	growth differentiation factor 15	Mus musculus	192-197
32694673-6	2019	In primary mouse hepatocytes, metformin stimulates the secretion of GDF15 by increasing the expression of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP; also known as DDIT3).	Metformin	30-39	growth differentiation factor 15	Mus musculus	68-73
31686542-4	2022	Importantly, miR-33b mimic inhibited the increasing effects of metformin on the expression of CPT1 and CROT.Conclusion: These findings suggest that metformin attenuates high glucose-induced lipid accumulation in HepG2 cell by downregulating the expression of miR-33b.	Metformin	63-72	microRNA 33b	Homo sapiens	259-266
31686542-4	2022	Importantly, miR-33b mimic inhibited the increasing effects of metformin on the expression of CPT1 and CROT.Conclusion: These findings suggest that metformin attenuates high glucose-induced lipid accumulation in HepG2 cell by downregulating the expression of miR-33b.	Metformin	148-157	microRNA 33b	Homo sapiens	13-20
31686542-4	2022	Importantly, miR-33b mimic inhibited the increasing effects of metformin on the expression of CPT1 and CROT.Conclusion: These findings suggest that metformin attenuates high glucose-induced lipid accumulation in HepG2 cell by downregulating the expression of miR-33b.	Metformin	148-157	microRNA 33b	Homo sapiens	259-266
31693126-14	2019	Frequency of PSA testing was higher for those receiving metformin (rate ratio, 1.07; 95% CI, 1.06-1.09) and sulfonylurea (rate ratio, 1.06; 95% CI, 1.03-1.08) but was lower for those receiving insulin (rate ratio, 0.79; 95% CI, 0.77- 0.81).	Metformin	56-65	kallikrein related peptidase 3	Homo sapiens	13-16
31693126-15	2019	Likelihood of biopsy after elevated PSA was lower among men receiving metformin (odds ratio, 0.87; 95% CI, 0.80-0.96) and insulin (odds ratio, 0.83; 95% CI, 0.74-0.93).	Metformin	70-79	kallikrein related peptidase 3	Homo sapiens	36-39
30930073-5	2019	The overview sums up the approaches implicated by the study that can potentially counteract the detrimental impact of hyperglycemia on vascular function in people with diabetes, including the clinical use of SGLT2 inhibitors for those with type 2 diabetes already being treated, for example, with metformin, along with dietary supplementation with broccoli-derived sulforaphane and tetrahydrobiopterin.	Metformin	297-306	solute carrier family 5 member 2	Homo sapiens	208-213
31405334-8	2019	Furthermore, co-treatment with TECOS and DMBG induced H19 expression via suppressing the PI3K/AKT-DNMT1 pathway.	Metformin	41-45	DNA methyltransferase 1	Rattus norvegicus	98-103
31319131-6	2019	We found that the metformin pretreatment alleviated the lung injury and decreased the levels of TNF-a, IL-1beta and IL-6 in the bronchoalveolar lavage fluid (BALF) and in lung tissues, as well as the levels of NLRP3, NLRC4 and cleaved caspase-1 associated with LPS-induced ALI in old mice.	Metformin	18-27	NLR family, pyrin domain containing 3	Mus musculus	210-215
32184858-8	2019	The lowest dose of the combination [Metformin (0.25 mM) and berberine (5 muM)] also synergistically reduced the expression of the FAS and SREBP-1c genes in HepG2 cells treated with high glucose.	Metformin	36-45	sterol regulatory element binding transcription factor 1	Homo sapiens	138-146
33033766-0	2020	Combination of Pancreastatin inhibitor PSTi8 with metformin inhibits Fetuin-A in type 2 diabetic mice.	Metformin	50-59	alpha-2-HS-glycoprotein	Mus musculus	69-77
33033527-4	2020	Results: In vitro and in vivo studies showed that treatment with a combination of celecoxib and metformin inhibited proliferation of HCC to a greater extent than either treatment alone, by reducing the phosphorylation of MTOR.	Metformin	96-105	mechanistic target of rapamycin kinase	Rattus norvegicus	221-225
22770240-4	2012	Metformin also enhances neurogenesis in the adult mouse brain in a CBP-dependent fashion, and in so doing enhances spatial reversal learning in the water maze.	Metformin	0-9	CREB binding protein	Mus musculus	67-70
34875507-4	2022	We demonstrate that both Metformin and Nano-PSO reduced aging hallmarks activities such as activated AMPK, the main energy sensor of cells as well as Nrf2 and COX IV1, regulators of oxidation, and mitochondrial activity.	Metformin	25-34	cytochrome c oxidase subunit 4I1	Mus musculus	159-166
34427052-0	2022	A 24-month metformin treatment study of children with obesity: Changes in circulating GDF-15 and associations with changes in body weight and visceral fat.	Metformin	11-20	growth differentiation factor 15	Homo sapiens	86-92
34427052-2	2022	OBJECTIVE: Here we study whether circulating GDF-15 levels were raised by such metformin treatment and whether they related to changes in body weight and visceral fat in children with obesity.	Metformin	79-88	growth differentiation factor 15	Homo sapiens	45-51
34427052-5	2022	RESULTS: Results showed that metformin-treated children had higher GDF-15 levels at 6 and 12 months.	Metformin	29-38	growth differentiation factor 15	Homo sapiens	67-73
34427052-7	2022	CONCLUSION: In conclusion, the concept that GDF-15 is among the mediators of metformin"s normalizing effects in individuals with obesity is herewith extended into childhood.	Metformin	77-86	growth differentiation factor 15	Homo sapiens	44-50
34806449-2	2022	Previous work showed that metformin reduces cyst growth in rapid ADPKD mouse models via inhibition of CFTR-mediated fluid secretion, mTOR, and cAMP pathways.	Metformin	26-35	cystic fibrosis transmembrane conductance regulator	Mus musculus	102-106
34637881-7	2022	Further, metformin induced AMPK phosphorylation and impaired AMPK-PI3k-AKT-mTOR pathway activation.	Metformin	9-18	mechanistic target of rapamycin kinase	Rattus norvegicus	75-79
34826740-6	2022	In vivo, we evaluated the therapeutic value of metformin on reversing INSM1 induced chemoresistance by BALB/c nude mice xenograft tumor model.	Metformin	47-56	insulinoma-associated 1	Mus musculus	70-75
34895333-11	2021	Furthermore, HK1 revertants but not HK2 revertants caused a strong increase of NADPH/NADP ratios independently on the presence of glucose or metformin.	Metformin	141-150	2,4-dienoyl-CoA reductase 1	Homo sapiens	79-84
34895333-13	2021	CONCLUSIONS: We provided the evidence that HK1 is involved in the so far unknown glycolysis-independent HK1-metformin axis and influences metabolism even in glucose-free conditions.	Metformin	108-117	hexokinase 1	Mus musculus	43-46
34895333-13	2021	CONCLUSIONS: We provided the evidence that HK1 is involved in the so far unknown glycolysis-independent HK1-metformin axis and influences metabolism even in glucose-free conditions.	Metformin	108-117	hexokinase 1	Mus musculus	104-107
31012983-1	2019	The organic cation transporters OCT1 and OCT2 and the multidrug and toxin extrusion transporter MATE1, encoded by the SLC22A1, SLC22A2, and SLC47A1 genes, respectively, are responsible for the absorption of metformin in enterocytes, hepatocytes, and kidney cells.	Metformin	207-216	solute carrier family 22 member 2	Homo sapiens	41-45
31012983-1	2019	The organic cation transporters OCT1 and OCT2 and the multidrug and toxin extrusion transporter MATE1, encoded by the SLC22A1, SLC22A2, and SLC47A1 genes, respectively, are responsible for the absorption of metformin in enterocytes, hepatocytes, and kidney cells.	Metformin	207-216	solute carrier family 22 member 2	Homo sapiens	127-134
31012983-2	2019	The aim of this study was to evaluate whether genetic variations in the SLC22A1, SLC22A2, and SLC47A1 genes could be associated with an altered response to metformin in patients with type 2 diabetes mellitus.	Metformin	156-165	solute carrier family 22 member 2	Homo sapiens	81-88
31929697-8	2019	E-selectin was declined significantly following metformin monotherapy and after metformin plus CoQ10 therapy (P = 0.0001).	Metformin	48-57	selectin E	Homo sapiens	0-10
31929697-8	2019	E-selectin was declined significantly following metformin monotherapy and after metformin plus CoQ10 therapy (P = 0.0001).	Metformin	80-89	selectin E	Homo sapiens	0-10
31686756-13	2019	After 4 months treatment with metformin for twenty-nine polycystic patients, there was a significant reduction in irisin level by (165.8 +- 55.6 mug/l) and the p value was significant.	Metformin	30-39	fibronectin type III domain containing 5	Homo sapiens	114-120
31325582-0	2019	Metformin reduces c-Fos and ATF3 expression in the dorsal root ganglia and protects against oxaliplatin-induced peripheral sensory neuropathy in mice.	Metformin	0-9	FBJ osteosarcoma oncogene	Mus musculus	18-23
34255273-8	2021	More importantly, here we noticed metformin decreased levels of SGLT2 in kidney, intestine, and pancreas of HFD mice markedly.	Metformin	34-43	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	64-69
34255273-9	2021	Expressions of SGLT1 in intestine and pancreas were reduced by metformin as well.	Metformin	63-72	solute carrier family 5 (sodium/glucose cotransporter), member 1	Mus musculus	15-20
34255273-11	2021	CONCLUSIONS: The present study provided evidence that expressions of SGLT1 and SGLT2 were significantly modulated by diabetes mellitus as well as by metformin and fluoxetine, which indicated the efficacy of SGLT2 inhibitors might be impacted by these factors.	Metformin	149-158	solute carrier family 5 (sodium/glucose cotransporter), member 1	Mus musculus	69-74
34255273-11	2021	CONCLUSIONS: The present study provided evidence that expressions of SGLT1 and SGLT2 were significantly modulated by diabetes mellitus as well as by metformin and fluoxetine, which indicated the efficacy of SGLT2 inhibitors might be impacted by these factors.	Metformin	149-158	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	79-84
34255273-11	2021	CONCLUSIONS: The present study provided evidence that expressions of SGLT1 and SGLT2 were significantly modulated by diabetes mellitus as well as by metformin and fluoxetine, which indicated the efficacy of SGLT2 inhibitors might be impacted by these factors.	Metformin	149-158	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	207-212
34432352-7	2021	In sum, the results suggested that metformin can ameliorate the MC-LR-induced AD-like phenotype by preventing tau phosphorylation at Ser202, which was mainly mediated by mTOR-dependent PP2A and GSK-3beta activation.	Metformin	35-44	mechanistic target of rapamycin kinase	Rattus norvegicus	170-174
34887262-10	2021	Low-dose SN-38 or metformin abrogated PD-L1 protein expression, promoted FOXO3 protein level, and significantly increased the animal survival rate in syngeneic mouse tumor models.	Metformin	18-27	forkhead box O3	Mus musculus	73-78
34887262-11	2021	SN-38 or metformin sensitized unresponsive tumors responding to anti-PD-1 therapy by engaging NK or CD8+ T cells to infiltrate the tumor microenvironment (TME) and secret interferon-gamma and granzyme B to kill tumors.	Metformin	9-18	CD8a molecule	Homo sapiens	100-103
34956455-8	2021	Metformin significantly suppressed the deposition of collagen and elastic fibers in the fibrotic pleura and decreased the expression of extracellular matrix (ECM)-related genes, including Col1a1, Col3a1, Fn1, and Eln, in pleural CD90-positive myofibroblasts.	Metformin	0-9	collagen type I alpha 1 chain	Homo sapiens	188-194
34956455-8	2021	Metformin significantly suppressed the deposition of collagen and elastic fibers in the fibrotic pleura and decreased the expression of extracellular matrix (ECM)-related genes, including Col1a1, Col3a1, Fn1, and Eln, in pleural CD90-positive myofibroblasts.	Metformin	0-9	elastin	Homo sapiens	213-216
34779127-5	2022	It has been also reported that the appetite-suppressing effect of metformin, whose mechanism of action was previously ambiguous, is mediated by the increase in serum growth and differentiation factor-15 (GDF15) concentration2 .	Metformin	66-75	growth differentiation factor 15	Homo sapiens	166-202
34779127-5	2022	It has been also reported that the appetite-suppressing effect of metformin, whose mechanism of action was previously ambiguous, is mediated by the increase in serum growth and differentiation factor-15 (GDF15) concentration2 .	Metformin	66-75	growth differentiation factor 15	Homo sapiens	204-209
31325582-10	2019	In addition, the oxaliplatin-associated nociception was significantly attenuated by metformin (P &lt; 0.05), which also reduced the expression of c-Fos and ATF3 (P &lt; 0.05).	Metformin	84-93	FBJ osteosarcoma oncogene	Mus musculus	146-151
31325582-11	2019	Therefore, metformin protected from the peripheral sensory neuropathy induced by oxaliplatin, which was confirmed by the reduction of c-Fos and ATF3 expression, two known neuronal activation and damage markers, respectively.	Metformin	11-20	FBJ osteosarcoma oncogene	Mus musculus	134-139
31645842-0	2019	Metformin restores the mitochondrial membrane potentials in association with a reduction in TIMM23 and NDUFS3 in MPP+-induced neurotoxicity in SH-SY5Y cells.	Metformin	0-9	NADH:ubiquinone oxidoreductase core subunit S3	Homo sapiens	103-109
31645842-7	2019	Pretreatment with metformin decreased the expression of TIMM23 and NDUFS3 in MPP+-treated SH-SY5Y cells.	Metformin	18-27	NADH:ubiquinone oxidoreductase core subunit S3	Homo sapiens	67-73
31581911-0	2019	Metformin inhibits angiogenesis of endothelial progenitor cells via miR-221-mediated p27 expression and autophagy.	Metformin	0-9	microRNA 221	Homo sapiens	68-75
31581911-2	2019	Results: EPC growth and miR-221 expression decreased concentration-dependence with metformin, and a negative correlation was observed between miR-221 expression and metformin concentration (p &lt; 0.001).	Metformin	83-92	microRNA 221	Homo sapiens	24-31
31581911-2	2019	Results: EPC growth and miR-221 expression decreased concentration-dependence with metformin, and a negative correlation was observed between miR-221 expression and metformin concentration (p &lt; 0.001).	Metformin	165-174	microRNA 221	Homo sapiens	142-149
31581911-3	2019	miR-221 overexpression using a mimic decreased the metformin-mediated angiogenic effects in EPCs (p &lt; 0.01).	Metformin	51-60	microRNA 221	Homo sapiens	0-7
31581911-4	2019	Metformin increased p27 and LC3II expression and AMP-activated protein kinase (AMPK) phosphorylation, and decreased p62 expression, while miR-221 overexpression reversed the effects of metformin.	Metformin	185-194	microRNA 221	Homo sapiens	138-145
31121610-10	2019	Three months metformin treatment decreased circulating irisin in PCOS women and improved IR.	Metformin	13-22	fibronectin type III domain containing 5	Homo sapiens	55-61
31121610-12	2019	Moreover, metformin as a confounding therapy in metabolic diseases can be used to regulate circulating irisin levels in PCOS women.	Metformin	10-19	fibronectin type III domain containing 5	Homo sapiens	103-109
31497348-6	2019	We found that knockdown of LKB1 significantly promoted in vitro proliferation, adhesion, invasion, and metformin-induced apoptosis, and simultaneously enhanced activation of ERK and mammalian-target of rapamycin (mTOR) signaling pathways in LKB1-compenent U87 and T98 glioblastoma cells.	Metformin	103-112	serine/threonine kinase 11	Homo sapiens	27-31
30973968-5	2019	As a secondary aim, we wished to correlate hepatic metformin distribution with OCT gene transcription determined in diagnostic liver biopsies.	Metformin	51-60	plexin A2	Homo sapiens	79-82
31188026-6	2019	Results: In the primary analysis, both ATM and OCT1 showed significant effects of genotype on change in body mass index z-scores, the primary outcome measure, during the first 16 weeks of treatment with metformin.	Metformin	203-212	ATM serine/threonine kinase	Homo sapiens	39-42
31153642-0	2019	The synergistic effect of PFK15 with metformin exerts anti-myeloma activity via PFKFB3.	Metformin	37-46	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3	Homo sapiens	80-86
31153642-5	2019	The oral hypoglycemic drug metformin (Met) was found to inhibit PFKFB3 protein expression by gene chip and Western blotting techniques in our study.	Metformin	27-36	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3	Homo sapiens	64-70
31448346-0	2019	Can metformin stabilize PCSK9 level in stable coronary artery disease patients treated with statins?	Metformin	4-13	proprotein convertase subtilisin/kexin type 9	Homo sapiens	24-29
31448346-2	2019	We aimed to study the influence of metformin on the level of circulating PCSK9 in patients with stable coronary artery disease (SCAD) and type 2 diabetes (T2DM) or metabolic syndrome (MetS), receiving moderate doses of statins used in routine clinical practice.	Metformin	35-44	proprotein convertase subtilisin/kexin type 9	Homo sapiens	73-78
31448346-10	2019	Conclusions: The addition of metformin to ongoing rosuvastatin therapy did not significantly affect serum lipid levels, but stabilized the level of circulating PCSK9, compared with the group without metformin treatment.	Metformin	29-38	proprotein convertase subtilisin/kexin type 9	Homo sapiens	160-165
31293042-11	2019	Furthermore, 50 muM metformin significantly upregulated the gene expression levels of ALP, BSP, OPN, OCN, and Runx2 and the protein expression of ALP and Runx2 (P &lt;  0.05).	Metformin	20-29	secreted phosphoprotein 1	Homo sapiens	96-99
31028998-6	2019	More importantly, metformin induced G2/M cell cycle phase arrest in RA-FLS via the IGF-IR/PI3K/AKT/ m-TOR pathway and inhibited m-TOR phosphorylation through both the IGF-IR/PI3K/AKT signaling pathways thereby further upregulating and down-regulating p70s6k and 4E-BP1 phosphorylation, respectively; however, metformin was found not to induce apoptosis in RA-FLSs.	Metformin	18-27	ribosomal protein S6 kinase B1	Homo sapiens	251-268
31028998-7	2019	In summary, these results demonstrate that metformin can effectively inhibit RA-FLS proliferation through inducing cell cycle and upregulating and down-regulating p70s6k and 4E-BP1 phosphorylation.	Metformin	43-52	ribosomal protein S6 kinase B1	Homo sapiens	163-180
31182682-10	2019	These results indicate that metformin can delay ovarian aging process, probably by inducing the expression of SIRT1 and reducing the oxidative damage.	Metformin	28-37	sirtuin 1	Mus musculus	110-115
31341409-0	2019	Metformin Inhibits Epithelial-to-Mesenchymal Transition of Keloid Fibroblasts via the HIF-1alpha/PKM2 Signaling Pathway.	Metformin	0-9	pyruvate kinase M1/2	Homo sapiens	97-101
31341409-9	2019	PKM2 is involved in hypoxia-induced EMT of KFs and metformin decreased the expression of p-p70s6k and PKM2.	Metformin	51-60	pyruvate kinase M1/2	Homo sapiens	102-106
31341409-10	2019	Conclusions: Metformin abolishes hypoxia-induced EMT in KFs by inhibiting the HIF-1alpha/PKM2 signaling pathway.	Metformin	13-22	pyruvate kinase M1/2	Homo sapiens	89-93
30851273-2	2019	Previous researches showed that metformin activates Adenosine Monophosphate Activated Protein Kinase (AMPK) and Protein Phosphatase 2A (PP2A).	Metformin	32-41	protein phosphatase 2 phosphatase activator	Homo sapiens	136-140
30617039-6	2019	Based on such preclinical evidence, the phase II FAME trial was designed to test the hypothesis that the addition of metformin, with or without cyclic FMD, to standard platinum-based chemotherapy improves the progression-free survival of patients with advanced, LKB-1 inactive lung adenocarcinoma.	Metformin	117-126	benign adult familial myoclonic epilepsy 1	Homo sapiens	49-53
30609212-1	2019	AIMS: To characterize the glycaemic efficacy and safety of initiation of the dipeptidyl peptidase-4 inhibitor sitagliptin during metformin dose escalation in people with type 2 diabetes (T2D) not at glycated haemoglobin (HbA1c) goal on a sub-maximal dose of metformin.	Metformin	129-138	dipeptidyl peptidase 4	Homo sapiens	77-99
30697897-6	2019	In as-treated analysis, the estimated hazard of LEA was increased among SGLT2 inhibitor initiators compared to DPP-4 inhibitor initiators (aHR 1.69, 95% CI 1.20-2.38), but not compared to SU initiators (aHR 1.02, 95% CI 0.67-1.55) or non-metformin, non-SGLT2 inhibitor initiators (aHR 1.02, 95% CI 0.54-1.93).	Metformin	238-247	solute carrier family 5 member 2	Homo sapiens	72-77
30904743-8	2019	The most commonly prescribed second-line therapies were combinations of metformin with a dipeptidyl peptidase-4 inhibitor (23.5%; ARR: 2.2-29.6%) or a sulfonylurea (20.9%; ARR: 13.6-57.1%).	Metformin	72-81	dipeptidyl peptidase 4	Homo sapiens	89-111
30835599-2	2019	In patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or those at high risk for CVD, subsequently to lifestyle changes and metformin therapy, the administration of an SGLT-2 inhibitor with established benefits for cardiovascular outcome (CVOT) should be considered.	Metformin	153-162	solute carrier family 5 member 2	Homo sapiens	197-203
34785232-3	2022	A national tap water assessment showed that metformin and C concentrations were higher in large, dense urban areas and surface water sources than in sparsely populated areas and groundwater sources.	Metformin	44-53	nuclear RNA export factor 1	Homo sapiens	11-14
34785232-7	2022	Combinedly, our work reveals that metformin byproducts have been disseminated to urban water cycle and contaminated tap water, increasing potential toxic risk for drinking water.	Metformin	34-43	nuclear RNA export factor 1	Homo sapiens	116-119
34516950-12	2021	Metformin normalized the changes of MGO and AGEs levels, Glo1 expression and activity, urothelium thickness and collagen content.	Metformin	0-9	glyoxalase 1	Mus musculus	57-61
30896786-11	2019	These results demonstrate the beneficial effect of miR-130a/PTEN on EPC functions, which can be regulated by metformin.	Metformin	109-118	phosphatase and tensin homolog	Homo sapiens	60-64
30896786-12	2019	The effects of metformin on improving PA-induced EPC dysfunction are mediated by miR-130a and PTEN, which may assist in the prevention and/or treatment of diabetic vascular disease.	Metformin	15-24	phosphatase and tensin homolog	Homo sapiens	94-98
30816444-0	2019	MUL1 E3 ligase regulates the antitumor effects of metformin in chemoresistant ovarian cancer cells via AKT degradation.	Metformin	50-59	mitochondrial E3 ubiquitin protein ligase 1	Homo sapiens	0-4
30816444-3	2019	The current study revealed that the novel antitumor mechanism of metformin is mediated by regulation of mitochondrial E3 ubiquitin protein ligase 1 (MUL1) expression that negatively regulates AKT.	Metformin	65-74	mitochondrial E3 ubiquitin protein ligase 1	Homo sapiens	104-147
34749618-3	2021	Potential mechanisms by which metformin may decrease colorectal cancer risk include its effects on ameliorating intestinal inflammation and dysbiosis, suppressing major proliferative pathways, preventing DNA replication, accelerating tumor cells apoptosis, inhibiting intra-tumor angiogenesis and epithelial-mesenchymal transition (EMT), increasing tumor-infiltrating lymphocytes and CD68+ tumor-associated macrophages, and enhancing T cell cytotoxicity activity.	Metformin	30-39	CD68 molecule	Homo sapiens	384-388
34464747-14	2021	DF-induced mitochondrial dysfunction which was demonstrated by decreased oxygen consumption rate, an increased ROS production and a reduced MnSOD level, were all reversed by metformin in an EPAC-dependent manner.	Metformin	174-183	superoxide dismutase 2	Rattus norvegicus	140-145
34649197-6	2021	The selective glucose deprivation would not only disrupt tumor energy metabolism, but also upregulate the PP2A regulatory subunit B56delta and sensitize tumor cells to the metformin-induced CIP2A inhibition, leading to efficient apoptosis induction via PP2A-GSK3beta-MCL-1 axis with negligible side effects.	Metformin	172-181	cellular inhibitor of PP2A	Homo sapiens	190-195
34517004-0	2021	Metformin attenuates the epithelial-mesenchymal transition of lens epithelial cells through the AMPK/TGF-beta/Smad2/3 signalling pathway.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	96-100
34815353-10	2021	However, we observed an increased number of CD8 T cells expressing PD-1, Ki-67, Tim-3, and CD62L as well as increased effector cytokine production after treatment with metformin and tumor membrane vesicle vaccine.	Metformin	168-177	antigen identified by monoclonal antibody Ki 67	Mus musculus	73-78
34593558-4	2021	IM156 significantly increased cellular AMPK phosphorylation and was 60-fold more potent than metformin.	Metformin	93-102	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	39-43
34716862-6	2021	METHODS AND RESULTS: Using iGEMDock software, a protein-ligand interaction was successful between Metformin and TSHR (receptor present in the thyroid follicular cells).	Metformin	98-107	thyroid stimulating hormone receptor	Homo sapiens	112-116
34716862-8	2021	Downregulation of ERK signaling, upregulation of AMPK pathway and precision in epithelial-mesenchymal transition (EMT) pathway which were assessed by RT-PCR and Western blot provide the evidence that the combination of drugs involved in the precision of altered molecular signaling Further our results suggest that Metformin act as a demethylating agent in anaplastic thyroid cancer cells by inducing the expression of NIS and TSHR.	Metformin	315-324	thyroid stimulating hormone receptor	Homo sapiens	427-431
30816444-3	2019	The current study revealed that the novel antitumor mechanism of metformin is mediated by regulation of mitochondrial E3 ubiquitin protein ligase 1 (MUL1) expression that negatively regulates AKT.	Metformin	65-74	mitochondrial E3 ubiquitin protein ligase 1	Homo sapiens	149-153
30816444-4	2019	The results demonstrated that metformin decreased the expression of AKT protein levels via MUL1 E3 ligase.	Metformin	30-39	mitochondrial E3 ubiquitin protein ligase 1	Homo sapiens	91-95
30816444-5	2019	In addition, metformin increased both mRNA and protein levels of MUL1 and promoted degradation of AKT in a proteasome-dependent manner.	Metformin	13-22	mitochondrial E3 ubiquitin protein ligase 1	Homo sapiens	65-69
30816444-6	2019	Silencing MUL1 expression suppressed the metformin-mediated AKT degradation and its downstream effects.	Metformin	41-50	mitochondrial E3 ubiquitin protein ligase 1	Homo sapiens	10-14
30816444-7	2019	Cell cycle analysis and a clonogenic assay demonstrated that knockdown of MUL1 significantly diminished the antitumor effects of metformin.	Metformin	129-138	mitochondrial E3 ubiquitin protein ligase 1	Homo sapiens	74-78
30816444-8	2019	Together, these data indicate that MUL1 regulates metformin-mediated AKT degradation and the antitumor effects of metformin in chemoresistant ovarian cancer cell lines.	Metformin	50-59	mitochondrial E3 ubiquitin protein ligase 1	Homo sapiens	35-39
30816444-8	2019	Together, these data indicate that MUL1 regulates metformin-mediated AKT degradation and the antitumor effects of metformin in chemoresistant ovarian cancer cell lines.	Metformin	114-123	mitochondrial E3 ubiquitin protein ligase 1	Homo sapiens	35-39
30032440-4	2019	Metformin (50 muM) significantly decreased SOST and DKK1 mRNA expression, stimulating alkaline phosphatase activity and proliferation of osteoblast, and increased OPG secretion and the ratio of OPG/RANKL, inhibiting osteoclastogenesis.	Metformin	0-9	tumor necrosis factor (ligand) superfamily, member 11	Mus musculus	198-203
30171747-9	2019	CONCLUSIONS: A comparison of GV with HMET versus LMET + DPP4 suggested that LMET + DPP4 might reduce post-breakfast GV to a greater degree than HMET in type 2 diabetes patients receiving low-dose metformin monotherapy.	Metformin	196-205	dipeptidyl peptidase 4	Homo sapiens	83-87
30742852-11	2019	Also Metformin could activate CREB (both forms), BDNF and Akt (both forms) proteins" expression and inhibited GSK3 (both forms) protein expression in methamphetamine treated rats.	Metformin	5-14	cAMP responsive element binding protein 1	Rattus norvegicus	30-34
30742852-12	2019	SIGNIFICANCE: According to obtained data, metformin could protect the brain against methamphetamine-induced neurodegeneration probably by mediation of CREB/BDNF or Akt/GSK3 signaling pathways.	Metformin	42-51	cAMP responsive element binding protein 1	Rattus norvegicus	151-155
30742852-13	2019	These data suggested that CREB/BDNF or Akt/GSK3 signaling pathways may have a critical role in methamphetamine induced neurotoxicity and/or neuroprotective effects of metformin.	Metformin	167-176	cAMP responsive element binding protein 1	Rattus norvegicus	26-30
31114366-3	2019	Metformin inhibits mTOR activity by activating ATM (ataxia telangiectasia mutated) and LKB1 (liver kinase B1) and then adenosine monophosphate-activated kinase (AMPK), and thus prevents protein synthesis and cell growth.	Metformin	0-9	ATM serine/threonine kinase	Homo sapiens	47-81
31114366-3	2019	Metformin inhibits mTOR activity by activating ATM (ataxia telangiectasia mutated) and LKB1 (liver kinase B1) and then adenosine monophosphate-activated kinase (AMPK), and thus prevents protein synthesis and cell growth.	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	87-91
31114366-3	2019	Metformin inhibits mTOR activity by activating ATM (ataxia telangiectasia mutated) and LKB1 (liver kinase B1) and then adenosine monophosphate-activated kinase (AMPK), and thus prevents protein synthesis and cell growth.	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	93-108
30959948-4	2019	In this study, we investigated the association between the polymorphisms of OCT1 and OCT2 and the treatment effectiveness of metformin in PCOS patients.	Metformin	125-134	solute carrier family 22 member 2	Homo sapiens	85-89
30594717-7	2019	In F0 female fish, metformin increased catalase activity compared with that of the control (p >  0.05).	Metformin	19-28	catalase	Oryzias latipes	39-47
31139382-5	2019	Therefore, metformin can promote INS-1 cell proliferation, enhance GSIS, and suppress apoptosis by activating AMPK/SIRT1/PGC-1alpha signal pathway, up-regulating irisin expression, and inducing autophagy in INS-1 cells in high-glucose environment.	Metformin	11-20	insulin 1	Rattus norvegicus	33-38
31139382-5	2019	Therefore, metformin can promote INS-1 cell proliferation, enhance GSIS, and suppress apoptosis by activating AMPK/SIRT1/PGC-1alpha signal pathway, up-regulating irisin expression, and inducing autophagy in INS-1 cells in high-glucose environment.	Metformin	11-20	insulin 1	Rattus norvegicus	207-212
30552782-7	2019	Suppression of LKB1 or promotion of AMP by metformin also abrogated the hyperproliferative phenotype caused by SIRT4 loss, which further confirmed that the LKB1/AMPKalpha/mTOR axis is required in SIRT4-deficiency-promoted HCC tumorigenesis.	Metformin	43-52	serine/threonine kinase 11	Homo sapiens	156-160
30710424-0	2019	Metformin and tenovin-6 synergistically induces apoptosis through LKB1-independent SIRT1 down-regulation in non-small cell lung cancer cells.	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	66-70
30710424-7	2019	Metformin in combination with tenovin-6 was found to be more effective in inhibiting cell growth than either agent alone in NSCLC cell lines with different liver kinase B1 (LKB1) status.	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	156-171
30710424-7	2019	Metformin in combination with tenovin-6 was found to be more effective in inhibiting cell growth than either agent alone in NSCLC cell lines with different liver kinase B1 (LKB1) status.	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	173-177
30710424-9	2019	The marked reduction in SIRT1 expression by combination of metformin and tenovin-6 increased acetylation of p53 at lysine 382 and enhanced p53 stability in LKB1-deficient A549 cells.	Metformin	59-68	serine/threonine kinase 11	Homo sapiens	156-160
30710424-12	2019	The study concluded that metformin with tenovin-6 may enhance antitumour effects through LKB1-independent SIRT1 down-regulation in NSCLC cells.	Metformin	25-34	serine/threonine kinase 11	Homo sapiens	89-93
30192003-0	2019	Long noncoding RNA H19 participates in metformin-mediated inhibition of gastric cancer cell invasion.	Metformin	39-48	H19 imprinted maternally expressed transcript	Homo sapiens	19-22
34450310-0	2021	Activated AMPK by metformin protects against fibroblast proliferation during pulmonary fibrosis by suppressing FOXM1.	Metformin	18-27	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	10-14
34450310-0	2021	Activated AMPK by metformin protects against fibroblast proliferation during pulmonary fibrosis by suppressing FOXM1.	Metformin	18-27	forkhead box M1	Mus musculus	111-116
34450310-5	2021	Here, the progression of lung fibroblast proliferation and the expression levels of AMPK and FOXM1 were observed by intratracheally instilled of bleomycin (BLM) and intraperitoneal injection of metformin in C57BL/6J mice.	Metformin	194-203	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	84-88
34450310-5	2021	Here, the progression of lung fibroblast proliferation and the expression levels of AMPK and FOXM1 were observed by intratracheally instilled of bleomycin (BLM) and intraperitoneal injection of metformin in C57BL/6J mice.	Metformin	194-203	forkhead box M1	Mus musculus	93-98
34450310-6	2021	Meanwhile, human fetal lung fibroblast1 (HFL1) cells were respectively treated with AMPK activator metformin or AMPK inhibitor Compound C, or FOXM1 depletion by transfected small interfering RNA (siRNA) to unveil roles of AMPK, FOXM1 and the link between them on platelet-derived growth factor (PDGF)-induced fibroblast proliferation.	Metformin	99-108	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	84-88
34450310-7	2021	Our results demonstrated that AMPK activated by metformin could down-regulate FOXM1 and alleviate BLM-induced mouse PF model.	Metformin	48-57	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	30-34
34450310-7	2021	Our results demonstrated that AMPK activated by metformin could down-regulate FOXM1 and alleviate BLM-induced mouse PF model.	Metformin	48-57	forkhead box M1	Mus musculus	78-83
34481229-5	2021	SC proliferation-inhibiting effect of metformin exposure was regulated by decreasing adenosine triphosphate level and respiratory enzyme activity in the mitochondria; this process was possibly mediated by the adenosine monophosphate-activated protein kinase (AMPK)/tuberous sclerosis complex 2 (TSC2)/mammalian target of rapamycin (mTOR) signaling pathway, which was regulated by the down-expressed miR-1764 and by the decreased antioxidant enzyme activity and excessive reactive oxygen species generation.	Metformin	38-47	TSC complex subunit 2	Homo sapiens	295-299
34481229-8	2021	Our findings suggest appropriate dose of exogenous 17beta-estradiol treatment can ameliorate the inhibitory effect of metformin on SC proliferation via the regulation of AMPK/TSC2/mTOR signaling pathway, this might reduce the risk of poor male fertility caused by the abuse of anti-diabetic agents.	Metformin	118-127	TSC complex subunit 2	Homo sapiens	175-179
34769067-5	2021	Interestingly, Metformin has been reported to rescue mitochondrial deficits in fibroblasts derived from a patient carrying a homozygous TRAP1 loss-of-function mutation.	Metformin	15-24	TNF receptor associated protein 1	Homo sapiens	136-141
34769067-10	2021	Metformin counteracted the deleterious effects of hypoxia in Trap1-deficient flies but had no protective effect in wild-type flies.	Metformin	0-9	TNF receptor associated protein 1	Homo sapiens	61-66
34769067-12	2021	Metformin appears to rescue Trap1-deficiency after hypoxia mitigating ROS production and downregulating the pro-apoptotic PERK (protein kinase R-like ER kinase) arm of the UPR.	Metformin	0-9	TNF receptor associated protein 1	Homo sapiens	28-33
34699735-8	2022	Significant changes in the metabolism of metoprolol and metformin with bean consumption suggested the presence of diet-drug interactions that may require adjustment of the prescribed dose.	Metformin	56-65	brain expressed associated with NEDD4 1	Homo sapiens	71-75
34699735-9	2022	ClinicalTrials.gov Identifier: NCT01382056 Novelty:   Bean consumption by people with PAD alters the levels of certain metabolites in serum and urine   Different bean types (black, red kidney, pinto, navy) have unique flavonoid profiles   Metabolomics revealed potential diet-dug interactions as serum and/or urinary levels of metoprolol and metformin are modified by bean consumption.	Metformin	342-351	brain expressed associated with NEDD4 1	Homo sapiens	54-58
34699735-9	2022	ClinicalTrials.gov Identifier: NCT01382056 Novelty:   Bean consumption by people with PAD alters the levels of certain metabolites in serum and urine   Different bean types (black, red kidney, pinto, navy) have unique flavonoid profiles   Metabolomics revealed potential diet-dug interactions as serum and/or urinary levels of metoprolol and metformin are modified by bean consumption.	Metformin	342-351	brain expressed associated with NEDD4 1	Homo sapiens	368-372
34689705-5	2022	Treatment of OZ rats with metformin, an activator of AMPK that blocks JNK activity, augments ZO-2 and claudin-1 expression in the liver, reduces the paracellular permeability of hepatocytes, and serum bile acid content.	Metformin	26-35	claudin 1	Rattus norvegicus	102-111
34332919-0	2021	Pharmacological activation of SIRT1 by metformin prevented trauma-induced heterotopic ossification through inhibiting macrophage mediated inflammation.	Metformin	39-48	sirtuin 1	Homo sapiens	30-35
34332919-11	2021	Furthermore, elevated SIRT1 expression and decreased NF-kappaB p65 acetylation were found in the beneficial effects of metformin.	Metformin	119-128	sirtuin 1	Homo sapiens	22-27
34332919-12	2021	Moreover, similar preventive effects were also found in SRT1720 HCI, a specific SIRT1 activator, while were remarkably reversed after the administration of EX527 (a specific SIRT1 inhibitor) with metformin.	Metformin	196-205	sirtuin 1	Homo sapiens	80-85
34332919-12	2021	Moreover, similar preventive effects were also found in SRT1720 HCI, a specific SIRT1 activator, while were remarkably reversed after the administration of EX527 (a specific SIRT1 inhibitor) with metformin.	Metformin	196-205	sirtuin 1	Homo sapiens	174-179
34332919-13	2021	Taken together, our results provide a novel evidence that metformin can effectively attenuate trauma-induced HO by mitigating macrophage inflammatory responses through inhibiting NF-kappaB signaling via SIRT1-dependent mechanisms, which favors future therapeutic investigations for trauma-related disease.	Metformin	58-67	sirtuin 1	Homo sapiens	203-208
34626114-6	2022	The results of q-PCR analysis showed that metformin reduced NF-kappaB mediated inflammatory response including decreased level of pro-inflammatory cytokine IL-8 and increased expression of anti-inflammatory cytokine IL-10 in gut of the fish with natural aging and poly I:C-injected 6-month-old fish.	Metformin	42-51	interleukin 10	Homo sapiens	216-221
34381196-1	2021	Growth differentiation factor 15 (GDF15) is a member of the TGFbeta superfamily whose expression is increased in response to cellular stress and disease as well as by metformin.	Metformin	167-176	growth differentiation factor 15	Homo sapiens	0-32
34381196-1	2021	Growth differentiation factor 15 (GDF15) is a member of the TGFbeta superfamily whose expression is increased in response to cellular stress and disease as well as by metformin.	Metformin	167-176	growth differentiation factor 15	Homo sapiens	34-39
34381196-5	2021	Furthermore, findings in both mice and humans have shown that metformin and exercise increase circulating levels of GDF15.	Metformin	62-71	growth differentiation factor 15	Homo sapiens	116-121
34599229-9	2021	Chronic metformin administration partially reversed oxidative damage in sucrose-fed animals, together with increased AMPK activation; probably by modulating BACE-1 and NFE2L2.	Metformin	8-17	beta-secretase 1	Rattus norvegicus	157-163
34658866-10	2021	The expression of mucin2, a prominent mucus barrier protein, was increased in the metformin-treated group compared to the DSS-treated group.	Metformin	82-91	mucin 2	Mus musculus	18-24
34564891-5	2022	Our results showed that topical application of metformin can effectively suppress the PDL-induced early stage of angiogenesis via inhibition of the AKT/mTOR/P70S6K pathway in animal models.	Metformin	47-56	mechanistic target of rapamycin kinase	Rattus norvegicus	152-156
34548527-0	2021	Metformin selectively dampens the acute inflammatory response through an AMPK-dependent mechanism.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	73-77
34548527-3	2021	In particular, metformin treatment has been shown to reduce expression of interleukin (IL-) 1beta during long-term exposure to the pro-inflammatory stimulus lipopolysaccharide (LPS) through a reduction in reactive oxygen species (ROS), which decreases the levels of the hypoxia-inducible factor (HIF) 1-alpha, and through enhanced expression of IL-10.	Metformin	15-24	interleukin 10	Homo sapiens	345-350
34548527-5	2021	Here, we show that metformin alters the acute inflammatory response through its activation of AMP-activated protein kinase (AMPK), but independently of HIF1-alpha and IL-10, in primary macrophages and two macrophage-like cell lines.	Metformin	19-28	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	94-122
34548527-5	2021	Here, we show that metformin alters the acute inflammatory response through its activation of AMP-activated protein kinase (AMPK), but independently of HIF1-alpha and IL-10, in primary macrophages and two macrophage-like cell lines.	Metformin	19-28	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	124-128
34368808-11	2021	Secondary objective was to evaluate the effects of metformin on the expression of CSC markers by measuring relative mRNA levels of CD133, OCT4 and NANOG by RT-PCR and immunohistochemistry.	Metformin	51-60	Nanog homeobox	Homo sapiens	147-152
34368808-16	2021	Comparison of markers of CCSC results showed that expression of CD133, OCT4 and NANOG expression were decreased following metformin.	Metformin	122-131	Nanog homeobox	Homo sapiens	80-85
34296521-0	2021	Metformin alleviates oxidative stress-induced senescence of human lens epithelial cells via AMPK activation and autophagic flux restoration.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	92-96
34296521-4	2021	In addition, we showed that metformin alleviated the oxidative stress-induced senescence of HLE-B3 cells via the activation of AMPK.	Metformin	28-37	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	127-131
34296521-6	2021	Subsequently, we found that metformin restored autophagic flux that had been impaired by oxidative stress by activating AMPK.	Metformin	28-37	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	120-124
34531248-0	2021	Mitochondrial reactive oxygen species trigger metformin-dependent antitumor immunity via activation of Nrf2/mTORC1/p62 axis in tumor-infiltrating CD8T lymphocytes.	Metformin	46-55	sequestosome 1	Homo sapiens	115-118
34531248-0	2021	Mitochondrial reactive oxygen species trigger metformin-dependent antitumor immunity via activation of Nrf2/mTORC1/p62 axis in tumor-infiltrating CD8T lymphocytes.	Metformin	46-55	CD8a molecule	Homo sapiens	146-149
34420660-4	2021	report results from the Trial of Administration of Metformin in PKD (TAME PKD) study, a phase 2 randomized controlled trial investigating the safety and tolerability of metformin in patients in the early stages of autosomal dominant polycystic kidney disease.	Metformin	51-60	protein kinase D1	Homo sapiens	64-67
34420660-4	2021	report results from the Trial of Administration of Metformin in PKD (TAME PKD) study, a phase 2 randomized controlled trial investigating the safety and tolerability of metformin in patients in the early stages of autosomal dominant polycystic kidney disease.	Metformin	169-178	protein kinase D1	Homo sapiens	64-67
34197875-5	2021	Moreover, hepatic SOCS2 expression levels are induced by metformin treatment.	Metformin	57-66	suppressor of cytokine signaling 2	Mus musculus	18-23
34197875-6	2021	Ablation of SOCS2 attenuates suppressing effects of metformin on gluconeogenesis in hepatocytes.	Metformin	52-61	suppressor of cytokine signaling 2	Mus musculus	12-17
34197875-10	2021	The inhibitory effect of metformin on gluconeogenesis is mediated, at least in part, by upregulating SOCS2 and therefore reducing hepatic gluconeogenic genes expression.	Metformin	25-34	suppressor of cytokine signaling 2	Mus musculus	101-106
34290400-2	2021	To date most of the anti-cancer properties of metformin have, in large part, been attributed either to the inhibition of mitochondrial NADH oxidase complex (Complex I in the electron transport chain) or the activation of AMP-activated kinase (AMPK).	Metformin	46-55	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	221-241
34290400-2	2021	To date most of the anti-cancer properties of metformin have, in large part, been attributed either to the inhibition of mitochondrial NADH oxidase complex (Complex I in the electron transport chain) or the activation of AMP-activated kinase (AMPK).	Metformin	46-55	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	243-247
34290400-3	2021	However, it is becoming increasingly clear that AMPK activation may be critical to alleviate metabolic and energetic stresses associated with tumor progression suggesting that it may, in fact, attenuate the toxicity of metformin instead of promoting it.	Metformin	219-228	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	48-52
34290400-5	2021	We also found that metformin forces cells to rewire their metabolic grid in a manner that depends on AMPK, with AMPK-competent cells upregulating glycolysis and AMPK-deficient cell resorting to ketogenesis.	Metformin	19-28	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	101-105
34290400-5	2021	We also found that metformin forces cells to rewire their metabolic grid in a manner that depends on AMPK, with AMPK-competent cells upregulating glycolysis and AMPK-deficient cell resorting to ketogenesis.	Metformin	19-28	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	112-116
34577590-6	2021	Metformin, a first line antihyperglycemic medication, is a 5"-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activator hypothesized to act as a geroprotective agent.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	118-122
34577590-9	2021	Moreover, it has been recently demonstrated that metformin enhances synaptophysin, sirtuin-1, AMPK, and brain-derived neuronal factor (BDNF) immunoreactivity, which are essential markers of plasticity.	Metformin	49-58	synaptophysin	Homo sapiens	68-81
34577590-9	2021	Moreover, it has been recently demonstrated that metformin enhances synaptophysin, sirtuin-1, AMPK, and brain-derived neuronal factor (BDNF) immunoreactivity, which are essential markers of plasticity.	Metformin	49-58	sirtuin 1	Homo sapiens	83-92
34577590-9	2021	Moreover, it has been recently demonstrated that metformin enhances synaptophysin, sirtuin-1, AMPK, and brain-derived neuronal factor (BDNF) immunoreactivity, which are essential markers of plasticity.	Metformin	49-58	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	94-98
34577590-9	2021	Moreover, it has been recently demonstrated that metformin enhances synaptophysin, sirtuin-1, AMPK, and brain-derived neuronal factor (BDNF) immunoreactivity, which are essential markers of plasticity.	Metformin	49-58	brain derived neurotrophic factor	Homo sapiens	104-133
34577590-9	2021	Moreover, it has been recently demonstrated that metformin enhances synaptophysin, sirtuin-1, AMPK, and brain-derived neuronal factor (BDNF) immunoreactivity, which are essential markers of plasticity.	Metformin	49-58	brain derived neurotrophic factor	Homo sapiens	135-139
34502359-0	2021	New Insight into the Effects of Metformin on Diabetic Retinopathy, Aging and Cancer: Nonapoptotic Cell Death, Immunosuppression, and Effects beyond the AMPK Pathway.	Metformin	32-41	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	152-156
34502359-3	2021	At the molecular level, the most well-known mechanism of metformin-mediated cytoprotection is AMPK pathway activation, which modulates metabolism and protects cells from degradation or pathogenic changes, such as those related to aging and diabetic retinopathy (DR).	Metformin	57-66	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	94-98
34502359-4	2021	Recently, it has been revealed that metformin acts via AMPK- and non-AMPK-mediated pathways to exert effects beyond those related to diabetes treatment that might prevent aging and ameliorate DR.	Metformin	36-45	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	55-59
34502359-4	2021	Recently, it has been revealed that metformin acts via AMPK- and non-AMPK-mediated pathways to exert effects beyond those related to diabetes treatment that might prevent aging and ameliorate DR.	Metformin	36-45	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	69-73
34659521-0	2021	Metformin and arsenic trioxide synergize to trigger Parkin/pink1-dependent mitophagic cell death in human cervical cancer HeLa cells.	Metformin	0-9	PTEN induced kinase 1	Homo sapiens	59-64
34512554-4	2021	This cross-sectional study enrolled 40 patients with T2DM treated with metformin monotherapy and 30 age-matched non-diabetic controls (NDM) to investigate the overexpression of RAGE in PBMC derived from patients with earlier stage diabetes, as well as to explore its determining factors.	Metformin	71-80	advanced glycosylation end-product specific receptor	Homo sapiens	177-181
34427916-13	2022	Metformin treatment significantly recovered the downregulated Akt phosphorylation and VEGF expression in high-glucose conditions.	Metformin	0-9	vascular endothelial growth factor A	Mus musculus	86-90
30192003-5	2019	We found that lncRNA H19 was greatly downregulated in gastric cancer cells treated with metformin using lncRNA microassays.	Metformin	88-97	H19 imprinted maternally expressed transcript	Homo sapiens	21-24
30192003-9	2019	In summary, metformin has a profound antitumor effect on gastric cancer cells, and H19 is a key component in the process of metformin suppressing gastric cancer cell invasion.	Metformin	124-133	H19 imprinted maternally expressed transcript	Homo sapiens	83-86
29934960-0	2019	Metformin inhibits TGF-beta 1-induced MCP-1 expression through BAMBI-mediated suppression of MEK/ERK1/2 signalling.	Metformin	0-9	C-C motif chemokine ligand 2	Rattus norvegicus	38-43
29934960-0	2019	Metformin inhibits TGF-beta 1-induced MCP-1 expression through BAMBI-mediated suppression of MEK/ERK1/2 signalling.	Metformin	0-9	BMP and activin membrane-bound inhibitor	Rattus norvegicus	63-68
29934960-4	2019	This study aimed to investigate the effects of metformin on transforming growth factor beta 1 (TGF-beta1)-induced MCP-1 expression and the underlying mechanisms in rat renal tubular epithelial cells.	Metformin	47-56	C-C motif chemokine ligand 2	Rattus norvegicus	114-119
30575815-6	2019	In vitro, glucose, insulin, VEGFA and hypoxia upregulated endothelial FABP4, which was reversed by metformin through mTOR pathway inhibition.	Metformin	99-108	fatty acid binding protein 4	Homo sapiens	70-75
30944551-9	2019	Metformin also decreased transforming growth factor beta level and increased interleukin-10 productions.	Metformin	0-9	distal membrane arm assembly component 2 like	Rattus norvegicus	45-56
30944551-9	2019	Metformin also decreased transforming growth factor beta level and increased interleukin-10 productions.	Metformin	0-9	interleukin 10	Rattus norvegicus	77-91
31182921-0	2019	Metformin Inhibits the NLRP3 Inflammasome via AMPK/mTOR-dependent Effects in Diabetic Cardiomyopathy.	Metformin	0-9	NLR family, pyrin domain containing 3	Mus musculus	23-28
31182921-0	2019	Metformin Inhibits the NLRP3 Inflammasome via AMPK/mTOR-dependent Effects in Diabetic Cardiomyopathy.	Metformin	0-9	mechanistic target of rapamycin kinase	Mus musculus	51-55
31182921-6	2019	The aim of this study was to investigate whether metformin can inhibit the NLRP3 inflammasome by activating the AMPK/mTOR pathway in DCM.	Metformin	49-58	NLR family, pyrin domain containing 3	Mus musculus	75-80
31182921-6	2019	The aim of this study was to investigate whether metformin can inhibit the NLRP3 inflammasome by activating the AMPK/mTOR pathway in DCM.	Metformin	49-58	mechanistic target of rapamycin kinase	Mus musculus	117-121
31182921-8	2019	Immunohistochemical staining, immunofluorescence staining and western blot assays indicated that the expression levels of mTOR, NLRP3, caspase-1, IL-1beta and GSDMD-N were decreased in the diabetic model treated with metformin and were reversed after the administration of an AMPK inhibitor in vivo and in vitro.	Metformin	217-226	mechanistic target of rapamycin kinase	Mus musculus	122-126
31182921-9	2019	Mechanistically, our results demonstrated that metformin can activate AMPK, thus improving autophagy via inhibiting the mTOR pathway and alleviating pyroptosis in DCM.	Metformin	47-56	mechanistic target of rapamycin kinase	Mus musculus	120-124
30639796-4	2019	Recent clinical guidelines have suggested the use of SGLT2 inhibitors as add-on therapy in patients for whom metformin alone does not achieve glycemic targets, or as initial dual therapy with metformin in patients who present with higher glycated hemoglobin (HbA1c) levels.	Metformin	109-118	solute carrier family 5 member 2	Homo sapiens	53-58
30649892-5	2019	Metformin counteracted glucose-dependent effects, and downregulated glutamate dehydrogenase, alanine aminotransferase, and mammalian target of rapamycin 5 h posttreatment in the absence of a glucose load, leading to decreased long-term activity of PFK1 and IDH.	Metformin	0-9	phosphofructokinase, muscle	Homo sapiens	248-252
30649892-5	2019	Metformin counteracted glucose-dependent effects, and downregulated glutamate dehydrogenase, alanine aminotransferase, and mammalian target of rapamycin 5 h posttreatment in the absence of a glucose load, leading to decreased long-term activity of PFK1 and IDH.	Metformin	0-9	isocitrate dehydrogenase (NADP(+)) 1	Homo sapiens	257-260
30841429-9	2019	Metformin might improve mitochondrial biogenesis in the BAT (nuclear respiratory factor 1, mitochondrial transcription factor A), lipolysis (perilipin, adipose triglyceride lipase, hormone-sensitive lipase), and fatty acid uptake (lipoprotein lipase, cluster of differentiation 36, adipocyte protein 2).	Metformin	0-9	patatin-like phospholipase domain containing 2	Mus musculus	152-179
30724637-3	2019	Areas covered: Ertugliflozin and metformin hydrochloride (ertugliflozin/metformin, SEGLUROMET) is a recently approved fixed-dose combination tablet containing the sodium-glucose co-transporter 2 (SGLT-2) inhibitor ertugliflozin and metformin.	Metformin	33-56	solute carrier family 5 member 2	Homo sapiens	163-194
30724637-3	2019	Areas covered: Ertugliflozin and metformin hydrochloride (ertugliflozin/metformin, SEGLUROMET) is a recently approved fixed-dose combination tablet containing the sodium-glucose co-transporter 2 (SGLT-2) inhibitor ertugliflozin and metformin.	Metformin	33-56	solute carrier family 5 member 2	Homo sapiens	196-202
30724637-3	2019	Areas covered: Ertugliflozin and metformin hydrochloride (ertugliflozin/metformin, SEGLUROMET) is a recently approved fixed-dose combination tablet containing the sodium-glucose co-transporter 2 (SGLT-2) inhibitor ertugliflozin and metformin.	Metformin	33-42	solute carrier family 5 member 2	Homo sapiens	196-202
30146703-9	2019	Contribution of mTOR signaling pathway in metformin-induced effect was shown by the inhibition of phosphorylation of S6K1 and 4E-BP1, the downstream targets of mTOR.	Metformin	42-51	ribosomal protein S6 kinase B1	Homo sapiens	117-121
30854043-2	2019	The current study demonstrated that metformin-induced suppression of cell proliferation is further potentiated by AMPK-mediated suppression of beta-catenin-dependent wingless-type (Wnt) signaling.	Metformin	36-45	catenin beta 1	Homo sapiens	143-155
30854043-4	2019	Metformin treatment also decreased beta-catenin expression in the cytoplasm and nucleus.	Metformin	0-9	catenin beta 1	Homo sapiens	35-47
30854043-8	2019	Furthermore, metformin-induced suppression of cell proliferation was partially recovered by AMPK inhibition, while metformin inhibited Wnt-mediated cell proliferation and beta-catenin expression.	Metformin	115-124	catenin beta 1	Homo sapiens	171-183
30854043-9	2019	The present results suggest that AMPK activation can suppress beta-catenin-dependent Wnt signaling by cytoplasmic sequestering of beta-catenin through AMPK, which further decreases cell proliferation in addition to metformin-induced mitochondrial dysfunction.	Metformin	215-224	catenin beta 1	Homo sapiens	62-74
30854043-9	2019	The present results suggest that AMPK activation can suppress beta-catenin-dependent Wnt signaling by cytoplasmic sequestering of beta-catenin through AMPK, which further decreases cell proliferation in addition to metformin-induced mitochondrial dysfunction.	Metformin	215-224	catenin beta 1	Homo sapiens	130-142
30745857-5	2019	Using endometrial tissues from PCOS patients with hyperplasia, we found that in response to metformin treatment in vitro, hexokinase 2 (HK2) expression was decreased, whereas phosphofructokinase (PFK), PKM2, and lactate dehydrogenase A (LDHA) expression was increased compared to controls.	Metformin	92-101	pyruvate kinase M1/2	Homo sapiens	202-206
30678275-6	2019	Further, we were interested in possibility of metformin affecting the Wnt3a signalling pathway and, thus, we determined mRNA and protein level of WNT3A and beta-catenin.	Metformin	46-55	Wnt family member 3A	Equus caballus	70-75
30678275-6	2019	Further, we were interested in possibility of metformin affecting the Wnt3a signalling pathway and, thus, we determined mRNA and protein level of WNT3A and beta-catenin.	Metformin	46-55	Wnt family member 3A	Equus caballus	146-151
30678275-10	2019	Additionally, metformin improved metabolism and viability of cells, which correlated with higher mitochondrial membrane potential, reduced apoptosis and increased WNT3A/beta-catenin expression.	Metformin	14-23	Wnt family member 3A	Equus caballus	163-168
30804991-0	2019	Combined Fluoxetine and Metformin Treatment Potentiates Antidepressant Efficacy Increasing IGF2 Expression in the Dorsal Hippocampus.	Metformin	24-33	insulin-like growth factor 2	Mus musculus	91-95
34439919-0	2021	Transcriptional Regulation of MECP2E1-E2 Isoforms and BDNF by Metformin and Simvastatin through Analyzing Nascent RNA Synthesis in a Human Brain Cell Line.	Metformin	62-71	brain derived neurotrophic factor	Homo sapiens	54-58
34439919-7	2021	Metformin was capable of post-transcriptionally inducing BDNF and/or MECP2E1, while transcriptionally inhibiting MECP2E2.	Metformin	0-9	brain derived neurotrophic factor	Homo sapiens	57-61
34439919-11	2021	Taken together, our results suggest that metformin controls MECP2E1/E2-BDNF transcriptionally and/or post-transcriptionally, and that simvastatin is a potent transcriptional inhibitor of BDNF.	Metformin	41-50	brain derived neurotrophic factor	Homo sapiens	71-75
34434111-8	2021	These results suggest that metformin could inhibit silica-induced pulmonary fibrosis by activating autophagy through the AMPK-mTOR pathway.	Metformin	27-36	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	121-125
34340683-0	2021	Correction to: Inhibition of mTORC1 through ATF4-induced REDD1 and Sestrin2 expression by Metformin.	Metformin	90-99	activating transcription factor 4	Homo sapiens	44-48
34340683-0	2021	Correction to: Inhibition of mTORC1 through ATF4-induced REDD1 and Sestrin2 expression by Metformin.	Metformin	90-99	DNA damage inducible transcript 4	Homo sapiens	57-62
34415985-8	2021	Treatment of lens epithelial cells with metformin reduced the level of the EMT markers  -SMA and pERK induced by TGF-beta2.	Metformin	40-49	transforming growth factor beta 2	Homo sapiens	113-122
34303707-0	2021	Metformin inhibits MAPK signaling and rescues pancreatic Aquaporin 7 expression to induce insulin secretion in type 2 diabetes mellitus.	Metformin	0-9	aquaporin 7	Rattus norvegicus	57-68
34303707-4	2021	The aim of this study was to investigate the effects of different doses of metformin on AQP7 expression and explore the possible mechanism of its protective effects in the pancreatic islets.	Metformin	75-84	aquaporin 7	Rattus norvegicus	88-92
34303707-8	2021	In addition, metformin upregulated AQP7 expression as well as inhibited activation of p38 and JNK MAPKs both in vivo and in vitro.	Metformin	13-22	aquaporin 7	Rattus norvegicus	35-39
34303707-10	2021	Our findings demonstrate a new mechanism by which metformin suppresses the p38 and JNK pathways, thereby upregulating pancreatic AQP7 expression, and promoting glycerol influx into pancreatic beta-cells and subsequent insulin secretion in T2DM.	Metformin	50-59	aquaporin 7	Rattus norvegicus	129-133
34164906-7	2021	The expression of Beclin1, VDAC1, LC3-II, CHOP and Bip was promoted in the cells received combinatorial treatment of metformin and MALAT1 knock-down.	Metformin	117-126	beclin 1	Homo sapiens	18-25
34299301-8	2021	Based on these results, we conclude that metformin treatment reduces the lipogenic enzyme SCD-1 and the accumulation of the lipotoxic intermediates diacylglycerols and lysophosphatidylcholine.	Metformin	41-50	stearoyl-CoA desaturase	Rattus norvegicus	90-95
34282122-6	2021	Moreover, both AMP-activated protein kinase (AMPK) agonist metformin and two mammalian targets of rapamycin (mTOR) inhibitors (INK128 and rapamycin) inhibited the percentage of M-MDSCs in lupus mice as well as in the TLR7- and IFN-alpha-induced bone marrow (BM) differentiation into MDSCs in vitro.	Metformin	59-68	toll-like receptor 7	Mus musculus	217-221
34282122-6	2021	Moreover, both AMP-activated protein kinase (AMPK) agonist metformin and two mammalian targets of rapamycin (mTOR) inhibitors (INK128 and rapamycin) inhibited the percentage of M-MDSCs in lupus mice as well as in the TLR7- and IFN-alpha-induced bone marrow (BM) differentiation into MDSCs in vitro.	Metformin	59-68	interferon alpha	Mus musculus	227-236
34115964-4	2021	By targeting electron transport chain complex 1 and independently of AMP-activated protein kinase (AMPK) or NF-kappaB, metformin blocked LPS-induced and ATP-dependent mitochondrial (mt) DNA synthesis and generation of oxidized mtDNA, an NLRP3 ligand.	Metformin	119-128	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	99-103
34234193-10	2021	Our results suggest that metformin in cancer cells differentially regulates cellular ROS levels via AMPK-FOXO3a-MnSOD pathway and combination of metformin/apigenin exerts anticancer activity through DNA damage-induced apoptosis, autophagy and necroptosis by cancer cell-specific ROS amplification.	Metformin	25-34	forkhead box O3	Mus musculus	105-111
34188521-0	2021	A Two-Stage Study Identifies Two Novel Polymorphisms in PRKAG2 Affecting Metformin Response in Chinese Type 2 Diabetes Patients.	Metformin	73-82	protein kinase AMP-activated non-catalytic subunit gamma 2	Homo sapiens	56-62
34188521-12	2021	Conclusion: Two variants rs2727528 and rs1105842 in PRKAG2, encoding gamma2 subunit of AMP-activated protein kinase (AMPK), were found to be associated with metformin response in Chinese T2D patients.	Metformin	157-166	protein kinase AMP-activated non-catalytic subunit gamma 2	Homo sapiens	52-58
34188521-12	2021	Conclusion: Two variants rs2727528 and rs1105842 in PRKAG2, encoding gamma2 subunit of AMP-activated protein kinase (AMPK), were found to be associated with metformin response in Chinese T2D patients.	Metformin	157-166	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	117-121
34078517-2	2021	Low concentration of metformin inhibited osteoclast differentiation and downregulated the expression of TRAP, RANK, Cathepsink, NFATC-1, MMP-9 and TRAF-6.	Metformin	21-30	TRAP	Homo sapiens	104-108
34078517-2	2021	Low concentration of metformin inhibited osteoclast differentiation and downregulated the expression of TRAP, RANK, Cathepsink, NFATC-1, MMP-9 and TRAF-6.	Metformin	21-30	nuclear factor of activated T cells 1	Homo sapiens	128-135
34078517-2	2021	Low concentration of metformin inhibited osteoclast differentiation and downregulated the expression of TRAP, RANK, Cathepsink, NFATC-1, MMP-9 and TRAF-6.	Metformin	21-30	matrix metallopeptidase 9	Homo sapiens	137-142
34277985-10	2021	Two proteins were significantly affected by metformin treatment, peptidoglycan recognition protein 2 (PGRP2; +23.4%, p = .0058) and alpha-2-macroglobulin (A2MG; +29.8%, p = .049).	Metformin	44-53	peptidoglycan recognition protein 2	Homo sapiens	65-100
34277985-10	2021	Two proteins were significantly affected by metformin treatment, peptidoglycan recognition protein 2 (PGRP2; +23.4%, p = .0058) and alpha-2-macroglobulin (A2MG; +29.8%, p = .049).	Metformin	44-53	peptidoglycan recognition protein 2	Homo sapiens	102-107
34277985-13	2021	Conclusions: Despite having little effect on HDL-C, metformin increased PGRP2 and A2MG protein on HDL in youth with T1D, but had no significant effect on CEC.	Metformin	52-61	peptidoglycan recognition protein 2	Homo sapiens	72-77
34217162-8	2021	Four hub genes (C3, THBS1, CXCL1, and TTN) were identified after treatment of Metformin (P<0.05, T-test).	Metformin	78-87	C-X-C motif chemokine ligand 1	Homo sapiens	27-32
34124601-3	2021	Here, we find that AMPK agonists, A769662, and Metformin, can inhibit GLI1 activity and synergize with Vismodegib to suppress MB cell growth in vitro and in vivo.	Metformin	47-56	GLI family zinc finger 1	Homo sapiens	70-74
34617056-10	2021	Metformin reduced total cholesterol and mRNA expression of SPP1 (encoding osteopontin), MMP12, and the glycoprotein genes Gpnmb and Clec7a.	Metformin	0-9	C-type lectin domain family 7, member a	Mus musculus	132-138
34238029-0	2021	Metformin Antagonizes Ovarian Cancer Cells Malignancy Through MSLN Mediated IL-6/STAT3 Signaling.	Metformin	0-9	mesothelin	Homo sapiens	62-66
34238029-8	2021	On mechanism, metformin treatment remarkably reduced mesothelin (MSLN) expression, downregulated IL-6/STAT3 signaling activity, subsequently resulted in VEGF and TGFbeta1 expression.	Metformin	14-23	mesothelin	Homo sapiens	53-63
34238029-8	2021	On mechanism, metformin treatment remarkably reduced mesothelin (MSLN) expression, downregulated IL-6/STAT3 signaling activity, subsequently resulted in VEGF and TGFbeta1 expression.	Metformin	14-23	mesothelin	Homo sapiens	65-69
34238029-10	2021	CONCLUSIONS: Collectively, our findings suggested that metformin exerts anticancer effects by suppressing ovarian cancer cell malignancy, which attributed to MSLN inhibition mediated IL6/STAT3 signaling and VEGF and TGFbeta1 downregulation.	Metformin	55-64	mesothelin	Homo sapiens	158-162
34630972-9	2021	Besides, we showed that the incubation of rabbit MSCs with HCQ increased cellular aging by induction of PARP-1 while Metformin increased rejuvenating factor Sirt-1 comparing with the normal group (P < 0.05).	Metformin	117-126	sirtuin 1	Homo sapiens	157-163
34514769-9	2021	Metformin has been shown to act through both AMP-activated protein kinase (AMPK)-dependent mechanisms and AMPK-independent mechanisms.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	45-73
34514769-9	2021	Metformin has been shown to act through both AMP-activated protein kinase (AMPK)-dependent mechanisms and AMPK-independent mechanisms.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	75-79
34514769-9	2021	Metformin has been shown to act through both AMP-activated protein kinase (AMPK)-dependent mechanisms and AMPK-independent mechanisms.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	106-110
34725288-7	2021	The women, who received the course of the preventive therapy with metformin, vitamin D3 and corvitin, showed a decrease in the concentration of pro-inflammatory cytokines and an increase in anti-inflammatory cytokine IL-10, normalization of the balance between iNOS and arginase activity, and the normalization of the M1 / M2 macrophages ratio.	Metformin	66-75	interleukin 10	Homo sapiens	217-222
35550195-9	2022	Signal transduction analysis of the paired cell lines indicated that c-Met-induced activation of STAT3 and AKT1, and upregulation of Gab1 are related to c-Met-modulated metformin responsiveness.	Metformin	169-178	GRB2 associated binding protein 1	Homo sapiens	133-137
35605453-8	2022	Mitophagy was altered in type 2 diabetic patients, evident in a decrease in the protein levels of PINK1 and Parkin in parallel to that of the mitochondrial biogenesis protein PGC1alpha, both of which effects were reversed by metformin.	Metformin	225-234	PTEN induced kinase 1	Homo sapiens	98-103
30701169-6	2018	Herein, we describe a 13-years-old child with LD due to a NHLRC1 (c.386C &gt; A, p.Pro129His) mutation, who has developed diabetes mellitus and was treated with metformin.	Metformin	161-170	NHL repeat containing E3 ubiquitin protein ligase 1	Homo sapiens	58-64
35459945-3	2022	WHAT IS KNOWN ALREADY: AMPK is expressed in the ovarian follicle, and its activation by pharmacological medications, such as metformin, inhibits the production of steroids.	Metformin	125-134	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	23-27
35240257-0	2022	The influence of SLC22A3 rs543159 and rs1317652 genetic variants on metformin therapeutic efficacy in newly diagnosed patients with type 2 diabetes mellitus: 25 weeks follow-up study.	Metformin	68-77	solute carrier family 22 member 3	Homo sapiens	17-24
35240257-3	2022	Genetic variations, especially within genes involved in pharmacokinetics and pharmacodynamics of metformin (e.g SLC22A3), have been suggested to be responsible for the observed inter-individual differences.	Metformin	97-106	solute carrier family 22 member 3	Homo sapiens	112-119
35240257-4	2022	By considering the undeniable role of organic cation transporter 3 in hepatic uptake of metformin, this study was aimed to investigate the association of rs543159 and rs1317652 variants in SLC22A3 gene with response to metformin monotherapy in newly diagnosed patients with T2DM.	Metformin	88-97	OCTN3	Homo sapiens	38-66
35240257-4	2022	By considering the undeniable role of organic cation transporter 3 in hepatic uptake of metformin, this study was aimed to investigate the association of rs543159 and rs1317652 variants in SLC22A3 gene with response to metformin monotherapy in newly diagnosed patients with T2DM.	Metformin	88-97	solute carrier family 22 member 3	Homo sapiens	189-196
35240257-4	2022	By considering the undeniable role of organic cation transporter 3 in hepatic uptake of metformin, this study was aimed to investigate the association of rs543159 and rs1317652 variants in SLC22A3 gene with response to metformin monotherapy in newly diagnosed patients with T2DM.	Metformin	219-228	solute carrier family 22 member 3	Homo sapiens	189-196
35240257-12	2022	CONCLUSION: Our results suggested that rs543159 and rs1317652 in SLC22A3 gene might be associated with variability in response to metformin therapy in T2DM patients.	Metformin	130-139	solute carrier family 22 member 3	Homo sapiens	65-72
35481401-0	2022	Metformin combats obesity by targeting FTO in an m6A-YTHDF2-dependent manner.	Metformin	0-9	YTH N6-methyladenosine RNA binding protein 2	Mus musculus	53-59
35571566-7	2022	In addition, ionized calcium-binding adapter molecule 1 (Iba-1) was significantly reduced in metformin-treated SAE mice compared with untreated SAE mice, suggesting that metformin can reduce microgliosis and inhibit central nervous system inflammation, thereby improving patient outcomes.	Metformin	93-102	allograft inflammatory factor 1	Mus musculus	13-55
35571566-7	2022	In addition, ionized calcium-binding adapter molecule 1 (Iba-1) was significantly reduced in metformin-treated SAE mice compared with untreated SAE mice, suggesting that metformin can reduce microgliosis and inhibit central nervous system inflammation, thereby improving patient outcomes.	Metformin	93-102	allograft inflammatory factor 1	Mus musculus	57-62
35571566-7	2022	In addition, ionized calcium-binding adapter molecule 1 (Iba-1) was significantly reduced in metformin-treated SAE mice compared with untreated SAE mice, suggesting that metformin can reduce microgliosis and inhibit central nervous system inflammation, thereby improving patient outcomes.	Metformin	170-179	allograft inflammatory factor 1	Mus musculus	13-55
35571566-7	2022	In addition, ionized calcium-binding adapter molecule 1 (Iba-1) was significantly reduced in metformin-treated SAE mice compared with untreated SAE mice, suggesting that metformin can reduce microgliosis and inhibit central nervous system inflammation, thereby improving patient outcomes.	Metformin	170-179	allograft inflammatory factor 1	Mus musculus	57-62
35227644-6	2022	We also showed that metformin treatment increased the ubiquitination and proteasomal degradation of NRF2 through a KEAP1-independent mechanism.	Metformin	20-29	kelch-like ECH-associated protein 1	Mus musculus	115-120
35563736-0	2022	Expression of Caspase-3 in Circulating Innate Lymphoid Cells Subtypes Is Altered by Treatment with Metformin and Fluvastatin in High-Fat Diet Fed C57BL/6 Mice.	Metformin	99-108	caspase 3	Mus musculus	14-23
35563736-2	2022	Another critical point was to assess the therapeutic effects of metformin and fluvastatin in modulating caspase-3 activation in ILCs within these HFD-fed mice.	Metformin	64-73	caspase 3	Mus musculus	104-113
35563736-5	2022	Notably, six-week treatment with metformin and fluvastatin reduced the caspase-3 activation in ILC subtypes.	Metformin	33-42	caspase 3	Mus musculus	71-80
35563736-6	2022	The reduced caspase-3 activation in ILC1 was inversely associated with HDL-c levels following metformin treatment.	Metformin	94-103	caspase 3	Mus musculus	12-21
35625721-0	2022	Metformin Protects against Diabetic Cardiomyopathy: An Association between Desmin-Sarcomere Injury and the iNOS/mTOR/TIMP-1 Fibrosis Axis.	Metformin	0-9	mechanistic target of rapamycin kinase	Rattus norvegicus	112-116
35625721-0	2022	Metformin Protects against Diabetic Cardiomyopathy: An Association between Desmin-Sarcomere Injury and the iNOS/mTOR/TIMP-1 Fibrosis Axis.	Metformin	0-9	TIMP metallopeptidase inhibitor 1	Rattus norvegicus	117-123
35497918-0	2022	Correlation of Serum IGF-1R, VEGF, and ET Levels with Bone Mineral Density in Type 2 Diabetic Mellitus Patients Treated with Metformin Plus alpha-Glucosidase Inhibitors.	Metformin	125-134	insulin like growth factor 1 receptor	Homo sapiens	21-27
35427214-10	2022	Western blotting analyses demonstrated that the apoptosis-related protein of cleaved caspase 3 was activated; the expressions of Mcl-1, IGF-1R, PI3K, pAKT, and pmTOR proteins were inhibited by metformin in H929, RPMI8226, and MM.1s cells.	Metformin	193-202	insulin like growth factor 1 receptor	Homo sapiens	136-142
35391603-2	2022	We report the case of a 76-year-old woman who developed muscle weakness, fatigue, and increased CK, following treatment with dapagliflozin, a sodium/glucose co-transporter 2 (SGLT2) inhibitor, and metformin.	Metformin	197-206	cytidine/uridine monophosphate kinase 1	Homo sapiens	96-98
35395467-8	2022	Furthermore, metformin altered T lymphocyte subsets and cellular senescent cells; the expression of FoxN1, Aire and Sox2 of thymic epithelial cells also increased.	Metformin	13-22	forkhead box N1	Mus musculus	100-105
35395467-8	2022	Furthermore, metformin altered T lymphocyte subsets and cellular senescent cells; the expression of FoxN1, Aire and Sox2 of thymic epithelial cells also increased.	Metformin	13-22	autoimmune regulator (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy)	Mus musculus	107-111
35395467-8	2022	Furthermore, metformin altered T lymphocyte subsets and cellular senescent cells; the expression of FoxN1, Aire and Sox2 of thymic epithelial cells also increased.	Metformin	13-22	SRY (sex determining region Y)-box 2	Mus musculus	116-120
35379885-9	2022	Hepatic lipogenesis-associated genes FAS and SCD1 were significantly upregulated in olanzapine-induced NAFLD mice and HepG2 cells overexpressing PCSK9, and genes related to lipid beta-oxidation (SCAD and PPARalpha) were downregulated, while metformin reversed these changes.	Metformin	241-250	stearoyl-Coenzyme A desaturase 1	Mus musculus	45-49
35085707-0	2022	Metformin alleviates ionizing radiation-induced senescence by restoring BARD1-mediated DNA repair in human aortic endothelial cells.	Metformin	0-9	BRCA1 associated RING domain 1	Homo sapiens	72-77
35085707-4	2022	Moreover, metformin increased BRCA1-associated RING domain protein 1 (BARD1) and RAD51 expression in both aging and IR-exposed cells.	Metformin	10-19	BRCA1 associated RING domain 1	Homo sapiens	30-68
35085707-4	2022	Moreover, metformin increased BRCA1-associated RING domain protein 1 (BARD1) and RAD51 expression in both aging and IR-exposed cells.	Metformin	10-19	BRCA1 associated RING domain 1	Homo sapiens	70-75
35085707-4	2022	Moreover, metformin increased BRCA1-associated RING domain protein 1 (BARD1) and RAD51 expression in both aging and IR-exposed cells.	Metformin	10-19	RAD51 recombinase	Homo sapiens	81-86
35085707-5	2022	Metformin-treated cells exhibited higher levels of the BRCA1-BARD1-RAD51 complex during irradiation, even in the presence of compound C, an AMP-activated protein kinase inhibitor.	Metformin	0-9	BRCA1 DNA repair associated	Homo sapiens	55-60
35085707-5	2022	Metformin-treated cells exhibited higher levels of the BRCA1-BARD1-RAD51 complex during irradiation, even in the presence of compound C, an AMP-activated protein kinase inhibitor.	Metformin	0-9	BRCA1 associated RING domain 1	Homo sapiens	61-66
35085707-5	2022	Metformin-treated cells exhibited higher levels of the BRCA1-BARD1-RAD51 complex during irradiation, even in the presence of compound C, an AMP-activated protein kinase inhibitor.	Metformin	0-9	RAD51 recombinase	Homo sapiens	67-72
35085707-6	2022	BARD1 knockdown confirmed its critical role in metformin-mediated inhibition of endothelial senescence.	Metformin	47-56	BRCA1 associated RING domain 1	Homo sapiens	0-5
35085707-8	2022	Collectively, our findings provide new insights into how metformin can prevent endothelial cell senescence by promoting BARD1-related DNA damage repair, suggesting that metformin may be an effective anti-aging agent and a promising therapeutic for protecting against radiation-induced cardiotoxicity.	Metformin	57-66	BRCA1 associated RING domain 1	Homo sapiens	120-125
35085707-8	2022	Collectively, our findings provide new insights into how metformin can prevent endothelial cell senescence by promoting BARD1-related DNA damage repair, suggesting that metformin may be an effective anti-aging agent and a promising therapeutic for protecting against radiation-induced cardiotoxicity.	Metformin	169-178	BRCA1 associated RING domain 1	Homo sapiens	120-125
35431946-0	2022	Acute Administration of Metformin Protects Against Neuronal Apoptosis Induced by Cerebral Ischemia-Reperfusion Injury via Regulation of the AMPK/CREB/BDNF Pathway.	Metformin	24-33	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	140-144
35431946-0	2022	Acute Administration of Metformin Protects Against Neuronal Apoptosis Induced by Cerebral Ischemia-Reperfusion Injury via Regulation of the AMPK/CREB/BDNF Pathway.	Metformin	24-33	cAMP responsive element binding protein 1	Homo sapiens	145-149
35431946-0	2022	Acute Administration of Metformin Protects Against Neuronal Apoptosis Induced by Cerebral Ischemia-Reperfusion Injury via Regulation of the AMPK/CREB/BDNF Pathway.	Metformin	24-33	brain derived neurotrophic factor	Homo sapiens	150-154
35431946-5	2022	Moreover, metformin up-regulated the brain-derived neurotrophic factor (BDNF) expression and increased phosphorylation levels of AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB) in the ischemia penumbra.	Metformin	10-19	brain derived neurotrophic factor	Homo sapiens	37-70
35431946-5	2022	Moreover, metformin up-regulated the brain-derived neurotrophic factor (BDNF) expression and increased phosphorylation levels of AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB) in the ischemia penumbra.	Metformin	10-19	brain derived neurotrophic factor	Homo sapiens	72-76
35431946-5	2022	Moreover, metformin up-regulated the brain-derived neurotrophic factor (BDNF) expression and increased phosphorylation levels of AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB) in the ischemia penumbra.	Metformin	10-19	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	129-157
35431946-5	2022	Moreover, metformin up-regulated the brain-derived neurotrophic factor (BDNF) expression and increased phosphorylation levels of AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB) in the ischemia penumbra.	Metformin	10-19	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	159-163
35431946-5	2022	Moreover, metformin up-regulated the brain-derived neurotrophic factor (BDNF) expression and increased phosphorylation levels of AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB) in the ischemia penumbra.	Metformin	10-19	cAMP responsive element binding protein 1	Homo sapiens	169-206
35431946-5	2022	Moreover, metformin up-regulated the brain-derived neurotrophic factor (BDNF) expression and increased phosphorylation levels of AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB) in the ischemia penumbra.	Metformin	10-19	cAMP responsive element binding protein 1	Homo sapiens	208-212
35431946-7	2022	Moreover, metformin could further promote BDNF expression and release in HUVECs under OGD/R conditions via the AMPK/CREB pathway.	Metformin	10-19	brain derived neurotrophic factor	Homo sapiens	42-46
35431946-7	2022	Moreover, metformin could further promote BDNF expression and release in HUVECs under OGD/R conditions via the AMPK/CREB pathway.	Metformin	10-19	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	111-115
35431946-7	2022	Moreover, metformin could further promote BDNF expression and release in HUVECs under OGD/R conditions via the AMPK/CREB pathway.	Metformin	10-19	cAMP responsive element binding protein 1	Homo sapiens	116-120
35431946-8	2022	The Transwell chamber assay showed that HUVECs treated with metformin could reduce apoptosis of SH-SY5Y cells under OGD/R conditions and this effect could be partially reversed by transfection of BDNF siRNA in HUVECs.	Metformin	60-69	brain derived neurotrophic factor	Homo sapiens	196-200
35431946-9	2022	In summary, our results suggest that metformin upregulates the level of BDNF in the cerebral ischemic penumbra via the AMPK/CREB pathway, thereby playing a protective effect in cerebral I/R injury.	Metformin	37-46	brain derived neurotrophic factor	Homo sapiens	72-76
35431946-9	2022	In summary, our results suggest that metformin upregulates the level of BDNF in the cerebral ischemic penumbra via the AMPK/CREB pathway, thereby playing a protective effect in cerebral I/R injury.	Metformin	37-46	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	119-123
35431946-9	2022	In summary, our results suggest that metformin upregulates the level of BDNF in the cerebral ischemic penumbra via the AMPK/CREB pathway, thereby playing a protective effect in cerebral I/R injury.	Metformin	37-46	cAMP responsive element binding protein 1	Homo sapiens	124-128
35378172-0	2022	Metformin treatment rescues CD8+ T cell response to immune checkpoint inhibitor therapy in mice with NAFLD.	Metformin	0-9	CD8a molecule	Homo sapiens	28-31
35378172-12	2022	LAY SUMMARY: Non-alcoholic fatty liver disease impairs motility, metabolic function and response to anti-PD-1 treatment of hepatic CD8+ T cells, which can be rescued by metformin treatment.	Metformin	169-178	CD8a molecule	Homo sapiens	131-134
35183887-11	2022	Altogether, our data suggest that tamsulosin could increase systemic exposure and reduce excretion of metformin via inhibiting Oct2 and Mate1-mediated transport cooperatively.	Metformin	102-111	solute carrier family 47 member 1	Homo sapiens	136-141
35414608-11	2022	Metformin administration decreased renal expression of necroptosis markers p-RIPK1 (phosphorylated receptor-interacting protein kinase 1) and p-MLKL, along with tubular injury marker KIM-1 (kidney injury molecule-1) in lupus mice.	Metformin	0-9	mixed lineage kinase domain-like	Mus musculus	144-148
35414608-12	2022	In addition, metformin alleviated the necroptosis of HK-2 cells stimulated by LPS and TNF-alpha, evidencing by a decrease in the expression of necroptosis markers p-RIPK1, p-RIPK3 and p-MLKL, and the inflammasome-related markers NLRP3 (NLR family pyrin domain containing 3), ASC (apoptosis-associated speck-like protein containing a CARD), caspase-1.	Metformin	13-22	receptor-interacting serine-threonine kinase 3	Mus musculus	174-179
35414608-12	2022	In addition, metformin alleviated the necroptosis of HK-2 cells stimulated by LPS and TNF-alpha, evidencing by a decrease in the expression of necroptosis markers p-RIPK1, p-RIPK3 and p-MLKL, and the inflammasome-related markers NLRP3 (NLR family pyrin domain containing 3), ASC (apoptosis-associated speck-like protein containing a CARD), caspase-1.	Metformin	13-22	mixed lineage kinase domain-like	Mus musculus	186-190
35386022-11	2022	In the metformin group, there was a reduction in cell apoptosis in the hippocampus, as well as GFAP-positive cells (P < 0.01).	Metformin	7-16	glial fibrillary acidic protein	Rattus norvegicus	95-99
35067907-7	2022	Recent studies have shown that metformin exerts its effects through the inhibition of mitochondrial respiratory chain complex 1 and the AMP-activated protein kinase (AMPK) activation, but it has been identified in the other studies that AMPK is not the sole hub in metformin mode of action or there are other unknown mechanisms which are involved and yet to be explored.	Metformin	31-40	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	136-164
35067907-7	2022	Recent studies have shown that metformin exerts its effects through the inhibition of mitochondrial respiratory chain complex 1 and the AMP-activated protein kinase (AMPK) activation, but it has been identified in the other studies that AMPK is not the sole hub in metformin mode of action or there are other unknown mechanisms which are involved and yet to be explored.	Metformin	31-40	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	166-170
35067907-7	2022	Recent studies have shown that metformin exerts its effects through the inhibition of mitochondrial respiratory chain complex 1 and the AMP-activated protein kinase (AMPK) activation, but it has been identified in the other studies that AMPK is not the sole hub in metformin mode of action or there are other unknown mechanisms which are involved and yet to be explored.	Metformin	31-40	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	237-241
35067907-7	2022	Recent studies have shown that metformin exerts its effects through the inhibition of mitochondrial respiratory chain complex 1 and the AMP-activated protein kinase (AMPK) activation, but it has been identified in the other studies that AMPK is not the sole hub in metformin mode of action or there are other unknown mechanisms which are involved and yet to be explored.	Metformin	265-274	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	237-241
35426808-9	2022	Moderate (5 mmol/L) and high (10 mmol/L) concentrations of metformin significantly upregulated the transcriptional activity of pGL3-1651 bp by up to 2.5 and 3 folds, respectively.	Metformin	59-68	succinate dehydrogenase complex subunit C	Homo sapiens	127-131
35426808-11	2022	The mutation in the RUNX2 binding site on pGL3-1651 bp obviously reduced metformin- and LPS-induced enhancement of pGL3-1651bp transcription by 1.7 and 2 folds, respectively.	Metformin	73-82	succinate dehydrogenase complex subunit C	Homo sapiens	42-46
35426808-11	2022	The mutation in the RUNX2 binding site on pGL3-1651 bp obviously reduced metformin- and LPS-induced enhancement of pGL3-1651bp transcription by 1.7 and 2 folds, respectively.	Metformin	73-82	succinate dehydrogenase complex subunit C	Homo sapiens	115-119
35426808-12	2022	CONCLUSION: pGL3-NFATc2-promoter can be transcribed and activated in 293F cells, and LPS and metformin can activate the transcription of pGL3- NFATc2-promoter in a RUNX2-dependent manner.	Metformin	93-102	succinate dehydrogenase complex subunit C	Homo sapiens	12-16
35426808-12	2022	CONCLUSION: pGL3-NFATc2-promoter can be transcribed and activated in 293F cells, and LPS and metformin can activate the transcription of pGL3- NFATc2-promoter in a RUNX2-dependent manner.	Metformin	93-102	succinate dehydrogenase complex subunit C	Homo sapiens	137-141
35292917-8	2022	MC4R TT homozygotes who took metformin alongside dietary intervention experienced increased weight loss and reductions in fat mass (p < 0.05).	Metformin	29-38	melanocortin 4 receptor	Homo sapiens	0-4
35511865-0	2022	Gadd45g, A Novel Antidepressant Target, Mediates Metformin-Induced Neuronal Differentiation of Neural Stem Cells Via DNA Demethylation.	Metformin	49-58	growth arrest and DNA-damage-inducible 45 gamma	Mus musculus	0-7
35222699-11	2022	Regarding the mechanism, in cartilage, metformin increased the expression of Col II and decreased the expression of MMP-13, NLRP3, caspase-1, GSDMD and IL-1beta.	Metformin	39-48	gasdermin D	Mus musculus	142-147
34987204-3	2022	This study"s objective was to determine the effects of a behavioral weight-loss intervention or metformin treatment on plasma LBP.	Metformin	96-105	lipopolysaccharide binding protein	Homo sapiens	126-129
35217236-0	2022	Sitagliptin/metformin improves the fertilization rate and embryo quality in polycystic ovary syndrome patients through increasing the expression of GDF9 and BMP15: A new alternative to metformin (a randomized trial).	Metformin	12-21	growth differentiation factor 9	Homo sapiens	148-152
35197629-0	2022	Low-dose metformin targets the lysosomal AMPK pathway through PEN2.	Metformin	9-18	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	41-45
35197629-0	2022	Low-dose metformin targets the lysosomal AMPK pathway through PEN2.	Metformin	9-18	presenilin enhancer, gamma-secretase subunit	Homo sapiens	62-66
35197629-2	2022	For clinical doses of metformin, AMP-activated protein kinase (AMPK) has a major role in its mechanism of action4,5; however, the direct molecular target of metformin remains unknown.	Metformin	22-31	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	33-61
35197629-2	2022	For clinical doses of metformin, AMP-activated protein kinase (AMPK) has a major role in its mechanism of action4,5; however, the direct molecular target of metformin remains unknown.	Metformin	22-31	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	63-67
35197629-2	2022	For clinical doses of metformin, AMP-activated protein kinase (AMPK) has a major role in its mechanism of action4,5; however, the direct molecular target of metformin remains unknown.	Metformin	157-166	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	33-61
35197629-2	2022	For clinical doses of metformin, AMP-activated protein kinase (AMPK) has a major role in its mechanism of action4,5; however, the direct molecular target of metformin remains unknown.	Metformin	157-166	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	63-67
35197629-3	2022	Here we show that clinically relevant concentrations of metformin inhibit the lysosomal proton pump v-ATPase, which is a central node for AMPK activation following glucose starvation6.	Metformin	56-65	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	138-142
35197629-4	2022	We synthesize a photoactive metformin probe and identify PEN2, a subunit of gamma-secretase7, as a binding partner of metformin with a dissociation constant at micromolar levels.	Metformin	28-37	presenilin enhancer, gamma-secretase subunit	Homo sapiens	57-61
35197629-4	2022	We synthesize a photoactive metformin probe and identify PEN2, a subunit of gamma-secretase7, as a binding partner of metformin with a dissociation constant at micromolar levels.	Metformin	118-127	presenilin enhancer, gamma-secretase subunit	Homo sapiens	57-61
35197629-5	2022	Metformin-bound PEN2 forms a complex with ATP6AP1, a subunit of the v-ATPase8, which leads to the inhibition of v-ATPase and the activation of AMPK without effects on cellular AMP levels.	Metformin	0-9	presenilin enhancer, gamma-secretase subunit	Homo sapiens	16-20
35197629-5	2022	Metformin-bound PEN2 forms a complex with ATP6AP1, a subunit of the v-ATPase8, which leads to the inhibition of v-ATPase and the activation of AMPK without effects on cellular AMP levels.	Metformin	0-9	ATPase H+ transporting accessory protein 1	Homo sapiens	42-49
35197629-5	2022	Metformin-bound PEN2 forms a complex with ATP6AP1, a subunit of the v-ATPase8, which leads to the inhibition of v-ATPase and the activation of AMPK without effects on cellular AMP levels.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	143-147
35197629-7	2022	In vivo, liver-specific knockout of Pen2 abolishes metformin-mediated reduction of hepatic fat content, whereas intestine-specific knockout of Pen2 impairs its glucose-lowering effects.	Metformin	51-60	presenilin enhancer, gamma-secretase subunit	Homo sapiens	36-40
35197629-7	2022	In vivo, liver-specific knockout of Pen2 abolishes metformin-mediated reduction of hepatic fat content, whereas intestine-specific knockout of Pen2 impairs its glucose-lowering effects.	Metformin	51-60	presenilin enhancer, gamma-secretase subunit	Homo sapiens	143-147
35197629-9	2022	Together, these findings reveal that metformin binds PEN2 and initiates a signalling route that intersects, through ATP6AP1, the lysosomal glucose-sensing pathway for AMPK activation.	Metformin	37-46	presenilin enhancer, gamma-secretase subunit	Homo sapiens	53-57
35197629-9	2022	Together, these findings reveal that metformin binds PEN2 and initiates a signalling route that intersects, through ATP6AP1, the lysosomal glucose-sensing pathway for AMPK activation.	Metformin	37-46	ATPase H+ transporting accessory protein 1	Homo sapiens	116-123
35197629-9	2022	Together, these findings reveal that metformin binds PEN2 and initiates a signalling route that intersects, through ATP6AP1, the lysosomal glucose-sensing pathway for AMPK activation.	Metformin	37-46	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	167-171
35228471-0	2022	Metformin ameliorates polycystic ovary syndrome in a rat model by decreasing excessive autophagy in ovarian granulosa cells via the PI3K/AKT/mTOR pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Rattus norvegicus	141-145
35228471-5	2022	In the present study, we first treated a letrozole-induced PCOS rat model with metformin, detected the pathological recovery of PCOS, and then assessed the effects of metformin on H2O2-induced autophagy in ovarian granulosa cells (GCs) by detecting the level of oxidative stress and the expression of autophagy-associated proteins and key proteins in the PI3K/AKT/mTOR pathway.	Metformin	167-176	mechanistic target of rapamycin kinase	Rattus norvegicus	364-368
35228471-6	2022	We demonstrated that metformin ameliorated PCOS in a rat model by downregulating autophagy in GCs, and metformin decreased the levels of oxidative stress and autophagy in H2O2-induced GCs and affected the PI3K/AKT/mTOR signaling pathway.	Metformin	21-30	mechanistic target of rapamycin kinase	Rattus norvegicus	214-218
35228471-6	2022	We demonstrated that metformin ameliorated PCOS in a rat model by downregulating autophagy in GCs, and metformin decreased the levels of oxidative stress and autophagy in H2O2-induced GCs and affected the PI3K/AKT/mTOR signaling pathway.	Metformin	103-112	mechanistic target of rapamycin kinase	Rattus norvegicus	214-218
35228471-7	2022	Taken together, our results indicate that metformin ameliorates PCOS in a rat model by decreasing excessive autophagy in GCs via the PI3K/AKT/mTOR pathway, and this study provides evidence for targeted reduction of excessive autophagy of ovarian granulosa cells and improvement of PCOS.	Metformin	42-51	mechanistic target of rapamycin kinase	Rattus norvegicus	142-146
35217990-5	2022	Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance.	Metformin	17-26	Rac family small GTPase 1	Homo sapiens	75-79
35217990-5	2022	Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance.	Metformin	120-129	Rac family small GTPase 1	Homo sapiens	75-79
35196199-8	2022	Treatment of APOE-mice with metformin or trehalose ameliorated the loss of retinal function and reduced Bruch"s membrane thickening, enhancing LC3 and LAMP1 labeling in the ocular tissues and restoring LC3-II:LC3-I ratio to WT levels.	Metformin	28-37	lysosomal-associated membrane protein 1	Mus musculus	151-156
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	germ cell-less 2, spermatogenesis associated	Homo sapiens	546-549
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	microtubule associated protein 1 light chain 3 alpha	Homo sapiens	730-733
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	sequestosome 1	Homo sapiens	1164-1170
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	sequestosome 1	Homo sapiens	1171-1174
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	sequestosome 1	Homo sapiens	1176-1190
35196199-11	2022	Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type.	Metformin	149-158	TSC complex subunit 2	Homo sapiens	1234-1238
35281267-0	2022	Metformin Combining PD-1 Inhibitor Enhanced Anti-Tumor Efficacy in STK11 Mutant Lung Cancer Through AXIN-1-Dependent Inhibition of STING Ubiquitination.	Metformin	0-9	axin 1	Homo sapiens	100-106
35281267-2	2022	The glucose-lowering drug metformin exerted anti-cancer effect and enhanced efficacy of chemotherapy in NSCLC with KRAS/STK11 co-mutation, yet it is unknown whether metformin may enhance ICI efficacy in STK11 mutant NSCLC.	Metformin	26-35	KRAS proto-oncogene, GTPase	Homo sapiens	115-119
35281267-8	2022	Next, we found that CRISPR/Cas9-mediated knockout of the scaffold protein AXIN-1 abolished the effect of metformin on T cell-mediated killing and STING stabilization.	Metformin	105-114	axin 1	Homo sapiens	74-80
35281267-9	2022	Immunoprecipitation and confocal macroscopy revealed that metformin enhanced the interaction and colocalization between AXIN-1 and STING.	Metformin	58-67	axin 1	Homo sapiens	120-126
35281267-11	2022	Next, we found that metformin decreased K48-linked ubiquitination of STING and inhibited the interaction of E3-ligand RNF5 and STING.	Metformin	20-29	ring finger protein 5	Homo sapiens	118-122
35281267-13	2022	Conclusion: Metformin combining PD-1 inhibitor enhanced anti-tumor efficacy in STK11 mutant lung cancer through inhibition of RNF5-mediated K48-linked ubiquitination of STING, which was dependent on AXIN-1.	Metformin	12-21	ring finger protein 5	Homo sapiens	126-130
35281267-13	2022	Conclusion: Metformin combining PD-1 inhibitor enhanced anti-tumor efficacy in STK11 mutant lung cancer through inhibition of RNF5-mediated K48-linked ubiquitination of STING, which was dependent on AXIN-1.	Metformin	12-21	axin 1	Homo sapiens	199-205
35064693-0	2022	Metformin ameliorates chronic colitis in a mouse model by regulating interferon-gamma-producing lamina propria CD4+ T cells through AMPK activation.	Metformin	0-9	CD4 antigen	Mus musculus	111-114
35064693-3	2022	Metformin is also reported to elicit anti-inflammatory responses in CD4+ T cells, resulting in improvement in experimental chronic inflammatory diseases, such as systemic lupus erythematosus.	Metformin	0-9	CD4 antigen	Mus musculus	68-71
35064693-6	2022	We observed that metformin suppresses the frequency of interferon (IFN) -gamma-producing LP CD4+ T cells in vitro, which were regulated by AMPK activation, a process possibly induced by the inhibition of oxidative phosphorylation.	Metformin	17-26	CD4 antigen	Mus musculus	92-95
35064693-8	2022	Metformin-treated mice showed AMPK activation in LP CD4+ T cells and ameliorated colitis.	Metformin	0-9	CD4 antigen	Mus musculus	52-55
35064693-9	2022	Our study demonstrates that metformin-induced AMPK activation in mucosal CD4+ T cells contributes to the improvement of IBD by suppressing IFN-gamma production.	Metformin	28-37	CD4 antigen	Mus musculus	73-76
30091464-10	2019	Possible underlying mechanisms include the higher prevalence of IDH mutations in WHO grade III glioma, which might sensitize to the metabolic drug metformin.	Metformin	147-156	isocitrate dehydrogenase (NADP(+)) 1	Homo sapiens	64-67
30428337-7	2019	Metformin (&gt;=1 or &gt;=0.3 mM) decreased berberine transport in MDCK-rOCT1, MDCK-rOCT2, and MDCK-rMATE1 cells.	Metformin	0-9	solute carrier family 22 member 2	Rattus norvegicus	84-89
30646605-1	2019	Metformin has been shown to inhibit glutaminase (GLS) activity and ammonia accumulation thereby reducing the risk of hepatic encephalopathy in type 2 diabetic patients.	Metformin	0-9	glutaminase	Homo sapiens	36-47
30646605-1	2019	Metformin has been shown to inhibit glutaminase (GLS) activity and ammonia accumulation thereby reducing the risk of hepatic encephalopathy in type 2 diabetic patients.	Metformin	0-9	glutaminase	Homo sapiens	49-52
30646605-2	2019	Since tumour cells are addicted to glutamine and often show an overexpression of glutaminase, we hypothesize that the antitumoral mechanism of metformin could be ascribed to inhibition of GLS and reduction of ammonia and ammonia-induced autophagy.	Metformin	143-152	glutaminase	Homo sapiens	81-92
30646605-2	2019	Since tumour cells are addicted to glutamine and often show an overexpression of glutaminase, we hypothesize that the antitumoral mechanism of metformin could be ascribed to inhibition of GLS and reduction of ammonia and ammonia-induced autophagy.	Metformin	143-152	glutaminase	Homo sapiens	188-191
30646605-3	2019	Our results show that, in different tumour cell lines, micromolar doses of metformin prevent cell growth by reducing glutamate, ammonia accumulation, autophagy markers such as MAP1LC3B-II and GABARAP as well as degradation of long-lived proteins.	Metformin	75-84	GABA type A receptor-associated protein	Homo sapiens	192-199
30646605-5	2019	Interestingly, GLS-silenced cells reproduce the effect of metformin treatment showing reduced MAP1LC3B-II and GABARAP as well as ammonia accumulation.	Metformin	58-67	glutaminase	Homo sapiens	15-18
30646605-5	2019	Interestingly, GLS-silenced cells reproduce the effect of metformin treatment showing reduced MAP1LC3B-II and GABARAP as well as ammonia accumulation.	Metformin	58-67	GABA type A receptor-associated protein	Homo sapiens	110-117
30646605-7	2019	In conclusion, our work demonstrates that the anti-tumoral action of metformin is due to the inhibition of glutaminase and autophagy and could be used to improve the efficacy of chemotherapy.	Metformin	69-78	glutaminase	Homo sapiens	107-118
30774659-0	2019	Metformin Counteracts HCC Progression and Metastasis Enhancing KLF6/p21 Expression and Downregulating the IGF Axis.	Metformin	0-9	H3 histone pseudogene 16	Homo sapiens	68-71
35093389-1	2022	OBJECTIVES: To study metformin hepatoprotective effects compared to silymarin on hepatic fibrosis caused by carbon tetrachloride (CCl4) in mice.	Metformin	21-30	chemokine (C-C motif) ligand 4	Mus musculus	130-134
35093389-7	2022	CONCLUSION: These findings highlight the anti-inflammatory, antioxidant and antifibrotic effects of metformin in CCl4-induced hepatic fibrosis in mice, but silymarin is more beneficial.	Metformin	100-109	chemokine (C-C motif) ligand 4	Mus musculus	113-117
35140900-0	2022	Clinical Study on the Relationship between the SNP rs8192675 (C/C) Site of SLC2A2 Gene and the Hypoglycemic Effect of Metformin in Type 2 Diabetes.	Metformin	118-127	solute carrier family 2 member 2	Homo sapiens	75-81
35140900-1	2022	This study investigates the correlation between the gene polymorphism of rs8192675 (C/C) locus of SLC2A2 in patients with type 2 diabetes (T2DM) and the efficacy of metformin.	Metformin	165-174	solute carrier family 2 member 2	Homo sapiens	98-104
35140900-4	2022	The patients in the T2DM group were treated with metformin and followed up for 90 days to analyze the relationship between the efficacy of metformin and the SLC2A2 gene polymorphism.	Metformin	139-148	solute carrier family 2 member 2	Homo sapiens	157-163
35140900-8	2022	SLC2A2 gene polymorphism site rs8192675 CC type T2DM patients are sensitive to metformin and have a better hypoglycemic effect.	Metformin	79-88	solute carrier family 2 member 2	Homo sapiens	0-6
35163393-7	2022	Dividing these values into the different Jmax values for transport of MPP, metformin, and atenolol mediated by MATE1 and OCT2 resulted in calculated TOR values (+-SE, n = 4) of 84.0 +- 22.0 s-1 and 2.9 +- 0.6 s-1; metformin, 461.0 +- 121.0 s-1 and 12.6 +- 2.4 s-1; atenolol, 118.0 +- 31.0 s-1, respectively.	Metformin	75-84	solute carrier family 47 member 1	Homo sapiens	111-116
35163393-7	2022	Dividing these values into the different Jmax values for transport of MPP, metformin, and atenolol mediated by MATE1 and OCT2 resulted in calculated TOR values (+-SE, n = 4) of 84.0 +- 22.0 s-1 and 2.9 +- 0.6 s-1; metformin, 461.0 +- 121.0 s-1 and 12.6 +- 2.4 s-1; atenolol, 118.0 +- 31.0 s-1, respectively.	Metformin	214-223	solute carrier family 47 member 1	Homo sapiens	111-116
35079096-0	2022	Metformin sensitizes leukemic cells to cytotoxic lymphocytes by increasing expression of intercellular adhesion molecule-1 (ICAM-1).	Metformin	0-9	intercellular adhesion molecule 1	Homo sapiens	89-122
35079096-0	2022	Metformin sensitizes leukemic cells to cytotoxic lymphocytes by increasing expression of intercellular adhesion molecule-1 (ICAM-1).	Metformin	0-9	intercellular adhesion molecule 1	Homo sapiens	124-130
35079096-4	2022	We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1).	Metformin	18-27	intercellular adhesion molecule 1	Homo sapiens	99-132
35079096-4	2022	We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1).	Metformin	18-27	intercellular adhesion molecule 1	Homo sapiens	134-140
35079115-13	2022	The combination of metformin and bicalutamide led to greater reductions in PD-1 expressing NK, CD4+ T, and CD8+ T-cell subsets compared to bicalutamide alone.	Metformin	19-28	CD4 molecule	Sus scrofa	95-98
35103058-6	2022	Metformin restored GRP78 to control, while PA increased it by 2.56-fold and metformin+PA-by 3.28-fold vs. T2DM.	Metformin	0-9	heat shock protein family A (Hsp70) member 5	Rattus norvegicus	19-24
35103058-14	2022	GFAP level did not change in T2DM but rose in metformin and PA groups vs. control.	Metformin	46-55	glial fibrillary acidic protein	Rattus norvegicus	0-4
35103058-15	2022	PA+metformin administration diminished GFAP vs. PA. T2DM-induced changes were associated with dramatically decreased ZO-1 levels, while PA treatment increased it almost to control values.	Metformin	3-12	glial fibrillary acidic protein	Rattus norvegicus	39-43
35181615-8	2022	CONCLUSION: By targeting the Sirt1, EZH2 and CXCR4 pathways using relatively non-toxic adjuvant therapeutic agents such as metformin, melatonin, curcumin, sulforaphane, vitamin D3 and plerixafor, we should be able to target the biology of DLBCL.	Metformin	123-132	sirtuin 1	Homo sapiens	29-34
35181615-8	2022	CONCLUSION: By targeting the Sirt1, EZH2 and CXCR4 pathways using relatively non-toxic adjuvant therapeutic agents such as metformin, melatonin, curcumin, sulforaphane, vitamin D3 and plerixafor, we should be able to target the biology of DLBCL.	Metformin	123-132	C-X-C motif chemokine receptor 4	Homo sapiens	45-50
34849709-6	2022	Prolonged endurance exercise increases circulating GDF15 to levels otherwise associated with certain pathological states and in response to metformin treatment.	Metformin	140-149	growth differentiation factor 15	Homo sapiens	51-56
33850550-0	2021	Metformin attenuates diabetic renal injury via the AMPK-autophagy axis.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	51-55
33850550-10	2021	These findings suggested that metformin may reduce DN damage via regulation of the AMPK-mTOR-autophagy axis and indicated that metformin may be considered as a potential target in the treatment of DN.	Metformin	30-39	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	83-87
33850550-10	2021	These findings suggested that metformin may reduce DN damage via regulation of the AMPK-mTOR-autophagy axis and indicated that metformin may be considered as a potential target in the treatment of DN.	Metformin	127-136	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	83-87
33838154-6	2021	The inhibitory effect of metformin on NFE2L1 was investigated to occur through the N-terminal domain (NTD) of NFE2L1 protein, and its downregulation by metformin was in an AMP-activated protein kinase (AMPK)-independent manner.	Metformin	25-34	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	172-200
33838154-6	2021	The inhibitory effect of metformin on NFE2L1 was investigated to occur through the N-terminal domain (NTD) of NFE2L1 protein, and its downregulation by metformin was in an AMP-activated protein kinase (AMPK)-independent manner.	Metformin	25-34	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	202-206
33838154-6	2021	The inhibitory effect of metformin on NFE2L1 was investigated to occur through the N-terminal domain (NTD) of NFE2L1 protein, and its downregulation by metformin was in an AMP-activated protein kinase (AMPK)-independent manner.	Metformin	152-161	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	172-200
33838154-6	2021	The inhibitory effect of metformin on NFE2L1 was investigated to occur through the N-terminal domain (NTD) of NFE2L1 protein, and its downregulation by metformin was in an AMP-activated protein kinase (AMPK)-independent manner.	Metformin	152-161	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	202-206
33838154-7	2021	But the activation of AMPK signaling pathway by metformin in NFE2L1 knockdown HepG2 cells is reversed, indicating that NFE2L1 may be an important regulator of AMPK signal.	Metformin	48-57	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	22-26
33838154-7	2021	But the activation of AMPK signaling pathway by metformin in NFE2L1 knockdown HepG2 cells is reversed, indicating that NFE2L1 may be an important regulator of AMPK signal.	Metformin	48-57	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	159-163
33952086-0	2021	Rutaecarpine enhances the anti-diabetic activity and hepatic distribution of metformin via up-regulation of Oct1 in diabetic rats.	Metformin	77-86	solute carrier family 22 member 1	Rattus norvegicus	108-112
33952086-7	2021	Furthermore, rutaecarpine increased Oct1-mediated metformin uptake into hepatocytes by upregulation of Oct1 expression in the liver.The above data indicate that rutaecarpine enhanced the anti-diabetic effect of metformin, which may be associated with the increased hepatic distribution of metformin through up-regulation of Oct1 in response to rutaecarpine.	Metformin	50-59	solute carrier family 22 member 1	Rattus norvegicus	36-40
33952086-7	2021	Furthermore, rutaecarpine increased Oct1-mediated metformin uptake into hepatocytes by upregulation of Oct1 expression in the liver.The above data indicate that rutaecarpine enhanced the anti-diabetic effect of metformin, which may be associated with the increased hepatic distribution of metformin through up-regulation of Oct1 in response to rutaecarpine.	Metformin	211-220	solute carrier family 22 member 1	Rattus norvegicus	36-40
33952086-7	2021	Furthermore, rutaecarpine increased Oct1-mediated metformin uptake into hepatocytes by upregulation of Oct1 expression in the liver.The above data indicate that rutaecarpine enhanced the anti-diabetic effect of metformin, which may be associated with the increased hepatic distribution of metformin through up-regulation of Oct1 in response to rutaecarpine.	Metformin	211-220	solute carrier family 22 member 1	Rattus norvegicus	36-40
33990102-6	2021	The alteration of insulin signaling pathways, involved in gastrointestinal manifestations, carcinogenesis, muscle function, cognitive and endocrinological aspects, gain further relevance in the light of recent evidence of metformin efficacy in DM1.	Metformin	222-231	DM1 protein kinase	Homo sapiens	244-247
33982074-10	2021	Along with the upregulation of phosphorylated AMPKalpha and ACCalpha, metformin at 1.5 and 3 mM inactivated NF-kappaB signalling components (p65 and IkappaBalpha) and the inflammatory genes (TNFA, IL6, IL1B and COX-2) which were activated by BHBA.	Metformin	70-79	NFKB inhibitor alpha	Bos taurus	149-161
33982074-15	2021	Altogether, metformin attenuates the BHBA-induced inflammation through the inactivation of NF-kappaB as a target for AMPK/SIRT1 signalling in bovine hepatocytes.	Metformin	12-21	sirtuin 1	Bos taurus	122-127
33980323-14	2021	Metformin suppresses the NF-kappaB/Snail/HK3 signaling axis that is activated by LPS and then inhibits LPS-induced metastasis.	Metformin	0-9	snail family zinc finger 1	Mus musculus	35-40
33980323-14	2021	Metformin suppresses the NF-kappaB/Snail/HK3 signaling axis that is activated by LPS and then inhibits LPS-induced metastasis.	Metformin	0-9	hexokinase 3	Mus musculus	41-44
33947424-9	2021	These results suggest that metformin treatment has anti-inflammatory effects on lymphocytes via the inhibition of IL-17 and cytokines related to Th17 differentiation, such as IL-1beta, IL-6, and TNF-alpha.	Metformin	27-36	interleukin 17A	Mus musculus	114-119
33634460-10	2021	Metformin normalized the alterations in the expression of glucose metabolism-related genes (PGC-1alpha, G6pc, Pepck, Gck, PYGL, Gys2, PKLR, GLUT4) and insulin resistance-related genes (AdipoR1, AdipoR2) in the muscles and livers of rats induced by CORT.	Metformin	0-9	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	110-115
33893356-7	2021	In addition, co-treatment with metformin and UPA was associated with significant increase in the Bax and significant reduction in Bcl-2, PCNA, Cyclin-D1and ER-alpha as compared to treatment with UPA alone.	Metformin	31-40	proliferating cell nuclear antigen	Rattus norvegicus	137-141
33953705-0	2021	Metformin Attenuates ROS via FOXO3 Activation in Immune Cells.	Metformin	0-9	forkhead box O3	Mus musculus	29-34
33141769-6	2021	After addition of metformin (10 mM), collagen types I and III and elastin mRNA levels were significantly decreased in HDFs, and collagen type I protein level was significantly decreased.	Metformin	18-27	elastin	Homo sapiens	66-73
33141769-7	2021	In addition, the expression levels of collagen types I and III, fibronectin, and elastin were significantly reduced in keloid spheroids after treatment with metformin (100 mM).	Metformin	157-166	elastin	Homo sapiens	81-88
33535788-2	2021	Approach and Results: In 2 dyslipidemia mouse models, administration of metformin significantly decreased serum cholesterol and PCSK9 (proprotein convertase subtilisin/kexin type 9) levels, accompanied by decreased expression of PCSK9 in both mRNA and protein levels resulting in a 3-fold increase of LDLR (low-density lipoprotein receptor) in the liver.	Metformin	72-81	low density lipoprotein receptor	Mus musculus	301-305
33535788-2	2021	Approach and Results: In 2 dyslipidemia mouse models, administration of metformin significantly decreased serum cholesterol and PCSK9 (proprotein convertase subtilisin/kexin type 9) levels, accompanied by decreased expression of PCSK9 in both mRNA and protein levels resulting in a 3-fold increase of LDLR (low-density lipoprotein receptor) in the liver.	Metformin	72-81	low density lipoprotein receptor	Mus musculus	307-339
33649289-0	2021	Metformin targets Clusterin to control lipogenesis and inhibit the growth of bladder cancer cells through SREBP-1c/FASN axis.	Metformin	0-9	fatty acid synthase	Homo sapiens	115-119
33520106-0	2021	Metformin regulates inflammation and fibrosis in diabetic kidney disease through TNC/TLR4/NF-kappaB/miR-155-5p inflammatory loop.	Metformin	0-9	tenascin C	Rattus norvegicus	81-84
33520106-0	2021	Metformin regulates inflammation and fibrosis in diabetic kidney disease through TNC/TLR4/NF-kappaB/miR-155-5p inflammatory loop.	Metformin	0-9	microRNA 155	Rattus norvegicus	100-107
33520106-20	2021	In addition, metformin treatment may relive the processes of inflammation and fibrosis in individuals with DKD by reducing the levels of the TNC, p-NF-kappaB p65, CTGF, and FN proteins.	Metformin	13-22	tenascin C	Rattus norvegicus	141-144
33488583-9	2020	In LT patients, addition of metformin increased the peripheral percentage of CD4+Treg and CD8+Treg cells and decreased CD4+Th17.	Metformin	28-37	CD8a molecule	Homo sapiens	90-93
33431790-0	2021	Metformin exhibits antiproliferation activity in breast cancer via miR-483-3p/METTL3/m6A/p21 pathway.	Metformin	0-9	cyclin-dependent kinase inhibitor 1A (P21)	Mus musculus	89-92
33431790-11	2021	Metformin can take p21 as the main target to inhibit such effect.	Metformin	0-9	cyclin-dependent kinase inhibitor 1A (P21)	Mus musculus	19-22
33431790-12	2021	To specify, this study exhibited that metformin can inhibit breast cancer cell proliferation through the pathway miR-483-3p/METTL3/m6A/p21.	Metformin	38-47	cyclin-dependent kinase inhibitor 1A (P21)	Mus musculus	135-138
33365058-6	2021	Metformin increased the number of autophagosomes, green fluorescent LC3 puncta and the levels of LC3II/I, beclin 1, alpha-SMA and phosphorylated (p)-AMPK in the VSMCs that were treated with beta-glycerophosphate when compared to controls; whereas, calcium deposition and the expression levels of RUNX2 and p-mTOR were found to be decreased.	Metformin	0-9	microtubule associated protein 1 light chain 3 alpha	Homo sapiens	68-71
33365058-6	2021	Metformin increased the number of autophagosomes, green fluorescent LC3 puncta and the levels of LC3II/I, beclin 1, alpha-SMA and phosphorylated (p)-AMPK in the VSMCs that were treated with beta-glycerophosphate when compared to controls; whereas, calcium deposition and the expression levels of RUNX2 and p-mTOR were found to be decreased.	Metformin	0-9	beclin 1	Homo sapiens	106-114
33161784-0	2021	Metformin as a potential therapeutic for neurological disease: mobilizing AMPK to repair the nervous system.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	74-78
33161784-2	2021	The mechanism of action of metformin involves activation of AMP-activated protein kinase (AMPK) to enhance mitochondrial function (for example, biogenesis, refurbishment and dynamics) and autophagy.	Metformin	27-36	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	60-88
33161784-2	2021	The mechanism of action of metformin involves activation of AMP-activated protein kinase (AMPK) to enhance mitochondrial function (for example, biogenesis, refurbishment and dynamics) and autophagy.	Metformin	27-36	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	90-94
33161784-6	2021	Expert opinion: Metformin, through activation of AMPK and autophagy, can enhance neuronal bioenergetics, promote nerve repair and reduce toxic protein aggregates in neurological diseases.	Metformin	16-25	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	49-53
33161784-8	2021	Future studies in animal models of neurological disease should strive to further dissect in a mechanistic manner the pathways downstream from metformin-dependent AMPK activation, and to further investigate mTOR dependent and independent signaling pathways driving neuroprotection.	Metformin	142-151	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	162-166
32798506-6	2020	Then, current therapeutic strategies (e.g., metformin, adiponectin) used to ameliorate I/R injury by modulating AMPK activity are reviewed in detail.	Metformin	44-53	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	112-116
33037045-2	2020	However, OCT1 deficiency leads to more pronounced reductions of metformin concentrations in mouse than in human liver.	Metformin	64-73	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	9-13
33037045-4	2020	Here, we compared the uptake characteristics of metformin and thiamine between human and mouse OCT1 using stably transfected HEK293 cells.	Metformin	48-57	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	95-99
33037045-5	2020	The affinity for metformin was 4.9-fold lower in human than in mouse OCT1, resulting in a 6.5-fold lower intrinsic clearance.	Metformin	17-26	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	69-73
33037045-8	2020	Using human-mouse chimeric OCT1 we showed that simultaneous substitution of transmembrane helices TMH2 and TMH3 resulted in the reversal of affinity for metformin.	Metformin	153-162	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	27-31
33037045-13	2020	Significance Statement OCT1 is a major hepatic uptake transporter of metformin and thiamine, but we report strong differences in the affinity for both compounds between human and mouse OCT1.	Metformin	69-78	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	185-189
30625181-4	2019	The present study found that treatment of breast cancer MDA-MB-231 cells with metformin significantly decreased cholesterol content with concomitant inhibition of various cholesterol regulatory genes (e.g., HMGCoR, LDLR and SREBP1).	Metformin	78-87	low density lipoprotein receptor	Homo sapiens	215-219
30625181-4	2019	The present study found that treatment of breast cancer MDA-MB-231 cells with metformin significantly decreased cholesterol content with concomitant inhibition of various cholesterol regulatory genes (e.g., HMGCoR, LDLR and SREBP1).	Metformin	78-87	sterol regulatory element binding transcription factor 1	Homo sapiens	224-230
30625181-6	2019	Similarly, metformin treatment suppressed expressions of anti-apoptotic genes BCL2 and Bcl-xL, and mesenchymal genes vimentin, N-cadherin, Zeb1 and Zeb2 with simultaneous enhancement of apoptotic caspase 3 and Bax, and epithelial genes E-cadherin and keratin 19 expressions, confirming an inhibitory effect of metformin in tumorigenesis.	Metformin	11-20	vimentin	Homo sapiens	117-125
30625181-6	2019	Similarly, metformin treatment suppressed expressions of anti-apoptotic genes BCL2 and Bcl-xL, and mesenchymal genes vimentin, N-cadherin, Zeb1 and Zeb2 with simultaneous enhancement of apoptotic caspase 3 and Bax, and epithelial genes E-cadherin and keratin 19 expressions, confirming an inhibitory effect of metformin in tumorigenesis.	Metformin	11-20	zinc finger E-box binding homeobox 2	Homo sapiens	148-152
30625181-9	2019	Similarly, cholesterol treatment inverted metformin-reduced several gene expressions (e.g., Bcl-xL, BCL2, Zeb1, vimentin, and BMI-1).	Metformin	42-51	vimentin	Homo sapiens	112-120
30621095-7	2019	Treatment with metformin resulted in a dose-dependent induction of the stem cell genes CD44, BMI-1, OCT-4, and NANOG.	Metformin	15-24	POU class 5 homeobox 1	Homo sapiens	100-105
30153063-9	2019	Metformin-flutamide treatment upregulated hepatic and intestinal insulin signaling, including insulin receptor, MAPK1, and AKT2.	Metformin	0-9	AKT serine/threonine kinase 2	Homo sapiens	123-127
30318707-12	2019	AMP-activated protein kinase (AMPK) activated by metformin-induced stimulation of forkhead box O3a (FoxO3a) transcriptional activity, followed by increased expression of GABAA receptor-associated protein (GABARAP) and its binding to GABAA receptors finally resulted in the membrane insertion of GABAA receptors.	Metformin	49-58	GABA type A receptor-associated protein	Rattus norvegicus	170-203
30318707-12	2019	AMP-activated protein kinase (AMPK) activated by metformin-induced stimulation of forkhead box O3a (FoxO3a) transcriptional activity, followed by increased expression of GABAA receptor-associated protein (GABARAP) and its binding to GABAA receptors finally resulted in the membrane insertion of GABAA receptors.	Metformin	49-58	GABA type A receptor-associated protein	Rattus norvegicus	205-212
30318707-13	2019	CONCLUSIONS AND IMPLICATIONS: Metformin increased mIPSCs by up-regulating the membrane insertion of GABAA receptors, via a pathway involving AMPK, FoxO3a, and the GABAA receptor-associated protein.	Metformin	30-39	GABA type A receptor-associated protein	Rattus norvegicus	163-196
30359174-6	2019	Metformin reduced levels of the NFkappaB signaling components p-IKKalpha/beta, p-NFkappaB, p-IkappaBalpha in colorectal mucosal cells.	Metformin	0-9	conserved helix-loop-helix ubiquitous kinase	Mus musculus	64-77
30320344-0	2019	Metformin suppresses gastric cancer progression through calmodulin-like protein 3 secreted from tumor-associated fibroblasts.	Metformin	0-9	calmodulin like 3	Homo sapiens	56-81
30320344-9	2019	Among these proteins, calmodulin-like protein 3 (Calml3) was 2.88-fold upregulated in the culture medium of gastric TAFs after metformin treatment and a further experiment using recombinant Calml3 indicated its suppressive effect on the clonogenicity of gastric cancer cells.	Metformin	127-136	calmodulin like 3	Homo sapiens	22-47
30320344-9	2019	Among these proteins, calmodulin-like protein 3 (Calml3) was 2.88-fold upregulated in the culture medium of gastric TAFs after metformin treatment and a further experiment using recombinant Calml3 indicated its suppressive effect on the clonogenicity of gastric cancer cells.	Metformin	127-136	calmodulin like 3	Homo sapiens	49-55
30320344-10	2019	It was concluded that metformin suppresses gastric cancer through stimulating Calml3 secretion from TAFs, which represents a novel anticancer mechanism of metformin.	Metformin	22-31	calmodulin like 3	Homo sapiens	78-84
30320344-10	2019	It was concluded that metformin suppresses gastric cancer through stimulating Calml3 secretion from TAFs, which represents a novel anticancer mechanism of metformin.	Metformin	155-164	calmodulin like 3	Homo sapiens	78-84
30733798-9	2018	In this study, we used computational approaches to investigate the effect of 270A &gt; S change in SLC22A2 on interaction with metformin and other drugs.	Metformin	127-136	solute carrier family 22 member 2	Homo sapiens	99-106
32877653-0	2020	Metformin promotes CNS remyelination and improves social interaction following focal demyelination through CBP Ser436 phosphorylation.	Metformin	0-9	CREB binding protein	Mus musculus	107-110
32877653-4	2020	This beneficial effect of metformin acts through stimulating Ser436 phosphorylation in CBP, a histone acetyltransferase.	Metformin	26-35	CREB binding protein	Mus musculus	87-90
32877653-6	2020	Metformin enhances OPC proliferation through early-stage autophagy inhibition, while metformin promotes OPC differentiation into mature oligodendrocytes through activating CBP Ser436 phosphorylation.	Metformin	85-94	CREB binding protein	Mus musculus	172-175
33037327-10	2020	Treatment of isolated CD4+ T cells with metformin was found to inhibit OCR in vitro and alter the expression of several activation markers.	Metformin	40-49	CD4 antigen	Mus musculus	22-25
33169942-9	2020	In conjuncture, AMPK activity and Smad6 and Smurf1 expression were enhanced by metformin treatment in the muscle of injured area, concurrently with the reduction of ALK2.	Metformin	79-88	activin A receptor, type 1	Mus musculus	165-169
33049108-10	2020	Moreover, metformin treatment enhanced the expression of pro-angiogenic/osteogenic growth factors BMP2 and VEGF but reduced the osteoclastogenic factor RANKL/OPG expression in SHEDs.	Metformin	10-19	TNF superfamily member 11	Homo sapiens	152-157
33049108-10	2020	Moreover, metformin treatment enhanced the expression of pro-angiogenic/osteogenic growth factors BMP2 and VEGF but reduced the osteoclastogenic factor RANKL/OPG expression in SHEDs.	Metformin	10-19	basic transcription factor 3 pseudogene 11	Homo sapiens	158-161
33174032-10	2020	In addition, metformin stimulated mitochondrial biogenesis, as indicated by increased expression levels of mitochondrial genes (NDUFA1, NDUFA2, NDUFA13 and manganese superoxide dismutase) and mitochondrial biogenesis-related transcription factors [peroxisome proliferator-activated receptor-gamma coactivator-1alpha, nuclear respiratory factor (NRF)-1, and NRF-2] in the metformin + HG group compared with the HG group.	Metformin	13-22	superoxide dismutase 2	Rattus norvegicus	156-186
33132177-9	2020	RESULTS: Metformin(50 mg/kg) promoted motor functional recovery in rats after SCI, increased the expressions of beta-catenin and brain derived neurotrophic factor (BDNF), inhibited neuron apoptosis and inflammatory response, and improved the recovery of pathological morphology at the injury site by activating the Wnt/beta-catenin signaling pathway.	Metformin	9-18	brain-derived neurotrophic factor	Rattus norvegicus	129-162
33132177-9	2020	RESULTS: Metformin(50 mg/kg) promoted motor functional recovery in rats after SCI, increased the expressions of beta-catenin and brain derived neurotrophic factor (BDNF), inhibited neuron apoptosis and inflammatory response, and improved the recovery of pathological morphology at the injury site by activating the Wnt/beta-catenin signaling pathway.	Metformin	9-18	brain-derived neurotrophic factor	Rattus norvegicus	164-168
33312159-0	2020	GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated With Metformin.	Metformin	77-86	growth differentiation factor 15	Homo sapiens	0-6
33312159-5	2020	Recently, the growth differentiation factor 15 (GDF-15), a member of the transforming growth factor beta superfamily, has been identified as a key mediator of metformin-induced weight loss.	Metformin	159-168	growth differentiation factor 15	Homo sapiens	14-46
33312159-5	2020	Recently, the growth differentiation factor 15 (GDF-15), a member of the transforming growth factor beta superfamily, has been identified as a key mediator of metformin-induced weight loss.	Metformin	159-168	growth differentiation factor 15	Homo sapiens	48-54
33312159-6	2020	Metformin increases the secretion of GDF-15, which binds exclusively to glial cell-derived neurotrophic factor family receptor alpha-like (GFRAL).	Metformin	0-9	growth differentiation factor 15	Homo sapiens	37-43
33312159-6	2020	Metformin increases the secretion of GDF-15, which binds exclusively to glial cell-derived neurotrophic factor family receptor alpha-like (GFRAL).	Metformin	0-9	GDNF family receptor alpha like	Homo sapiens	139-144
33312159-8	2020	Herein, we critically review advances in the understanding of the weight-reducing effects of metformin via the GDF-15 pathway.	Metformin	93-102	growth differentiation factor 15	Homo sapiens	111-117
33172126-0	2020	Medroxyprogesterone Reverses Tolerable Dose Metformin-Induced Inhibition of Invasion via Matrix Metallopeptidase-9 and Transforming Growth Factor-beta1 in KLE Endometrial Cancer Cells.	Metformin	44-53	matrix metallopeptidase 9	Homo sapiens	89-114
33172126-6	2020	Changes of MMP-9 and TGF-beta1 according to combinations of MPA and metformin were similar to those of invasion in KLE cells.	Metformin	68-77	matrix metallopeptidase 9	Homo sapiens	11-16
33172126-8	2020	Anti-invasive effect of metformin in KLE cells was completely reversed by the addition of MPA; this might be associated with MMP-9 and TGF-beta1.	Metformin	24-33	matrix metallopeptidase 9	Homo sapiens	125-130
33520876-2	2020	Introduction: Changes in hepatic clearance and CYP2D1 activity after combination therapy with insulin and metformin in type-1 diabetes and insulin administration in type-2 diabetes was assessed in an animal model.	Metformin	106-115	cytochrome P450, family 2, subfamily d, polypeptide 1	Rattus norvegicus	47-53
33520876-9	2020	Conclusions: Administration of insulin plus metformin in type-1 diabetes could modulate the function of CYP2D1 to the observed levels in the control group and made it clearer to predict the fate of drugs that are metabolized by this enzyme.	Metformin	44-53	cytochrome P450, family 2, subfamily d, polypeptide 1	Rattus norvegicus	104-110
32926965-0	2020	Metformin-induced suppression of Nemo-like kinase improves erythropoiesis in preclinical models of Diamond-Blackfan anemia through induction of miR-26a.	Metformin	0-9	nemo like kinase	Homo sapiens	33-49
32934682-13	2020	In conclusion, the present results suggested that metformin attenuated RIF of UUO rats, and the mechanism of action was found to be associated with the increase in Deptor expression and inhibition of the mTOR/p70S6K pathway in the kidneys of UUO rats.	Metformin	50-59	mechanistic target of rapamycin kinase	Rattus norvegicus	204-208
33067434-0	2020	Metformin enhances anti-mycobacterial responses by educating CD8+ T-cell immunometabolic circuits.	Metformin	0-9	CD8a molecule	Homo sapiens	61-64
33067434-3	2020	Here, we use mass cytometry to show that metformin treatment expands a population of memory-like antigen-inexperienced CD8+CXCR3+ T cells in naive mice, and in healthy individuals and patients with T2D.	Metformin	41-50	CD8a molecule	Homo sapiens	119-122
33067434-4	2020	Metformin-educated CD8+ T cells have increased (i) mitochondrial mass, oxidative phosphorylation, and fatty acid oxidation; (ii) survival capacity; and (iii) anti-mycobacterial properties.	Metformin	0-9	CD8a molecule	Homo sapiens	19-22
33067434-7	2020	Collectively, these results demonstrate an important function of CD8+ T cells in metformin-derived host metabolic-fitness towards M. tuberculosis infection.	Metformin	81-90	CD8a molecule	Homo sapiens	65-68
33081077-6	2020	Metformin decreased the NGF-induced transcriptional activity of MYC and beta-catenin/T-cell factor/lymphoid enhancer-binding factor (TCF-Lef), as well as the expression of c-MYC, survivin and VEGF in EOC cells, while it increased miR-23b and miR-145 levels.	Metformin	0-9	microRNA 23b	Homo sapiens	230-237
33194016-13	2020	Immunofluorescence staining showed that metformin enhanced the expression of Ki-67 in vascular endothelial cells.	Metformin	40-49	antigen identified by monoclonal antibody Ki 67	Mus musculus	77-82
33058005-4	2021	By influencing IRS1 phosphorylation pattern, metformin may sensitize TSHR to TSH, thus explaining the findings of clinical studies.	Metformin	45-54	thyroid stimulating hormone receptor	Homo sapiens	69-73
33050392-1	2020	Metformin, which is suggested to have anti-cancer effects, activates KDM2A to reduce rRNA transcription and proliferation of cancer cells.	Metformin	0-9	lysine demethylase 2A	Homo sapiens	69-74
33050392-8	2020	Gallic acid did not reduce the succinate level, which was required for KDM2A activation by metformin.	Metformin	91-100	lysine demethylase 2A	Homo sapiens	71-76
33025801-11	2021	Metformin slightly reduced expression in ADAMTS5 (beta = 0.34, P = 0.04), HIF-1a (beta = 0.39, P = 0.04), IL4 (beta = 0.30, P = 0.02), MMP1 (beta = 0.47, P < 0.01), and SOX9 (beta = 0.37, P = 0.03).	Metformin	0-9	ADAM metallopeptidase with thrombospondin type 1 motif 5	Homo sapiens	41-48
33025801-15	2021	Metformin reduced the expression of catabolic genes ADAMTS5 and MMP1 and might play a role in disease prevention.	Metformin	0-9	ADAM metallopeptidase with thrombospondin type 1 motif 5	Homo sapiens	52-59
32347398-1	2020	Metformin, a potent AMPK activator is the most commonly used drug for diabetes.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	20-24
33098389-0	2020	Evaluation of Muc1 Gene Expression at The Time of Implantation in Diabetic Rat Models Treated with Insulin, Metformin and Pioglitazone in The Normal Cycle and Ovulation Induction Cycle.	Metformin	108-117	mucin 1, cell surface associated	Rattus norvegicus	14-18
32967076-5	2020	Patients treated with metformin showed decreased levels of all analyzed serum pro-inflammatory markers (TNFalpha, IL6, IL1beta and MCP1) and a downwards trend in IL18 levels associated with a lower production of oxidative stress markers in leukocytes (mitochondrial ROS and myeloperoxidase (MPO)).	Metformin	22-31	interleukin 18	Homo sapiens	162-166
32940892-8	2021	The AMPK activator AICAR alone lowered TF expression in THP-1, while the AMPK inhibitor compound C abrogated the metformin-dependent reduction in TF expression.	Metformin	113-122	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	4-8
32940892-8	2021	The AMPK activator AICAR alone lowered TF expression in THP-1, while the AMPK inhibitor compound C abrogated the metformin-dependent reduction in TF expression.	Metformin	113-122	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	73-77
32982447-7	2020	In addition, metformin"s effects in the prevention and treatment for GC involve multiple pathways mainly via AMPK and IGF-1R.	Metformin	13-22	insulin like growth factor 1 receptor	Homo sapiens	118-124
32646922-7	2020	However, metformin reprogrammed the TIME towards "infiltrated-inflamed" and increased the numbers of infiltrated CD8+ cytotoxic T-lymphocyte and CD20+ B-lymphocyte.	Metformin	9-18	CD8a molecule	Homo sapiens	113-116
32646922-11	2020	In both humans and mice, metformin triggered AMPK activation and STAT3 inactivation, and altered the production of effector cytokines (i.e. TNF-alpha, IFN-gamma, IL-10) in the immune cells.	Metformin	25-34	interleukin 10	Homo sapiens	162-167
32619406-7	2020	Furthermore, we identify that metformin-stimulated AMPK signaling converges at FOXO3 to stimulate SETD2 expression.	Metformin	30-39	forkhead box O3	Mus musculus	79-84
32913271-2	2020	In C57BL/6JJcl mice fed with high fat-high sucrose chow (HFS), multifunctionality of CD8 + splenic and tumor-infiltrating lymphocytes (TILs) was impaired and associated with enhanced tumor growth, which were inhibited by metformin.	Metformin	221-230	CD8a molecule	Homo sapiens	85-88
32913271-3	2020	In CD8 + splenic T cells from the HFS mice, glycolysis/basal respiration ratio was significantly reduced and reversed by metformin.	Metformin	121-130	CD8a molecule	Homo sapiens	3-6
32913271-6	2020	The disturbance of the link between metabolism and immune function in CD8 + PD-1 + T cells in T2D was proved by recovery of antigen-specific and non-specific cytokine production via metformin-mediated increase in glycolytic activity.	Metformin	182-191	CD8a molecule	Homo sapiens	70-73
29746885-5	2018	RESULTS: Oral administration of curcumin and metformin combated mitochondrial fatty acid oxidation and reduced hepatic succinate accumulation due to the inhibition of succinate dehydrogenase (SDH) activity and demonstrated inhibitory effect on hepatic fibrosis.	Metformin	45-54	aminoadipate-semialdehyde synthase	Mus musculus	167-190
29746885-5	2018	RESULTS: Oral administration of curcumin and metformin combated mitochondrial fatty acid oxidation and reduced hepatic succinate accumulation due to the inhibition of succinate dehydrogenase (SDH) activity and demonstrated inhibitory effect on hepatic fibrosis.	Metformin	45-54	aminoadipate-semialdehyde synthase	Mus musculus	192-195
30442142-4	2018	METHODS: We first examined the cytotoxic effects of metformin in the HeLa human cervical carcinoma and ZR-75-1 breast cancer cell lines using assays of cell viability, cleaved poly-ADP-ribose polymerase, and Annexin V-fluorescein isothiocyanate apoptosis, as well as flow cytometric analyses of the cell cycle profile and reactive oxygen species (ROS).	Metformin	52-61	annexin A5	Homo sapiens	208-217
30607342-16	2018	Treatment with metformin showed ability to attenuate upregulation of IL-4-DUOX2 pathway and other pathological damages to the lung after exposure to a high dose of IR.	Metformin	15-24	dual oxidase 2	Rattus norvegicus	74-79
29630425-8	2018	RESULTS: Metformin suppressed LPS-induced IP-10 and MCP-1 production as well as LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38, extracellular signal-regulated kinase (ERK), and nuclear factor-kappa B (NF-kappaB).	Metformin	9-18	C-C motif chemokine ligand 2	Homo sapiens	52-57
29380373-10	2018	Folic acid induced nephropathy was associated with the overexpression of inflammatory markers MCP-1, F4/80, type IV collagen, fibronectin and TGF-beta1 compared to control groups, which were partially attenuated by metformin treatment.	Metformin	215-224	fibronectin 1	Mus musculus	126-137
30230981-10	2018	Our results showed that metformin inhibited the phosphorylation of I-kappaBalpha and p65 while it activated AMPK.	Metformin	24-33	v-rel reticuloendotheliosis viral oncogene homolog A (avian)	Mus musculus	85-88
30009823-10	2018	In addition, activation of AMPK by metformin suppressed NF-kappaB-mediated autophagy activation and down-regulation of RND3 and therefore reduced RVSP, RVHI, and %MT in MCT-induced PAH.	Metformin	35-44	Rho family GTPase 3	Rattus norvegicus	119-123
30646124-3	2018	Objective: To identify which drug classes among sulfonylureas, dipeptidyl peptidase 4 (DPP-4) inhibitors, and thiazolidinediones are associated with reduced hemoglobin A1c (HbA1c) levels and lower risk of myocardial infarction, kidney disorders, and eye disorders in patients with T2D treated with metformin as a first-line therapy.	Metformin	298-307	dipeptidyl peptidase 4	Homo sapiens	63-85
32982345-8	2020	Results: The combination of lycopene with metformin maintained the beneficial effects of the isolated treatments, improving the glucose tolerance and lipid profile, lessening biomarkers of oxidative damage, and increasing the paraoxonase 1 activity.	Metformin	42-51	paraoxonase 1	Rattus norvegicus	226-239
32996739-13	2020	Instead, in tumors treated with MTF alone and in combination with DCA the total CD68+ TAMs count was almost 27% (p < 0.05) and 43% lower (p < 0.05) correspondingly than that in control, but this decrease was not accompanied by redistribution of CD68+/CD206+ and CD68+/D206- subsets.	Metformin	32-35	mannose receptor, C type 1	Mus musculus	251-256
31593308-0	2020	Metformin effects on FOXP3+ and CD8+ T cell infiltrates of head and neck squamous cell carcinoma.	Metformin	0-9	CD8a molecule	Homo sapiens	32-35
32974191-12	2020	Importantly, the increase in fold of PTEN expression and decrease in folds of Akt phosphorylation level and MMP2 and MMP9 expressions in the treated HCC cells with metformin on 16-kPa stiffness substrate were evidently weakened compared with those in the controls on the 6-kPa stiffness substrate.	Metformin	164-173	matrix metallopeptidase 9	Homo sapiens	117-121
32606000-6	2020	The anti-diabetic drug metformin suppressed insulin-induced hepatic Cyclin D1 expression and protected against obese/diabetic hepatocarcinogenesis.	Metformin	23-32	cyclin D1	Mus musculus	68-77
32480011-6	2020	GSDMD positive cells and NLRP3 inflammasome expression were augmented in gingival tissue, which were partly reversed by metformin.	Metformin	120-129	gasdermin D	Mus musculus	0-5
32774666-8	2020	Autophagy was stimulated by metformin, and inhibition of autophagy by 3-methyladenine (3-MA) and chloroquine (CQ) or knockdown of Beclin1 and LC3B blocked the protective effects of metformin.	Metformin	181-190	beclin 1	Homo sapiens	130-137
32703218-10	2020	On the contrary, the activation of AMPK by metformin (Met) or 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) could overcome the KRAS-induced resistance to the anti-EGFR antibody in vivo and in vitro.	Metformin	43-52	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	35-39
32703218-10	2020	On the contrary, the activation of AMPK by metformin (Met) or 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) could overcome the KRAS-induced resistance to the anti-EGFR antibody in vivo and in vitro.	Metformin	43-52	KRAS proto-oncogene, GTPase	Homo sapiens	135-139
32703218-10	2020	On the contrary, the activation of AMPK by metformin (Met) or 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) could overcome the KRAS-induced resistance to the anti-EGFR antibody in vivo and in vitro.	Metformin	54-57	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	35-39
32703218-10	2020	On the contrary, the activation of AMPK by metformin (Met) or 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) could overcome the KRAS-induced resistance to the anti-EGFR antibody in vivo and in vitro.	Metformin	54-57	KRAS proto-oncogene, GTPase	Homo sapiens	135-139
32695253-15	2020	Metformin exerted its protection against oxidative stress possibly via activating AMPK/Sirt1 and increasing TXNIP.	Metformin	0-9	sirtuin 1	Homo sapiens	87-92
32779431-10	2020	Metformin decreased the expression of S100b, neuron specific enolase (Nse), and glial fibrillary acidic protein (Gfap).	Metformin	0-9	S100 calcium binding protein B	Rattus norvegicus	38-43
32779431-10	2020	Metformin decreased the expression of S100b, neuron specific enolase (Nse), and glial fibrillary acidic protein (Gfap).	Metformin	0-9	glial fibrillary acidic protein	Rattus norvegicus	80-111
32779431-10	2020	Metformin decreased the expression of S100b, neuron specific enolase (Nse), and glial fibrillary acidic protein (Gfap).	Metformin	0-9	glial fibrillary acidic protein	Rattus norvegicus	113-117
31283677-8	2020	KRAS, GRB2, PCK2, BCL2L1, INSL3, DOK3, and PTPN1 were among the most significantly upregulated genes in both immunosuppression and diabetes subsets and were appropriately reverted by metformin as confirmed in vitro.	Metformin	183-192	KRAS proto-oncogene, GTPase	Homo sapiens	0-4
31283677-8	2020	KRAS, GRB2, PCK2, BCL2L1, INSL3, DOK3, and PTPN1 were among the most significantly upregulated genes in both immunosuppression and diabetes subsets and were appropriately reverted by metformin as confirmed in vitro.	Metformin	183-192	phosphoenolpyruvate carboxykinase 2, mitochondrial	Homo sapiens	12-16
31283677-8	2020	KRAS, GRB2, PCK2, BCL2L1, INSL3, DOK3, and PTPN1 were among the most significantly upregulated genes in both immunosuppression and diabetes subsets and were appropriately reverted by metformin as confirmed in vitro.	Metformin	183-192	docking protein 3	Homo sapiens	33-37
31283677-8	2020	KRAS, GRB2, PCK2, BCL2L1, INSL3, DOK3, and PTPN1 were among the most significantly upregulated genes in both immunosuppression and diabetes subsets and were appropriately reverted by metformin as confirmed in vitro.	Metformin	183-192	protein tyrosine phosphatase non-receptor type 1	Homo sapiens	43-48
31907158-14	2019	Metformin alone did not obviously affect CD4+ cells or CD8+ cells but significantly decreased the percentage of CD4+Foxp3+ (P < 0.05); the vaccine alone significantly increased CD4+ cells and CD8+ cells (P < 0.001) and also the percentage of CD4+Foxp3+ cells (P < 0.05).	Metformin	0-9	CD4 antigen	Mus musculus	112-115
31907158-14	2019	Metformin alone did not obviously affect CD4+ cells or CD8+ cells but significantly decreased the percentage of CD4+Foxp3+ (P < 0.05); the vaccine alone significantly increased CD4+ cells and CD8+ cells (P < 0.001) and also the percentage of CD4+Foxp3+ cells (P < 0.05).	Metformin	0-9	CD4 antigen	Mus musculus	112-115
31907158-14	2019	Metformin alone did not obviously affect CD4+ cells or CD8+ cells but significantly decreased the percentage of CD4+Foxp3+ (P < 0.05); the vaccine alone significantly increased CD4+ cells and CD8+ cells (P < 0.001) and also the percentage of CD4+Foxp3+ cells (P < 0.05).	Metformin	0-9	CD4 antigen	Mus musculus	112-115
31882570-7	2019	The process was detected by measuring autophagosomes and the expression of microtubule-associated protein 1A/1B-light chain 3 upon metformin treatment of sciatic nerve crush-injured rats.	Metformin	131-140	microtubule-associated protein 1A	Rattus norvegicus	75-111
31882570-10	2019	Motor function was also recovered after metformin treatment, which was accompanied by upregulation of MBP and NF200 through autophagy induction.	Metformin	40-49	myelin basic protein	Rattus norvegicus	102-105
31920356-0	2019	Differential Expression of Human N-Alpha-Acetyltransferase 40 (hNAA40), Nicotinamide Phosphoribosyltransferase (NAMPT) and Sirtuin-1 (SIRT-1) Pathway in Obesity and T2DM: Modulation by Metformin and Macronutrient Intake.	Metformin	185-194	sirtuin 1	Homo sapiens	134-140
31920356-7	2019	Metformin treatment reverted hNAA40, NAMPT, and SIRT-1 expression levels to normal levels.	Metformin	0-9	sirtuin 1	Homo sapiens	48-54
31950065-0	2019	Metformin Reduces Lipotoxicity-Induced Meta-Inflammation in beta-Cells through the Activation of GPR40-PLC-IP3 Pathway.	Metformin	0-9	free fatty acid receptor 1	Rattus norvegicus	97-102
31950065-4	2019	Results: Metformin-reduced lipotoxicity-induced beta-cell meta-inflammatory injury was associated with the expression of GPR40.	Metformin	9-18	free fatty acid receptor 1	Rattus norvegicus	121-126
31705902-4	2019	Growth differentiation factor 15, also mainly produced in the gut, was first identified as a biomarker for metformin use but is now suggested to play a significant role in e.g. weight loss of prediabetics.	Metformin	107-116	growth differentiation factor 15	Homo sapiens	0-32
31822720-0	2019	Metformin activates KDM2A to reduce rRNA transcription and cell proliferation by dual regulation of AMPK activity and intracellular succinate level.	Metformin	0-9	lysine demethylase 2A	Homo sapiens	20-25
31822720-5	2019	We found that treatment of MCF-7 cells with metformin induced the demethylase activity of KDM2A in the rDNA promoter, which resulted in reductions of rRNA transcription and cell proliferation.	Metformin	44-53	lysine demethylase 2A	Homo sapiens	90-95
31822720-6	2019	AMPK activity was required for activation of KDM2A by metformin.	Metformin	54-63	lysine demethylase 2A	Homo sapiens	45-50
31886236-9	2019	In addition, metformin effectively increased matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) levels in the placenta.	Metformin	13-22	matrix metallopeptidase 2	Mus musculus	45-71
31886236-9	2019	In addition, metformin effectively increased matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) levels in the placenta.	Metformin	13-22	matrix metallopeptidase 2	Mus musculus	73-78
31886236-9	2019	In addition, metformin effectively increased matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) levels in the placenta.	Metformin	13-22	vascular endothelial growth factor A	Mus musculus	84-118
31886236-9	2019	In addition, metformin effectively increased matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) levels in the placenta.	Metformin	13-22	vascular endothelial growth factor A	Mus musculus	120-124
31620963-7	2019	RESULTS: Our finding indicated that consumption of metformin during the recovery period potentially induced an active form of AMPK (p-AMPK) and promoted repopulation of mature OLGs (MOG+ cells, MBP+ cells) in CC through up-regulation of BDNF, CNTF, and NGF as well as down-regulation of NogoA and recruitment of Olig2+ precursor cells.	Metformin	51-60	nerve growth factor	Mus musculus	253-256
31455870-8	2019	Further mechanistic study identified that specific unsaturated fatty acid, the oleic acid (C18:1 n-9), incorporated DAGs produced by hepatic lipogenesis are the key molecules to enhance the AR activity, through activation of Akt kinase, and this novel mechanism is targeted by metformin.	Metformin	277-286	androgen receptor	Mus musculus	190-192
32694673-8	2019	An increase in serum GDF15 is also associated with weight loss in patients with type 2 diabetes who take metformin.	Metformin	105-114	growth differentiation factor 15	Homo sapiens	21-26
32694673-9	2019	Although further studies will be required to determine the tissue source(s) of GDF15 produced in response to metformin in vivo, our data indicate that the therapeutic benefits of metformin on appetite, body mass and serum insulin depend on GDF15.	Metformin	109-118	growth differentiation factor 15	Homo sapiens	79-84
32694673-9	2019	Although further studies will be required to determine the tissue source(s) of GDF15 produced in response to metformin in vivo, our data indicate that the therapeutic benefits of metformin on appetite, body mass and serum insulin depend on GDF15.	Metformin	179-188	growth differentiation factor 15	Homo sapiens	240-245
31871550-0	2019	Metformin Ameliorates Testicular Damage in Male Mice with Streptozotocin-Induced Type 1 Diabetes through the PK2/PKR Pathway.	Metformin	0-9	eukaryotic translation initiation factor 2-alpha kinase 2	Mus musculus	113-116
31582211-9	2019	Taken together, we found that administration of metformin prevents pre-eclampsia by suppressing migration of trophoblast cells via modulating the signaling pathway of UCA1/miR-204/MMP-9.	Metformin	48-57	matrix metallopeptidase 9	Homo sapiens	180-185
31703101-5	2019	Significantly elevated faecal sIgA levels during administration of metformin, and its correlation with the expression of genes associated with immune response (CXCR4, HLA-DQA1, MAP3K14, TNFRSF21, CCL4, ACVR1B, PF4, EPOR, CXCL8) supports a novel hypothesis of strong association between metformin and intestinal immune system, and for the first time provide evidence for altered RNA expression as a contributing mechanism of metformin"s action.	Metformin	67-76	C-X-C motif chemokine receptor 4	Homo sapiens	160-165
31703101-5	2019	Significantly elevated faecal sIgA levels during administration of metformin, and its correlation with the expression of genes associated with immune response (CXCR4, HLA-DQA1, MAP3K14, TNFRSF21, CCL4, ACVR1B, PF4, EPOR, CXCL8) supports a novel hypothesis of strong association between metformin and intestinal immune system, and for the first time provide evidence for altered RNA expression as a contributing mechanism of metformin"s action.	Metformin	67-76	activin A receptor type 1B	Homo sapiens	202-208
31698699-0	2019	Treatment with a Combination of Metformin and 2-Deoxyglucose Upregulates Thrombospondin-1 in Microvascular Endothelial Cells: Implications in Anti-Angiogenic Cancer Therapy.	Metformin	32-41	thrombospondin 1	Mus musculus	73-89
31698699-7	2019	Additionally, treatment with metformin and 2DG (5 mM) inhibited the Akt/mTOR pathway and down-regulated the cell-cycle-related proteins such as p-cyclin B1 (S147) and cyclins D1 and D2 when compared to cells that were treated with either 2DG or metformin alone.	Metformin	29-38	cyclin D1	Mus musculus	167-184
31416838-6	2019	In a murine xenograft model, combining metformin or shCDX1 with cisplatin reduced tumor growth, increased caspase-3 cleavage, and reduced expression of CD44 and MMP-9 to a greater degree than cisplatin alone.	Metformin	39-48	caspase 3	Mus musculus	106-115
31416838-6	2019	In a murine xenograft model, combining metformin or shCDX1 with cisplatin reduced tumor growth, increased caspase-3 cleavage, and reduced expression of CD44 and MMP-9 to a greater degree than cisplatin alone.	Metformin	39-48	CD44 antigen	Mus musculus	152-156
31161347-0	2019	The impact of GDF-15, a biomarker for metformin, on the risk of coronary artery disease, breast and colorectal cancer, and type 2 diabetes and metabolic traits: a Mendelian randomisation study.	Metformin	38-47	growth differentiation factor 15	Homo sapiens	14-20
31161347-1	2019	AIMS/HYPOTHESIS: Growth differentiation factor 15 (GDF-15), a suggested biomarker for metformin use, may explain the potential cardioprotective and anti-cancer properties of metformin.	Metformin	86-95	growth differentiation factor 15	Homo sapiens	17-49
31161347-1	2019	AIMS/HYPOTHESIS: Growth differentiation factor 15 (GDF-15), a suggested biomarker for metformin use, may explain the potential cardioprotective and anti-cancer properties of metformin.	Metformin	86-95	growth differentiation factor 15	Homo sapiens	51-57
31161347-1	2019	AIMS/HYPOTHESIS: Growth differentiation factor 15 (GDF-15), a suggested biomarker for metformin use, may explain the potential cardioprotective and anti-cancer properties of metformin.	Metformin	174-183	growth differentiation factor 15	Homo sapiens	17-49
31161347-1	2019	AIMS/HYPOTHESIS: Growth differentiation factor 15 (GDF-15), a suggested biomarker for metformin use, may explain the potential cardioprotective and anti-cancer properties of metformin.	Metformin	174-183	growth differentiation factor 15	Homo sapiens	51-57
31452705-8	2019	The administration of metformin also promoted autophagy of ovarian cancer The expression level of microtubule associated protein 1 light chain 3-alpha protein was markedly upregulated.	Metformin	22-31	microtubule associated protein 1 light chain 3 alpha	Homo sapiens	98-150
31452705-9	2019	The mRNA expression level of metastasis-associated 1 (MTA1) was significantly downregulated following metformin treatment.	Metformin	102-111	metastasis associated 1	Homo sapiens	29-58
31452705-12	2019	It was hypothesized that the underlying mechanism of metformin"s effect may involve MTA1 downregulation.	Metformin	53-62	metastasis associated 1	Homo sapiens	84-88
30936409-1	2019	OBJECTIVE: To assess the association of metformin prescription with the risk of aortic aneurysm, aortic aneurysm events and the enlargement of abdominal aortic aneurysm (AAA).	Metformin	40-49	AAA1	Homo sapiens	170-173
30936409-9	2019	We found that metformin prescription could significantly limit the enlargement of aortic aneurysm (weighted mean difference: -0.83 mm/year, 95% CI -1.38 to -0.28, I2=89.6%) among patients with AAA.	Metformin	14-23	AAA1	Homo sapiens	193-196
30936409-11	2019	CONCLUSIONS: According to the available epidemiological evidence, metformin prescription could limit the expansion of AAA among patients with this disease, and may be involved with a lower incidence of aortic aneurysm and aortic aneurysm events.	Metformin	66-75	AAA1	Homo sapiens	118-121
30936409-12	2019	Randomised controlled trials are needed to confirm whether metformin could reduce the enlargement of AAA in patients with or without diabetes.	Metformin	59-68	AAA1	Homo sapiens	101-104
31203154-1	2019	Metformin (Met) has been found to modify the methylation of H19 and to alter its expression.	Metformin	0-9	H19, imprinted maternally expressed transcript (non-protein coding)	Rattus norvegicus	60-63
29645341-10	2018	CONCLUSIONS: Elderly subjects with metformin-treated type 2 diabetes have lower glucagon levels at 3.5 mmol/L glucose, but maintain the glucagon response to hypoglycaemia at 3.1 mmol/L during DPP-4 inhibition, which safeguards against hypoglycaemia and may contribute to decreasing the risk of hypoglycaemia by DPP-4 inhibition in this age group.	Metformin	35-44	dipeptidyl peptidase 4	Homo sapiens	192-197
29645341-10	2018	CONCLUSIONS: Elderly subjects with metformin-treated type 2 diabetes have lower glucagon levels at 3.5 mmol/L glucose, but maintain the glucagon response to hypoglycaemia at 3.1 mmol/L during DPP-4 inhibition, which safeguards against hypoglycaemia and may contribute to decreasing the risk of hypoglycaemia by DPP-4 inhibition in this age group.	Metformin	35-44	dipeptidyl peptidase 4	Homo sapiens	311-316
30068236-1	2018	INTRODUCTION: Metformin is the first-line glucose-lowering medication in type 2 diabetes mellitus (T2DM), but it generally requires soon or later the addition of a second-line therapy, among which a sodium-glucose cotransporter type 2 (SGLT-2) inhibitor, to reach and maintain adequate glucose control.	Metformin	14-23	solute carrier family 5 member 2	Homo sapiens	199-234
30068236-1	2018	INTRODUCTION: Metformin is the first-line glucose-lowering medication in type 2 diabetes mellitus (T2DM), but it generally requires soon or later the addition of a second-line therapy, among which a sodium-glucose cotransporter type 2 (SGLT-2) inhibitor, to reach and maintain adequate glucose control.	Metformin	14-23	solute carrier family 5 member 2	Homo sapiens	236-242
30068236-2	2018	Areas covered: This narrative review provides an analysis of both efficacy and safety of a dual therapy combining metformin and empagliflozin, a SGLT-2 inhibitor that has proven its" potential to reduce major cardiovascular (CV) events, mortality, and renal outcomes in patients with T2DM and established CV disease.	Metformin	114-123	solute carrier family 5 member 2	Homo sapiens	145-151
30178862-16	2018	After NR8383 was treated with metformin and LPS, the expression of SIRT1 was higher than that of LPS treatment alone, but the expression of p-p38, p-ERK, and p-NF-kappaB was significantly decreased.	Metformin	30-39	sirtuin 1	Mus musculus	67-72
30178862-17	2018	After the addition of metformin in NR8383 after LPS treatment, the expression level of miR-138-5p was significantly decreased, and miR-138-5p was confirmed to target SIRT1 and regulate its expression.	Metformin	22-31	sirtuin 1	Mus musculus	166-171
30178862-19	2018	A possible mechanism might be that metformin-induced low expression of mir-138-5p could target SIRT1 to increase its expression and suppress the MAPK pathway, thus alleviating ARDS.	Metformin	35-44	sirtuin 1	Mus musculus	95-100
29922884-0	2018	Comment on "Targeting AMPK, mTOR and beta-Catenin by Combined Metformin and Aspirin Therapy in HCC: An Appraisal in Egyptian HCC Patients".	Metformin	62-71	catenin beta 1	Homo sapiens	37-49
30013414-2	2018	The addition of the sodium-glucose cotransporter-2 (SGLT2) inhibitor, empagliflozin, to metformin therapy has been shown to be effective and well tolerated in patients with T2DM and is 1 of the several recommended treatment options.	Metformin	88-97	solute carrier family 5 member 2	Homo sapiens	20-50
30013414-2	2018	The addition of the sodium-glucose cotransporter-2 (SGLT2) inhibitor, empagliflozin, to metformin therapy has been shown to be effective and well tolerated in patients with T2DM and is 1 of the several recommended treatment options.	Metformin	88-97	solute carrier family 5 member 2	Homo sapiens	52-57
29977599-2	2018	Studying the molecular changes associated with the tumor-suppressive action of Metformin we found that the oncogene SOX4, which is upregulated in solid tumors and associated with poor prognosis, was induced by Wnt/beta-catenin signaling and blocked by Metformin.	Metformin	79-88	SRY (sex determining region Y)-box 4	Mus musculus	116-120
29977599-2	2018	Studying the molecular changes associated with the tumor-suppressive action of Metformin we found that the oncogene SOX4, which is upregulated in solid tumors and associated with poor prognosis, was induced by Wnt/beta-catenin signaling and blocked by Metformin.	Metformin	252-261	SRY (sex determining region Y)-box 4	Mus musculus	116-120
29650774-0	2018	Genetic Variants in CPA6 and PRPF31 Are Associated With Variation in Response to Metformin in Individuals With Type 2 Diabetes.	Metformin	81-90	pre-mRNA processing factor 31	Mus musculus	29-35
29650774-4	2018	Common variants in PRPF31 and CPA6 were associated with worse and better metformin response, respectively (P &lt; 5 x 10-6), and meta-analysis in independent cohorts displayed similar associations with metformin response (P = 1.2 x 10-8 and P = 0.005, respectively).	Metformin	73-82	pre-mRNA processing factor 31	Mus musculus	19-25
29650774-8	2018	Here, we provide novel evidence for associations of common and rare variants in PRPF31, CPA6, and STAT3 with metformin response that may provide insight into mechanisms important for metformin efficacy in T2D.	Metformin	109-118	pre-mRNA processing factor 31	Mus musculus	80-86
29650774-8	2018	Here, we provide novel evidence for associations of common and rare variants in PRPF31, CPA6, and STAT3 with metformin response that may provide insight into mechanisms important for metformin efficacy in T2D.	Metformin	183-192	pre-mRNA processing factor 31	Mus musculus	80-86
31565651-11	2018	Results showed an upregulation of both DUOX1 and DUOX2 pathways in the presence of metformin, while the level of IL-13 did not show any significant change.	Metformin	83-92	dual oxidase 2	Rattus norvegicus	49-54
29369427-0	2018	Pioglitazone/metformin adduct regulates insulin secretion and inhibits high glucose-induced apoptosis via p21-p53-MDM2 signaling in INS-1 cells.	Metformin	13-22	Wistar clone pR53P1 p53 pseudogene	Rattus norvegicus	110-113
31222939-6	2019	The activation of AMPK with metformin reversed the BZP-induced suppression of autophagy.	Metformin	28-37	zinc finger E-box binding homeobox 1	Homo sapiens	51-54
30945296-0	2019	Metformin ameliorates experimental diabetic periodontitis independently of mammalian target of rapamycin (mTOR) inhibition by reducing NIMA-related kinase 7 (Nek7) expression.	Metformin	0-9	NIMA related kinase 7	Homo sapiens	135-156
30945296-0	2019	Metformin ameliorates experimental diabetic periodontitis independently of mammalian target of rapamycin (mTOR) inhibition by reducing NIMA-related kinase 7 (Nek7) expression.	Metformin	0-9	NIMA related kinase 7	Homo sapiens	158-162
31273790-0	2019	AMPK-SIRT1-independent inhibition of ANGPTL3 gene expression is a potential lipid-lowering mechanism of metformin.	Metformin	104-113	sirtuin 1	Homo sapiens	5-10
31273790-6	2019	The role of AMPK-SIRT1 pathway in metformin regulation of ANGPTL3 was determined using pharmacological, RNAi and reporter assays.	Metformin	34-43	sirtuin 1	Homo sapiens	17-22
31273790-8	2019	KEY FINDINGS: Metformin and pharmacological activators of AMPK and SIRT1 inhibited the expression of ANGPTL3 in HepG2 cells.	Metformin	14-23	sirtuin 1	Homo sapiens	67-72
31273790-12	2019	CONCLUSIONS: Metformin inhibits ANGPTL3 expression in the liver in an AMPK-SIRT1-independent manner as a potential mechanism to regulate LPL and lower plasma lipids.	Metformin	13-22	sirtuin 1	Homo sapiens	75-80
31455378-0	2019	Metformin targets a YAP1-TEAD4 complex via AMPKalpha to regulate CCNE1/2 in bladder cancer cells.	Metformin	0-9	TEA domain transcription factor 4	Homo sapiens	25-30
31455378-0	2019	Metformin targets a YAP1-TEAD4 complex via AMPKalpha to regulate CCNE1/2 in bladder cancer cells.	Metformin	0-9	cyclin E1	Homo sapiens	65-72
31455378-6	2019	Western Blot was performed to detect the expressions of AMPKalpha, Yap1, CCND1, CCNE1/2 and CDK2/4/6 in the metformin-treated BLCA cell lines.	Metformin	108-117	cyclin E1	Homo sapiens	80-87
31455378-12	2019	And metformin upregulated the phosphorylated AMPKalpha and decreased the expressions of Yap1 and CCND1, CCNE1/2 and CDK4/6.	Metformin	4-13	cyclin E1	Homo sapiens	104-111
31455378-17	2019	Furthermore, we observed that metformin inhibited the cell proliferation by decreasing the expressions of Yap1 and both CCNE1 and CCNE2 in xenograft model.	Metformin	30-39	cyclin E1	Homo sapiens	120-125
31455378-18	2019	CONCLUSIONS: The results of our study reveal a new potential regulatory pathway in which metformin inhibits cell proliferation via AMPKalpha/Yap1/TEAD4/CCNE1/2 axis in BLCA cells, providing new insights into novel molecular therapeutic targets for BLCA.	Metformin	89-98	TEA domain transcription factor 4	Homo sapiens	146-151
31455378-18	2019	CONCLUSIONS: The results of our study reveal a new potential regulatory pathway in which metformin inhibits cell proliferation via AMPKalpha/Yap1/TEAD4/CCNE1/2 axis in BLCA cells, providing new insights into novel molecular therapeutic targets for BLCA.	Metformin	89-98	cyclin E1	Homo sapiens	152-159
31150647-2	2019	Here we found that PPARdelta agonist GW501516 significantly increased Glut1 (Glucose transporter 1) and SLC1A5 (solutecarrier family 1 member 5) gene and protein expressions in HCT-116, SW480, HeLa, and MCF-7 cancer cell lines, while metformin inhibited this event, which was associated with metformin-mediated inhibition of PPARdelta activity in response to GW501516.	Metformin	234-243	peroxisome proliferator activated receptor delta	Homo sapiens	19-28
31150647-2	2019	Here we found that PPARdelta agonist GW501516 significantly increased Glut1 (Glucose transporter 1) and SLC1A5 (solutecarrier family 1 member 5) gene and protein expressions in HCT-116, SW480, HeLa, and MCF-7 cancer cell lines, while metformin inhibited this event, which was associated with metformin-mediated inhibition of PPARdelta activity in response to GW501516.	Metformin	292-301	peroxisome proliferator activated receptor delta	Homo sapiens	19-28
31150647-4	2019	Metformin inhibited Glut1 and SLC1A5 expressions leading to reduced influx of glucose and glutamine in cancer cells, which is associated with reduced tumor growth.	Metformin	0-9	solute carrier family 2 member 1	Homo sapiens	20-25
31150647-4	2019	Metformin inhibited Glut1 and SLC1A5 expressions leading to reduced influx of glucose and glutamine in cancer cells, which is associated with reduced tumor growth.	Metformin	0-9	solute carrier family 1 member 5	Homo sapiens	30-36
31150647-5	2019	These findings suggest that metformin inhibited PPARdelta agonist GW501516-induced cancer cell metabolism and tumor growth.	Metformin	28-37	peroxisome proliferator activated receptor delta	Homo sapiens	48-57
30445633-0	2019	Metformin suppresses the esophageal carcinogenesis in rats treated with NMBzA through inhibiting AMPK/mTOR signaling pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Rattus norvegicus	102-106
30445633-9	2019	Treatment of metformin led to activation of AMP-activated protein kinase (AMPK) and attenuated signaling of the downstream molecules such as p-mTOR, p-p70S6K and cyclin D1 expression both in vivo and in vitro.	Metformin	13-22	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	74-78
30445633-10	2019	Taken together, our study demonstrated that metformin suppressed the carcinogenesis of ESCC through inhibiting AMPK/mammalian target of the rapamycin (mTOR) signaling pathway, resulting in its chemopreventive effects on the carcinogenesis of ESCC.	Metformin	44-53	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	111-115
31273547-3	2019	In this study, the application of DMBG partially alleviates the pathological changes in the kidneys of db/db mice, increases the level of the klotho protein in the blood, urine and kidney tissues of the mice, and reduces the levels of the mTOR and p-mTOR proteins.	Metformin	34-38	klotho	Mus musculus	142-148
31600602-0	2019	Metformin Effect on Endocan Biogenesis in Human Endothelial Cells Under Diabetic Condition.	Metformin	0-9	endothelial cell specific molecule 1	Homo sapiens	20-27
31600602-11	2019	Endocan transcription and protein levels were increased in diabetic HUVECs exposed to metformin (p &lt; 0.05).	Metformin	86-95	endothelial cell specific molecule 1	Homo sapiens	0-7
31600602-16	2019	CONCLUSION: Data demonstrated that metformin could promote angiogenic potential of endothelial cells which its reduction is a main cause in the development of diabetic foot ulcer, probably by the regulation of endocan dynamics under high glucose condition.	Metformin	35-44	endothelial cell specific molecule 1	Homo sapiens	210-217
31060005-8	2019	Transcription factor (TF)-target network analysis revealed that metformin regulated gene expression potentially via TFs including Tp53, Est1, Sp1 and Hif1alpha.	Metformin	64-73	tumor protein p53	Rattus norvegicus	130-134
31060005-8	2019	Transcription factor (TF)-target network analysis revealed that metformin regulated gene expression potentially via TFs including Tp53, Est1, Sp1 and Hif1alpha.	Metformin	64-73	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	150-159
31082618-0	2019	Metformin inhibits beta-catenin phosphorylation on Ser-552 through an AMPK/PI3K/Akt pathway in colorectal cancer cells.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	70-74
31082618-4	2019	Here we report that a non-canonical Ser552 phosphorylation in beta-catenin, which promotes its nuclear accumulation and transcriptional activity, is blocked by metformin via AMPK-mediated PI3K/Akt signaling inhibition.	Metformin	160-169	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	174-178
31142603-7	2019	Our data show that metformin increased IL-10 and IDO expression in Ad-hMSCs and decreased high-mobility group box 1 protein, IL-1beta, and IL-6 expression.	Metformin	19-28	high mobility group box 1	Rattus norvegicus	90-115
31142603-9	2019	In cocultures, metformin-stimulated Ad-hMSCs inhibited the mRNA expression of RUNX2, COL X, VEGF, MMP1, MMP3, and MMP13 in IL-1beta-stimulated OA chondrocytes and increased the expression of TIMP1 and TIMP3.	Metformin	15-24	matrix metallopeptidase 3	Rattus norvegicus	104-108
31142603-9	2019	In cocultures, metformin-stimulated Ad-hMSCs inhibited the mRNA expression of RUNX2, COL X, VEGF, MMP1, MMP3, and MMP13 in IL-1beta-stimulated OA chondrocytes and increased the expression of TIMP1 and TIMP3.	Metformin	15-24	matrix metallopeptidase 13	Rattus norvegicus	114-119
31142603-9	2019	In cocultures, metformin-stimulated Ad-hMSCs inhibited the mRNA expression of RUNX2, COL X, VEGF, MMP1, MMP3, and MMP13 in IL-1beta-stimulated OA chondrocytes and increased the expression of TIMP1 and TIMP3.	Metformin	15-24	TIMP metallopeptidase inhibitor 1	Rattus norvegicus	191-196
31164166-10	2019	Moreover, metformin reduced the interleukin (IL)-6, tumor necrosis factor-alpha, IL-17 mRNA, and protein levels in the salivary glands.	Metformin	10-19	interleukin 17A	Mus musculus	81-86
31210335-0	2019	Metformin inhibits LPS-induced inflammatory response in VSMCs by regulating TLR4 and PPAR-gamma.	Metformin	0-9	peroxisome proliferator-activated receptor gamma	Rattus norvegicus	85-95
30334569-5	2019	Metformin also significantly ( p < 0.05) inhibited TAA-induced HIF-1alpha, mTOR, the profibrogenic biomarker alpha-smooth muscle actin, tissue inhibitor of metalloproteinases-1, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase in harvested liver homogenates and blood samples.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	63-73
30334569-5	2019	Metformin also significantly ( p < 0.05) inhibited TAA-induced HIF-1alpha, mTOR, the profibrogenic biomarker alpha-smooth muscle actin, tissue inhibitor of metalloproteinases-1, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase in harvested liver homogenates and blood samples.	Metformin	0-9	mechanistic target of rapamycin kinase	Rattus norvegicus	75-79
30334569-7	2019	We conclude that metformin protects against TAA-induced hepatic injuries in rats, which is associated with the inhibition of mTOR-HIF-1alpha axis and profibrogenic and inflammatory biomarkers; thus, may offer therapeutic potential in humans.	Metformin	17-26	mechanistic target of rapamycin kinase	Rattus norvegicus	125-129
30334569-7	2019	We conclude that metformin protects against TAA-induced hepatic injuries in rats, which is associated with the inhibition of mTOR-HIF-1alpha axis and profibrogenic and inflammatory biomarkers; thus, may offer therapeutic potential in humans.	Metformin	17-26	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	130-140
31042624-4	2019	This study shows that metformin suppressed CD133 expression mainly by affecting the CD133 P1 promoter via adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling but not the mammalian target of rapamycin (mTOR).	Metformin	22-31	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	162-166
31042624-5	2019	AMPK inhibition rescued the reduction of CD133 by metformin.	Metformin	50-59	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	0-4
31042624-9	2019	Our results indicated that metformin-AMPK-CEBPbeta signaling plays a crucial role in regulating the gene expression of CD133.	Metformin	27-36	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	37-41
31031016-5	2019	Mechanistically, specific activation of the PP2A-GSK3beta axis was the sum of metformin-induced inhibition of CIP2A, a PP2A suppressor, and of upregulation of the PP2A regulatory subunit B56delta by low glucose, leading to an active PP2A-B56delta complex with high affinity toward GSK3beta.	Metformin	78-87	cellular inhibitor of PP2A	Homo sapiens	110-115
30703397-6	2019	At the molecular level, we found that metformin pretreatment not only prevented the changes of FOS, JUNB and BDNF at both mRNA and protein levels, but also increased the expression of the postsynaptic scaffold genes HOMER and PSD95 after exposure to hypobaric hypoxia.	Metformin	38-47	Fos proto-oncogene, AP-1 transcription factor subunit	Rattus norvegicus	95-98
30703397-6	2019	At the molecular level, we found that metformin pretreatment not only prevented the changes of FOS, JUNB and BDNF at both mRNA and protein levels, but also increased the expression of the postsynaptic scaffold genes HOMER and PSD95 after exposure to hypobaric hypoxia.	Metformin	38-47	brain-derived neurotrophic factor	Rattus norvegicus	109-113
30032440-2	2019	We found that, in ultra-high-molecular-weight polyethylene particle-induced osteolysis mouse models, metformin had bone protect property and reduced the negative regulator of bone formation sclerostin (SOST) and Dickkopf-related protein 1 (DKK1), and increased osteoprotegerin (OPG) secretion and the ratio of OPG/Receptor Activator for Nuclear Factor-kappaB Ligand (RANKL).	Metformin	101-110	sclerostin	Mus musculus	202-206
30032440-2	2019	We found that, in ultra-high-molecular-weight polyethylene particle-induced osteolysis mouse models, metformin had bone protect property and reduced the negative regulator of bone formation sclerostin (SOST) and Dickkopf-related protein 1 (DKK1), and increased osteoprotegerin (OPG) secretion and the ratio of OPG/Receptor Activator for Nuclear Factor-kappaB Ligand (RANKL).	Metformin	101-110	tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)	Mus musculus	261-276
30032440-2	2019	We found that, in ultra-high-molecular-weight polyethylene particle-induced osteolysis mouse models, metformin had bone protect property and reduced the negative regulator of bone formation sclerostin (SOST) and Dickkopf-related protein 1 (DKK1), and increased osteoprotegerin (OPG) secretion and the ratio of OPG/Receptor Activator for Nuclear Factor-kappaB Ligand (RANKL).	Metformin	101-110	tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)	Mus musculus	278-281
30032440-2	2019	We found that, in ultra-high-molecular-weight polyethylene particle-induced osteolysis mouse models, metformin had bone protect property and reduced the negative regulator of bone formation sclerostin (SOST) and Dickkopf-related protein 1 (DKK1), and increased osteoprotegerin (OPG) secretion and the ratio of OPG/Receptor Activator for Nuclear Factor-kappaB Ligand (RANKL).	Metformin	101-110	tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)	Mus musculus	310-313
30032440-4	2019	Metformin (50 muM) significantly decreased SOST and DKK1 mRNA expression, stimulating alkaline phosphatase activity and proliferation of osteoblast, and increased OPG secretion and the ratio of OPG/RANKL, inhibiting osteoclastogenesis.	Metformin	0-9	sclerostin	Mus musculus	43-47
29659176-9	2018	A specific AMPK activator metformin increased Wnt3a, beta-catenin, Nrf2 phosphorylation and activation but reduced the levels of IL-6 and IL-8 in NHBE cells and mouse lungs exposed to CSE.	Metformin	26-35	wingless-type MMTV integration site family, member 3A	Mus musculus	46-51
28727687-8	2018	Administering Dnmt1 inhibitor to control neonates resulted in FAE-like deficits in fear memory and hippocampal allele-specific expression of Igf2, which were reversed by metformin.	Metformin	170-179	DNA methyltransferase 1	Rattus norvegicus	14-19
28727687-9	2018	We propose that neonatal administration of T4 and metformin post FAE affect memory via elevating Dnmt1 and consequently normalizing hippocampal Dio3 and Igf2 expressions in the adult offspring.	Metformin	50-59	DNA methyltransferase 1	Rattus norvegicus	97-102
29914345-5	2018	RESULTS: Our association analysis revealed that SLC22A2 rs316019 and SLC47A2 rs12943590 were significantly associated with metformin drug response across co-dominant and dominant models, respectively.	Metformin	123-132	solute carrier family 22 member 2	Homo sapiens	48-55
29914345-7	2018	CONCLUSION: The present study proposes a role of SLC22A2 rs316019 and SLC47A2 rs12943590 in the pharmacokinetic action of metformin.	Metformin	122-131	solute carrier family 22 member 2	Homo sapiens	49-56
29635803-9	2018	Metformin inhibited vimentin expression in both normal and tumor cells.	Metformin	0-9	vimentin	Homo sapiens	20-28
30050950-6	2018	We observed that TGF-beta1 significantly reduced E-cadherin expression and upregulated the expressions of FN, alpha-SMA, and Egr-1, which can be reversed by metformin.	Metformin	157-166	cadherin 1	Rattus norvegicus	49-59
29954074-5	2018	The linear range of the assay was 100 to 5000 ng mL-1 and 2 to 100 ng mL-1 for metformin and rosuvastatin, respectively.	Metformin	79-88	L1 cell adhesion molecule	Mus musculus	49-59
32055553-0	2018	Effect of plasma membrane monoamine transporter genetic variants on pharmacokinetics of metformin in humans.	Metformin	88-97	solute carrier family 29 member 4	Homo sapiens	10-47
32055553-1	2018	Metformin, an oral hypoglycemic agent belonging to biguanide class, is widely used to treat type 2 diabetes mellitus, and several drug transporters such as organic cation transporters (OCTs), multidrug and toxin extrusion transporter (MATE), and plasma membrane monoamine transporter (PMAT) are thought to affect its disposition.	Metformin	0-9	solute carrier family 29 member 4	Homo sapiens	246-283
32055553-1	2018	Metformin, an oral hypoglycemic agent belonging to biguanide class, is widely used to treat type 2 diabetes mellitus, and several drug transporters such as organic cation transporters (OCTs), multidrug and toxin extrusion transporter (MATE), and plasma membrane monoamine transporter (PMAT) are thought to affect its disposition.	Metformin	0-9	solute carrier family 29 member 4	Homo sapiens	285-289
29759071-14	2018	Additionally, the phosphorylation of AMPK after metformin treatment was 2-fold higher, and the expression of sterol regulatory element-binding protein-1c (SREBP-1c) after metformin treatment was about 2-fold lower compared to high glucose and high insulin group in HepG2 cells.	Metformin	171-180	sterol regulatory element binding transcription factor 1	Homo sapiens	155-163
29922426-6	2018	Results: The MPO activity and MDA level were decreased in the metformin-treated groups (P&lt;0.05).	Metformin	62-71	myeloperoxidase	Rattus norvegicus	13-16
31061679-3	2019	The purpose of this study was to investigate if yoghurt enriched with curcumin and metformin, individually or as mixtures, ameliorates physiometabolic parameters, glycoxidative stress biomarkers, and paraoxonase 1 (PON 1) activity in diabetic rats.	Metformin	83-92	paraoxonase 1	Rattus norvegicus	200-213
31061679-3	2019	The purpose of this study was to investigate if yoghurt enriched with curcumin and metformin, individually or as mixtures, ameliorates physiometabolic parameters, glycoxidative stress biomarkers, and paraoxonase 1 (PON 1) activity in diabetic rats.	Metformin	83-92	paraoxonase 1	Rattus norvegicus	215-220
31091555-9	2019	Both metformin and CO can differentially induce several protein factors, including fibroblast growth factor 21 (FGF21) and sestrin2 (SESN2), which maintain metabolic homeostasis; nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of the antioxidant response; and REDD1, which exhibits an anticancer effect.	Metformin	5-14	DNA damage inducible transcript 4	Homo sapiens	283-288
31105845-8	2019	Treatment of NOD mice with metformin significantly mitigated autoimmune insulitis and substantially decreased the number of pro-inflammatory IFN-gamma+ as well as IL17+ CD4 T cells in the spleens of NOD mice.	Metformin	27-36	interleukin 17A	Mus musculus	163-167
31105845-8	2019	Treatment of NOD mice with metformin significantly mitigated autoimmune insulitis and substantially decreased the number of pro-inflammatory IFN-gamma+ as well as IL17+ CD4 T cells in the spleens of NOD mice.	Metformin	27-36	CD4 antigen	Mus musculus	169-172
31205529-0	2019	Metformin Induces Apoptosis and Inhibits Proliferation through the AMP-Activated Protein Kinase and Insulin-like Growth Factor 1 Receptor Pathways in the Bile Duct Cancer Cells.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	100-137
31205529-9	2019	Metformin inhibited mammalian target of rapamycin (mTOR) by activation of tuberous sclerosis complex 2 (TSC-2) through phosphorylation of adenosine monophosphate-activated protein kinase at threonine-172 (AMPKThr172).	Metformin	0-9	TSC complex subunit 2	Homo sapiens	74-102
31205529-9	2019	Metformin inhibited mammalian target of rapamycin (mTOR) by activation of tuberous sclerosis complex 2 (TSC-2) through phosphorylation of adenosine monophosphate-activated protein kinase at threonine-172 (AMPKThr172).	Metformin	0-9	TSC complex subunit 2	Homo sapiens	104-109
31205529-11	2019	Metformin blocked the inhibitory effect of insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor substrate 1 (IRS-1) pathway on TSC-2, and hyperglycemia impaired metformin-induced inhibition of IGF-1R/IRS-1 pathway and modulated the invasiveness of bile duct cancer cells; however, this effect was impaired by hyperglycemia.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	43-80
31205529-11	2019	Metformin blocked the inhibitory effect of insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor substrate 1 (IRS-1) pathway on TSC-2, and hyperglycemia impaired metformin-induced inhibition of IGF-1R/IRS-1 pathway and modulated the invasiveness of bile duct cancer cells; however, this effect was impaired by hyperglycemia.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	82-88
31205529-11	2019	Metformin blocked the inhibitory effect of insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor substrate 1 (IRS-1) pathway on TSC-2, and hyperglycemia impaired metformin-induced inhibition of IGF-1R/IRS-1 pathway and modulated the invasiveness of bile duct cancer cells; however, this effect was impaired by hyperglycemia.	Metformin	0-9	TSC complex subunit 2	Homo sapiens	138-143
31205529-11	2019	Metformin blocked the inhibitory effect of insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor substrate 1 (IRS-1) pathway on TSC-2, and hyperglycemia impaired metformin-induced inhibition of IGF-1R/IRS-1 pathway and modulated the invasiveness of bile duct cancer cells; however, this effect was impaired by hyperglycemia.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	204-210
31205529-11	2019	Metformin blocked the inhibitory effect of insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor substrate 1 (IRS-1) pathway on TSC-2, and hyperglycemia impaired metformin-induced inhibition of IGF-1R/IRS-1 pathway and modulated the invasiveness of bile duct cancer cells; however, this effect was impaired by hyperglycemia.	Metformin	172-181	insulin like growth factor 1 receptor	Homo sapiens	43-80
31205529-11	2019	Metformin blocked the inhibitory effect of insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor substrate 1 (IRS-1) pathway on TSC-2, and hyperglycemia impaired metformin-induced inhibition of IGF-1R/IRS-1 pathway and modulated the invasiveness of bile duct cancer cells; however, this effect was impaired by hyperglycemia.	Metformin	172-181	insulin like growth factor 1 receptor	Homo sapiens	82-88
31205529-11	2019	Metformin blocked the inhibitory effect of insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor substrate 1 (IRS-1) pathway on TSC-2, and hyperglycemia impaired metformin-induced inhibition of IGF-1R/IRS-1 pathway and modulated the invasiveness of bile duct cancer cells; however, this effect was impaired by hyperglycemia.	Metformin	172-181	TSC complex subunit 2	Homo sapiens	138-143
31205529-11	2019	Metformin blocked the inhibitory effect of insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor substrate 1 (IRS-1) pathway on TSC-2, and hyperglycemia impaired metformin-induced inhibition of IGF-1R/IRS-1 pathway and modulated the invasiveness of bile duct cancer cells; however, this effect was impaired by hyperglycemia.	Metformin	172-181	insulin like growth factor 1 receptor	Homo sapiens	204-210
29504694-9	2018	We suggest that Glo1, together with miR-101, might be potential therapeutic targets for metastatic PCa, possibly by metformin administration.	Metformin	116-125	glyoxalase I	Homo sapiens	16-20
29728793-9	2018	Taken together, these findings suggest that metformin functions as a neuroprotective agent following SCI by promoting autophagy and inhibiting apoptosis by regulating the mTOR/P70S6K signaling pathway.	Metformin	44-53	ribosomal protein S6 kinase B1	Homo sapiens	176-182
29232177-15	2018	Fibroblast CAV1 expression is required for metformin to disrupt metabolic coupling and decrease xenograft size.	Metformin	43-52	caveolin 1, caveolae protein	Mus musculus	11-15
29693804-0	2018	Synergistic Growth Inhibitory Effects of Chrysin and Metformin Combination on Breast Cancer Cells through hTERT and Cyclin D1 Suppression Objective: To explore the possibility of a novel chemopreventive strategy for improving breast cancer treatment,the anticancer effects of a combination two natural compounds, Chrysin and Metformin, against T47D breast cancercells were investigated.	Metformin	53-62	telomerase reverse transcriptase	Homo sapiens	106-111
29693804-5	2018	Conclusion: The conmbinationof metformin and chrysin suppressing hTERT and cyclin D1 gene expression might offer an appropriate approach forbreast cancer therapy.	Metformin	31-40	telomerase reverse transcriptase	Homo sapiens	65-70
29576625-2	2018	Previous studies suggest an increased dependency on glutaminolysis in IDH1/2 mutant cells, which resulted in clinical trials with the drugs CB-839, metformin and chloroquine.	Metformin	148-157	isocitrate dehydrogenase (NADP(+)) 1	Homo sapiens	70-74
29719841-6	2018	Results: Histopathological analysis showed that metformin pre-treatment significantly decreased leukocyte infiltration, myeloperoxidase activity and also malondialdehyde level.	Metformin	48-57	myeloperoxidase	Rattus norvegicus	120-135
29393487-0	2018	Effects of metformin on the expression of AMPK and STAT3 in the spinal dorsal horn of rats with neuropathic pain.	Metformin	11-20	signal transducer and activator of transcription 3	Rattus norvegicus	51-56
29393487-7	2018	The present study investigated the analgesic effect of metformin on NP induced by chronic constriction injury (CCI), and the influence of metformin on the expression of AMPK and STAT3 in the spinal dorsal horn (SDH).	Metformin	138-147	signal transducer and activator of transcription 3	Rattus norvegicus	178-183
29393487-9	2018	Administering intraperitoneal injections of metformin (200 mg/kg) for 6 successive days activated AMPK and suppressed the expression of p-STAT3, in addition to reversing hyperalgesia.	Metformin	44-53	signal transducer and activator of transcription 3	Rattus norvegicus	138-143
29253574-8	2018	Meanwhile, metformin notably suppressed the activation of P65 NF-kappaB, mTOR and S6K, reduced Bace1 protein expression.	Metformin	11-20	v-rel reticuloendotheliosis viral oncogene homolog A (avian)	Mus musculus	58-71
29253574-8	2018	Meanwhile, metformin notably suppressed the activation of P65 NF-kappaB, mTOR and S6K, reduced Bace1 protein expression.	Metformin	11-20	mechanistic target of rapamycin kinase	Mus musculus	73-77
29253574-8	2018	Meanwhile, metformin notably suppressed the activation of P65 NF-kappaB, mTOR and S6K, reduced Bace1 protein expression.	Metformin	11-20	beta-site APP cleaving enzyme 1	Mus musculus	95-100
29253574-9	2018	Our data suggest that metformin can exert functional recovery of memory deficits and neuroprotective effect on APP/PS1 mice via triggering neurogenesis and anti-inflammation mediated by regulating AMPK/mTOR/S6K/Bace1 and AMPK/P65 NF-kappaB signaling pathways in the hippocampus, which may contribute to improvement in neurological deficits.	Metformin	22-31	presenilin 1	Mus musculus	115-118
29253574-9	2018	Our data suggest that metformin can exert functional recovery of memory deficits and neuroprotective effect on APP/PS1 mice via triggering neurogenesis and anti-inflammation mediated by regulating AMPK/mTOR/S6K/Bace1 and AMPK/P65 NF-kappaB signaling pathways in the hippocampus, which may contribute to improvement in neurological deficits.	Metformin	22-31	mechanistic target of rapamycin kinase	Mus musculus	202-206
29253574-9	2018	Our data suggest that metformin can exert functional recovery of memory deficits and neuroprotective effect on APP/PS1 mice via triggering neurogenesis and anti-inflammation mediated by regulating AMPK/mTOR/S6K/Bace1 and AMPK/P65 NF-kappaB signaling pathways in the hippocampus, which may contribute to improvement in neurological deficits.	Metformin	22-31	beta-site APP cleaving enzyme 1	Mus musculus	211-216
29253574-9	2018	Our data suggest that metformin can exert functional recovery of memory deficits and neuroprotective effect on APP/PS1 mice via triggering neurogenesis and anti-inflammation mediated by regulating AMPK/mTOR/S6K/Bace1 and AMPK/P65 NF-kappaB signaling pathways in the hippocampus, which may contribute to improvement in neurological deficits.	Metformin	22-31	v-rel reticuloendotheliosis viral oncogene homolog A (avian)	Mus musculus	226-239
29490689-0	2018	Metformin improves ovarian follicle dynamics by reducing theca cell proliferation and CYP-17 expression in an androgenized rat model.	Metformin	0-9	cytochrome P450, family 17, subfamily a, polypeptide 1	Rattus norvegicus	86-92
29490689-3	2018	The aim of this study was to analyze the effect of metformin on CYP-17 expression, follicular dynamics, and proliferative parameters in neonatally androgenized female rats.	Metformin	51-60	cytochrome P450, family 17, subfamily a, polypeptide 1	Rattus norvegicus	64-70
29490689-10	2018	RESULTS: The comparison of the GA and GAmet animals revealed that metformin decreased the weight as well as the glucose and insulin levels, slowed the proliferation of the theca interna and interstitial cells, as evidenced by Ki-67 and VEGF-A expression, and diminished CYP17 expression in the analyzed ovarian structures.	Metformin	66-75	vascular endothelial growth factor A	Rattus norvegicus	236-242
29490689-10	2018	RESULTS: The comparison of the GA and GAmet animals revealed that metformin decreased the weight as well as the glucose and insulin levels, slowed the proliferation of the theca interna and interstitial cells, as evidenced by Ki-67 and VEGF-A expression, and diminished CYP17 expression in the analyzed ovarian structures.	Metformin	66-75	cytochrome P450, family 17, subfamily a, polypeptide 1	Rattus norvegicus	270-275
29490689-12	2018	CONCLUSION: Metformin improves the carbohydrate metabolism, reduces proliferation, and decreases CYP-17 expression in the follicular structures of androgenized rats.	Metformin	12-21	cytochrome P450, family 17, subfamily a, polypeptide 1	Rattus norvegicus	97-103
29681936-0	2018	Metformin Regulating miR-34a Pathway to Inhibit Egr1 in Rat Mesangial Cells Cultured with High Glucose.	Metformin	0-9	microRNA 34a	Rattus norvegicus	21-28
29681936-3	2018	Aim of the Study: To clarify the function of Egr1 on the inflammation and fibrosis in high glucose-cultured MCs, as well as to explore the effects of metformin on miR-34a pathway and Egr1 expression.	Metformin	150-159	microRNA 34a	Rattus norvegicus	163-170
29681936-11	2018	Metformin attenuates high glucose-stimulated inflammation and fibrosis in MCs by regulating miR-34a-mediated SIRT1/AMPKalpha activity and the downstream Egr1 protein.	Metformin	0-9	microRNA 34a	Rattus norvegicus	92-99
29444159-0	2018	Antitumor effects of metformin via indirect inhibition of protein phosphatase 2A in patients with endometrial cancer.	Metformin	21-30	protein phosphatase 2 phosphatase activator	Homo sapiens	66-80
30922066-8	2019	Autophagy was enhanced in the hearts from metformin-treated mice, as indicated by increase of myocardial microtubule-associated protein-1 LC-3 (light chain 3)-II levels and LC3-II/-I ratios as well as levels of cathepsin D and ATP.	Metformin	42-51	cathepsin D	Mus musculus	211-222
30922066-10	2019	Finally, autophagic flux assays using short-term chloroquine treatment revealed that autophagy was activated in delta-sarcoglycan-deficient hearts and was further augmented by metformin treatment.	Metformin	176-185	sarcoglycan, delta (dystrophin-associated glycoprotein)	Mus musculus	112-129
29319171-10	2018	Two target genes of Metformin were significantly interacted with six hub genes (HADHB, NDUFS3, TAF1, MYC, HNFF4A, and MAX) with significant changes in expression values (P &lt; 0.05, t-test).	Metformin	20-29	hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta	Homo sapiens	80-85
30188871-0	2018	Metformin Regulates the Expression of SK2 and SK3 in the Atria of Rats With Type 2 Diabetes Mellitus Through the NOX4/p38MAPK Signaling Pathway.	Metformin	0-9	NADPH oxidase 4	Rattus norvegicus	113-117
30188871-2	2018	In this study, we hypothesized that the nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4)/p38 mitogen-activated protein kinase (p38MAPK) signaling pathway was involved in the metformin-mediated regulation of SK2 and SK3 expression in the atria of rats with T2DM.	Metformin	186-195	NADPH oxidase 4	Rattus norvegicus	40-93
30188871-2	2018	In this study, we hypothesized that the nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4)/p38 mitogen-activated protein kinase (p38MAPK) signaling pathway was involved in the metformin-mediated regulation of SK2 and SK3 expression in the atria of rats with T2DM.	Metformin	186-195	NADPH oxidase 4	Rattus norvegicus	95-99
30188871-7	2018	The 8-week treatment with metformin markedly reduced the expression levels of NOX4 mRNA and protein and p-p38MAPK protein, upregulated the SK2 expression, and downregulated the SK3 expression.	Metformin	26-35	NADPH oxidase 4	Rattus norvegicus	78-82
30188871-12	2018	Long-term metformin treatment upregulates SK2 protein expression and downregulates SK3 protein expression by inhibiting the NOX4/p38MAPK signaling pathway.	Metformin	10-19	NADPH oxidase 4	Rattus norvegicus	124-128
30149143-0	2018	Metformin Enhances Cisplatin-Induced Apoptosis and Prevents Resistance to Cisplatin in Co-mutated KRAS/LKB1 NSCLC.	Metformin	0-9	KRAS proto-oncogene, GTPase	Homo sapiens	98-102
30149143-7	2018	In preclinical experiments, metformin produced pro-apoptotic effects and enhanced cisplatin anticancer activity specifically in KRAS/LKB1 co-mutated patient-derived xenografts.	Metformin	28-37	KRAS proto-oncogene, GTPase	Homo sapiens	128-132
30149143-10	2018	Metformin synergizes with cisplatin against KRAS/LKB1 co-mutated tumors, and may prevent or delay the onset of resistance to cisplatin by targeting CD133+ cancer stem cells.	Metformin	0-9	KRAS proto-oncogene, GTPase	Homo sapiens	44-48
30149143-11	2018	This study lays the foundations for combining metformin with standard platinum-based chemotherapy in the treatment of KRAS/LKB1 co-mutated NSCLC.	Metformin	46-55	KRAS proto-oncogene, GTPase	Homo sapiens	118-122
30221473-0	2018	Metformin blocks MYC protein synthesis in colorectal cancer via mTOR-4EBP-eIF4E and MNK1-eIF4G-eIF4E signaling.	Metformin	0-9	MAPK interacting serine/threonine kinase 1	Homo sapiens	84-88
30221473-0	2018	Metformin blocks MYC protein synthesis in colorectal cancer via mTOR-4EBP-eIF4E and MNK1-eIF4G-eIF4E signaling.	Metformin	0-9	eukaryotic translation initiation factor 4 gamma 1	Homo sapiens	89-94
30221473-8	2018	Repression of protein synthesis by metformin preferentially affects cell cycle-associated proteins, by altering signaling through the mTOR-4EBP-eIF4E and MNK1-eIF4G-eIF4E axes.	Metformin	35-44	MAPK interacting serine/threonine kinase 1	Homo sapiens	154-158
30221473-8	2018	Repression of protein synthesis by metformin preferentially affects cell cycle-associated proteins, by altering signaling through the mTOR-4EBP-eIF4E and MNK1-eIF4G-eIF4E axes.	Metformin	35-44	eukaryotic translation initiation factor 4 gamma 1	Homo sapiens	159-164
29739273-8	2018	Metformin is used to treat hyperglycemic endothelial dysfunction through the enhancement of the nitric oxide system, endothelin-derived hyperpolarizing factor and sirtuin 1.	Metformin	0-9	sirtuin 1	Homo sapiens	163-172
30348113-6	2018	RESULTS: During the first year, the GFR decreased by 2.5% in Metformin Group and by 16% in Controls; thereafter, renal function remained stable in Metformin Group and further decreased in Controls, reaching a 50% difference after 3 years of observation.	Metformin	61-70	Rap guanine nucleotide exchange factor 5	Homo sapiens	36-39
30348113-7	2018	Accordingly, the overall crude loss of GFR, estimated by a linear mixed model, resulted slower in the Metformin than in Control Group (- 0.9; 95% C.I.	Metformin	102-111	Rap guanine nucleotide exchange factor 5	Homo sapiens	39-42
30416652-9	2018	Metformin and cisplatin co-treatment significantly inhibited N-cadherin and MMP-9 expression.	Metformin	0-9	cadherin 2	Homo sapiens	61-71
30416652-9	2018	Metformin and cisplatin co-treatment significantly inhibited N-cadherin and MMP-9 expression.	Metformin	0-9	matrix metallopeptidase 9	Homo sapiens	76-81
30118850-1	2018	The aim of this study was to explore the influence of food on P-glycoprotein (P-gp) relative expression in both male and female rats, and its effect on intestinal permeation of P-gp substrates (ranitidine and ganciclovir) and a P-gp non-substrate (metformin).	Metformin	248-257	ATP-binding cassette, subfamily B (MDR/TAP), member 1B	Rattus norvegicus	62-76
30118850-1	2018	The aim of this study was to explore the influence of food on P-glycoprotein (P-gp) relative expression in both male and female rats, and its effect on intestinal permeation of P-gp substrates (ranitidine and ganciclovir) and a P-gp non-substrate (metformin).	Metformin	248-257	ATP-binding cassette, subfamily B (MDR/TAP), member 1B	Rattus norvegicus	78-82
30118850-1	2018	The aim of this study was to explore the influence of food on P-glycoprotein (P-gp) relative expression in both male and female rats, and its effect on intestinal permeation of P-gp substrates (ranitidine and ganciclovir) and a P-gp non-substrate (metformin).	Metformin	248-257	ATP-binding cassette, subfamily B (MDR/TAP), member 1B	Rattus norvegicus	177-181
30118850-1	2018	The aim of this study was to explore the influence of food on P-glycoprotein (P-gp) relative expression in both male and female rats, and its effect on intestinal permeation of P-gp substrates (ranitidine and ganciclovir) and a P-gp non-substrate (metformin).	Metformin	248-257	ATP-binding cassette, subfamily B (MDR/TAP), member 1B	Rattus norvegicus	177-181
30364350-8	2018	Analysis of the stroma at the invasive front in ECE nodal specimens from both HPV-HNSCC and HPV+ OPSCC metformin treated specimens showed increased CD8+ effector T cell infiltrate (mean 22.8%) compared to archival specimens (mean 10.7%) (p = 0.006).	Metformin	103-112	CD8a molecule	Homo sapiens	148-151
30364350-11	2018	Moreover, we present the first in vivo human evidence that metformin may also trigger increased CD8+ Teff and FoxP3+ Tregs in the TME, suggesting an immunomodulatory effect in HNSCC.	Metformin	59-68	CD8a molecule	Homo sapiens	96-99
30275441-0	2018	Metformin Increases Cardiac Rupture After Myocardial Infarction via the AMPK-MTOR/PGC-1alpha Signaling Pathway in Rats with Acute Myocardial Infarction.	Metformin	0-9	mechanistic target of rapamycin kinase	Rattus norvegicus	77-81
30003335-10	2018	In conclusion, metformin or L-citrulline supplementation to BMD patients results in remarkable antidromic changes of the AGAT and GAMT pathways.	Metformin	15-24	glycine amidinotransferase	Homo sapiens	121-125
29334602-9	2018	Expression of fatty acid synthase (FASN) was significantly decreased in tumor specimens treated with metformin and TMZ.	Metformin	101-110	fatty acid synthase	Homo sapiens	14-33
29334602-9	2018	Expression of fatty acid synthase (FASN) was significantly decreased in tumor specimens treated with metformin and TMZ.	Metformin	101-110	fatty acid synthase	Homo sapiens	35-39
29334602-11	2018	The combination of high-dose metformin and TMZ inhibited FASN expression in an orthotopic model.	Metformin	29-38	fatty acid synthase	Homo sapiens	57-61
29862627-8	2018	Gene knockdown by RNAi showed that MATE1 and PMAT reduction attenuated the antilipolytic effect of metformin but only PMAT knockdown decreased the effect of all three biguanides.	Metformin	99-108	solute carrier family 47 member 1	Homo sapiens	35-40
30093416-2	2018	OCT2-expressing HEK293 and MDCKII cells were used to predict in vivo renal secretory clearance (CLr,sec) of metformin.	Metformin	108-117	POU class 2 homeobox 2	Homo sapiens	0-4
30093416-6	2018	After correcting for percent of OCT2 expressed in the plasma membrane and the resting membrane potential (millivolts) difference between the OCT2-expressing cells and the renal epithelial cells, the predicted CLr,sec of metformin was 250.7 ml/min, a value within the range of the observed CLr,sec of metformin.	Metformin	220-229	POU class 2 homeobox 2	Homo sapiens	141-145
30307162-8	2018	Presence of metformin during 7-day culture with palmitate normalized the level of p-AMPK, p-EIF2alpha, CHOP and cleaved caspase 3 but significantly increased the level of sorcin.	Metformin	12-21	eukaryotic translation initiation factor 2A	Homo sapiens	92-101
30146065-6	2018	Metformin significantly reduced the GDF15 production from treatment-damaged HCC cells by targeting JNK.	Metformin	0-9	growth differentiation factor 15	Homo sapiens	36-41
30146065-7	2018	The use of metformin could attenuate the in vivo fibrotic activities of HSCs promoted by treatment-damaged HCC cells and inhibit GDF15 expression.	Metformin	11-20	growth differentiation factor 15	Homo sapiens	129-134
30146065-8	2018	In conclusion, treatment-damaged HCC accelerates fibrosis by promoting the activities of HSCs via GDF15 secretion, which could be reversed by metformin.	Metformin	142-151	growth differentiation factor 15	Homo sapiens	98-103
30210899-6	2018	Reactivating AMPKalpha by metformin treatment successfully prevents premature bone ageing in Alpl+/- mice by improving the function of endogenous MSCs.	Metformin	26-35	alkaline phosphatase, liver/bone/kidney	Mus musculus	93-97
30206977-0	2018	A unified mitochondria mechanistic target of rapamycin acyl-coenzyme A dehydrogenase 10 signal relay modulation for metformin growth inhibition in human immortalized keratinocytes cells.	Metformin	116-125	acyl-CoA dehydrogenase family member 10	Homo sapiens	55-87
30206977-2	2018	In the current study, we found that after metformin treatment the proliferation of human immortalized keratinocytes (HaCaT) was significantly inhibited, while cell apoptosis was increased in a dose-dependent manner, accompanied with enhanced protein expression of acyl-coenzyme A dehydrogenase 10 (ACAD10).	Metformin	42-51	acyl-CoA dehydrogenase family member 10	Homo sapiens	264-296
30206977-2	2018	In the current study, we found that after metformin treatment the proliferation of human immortalized keratinocytes (HaCaT) was significantly inhibited, while cell apoptosis was increased in a dose-dependent manner, accompanied with enhanced protein expression of acyl-coenzyme A dehydrogenase 10 (ACAD10).	Metformin	42-51	acyl-CoA dehydrogenase family member 10	Homo sapiens	298-304
30206977-6	2018	This study showed that the metformin treatment inhibited HaCaT cells proliferation and promoted apoptosis by affecting the mitochondrial-mTORC1 signaling and elevated the ACAD10 expression.	Metformin	27-36	acyl-CoA dehydrogenase family member 10	Homo sapiens	171-177
29990526-9	2018	In vivo, metformin HCl was detected in rat plasma at 1 h post MN application at a concentration of 0.62 +- 0.51 mug/mL, increasing to 3.76 +- 2.58 mug/ml at 3 h. A maximal concentration of 3.77 +- 2.09 mug/ml was achieved at 24 h. Css was 3.2 mug/mL.	Metformin	9-22	thrombopoietin	Mus musculus	116-118
29990526-9	2018	In vivo, metformin HCl was detected in rat plasma at 1 h post MN application at a concentration of 0.62 +- 0.51 mug/mL, increasing to 3.76 +- 2.58 mug/ml at 3 h. A maximal concentration of 3.77 +- 2.09 mug/ml was achieved at 24 h. Css was 3.2 mug/mL.	Metformin	9-22	thrombopoietin	Mus musculus	151-153
29990526-9	2018	In vivo, metformin HCl was detected in rat plasma at 1 h post MN application at a concentration of 0.62 +- 0.51 mug/mL, increasing to 3.76 +- 2.58 mug/ml at 3 h. A maximal concentration of 3.77 +- 2.09 mug/ml was achieved at 24 h. Css was 3.2 mug/mL.	Metformin	9-22	thrombopoietin	Mus musculus	206-208
29990526-9	2018	In vivo, metformin HCl was detected in rat plasma at 1 h post MN application at a concentration of 0.62 +- 0.51 mug/mL, increasing to 3.76 +- 2.58 mug/ml at 3 h. A maximal concentration of 3.77 +- 2.09 mug/ml was achieved at 24 h. Css was 3.2 mug/mL.	Metformin	9-22	thrombopoietin	Mus musculus	247-249
30191328-3	2018	METHODS: The inhibition by select compounds on the uptake of the probe substrate metformin was assessed in HEK293 cells overexpressing human OCT2, OCT1, MATE1, MATE2-K, and mouse Oct2, Oct1, and Mate1.	Metformin	81-90	POU class 2 homeobox 2	Homo sapiens	141-145
30191328-3	2018	METHODS: The inhibition by select compounds on the uptake of the probe substrate metformin was assessed in HEK293 cells overexpressing human OCT2, OCT1, MATE1, MATE2-K, and mouse Oct2, Oct1, and Mate1.	Metformin	81-90	solute carrier family 47 member 1	Homo sapiens	153-158
30191328-3	2018	METHODS: The inhibition by select compounds on the uptake of the probe substrate metformin was assessed in HEK293 cells overexpressing human OCT2, OCT1, MATE1, MATE2-K, and mouse Oct2, Oct1, and Mate1.	Metformin	81-90	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	185-189
30017802-9	2018	For the [SNAIL/miR-34]:[ZEB/miR-200] system, metformin increased miR-200a, miR-200c and miR-429 levels and decreased miR-34a, SNAIL1 and ZEB1 levels in the TGF-beta-induced EMT.	Metformin	45-54	zinc finger E-box binding homeobox 1	Homo sapiens	137-141
30017802-10	2018	From immunofluorescence, we observed increased E-cadherin and ZEB1 co-expression in metformin-treated cells.	Metformin	84-93	zinc finger E-box binding homeobox 1	Homo sapiens	62-66
30233578-5	2018	Based on the therapeutic effects of the combination of metformin and 2-deoxyglucose (2DG) in lupus models that normalized the expansion of effector CD4+ T cells.	Metformin	55-64	CD4 antigen	Mus musculus	148-151
29884691-2	2018	But reliance on decision tree-based predictions of DDIs at OCT2 that depend on IC50 values can be suspect because they can be influenced by choice of transported substrate; for example, IC50 values for the inhibition of metformin versus MPP transport can vary by 5- to 10-fold.	Metformin	220-229	POU class 2 homeobox 2	Homo sapiens	59-63
29884691-4	2018	To address this question, we screened the inhibitory effectiveness of 20 microM concentrations of several hundred compounds against OCT2-mediated uptake of six structurally distinct substrates: MPP, metformin, N,N,N-trimethyl-2-[methyl(7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino]ethanaminium (NBD-MTMA), TEA, cimetidine, and 4-4-dimethylaminostyryl-N-methylpyridinium (ASP).	Metformin	199-208	POU class 2 homeobox 2	Homo sapiens	132-136
29884691-10	2018	Instead, metformin appears to be a comparatively representative OCT2 substrate for both in vitro and in vivo (clinical) use.	Metformin	9-18	POU class 2 homeobox 2	Homo sapiens	64-68
30154647-0	2018	Combined treatment with metformin and gefitinib overcomes primary resistance to EGFR-TKIs with EGFR mutation via targeting IGF-1R signaling pathway.	Metformin	24-33	insulin like growth factor 1 receptor	Homo sapiens	123-129
29740925-7	2018	Pharmacological doses of metformin in drinking water or intraperitoneal injection significantly elevated the global levels of H3K27me3 in the hepatic tissue of low-density lipoprotein receptor-deficient mice and in the tumor tissues of highly aggressive breast cancer xenograft-bearing mice.	Metformin	25-34	low density lipoprotein receptor	Mus musculus	160-192
30116349-8	2018	Furthermore, secretion of TNF-alpha, IL-1alpha, M-CSF and TCA-3 into the conditioned media was significantly decreased by metformin (5 and 10 mM; P&lt;0.05).	Metformin	122-131	colony stimulating factor 1 (macrophage)	Mus musculus	48-53
29898754-9	2018	We also found a decrease in the number of aromatase-positive, CD68-positive macrophages within the tumor microenvironment, suggesting that metformin targets the immune microenvironment in addition to improving whole-body metabolism.	Metformin	139-148	CD68 molecule	Homo sapiens	62-66
29866066-11	2018	Furthermore, synergy was identified between STF31 (a novel GLUT1 inhibitor) or oxamic acid (an LDH inhibitor) when combined with metformin, an inhibitor of oxidative phosphorylation, resulting in marked inhibition of ovarian cancer cell growth.	Metformin	129-138	solute carrier family 2 member 1	Homo sapiens	59-64
30023463-4	2018	We previously reported that metformin inhibits the phosphorylation of ERK and BEZ235, a dual inhibitor of PI3K and mTOR, has anti-tumor activity against HCT15 CRC cells harboring mutations of KRAS and PIK3CA.	Metformin	28-37	KRAS proto-oncogene, GTPase	Homo sapiens	192-196
29231260-8	2018	This study indicated that metformin imposed inhibitory effect on the HBV-associated HCC by negatively regulating the HULC/p18/miR-200a/ZEB1 signaling pathway.	Metformin	26-35	zinc finger E-box binding homeobox 1	Homo sapiens	135-139
32055553-5	2018	Similarly, subjects with variant rs316019 SNP in OCT2 showed decreased renal clearance of metformin compared to wild-type subjects (586.01 +- 160.54 vs. 699.13 +- 291.40 mL/min, p=0.048).	Metformin	90-99	POU class 2 homeobox 2	Homo sapiens	49-53
29899823-6	2018	Metformin treatment increased the number of lung CD8-effector-memory T and CD4+Foxp3+IL-10+ T cells in B16F10-transplanted mice.	Metformin	0-9	CD4 antigen	Mus musculus	75-78
29795113-0	2018	Inhibition of LCMR1 and ATG12 by demethylation-activated miR-570-3p is involved in the anti-metastasis effects of metformin on human osteosarcoma.	Metformin	114-123	mediator complex subunit 19	Homo sapiens	14-19
29795113-7	2018	Mechanistically, metformin increases miR-570-3p by the demethylation of DNA, and the upregulation of miR-570-3p repressed the translation of its target, LCMR1 and ATG12.	Metformin	17-26	microRNA 5703	Homo sapiens	37-47
29795113-7	2018	Mechanistically, metformin increases miR-570-3p by the demethylation of DNA, and the upregulation of miR-570-3p repressed the translation of its target, LCMR1 and ATG12.	Metformin	17-26	mediator complex subunit 19	Homo sapiens	153-158
29759071-0	2018	Metformin attenuates triglyceride accumulation in HepG2 cells through decreasing stearyl-coenzyme A desaturase 1 expression.	Metformin	0-9	stearoyl-Coenzyme A desaturase 1	Mus musculus	81-112
29759071-4	2018	Therefore, the aim of this study was to investigate whether SCD1 mediated the effect of metformin on TG accumulation.	Metformin	88-97	stearoyl-CoA desaturase	Homo sapiens	60-64
29759071-9	2018	A dual-luciferase reporter assay was used to determine the effect of metformin on the transcriptional activity of the SCD1 promoter.	Metformin	69-78	stearoyl-CoA desaturase	Homo sapiens	118-122
29759071-11	2018	The expression of SCD1 and fatty acid synthetase (FAS) was also decreased to normal level by metformin.	Metformin	93-102	stearoyl-CoA desaturase	Homo sapiens	18-22
29759071-12	2018	Knockdown of SCD1 mimicked the effect of metformin on decreasing TG levels in AML12 cells, and the overexpression of SCD1 attenuated the effect of metformin on decreasing TG accumulation in HepG2 cells.	Metformin	41-50	stearoyl-Coenzyme A desaturase 1	Mus musculus	13-17
29759071-12	2018	Knockdown of SCD1 mimicked the effect of metformin on decreasing TG levels in AML12 cells, and the overexpression of SCD1 attenuated the effect of metformin on decreasing TG accumulation in HepG2 cells.	Metformin	147-156	stearoyl-Coenzyme A desaturase 1	Mus musculus	117-121
29759071-13	2018	The dual-luciferase reporter assay showed that the transcriptional activity of the SCD1 promoter (- 550/+ 199) after metformin treatment was 2-fold lower compared to control group in HepG2 cells.	Metformin	117-126	stearoyl-CoA desaturase	Homo sapiens	83-87
29635345-3	2018	Metformin and the bis-indole substituted analogs also induced expression of several glycolytic genes and Rab4, which has previously been linked to enhancing cell membrane accumulation of Glut4 and overall glucose uptake in C2C12 cells, and these responses were also observed after treatment with metformin and the NR4A1 ligands.	Metformin	0-9	RAB4A, member RAS oncogene family	Mus musculus	105-109
29635345-3	2018	Metformin and the bis-indole substituted analogs also induced expression of several glycolytic genes and Rab4, which has previously been linked to enhancing cell membrane accumulation of Glut4 and overall glucose uptake in C2C12 cells, and these responses were also observed after treatment with metformin and the NR4A1 ligands.	Metformin	296-305	RAB4A, member RAS oncogene family	Mus musculus	105-109
29520103-0	2018	Metformin suppresses melanoma progression by inhibiting KAT5-mediated SMAD3 acetylation, transcriptional activity and TRIB3 expression.	Metformin	0-9	tribbles pseudokinase 3	Mus musculus	118-123
29520103-5	2018	In this study, we found that metformin attenuates melanoma growth and metastasis by reducing TRIB3 expression in non-diabetic C57BL/6 mice and diabetic KK-Ay mice; overexpression of TRIB3 protects metformin from the activation of autophagic flux, the clearance of accumulated tumour-promoting factors and the attenuation of tumour progression.	Metformin	29-38	tribbles pseudokinase 3	Mus musculus	93-98
29520103-5	2018	In this study, we found that metformin attenuates melanoma growth and metastasis by reducing TRIB3 expression in non-diabetic C57BL/6 mice and diabetic KK-Ay mice; overexpression of TRIB3 protects metformin from the activation of autophagic flux, the clearance of accumulated tumour-promoting factors and the attenuation of tumour progression.	Metformin	29-38	tribbles pseudokinase 3	Mus musculus	182-187
29520103-5	2018	In this study, we found that metformin attenuates melanoma growth and metastasis by reducing TRIB3 expression in non-diabetic C57BL/6 mice and diabetic KK-Ay mice; overexpression of TRIB3 protects metformin from the activation of autophagic flux, the clearance of accumulated tumour-promoting factors and the attenuation of tumour progression.	Metformin	197-206	tribbles pseudokinase 3	Mus musculus	182-187
29520103-7	2018	Metformin suppresses SMAD3 phosphorylation and decreases the KAT5/SMAD3 interaction, to attenuate the KAT5-mediated K333 acetylation of SMAD3, reduce the SMAD3 transcriptional activity and subsequent TRIB3 expression, thereby antagonizes melanoma progression.	Metformin	0-9	tribbles pseudokinase 3	Mus musculus	200-205
29520103-8	2018	Together, our study not only defines a molecular mechanism by which metformin protects against melanoma progression by disturbing the KAT5/TRIB3/SMAD3 positive feedback loop in diabetes and non-diabetes mice, but also suggests a candidate diverse utility of metformin in tumour prevention and therapy because of suppressing stress protein TRIB3 expression.	Metformin	68-77	tribbles pseudokinase 3	Mus musculus	139-144
29520103-8	2018	Together, our study not only defines a molecular mechanism by which metformin protects against melanoma progression by disturbing the KAT5/TRIB3/SMAD3 positive feedback loop in diabetes and non-diabetes mice, but also suggests a candidate diverse utility of metformin in tumour prevention and therapy because of suppressing stress protein TRIB3 expression.	Metformin	68-77	tribbles pseudokinase 3	Mus musculus	339-344
29654226-0	2018	Metformin Enhances the Effect of Regorafenib and Inhibits Recurrence and Metastasis of Hepatic Carcinoma After Liver Resection via Regulating Expression of Hypoxia Inducible Factors 2alpha (HIF-2alpha) and 30 kDa HIV Tat-Interacting Protein (TIP30).	Metformin	0-9	HIV-1 Tat interactive protein 2	Mus musculus	242-247
29499335-7	2018	Metformin-mediated activation of AMPK was able to significantly abrogate cholesterol uptake by inhibiting SREBP2-M. Interestingly, although metformin administration attenuated angiotensin (Ang)-II-impaired lipid homeostasis in both aorta and liver tissues of ApoE-/- mice, the results indicate that SREBP2 through LDLR regulates lipid homeostasis in aorta but not in liver tissue.	Metformin	0-9	sterol regulatory element binding factor 2	Mus musculus	106-112
29499335-7	2018	Metformin-mediated activation of AMPK was able to significantly abrogate cholesterol uptake by inhibiting SREBP2-M. Interestingly, although metformin administration attenuated angiotensin (Ang)-II-impaired lipid homeostasis in both aorta and liver tissues of ApoE-/- mice, the results indicate that SREBP2 through LDLR regulates lipid homeostasis in aorta but not in liver tissue.	Metformin	0-9	sterol regulatory element binding factor 2	Mus musculus	299-305
29499335-7	2018	Metformin-mediated activation of AMPK was able to significantly abrogate cholesterol uptake by inhibiting SREBP2-M. Interestingly, although metformin administration attenuated angiotensin (Ang)-II-impaired lipid homeostasis in both aorta and liver tissues of ApoE-/- mice, the results indicate that SREBP2 through LDLR regulates lipid homeostasis in aorta but not in liver tissue.	Metformin	0-9	low density lipoprotein receptor	Mus musculus	314-318
29499335-7	2018	Metformin-mediated activation of AMPK was able to significantly abrogate cholesterol uptake by inhibiting SREBP2-M. Interestingly, although metformin administration attenuated angiotensin (Ang)-II-impaired lipid homeostasis in both aorta and liver tissues of ApoE-/- mice, the results indicate that SREBP2 through LDLR regulates lipid homeostasis in aorta but not in liver tissue.	Metformin	140-149	sterol regulatory element binding factor 2	Mus musculus	299-305
29499335-7	2018	Metformin-mediated activation of AMPK was able to significantly abrogate cholesterol uptake by inhibiting SREBP2-M. Interestingly, although metformin administration attenuated angiotensin (Ang)-II-impaired lipid homeostasis in both aorta and liver tissues of ApoE-/- mice, the results indicate that SREBP2 through LDLR regulates lipid homeostasis in aorta but not in liver tissue.	Metformin	140-149	low density lipoprotein receptor	Mus musculus	314-318
29499335-8	2018	Taken together, AMPK activation inhibits oxidative stress-mediated SREBP2-dependent cholesterol uptake, and moreover, metformin-induced prevention of atheromatic events are in part due to its ability to regulate the SREBP2-LDLR axis.	Metformin	118-127	sterol regulatory element binding factor 2	Mus musculus	216-222
29499335-8	2018	Taken together, AMPK activation inhibits oxidative stress-mediated SREBP2-dependent cholesterol uptake, and moreover, metformin-induced prevention of atheromatic events are in part due to its ability to regulate the SREBP2-LDLR axis.	Metformin	118-127	low density lipoprotein receptor	Mus musculus	223-227
29272251-4	2018	The effects of metformin in cancer cells resemble the patterns observed after treatment with drugs that downregulate specificity protein 1 (Sp1), Sp3 and Sp4 or by knockdown of Sp1, Sp3 and Sp4 by RNA interference.	Metformin	15-24	Sp4 transcription factor	Homo sapiens	154-157
29272251-4	2018	The effects of metformin in cancer cells resemble the patterns observed after treatment with drugs that downregulate specificity protein 1 (Sp1), Sp3 and Sp4 or by knockdown of Sp1, Sp3 and Sp4 by RNA interference.	Metformin	15-24	Sp4 transcription factor	Homo sapiens	190-193
29272251-5	2018	Studies in pancreatic cancer cells clearly demonstrate that metformin decreases expression of Sp1, Sp3, Sp4 and pro-oncogenic Sp-regulated genes, demonstrating that one of the underlying mechanisms of action of metformin as an anticancer agent involves targeting of Sp transcription factors.	Metformin	60-69	Sp4 transcription factor	Homo sapiens	104-107
29272251-5	2018	Studies in pancreatic cancer cells clearly demonstrate that metformin decreases expression of Sp1, Sp3, Sp4 and pro-oncogenic Sp-regulated genes, demonstrating that one of the underlying mechanisms of action of metformin as an anticancer agent involves targeting of Sp transcription factors.	Metformin	211-220	Sp4 transcription factor	Homo sapiens	104-107
29900050-0	2018	Metformin blocks myeloid-derived suppressor cell accumulation through AMPK-DACH1-CXCL1 axis.	Metformin	0-9	dachshund family transcription factor 1	Mus musculus	75-80
29900050-11	2018	Metformin inhibited CXCL1 secretion in ESCC cells and tumor xenografts by enhancing AMPK phosphorylation and inducing DACH1 expression, leading to NF-kappaB inhibition and reducing MDSC migration.	Metformin	0-9	dachshund family transcription factor 1	Mus musculus	118-123
29900050-12	2018	Knockdown of AMPK and DACH1 expression blocked the effect of metformin on MDSC chemotaxis.	Metformin	61-70	dachshund family transcription factor 1	Mus musculus	22-27
29900050-13	2018	Conclusions: A novel anti-tumor effect of metformin, which is mediated by reducing PMN-MDSC accumulation in the tumor microenvironment via AMPK/DACH1/CXCL1 axis.	Metformin	42-51	dachshund family transcription factor 1	Mus musculus	144-149
29390122-0	2018	14-3-3zeta is involved in the anticancer effect of metformin in colorectal carcinoma.	Metformin	51-60	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta	Homo sapiens	0-10
29390122-2	2018	We aimed to test whether 14-3-3zeta affects the anticancer effect of metformin on colorectal carcinoma (CRC).	Metformin	69-78	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta	Homo sapiens	25-35
29390122-6	2018	Of note, metformin induced apoptosis and retarded tumor growth in the CRCs with overexpressed 14-3-3zeta, whereas this action was attenuated when 14-3-3zeta was knocked down.	Metformin	9-18	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta	Homo sapiens	94-104
29390122-6	2018	Of note, metformin induced apoptosis and retarded tumor growth in the CRCs with overexpressed 14-3-3zeta, whereas this action was attenuated when 14-3-3zeta was knocked down.	Metformin	9-18	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta	Homo sapiens	146-156
29390122-7	2018	Moreover, either metformin or downregulation of 14-3-3zeta noticeably activated AMP-dependent protein kinase (AMPK) signaling, whereas the effect of metformin was attenuated when the 14-3-3zeta expression was decreased.	Metformin	149-158	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta	Homo sapiens	183-193
29390122-8	2018	Taken together, our results suggest that 14-3-3zeta may be associated with carcinogenesis and poor prognosis of CRCs associated with diabetes, and metformin may reverse the AMPK inhibition caused by 14-3-3zeta in CRCs in the background of diabetes.	Metformin	147-156	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta	Homo sapiens	199-209
29390122-9	2018	Our study should lead to a better understanding of the anticancer activity of metformin and points to possible application of metformin to the treatment of cancers overexpressing 14-3-3zeta.	Metformin	126-135	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta	Homo sapiens	179-189
29513760-6	2018	Several inflammatory molecules upregulated by tumor necrosis factor-alpha in human retinal vascular endothelial cells were markedly reduced by metformin, including nuclear factor kappa B p65 (NFkappaB p65), intercellular adhesion molecule-1 (ICAM-1), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8).	Metformin	143-152	intercellular adhesion molecule 1	Homo sapiens	207-240
29513760-6	2018	Several inflammatory molecules upregulated by tumor necrosis factor-alpha in human retinal vascular endothelial cells were markedly reduced by metformin, including nuclear factor kappa B p65 (NFkappaB p65), intercellular adhesion molecule-1 (ICAM-1), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8).	Metformin	143-152	intercellular adhesion molecule 1	Homo sapiens	242-248
29513760-8	2018	Activation of AMP-activated protein kinase was found to play a partial role in the suppression of ICAM-1 and MCP-1 by metformin, but not in those of NFkappaB p65 and IL-8.	Metformin	118-127	intercellular adhesion molecule 1	Homo sapiens	98-104
29456653-5	2018	Increased expression of endoplasmic reticulum (ER) stress marker proteins, including C/EBP-homologous protein, eukaryotic translation initiation factor 2A, and glucose-regulated protein 78 kDa, induced by ox-LDL was also reversed by metformin.	Metformin	233-242	eukaryotic translation initiation factor 2A	Homo sapiens	111-192
29435022-5	2018	A Transwell assay and western blot analysis revealed that metformin inhibited the migration and invasion of EC109 cells, nuclear factor-kappaB activation, matrix metallopeptidase 9 and N-cadherin expression in a phosphorylated-AKT dependent manner.	Metformin	58-67	matrix metallopeptidase 9	Homo sapiens	155-180
29435022-5	2018	A Transwell assay and western blot analysis revealed that metformin inhibited the migration and invasion of EC109 cells, nuclear factor-kappaB activation, matrix metallopeptidase 9 and N-cadherin expression in a phosphorylated-AKT dependent manner.	Metformin	58-67	cadherin 2	Homo sapiens	185-195
29415987-8	2018	Mechanistically, both HSP60 knockdown and oxidative phosphorylation (OXPHOS) inhibition by metformin decreased Erk1/2 phosphorylation and induced apoptosis and cell cycle arrest, whereas Erk1/2 reactivation with EGF promoted cell proliferation.	Metformin	91-100	heat shock protein family D (Hsp60) member 1	Homo sapiens	22-27
29415987-11	2018	Thus, our findings indicate for the first time that HSP60 may serve as a novel diagnostic target of human pancreatic cancer, and that inhibition of mitochondrial function using drugs such as metformin may be a beneficial therapeutic strategy targeting pancreatic cancer cells with aberrant function of the HSP60/OXPHOS/Erk1/2 phosphorylation axis.	Metformin	191-200	heat shock protein family D (Hsp60) member 1	Homo sapiens	306-311
29385181-10	2018	In human primary hepatocytes, metformin treatment inhibited mTOR and PTEN, but up-regulated p62, LC3BII and Caspase 3.	Metformin	30-39	nucleoporin 62	Homo sapiens	92-95
29278707-0	2018	Metformin ameliorates activation of hepatic stellate cells and hepatic fibrosis by succinate and GPR91 inhibition.	Metformin	0-9	succinate receptor 1	Homo sapiens	97-102
29278707-10	2018	RESULTS: In our study, metformin and 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR), which is an analog of adenosine monophosphate, were shown to suppress alpha-SMA expression via enhanced phosphorylation of AMP-activated protein kinase (AMPK) and inhibition of succinate-GPR91 signaling in activated LX-2 cells induced by palmitate- or succinate.	Metformin	23-32	succinate receptor 1	Homo sapiens	288-293
29278707-16	2018	CONCLUSION: This study shows that metformin can attenuate activation of HSCs by activating the AMPK pathway and inhibiting the succinate-GPR91 pathway.	Metformin	34-43	succinate receptor 1	Homo sapiens	137-142
29351188-8	2018	Metformin promoted HUVEC migration and inhibited apoptosis via upregulation of vascular endothelial growth factor (VEGF) receptors (VEGFR1/R2), fatty acid binding protein 4 (FABP4), ERK/mitogen-activated protein kinase signaling, chemokine ligand 8, lymphocyte antigen 96, Rho kinase 1 (ROCK1), matrix metalloproteinase 16 (MMP16) and tissue factor inhibitor-2 under hyperglycemia-chemical hypoxia.	Metformin	0-9	lymphocyte antigen 96	Homo sapiens	250-271
28689771-8	2018	Therapeutic interventions with tacrolimus or metformin normalized the expression of decidual IFNgamma, PGR and FKBP52, increased co-localization of protein inhibitor of activated STATy (PIASy) to PGR and resulted in the upregulation of uterine IL11and LIF.	Metformin	45-54	progesterone receptor	Mus musculus	103-106
28689771-8	2018	Therapeutic interventions with tacrolimus or metformin normalized the expression of decidual IFNgamma, PGR and FKBP52, increased co-localization of protein inhibitor of activated STATy (PIASy) to PGR and resulted in the upregulation of uterine IL11and LIF.	Metformin	45-54	progesterone receptor	Mus musculus	196-199
28689771-8	2018	Therapeutic interventions with tacrolimus or metformin normalized the expression of decidual IFNgamma, PGR and FKBP52, increased co-localization of protein inhibitor of activated STATy (PIASy) to PGR and resulted in the upregulation of uterine IL11and LIF.	Metformin	45-54	interleukin 11	Mus musculus	244-248
28689771-10	2018	To our knowledge this is the first report to show that the impact of HFD on the hemochorial implantation is at least in part mediated through disruption of PGR signaling at nidation and that immunosuppression with tacrolimus or treatment with metformin restores PGR-mediated influences during implantation in the obese and diabetic subjects.	Metformin	243-252	progesterone receptor	Mus musculus	156-159
28689771-10	2018	To our knowledge this is the first report to show that the impact of HFD on the hemochorial implantation is at least in part mediated through disruption of PGR signaling at nidation and that immunosuppression with tacrolimus or treatment with metformin restores PGR-mediated influences during implantation in the obese and diabetic subjects.	Metformin	243-252	progesterone receptor	Mus musculus	262-265
29552319-8	2018	Compared with metformin, thiazolidinediones significantly reduced the alanine transaminase, aspartate aminotransferase and gamma-glutamyl transpeptidase.	Metformin	14-23	inactive glutathione hydrolase 2	Homo sapiens	123-152
29323154-3	2018	Herein, metformin induced pAMPK activation and pS6 suppression in metformin-sensitive (HT29) cells, but not in metformin-resistant (SW620) cells.	Metformin	8-17	taste 2 receptor member 63 pseudogene	Homo sapiens	47-50
29323154-3	2018	Herein, metformin induced pAMPK activation and pS6 suppression in metformin-sensitive (HT29) cells, but not in metformin-resistant (SW620) cells.	Metformin	66-75	taste 2 receptor member 63 pseudogene	Homo sapiens	47-50
29323154-3	2018	Herein, metformin induced pAMPK activation and pS6 suppression in metformin-sensitive (HT29) cells, but not in metformin-resistant (SW620) cells.	Metformin	66-75	taste 2 receptor member 63 pseudogene	Homo sapiens	47-50
29323154-8	2018	Knockdown of glutaminase 1, ASCT2, and c-Myc induced significant CSC-suppression and enhanced CSC-suppressing effect of metformin and compound 968.	Metformin	120-129	solute carrier family 1 member 5	Homo sapiens	28-33
29056513-0	2018	Metformin Alters Upper Small Intestinal Microbiota that Impact a Glucose-SGLT1-Sensing Glucoregulatory Pathway.	Metformin	0-9	solute carrier family 5 member 1	Rattus norvegicus	73-78
29056513-2	2018	In parallel, metformin regulates upper small intestinal sodium glucose cotransporter-1 (SGLT1), but whether changes of the microbiota or SGLT1-dependent pathways in the upper small intestine mediate metformin action is unknown.	Metformin	13-22	solute carrier family 5 member 1	Rattus norvegicus	56-86
29056513-2	2018	In parallel, metformin regulates upper small intestinal sodium glucose cotransporter-1 (SGLT1), but whether changes of the microbiota or SGLT1-dependent pathways in the upper small intestine mediate metformin action is unknown.	Metformin	13-22	solute carrier family 5 member 1	Rattus norvegicus	88-93
29056513-5	2018	Upper small intestinal metformin treatment restores SGLT1 expression and glucose sensing while shifting the upper small intestinal microbiota partly by increasing the abundance of Lactobacillus.	Metformin	23-32	solute carrier family 5 member 1	Rattus norvegicus	52-57
29056513-6	2018	Transplantation of upper small intestinal microbiota from metformin-treated HFD rats to the upper small intestine of untreated HFD rats also increases the upper small intestinal abundance of Lactobacillus and glucose sensing via an upregulation of SGLT1 expression.	Metformin	58-67	solute carrier family 5 member 1	Rattus norvegicus	248-253
29056513-7	2018	Thus, we demonstrate that metformin alters upper small intestinal microbiota and impacts a glucose-SGLT1-sensing glucoregulatory pathway.	Metformin	26-35	solute carrier family 5 member 1	Rattus norvegicus	99-104
29779024-1	2018	BACKGROUND: Metformin inhibits cyclic AMP generation and activates AMP-activated protein kinase (AMPK), which inhibits the cystic fibrosis transmembrane conductance regulator and Mammalian Target of Rapamycin pathways.	Metformin	12-21	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	67-95
29779024-1	2018	BACKGROUND: Metformin inhibits cyclic AMP generation and activates AMP-activated protein kinase (AMPK), which inhibits the cystic fibrosis transmembrane conductance regulator and Mammalian Target of Rapamycin pathways.	Metformin	12-21	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	97-101
29779024-10	2018	Furthermore, results may support or refute the hypothesis that metformin effects on disease progression are mediated through the activation of the AMPK pathway.	Metformin	63-72	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	147-151
29991051-11	2018	Activation of AMPK by AICAR and metformin significantly improved sperm motility, membrane integrity and acrosome reaction, largely maintained sperm mitochondrial membrane potentials, lactate content and ATP content, and enhanced the activity of AMPK, PK and LDH, whereas inhibition by Compound C triggered the converse effects.	Metformin	32-41	lactate dehydrogenase	Capra hircus	258-261
30036874-0	2018	Metformin Alleviates Radiation-Induced Skin Fibrosis via the Downregulation of FOXO3.	Metformin	0-9	forkhead box O3	Mus musculus	79-84
30036874-3	2018	Metformin has been reported to target the PIK3-FOXO3 pathway.	Metformin	0-9	forkhead box O3	Mus musculus	47-52
30036874-9	2018	RESULTS: The oral administration of metformin significantly reduced radiation-induced skin thickening and collagen accumulation and significantly reduced the radiation-induced expression of FOXO3 in murine skin.	Metformin	36-45	forkhead box O3	Mus musculus	190-195
30036874-11	2018	CONCLUSIONS: The results indicated that metformin suppresses radiation-induced skin injuries by modulating the expression of FOXO3 through PIK3r1.	Metformin	40-49	forkhead box O3	Mus musculus	125-130
30786670-4	2018	Decreased activation of JNK p54 and p38 was associated with increased Bcl-XL expression and decreased mitochondrial leakage of cytochrome c. However, only cell viability and partially the fraction of apoptotic nuclei varied concomitantly with changes in AMPK activity, suggesting that AMPK is critical for metformin-mediated effects and regulates programmed cell death in a caspase-independent manner.	Metformin	306-315	ETS proto-oncogene 1, transcription factor	Rattus norvegicus	28-31
29043702-2	2018	The aim of this study was to investigate the effects of metformin (MET), N-acetylcysteine (NAC) and their combination on the hormonal levels and expression profile of GDF-9, BMP-15 and c-kit, as hallmarks of oocyte quality, in PCOS patients.	Metformin	56-65	growth differentiation factor 9	Homo sapiens	167-172
28840963-0	2018	The enhancement of combination of berberine and metformin in inhibition of DNMT1 gene expression through interplay of SP1 and PDPK1.	Metformin	48-57	DNA methyltransferase 1	Homo sapiens	75-80
28840963-0	2018	The enhancement of combination of berberine and metformin in inhibition of DNMT1 gene expression through interplay of SP1 and PDPK1.	Metformin	48-57	3-phosphoinositide dependent protein kinase 1	Homo sapiens	126-131
29444159-8	2018	RESULTS: Preoperative metformin treatment significantly reduced the expression of PP2A-B, as determined using IHC, and the mRNA expression of PPP2R4, as determined using RT-PCR, in the patients with endometrial cancer.	Metformin	22-31	protein phosphatase 2 phosphatase activator	Homo sapiens	82-86
29444159-8	2018	RESULTS: Preoperative metformin treatment significantly reduced the expression of PP2A-B, as determined using IHC, and the mRNA expression of PPP2R4, as determined using RT-PCR, in the patients with endometrial cancer.	Metformin	22-31	protein phosphatase 2 phosphatase activator	Homo sapiens	142-148
29780974-5	2018	We have previously demonstrated that metformin inhibits lipid metabolism, specifically targeting fatty acid synthase (FASN), cholesterol biosynthesis and GM1 lipid rafts in TNBC.	Metformin	37-46	fatty acid synthase	Homo sapiens	97-116
29780974-5	2018	We have previously demonstrated that metformin inhibits lipid metabolism, specifically targeting fatty acid synthase (FASN), cholesterol biosynthesis and GM1 lipid rafts in TNBC.	Metformin	37-46	fatty acid synthase	Homo sapiens	118-122
29444159-11	2018	CONCLUSIONS: Downregulation of the PP2A-B subunit, including PPP2R4, is an important indirect target of metformin.	Metformin	104-113	protein phosphatase 2 phosphatase activator	Homo sapiens	35-39
29444159-11	2018	CONCLUSIONS: Downregulation of the PP2A-B subunit, including PPP2R4, is an important indirect target of metformin.	Metformin	104-113	protein phosphatase 2 phosphatase activator	Homo sapiens	61-67
29228105-5	2018	Because metformin is known to inhibit mTOR and p38 signaling pathways, Faah-/- females were treated with metformin.	Metformin	8-17	fatty acid amide hydrolase	Mus musculus	71-75
29228105-5	2018	Because metformin is known to inhibit mTOR and p38 signaling pathways, Faah-/- females were treated with metformin.	Metformin	105-114	fatty acid amide hydrolase	Mus musculus	71-75
29285650-0	2018	Synergistic cytotoxicity of the dipeptidyl peptidase-IV inhibitor gemigliptin with metformin in thyroid carcinoma cells.	Metformin	83-92	dipeptidyl peptidase 4	Homo sapiens	32-55
29285650-10	2018	Furthermore, gemigliptin augments the inhibitory effect of metformin on proliferation and migration through involvement of matrix metalloproteinase-2, matrix metalloproteinase-9, p53, p21, VCAM-1, and ERK in thyroid carcinoma cells.	Metformin	59-68	H3 histone pseudogene 16	Homo sapiens	184-187
28494141-7	2018	Inhibition of LKB1 activity, a common upstream AMPK kinase, markedly reversed metformin-induced AMPK activation, RUNX2 expression and nuclear localization.	Metformin	78-87	serine/threonine kinase 11	Homo sapiens	14-18
28494141-9	2018	Collectively, functional OCT-expressing iPSC-MSCs responded to metformin by inducing an osteogenic effect in part mediated by the LKB1/AMPK pathway.	Metformin	63-72	serine/threonine kinase 11	Homo sapiens	130-134
29094287-0	2018	Targeting AMPK, mTOR and beta-Catenin by Combined Metformin and Aspirin Therapy in HCC: An Appraisal in Egyptian HCC Patients.	Metformin	50-59	catenin beta 1	Homo sapiens	25-37
29094287-3	2018	OBJECTIVE: The current work aimed to investigate the possibility of targeting AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and beta-catenin proteins through combined metformin/aspirin treatment in the HepG2 cell line, and to explore such molecular targets in Egyptian HCC patients.	Metformin	196-205	catenin beta 1	Homo sapiens	157-169
29094287-8	2018	Additionally, metformin/aspirin combined treatment enhanced cell-cell membrane localization of beta-catenin expression in HepG2 cells, which might inhibit the metastatic potential of HepG2 cells.	Metformin	14-23	catenin beta 1	Homo sapiens	95-107
29094287-10	2018	CONCLUSIONS: Targeting AMPK, mTOR and beta-catenin by combined metformin/aspirin treatment could be a promising therapeutic strategy for Egyptian HCC patients, and possibly other HCC patients.	Metformin	63-72	catenin beta 1	Homo sapiens	38-50
29412816-10	2018	Treatment of HFF mice with metformin for 21-days resulted in inhibition of circulating DPP-4 activity (p &lt; .05), decreased blood glucose (p &lt; .05) and increased GLP-1 gene expression (p &lt; .001).	Metformin	27-36	dipeptidylpeptidase 4	Mus musculus	87-92
29911024-0	2018	Metformin reduces insulin resistance and the tendency toward hyperglycaemia and dyslipidaemia in dogs with hyperadrenocorticism.	Metformin	0-9	insulin	Canis lupus familiaris	18-25
29911024-2	2018	Metformin reduces hepatic glucose production and insulin resistance of the skeletal muscle and adipose tissue.	Metformin	0-9	insulin	Canis lupus familiaris	49-56
29412816-10	2018	Treatment of HFF mice with metformin for 21-days resulted in inhibition of circulating DPP-4 activity (p &lt; .05), decreased blood glucose (p &lt; .05) and increased GLP-1 gene expression (p &lt; .001).	Metformin	27-36	zinc finger, GATA-like protein 1	Mus musculus	167-172
29136782-4	2018	The results indicated an improvement effect of MNCs and metformin on STZ-induced DN in rats, which was evidenced by significant decrease in urinary albumin/creatinine ratio, N-acetyl-beta-d-glucosaminidase (NAG), urinary kidney injury molecule-1 (KIM-1), serum urea, serum creatinine and fasting blood glucose and significant increase in C- peptide level, compared to diabetic control group.	Metformin	56-65	hepatitis A virus cellular receptor 1	Rattus norvegicus	221-245
29136782-4	2018	The results indicated an improvement effect of MNCs and metformin on STZ-induced DN in rats, which was evidenced by significant decrease in urinary albumin/creatinine ratio, N-acetyl-beta-d-glucosaminidase (NAG), urinary kidney injury molecule-1 (KIM-1), serum urea, serum creatinine and fasting blood glucose and significant increase in C- peptide level, compared to diabetic control group.	Metformin	56-65	hepatitis A virus cellular receptor 1	Rattus norvegicus	247-252
29144805-0	2018	DPP4 INHIBITOR SITAGLIPTIN AS A POTENTIAL TREATMENT OPTION IN METFORMIN-INTOLERANT OBESE WOMEN WITH POLYCYSTIC OVARY SYNDROME: A PILOT RANDOMIZED STUDY.	Metformin	62-71	dipeptidyl peptidase 4	Homo sapiens	0-4
28963087-5	2018	Values of glucose, insulin, HOMA; VEGF-a and collagen demonstrate the partial ability of metformin to improve the effects of obesity.	Metformin	89-98	vascular endothelial growth factor A	Mus musculus	34-40
28964787-0	2017	Negative regulation of Sirtuin 1 by AMP-activated protein kinase promotes metformin-induced senescence in hepatocellular carcinoma xenografts.	Metformin	74-83	sirtuin 1	Homo sapiens	23-32
28964787-2	2017	Our previous in vitro studies have demonstrated that a low dose of metformin promoted hepatoma cell senescence instead of apoptosis via activation of AMP-activated protein kinase (AMPK) and inactivation of Sirtuin 1 (SIRT1) deacetylase activity.	Metformin	67-76	sirtuin 1	Homo sapiens	206-215
28964787-2	2017	Our previous in vitro studies have demonstrated that a low dose of metformin promoted hepatoma cell senescence instead of apoptosis via activation of AMP-activated protein kinase (AMPK) and inactivation of Sirtuin 1 (SIRT1) deacetylase activity.	Metformin	67-76	sirtuin 1	Homo sapiens	217-222
28964787-5	2017	Intriguingly, AMPK counter-regulated SIRT1 via direct phosphorylation in metformin-mediated senescence in hepatoma cells.	Metformin	73-82	sirtuin 1	Homo sapiens	37-42
29241458-9	2017	IGF1, IGF1R, AKT p-IGF1, p-IGF1R, and p-Akt protein expression was enhanced dose-dependently with metformin, and was also significantly changed by treatment of CP70 cells with 0 mM metformin +10 mM LY294002.	Metformin	98-107	insulin like growth factor 1 receptor	Homo sapiens	6-11
29241458-9	2017	IGF1, IGF1R, AKT p-IGF1, p-IGF1R, and p-Akt protein expression was enhanced dose-dependently with metformin, and was also significantly changed by treatment of CP70 cells with 0 mM metformin +10 mM LY294002.	Metformin	98-107	insulin like growth factor 1 receptor	Homo sapiens	27-32
29241458-10	2017	Moreover, changes in the expression of MRP2, IGF1, IGF1R, and AKT was metformin-concentration dependent, and was significantly different from that in the untreated control group (P &lt; 0.05).	Metformin	70-79	kelch like family member 1	Homo sapiens	39-43
29241458-10	2017	Moreover, changes in the expression of MRP2, IGF1, IGF1R, and AKT was metformin-concentration dependent, and was significantly different from that in the untreated control group (P &lt; 0.05).	Metformin	70-79	insulin like growth factor 1 receptor	Homo sapiens	51-56
29241458-12	2017	CONCLUSION: Metformin can improve the sensitivity of ovarian cancer CP70 cells to cisplatin in a concentration-dependent manner by activating the AKT signaling pathway, inhibiting the IGF1R signaling pathway, and reducing MRP2 expression.	Metformin	12-21	insulin like growth factor 1 receptor	Homo sapiens	184-189
29241458-12	2017	CONCLUSION: Metformin can improve the sensitivity of ovarian cancer CP70 cells to cisplatin in a concentration-dependent manner by activating the AKT signaling pathway, inhibiting the IGF1R signaling pathway, and reducing MRP2 expression.	Metformin	12-21	kelch like family member 1	Homo sapiens	222-226
28467723-3	2017	Leukocytes from T2D patients exhibited enhanced levels of mitochondrial ROS and decreased mRNA levels of glutathione peroxidase 1 (gpx1) and sirtuin 3 (sirt3) with respect to controls, whereas metformin was shown to revert these effects.	Metformin	193-202	glutathione peroxidase 1	Homo sapiens	105-129
28467723-6	2017	Our findings raise the question of whether metformin could modulate the appearance of atherosclerosis in T2D patients and reduce vascular events by decreasing leukocyte oxidative stress through an increase in gpx1 and sirt3 expression, and undermining adhesion molecule levels and leukocyte-endothelium interactions.	Metformin	43-52	glutathione peroxidase 1	Homo sapiens	209-213
29215608-3	2017	Here we report that metformin-exposed mouse fetuses exhibit elevated expression of the H19 long noncoding RNA, which induces hypomethylation and increased expression of hepatocyte nuclear factor 4alpha (HNF4alpha).	Metformin	20-29	hepatic nuclear factor 4, alpha	Mus musculus	169-201
29215608-3	2017	Here we report that metformin-exposed mouse fetuses exhibit elevated expression of the H19 long noncoding RNA, which induces hypomethylation and increased expression of hepatocyte nuclear factor 4alpha (HNF4alpha).	Metformin	20-29	hepatic nuclear factor 4, alpha	Mus musculus	203-212
28847510-4	2017	The activity of the mutated ALK2 was suppressed by pharmacological AMPK activators such as metformin and aspirin, while their actions were blocked by the dominant negative mutant of AMPK and mimicked by the constitutively active mutant of AMPK.	Metformin	91-100	activin A receptor type 1	Homo sapiens	28-32
28847510-4	2017	The activity of the mutated ALK2 was suppressed by pharmacological AMPK activators such as metformin and aspirin, while their actions were blocked by the dominant negative mutant of AMPK and mimicked by the constitutively active mutant of AMPK.	Metformin	91-100	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	67-71
28847510-6	2017	In contrast, knockdown of Smad6 or Smurf1 prevented metformin-induced reduction of ALK2.	Metformin	52-61	activin A receptor type 1	Homo sapiens	83-87
28847510-7	2017	To evaluate the biological relevance of AMPK action on ALK2 activity, we induced FOP fibroblasts into iPS cells and found that their osteogenic differentiation in vitro was inhibited by metformin.	Metformin	186-195	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	40-44
28847510-7	2017	To evaluate the biological relevance of AMPK action on ALK2 activity, we induced FOP fibroblasts into iPS cells and found that their osteogenic differentiation in vitro was inhibited by metformin.	Metformin	186-195	activin A receptor type 1	Homo sapiens	55-59
28847510-8	2017	Our studies provide novel insight into potential approaches to treatment of FOP, since several AMPK activators (e.g. metformin, berberine, and aspirin) are already in clinical use for the treatment of diabetes and metabolic syndromes.	Metformin	117-126	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	95-99
28643448-10	2017	Metformin synchronized the apoptotic proteins such as FasL and antiapoptotic proteins such as Bcl2, Bcl-xL and p21 which can be attributed as the major mechanism of cardioprotection.	Metformin	0-9	KRAS proto-oncogene, GTPase	Rattus norvegicus	111-114
28158902-5	2017	In addition, metformin treatment attenuated the albumin-induced phosphorylation of AKT and the downstream targets of mTOR, and prevented albumin-mediated inductions of EMT marker (alpha-SMA), pro-apoptotic ER stress marker CHOP, and apoptotic caspases -12 and -3 in renal cells.	Metformin	13-22	mechanistic target of rapamycin kinase	Rattus norvegicus	117-121
28158902-7	2017	Our studies suggest that metformin protects renal cells against proteinuric cytotoxicity via suppression of AKT and mTOR activation, inhibition of EMT and apoptosis, and augmentation of autophagy and ER defense response through AMPK-independent and AMPK-dependent mechanisms, respectively.	Metformin	25-34	mechanistic target of rapamycin kinase	Rattus norvegicus	116-120
28699677-0	2017	Metformin ameliorates BSCB disruption by inhibiting neutrophil infiltration and MMP-9 expression but not direct TJ proteins expression regulation.	Metformin	0-9	matrix metallopeptidase 9	Homo sapiens	80-85
28699677-7	2017	Our results showed that metformin decreased MMP-9 production and blocked neutrophils infiltration at day 1 after injury, which might be related to ICAM-1 down-regulation.	Metformin	24-33	matrix metallopeptidase 9	Homo sapiens	44-49
28699677-7	2017	Our results showed that metformin decreased MMP-9 production and blocked neutrophils infiltration at day 1 after injury, which might be related to ICAM-1 down-regulation.	Metformin	24-33	intercellular adhesion molecule 1	Homo sapiens	147-153
28699677-8	2017	Also, our in vitro study showed that metformin inhibited TNF-alpha-induced MMP-9 up-regulation in neutrophils, which might be mediated via an AMPK-dependent pathway.	Metformin	37-46	matrix metallopeptidase 9	Homo sapiens	75-80
28699677-9	2017	Together, it illustrated that metformin prevented the breakdown of BSCB by inhibiting neutrophils infiltration and MMP-9 production, but not by up-regulating TJ proteins expression.	Metformin	30-39	matrix metallopeptidase 9	Homo sapiens	115-120
28972173-0	2017	Identification of the signals for glucose-induced insulin secretion in INS1 (832/13) beta-cells using metformin-induced metabolic deceleration as a model.	Metformin	102-111	forkhead box M1	Homo sapiens	71-75
28972173-2	2017	Here, we used acute metformin treatment as a tool to induce metabolic deceleration in INS1 (832/13) beta-cells, with the goal of identifying key pathways and metabolites involved in GIIS.	Metformin	20-29	forkhead box M1	Homo sapiens	86-90
29285270-0	2017	Metformin alleviates nickel-induced autophagy and apoptosis via inhibition of hexokinase-2, activating lipocalin-2, in human bronchial epithelial cells.	Metformin	0-9	lipocalin 2	Homo sapiens	103-114
29285270-12	2017	Taken together, our results demonstrated that metformin alleviates NiCl2-induced autophagy and apoptosis via HK2-driven LCN2 activation in human bronchial epithelial cells.	Metformin	46-55	lipocalin 2	Homo sapiens	120-124
29066174-2	2017	We found that metformin (Met) reduced tumor-infiltrating Treg (Ti-Treg), particularly the terminally-differentiated CD103+KLRG1+ population, and also decreased effector molecules such as CTLA4 and IL-10.	Metformin	14-23	interleukin 10	Homo sapiens	197-202
29085821-7	2017	Additionally, metformin increased the expression levels of p53, Bax, Bad while it reduced expression levels of Akt, Bcl-2, and Mdm2.	Metformin	14-23	MDM2 proto-oncogene	Homo sapiens	127-131
28821394-5	2017	Here, we show that AGE exposure decreases cell viability of human neural stem cells (hNSCs), and that the AMPK agonist metformin reverses this effect, via AMPK-dependent downregulation of RAGE levels.	Metformin	119-128	advanced glycosylation end-product specific receptor	Homo sapiens	188-192
28822889-7	2017	This effect was confirmed by the study of the expression of CSC markers (CD44 and Sox2) and differentiation markers (Kruppel-like factor 4 and MUC5AC), which were decreased or increased in response to metformin, respectively.	Metformin	201-210	CD44 molecule (Indian blood group)	Homo sapiens	73-77
28822889-7	2017	This effect was confirmed by the study of the expression of CSC markers (CD44 and Sox2) and differentiation markers (Kruppel-like factor 4 and MUC5AC), which were decreased or increased in response to metformin, respectively.	Metformin	201-210	SRY-box transcription factor 2	Homo sapiens	82-86
28822889-7	2017	This effect was confirmed by the study of the expression of CSC markers (CD44 and Sox2) and differentiation markers (Kruppel-like factor 4 and MUC5AC), which were decreased or increased in response to metformin, respectively.	Metformin	201-210	Kruppel like factor 4	Homo sapiens	117-138
29131265-0	2017	Metformin reduces SATB2-mediated osteosarcoma stem cell-like phenotype and tumor growth via inhibition of N-cadherin/NF-kB signaling.	Metformin	0-9	cadherin 2	Homo sapiens	106-116
29131265-13	2017	Metformin treatment of osteosarcoma cells enhanced the effects of chemotherapy via suppression of N-cadherin.	Metformin	0-9	cadherin 2	Homo sapiens	98-108
28664399-12	2017	Furthermore, metformin downregulated the levels of apoptotic factors (p-JNK3, p-c-Jun and cleaved caspase-3) as well as pro-inflammatory cytokines (IL-1beta, IL-4 and IL-6 and TNF-alpha).	Metformin	13-22	mitogen activated protein kinase 10	Rattus norvegicus	72-76
28754674-10	2017	High-dose metformin inhibited GM-CSF and MMP9 release from WAT progenitors in in vitro and xenograft models.	Metformin	10-19	colony stimulating factor 2 (granulocyte-macrophage)	Mus musculus	30-36
28754674-11	2017	In obese syngeneic mice, metformin treatment mimicked the effects observed with GM-CSF neutralization and MMP9 inhibition, suggesting these proteins as new targets for metformin.	Metformin	25-34	colony stimulating factor 2 (granulocyte-macrophage)	Mus musculus	80-86
29340030-5	2017	In the K18-gT121+/-; p53fl/fl; Brca1fl/fl (KpB) mouse model, metformin inhibited tumor growth in both lean and obese mice.	Metformin	61-70	breast cancer 1, early onset	Mus musculus	31-36
28495567-4	2017	Furthermore, a recent genome-wide association study in a large multi-ethnic population implicated polymorphisms in SLC2A2, encoding the glucose transporter, GLUT2, as important determinants of response to metformin.	Metformin	205-214	solute carrier family 2 member 2	Homo sapiens	115-121
28495567-4	2017	Furthermore, a recent genome-wide association study in a large multi-ethnic population implicated polymorphisms in SLC2A2, encoding the glucose transporter, GLUT2, as important determinants of response to metformin.	Metformin	205-214	solute carrier family 2 member 2	Homo sapiens	157-162
28928832-0	2017	Downregulation of Rab27A contributes to metformin-induced suppression of breast cancer stem cells.	Metformin	40-49	RAB27A, member RAS oncogene family	Homo sapiens	18-24
28928832-6	2017	The present study revealed that downregulation of Rab27A enhanced the capacity of metformin, the most widely used oral hypoglycemic drug for the treatment of type II diabetes, to inhibit mammosphere growth.	Metformin	82-91	RAB27A, member RAS oncogene family	Homo sapiens	50-56
28928832-7	2017	Metformin reduced the expression of Rab27A dose-dependently.	Metformin	0-9	RAB27A, member RAS oncogene family	Homo sapiens	36-42
28859084-6	2017	We observe that metformin treatment modulates the expression of cyclins and cyclin inhibitors thereby inducing a cell cycle perturbation that causes a delay in the G2/M transition.	Metformin	16-25	proliferating cell nuclear antigen	Mus musculus	64-70
28859084-9	2017	Although the details of the molecular mechanisms underlying the effect of the drug on myoblasts still need to be clarified, we propose that metformin negatively affects myogenic differentiation by inhibiting irreversible exit from the cell cycle through reduction of MyoD and p21cip1 levels.	Metformin	140-149	cyclin-dependent kinase inhibitor 1A (P21)	Mus musculus	276-283
29228671-0	2017	Metformin ameliorates skeletal muscle insulin resistance by inhibiting miR-21 expression in a high-fat dietary rat model.	Metformin	0-9	microRNA 21	Rattus norvegicus	71-77
29228671-3	2017	However, it remained elusive whether metformin improved skeletal muscle insulin resistance (IRSM) by regulating miR-21 and its target signal TGF-beta1/smads expression.	Metformin	37-46	microRNA 21	Rattus norvegicus	112-118
29228671-5	2017	Here, we found that metformin dose-dependently decreased miR-21 expression, accompanied by the decrease of HOMA-IR and the increase of HOMA-ISI.	Metformin	20-29	microRNA 21	Rattus norvegicus	57-63
29228671-9	2017	In conclusion, our results demonstrated that metformin improved IRSM by inhibiting miR-21 expression, and that miR-21 may be one of the therapeutic targets for IR.	Metformin	45-54	microRNA 21	Rattus norvegicus	83-89
28732480-13	2017	The primary endpoint is the difference in expression levels of markers of the Fatty acid synthase (FASN)/AMPK pathway pre and post treatment between the placebo and metformin arms.	Metformin	165-174	fatty acid synthase	Homo sapiens	78-97
28732480-13	2017	The primary endpoint is the difference in expression levels of markers of the Fatty acid synthase (FASN)/AMPK pathway pre and post treatment between the placebo and metformin arms.	Metformin	165-174	fatty acid synthase	Homo sapiens	99-103
28947975-1	2017	Reports suggest that metformin, a popular anti-diabetes drug, prevents breast cancer through various systemic effects, including insulin-like growth factor receptor (IGFR) regulation.	Metformin	21-30	insulin like growth factor 1 receptor	Homo sapiens	129-164
28947975-1	2017	Reports suggest that metformin, a popular anti-diabetes drug, prevents breast cancer through various systemic effects, including insulin-like growth factor receptor (IGFR) regulation.	Metformin	21-30	insulin like growth factor 1 receptor	Homo sapiens	166-170
27857021-9	2017	Further study revealed that metformin could suppress the expression of insulin-like growth factor 1 receptor and its downstream proteins, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT/PKB), phosphorylation of AKT (pAKT), mammalian target of rapamycin (mTOR), p70S6K, and PKM2.	Metformin	28-37	insulin like growth factor 1 receptor	Homo sapiens	71-108
28321905-0	2017	Differential increments of basal glucagon-like-1 peptide concentration among SLC47A1 rs2289669 genotypes were associated with inter-individual variability in glycaemic response to metformin in Chinese people with newly diagnosed Type 2 diabetes.	Metformin	180-189	solute carrier family 47 member 1	Homo sapiens	77-84
28321905-1	2017	AIM: To elucidate the effects of rs2289669, an intron variant of the SLC47A1 gene, on glucose response to metformin in Chinese people with newly diagnosed Type 2 diabetes.	Metformin	106-115	solute carrier family 47 member 1	Homo sapiens	69-76
28559290-0	2017	A role for PFKFB3/iPFK2 in metformin suppression of adipocyte inflammatory responses.	Metformin	27-36	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3	Mus musculus	11-17
28559290-0	2017	A role for PFKFB3/iPFK2 in metformin suppression of adipocyte inflammatory responses.	Metformin	27-36	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3	Mus musculus	18-23
28559290-5	2017	In addition, PFKFB3/iPFK2-knockdown adipocytes were treated with metformin and examined for changes in the proinflammatory responses.	Metformin	65-74	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3	Mus musculus	13-19
28559290-8	2017	In addition, treatment with metformin increased the expression of PFKFB3/iPFK2, but failed to significantly alter the phosphorylation states of AMPK.	Metformin	28-37	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3	Mus musculus	66-72
28559290-8	2017	In addition, treatment with metformin increased the expression of PFKFB3/iPFK2, but failed to significantly alter the phosphorylation states of AMPK.	Metformin	28-37	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3	Mus musculus	73-78
28559290-11	2017	Also, metformin increases adipocyte expression of PFKFB3/iPFK2, which is involved in the anti-inflammatory effect of metformin.	Metformin	6-15	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3	Mus musculus	50-56
28559290-11	2017	Also, metformin increases adipocyte expression of PFKFB3/iPFK2, which is involved in the anti-inflammatory effect of metformin.	Metformin	6-15	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3	Mus musculus	57-62
28559290-11	2017	Also, metformin increases adipocyte expression of PFKFB3/iPFK2, which is involved in the anti-inflammatory effect of metformin.	Metformin	117-126	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3	Mus musculus	50-56
28559290-11	2017	Also, metformin increases adipocyte expression of PFKFB3/iPFK2, which is involved in the anti-inflammatory effect of metformin.	Metformin	117-126	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3	Mus musculus	57-62
27167128-9	2017	Activation of AMPK as well as inhibition of its downstream mTOR signaling were detected under metformin treatment in vivo and in vitro; inhibition of AMPK signaling by compound C suppressed autophagy flux induced by metformin in vitro, indicating that AMPK signaling was involved in the effect of metformin on autophagy flux regulation.	Metformin	94-103	mechanistic target of rapamycin kinase	Rattus norvegicus	59-63
27167128-9	2017	Activation of AMPK as well as inhibition of its downstream mTOR signaling were detected under metformin treatment in vivo and in vitro; inhibition of AMPK signaling by compound C suppressed autophagy flux induced by metformin in vitro, indicating that AMPK signaling was involved in the effect of metformin on autophagy flux regulation.	Metformin	216-225	mechanistic target of rapamycin kinase	Rattus norvegicus	59-63
27167128-9	2017	Activation of AMPK as well as inhibition of its downstream mTOR signaling were detected under metformin treatment in vivo and in vitro; inhibition of AMPK signaling by compound C suppressed autophagy flux induced by metformin in vitro, indicating that AMPK signaling was involved in the effect of metformin on autophagy flux regulation.	Metformin	216-225	mechanistic target of rapamycin kinase	Rattus norvegicus	59-63
28440424-8	2017	Additionally, metformin reduced the levels of phosphorylated epidermal growth factor receptor and ROR2 as well as markedly altered miRNA expression in HuTu80 cells.	Metformin	14-23	receptor tyrosine kinase like orphan receptor 2	Homo sapiens	98-102
28504725-3	2017	Here we show that metformin, the most widely used drug for type 2 diabetes, rescues core phenotypes in Fmr1-/y mice and selectively normalizes ERK signaling, eIF4E phosphorylation and the expression of MMP-9.	Metformin	18-27	fragile X messenger ribonucleoprotein 1	Mus musculus	103-107
27897089-10	2017	Metformin supplementation downregulated the d-galactose induced expressions of sirtuin-2, IL-6, and TNF-alpha expression, whereas upregulated the Beclin-1 expression.	Metformin	0-9	sirtuin 2	Rattus norvegicus	79-88
28413172-1	2017	To understand metformin"s effects on fibroblast growth factors (FGFs) and fibroblast growth factor receptor 1 (FGFR1), we investigated circulating fibroblast growth factor-19 (FGF19), FGF21 levels, and FGFR1 in type 2 diabetes mellitus (T2DM).	Metformin	14-23	Fibroblast growth factor receptor 1	Rattus norvegicus	74-109
28413172-1	2017	To understand metformin"s effects on fibroblast growth factors (FGFs) and fibroblast growth factor receptor 1 (FGFR1), we investigated circulating fibroblast growth factor-19 (FGF19), FGF21 levels, and FGFR1 in type 2 diabetes mellitus (T2DM).	Metformin	14-23	Fibroblast growth factor receptor 1	Rattus norvegicus	111-116
28413172-13	2017	The altered glucose and lipid profiles by metformin treatment may be associated with the increased circulating FGF21 and tissue-specific expressions of FGFR1.	Metformin	42-51	Fibroblast growth factor receptor 1	Rattus norvegicus	152-157
28389241-5	2017	Additionally, metformin down regulated inflammatory markers like TLR2, TLR4, CD80, CD86, NF-kappaB, STAT1 and suppressed adipose tissue inflammation by efficiently polarizing adipose tissue macrophages toward anti-inflammatory state by way of indirect inhibition of SHP-1 mRNA and protein expressions.	Metformin	14-23	signal transducer and activator of transcription 1	Mus musculus	100-105
28427181-7	2017	Furthermore, metformin suppressed BMP9-induced angiogenesis in mouse matrigel plug.	Metformin	13-22	growth differentiation factor 2	Mus musculus	34-38
28339020-0	2017	Metformin inhibits endothelial progenitor cell migration by decreasing matrix metalloproteinases, MMP-2 and MMP-9, via the AMPK/mTOR/autophagy pathway.	Metformin	0-9	matrix metallopeptidase 9	Homo sapiens	108-113
28339020-5	2017	Metformin treatment significantly downregulated matrix metalloproteinase-2 (MMP-2) and MMP-9 expression, and subsequently decreased the migration of EPCs.	Metformin	0-9	matrix metallopeptidase 9	Homo sapiens	87-92
28339020-8	2017	In conclusion, our results showed that metformin inhibited the migration of EPCs by decreasing MMP-2 and MMP-9.	Metformin	39-48	matrix metallopeptidase 9	Homo sapiens	105-110
28579878-8	2017	Compared with the model group, groups treated with the metformin and with different proportions of astragaloside and curcumin help lower the blood glucose levels and GSP levels, increase glycogen stores of model mice by different degrees, and avoid pathological changes of pancreas in the model mice.	Metformin	55-64	GNAS (guanine nucleotide binding protein, alpha stimulating) complex locus	Mus musculus	166-169
28459206-8	2017	The anti-tumorigenic effect of metformin was mediated by enhancement of adenosine monophosphate protein kinase activity and elevation of P53 protein as well as the suppression of nuclear factor-kappa B, DNA contents, and cyclin D1 gene expression.	Metformin	31-40	cyclin D1	Mus musculus	221-230
28459206-9	2017	Metformin and doxorubicin mono-treatments exhibited opposing action regarding cyclin D1 gene expression, phosphorylated adenosine monophosphate protein kinase, and nuclear factor-kappa B levels.	Metformin	0-9	cyclin D1	Mus musculus	78-87
28502303-5	2017	The expressions of P21 and c-caspase-3 increased, meanwhile, the expressions of CDK4, cyclin D1, caspase-3 and Bcl-2 decreased by metformin.	Metformin	130-139	KRAS proto-oncogene, GTPase	Rattus norvegicus	19-22
28502303-8	2017	Conclusion Metformin could inhibit cell proliferation, induce cell cycle arrest and apoptosis in MMQ cells by activating AMPK/mTOR signaling pathway and inhibiting IGF-1R signaling pathway.	Metformin	11-20	mechanistic target of rapamycin kinase	Rattus norvegicus	126-130
28445726-6	2017	In cancer patients, the SIRT1 agonist metformin reduced the frequency of Th17 cells and STAT3 acetylation levels.	Metformin	38-47	sirtuin 1	Homo sapiens	24-29
28092166-6	2017	Pretreatment of the I-R animals with metformin increased phosphorylated cyclic-AMP response element-binding protein (pCREB) and c-fos levels compared to the I-R group (P &lt; 0.001 for both).	Metformin	37-46	Fos proto-oncogene, AP-1 transcription factor subunit	Rattus norvegicus	128-133
27964938-0	2017	High-Dose Metformin May Increase the Concentration of Atorvastatin in the Liver by Inhibition of Multidrug Resistance-Associated Protein 2.	Metformin	10-19	ATP binding cassette subfamily C member 2	Rattus norvegicus	97-138
27964938-5	2017	However, metformin significantly inhibited the transport of atorvastatin and 2-hydroxyatorvastatin via MRP2 (apparent IC50 = 12 and 2 muM).	Metformin	9-18	ATP binding cassette subfamily C member 2	Rattus norvegicus	103-107
27964938-9	2017	Therefore, coadministered metformin increases the liver concentration of atorvastatin via inhibition of the Mrp2 in rats, without affecting the plasma concentration.	Metformin	26-35	ATP binding cassette subfamily C member 2	Rattus norvegicus	108-112
28157701-4	2017	Metformin treated cancer cells increased macrophage expression of M1-related cytokines IL-12 and TNF-alpha and attenuated M2-related cytokines IL-8, IL-10, and TGF-beta expression.	Metformin	0-9	interleukin 10	Homo sapiens	149-154
28157701-5	2017	Furthermore, metformin treated cancer cells displayed inhibited secretion of IL-4, IL-10 and IL-13; cytokines important for inducing M2 macrophages.	Metformin	13-22	interleukin 10	Homo sapiens	83-88
28278159-5	2017	METHODS: Two human lightly pigmented melanoma cell lines: WM35 and M1/15 subjected to previous Metformin exposure were treated by GaPc-PDT.	Metformin	95-104	cholinergic receptor muscarinic 1	Homo sapiens	67-72
28278159-8	2017	Metformin addition enhanced cell killing by mechanisms dependent on the cell line, namely apoptosis in the metastatic M1/15 and necrosis in the radial growth phase, WM35.	Metformin	0-9	cholinergic receptor muscarinic 1	Homo sapiens	118-123
28253329-4	2017	Here, we seek to understand if metformin, a first line medication for the treatment of type 2 diabetes, inhibits the proliferation of benign prostatic epithelial cells through reducing the expression of IGF-1 receptor (IGF-1R) and regulating cell cycle.	Metformin	31-40	insulin like growth factor 1 receptor	Homo sapiens	203-217
28253329-4	2017	Here, we seek to understand if metformin, a first line medication for the treatment of type 2 diabetes, inhibits the proliferation of benign prostatic epithelial cells through reducing the expression of IGF-1 receptor (IGF-1R) and regulating cell cycle.	Metformin	31-40	insulin like growth factor 1 receptor	Homo sapiens	219-225
28253329-16	2017	CONCLUSIONS: Our study demonstrates that metformin inhibits the proliferation of benign prostatic epithelial cells by suppressing the expression of IGF-1R and IGF-1 secretion in stromal cells.	Metformin	41-50	insulin like growth factor 1 receptor	Homo sapiens	148-154
28017679-0	2017	Metformin protects the brain against ischemia/reperfusion injury through PI3K/Akt1/JNK3 signaling pathways in rats.	Metformin	0-9	mitogen activated protein kinase 10	Rattus norvegicus	83-87
28017679-2	2017	Therefore, the aim of this study was to investigate the neuroprotective mechanisms of metformin against ischemic brain damage induced by cerebral I/R and to explore whether the Akt-mediated down-regulation of the phosphorylation of JNK3 signaling pathway contributed to the protection provided by metformin.	Metformin	297-306	mitogen activated protein kinase 10	Rattus norvegicus	232-236
28017679-8	2017	The western blot data showed that metformin could promote the activation of Akt1 and reduce the phosphorylation of JNK3 and c-Jun as well as elevation of cleaved caspase-3 in I/R brains.	Metformin	34-43	mitogen activated protein kinase 10	Rattus norvegicus	115-119
28017679-9	2017	PI3K inhibitor reversed all the protective effects, further indicating that metformin protect hippocampus from ischemic damage through PI3K/Akt1/JNK3/c-Jun signaling pathway.	Metformin	76-85	mitogen activated protein kinase 10	Rattus norvegicus	145-149
28099155-0	2017	Metformin promotes apoptosis in hepatocellular carcinoma through the CEBPD-induced autophagy pathway.	Metformin	0-9	CCAAT enhancer binding protein delta	Homo sapiens	69-74
28099155-5	2017	In this study, we found that CEBPD and autophagy are involved in metformin-induced cell apoptosis in Huh7 cells.	Metformin	65-74	CCAAT enhancer binding protein delta	Homo sapiens	29-34
28099155-6	2017	The underlying mechanisms in this process included a reduction in Src-mediated CEBPD protein degradation and an increase in CEBPD-regulated LC3B and ATG3 gene transcription under metformin treatment.	Metformin	179-188	CCAAT enhancer binding protein delta	Homo sapiens	124-129
28099155-6	2017	The underlying mechanisms in this process included a reduction in Src-mediated CEBPD protein degradation and an increase in CEBPD-regulated LC3B and ATG3 gene transcription under metformin treatment.	Metformin	179-188	autophagy related 3	Homo sapiens	149-153
28099155-7	2017	We also found that AMPK is involved in metformin-induced CEBPD expression.	Metformin	39-48	CCAAT enhancer binding protein delta	Homo sapiens	57-62
28104448-0	2017	Metformin and low dose radiation modulates cisplatin-induced oxidative injury in rat via PPAR-gamma and MAPK pathways.	Metformin	0-9	peroxisome proliferator-activated receptor gamma	Rattus norvegicus	89-99
28337263-3	2017	Cell cycle arrest and apoptosis as well as alternations of relative protein levels were also found in diabetic rats and HaCaT cells with overexpression of RAGE that were rectified by metformin (Met) treatment.	Metformin	183-192	advanced glycosylation end-product specific receptor	Homo sapiens	155-159
29144805-3	2018	The present study evaluated the dipeptidyl peptidase 4 inhibitor sitagliptin as a potential treatment option in metformin-intolerant PCOS.	Metformin	112-121	dipeptidyl peptidase 4	Homo sapiens	32-54
29185833-0	2018	Disruption of Hif-1alpha enhances cytotoxic effects of metformin in murine squamous cell carcinoma.	Metformin	55-64	hypoxia inducible factor 1, alpha subunit	Mus musculus	14-24
28208838-7	2017	Metformin was shown to interact with Hh signaling by inhibiting the effector protein glioma-associated oncogene homolog 1 (GLI1) in PCa cells both in vitro and in vivo.	Metformin	0-9	GLI family zinc finger 1	Homo sapiens	123-127
28122334-2	2017	The drop in energy charge resulting from the metformin mediated inhibition of mitochondrial activity affects the function of the nuclear pore complex, blocks mTOR signaling and enhances the expression of ACAD10.	Metformin	45-54	acyl-CoA dehydrogenase family member 10	Homo sapiens	204-210
28158227-10	2017	Metformin treatment brought about a significant reduction of visceral fat mass compared to controls accompanied by an up-regulation of fat oxidation-related enzyme in the liver, UCP-1 in the brown adipose tissue and UCP-3 in the skeletal muscle.	Metformin	0-9	uncoupling protein 3	Homo sapiens	216-221
27305912-9	2017	RESULTS: After adjusting for multiple comparisons in the 32 tumors from metformin-treated patients vs. 34 untreated historical controls, 11 proteins were significantly different between cases vs. CONTROLS: increases in Raptor, C-Raf, Cyclin B1, Cyclin D1, TRFC, and Syk; and reductions in pMAPKpT202,Y204, JNKpT183,pT185, BadpS112, PKC.alphapS657, and SrcpY416.	Metformin	72-81	spleen associated tyrosine kinase	Homo sapiens	266-269
27845161-5	2017	Treatment of PCOS patients with metformin (2 g/day for 3 months) significantly increased the endometrial mRNA levels of FOXO1, ATG3, and UV radiation resistance-associated gene.	Metformin	32-41	autophagy related 3	Homo sapiens	127-131
28764958-3	2017	Interestingly, metformin can enhance mitochondrial function and may affect atrogin-1 expression.	Metformin	15-24	F-box protein 32	Homo sapiens	75-84
27920093-8	2017	18F-FDG uptake reduced after metformin treatment in a dose-dependent manner, corresponding to the reduced expression level of HK2 and GLUT1 in vitro Xenograft model of PTC using BCPAP cells was achieved successfully.	Metformin	29-38	solute carrier family 2 member 1	Homo sapiens	134-139
27920093-10	2017	Immunohistochemistry staining further confirmed the reduction of HK2 and GLUT1 expression in the tumor tissue of metformin-treated PTC xenograft model.	Metformin	113-122	solute carrier family 2 member 1	Homo sapiens	73-78
28606576-9	2017	The insulin sensitizers, metformin and pioglitazone, improved insulin resistance and the concentration of circulating GLP-1, increased the relative number of intestinal L cells to a certain degree.	Metformin	25-34	glucagon	Rattus norvegicus	118-123
28298952-7	2017	Antihyperglycemic agent metformin and newly found free radicals scavengers, Sirt1 and CTRP9, may serve as promising pharmacological therapeutic targets.	Metformin	24-33	sirtuin 1	Homo sapiens	76-81
27871888-7	2017	Cd2+ could inhibit the uptake of metformin, a substrate of MATE transporters, with the half maximal inhibitory concentration (IC50) of 97.5+-6.0muM, 20.2+-2.6muM, and 49.9+-6.9muM in HEK-hMATE1, HEK-hMATE2-K, and HEK-mMate1 cells, respectively.	Metformin	33-42	solute carrier family 47 member 1	Homo sapiens	187-193
29185833-7	2018	RESULTS: The disruption of Hif-1alpha increased the sensitivity of SCC VII cells to metformin in glucose-free medium.	Metformin	84-93	hypoxia inducible factor 1, alpha subunit	Mus musculus	27-37
29185833-8	2018	Metformin-induced decreases in the percentage of dead cells in the presence of CoCl2 were partially reduced when Hif-1alpha was disrupted.	Metformin	0-9	hypoxia inducible factor 1, alpha subunit	Mus musculus	113-123
29185833-9	2018	In vivo, metformin increased the radiosensitivity of SCC VII Hif-1alpha-deficient cells.	Metformin	9-18	hypoxia inducible factor 1, alpha subunit	Mus musculus	61-71
28418203-1	2018	BACKGROUND: Vildagliptin is a dipeptidyl peptidase-4 inhibitor commonly used as a dual oral agent with metformin, thiazolidinediones, or sulfonylurea for the treatment of type 2 diabetes mellitus (T2DM).	Metformin	103-112	dipeptidyl peptidase 4	Homo sapiens	30-52
29170542-0	2018	Diabetes: Metformin - a cardiovascular moderator of DPP4 inhibitors?	Metformin	10-19	dipeptidyl peptidase 4	Homo sapiens	52-56
29560149-3	2017	The aim of this study was to assess the effect of metformin on AMH level in PCOS patients suffering from infertility.	Metformin	50-59	anti-Mullerian hormone	Homo sapiens	63-66
29560149-5	2017	The serum AMH level was recorded before and after 8 weeks of treatment with metformin (1500 mg daily).	Metformin	76-85	anti-Mullerian hormone	Homo sapiens	10-13
29560149-7	2017	Results: Serum AMH level was significantly decreased after 8 weeks of treatment with metformin [10+-3.75 (ng/ml) versus 7.8+-3.7 (ng/ml)] (p=0.008, 95% CI: 0.60-3.75).	Metformin	85-94	anti-Mullerian hormone	Homo sapiens	15-18
29560149-9	2017	In other words, in these patients, a higher BMI led to more decrease in AMH level after metformin treatment.	Metformin	88-97	anti-Mullerian hormone	Homo sapiens	72-75
29560149-10	2017	Conclusion: Eight weeks" treatment with metformin would significantly decrease AMH.	Metformin	40-49	anti-Mullerian hormone	Homo sapiens	79-82
29390570-0	2017	Impact of metformin on serum prostate-specific antigen levels: Data from the national health and nutrition examination survey 2007 to 2008.	Metformin	10-19	kallikrein related peptidase 3	Homo sapiens	29-54
27705937-0	2016	Metformin potentiates anti-tumor effect of resveratrol on pancreatic cancer by down-regulation of VEGF-B signaling pathway.	Metformin	0-9	vascular endothelial growth factor B	Homo sapiens	98-104
27756748-4	2016	Here we show that the widely used diabetes drug metformin improves hematopoiesis and delays tumor formation in Fancd2-/- mice.	Metformin	48-57	Fanconi anemia, complementation group D2	Mus musculus	111-117
27756748-7	2016	In this preclinical model of FA, metformin outperformed the current standard of care, oxymetholone, by improving peripheral blood counts in Fancd2-/- mice significantly faster.	Metformin	33-42	Fanconi anemia, complementation group D2	Mus musculus	140-146
27756748-9	2016	In tumor-prone Fancd2-/-Trp53+/- mice, metformin delayed the onset of tumors and significantly extended the tumor-free survival time.	Metformin	39-48	Fanconi anemia, complementation group D2	Mus musculus	15-21
27984715-3	2016	A key transcriptional target, ACAD10, is activated when metformin induces nuclear exclusion of the GTPase RagC, thereby inhibiting mTORC1 through an unexpected mechanism.	Metformin	56-65	acyl-CoA dehydrogenase family member 10	Homo sapiens	30-36
27609360-0	2016	Single nucleotide polymorphisms in the intergenic region between metformin transporter OCT2 and OCT3 coding genes are associated with short-term response to metformin monotherapy in type 2 diabetes mellitus patients.	Metformin	65-74	solute carrier family 22 member 3	Homo sapiens	96-100
27609360-9	2016	CONCLUSIONS: For the first time, we have identified an association between the lack of metformin response and SNPs rs3119309 and rs7757336 located in the 5" flanking region of the genes coding for Organic cation transporter 2 and rs2481030 located in the 5" flanking region of Organic cation transporter 3 that was supported by the results of a pharmacokinetic study on 25 healthy volunteers.	Metformin	87-96	OCTN3	Homo sapiens	277-305
27576133-5	2016	First, metformin increases reactive oxygen species levels in these cells, leading to the inhibition of SHP-2, a positive regulator of JAK2V617F.	Metformin	7-16	protein tyrosine phosphatase non-receptor type 11	Homo sapiens	103-108
27534967-6	2016	We demonstrated that metformin attenuates ERK signaling by activating AMPK pathway leading to suppression of Snail and Slug resulting in upregulation of crucial tumor suppressor gene E-cadherin.	Metformin	21-30	snail family transcriptional repressor 2	Homo sapiens	119-123
27245553-2	2016	The in vitro inhibition assays on metformin transport were carried out and showed that the half maximal inhibitory concentration (IC50) of rabeprazole on OCT2-mediated metformin transport was 26.0 muM, whereas the IC50 on MATE1-mediated metformin transport inhibition was 4.6 muM.	Metformin	34-43	POU class 2 homeobox 2	Homo sapiens	154-158
27245553-2	2016	The in vitro inhibition assays on metformin transport were carried out and showed that the half maximal inhibitory concentration (IC50) of rabeprazole on OCT2-mediated metformin transport was 26.0 muM, whereas the IC50 on MATE1-mediated metformin transport inhibition was 4.6 muM.	Metformin	168-177	POU class 2 homeobox 2	Homo sapiens	154-158
27245553-2	2016	The in vitro inhibition assays on metformin transport were carried out and showed that the half maximal inhibitory concentration (IC50) of rabeprazole on OCT2-mediated metformin transport was 26.0 muM, whereas the IC50 on MATE1-mediated metformin transport inhibition was 4.6 muM.	Metformin	168-177	POU class 2 homeobox 2	Homo sapiens	154-158
27245553-9	2016	Although rabeprazole showed inhibition effect on OCT2-mediated metformin transport, the glucose-lowering effect of metformin remained the same regardless of its PK changes.	Metformin	63-72	POU class 2 homeobox 2	Homo sapiens	49-53
29390570-2	2017	However, there is limited information on the impact of long-term metformin use on serum prostate-specific antigen (PSA) levels.	Metformin	65-74	kallikrein related peptidase 3	Homo sapiens	88-119
29390570-3	2017	We investigated the association between exposure to metformin and PSA levels among diabetic patients who were not previously diagnosed with PCa.	Metformin	52-61	kallikrein related peptidase 3	Homo sapiens	66-69
29390570-6	2017	Multivariate logistic regression analyses were used to evaluate the association between PSA levels and metformin use by adjusting for potential confounders.	Metformin	103-112	kallikrein related peptidase 3	Homo sapiens	88-91
29390570-9	2017	Among patients with diabetes, metformin users exhibited significantly lower PSA levels compared with nonmetformin users (odds ratio = 0.790; 95% confidence interval 0.666-0.938; P = .007).	Metformin	30-39	kallikrein related peptidase 3	Homo sapiens	76-79
29390570-11	2017	CONCLUSION: A negative association between serum PSA levels and metformin use was observed in patients with diabetes.	Metformin	64-73	kallikrein related peptidase 3	Homo sapiens	49-52
29390570-13	2017	Further studies are warranted to elucidate whether the reduction in PSA level with metformin truly reflects reduced risk of PCa development and progression.	Metformin	83-92	kallikrein related peptidase 3	Homo sapiens	68-71
28990055-7	2017	The results demonstrated that IRS-2 and PI3K expression was markedly decreased in PCOS ovaries, which was rescued by DMBG treatment.	Metformin	117-121	insulin receptor substrate 2	Homo sapiens	30-35
28990055-8	2017	These results indicate that IRS-2/PI3K signaling may be involved in the development of PCOS and the therapeutic effects of DMBG on PCOS.	Metformin	123-127	insulin receptor substrate 2	Homo sapiens	28-33
29025968-8	2017	Moreover, we found that activation of autophagy by the AMPK activator metformin increases dopaminergic neuronal survival in vitro and in the MPTP-induced PD model in Clk1 mutant mice.	Metformin	70-79	CDC-like kinase 1	Mus musculus	166-170
28142314-0	2017	Metformin attenuates hepatic insulin resistance in type-2 diabetic rats through PI3K/Akt/GLUT-4 signalling independent to bicuculline-sensitive GABAA receptor stimulation.	Metformin	0-9	solute carrier family 2 member 4	Rattus norvegicus	89-95
28142314-1	2017	CONTEXT: Metformin attenuates type-2 diabetes mellitus (T2DM)-induced hepatic dysfunction and altered PI3K/Akt/GLUT-4 signalling in experimental studies.	Metformin	9-18	solute carrier family 2 member 4	Rattus norvegicus	111-117
28142314-14	2017	Further, metformin mitigated T2DM-induced decrease in hepatic phosphorylated Akt and GLUT-4 translocation in the animals.	Metformin	9-18	solute carrier family 2 member 4	Rattus norvegicus	85-91
28142314-16	2017	DISCUSSION AND CONCLUSION: These results suggest that metformin ameliorated T2DM-induced hepatic insulin resistance through bicuculline-sensitive GABAA receptor-independent PI3K/Akt/GLUT-4 signalling pathway in animals.	Metformin	54-63	solute carrier family 2 member 4	Rattus norvegicus	182-188
29040818-15	2017	Metformin prevented the THAP-induced mitochondrial dysfunction and reduced CHOP content in cytosol and nucleus.	Metformin	0-9	DNA-damage inducible transcript 3	Mus musculus	75-79
27758931-3	2016	Using metformin and atenolol as the probe substrates, we found that the classic inhibitors (e.g., cimetidine) of renal organic cation secretion were approximately 10-fold more potent for hOCT2 when atenolol was used, suggesting that atenolol is a more sensitive in vitro substrate for hOCT2 than metformin.	Metformin	6-15	POU class 2 homeobox 2	Homo sapiens	187-192
27758931-3	2016	Using metformin and atenolol as the probe substrates, we found that the classic inhibitors (e.g., cimetidine) of renal organic cation secretion were approximately 10-fold more potent for hOCT2 when atenolol was used, suggesting that atenolol is a more sensitive in vitro substrate for hOCT2 than metformin.	Metformin	296-305	POU class 2 homeobox 2	Homo sapiens	187-192
27252117-13	2016	The tissue levels of IL-6, TNF-alpha and CRP were markedly decreased by 21-day treatment with metformin (200 mg/kg/d) (p &lt; 0.001).	Metformin	94-103	C-reactive protein, pentraxin-related	Mus musculus	41-44
28721276-4	2016	For this purpose, we evaluated the antidiabetic drug metformin and demonstrated that 48 h treatment with 5 mmol/l metformin decreases SRSF1 and progerin expression in mesenchymal stem cells derived from HGPS induced pluripotent stem cells (HGPS MSCs).	Metformin	114-123	serine and arginine rich splicing factor 1	Homo sapiens	134-139
27389807-13	2016	The AMPK activator metformin is a promising therapeutic agent for treating ageing-related cardiac remodelling upon beta-AR over-activation.	Metformin	19-28	adrenergic receptor, beta 1	Mus musculus	115-122
27324407-8	2016	The LSS model reproduced previously reported results for effects of polymorphisms in OCT2 and MATE1 genes on AUC(0,24 h) and renal clearance of metformin.	Metformin	144-153	POU class 2 homeobox 2	Homo sapiens	85-89
27324407-8	2016	The LSS model reproduced previously reported results for effects of polymorphisms in OCT2 and MATE1 genes on AUC(0,24 h) and renal clearance of metformin.	Metformin	144-153	solute carrier family 47 member 1	Homo sapiens	94-99
27688683-6	2016	Results Metformin significantly inhibited FaDu cell proliferation in a dose- (25-100 mmol/l) and time-dependent manner (12 h-36 h), significantly downregulated miR-21-5p, and upregulated PDCD4 mRNA and protein expression.	Metformin	8-17	microRNA 215	Homo sapiens	160-169
27688683-7	2016	Conclusions Metformin significantly inhibited FaDu cell proliferation , possibly via downregulation of miR-21-5p and upregulation of PDCD4.	Metformin	12-21	microRNA 215	Homo sapiens	103-112
27569287-6	2016	Furthermore, we found that activation of JNK and c-Jun is responsible for upregulation of DR5 induced by DCA/metformin.	Metformin	109-118	Jun proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	49-54
27207919-0	2016	Metformin Prevents Dopaminergic Neuron Death in MPTP/P-Induced Mouse Model of Parkinson"s Disease via Autophagy and Mitochondrial ROS Clearance.	Metformin	0-9	protein tyrosine phosphatase, non-receptor type 2	Mus musculus	48-52
27725874-0	2016	Metformin inhibits development of diabetic retinopathy through inducing alternative splicing of VEGF-A.	Metformin	0-9	vascular endothelial growth factor A	Mus musculus	96-102
27725874-5	2016	Further analysis showed that metformin may induce VEGF-A mRNA splicing to VEGF120 isoform to reduce its activation of the VEGFR2.	Metformin	29-38	vascular endothelial growth factor A	Mus musculus	50-56
27246734-6	2016	Western blot revealed that the expression of Beclin-1 and LC3B-II was enhanced, and the phosphorylation levels of the mammalian target of rapamycin (mTOR) protein and p70S6K were reduced by metformin after SCI.	Metformin	190-199	beclin 1	Homo sapiens	45-53
27343375-6	2016	Metformin and resveratrol inhibited lipolysis through prevention of PKA/HSL activation by decreasing the accumulation of cAMP via preserving PDE3B.	Metformin	0-9	lipase, hormone sensitive	Mus musculus	72-75
27343375-7	2016	Metformin and resveratrol reduced FFAs influx and DAG accumulation, and thus improved insulin signaling in the muscle by inhibiting PKCtheta translocation.	Metformin	0-9	protein kinase C, theta	Mus musculus	132-140
27500523-0	2016	Variation in the glucose transporter gene SLC2A2 is associated with glycemic response to metformin.	Metformin	89-98	solute carrier family 2 member 2	Homo sapiens	42-48
27500523-3	2016	The C allele of rs8192675 in the intron of SLC2A2, which encodes the facilitated glucose transporter GLUT2, was associated with a 0.17% (P = 6.6 x 10(-14)) greater metformin-induced reduction in hemoglobin A1c (HbA1c) in 10,577 participants of European ancestry.	Metformin	164-173	solute carrier family 2 member 2	Homo sapiens	43-49
27500523-3	2016	The C allele of rs8192675 in the intron of SLC2A2, which encodes the facilitated glucose transporter GLUT2, was associated with a 0.17% (P = 6.6 x 10(-14)) greater metformin-induced reduction in hemoglobin A1c (HbA1c) in 10,577 participants of European ancestry.	Metformin	164-173	solute carrier family 2 member 2	Homo sapiens	101-106
27500523-4	2016	rs8192675 was the top cis expression quantitative trait locus (cis-eQTL) for SLC2A2 in 1,226 human liver samples, suggesting a key role for hepatic GLUT2 in regulation of metformin action.	Metformin	171-180	solute carrier family 2 member 2	Homo sapiens	77-83
27500523-4	2016	rs8192675 was the top cis expression quantitative trait locus (cis-eQTL) for SLC2A2 in 1,226 human liver samples, suggesting a key role for hepatic GLUT2 in regulation of metformin action.	Metformin	171-180	solute carrier family 2 member 2	Homo sapiens	148-153
27578220-2	2016	OBJECTIVES    The aim of the study was to determine the influence of metformin on the metabolism of atherogenic lipid fractions in relation to Lp-PLA2 and CEL levels, as well as assess consequent improvement in the intima-media thickness (IMT) of the common carotid artery in young type 1 diabetes patients with excess body fat.	Metformin	69-78	phospholipase A2 group VII	Homo sapiens	143-150
27578220-12	2016	Additionally, in patients receiving metformin, glycated LDL levels were inversely correlated with Lp-PLA2 levels (r = -0.31, P &lt;0.05).	Metformin	36-45	phospholipase A2 group VII	Homo sapiens	98-105
27418629-4	2016	Metformin suppressed IKKalpha/beta activation, an effect that could be separated from some metabolic actions, in that BI605906 did not mimic effects of metformin on lipogenic gene expression, glucose production, and AMP-activated protein kinase activation.	Metformin	0-9	component of inhibitor of nuclear factor kappa B kinase complex	Homo sapiens	21-29
27259235-7	2016	Metformin-induced restriction of mitochondrial biosynthetic capacity was sufficient to impair the tumor-initiating capacity of BRCA1 one-hit cells in mammosphere assays.	Metformin	0-9	BRCA1 DNA repair associated	Homo sapiens	127-132
27259235-9	2016	The ability of metformin to constrain the production of mitochondrial-dependent biosynthetic intermediates might open a new avenue for "starvation" chemopreventive strategies in BRCA1 carriers.	Metformin	15-24	BRCA1 DNA repair associated	Homo sapiens	178-183
27513844-7	2016	In line with the role of AMPK in GR expression, AMPK activator metformin reversed glucocorticoid-induced reduction of AMPK phosphorylation and GR expression as well as behavioral alteration of rats.	Metformin	63-72	nuclear receptor subfamily 3, group C, member 1	Rattus norvegicus	33-35
27513844-7	2016	In line with the role of AMPK in GR expression, AMPK activator metformin reversed glucocorticoid-induced reduction of AMPK phosphorylation and GR expression as well as behavioral alteration of rats.	Metformin	63-72	nuclear receptor subfamily 3, group C, member 1	Rattus norvegicus	143-145
27555891-7	2016	Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters (SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin.	Metformin	310-319	solute carrier family 22 member 3	Homo sapiens	226-233
27555891-7	2016	Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters (SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin.	Metformin	310-319	solute carrier family 47 member 1	Homo sapiens	235-242
27163626-3	2016	As transforming growth factor beta 2 (TGF-beta2) has been reported to promote high-grade glioma and is inhibited by metformin in other tumors, we explored whether metformin directly interferes with TGF-beta2-signaling.	Metformin	116-125	transforming growth factor beta 2	Homo sapiens	38-47
27163626-4	2016	Functional investigation of proliferation and migration of primary BTICs after treatment with metformin+/-TGF-beta2 revealed that metformin doses as low as 0.01 mM metformin thrice a day were able to inhibit proliferation of susceptible cell lines, whereas migration was impacted only at higher doses.	Metformin	130-139	transforming growth factor beta 2	Homo sapiens	106-115
27163626-4	2016	Functional investigation of proliferation and migration of primary BTICs after treatment with metformin+/-TGF-beta2 revealed that metformin doses as low as 0.01 mM metformin thrice a day were able to inhibit proliferation of susceptible cell lines, whereas migration was impacted only at higher doses.	Metformin	130-139	transforming growth factor beta 2	Homo sapiens	106-115
27163626-5	2016	Known cellular mechanisms of metformin, such as increased lactate secretion, reduced oxygen consumption and activated AMPK-signaling, could be confirmed.	Metformin	29-38	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	118-122
27210058-7	2016	MTT assay and TUNEL assay revealed that metformin (4 mg/ml) and 5-FU (2.5 microg/ml) combination treatment effectively inhibited cell growth and induced apoptosis in OSCC cell lines (HSC2, HSC3 and HSC4) compared to either agent alone.	Metformin	40-49	DnaJ heat shock protein family (Hsp40) member B7	Homo sapiens	189-193
29040818-16	2017	Thus, metformin reduces cardiac injury during ER stress through the protection of cardiac mitochondria and attenuation of CHOP expression.	Metformin	6-15	DNA-damage inducible transcript 3	Mus musculus	122-126
29230104-0	2017	Metformin Sensitizes Non-small Cell Lung Cancer Cells to an Epigallocatechin-3-Gallate (EGCG) Treatment by Suppressing the Nrf2/HO-1 Signaling Pathway.	Metformin	0-9	heme oxygenase 1	Homo sapiens	128-132
29230104-6	2017	In this study, metformin inhibited HO-1 expression and augmented the anti-tumor effect of EGCG.	Metformin	15-24	heme oxygenase 1	Homo sapiens	35-39
29230104-9	2017	Mechanistically, metformin modulated the EGCG-activated Nrf2/HO-1 pathway through Sirtuin 1 (SIRT1)-dependent deacetylation of Nrf2.	Metformin	17-26	heme oxygenase 1	Homo sapiens	61-65
29230104-12	2017	Based on our findings, metformin sensitized NSCLC cells to the EGCG treatment by suppressing the Nrf2/HO-1 signaling pathway.	Metformin	23-32	heme oxygenase 1	Homo sapiens	102-106
28947430-6	2017	Metformin (200 mg/kg/d) was used to treat wild-type and Sirt2 knockout mice infused with Ang II.	Metformin	0-9	sirtuin 2	Mus musculus	56-61
28947430-14	2017	Remarkably, the loss of SIRT2 blunted the response of AMPK to metformin treatment in mice infused with Ang II and repressed the metformin-mediated reduction of cardiac hypertrophy and protection of cardiac function.	Metformin	62-71	sirtuin 2	Mus musculus	24-29
28947430-14	2017	Remarkably, the loss of SIRT2 blunted the response of AMPK to metformin treatment in mice infused with Ang II and repressed the metformin-mediated reduction of cardiac hypertrophy and protection of cardiac function.	Metformin	128-137	sirtuin 2	Mus musculus	24-29
28947430-16	2017	Loss of SIRT2 reduces AMPK activation, promotes aging-related and Ang II-induced cardiac hypertrophy, and blunts metformin-mediated cardioprotective effects.	Metformin	113-122	sirtuin 2	Mus musculus	8-13
29696037-6	2018	Metformin is the most widely used drug, together with sodium-glucose co-transporters 2 (SGLT2) inhibitors, amylin analogues, glucagon-like peptide 1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors.	Metformin	0-9	dipeptidyl peptidase 4	Homo sapiens	204-209
27752788-11	2017	CONCLUSIONS: According to the WHO threshold applied to the country and year of each study, DPP-4 inhibitors were highly cost-effective as second-line, as add-ons to metformin, in comparison with sulfonylureas.	Metformin	165-174	dipeptidyl peptidase 4	Homo sapiens	91-96
29228440-0	2017	Metformin regulates tight junction of intestinal epithelial cells via MLCK-MLC signaling pathway.	Metformin	0-9	myosin light chain kinase	Homo sapiens	70-74
29228440-7	2017	RESULTS: Metformin attenuates the effects of TNF-alpha on Caco-2 cell TEER and paracellular permeability, prevents TNF-alpha-induced morphological disruption of tight junctions, ameliorates the inhibiting effect of TNF-alpha on epithelial tight junction-related protein expression and suppresses the TNF-alpha-induced increase in MLCK production.	Metformin	9-18	myosin light chain kinase	Homo sapiens	330-334
29228440-8	2017	CONCLUSIONS: Metformin can stabilize and up-regulate tight junction protein by inhibiting MLCK-MLC signaling pathway, thus ameliorating the tight junction of intestinal epithelial cells.	Metformin	13-22	myosin light chain kinase	Homo sapiens	90-94
28771933-9	2017	Our concomitancy analysis showed that DPP-4 inhibitors have overtaken sulfonylureas since 2014 as the most common add-on to metformin.	Metformin	124-133	dipeptidyl peptidase 4	Homo sapiens	38-43
28921708-4	2017	Both scopoletin and metformin lowered blood glucose and HbA1c , serum ALT, TNF-alpha and IL-6 levels, glucose intolerance, and hepatic lipid accumulation compared with the diabetic control group.	Metformin	20-29	glutamic pyruvic transaminase, soluble	Mus musculus	70-73
28791487-11	2017	In addition, metformin treatment decreased p-JNK independently of TLR2 signal in diabetic rats.	Metformin	13-22	mitogen-activated protein kinase 8	Rattus norvegicus	45-48
28795250-0	2017	Metformin reduces total microparticles and microparticles-expressing tissue factor in women with polycystic ovary syndrome.	Metformin	0-9	coagulation factor III, tissue factor	Homo sapiens	69-82
28729113-8	2017	Importantly, intrathecal injection of metformin, a known scavenger of methylglyoxal, significantly attenuated the upregulation of methylglyoxal and RAGE in dorsal horn, central sensitization and mechanical allodynia induced by bortezomib treatment, and blockage of RAGE also prevented the upregulation of p-STAT3, central sensitization and mechanical allodynia induced by bortezomib treatment.	Metformin	38-47	signal transducer and activator of transcription 3	Rattus norvegicus	307-312
28807678-0	2017	Metformin lowers alpha-synuclein phosphorylation and upregulates neurotrophic factor in the MPTP mouse model of Parkinson"s disease.	Metformin	0-9	synuclein, alpha	Mus musculus	17-32
27106243-10	2016	In experimental modeling, metformin dramatically suppressed the formation and progression, with medial elastin and smooth muscle preservation and reduced aortic mural macrophage, CD8 T cell, and neovessel density.	Metformin	26-35	elastin	Homo sapiens	103-110
27106243-10	2016	In experimental modeling, metformin dramatically suppressed the formation and progression, with medial elastin and smooth muscle preservation and reduced aortic mural macrophage, CD8 T cell, and neovessel density.	Metformin	26-35	CD8a molecule	Homo sapiens	179-182
26597253-0	2016	The Effect of Famotidine, a MATE1-Selective Inhibitor, on the Pharmacokinetics and Pharmacodynamics of Metformin.	Metformin	103-112	solute carrier family 47 member 1	Homo sapiens	28-33
26597253-2	2016	The goal of our study was to determine the effects of selective inhibition of multidrug and toxin extrusion protein 1 (MATE1), using famotidine, on the pharmacokinetics and pharmacodynamics of metformin in healthy volunteers.	Metformin	193-202	solute carrier family 47 member 1	Homo sapiens	78-117
26597253-2	2016	The goal of our study was to determine the effects of selective inhibition of multidrug and toxin extrusion protein 1 (MATE1), using famotidine, on the pharmacokinetics and pharmacodynamics of metformin in healthy volunteers.	Metformin	193-202	solute carrier family 47 member 1	Homo sapiens	119-124
26993065-5	2016	Ablation of OCT1 and OCT2 significantly reduced the distribution of metformin in the liver and small intestine.	Metformin	68-77	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	12-16
27035653-11	2016	Finally, treatment of INS-1E cells with metformin for 24 h resulted in inhibition of SREBP-1C expression, increased PDX-1 and GLP-1 receptor levels, consequently, enhancement of exendin-4-induced insulin release.	Metformin	40-49	glucagon-like peptide 1 receptor	Rattus norvegicus	126-140
27035653-13	2016	Metformin counteracts the impairment of GLP-1 receptor signaling induced by palmitate.	Metformin	0-9	glucagon-like peptide 1 receptor	Rattus norvegicus	40-54
28807678-8	2017	Western blot analysis revealed that metformin ameliorated MPTP-induced alpha-synuclein phosphorylation which was accompanied by increased methylation of protein phosphatase 2A (PP2A), a phosphatase related to alpha-synuclein dephosphorylation.	Metformin	36-45	synuclein, alpha	Mus musculus	71-86
28807678-8	2017	Western blot analysis revealed that metformin ameliorated MPTP-induced alpha-synuclein phosphorylation which was accompanied by increased methylation of protein phosphatase 2A (PP2A), a phosphatase related to alpha-synuclein dephosphorylation.	Metformin	36-45	synuclein, alpha	Mus musculus	209-224
28807678-9	2017	Moreover, the metformin regimen significantly increased the level of brain derived neurotrophic factor in the substantia nigra, and activated signaling pathways related to cell survival.	Metformin	14-23	brain derived neurotrophic factor	Mus musculus	69-102
28807678-10	2017	Proof of concept study revealed that inhibition of PP2A or tropomyosin receptor kinase B reversed neuroprotective property of metformin in SH-SY5Y cells.	Metformin	126-135	protein phosphatase 2 phosphatase activator	Homo sapiens	51-55
28807678-11	2017	Our results indicate that metformin provides neuroprotection against MPTP neurotoxicity, which might be mediated by inhibition of alpha-synuclein phosphorylation and induction of neurotrophic factors.	Metformin	26-35	synuclein, alpha	Mus musculus	130-145
28791376-5	2017	Furthermore, MACC1 knockdown inactivated AMPK-ULK1 signaling pathway, and metformin could rescue MACC1-induced autophagy in ESCC cells.	Metformin	74-83	MET transcriptional regulator MACC1	Homo sapiens	97-102
29085506-6	2017	Metformin significantly decreased E2-stimulated cell proliferation; an effect that was rescued in the presence of compound C. Metformin treatment markedly increased the phosphorylation of AMPK while decreasing p70S6K phosphorylation, indicating that metformin exerts its effects through stimulation of AMPK and subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	210-216
29085506-6	2017	Metformin significantly decreased E2-stimulated cell proliferation; an effect that was rescued in the presence of compound C. Metformin treatment markedly increased the phosphorylation of AMPK while decreasing p70S6K phosphorylation, indicating that metformin exerts its effects through stimulation of AMPK and subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway.	Metformin	126-135	ribosomal protein S6 kinase B1	Homo sapiens	210-216
29085506-8	2017	Reverse transcription-quantitative polymerase chain reaction analysis demonstrated that c-fos and c-myc expression were attenuated by metformin, an effect that was rescued in the presence of compound C. Therefore, metformin regulates the expression of ERs, and inhibits estrogen-mediated proliferation of human EC cells through the activation of AMPK and subsequent inhibition of the mTOR signaling pathway.	Metformin	214-223	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	98-103
29088858-7	2017	Mechanically, metformin decreased expression of PKM2 and subsequently inhibited the glucose uptake, lactate generation and ATP production in A549/R and PC9/R.	Metformin	14-23	pyruvate kinase M1/2	Homo sapiens	48-52
29088858-7	2017	Mechanically, metformin decreased expression of PKM2 and subsequently inhibited the glucose uptake, lactate generation and ATP production in A549/R and PC9/R.	Metformin	14-23	proprotein convertase subtilisin/kexin type 9	Homo sapiens	152-155
29088858-9	2017	In addition, we demonstrated that metformin treatment also impaired the cross-resistance of A549/R and PC9/R to cisplatin, etoposide and 5-fluorouracil.	Metformin	34-43	proprotein convertase subtilisin/kexin type 9	Homo sapiens	103-106
28619690-5	2017	The mechanisms by which metformin may prevent preeclampsia include a reduction in the production of antiangiogenic factors (soluble vascular endothelial growth factor receptor-1 and soluble endoglin) and the improvement of endothelial dysfunction, probably through an effect on the mitochondria.	Metformin	24-33	endoglin	Homo sapiens	190-198
26835542-10	2016	Dehydroepiandrosterone (DHEAS) tended to be higher in the metformin group.	Metformin	58-67	sulfotransferase family 2A member 1	Homo sapiens	24-29
27274280-0	2016	Metformin induces apoptosis of human hepatocellular carcinoma HepG2 cells by activating an AMPK/p53/miR-23a/FOXA1 pathway.	Metformin	0-9	microRNA 23a	Homo sapiens	100-107
27274280-3	2016	In this work, we showed that miR-23a was significantly induced upon metformin treatment; inhibition of miR-23a abrogated the proapoptotic effect of metformin in HepG2 cells.	Metformin	68-77	microRNA 23a	Homo sapiens	29-36
27274280-3	2016	In this work, we showed that miR-23a was significantly induced upon metformin treatment; inhibition of miR-23a abrogated the proapoptotic effect of metformin in HepG2 cells.	Metformin	68-77	microRNA 23a	Homo sapiens	103-110
27274280-3	2016	In this work, we showed that miR-23a was significantly induced upon metformin treatment; inhibition of miR-23a abrogated the proapoptotic effect of metformin in HepG2 cells.	Metformin	148-157	microRNA 23a	Homo sapiens	29-36
27274280-3	2016	In this work, we showed that miR-23a was significantly induced upon metformin treatment; inhibition of miR-23a abrogated the proapoptotic effect of metformin in HepG2 cells.	Metformin	148-157	microRNA 23a	Homo sapiens	103-110
27274280-4	2016	We next established forkhead box protein A1 (FOXA1) as the functional target of miR-23a, and silencing FOXA1 mimicked the effect of metformin.	Metformin	132-141	microRNA 23a	Homo sapiens	80-87
27274280-5	2016	Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin.	Metformin	115-124	microRNA 23a	Homo sapiens	189-196
27274280-5	2016	Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin.	Metformin	115-124	microRNA 23a	Homo sapiens	287-294
27274280-5	2016	Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin.	Metformin	200-209	microRNA 23a	Homo sapiens	189-196
27274280-5	2016	Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin.	Metformin	200-209	microRNA 23a	Homo sapiens	287-294
27274280-5	2016	Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin.	Metformin	200-209	microRNA 23a	Homo sapiens	189-196
27274280-5	2016	Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin.	Metformin	200-209	microRNA 23a	Homo sapiens	287-294
27274280-6	2016	In summary, we unraveled a novel AMPK/p53/miR-23a/FOXA1 axis in the regulation of apoptosis in HCC, and the application of metformin could, therefore, be effective in the treatment of HCC.	Metformin	123-132	microRNA 23a	Homo sapiens	42-49
27058422-5	2016	And also metformin represses bladder cancer CSC repopulation evidenced by reducing cytokeratin 14 (CK14+) and octamer-binding transcription factor 3/4 (OCT3/4+) cells in both animal and cellular models.	Metformin	9-18	keratin 14	Rattus norvegicus	83-97
26669511-7	2016	Metformin uptake was minimal in BT-20 cells, but increased by &gt;13-fold in OCT3-BT20 cells, and its antiproliferative potency was &gt;4-fold in OCT3-BT20 versus BT-20 cells.	Metformin	0-9	OCTN3	Homo sapiens	77-81
26669511-7	2016	Metformin uptake was minimal in BT-20 cells, but increased by &gt;13-fold in OCT3-BT20 cells, and its antiproliferative potency was &gt;4-fold in OCT3-BT20 versus BT-20 cells.	Metformin	0-9	OCTN3	Homo sapiens	146-150
26992204-6	2016	Treatment with metformin resulted in slight increase in the accumulation of microtubule-associated protein light chain LC3-II and significantly decreased the p62 protein levels by dose-dependent manner indicated that metformin induced autophagy flux activation in the lung cancer cells.	Metformin	15-24	nucleoporin 62	Homo sapiens	158-161
26992204-6	2016	Treatment with metformin resulted in slight increase in the accumulation of microtubule-associated protein light chain LC3-II and significantly decreased the p62 protein levels by dose-dependent manner indicated that metformin induced autophagy flux activation in the lung cancer cells.	Metformin	217-226	nucleoporin 62	Homo sapiens	158-161
27101310-11	2016	Interestingy, activation of AMPKalpha by metformin was associated with a reversal of the suppressed GRIM-19 expression in H9C2 cells, the fold of changes in GRIM-19 expression by metformin were much less in HeLa cells.	Metformin	41-50	NADH:ubiquinone oxidoreductase subunit A13	Homo sapiens	100-107
27101310-11	2016	Interestingy, activation of AMPKalpha by metformin was associated with a reversal of the suppressed GRIM-19 expression in H9C2 cells, the fold of changes in GRIM-19 expression by metformin were much less in HeLa cells.	Metformin	179-188	NADH:ubiquinone oxidoreductase subunit A13	Homo sapiens	157-164
26824324-0	2016	Metformin inhibits 17beta-estradiol-induced epithelial-to-mesenchymal transition via betaKlotho-related ERK1/2 signaling and AMPKalpha signaling in endometrial adenocarcinoma cells.	Metformin	0-9	klotho beta	Homo sapiens	85-95
26824324-5	2016	In addition, metformin increased the expression of betaKlotho, a fibroblast growth factors (FGFs) coreceptor, and decreased ERK1/2 phosphorylation in both Ishikawa and KLE cells.	Metformin	13-22	klotho beta	Homo sapiens	51-61
26824324-9	2016	In conclusion, metformin abolishes 17beta-estradiol-induced cell proliferation and EMT in endometrial adenocarcinoma cells by upregulating betaKlotho expression, inhibiting ERK1/2 signaling, and activating AMPKalpha signaling.	Metformin	15-24	klotho beta	Homo sapiens	139-149
25663310-0	2016	Autophagy and protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 alpha kinase (eIF2alpha) pathway protect ovarian cancer cells from metformin-induced apoptosis.	Metformin	172-181	eukaryotic translation initiation factor 2A	Homo sapiens	119-128
25663310-4	2016	In this study, we observed that metformin-induced apoptosis was relieved by autophagy and the PERK/eIF2alpha pathway in ovarian cancer cells, but not in peripheral blood mononuclear cells (PBMC) or "normal" ovarian surface epithelial cells (OSE).	Metformin	32-41	eukaryotic translation initiation factor 2A	Homo sapiens	99-108
25663310-7	2016	Interestingly, metformin induced interdependent activation between autophagy and the UPR, especially the PERK/eIF2alpha pathway.	Metformin	15-24	eukaryotic translation initiation factor 2A	Homo sapiens	110-119
26795347-10	2016	Suppression of miR-155 resulted in sensitization of MCF7-LTED cells to metformin treatment and impairment of 2-DG-induced motility.	Metformin	71-80	microRNA 155	Homo sapiens	15-22
26957312-13	2016	Cell Counting Kit-8 (CCK8) cell viability assay and Annexin V-FITC apoptosis assay showed that metformin in combination with sorafenib suppressed cell proliferation and promoted cell apoptosis.	Metformin	95-104	annexin A5	Mus musculus	52-61
26957312-17	2016	CONCLUSIONS: Metformin may potentially enhance the effect of sorafenib to inhibit HCC recurrence and metastasis after liver resection by regulating the expression of HIF-2alpha and TIP30.	Metformin	13-22	HIV-1 Tat interactive protein 2	Mus musculus	181-186
26885898-0	2016	Metformin regulates oxLDL-facilitated endothelial dysfunction by modulation of SIRT1 through repressing LOX-1-modulated oxidative signaling.	Metformin	0-9	sirtuin 1	Homo sapiens	79-84
26885898-3	2016	In this present study, we confirmed that metformin enhanced SIRT1 and AMPK expression in human umbilical vein endothelial cells (HUVECs).	Metformin	41-50	sirtuin 1	Homo sapiens	60-65
26885898-5	2016	However, silencing SIRT1 and AMPK diminished the protective function of metformin against oxidative injuries.	Metformin	72-81	sirtuin 1	Homo sapiens	19-24
27420623-3	2016	In this study we have investigated the effect of metformin on the activity of adenosine deaminase and respectively adenosinergic immunosuppression in tumors and their microenvironment.	Metformin	49-58	adenosine deaminase	Homo sapiens	78-97
27420623-7	2016	However, the metformin-induced increase in the adenosine deaminase activity is not sufficient to reduce the level of adenosine in cancer tissue.	Metformin	13-22	adenosine deaminase	Homo sapiens	47-66
26861514-0	2016	Neuroprotective effects of metformin against Abeta-mediated inhibition of long-term potentiation in rats fed a high-fat diet.	Metformin	27-36	amyloid beta precursor protein	Rattus norvegicus	45-50
26387747-0	2016	Serum vascular endothelial growth factor B is elevated in women with polycystic ovary syndrome and can be decreased with metformin treatment.	Metformin	121-130	vascular endothelial growth factor B	Homo sapiens	6-42
26387747-6	2016	RESULTS: Women with polycystic ovary syndrome had higher serum VEGF-B levels, which decreased with metformin treatment.	Metformin	99-108	vascular endothelial growth factor B	Homo sapiens	63-69
26387747-11	2016	Metformin treatment reduces VEGF-B levels and ameliorates insulin resistance.	Metformin	0-9	vascular endothelial growth factor B	Homo sapiens	28-34
26921394-0	2016	High Sensitivity of an Ha-RAS Transgenic Model of Superficial Bladder Cancer to Metformin Is Associated with ~240-Fold Higher Drug Concentration in Urine than Serum.	Metformin	80-89	Harvey rat sarcoma virus oncogene	Mus musculus	23-29
26896068-9	2016	Moreover, metformin enhanced the anti-inflammatory effect of 5-ASA by decreasing the gene expression of IL-1beta, IL-6, COX-2 and TNF-alpha and its receptors; TNF-R1 and TNF-R2.	Metformin	10-19	TNF receptor superfamily member 1B	Homo sapiens	170-176
26896068-11	2016	Metformin also enhanced the inhibitory effect of 5-ASA on MMP-2 and MMP-9 enzyme activity, indicating a decrease in metastasis.	Metformin	0-9	matrix metallopeptidase 9	Homo sapiens	68-73
26858121-8	2016	In addition, metformin exacerbates hindlimb atrophy, increases P301S hyperactive behavior, induces tau cleavage by caspase 3 and disrupts synaptic structures.	Metformin	13-22	caspase 3	Mus musculus	115-124
26841718-6	2016	Notably, kinases, particularly SGK1 and EGFR were identified as key molecular targets of metformin.	Metformin	89-98	serum/glucocorticoid regulated kinase 1	Homo sapiens	31-35
26529121-5	2016	Metformin treatment prompted a delay in delamination of NCC by inhibiting key markers like Sox-1, Sox-9, HNK-1, and p-75.	Metformin	0-9	SRY-box transcription factor 1	Homo sapiens	91-96
26529121-8	2016	Further studies involving loss and gain of function confirmed that NCC specifiers like Sox-1 and Sox-9 are direct targets of miR-200 and miR-145, respectively and that they are essentially modulated by metformin.	Metformin	202-211	SRY-box transcription factor 1	Homo sapiens	87-92
25913633-5	2016	In contrast, metformin has a positive effect on osteoblast differentiation due to increased activity of Runx2 via the AMPK/USF-1/SHP regulatory cascade resulting in a neutral or potentially protective effect on bone.	Metformin	13-22	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	118-122
27633039-10	2016	A study in mice deficient in PON1 showed that in this experimental model, metformin administration increased the severity of steatosis, increased CCL2 expression, did not activate AMPK, and increased the expression of the apoptosis marker caspase-9.	Metformin	74-83	chemokine (C-C motif) ligand 2	Mus musculus	146-150
26977146-0	2016	The Impacts of SLC22A1 rs594709 and SLC47A1 rs2289669 Polymorphisms on Metformin Therapeutic Efficacy in Chinese Type 2 Diabetes Patients.	Metformin	71-80	solute carrier family 47 member 1	Homo sapiens	36-43
26977146-2	2016	We aimed to investigate the distributive characteristics of SLC22A1 rs594709 and SLC47A1 rs2289669 polymorphisms and their influence on metformin efficacy in Chinese T2DM patients.	Metformin	136-145	solute carrier family 47 member 1	Homo sapiens	81-88
26977146-13	2016	Our data suggest that SLC22A1 rs594709 and SLC47A1 rs2289669 polymorphisms may influence metformin efficacy together in Chinese T2DM patients.	Metformin	89-98	solute carrier family 47 member 1	Homo sapiens	43-50
26304716-4	2015	Mechanistically, metformin caused abrogation of the G2 checkpoint and increase of mitotic catastrophe, associated with suppression of Wee1 kinase and in turn CDK1 Tyr15 phosphorylation.	Metformin	17-26	WEE1 G2 checkpoint kinase	Homo sapiens	134-138
26304716-5	2015	Furthermore, metformin inhibited both expression and irradiation-induced foci formation of Rad51, a key player in homologous recombination repair, ultimately leading to persistent DNA damage, as reflected by gamma-H2AX and 53BP1 signaling.	Metformin	13-22	RAD51 recombinase	Homo sapiens	91-96
26304716-6	2015	Finally, metformin-mediated AMPK/mTOR/p70S6K was identified as a possible upstream pathway controlling translational regulation of Wee1 and Rad51.	Metformin	9-18	WEE1 G2 checkpoint kinase	Homo sapiens	131-135
26304716-6	2015	Finally, metformin-mediated AMPK/mTOR/p70S6K was identified as a possible upstream pathway controlling translational regulation of Wee1 and Rad51.	Metformin	9-18	RAD51 recombinase	Homo sapiens	140-145
26725558-11	2015	MMP-9 zymography analysis revealed that the highest inhibition of MMP-9 activity was observed in hypoxia condition by 20mM of metformin concentration only in cancer cell.	Metformin	126-135	matrix metallopeptidase 9	Homo sapiens	0-5
26725558-11	2015	MMP-9 zymography analysis revealed that the highest inhibition of MMP-9 activity was observed in hypoxia condition by 20mM of metformin concentration only in cancer cell.	Metformin	126-135	matrix metallopeptidase 9	Homo sapiens	66-71
26164004-4	2015	Metformin suppressed OS MG63 cell proliferation in a dose- and time-dependent manner and markedly blocked anti-metastatic potentials, migration, and invasion, by downregulating matrix metalloproteinase 2 (MMP2) and MMP9.	Metformin	0-9	matrix metallopeptidase 9	Homo sapiens	215-219
26576639-8	2015	Treatment with metformin markedly suppressed PKM2 and SDC2 expression at both the transcriptional and posttranscriptional levels and inhibited HC cell proliferation and tumor growth.	Metformin	15-24	syndecan 2	Homo sapiens	54-58
26576639-10	2015	Inhibition of PKM2 and SDC2 expression contributes to the therapeutic effect of metformin on HC.	Metformin	80-89	syndecan 2	Homo sapiens	23-27
26484566-4	2015	We show that inhibition of complex I by metformin promotes melanoma growth in mice via elevating lactate and VEGF levels.	Metformin	40-49	vascular endothelial growth factor A	Mus musculus	109-113
26420354-0	2015	Deficiency in apolipoprotein A-I ablates the pharmacological effects of metformin on plasma glucose homeostasis and hepatic lipid deposition.	Metformin	72-81	apolipoprotein A-I	Mus musculus	14-32
26420354-2	2015	Here we investigated the potential involvement of ApoA-I in the pharmacological effects of metformin on glucose intolerance and NAFLD development.	Metformin	91-100	apolipoprotein A-I	Mus musculus	50-56
26420354-5	2015	Metformin treatment led to a comparable reduction in plasma insulin levels in both C57BL/6 and apoa1(-/-) mice following intraperitoneal glucose tolerance test.	Metformin	0-9	apolipoprotein A-I	Mus musculus	95-100
26420354-7	2015	Similarly, deficiency in ApoA-I ablated the effect of metformin on hepatic lipid deposition and NAFLD development.	Metformin	54-63	apolipoprotein A-I	Mus musculus	25-31
26420354-8	2015	Gene expression analysis indicated that the effects of ApoA-I on metformin treatment may be independent of adenosine monophosphate-activated protein kinase (AMPK) activation and de novo lipogenesis.	Metformin	65-74	apolipoprotein A-I	Mus musculus	55-61
26420354-9	2015	Interestingly, metformin treatment reduced mitochondrial oxidative phosphorylation function only in apoa1(-/-) mice.	Metformin	15-24	apolipoprotein A-I	Mus musculus	100-105
26420354-10	2015	Our data show that the role of ApoA-I in diabetes extends to the modulation of the pharmacological actions of metformin, a common drug for the treatment of type 2 diabetes.	Metformin	110-119	apolipoprotein A-I	Mus musculus	31-37
28827024-9	2017	IMPLICATIONS: The network meta-analysis found that compared with glucagon-like peptide 1 receptor agonists, metformin, and alpha-glucosidase inhibitor, dipeptidyl peptidase 4 inhibitors are associated with a lower incidence of gastrointestinal adverse events.	Metformin	108-117	dipeptidyl peptidase 4	Homo sapiens	152-174
26528939-4	2015	The effects of metformin treatment were tested on myotonic dystrophy type I (DM1), a multisystemic disease considered to be a spliceopathy.	Metformin	15-24	DM1 protein kinase	Homo sapiens	77-80
26201966-12	2015	When stratified by metformin use, IGF-1R remained significantly elevated (P = 0.01) in men with PCa detected whereas p-AMPK (P = 0.05) was elevated only in those without PCa.	Metformin	19-28	insulin like growth factor 1 receptor	Homo sapiens	34-40
26201966-15	2015	The finding of IGF-1R elevation in positive PNBs versus p-AMPK elevation in negative PNBs suggests altered metabolic pathway activation precipitated by metformin use.	Metformin	152-161	insulin like growth factor 1 receptor	Homo sapiens	15-21
26141671-0	2015	Metformin ameliorates the proinflammatory state in patients with carotid artery atherosclerosis through sirtuin 1 induction.	Metformin	0-9	sirtuin 1	Homo sapiens	104-113
26141671-8	2015	Furthermore, metformin significantly induced sirtuin 1 (SIRT1) expression in MNCs.	Metformin	13-22	sirtuin 1	Homo sapiens	45-54
26141671-8	2015	Furthermore, metformin significantly induced sirtuin 1 (SIRT1) expression in MNCs.	Metformin	13-22	sirtuin 1	Homo sapiens	56-61
26141671-9	2015	Moreover, we found that metformin treatment dramatically induced SIRT1 expression, blocked p65 acetylation, and inhibited NF-kappaB activity and the expression of inflammatory factors in MNCs in vitro.	Metformin	24-33	sirtuin 1	Homo sapiens	65-70
26141671-10	2015	We conclude that metformin has a novel direct protective role to ameliorate the proinflammatory response through SIRT1 induction, p65 acetylation reduction, NF-kappaB inactivation, and inflammatory inhibition in peripheral blood MNCs of patients with carotid artery AS.	Metformin	17-26	sirtuin 1	Homo sapiens	113-118
26503334-0	2015	NLK functions to maintain proliferation and stemness of NSCLC and is a target of metformin.	Metformin	81-90	nemo like kinase	Homo sapiens	0-3
26503334-13	2015	Furthermore, metformin selectively inhibits NLK expression and proliferation in NSCLC cells, but not immortalized noncancerous lung bronchial epithelial cells.	Metformin	13-22	nemo like kinase	Homo sapiens	44-47
26503334-17	2015	Metformin inhibits NLK expression and might be a potential treatment strategy for NSCLC.	Metformin	0-9	nemo like kinase	Homo sapiens	19-22
26302449-0	2015	Metformin ameliorates lipotoxicity-induced mesangial cell apoptosis partly via upregulation of glucagon like peptide-1 receptor (GLP-1R).	Metformin	0-9	glucagon-like peptide 1 receptor	Mus musculus	95-127
26302449-0	2015	Metformin ameliorates lipotoxicity-induced mesangial cell apoptosis partly via upregulation of glucagon like peptide-1 receptor (GLP-1R).	Metformin	0-9	glucagon-like peptide 1 receptor	Mus musculus	129-135
26302449-5	2015	Interestingly, metformin, one of the biguanide drugs that has anti-diabetic effects, attenuated lipotoxicity-induced mesangial cell apoptosis and restored GLP-1R expression.	Metformin	15-24	glucagon-like peptide 1 receptor	Mus musculus	155-161
26302449-12	2015	Furthermore, we provided the evidence that metformin treatment has a renal protective effect partly via increased mesangial GLP-1R expression.	Metformin	43-52	glucagon-like peptide 1 receptor	Mus musculus	124-130
26302449-13	2015	Our data suggested that regulation of GLP-1R expression could be a promising approach to treat diabetic nephropathy and the novel mechanism of metformin mediated GLP-1R regulation.	Metformin	143-152	glucagon-like peptide 1 receptor	Mus musculus	38-44
26302449-13	2015	Our data suggested that regulation of GLP-1R expression could be a promising approach to treat diabetic nephropathy and the novel mechanism of metformin mediated GLP-1R regulation.	Metformin	143-152	glucagon-like peptide 1 receptor	Mus musculus	162-168
26692929-8	2015	PGC-1alpha, p-AMPK and p-ERK protein expression was up-regulated by Metformin in skeletal muscle and C2C12 cells.	Metformin	68-77	eukaryotic translation initiation factor 2 alpha kinase 3	Mus musculus	23-28
26254015-7	2015	Metformin had a similar effect on ANGPTL8 expression to that of AICAR.	Metformin	0-9	angiopoietin like 8	Homo sapiens	34-41
28533436-0	2017	Metformin Synergizes with BCL-XL/BCL-2 Inhibitor ABT-263 to Induce Apoptosis Specifically in p53-Defective Cancer Cells.	Metformin	0-9	transformation related protein 53, pseudogene	Mus musculus	93-96
28533436-4	2017	However, it remains unknown whether mTORC1 activation confers ABT-263 resistance and whether metformin can overcome it in the p53-defective contexts.	Metformin	93-102	transformation related protein 53, pseudogene	Mus musculus	126-129
28533436-5	2017	In this study, we for the first time demonstrated that metformin and ABT-263 synergistically elicited remarkable apoptosis through orchestrating the proapoptotic machineries in various p53-defective cancer cells.	Metformin	55-64	transformation related protein 53, pseudogene	Mus musculus	185-188
28533436-8	2017	Blocking the axis using corresponding kinase inhibitors or neutralizing antibodies against different SASP components sensitized the cotreatment effect of metformin and ABT-263 in p53-WT cancer cells.	Metformin	154-163	transformation related protein 53, pseudogene	Mus musculus	179-182
28533436-9	2017	The in vivo experiments showed that metformin and ABT-263 synergistically inhibited the growth of p53-defective (but not p53-WT) cancer cells in tumor xenograft nude mice.	Metformin	36-45	transformation related protein 53, pseudogene	Mus musculus	98-101
28533436-10	2017	These results suggest that the combination of metformin and ABT-263 may be a novel targeted therapeutic strategy for p53-defective cancers.	Metformin	46-55	transformation related protein 53, pseudogene	Mus musculus	117-120
27923278-8	2017	Most importantly, the AMPK activator metformin was associated with decreased serum hepcidin content and anemia morbidity in Chinese type 2 diabetes mellitus patients.	Metformin	37-46	hepcidin antimicrobial peptide	Homo sapiens	83-91
28206714-9	2017	Metformin counteracted the effect of high glucose on the elevated G6P and fructose 2,6-bisphosphate and on Gck repression, recruitment of Mlx-ChREBP to the G6pc and Pklr promoters and induction of these genes.	Metformin	0-9	MAX dimerization protein MLX	Homo sapiens	138-141
28383657-4	2017	The validation parameters were acceptable over concentration ranges of 5-1,000 ng mL-1 and 50-25,000 ng mL-1 for empagliflozin and metformin, respectively.	Metformin	131-140	L1 cell adhesion molecule	Mus musculus	82-96
28816632-6	2017	Liver-specific ablation of Bmal1 expression alters metformin induction of AMPK and blood glucose response but does not completely abolish time of day differences.	Metformin	51-60	aryl hydrocarbon receptor nuclear translocator-like	Mus musculus	27-32
28455750-1	2017	In type 2 diabetes patients treated in German primary care practices, the use of dipeptidyl peptidase-4 inhibitor (DPP4i) in combination with metformin was associated with a significant decrease in the risk of developing bone fractures compared to metformin monotherapy.	Metformin	248-257	dipeptidyl peptidase 4	Homo sapiens	81-103
28720775-6	2017	Metformin inhibited the activation of Smad2/3 and MAPK, GSK-3beta phosphorylation, nuclear translocalization of beta-catenin and Snail in HPMCs.	Metformin	0-9	catenin beta 1	Homo sapiens	112-124
28698800-0	2017	Metformin-induced ablation of microRNA 21-5p releases Sestrin-1 and CAB39L antitumoral activities.	Metformin	0-9	sestrin 1	Homo sapiens	54-63
28698800-5	2017	Interestingly, the inhibition of miR-21-5p following metformin treatment was also observed in mouse breast cancer xenografts and in sera from 96 breast cancer patients.	Metformin	53-62	microRNA 215	Mus musculus	33-42
28675758-7	2017	Furthermore, metformin exposure led to an increased apoptosis rate and cell-cycle arrest accompanied with downregulation of Ccna2 and Ccnb2.	Metformin	13-22	cyclin A2	Rattus norvegicus	124-129
28819383-0	2017	Metformin Inhibits Tumorigenesis and Tumor Growth of Breast Cancer Cells by Upregulating miR-200c but Downregulating AKT2 Expression.	Metformin	0-9	AKT serine/threonine kinase 2	Homo sapiens	117-121
28819383-10	2017	Metformin treatment was associated with increased miR-200c expression and decreased c-Myc and AKT2 protein expression in both breast cancer cells and tumor tissues.	Metformin	0-9	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	84-89
28819383-10	2017	Metformin treatment was associated with increased miR-200c expression and decreased c-Myc and AKT2 protein expression in both breast cancer cells and tumor tissues.	Metformin	0-9	AKT serine/threonine kinase 2	Homo sapiens	94-98
28819383-13	2017	Conclusion: Metformin inhibits the growth and invasiveness of breast cancer cells by upregulation of miR-200c expression by targeting AKT2.	Metformin	12-21	AKT serine/threonine kinase 2	Homo sapiens	134-138
28385910-6	2017	Finally, it was demonstrated that metformin had disparate effects on proliferation, migration, and prostate-specific antigen secretion from different cell lines.	Metformin	34-43	kallikrein related peptidase 3	Homo sapiens	99-124
28560428-6	2017	Metformin treatment ameliorated HFD-induced hepatic steatosis and serum levels of triglycerides, which was consistent with a marked increase in the expression levels of microtubule-associated protein 1 light chain 3 (LC3) and AMP-activated protein kinase (AMPK) in the liver following metformin treatment.	Metformin	0-9	microtubule-associated protein 1 light chain 3 alpha	Mus musculus	217-220
28560428-7	2017	However, metformin suppressed the expression of LC3 in the eWAT without altering the expression of AMPK, compared with that in the HFD mice.	Metformin	9-18	microtubule-associated protein 1 light chain 3 alpha	Mus musculus	48-51
28632780-3	2017	Recent work suggests that treating invertebrate and mice HD models with metformin, a well-known AMPK activator which is used worldwide to treat type 2-diabetes, reduces mutant huntingtin from cells and alleviates many of the phenotypes associated to HD.	Metformin	72-81	huntingtin	Mus musculus	176-186
28601826-0	2017	Study protocol of a phase IB/II clinical trial of metformin and chloroquine in patients with IDH1-mutated or IDH2-mutated solid tumours.	Metformin	50-59	isocitrate dehydrogenase (NADP(+)) 1	Homo sapiens	93-97
28601826-4	2017	IDH1/2-mutated cancer cells produce the oncometabolite D-2-hydroxyglutarate (D-2HG) and are metabolically vulnerable to treatment with the oral antidiabetic metformin and the oral antimalarial drug chloroquine.	Metformin	157-166	isocitrate dehydrogenase (NADP(+)) 1	Homo sapiens	0-4
28380462-6	2017	In addition, GH secretion was inhibited by metformin through suppression of STAT3 activity independently of AMPK.	Metformin	43-52	signal transducer and activator of transcription 3	Rattus norvegicus	76-81
28542373-6	2017	The relative risks of all-cause mortality with SGLT2 inhibitor use were 0.68 (95% credible interval: 0.57-0.80), 0.74 (0.49-1.10), 0.63 (0.46-0.87), 0.71 (0.55-0.90), and 0.65 (0.54-0.78), compared with placebo, metformin, sulfonylurea, TZD, and DPP4 inhibitor, respectively.	Metformin	212-221	solute carrier family 5 member 2	Homo sapiens	47-52
28542373-7	2017	The relative risks of cardiovascular-related mortality with SGLT2 inhibitor use were 0.61 (0.50-0.76), 0.81(0.36-1.90), 0.52(0.31-0.88), 0.66(0.49-0.91), and 0.61(0.48-0.77), compared with placebo, metformin, sulfonylurea, TZD, and DPP4 inhibitor, respectively.	Metformin	198-207	solute carrier family 5 member 2	Homo sapiens	60-65
28761738-1	2017	PURPOSE: Our previous works demonstrated the ability of metformin to revert resistance to gefitinib, a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in non-small-cell lung cancer (NSCLC) EGFR/LKB1 wild-type (WT) cell lines.	Metformin	56-65	serine/threonine kinase 11	Homo sapiens	223-227
28233033-10	2017	In humans, adipose tissue expression of DHH and serum IHH decrease with obesity and type 2 diabetes, which might be explained by the intake of metformin.	Metformin	143-152	Indian hedgehog signaling molecule	Homo sapiens	54-57
28233033-11	2017	Interestingly, metformin reduced Dhh and Ihh expression in mouse adipose tissue explants.	Metformin	15-24	desert hedgehog	Mus musculus	33-36
28238946-0	2017	Involvement of pregnane X receptor in the suppression of carboxylesterases by metformin in vivo and in vitro, mediated by the activation of AMPK and JNK signaling pathway.	Metformin	78-87	carboxylesterase 1D	Mus musculus	57-74
28238946-4	2017	In the present study, experiments are designed to investigate the effects and mechanisms of metformin on Ces1d and Ces1e in vivo and in vitro.	Metformin	92-101	carboxylesterase 1D	Mus musculus	105-110
28238946-5	2017	In results, metformin suppresses the expression and activity of Ces1d and Ces1e in a dose- and time-dependent manner.	Metformin	12-21	carboxylesterase 1D	Mus musculus	64-69
28238946-6	2017	The decreased expression of nuclear receptor PXR and its target gene P-gp indicates the involvements of PXR in the suppressed expression of carboxylesterases by metformin.	Metformin	161-170	phosphoglycolate phosphatase	Homo sapiens	69-73
28238946-6	2017	The decreased expression of nuclear receptor PXR and its target gene P-gp indicates the involvements of PXR in the suppressed expression of carboxylesterases by metformin.	Metformin	161-170	carboxylesterase 1D	Mus musculus	140-157
28238946-7	2017	Furthermore, metformin significantly suppresses the phosphorylation of AMPK and JNK, and the suppression of carboxylesterases induced by metformin is repeatedly abolished by AMPK inhibitor Compound C and JNK inhibitor SP600125.	Metformin	13-22	carboxylesterase 1D	Mus musculus	108-125
28238946-7	2017	Furthermore, metformin significantly suppresses the phosphorylation of AMPK and JNK, and the suppression of carboxylesterases induced by metformin is repeatedly abolished by AMPK inhibitor Compound C and JNK inhibitor SP600125.	Metformin	137-146	carboxylesterase 1D	Mus musculus	108-125
28238946-8	2017	It implies that the activation of AMPK and JNK pathways mediates the suppression of carboxylesterases by metformin.	Metformin	105-114	carboxylesterase 1D	Mus musculus	84-101
28393220-0	2017	Metformin increases sensitivity of osteosarcoma stem cells to cisplatin by inhibiting expression of PKM2.	Metformin	0-9	pyruvate kinase M1/2	Homo sapiens	100-104
28393220-7	2017	As a potential strategy, we found that co-treatment with metformin significantly decreased the half maximal inhibitory concentration (IC50) of cisplatin to HOS OS stem cells by downregulating the expression of PKM2.	Metformin	57-66	pyruvate kinase M1/2	Homo sapiens	210-214
28393220-8	2017	PKM2 downregulation resulted in, metformin inhibited glucose uptake, lactate production and ATP production in HOS CSCs.	Metformin	33-42	pyruvate kinase M1/2	Homo sapiens	0-4
28494038-10	2017	CONCLUSION: Metformin did not modulate the damaging effect of hyperglycemia on bone healing around implants at histometric levels, but increased the expression of OPG and decreased the RANKL/OPG ratio in the medullary area, yielding some molecular benefits in the osseointegration of implants under the hyperglycemic state.	Metformin	12-21	TNF receptor superfamily member 11B	Rattus norvegicus	163-166
28494038-10	2017	CONCLUSION: Metformin did not modulate the damaging effect of hyperglycemia on bone healing around implants at histometric levels, but increased the expression of OPG and decreased the RANKL/OPG ratio in the medullary area, yielding some molecular benefits in the osseointegration of implants under the hyperglycemic state.	Metformin	12-21	TNF receptor superfamily member 11B	Rattus norvegicus	191-194
28152176-0	2017	Metformin-SGLT2, Dehydration, and Acidosis Potential.	Metformin	0-9	solute carrier family 5 member 2	Homo sapiens	10-15
27248136-0	2017	Metformin ameliorates podocyte damage by restoring renal tissue nephrin expression in type 2 diabetic rats.	Metformin	0-9	NPHS1 adhesion molecule, nephrin	Rattus norvegicus	64-71
27248136-2	2017	In the present study, we evaluated the effects of different doses of metformin on the expression of renal tissue nephrin in type 2 diabetes mellitus (T2DM) model rats and the possible mechanism underlying its protective effect in kidney podocytes.	Metformin	69-78	NPHS1 adhesion molecule, nephrin	Rattus norvegicus	113-120
27248136-8	2017	RESULTS: Metformin treatment of T2DM rats produced dose-dependent significant reductions in urinary albumin and nephrin concentrations, glomerular basement membrane thickness (GBMT), and the foot process fusion rate (FPFR) compared with control T2DM model rats, whereas renal expression of nephrin protein and Nphs1 mRNA was dose-dependently increased by metformin treatment.	Metformin	9-18	NPHS1 adhesion molecule, nephrin	Rattus norvegicus	112-119
27248136-8	2017	RESULTS: Metformin treatment of T2DM rats produced dose-dependent significant reductions in urinary albumin and nephrin concentrations, glomerular basement membrane thickness (GBMT), and the foot process fusion rate (FPFR) compared with control T2DM model rats, whereas renal expression of nephrin protein and Nphs1 mRNA was dose-dependently increased by metformin treatment.	Metformin	9-18	NPHS1 adhesion molecule, nephrin	Rattus norvegicus	290-297
27248136-8	2017	RESULTS: Metformin treatment of T2DM rats produced dose-dependent significant reductions in urinary albumin and nephrin concentrations, glomerular basement membrane thickness (GBMT), and the foot process fusion rate (FPFR) compared with control T2DM model rats, whereas renal expression of nephrin protein and Nphs1 mRNA was dose-dependently increased by metformin treatment.	Metformin	9-18	NPHS1 adhesion molecule, nephrin	Rattus norvegicus	310-315
27248136-9	2017	CONCLUSION: Metformin protects kidney podocytes in T2DM model rats by dose-dependently adjusting renal nephrin expression.	Metformin	12-21	NPHS1 adhesion molecule, nephrin	Rattus norvegicus	103-110
27380451-0	2017	Effects of metformin treatment on blood leptin and ghrelin levels in patients with type 2 diabetes mellitus.	Metformin	11-20	leptin	Homo sapiens	40-46
27380451-1	2017	BACKGROUND: The aim of the present study was to conduct a meta-analysis of randomized controlled trials (RCTs) that investigated the effects of metformin on blood leptin and ghrelin levels in patients with type 2 diabetes mellitus (T2DM).	Metformin	144-153	leptin	Homo sapiens	163-169
27380451-9	2017	However, blood leptin levels were significantly lower in the metformin compared with the other OADs group.	Metformin	61-70	leptin	Homo sapiens	15-21
28485785-0	2017	Study on the influence of metformin on castration-resistant prostate cancer PC-3 cell line biological behavior by its inhibition on PLCepsilon gene-mediated Notch1/Hes and androgen receptor signaling pathway.	Metformin	26-35	ribosome binding protein 1	Homo sapiens	164-167
28485785-1	2017	OBJECTIVE: To study the regulation of metformin on the biological behaviors of the castration-resistant prostate cancer (CRPC) PC-3 cell such as proliferation, invasion, apoptosis through influencing Notch1/Hes and androgen receptor (AR) signaling pathway activity by its inhibition on the expression of PLCepsilon gene.	Metformin	38-47	ribosome binding protein 1	Homo sapiens	207-210
28485785-10	2017	CONCLUSIONS: Metformin can regulate the biological behaviors of CRPC PC-3 cell line such as proliferation, invasion, migration and apoptosis through influencing Notch1/Hes and AR signaling pathway activity by its inhibition on the expression of PLCepsilon gene.	Metformin	13-22	ribosome binding protein 1	Homo sapiens	168-171
28403729-1	2017	INTRODUCTION: Vildagliptin is an inhibitor of the enzyme dipeptidyl peptidase 4, indicated for the treatment of type 2 diabetes mellitus, combined or not with metformin.	Metformin	159-168	dipeptidyl peptidase 4	Homo sapiens	57-79
28242651-0	2017	Metformin Suppresses Systemic Autoimmunity in Roquinsan/san Mice through Inhibiting B Cell Differentiation into Plasma Cells via Regulation of AMPK/mTOR/STAT3.	Metformin	0-9	mechanistic target of rapamycin kinase	Mus musculus	148-152
28242651-4	2017	We assessed the effect of metformin, which inhibits mTOR, on the development of autoimmunity using Roquinsan/san mice.	Metformin	26-35	mechanistic target of rapamycin kinase	Mus musculus	52-56
28242651-10	2017	These alterations in B and T cell subsets by metformin were associated with enhanced AMPK expression and inhibition of mTOR-STAT3 signaling.	Metformin	45-54	mechanistic target of rapamycin kinase	Mus musculus	119-123
28242651-11	2017	Furthermore, metformin induced p53 and NF erythroid-2-related factor-2 activity in splenic CD4+ T cells.	Metformin	13-22	transformation related protein 53, pseudogene	Mus musculus	31-34
28242651-12	2017	Taken together, metformin-induced alterations in AMPK-mTOR-STAT3 signaling may have therapeutic value in SLE by inhibiting B cell differentiation into PCs and GCs.	Metformin	16-25	mechanistic target of rapamycin kinase	Mus musculus	54-58
28260041-0	2017	Metformin suppresses the expression of Sonic hedgehog in gastric cancer cells.	Metformin	0-9	sonic hedgehog signaling molecule	Homo sapiens	39-53
28260041-3	2017	The aim of the present study was to investigate whether metformin has an effect on the Shh signaling pathway in gastric cancer cells.	Metformin	56-65	sonic hedgehog signaling molecule	Homo sapiens	87-90
28260041-6	2017	RNA interference was used to detect whether the effects of metformin treatment on the Shh signaling pathway were dependent on AMP-activated protein kinase (AMPK).	Metformin	59-68	sonic hedgehog signaling molecule	Homo sapiens	86-89
28260041-7	2017	The results revealed that the protein and mRNA levels of Shh and Gli-1 were decreased by metformin treatment in the two cell lines in a dose- and time-dependent manner.	Metformin	89-98	sonic hedgehog signaling molecule	Homo sapiens	57-60
28260041-8	2017	Metformin also significantly inhibited the gene and protein expression levels of SMO, Gli-2 and Gli-3.	Metformin	0-9	smoothened, frizzled class receptor	Homo sapiens	81-84
28260041-9	2017	The small interfering RNA-induced depletion of AMPK reversed the suppressive effect of metformin on recombinant human Shh-induced expression of Gli-1 in HGC-27 gastric cancer cells.	Metformin	87-96	sonic hedgehog signaling molecule	Homo sapiens	118-121
28260041-10	2017	Therefore, metformin inhibited the Shh signaling pathway in the gastric cancer cell lines and the inhibitory effect of metformin on the Shh pathway was AMPK-dependent.	Metformin	11-20	sonic hedgehog signaling molecule	Homo sapiens	35-38
26359363-0	2015	Metformin represses cancer cells via alternate pathways in N-cadherin expressing vs. N-cadherin deficient cells.	Metformin	0-9	cadherin 2	Homo sapiens	59-69
26359363-0	2015	Metformin represses cancer cells via alternate pathways in N-cadherin expressing vs. N-cadherin deficient cells.	Metformin	0-9	cadherin 2	Homo sapiens	85-95
28260041-10	2017	Therefore, metformin inhibited the Shh signaling pathway in the gastric cancer cell lines and the inhibitory effect of metformin on the Shh pathway was AMPK-dependent.	Metformin	119-128	sonic hedgehog signaling molecule	Homo sapiens	136-139
28491145-0	2017	Combination of metformin and curcumin targets breast cancer in mice by angiogenesis inhibition, immune system modulation and induction of p53 independent apoptosis.	Metformin	15-24	transformation related protein 53	Mus musculus	138-141
26359363-2	2015	Here, we demonstrate that metformin plays an anti-tumor role via repressing N-cadherin, independent of AMPK, in wild-type N-cadherin cancer cells.	Metformin	26-35	cadherin 2	Homo sapiens	76-86
26359363-2	2015	Here, we demonstrate that metformin plays an anti-tumor role via repressing N-cadherin, independent of AMPK, in wild-type N-cadherin cancer cells.	Metformin	26-35	cadherin 2	Homo sapiens	122-132
26359363-3	2015	Ectopic-expression of N-cadherin develops metformin-resistant cancer cells, while suppression of N-cadherin sensitizes cancer to metformin.	Metformin	42-51	cadherin 2	Homo sapiens	22-32
26359363-3	2015	Ectopic-expression of N-cadherin develops metformin-resistant cancer cells, while suppression of N-cadherin sensitizes cancer to metformin.	Metformin	129-138	cadherin 2	Homo sapiens	97-107
26359363-5	2015	We show that NF-kappaB is a downstream molecule of N-cadherin and metformin regulates NF-kappaB signaling via suppressing N-cadherin.	Metformin	66-75	cadherin 2	Homo sapiens	51-61
26359363-5	2015	We show that NF-kappaB is a downstream molecule of N-cadherin and metformin regulates NF-kappaB signaling via suppressing N-cadherin.	Metformin	66-75	cadherin 2	Homo sapiens	122-132
26359363-6	2015	Moreover, we also suggest that TWIST1 is an upstream molecule of N-cadherin/NF-kappaB signaling and manipulation of TWIST1 expression changes the sensitivity of cancer cells to metformin.	Metformin	177-186	cadherin 2	Homo sapiens	65-75
26359363-7	2015	In contrast to the cells that express N-cadherin, in N-cadherin deficient cells, metformin plays an anti-tumor role via activation of AMPK.	Metformin	81-90	cadherin 2	Homo sapiens	53-63
26260219-11	2015	The expression of the mesenchymal marker MMP9 was decreased in the metformin-treated group.	Metformin	67-76	matrix metallopeptidase 9	Homo sapiens	41-45
26426900-5	2015	OCT1-, OCT2-, MATE1- and MATE2-K-mediated metformin uptake was significantly reduced in the presence of green tea and EGCG (P &lt; 0.05).	Metformin	42-51	POU class 2 homeobox 2	Homo sapiens	7-11
26426900-5	2015	OCT1-, OCT2-, MATE1- and MATE2-K-mediated metformin uptake was significantly reduced in the presence of green tea and EGCG (P &lt; 0.05).	Metformin	42-51	solute carrier family 47 member 1	Homo sapiens	14-19
26360050-9	2015	Treatment with metformin inhibited the expression of interleukin (IL)-17, p-STAT3, and p-mTOR.	Metformin	15-24	interleukin 17A	Homo sapiens	53-72
26360050-12	2015	CONCLUSIONS: Metformin attenuates IBD severity and reduces inflammation through the inhibition of p-STAT3 and IL-17 expression.	Metformin	13-22	interleukin 17A	Homo sapiens	110-115
26622758-8	2015	BFPs combined with metformin significantly affected PCOS, and the possible mechanism involved in the treatment may have been through the reduction of P450scc generation.	Metformin	19-28	cytochrome P450, family 11, subfamily a, polypeptide 1	Rattus norvegicus	150-157
25971328-4	2015	The NCBI Gene Expression Omnibus (GEO) database was analyzed to identify micro-RNA change in BrCa cells treated by metformin, a common drug for DM worldwide.	Metformin	115-124	BRCA1 DNA repair associated	Homo sapiens	93-97
25971328-11	2015	BrCa patients with DM could possibly benefit from metformin treatment via DICER mediation.	Metformin	50-59	BRCA1 DNA repair associated	Homo sapiens	0-4
26327616-0	2015	Substrate-Dependent Inhibition of the Human Organic Cation Transporter OCT2: A Comparison of Metformin with Experimental Substrates.	Metformin	93-102	POU class 2 homeobox 2	Homo sapiens	71-75
26327616-2	2015	In fact, there are clinically significant interactions for drugs that are known substrates of OCT2 such as metformin.	Metformin	107-116	POU class 2 homeobox 2	Homo sapiens	94-98
26327616-5	2015	Here we compared the OCT2 inhibition profile data for the substrates metformin, MPP+ and ASP+.	Metformin	69-78	POU class 2 homeobox 2	Homo sapiens	21-25
26327616-6	2015	We used human embryonic kidney (HEK 293) cells stably overexpressing human OCT2 as the test system to screen 125 frequently prescribed drugs as inhibitors of OCT2-mediated metformin and MPP+ uptake.	Metformin	172-181	POU class 2 homeobox 2	Homo sapiens	75-79
26327616-6	2015	We used human embryonic kidney (HEK 293) cells stably overexpressing human OCT2 as the test system to screen 125 frequently prescribed drugs as inhibitors of OCT2-mediated metformin and MPP+ uptake.	Metformin	172-181	POU class 2 homeobox 2	Homo sapiens	158-162
26327616-8	2015	A moderate correlation between the inhibition of OCT2-mediated MPP+, ASP+, and metformin uptake was observed (pairwise rs between 0.27 and 0.48, all P &lt; 0.05).	Metformin	79-88	POU class 2 homeobox 2	Homo sapiens	49-53
26058395-9	2015	CONCLUSION: Metformin could inhibit PGE2-induced CYP19A1 mRNA expression and aromatase activity via AMPK activation and inhibition of CREB to CYP19A1 PII in human ESCs.	Metformin	12-21	cAMP responsive element binding protein 1	Homo sapiens	134-138
25871950-10	2015	Additionally, metformin treatment significantly inhibited SirT7, SirT1, and p16(INK4a) mRNA expression in WBCs at 1, 2, and 3 hr, whereas p53 was inhibited significantly at 2 hr after LPS injection.	Metformin	14-23	sirtuin 7	Mus musculus	58-63
25871950-12	2015	The data suggest that metformin may exert its potential antisenescence and anti-inflammatory effects by targeting SirT7 and SirT1 pathways.	Metformin	22-31	sirtuin 7	Mus musculus	114-119
25854169-7	2015	Moreover, metformin regulated expression of the EMT-related markers E-cadherin, N-cadherin, and Snail.	Metformin	10-19	cadherin 2	Homo sapiens	80-90
25854169-8	2015	Additionally, knockdown of TSC2, the upstream regulatory molecule of mTOR pathway, or treatment of rapamycin, the mTOR inhibitor, could abolish the effects of metformin to regulate thyroid cancer cell proliferation, migration, EMT, and mTOR pathway molecules.	Metformin	159-168	TSC complex subunit 2	Homo sapiens	27-31
28043910-3	2017	In this study, we demonstrated that metformin is capable of inhibiting prostate cancer cell migration and invasion by repressing EMT evidenced by downregulating the mesenchymal markers N-cadherin, Vimentin, and Twist and upregulating the epithelium E-cadherin.	Metformin	36-45	vimentin	Homo sapiens	197-205
28174122-1	2017	AIMS: To investigate the roles of salt inducible kinase (SIK1) in high glucose-induced triglyceride accumulation in human hepatoma HepG2 cells as well as in the molecular mechanism by which metformin, a drug to treat diabetes, suppresses high glucose-induced lipogenesis.	Metformin	190-199	salt inducible kinase 1	Homo sapiens	57-61
28174122-9	2017	Furthermore, treatment with metformin upregulated SIK1 mRNA and protein levels, as well as the active form of SIK1.	Metformin	28-37	salt inducible kinase 1	Homo sapiens	50-54
28174122-9	2017	Furthermore, treatment with metformin upregulated SIK1 mRNA and protein levels, as well as the active form of SIK1.	Metformin	28-37	salt inducible kinase 1	Homo sapiens	110-114
28174122-10	2017	SIGNIFICANCE: SIK1 plays a vital role in high glucose-induced lipid accumulation, and metformin suppresses lipogenesis via the induction and activation of SIK1.	Metformin	86-95	salt inducible kinase 1	Homo sapiens	155-159
28069720-2	2017	As pregnancy increased the renal secretion of metformin, a substrate for OCT2, MATE1, and MATE2-K, we hypothesized that the renal secretion of 1-NMN would be similarly affected.	Metformin	46-55	solute carrier family 22 member 2	Homo sapiens	73-77
28104298-9	2017	Metformin, an anti-diabetic agent, was found to increase Klf10 and suppress UVRAG expression to improve radiation cytotoxicity in pancreatic cancer.	Metformin	0-9	Kruppel like factor 10	Homo sapiens	57-62
27995594-4	2017	METHODS: We aimed to evaluate the relative efficacy, using network meta-analysis (NMA), of treatment intensification with liraglutide and SGLT-2 inhibitors people with T2DM who have been treated with metformin (alone or in combination with SU, DPP-4, and TZD).	Metformin	200-209	solute carrier family 5 member 2	Homo sapiens	138-144
25981932-8	2015	However, subsequent AMPK activation and mTOR pathway inhibition were prominent only in metformin-insensitive non-metastatic cells.	Metformin	87-96	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	20-24
25981932-8	2015	However, subsequent AMPK activation and mTOR pathway inhibition were prominent only in metformin-insensitive non-metastatic cells.	Metformin	87-96	mechanistic target of rapamycin kinase	Canis lupus familiaris	40-44
25981932-11	2015	In conclusion, metformin exhibited an anti-tumour effect in metastatic CMGT cells through AMPK-independent cell cycle arrest.	Metformin	15-24	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	90-94
25940306-2	2015	Salicylate activates the AMP-activated protein kinase (AMPK) by binding at the A-769662 drug binding site on the AMPK beta1-subunit, a mechanism that is distinct from metformin which disrupts the adenylate charge of the cell.	Metformin	167-176	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	55-59
25940306-6	2015	Salicylate concentrations of 1 mM increased the phosphorylation of ACC and suppressed de novo lipogenesis and these effects were enhanced with the addition of clinical concentrations of metformin (100 muM) and eliminated in mouse embryonic fibroblasts (MEFs) deficient in AMPK beta1.	Metformin	186-195	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	272-276
27856287-4	2017	Spinal local application of AMPK agonist metformin (25mug) prevented the long term potentiation (LTP) induction and the activation of mTOR/p70S6K signal pathway, and significantly attenuated the acute thermal hyperalgesia and mechanical allodynia following single oxaliplatin treatment.	Metformin	41-50	ribosomal protein S6 kinase B1	Homo sapiens	139-145
27856287-8	2017	Local application of metformin significantly decreased the mTOR and p70S6K activation induced by tetanus stimulation or oxaliplatin (i.p.).	Metformin	21-30	ribosomal protein S6 kinase B1	Homo sapiens	68-74
28239505-0	2017	Statins and Metformin Use Is Associated with Lower PSA Levels in Prostate Cancer Patients Presenting for Radiation Therapy.	Metformin	12-21	kallikrein related peptidase 3	Homo sapiens	51-54
26004431-0	2015	SLC47A1 gene rs2289669 G&gt;A variants enhance the glucose-lowering effect of metformin via delaying its excretion in Chinese type 2 diabetes patients.	Metformin	78-87	solute carrier family 47 member 1	Homo sapiens	0-7
26004431-1	2015	AIMS: The SLC47A1 gene encodes the multi-drug and toxic excretion-1(MATE1) protein, which plays a key role in the transport and excretion of metformin.	Metformin	141-150	solute carrier family 47 member 1	Homo sapiens	10-17
26004431-1	2015	AIMS: The SLC47A1 gene encodes the multi-drug and toxic excretion-1(MATE1) protein, which plays a key role in the transport and excretion of metformin.	Metformin	141-150	solute carrier family 47 member 1	Homo sapiens	68-73
26004431-2	2015	This study is to clarify the influence of variants in SLC47A1 (rs2289669 G A) on metformin pharmacokinetics and the long-term glucose-lowering effect of metformin.	Metformin	81-90	solute carrier family 47 member 1	Homo sapiens	54-61
26004431-2	2015	This study is to clarify the influence of variants in SLC47A1 (rs2289669 G A) on metformin pharmacokinetics and the long-term glucose-lowering effect of metformin.	Metformin	153-162	solute carrier family 47 member 1	Homo sapiens	54-61
26004431-8	2015	Pharmacokinetic parameters of metformin indicated that patients carrying MATE1 homozygous A had higher area under the plasma concentration versus time curve (AUC12h), but lower renal clearance (CLR) and renal clearance by secretion (CLSR) than other patients (all P&lt;0.01).	Metformin	30-39	solute carrier family 47 member 1	Homo sapiens	73-78
26004431-9	2015	Multivariate lineal stepwise analysis further revealed that SLC47A1 genotype was an independent impact factor for urine excretion of metformin (P&lt;0.01).	Metformin	133-142	solute carrier family 47 member 1	Homo sapiens	60-67
26004431-10	2015	CONCLUSIONS: SLC47A1 rs2289669 G&gt;A variants improve the glucose-lowering effect of metformin through slowing its excretion in type 2 diabetes populations.	Metformin	86-95	solute carrier family 47 member 1	Homo sapiens	13-20
25999130-9	2015	Furthermore, the small interfering RNA (siRNA)-mediated downregulation of AMPK reversed the inhibitory effects of metformin on rhShh-induced Gli-1 expression and stemness.	Metformin	114-123	GLI family zinc finger 1	Homo sapiens	141-146
25681557-0	2015	Metformin ameliorates acetaminophen hepatotoxicity via Gadd45beta-dependent regulation of JNK signaling in mice.	Metformin	0-9	mitogen-activated protein kinase 8	Mus musculus	90-93
25681557-7	2015	RESULTS: Metformin pretreatment protected against APAP toxicity with decreased liver damage, and inhibited APAP-induced prolonged hepatic JNK phosphorylation in WT mice.	Metformin	9-18	mitogen-activated protein kinase 8	Mus musculus	138-141
25681557-13	2015	CONCLUSIONS: This study is the first to demonstrate that metformin shows protective and therapeutic effects against APAP overdose-evoked hepatotoxicity via Gadd45beta-dependent JNK regulation.	Metformin	57-66	mitogen-activated protein kinase 8	Mus musculus	177-180
26261558-9	2015	Metformin is also capable of maintaining the biological activities of SCs after hypoxia injury, such as increasing the expression and secretion of BDNF, NGF, GDNF, and N-CAM.	Metformin	0-9	brain derived neurotrophic factor	Homo sapiens	147-151
25413451-8	2015	Pretreatment by metformin increased the level of Nrf2 and heme oxygenase-1 in the hippocampus of ischemic rats compared with untreated ischemic group.	Metformin	16-25	heme oxygenase 1	Rattus norvegicus	58-74
25909163-4	2015	In addition to activation of AMPK and suppression of the mTOR pathway, a series of increased and decreased genes expression were induced by metformin, including PTEN, MMP7, and FN1.	Metformin	140-149	matrix metallopeptidase 7	Mus musculus	167-171
25742316-0	2015	Metformin and salicylate synergistically activate liver AMPK, inhibit lipogenesis and improve insulin sensitivity.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	56-60
25742316-2	2015	Metformin and salicylate both increase AMP-activated protein kinase (AMPK) activity but by distinct mechanisms, with metformin altering cellular adenylate charge (increasing AMP) and salicylate interacting directly at the AMPK beta1 drug-binding site.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	39-67
25742316-2	2015	Metformin and salicylate both increase AMP-activated protein kinase (AMPK) activity but by distinct mechanisms, with metformin altering cellular adenylate charge (increasing AMP) and salicylate interacting directly at the AMPK beta1 drug-binding site.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	69-73
25742316-2	2015	Metformin and salicylate both increase AMP-activated protein kinase (AMPK) activity but by distinct mechanisms, with metformin altering cellular adenylate charge (increasing AMP) and salicylate interacting directly at the AMPK beta1 drug-binding site.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	222-226
25742316-2	2015	Metformin and salicylate both increase AMP-activated protein kinase (AMPK) activity but by distinct mechanisms, with metformin altering cellular adenylate charge (increasing AMP) and salicylate interacting directly at the AMPK beta1 drug-binding site.	Metformin	117-126	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	222-226
25742316-4	2015	We find doses of metformin and salicylate used clinically synergistically activate AMPK in vitro and in vivo, resulting in reduced liver lipogenesis, lower liver lipid levels and improved insulin sensitivity in mice.	Metformin	17-26	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	83-87
25843797-0	2015	DEPTOR-related mTOR suppression is involved in metformin"s anti-cancer action in human liver cancer cells.	Metformin	47-56	DEP domain containing MTOR interacting protein	Homo sapiens	0-6
25843797-6	2015	We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells.	Metformin	108-117	DEP domain containing MTOR interacting protein	Homo sapiens	14-20
25843797-7	2015	Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling.	Metformin	0-9	DEP domain containing MTOR interacting protein	Homo sapiens	42-48
25843797-8	2015	This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner.	Metformin	36-45	DEP domain containing MTOR interacting protein	Homo sapiens	26-32
25843797-8	2015	This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner.	Metformin	36-45	DEP domain containing MTOR interacting protein	Homo sapiens	182-188
25843797-8	2015	This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner.	Metformin	123-132	DEP domain containing MTOR interacting protein	Homo sapiens	26-32
25843797-8	2015	This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner.	Metformin	123-132	DEP domain containing MTOR interacting protein	Homo sapiens	182-188
25843797-9	2015	Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner.	Metformin	13-22	DEP domain containing MTOR interacting protein	Homo sapiens	75-81
25843797-10	2015	We conclude that DEPTOR-related mTOR suppression is involved in metformin"s anti-cancer action in liver, and could be a novel target for anti-cancer therapy.	Metformin	64-73	DEP domain containing MTOR interacting protein	Homo sapiens	17-23
25895126-5	2015	Metformin treatment in RD and HED mice resulted in a significant reduction in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by decreased levels of growth factors (IGF-1, insulin and leptin), inflammatory cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet mice.	Metformin	0-9	vascular endothelial growth factor A	Mus musculus	262-266
25595658-9	2015	Furthermore, co-treatment of hNSCs with metformin significantly blocked AGE-mediated reductions in the expression levels of several neuroprotective genes (PPARgamma, Bcl-2 and CREB).	Metformin	40-49	cAMP responsive element binding protein 1	Homo sapiens	176-180
25497570-8	2015	Treatment with metformin, an activator of AMPK, significantly reduced cartilage matrix formation and inhibited gene expression of sox6, sox9, col2a1 and aggrecan core protein (acp).	Metformin	15-24	aggrecan	Homo sapiens	153-174
25576058-5	2015	Metformin (but not rapamycin) reduced glucose and insulin levels and expression of miR-34a and its direct targets Notch, Slug, and Snail.	Metformin	0-9	snail family zinc finger 1	Mus musculus	131-136
25053715-12	2015	Among the KLF5/GATA4/GATA6 direct target genes relevant for cancer development, one target gene, HNF4alpha, was also required for GC proliferation and could be targeted by the antidiabetic drug metformin, revealing a therapeutic opportunity for KLF5/GATA4/GATA6 amplified GCs.	Metformin	194-203	hepatic nuclear factor 4, alpha	Mus musculus	97-106
25709052-6	2015	In addition, metformin reduced the phosphorylation of epidermal growth factor receptor and insulin-like growth factor and insulin-like growth factor-1 receptor, as well as angiogenesis-related proteins, such as vascular endothelial growth factor, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2.	Metformin	13-22	TIMP metallopeptidase inhibitor 2	Homo sapiens	300-306
25805502-7	2015	Consistently, hepatic Sort1 was down-regulated in diabetic mice, which was partially restored after the administration of the insulin sensitizer metformin.	Metformin	145-154	sortilin 1	Mus musculus	22-27
28239505-3	2017	We reported on the association between the initial PSA level and the use of statins, metformin and alpha-blockers in patients who were diagnosed with prostate cancer and presented for radiation therapy.	Metformin	85-94	kallikrein related peptidase 3	Homo sapiens	51-54
28239505-7	2017	RESULTS: Compared with men who were not on these medications, the PSA level at presentation was 20% lower for statin users (p = 0.002) and 33% lower for metformin users (p = 0.004).	Metformin	153-162	kallikrein related peptidase 3	Homo sapiens	66-69
28239505-10	2017	CONCLUSIONS: We found that statins and metformin were associated with lower PSA levels in prostate cancer patients to an extent that could influence management decisions.	Metformin	39-48	kallikrein related peptidase 3	Homo sapiens	76-79
27128966-8	2017	The activation of GSK3beta correlated with the inhibitory phosphorylation by Akt as well as p70S6K through AMPK activation in response to metformin.	Metformin	138-147	ribosomal protein S6 kinase B1	Homo sapiens	92-98
28035400-4	2017	In the present study, the AMPK activator metformin impaired breast cancer cell growth by reducing dishevelled segment polarity protein 3 (DVL3) and beta-catenin levels.	Metformin	41-50	catenin beta 1	Homo sapiens	148-160
28035400-7	2017	To elucidate the underlying mechanism of these effects, the present study verified that metformin resulted in a downregulation of DVL3 and beta-catenin in a dose-dependent manner, and induced phosphorylation of AMPK.	Metformin	88-97	catenin beta 1	Homo sapiens	139-151
28045889-11	2017	It was shown that metformin downregulates the expression of cyclin D1 and increases the p27KIP1 level.	Metformin	18-27	cyclin dependent kinase inhibitor 1B	Homo sapiens	88-95
28011481-6	2017	A low dose of metformin significantly increased anoikis and inhibited migration/ invasion of CCA cells that was in concert with the decrease of vimentin, matrix metalloproteinase (MMP)-2 and -7.	Metformin	14-23	vimentin	Homo sapiens	144-152
28042775-6	2017	RESULTS: There was a lower protein expression of ROCK-1, vimentin, CD44 and CD24 in both cell lines after treatment with metformin and Y27632.	Metformin	121-130	vimentin	Homo sapiens	57-65
27816442-0	2017	Metformin impairs systemic bile acid homeostasis through regulating SIRT1 protein levels.	Metformin	0-9	sirtuin 1	Mus musculus	68-73
27816442-3	2017	Here we show that metformin decreases SIRT1 protein levels in primary hepatocytes and liver.	Metformin	18-27	sirtuin 1	Mus musculus	38-43
27816442-4	2017	Both metformin-treated wild-type C57 mice and hepatic SIRT1-mutant mice had increased hepatic and serum bile acid levels.	Metformin	5-14	sirtuin 1	Mus musculus	54-59
27816442-8	2017	Our data clearly suggest that hepatic SIRT1 mediates metformin effects on systemic bile acid metabolism and modulation of SIRT1 activity in liver may be an attractive approach for treatment of bile acid-related diseases such as cholestasis.	Metformin	53-62	sirtuin 1	Mus musculus	38-43
29073599-0	2017	Combination of Solamargine and Metformin Strengthens IGFBP1 Gene Expression Through Inactivation of Stat3 and Reciprocal Interaction Between FOXO3a and SP1.	Metformin	31-40	insulin like growth factor binding protein 1	Homo sapiens	53-59
27803295-6	2017	Metformin had a dose-dependent inhibitory effect on cell proliferation and apoptosis in vitro through the deregulation of mTOR/AMPK, AKT and extracellular signal regulated kinase (ERK) signalling pathways.	Metformin	0-9	mechanistic target of rapamycin kinase	Mus musculus	122-126
28775741-0	2017	STK11 rs2075604 Polymorphism Is Associated with Metformin Efficacy in Chinese Type 2 Diabetes Mellitus.	Metformin	48-57	serine/threonine kinase 11	Homo sapiens	0-5
28775741-7	2017	The T allele in the STK11 rs2075604 had a 2.133 times great chance of responding to metformin treatment.	Metformin	84-93	serine/threonine kinase 11	Homo sapiens	20-25
28775741-8	2017	In conclusion, this study suggested that the STK11 rs2075604 genetic polymorphism was significantly associated with metformin efficacy in Chinese T2DM patients and the carriers of the T allele may gain a better therapeutic metformin efficacy compared with the G allele.	Metformin	116-125	serine/threonine kinase 11	Homo sapiens	45-50
28775741-8	2017	In conclusion, this study suggested that the STK11 rs2075604 genetic polymorphism was significantly associated with metformin efficacy in Chinese T2DM patients and the carriers of the T allele may gain a better therapeutic metformin efficacy compared with the G allele.	Metformin	223-232	serine/threonine kinase 11	Homo sapiens	45-50
27534996-10	2016	Metformin stimulates AMPK to phosphorylate and activate AQP2 and UT-A1, and it increases urine concentrating ability in two rodent models of NDI.	Metformin	0-9	aquaporin 2	Homo sapiens	56-60
27696771-0	2016	Metformin Represses Interferonopathy Through Suppression of Melanoma Differentiation-Associated Protein 5 and Mitochondrial Antiviral Signaling Protein Activation: Comment on the Article by Wang et al.	Metformin	0-9	interferon induced with helicase C domain 1	Homo sapiens	60-105
27696771-0	2016	Metformin Represses Interferonopathy Through Suppression of Melanoma Differentiation-Associated Protein 5 and Mitochondrial Antiviral Signaling Protein Activation: Comment on the Article by Wang et al.	Metformin	0-9	mitochondrial antiviral signaling protein	Homo sapiens	110-151
27636742-8	2016	A xenograft mouse model further revealed that metformin suppressed HEC-1B tumor growth, accompanied by downregulated ki-67 and upregulated AMPK phosphorylation and nuclear FOXO1 protein.	Metformin	46-55	forkhead box O1	Mus musculus	172-177
27734321-1	2016	BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used as second-option medications when metformin fails.	Metformin	104-113	dipeptidyl peptidase 4	Homo sapiens	12-34
27734321-1	2016	BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used as second-option medications when metformin fails.	Metformin	104-113	dipeptidyl peptidase 4	Homo sapiens	36-41
27404348-6	2016	Metformin activated the AMPK/mTOR signaling pathway as shown by increased p-AMPK and decreased p-p70S6K.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	97-103
27562556-8	2016	Our data showed that pretreatment with metformin protected against APAP hepatotoxicity, as indicated by the over 80% reduction in plasma alanine aminotransferase (ALT) activities and significant decrease in centrilobular necrosis.	Metformin	39-48	glutamic pyruvic transaminase, soluble	Mus musculus	137-161
27562556-8	2016	Our data showed that pretreatment with metformin protected against APAP hepatotoxicity, as indicated by the over 80% reduction in plasma alanine aminotransferase (ALT) activities and significant decrease in centrilobular necrosis.	Metformin	39-48	glutamic pyruvic transaminase, soluble	Mus musculus	163-166
27916907-0	2016	Metformin Inhibits TGF-beta1-Induced Epithelial-to-Mesenchymal Transition via PKM2 Relative-mTOR/p70s6k Signaling Pathway in Cervical Carcinoma Cells.	Metformin	0-9	pyruvate kinase M1/2	Homo sapiens	78-82
27916907-0	2016	Metformin Inhibits TGF-beta1-Induced Epithelial-to-Mesenchymal Transition via PKM2 Relative-mTOR/p70s6k Signaling Pathway in Cervical Carcinoma Cells.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	97-103
27916907-9	2016	Metformin decreased the p-p70s6k expression and the blockade of mTOR/p70s6k signaling decreased PKM2 expression.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	26-32
27916907-10	2016	CONCLUSION: Metformin abolishes TGF-beta1-induced EMT in cervical carcinoma cells by inhibiting mTOR/p70s6k signaling to down-regulate PKM2 expression.	Metformin	12-21	ribosomal protein S6 kinase B1	Homo sapiens	101-107
27916907-10	2016	CONCLUSION: Metformin abolishes TGF-beta1-induced EMT in cervical carcinoma cells by inhibiting mTOR/p70s6k signaling to down-regulate PKM2 expression.	Metformin	12-21	pyruvate kinase M1/2	Homo sapiens	135-139
27902686-6	2016	These include an enhancer in an ataxia telangiectasia mutated (ATM) intron that has SNPs in linkage disequilibrium with a metformin treatment response GWAS lead SNP (rs11212617) that showed increased enhancer activity for the associated haplotype.	Metformin	122-131	ATM serine/threonine kinase	Homo sapiens	63-66
27902686-8	2016	Using ChIP-seq and siRNA knockdown, we further show that activating transcription factor 3 (ATF3), our top metformin upregulated AMPK-dependent gene, could have an important role in gluconeogenesis repression.	Metformin	107-116	activating transcription factor 3	Homo sapiens	57-90
27902686-8	2016	Using ChIP-seq and siRNA knockdown, we further show that activating transcription factor 3 (ATF3), our top metformin upregulated AMPK-dependent gene, could have an important role in gluconeogenesis repression.	Metformin	107-116	activating transcription factor 3	Homo sapiens	92-96
27893782-0	2016	Beneficial Effects of Metformin and/or Salicylate on Palmitate- or TNFalpha-Induced Neuroinflammatory Marker and Neuropeptide Gene Regulation in Immortalized NPY/AgRP Neurons.	Metformin	22-31	neuropeptide Y	Homo sapiens	158-161
27893782-8	2016	We determined co-treatment with metformin or sodium salicylate alone was successful in alleviating changes observed in feeding peptide mRNA regulation, whereas a preventative pre-treatment with metformin and sodium salicylate together was able to alleviate palmitate- and TNFalpha-induced induction of NPY and/or AgRP mRNA levels.	Metformin	194-203	neuropeptide Y	Homo sapiens	302-305
27904436-6	2016	RESULTS: We found that metformin reduced the levels of IL-6 in blood and MCP-1 in urine, but increased IL-10 levels in blood of patients with type 2 diabetes.	Metformin	23-32	C-C motif chemokine ligand 2	Homo sapiens	73-78
27904436-8	2016	Furthermore, compared to individual drug treatment, metformin significantly reduced the levels of serum IL-6 and TNF-alpha, as well as urine MCP-1.	Metformin	52-61	C-C motif chemokine ligand 2	Homo sapiens	141-146
27904436-10	2016	Metformin (1.5 g) treatment reduced the urinary levels of MCP-1 as compared with dose of 1.0 g in patients with type 2 diabetes.	Metformin	0-9	C-C motif chemokine ligand 2	Homo sapiens	58-63
27760406-7	2016	The combination of 6-BT with metformin resulted in significant cytotoxicity (60-70%) in monocytic AML cell lines and was associated with inhibition of FLT3-ITD activated STAT5 and reduced c-Myc and GLUT-1 expression.	Metformin	29-38	signal transducer and activator of transcription 5A	Homo sapiens	170-175
27760406-7	2016	The combination of 6-BT with metformin resulted in significant cytotoxicity (60-70%) in monocytic AML cell lines and was associated with inhibition of FLT3-ITD activated STAT5 and reduced c-Myc and GLUT-1 expression.	Metformin	29-38	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	188-193
27760406-8	2016	Therefore, although the anti-tumor and metabolic effects of metformin have been limited by the metabolic reprogramming within cells, the novel combination of 6-BT and metformin targets this bypass mechanism resulting in reduced glycolysis, STAT5 inhibition, and increased cell death.	Metformin	167-176	signal transducer and activator of transcription 5A	Homo sapiens	240-245
28760225-5	2016	Due to their insulin-independent mechanism of action, SGLT2 inhibitors can be used in monotherapy, in patients with metformin intolerance, or in combination with other glucose-lowering drugs, including insulin.	Metformin	116-125	solute carrier family 5 member 2	Homo sapiens	54-59
27456392-2	2016	Metformin (Met) converges on this pathway both indirectly (via AMPK) and by direct activation of Sirt1, and we recently found Leu to synergize with Met to improve insulin sensitivity and glycemic control while achieving ~80% dose-reduction in diet-induced obese mice.	Metformin	0-9	sirtuin 1	Mus musculus	97-102
25547067-8	2015	The inhibitor of AMPK, compound C blocked, while an activator of AMPK, metformin augmented the effect of UA on DNMT1 expression.	Metformin	71-80	DNA methyltransferase 1	Homo sapiens	111-116
26306225-3	2015	In this electronic health record(EHR)-based study we explore the potential association of the flavin-containing monooxygenase(FMO)-5 gene, a biologically plausible biotransformer of metformin, and modifying glycemic response to metformin treatment.	Metformin	182-191	flavin containing dimethylaniline monoxygenase 5	Homo sapiens	94-132
26306225-3	2015	In this electronic health record(EHR)-based study we explore the potential association of the flavin-containing monooxygenase(FMO)-5 gene, a biologically plausible biotransformer of metformin, and modifying glycemic response to metformin treatment.	Metformin	228-237	flavin containing dimethylaniline monoxygenase 5	Homo sapiens	94-132
26306225-5	2015	Gene-level and SNP-level analysis identified marginally significant associations for FMO5 variation, representing an EHR-driven pharmacogenetics hypothesis for a potential novel mechanism for metformin biotransformation.	Metformin	192-201	flavin containing dimethylaniline monoxygenase 5	Homo sapiens	85-89
25785990-10	2015	Moreover, metformin inhibited VEGF-induced cell proliferation and decreased levels of Flk1 and pFlk1, consistent with the interpretation that metformin inhibits vascular growth by reducing Flk1 levels.	Metformin	10-19	vascular endothelial growth factor A	Mus musculus	30-34
25785990-10	2015	Moreover, metformin inhibited VEGF-induced cell proliferation and decreased levels of Flk1 and pFlk1, consistent with the interpretation that metformin inhibits vascular growth by reducing Flk1 levels.	Metformin	142-151	vascular endothelial growth factor A	Mus musculus	30-34
25681087-0	2015	Prevention of tumor growth driven by PIK3CA and HPV oncogenes by targeting mTOR signaling with metformin in oral squamous carcinomas expressing OCT3.	Metformin	95-104	solute carrier family 22 member 3	Homo sapiens	144-148
25681087-7	2015	We found that metformin inhibits mTOR signaling and tumor growth in HNSCC cells expressing mutated PIK3CA and HPV oncogenes, and that these activities require the expression of organic cation transporter 3 (OCT3/SLC22A3), a metformin uptake transporter.	Metformin	14-23	OCTN3	Homo sapiens	177-205
25681087-7	2015	We found that metformin inhibits mTOR signaling and tumor growth in HNSCC cells expressing mutated PIK3CA and HPV oncogenes, and that these activities require the expression of organic cation transporter 3 (OCT3/SLC22A3), a metformin uptake transporter.	Metformin	14-23	solute carrier family 22 member 3	Homo sapiens	207-211
25681087-7	2015	We found that metformin inhibits mTOR signaling and tumor growth in HNSCC cells expressing mutated PIK3CA and HPV oncogenes, and that these activities require the expression of organic cation transporter 3 (OCT3/SLC22A3), a metformin uptake transporter.	Metformin	14-23	solute carrier family 22 member 3	Homo sapiens	212-219
25681087-7	2015	We found that metformin inhibits mTOR signaling and tumor growth in HNSCC cells expressing mutated PIK3CA and HPV oncogenes, and that these activities require the expression of organic cation transporter 3 (OCT3/SLC22A3), a metformin uptake transporter.	Metformin	224-233	OCTN3	Homo sapiens	177-205
25681087-7	2015	We found that metformin inhibits mTOR signaling and tumor growth in HNSCC cells expressing mutated PIK3CA and HPV oncogenes, and that these activities require the expression of organic cation transporter 3 (OCT3/SLC22A3), a metformin uptake transporter.	Metformin	224-233	solute carrier family 22 member 3	Homo sapiens	207-211
25681087-7	2015	We found that metformin inhibits mTOR signaling and tumor growth in HNSCC cells expressing mutated PIK3CA and HPV oncogenes, and that these activities require the expression of organic cation transporter 3 (OCT3/SLC22A3), a metformin uptake transporter.	Metformin	224-233	solute carrier family 22 member 3	Homo sapiens	212-219
25598321-6	2015	Interestingly, metformin not only reversed the effect of beta-elemene on phosphorylation of Akt but also strengthened the beta-elemene-reduced DNMT1.	Metformin	15-24	DNA methyltransferase 1	Homo sapiens	143-148
25598321-10	2015	Metformin augments the effect of beta-elemene by blockade of Akt signalling and additively inhibition of DNMT1 protein expression.	Metformin	0-9	DNA methyltransferase 1	Homo sapiens	105-110
26120598-6	2015	Further investigation into the effects of metformin suggest that the drug directly activates AMPK and dose-dependently suppressed the release of TNF-alpha, IL-6, and MCP-1 by macrophages while enhancing the release of IL-10 in vitro.	Metformin	42-51	interleukin 10	Homo sapiens	218-223
25673763-6	2015	Metformin also restored the defective interleukin-2 (IL-2) production by TC CD4(+) T cells.	Metformin	0-9	CD4 antigen	Mus musculus	76-79
25527635-0	2015	Inhibition of the GTPase Rac1 mediates the antimigratory effects of metformin in prostate cancer cells.	Metformin	68-77	Rac family small GTPase 1	Homo sapiens	25-29
25527635-6	2015	We report that metformin leads to a major inhibition of Rac1 GTPase activity by interfering with some of its multiple upstream signaling pathways, namely P-Rex1 (a Guanine nucleotide exchange factor and activator of Rac1), cAMP, and CXCL12/CXCR4, resulting in decreased migration of prostate cancer cells.	Metformin	15-24	Rac family small GTPase 1	Homo sapiens	56-60
25527635-6	2015	We report that metformin leads to a major inhibition of Rac1 GTPase activity by interfering with some of its multiple upstream signaling pathways, namely P-Rex1 (a Guanine nucleotide exchange factor and activator of Rac1), cAMP, and CXCL12/CXCR4, resulting in decreased migration of prostate cancer cells.	Metformin	15-24	Rac family small GTPase 1	Homo sapiens	216-220
25527635-6	2015	We report that metformin leads to a major inhibition of Rac1 GTPase activity by interfering with some of its multiple upstream signaling pathways, namely P-Rex1 (a Guanine nucleotide exchange factor and activator of Rac1), cAMP, and CXCL12/CXCR4, resulting in decreased migration of prostate cancer cells.	Metformin	15-24	C-X-C motif chemokine receptor 4	Homo sapiens	240-245
25527635-7	2015	Importantly, overexpression of a constitutively active form of Rac1, or P-Rex, as well as the inhibition of the adenylate cyclase, was able to reverse the antimigratory effects of metformin.	Metformin	180-189	Rac family small GTPase 1	Homo sapiens	63-67
25634597-0	2015	Antihyperglycemic mechanism of metformin occurs via the AMPK/LXRalpha/POMC pathway.	Metformin	31-40	proopiomelanocortin	Rattus norvegicus	70-74
25634597-8	2015	Actually we found that metformin induced AMPK/liver X receptor alpha (LXRalpha) phosphorylation, followed by pro-opiomelanocortin (POMC) suppression in rat pituitary cells.	Metformin	23-32	proopiomelanocortin	Rattus norvegicus	109-129
25634597-8	2015	Actually we found that metformin induced AMPK/liver X receptor alpha (LXRalpha) phosphorylation, followed by pro-opiomelanocortin (POMC) suppression in rat pituitary cells.	Metformin	23-32	proopiomelanocortin	Rattus norvegicus	131-135
25634597-10	2015	Given that cortisol stimulates gluconeogenesis, we propose the anti-hyperglycemic effect of metformin is attributed to reduced POMC/adrenocorticotropic hormone (ACTH)/cortisol levels following AMPK/LXRalpha phosphorylation in the pituitaries.	Metformin	92-101	proopiomelanocortin	Rattus norvegicus	127-131
25305450-6	2015	Western blot showed that metformin activated caspase 3, caspase 9, PARP-1, Bak, and p21 and inactivated Mcl-1, HIAP-1, cyclin D1, CDK4, and CDK6.	Metformin	25-34	BCL2 antagonist/killer 1	Homo sapiens	75-78
25305450-7	2015	Metformin inhibited the expression of insulin growth factor-I receptor (IGF-IR), and phosphatidyl inositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and the downstream mammalian target of rapamycin (mTOR).	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	38-70
25305450-7	2015	Metformin inhibited the expression of insulin growth factor-I receptor (IGF-IR), and phosphatidyl inositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and the downstream mammalian target of rapamycin (mTOR).	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	72-78
25305450-10	2015	We conclude that metformin inhibits MM cell proliferation through the IGF-1R/PI3K/AKT/mTOR signaling pathway.	Metformin	17-26	insulin like growth factor 1 receptor	Homo sapiens	70-76
26745042-6	2015	Furthermore, metformin inhibited CCA tumor growth via the regulation of Drosha-mediated expression of multiple carcinogenic miRNAs.	Metformin	13-22	drosha ribonuclease III	Homo sapiens	72-78
25484077-1	2015	Metformin activates both PRKA and SIRT1.	Metformin	0-9	A kinase (PRKA) anchor protein 6	Mus musculus	25-29
25484077-3	2015	We aimed to elucidate the mechanism by which metformin alleviates hepatosteatosis by examining the molecular interplay between SIRT1, PRKA, and autophagy.	Metformin	45-54	A kinase (PRKA) anchor protein 6	Mus musculus	134-138
25484077-9	2015	Interestingly, metformin treatment upregulated SIRT1 expression and activated PRKA even after siRNA-mediated knockdown of PRKAA1/2 and SIRT1, respectively.	Metformin	15-24	A kinase (PRKA) anchor protein 6	Mus musculus	78-82
25484077-10	2015	Taken together, these results suggest that metformin alleviates hepatic steatosis through PRKA-independent, SIRT1-mediated effects on the autophagy machinery.	Metformin	43-52	A kinase (PRKA) anchor protein 6	Mus musculus	90-94
25838947-5	2015	Metformin and sitagliptin increased serum adiponectin level, whereas they decreased serum leptin level.	Metformin	0-9	adiponectin, C1Q and collagen domain containing	Rattus norvegicus	42-53
25945347-6	2015	Vaspin gene expression is influenced by age and gender, and the administration of insulin sensitizers enhances it in mice, whereas the use of metformin decreases serum vaspin levels in humans, probably due to different regulatory mechanisms.	Metformin	142-151	serine (or cysteine) peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 12	Mus musculus	168-174
26682070-10	2015	Patients that presented with acute MI that received metformin show a significant difference in all biochemical parameters (p &lt; 0.001); metformin increases serum omentin-1 level and decreases serum cardiac troponin-I level compared with control subjects and nonmetformin treated patients.	Metformin	52-61	troponin I3, cardiac type	Homo sapiens	200-218
26682070-10	2015	Patients that presented with acute MI that received metformin show a significant difference in all biochemical parameters (p &lt; 0.001); metformin increases serum omentin-1 level and decreases serum cardiac troponin-I level compared with control subjects and nonmetformin treated patients.	Metformin	138-147	troponin I3, cardiac type	Homo sapiens	200-218
25503637-8	2014	Agonist induction of AMPK activity with AICAR or metformin increased macroautophagy protein LC3 and normalized p62/SQSTM1 expression and mTOR activity.	Metformin	49-58	microtubule associated protein 1 light chain 3 alpha	Homo sapiens	92-95
25503637-8	2014	Agonist induction of AMPK activity with AICAR or metformin increased macroautophagy protein LC3 and normalized p62/SQSTM1 expression and mTOR activity.	Metformin	49-58	sequestosome 1	Homo sapiens	111-114
25503637-8	2014	Agonist induction of AMPK activity with AICAR or metformin increased macroautophagy protein LC3 and normalized p62/SQSTM1 expression and mTOR activity.	Metformin	49-58	sequestosome 1	Homo sapiens	115-121
25245054-0	2014	Metformin inhibits the invasion of human hepatocellular carcinoma cells and enhances the chemosensitivity to sorafenib through a downregulation of the ERK/JNK-mediated NF-kappaB-dependent pathway that reduces uPA and MMP-9 expression.	Metformin	0-9	matrix metallopeptidase 9	Homo sapiens	217-222
25245054-5	2014	Metformin was also found to significantly inhibit the expression and secretion of MMP-9 and uPA in HCC cells, and suppress the phosphorylation of ERK1/2 and JNK1/2.	Metformin	0-9	matrix metallopeptidase 9	Homo sapiens	82-87
25245054-7	2014	Moreover, metformin-induced inhibition of MMP-9 and uPA promoter activity also blocked the nuclear translocation of NF-kappaB and its binding to the MMP-9 and uPA promoters, and these suppressive effects were further enhanced by PD98059 or SP600125.	Metformin	10-19	matrix metallopeptidase 9	Homo sapiens	42-47
25245054-7	2014	Moreover, metformin-induced inhibition of MMP-9 and uPA promoter activity also blocked the nuclear translocation of NF-kappaB and its binding to the MMP-9 and uPA promoters, and these suppressive effects were further enhanced by PD98059 or SP600125.	Metformin	10-19	matrix metallopeptidase 9	Homo sapiens	149-154
24903160-5	2014	Metformin may ameliorate LYRM1-induced insulin resistance and mitochondrial dysfunction in part via a direct antioxidant effect and in part by activating the adenosine monophosphate-activated protein kinase (AMPK)-PGC1/NRFs pathway.	Metformin	0-9	LYR motif containing 1	Homo sapiens	25-30
25213330-4	2014	Expression profiling of metformin-treated TNBC lines revealed fatty acid synthase (FASN) as one of the genes most significantly downregulated following 24 h of treatment, and a decrease in FASN protein was also observed.	Metformin	24-33	fatty acid synthase	Homo sapiens	83-87
25213330-4	2014	Expression profiling of metformin-treated TNBC lines revealed fatty acid synthase (FASN) as one of the genes most significantly downregulated following 24 h of treatment, and a decrease in FASN protein was also observed.	Metformin	24-33	fatty acid synthase	Homo sapiens	189-193
25213330-5	2014	Since FASN is critical for de novo fatty acid synthesis and is important for the survival of TNBC, we hypothesized that FASN downregulation facilitates metformin-induced apoptosis.	Metformin	152-161	fatty acid synthase	Homo sapiens	6-10
25213330-5	2014	Since FASN is critical for de novo fatty acid synthesis and is important for the survival of TNBC, we hypothesized that FASN downregulation facilitates metformin-induced apoptosis.	Metformin	152-161	fatty acid synthase	Homo sapiens	120-124
25213330-8	2014	Conversely, antagonizing miR-193 activity impaired the ability of metformin to decrease FASN and cause cell death.	Metformin	66-75	fatty acid synthase	Homo sapiens	88-92
25333332-11	2014	In addition, metformin plus radiation significantly upregulated the expression of p-ATM, p-ATR, gamma-H2AX and downregulated the expression of ATM, ATR, p95/NBS1, Rad50, DNA-PK, Ku70 and Ku80.	Metformin	13-22	X-ray repair cross complementing 6	Homo sapiens	178-182
25365944-9	2014	Additionally, inhibition of JNK activity along with Rac1 or Cdc42 attenuated cytotoxic effects of metformin.	Metformin	98-107	mitogen-activated protein kinase 8	Mus musculus	28-31
25365944-10	2014	These studies demonstrated that metformin impairs Rho GTPases signaling to induce apoptosis via JNK pathway.	Metformin	32-41	mitogen-activated protein kinase 8	Mus musculus	96-99
25608995-9	2014	By real-time FQ-PCR tested, the expression levels of c-fos and c-myc in both cell lines gradually declined subsequent to metformin treatment at different concentrations (1, 5 and 15 mmol/L).	Metformin	121-130	Fos proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	53-58
25608995-10	2014	As compared with the control group, the c-myc and c-fos expressions in both cell lines in metformin groups had significant differences (P &lt; 0.05) except for the c-myc expression of the concentration of 1 mmol/L in HEC-1A cell line (P = 0.074).	Metformin	90-99	Fos proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	50-55
25394090-3	2014	In vitro, DTG inhibits organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporter 1 (MATE 1) which are known to be involved in the disposition of metformin.	Metformin	169-178	solute carrier family 47 member 1	Homo sapiens	63-106
25394090-3	2014	In vitro, DTG inhibits organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporter 1 (MATE 1) which are known to be involved in the disposition of metformin.	Metformin	169-178	solute carrier family 47 member 1	Homo sapiens	108-114
24840107-6	2014	RESULTS: PAF-AH and ox-LDL levels were statistically significantly higher in untreated PCOS patients than controls, and they were statistically significantly lower in patients treated with metformin or Diane-35 than untreated PCOS patients.	Metformin	189-198	phospholipase A2 group VII	Homo sapiens	9-15
24840107-10	2014	The treatment of PCOS with metformin or Diane-35 had positive effects on lipid profile, increased PON1 level, which is a protector from atherosclerosis and decreased the proatherogenic PAF-AH and ox-LDL levels.	Metformin	27-36	phospholipase A2 group VII	Homo sapiens	185-191
25289085-7	2014	Metformin was observed to downregulate IGF-1R and upregulate IGF binding protein-1 (IGFBP-1) mRNA and protein expression, while compound C, an adenosine monophosphate protein kinase inhibitor, reversed this effect.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	39-45
25289085-10	2014	Metformin combined with IGF-1R axis inhibitors may act synergistically to kill tumor cells, as metformin was shown to delay and prevent IGF-1R feedback.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	136-142
25289085-10	2014	Metformin combined with IGF-1R axis inhibitors may act synergistically to kill tumor cells, as metformin was shown to delay and prevent IGF-1R feedback.	Metformin	95-104	insulin like growth factor 1 receptor	Homo sapiens	24-30
25289085-10	2014	Metformin combined with IGF-1R axis inhibitors may act synergistically to kill tumor cells, as metformin was shown to delay and prevent IGF-1R feedback.	Metformin	95-104	insulin like growth factor 1 receptor	Homo sapiens	136-142
25315906-10	2014	MPO+ cells, Gr1+ cells, MPO activity and BBB permeability were decreased after metformin administration (P &lt; 0.05).	Metformin	79-88	myeloperoxidase	Mus musculus	0-3
25315906-10	2014	MPO+ cells, Gr1+ cells, MPO activity and BBB permeability were decreased after metformin administration (P &lt; 0.05).	Metformin	79-88	myeloperoxidase	Mus musculus	24-27
25143389-2	2014	A recent study showed that metformin down-regulated specificity protein (Sp) transcription factors (TFs) Sp1, Sp3, and Sp4 in pancreatic cancer cells and tumors, and this was accompanied by down-regulation of several pro-oncogenic Sp-regulated genes.	Metformin	27-36	Sp4 transcription factor	Homo sapiens	119-122
25143389-4	2014	Metformin and Sp knockdown by RNAi decreased expression of the insulin-like growth factor-1 receptor (IGF-1R), resulting in inhibition of mTOR signaling.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	63-100
25143389-4	2014	Metformin and Sp knockdown by RNAi decreased expression of the insulin-like growth factor-1 receptor (IGF-1R), resulting in inhibition of mTOR signaling.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	102-108
25143389-6	2014	Thus, the antineoplastic activities of metformin in pancreatic cancer are due, in part, to down-regulation of Sp TFs and Sp-regulated IGF-1R and EGFR, which in turn results in inhibition of mTOR and Ras signaling, respectively.	Metformin	39-48	insulin like growth factor 1 receptor	Homo sapiens	134-140
25212175-12	2014	Metformin-induced oxidative damage is enhanced by DCA through PDK1 inhibition which also diminishes metformin promoted lactate production.	Metformin	0-9	pyruvate dehydrogenase kinase 1	Homo sapiens	62-66
25212175-12	2014	Metformin-induced oxidative damage is enhanced by DCA through PDK1 inhibition which also diminishes metformin promoted lactate production.	Metformin	100-109	pyruvate dehydrogenase kinase 1	Homo sapiens	62-66
25175747-5	2014	Specific uptake of cimetidine, acyclovir, metformin, and terbutaline was observed in human embryonic kidney 293 cells transfected with murine Oct1 or Oct2.	Metformin	42-51	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	142-146
25110054-7	2014	Metformin inhibited endogenous AhR ligand-induced CYP1A1 and CYP1B1 expression by suppressing tryptophan-2,3-dioxygenase (TDO) expression in MCF-7 cells.	Metformin	0-9	tryptophan 2,3-dioxygenase	Homo sapiens	94-120
25110054-7	2014	Metformin inhibited endogenous AhR ligand-induced CYP1A1 and CYP1B1 expression by suppressing tryptophan-2,3-dioxygenase (TDO) expression in MCF-7 cells.	Metformin	0-9	tryptophan 2,3-dioxygenase	Homo sapiens	122-125
25110054-8	2014	Finally, metformin inhibits TDO expression through a down-regulation of Sp1 and glucocorticoid receptor (GR) protein levels.	Metformin	9-18	tryptophan 2,3-dioxygenase	Homo sapiens	28-31
25249538-0	2014	Activation of EGFR, HER2 and HER3 by neurotensin/neurotensin receptor 1 renders breast tumors aggressive yet highly responsive to lapatinib and metformin in mice.	Metformin	144-153	erb-b2 receptor tyrosine kinase 3	Mus musculus	29-33
25249538-0	2014	Activation of EGFR, HER2 and HER3 by neurotensin/neurotensin receptor 1 renders breast tumors aggressive yet highly responsive to lapatinib and metformin in mice.	Metformin	144-153	neurotensin	Mus musculus	37-48
25249538-8	2014	Accordingly, lapatinib, an EGFR/HER2 tyrosine kinase inhibitor, as well as metformin, reduced the tumor growth of cells overexpressing NTS and NTSR1.	Metformin	75-84	neurotensin	Mus musculus	135-138
25201727-0	2014	Metformin inhibits epithelial-mesenchymal transition in prostate cancer cells: involvement of the tumor suppressor miR30a and its target gene SOX4.	Metformin	0-9	SRY-box transcription factor 4	Homo sapiens	142-146
25201727-7	2014	Metformin could inhibit TGF-beta-induced EMT in Vcap cells, as manifested by inhibition of the increase of N-cadherin (p=0.013), Vimentin (p=0.002) and the decrease of E-cadherin (p=0.0023) and beta-catenin (p=0.034) at mRNA and protein levels.	Metformin	0-9	cadherin 2	Homo sapiens	107-117
25201727-12	2014	In all, our study suggested that inhibition of EMT by metformin in PCa cells may involve upregulation of miR30a and downregulation of SOX4.	Metformin	54-63	SRY-box transcription factor 4	Homo sapiens	134-138
24714080-8	2014	Taken together, our results indicate that metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through downregulation of c-FLIP, which is mediated by the mTOR/S6K1 pathway, but independent of AMPK; furthermore, these findings provide a rationale for the combined application of metformin with TRAIL in the treatment of bladder cancer.	Metformin	42-51	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	214-218
24970682-0	2014	Metformin induces microRNA-34a to downregulate the Sirt1/Pgc-1alpha/Nrf2 pathway, leading to increased susceptibility of wild-type p53 cancer cells to oxidative stress and therapeutic agents.	Metformin	0-9	sirtuin 1	Homo sapiens	51-56
24970682-3	2014	Here, we investigated the effects of metformin on Sirt1 expression in several cancer cell lines.	Metformin	37-46	sirtuin 1	Homo sapiens	50-55
24970682-4	2014	Using human cancer cell lines that exhibit differential expression of p53, we found that metformin reduced Sirt1 protein levels in cancer cells bearing wild-type p53, but did not affect Sirt1 protein levels in cancer cell lines harboring mutant forms of p53.	Metformin	89-98	sirtuin 1	Homo sapiens	107-112
24970682-6	2014	The use of a miR-34a inhibitor confirmed that metformin-induced miR-34a was required for Sirt1 downregulation.	Metformin	46-55	sirtuin 1	Homo sapiens	89-94
24970682-8	2014	Genetic tools demonstrated that the reduction of Sirt1 and Pgc-1alpha by metformin caused Nrf2 downregulation via suppression of PPARgamma transcriptional activity.	Metformin	73-82	sirtuin 1	Homo sapiens	49-54
24823468-0	2014	Metformin inhibits StAR expression in human endometriotic stromal cells via AMPK-mediated disruption of CREB-CRTC2 complex formation.	Metformin	0-9	cAMP responsive element binding protein 1	Homo sapiens	104-108
24823468-0	2014	Metformin inhibits StAR expression in human endometriotic stromal cells via AMPK-mediated disruption of CREB-CRTC2 complex formation.	Metformin	0-9	CREB regulated transcription coactivator 2	Homo sapiens	109-114
24823468-9	2014	4) Metformin prevents the nuclear translocation of CRTC2 by increasing AMP-activated protein kinase phosphorylation.	Metformin	3-12	CREB regulated transcription coactivator 2	Homo sapiens	51-56
24823468-12	2014	Our data highlight a role for CRTC2 in the mechanism by which metformin inhibits StAR expression.	Metformin	62-71	CREB regulated transcription coactivator 2	Homo sapiens	30-35
24961373-0	2014	OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin.	Metformin	97-106	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	0-4
24961373-1	2014	Organic cation transporter 1, OCT1 (SLC22A1), is the major hepatic uptake transporter for metformin, the most prescribed antidiabetic drug.	Metformin	90-99	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	0-28
24961373-1	2014	Organic cation transporter 1, OCT1 (SLC22A1), is the major hepatic uptake transporter for metformin, the most prescribed antidiabetic drug.	Metformin	90-99	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	30-34
24961373-1	2014	Organic cation transporter 1, OCT1 (SLC22A1), is the major hepatic uptake transporter for metformin, the most prescribed antidiabetic drug.	Metformin	90-99	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	36-43
24961373-3	2014	Here we show that similar to metformin treatment, loss of Oct1 caused an increase in the ratio of AMP to ATP, activated the energy sensor AMP-activated kinase (AMPK), and substantially reduced triglyceride (TG) levels in livers from healthy and leptin-deficient mice.	Metformin	29-38	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	58-62
24961373-7	2014	Metformin and the biguanide analog, phenformin, competitively inhibited OCT1-mediated thiamine uptake.	Metformin	0-9	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	72-76
24961373-10	2014	The studies implicate OCT1 as well as metformin in thiamine disposition, suggesting an intriguing and parallel mechanism for metformin and its major hepatic transporter in metabolic function.	Metformin	125-134	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	22-26
24806290-8	2014	Metformin inhibited the proliferation of Alex, HLE and Huh7 cells in vitro and in vivo.	Metformin	0-9	MIR7-3 host gene	Homo sapiens	55-59
27403913-0	2016	The Relationship Between Metformin and Serum Prostate-Specific Antigen Levels.	Metformin	25-34	kallikrein related peptidase 3	Homo sapiens	45-70
27403913-4	2016	We aimed to study the association between metformin and serum prostate-specific antigen (PSA) levels-the primary prostate cancer biomarker.	Metformin	42-51	kallikrein related peptidase 3	Homo sapiens	62-93
27403913-7	2016	Multivariate linear regressions quantified the association between metformin dose and log-PSA.	Metformin	67-76	kallikrein related peptidase 3	Homo sapiens	90-93
27403913-11	2016	In multivariate models, PSA changed by -8% (95%CI: -13 to -2%, P = 0.011) per 500-mg/d increase in metformin.	Metformin	99-108	kallikrein related peptidase 3	Homo sapiens	24-27
27403913-12	2016	Men with diabetes for &gt;=6 years (n = 163) saw a greater difference in PSA per 500-mg/d metformin (-12% [95% CI: -19 to -4%, P = 0.002], P-interaction = 0.018).	Metformin	90-99	kallikrein related peptidase 3	Homo sapiens	73-76
27403913-15	2016	CONCLUSIONS: Metformin dose-dependently inversely associated with serum PSA, independent of other antihyperglycemic medications.	Metformin	13-22	kallikrein related peptidase 3	Homo sapiens	72-75
27787519-8	2016	In addition, metformin was shown to promote the expression of anabolic genes such as Col2a1 and Acan expression while inhibiting the expression of catabolic genes such as Mmp3 and Adamts5 in nucleus pulposus cells.	Metformin	13-22	collagen type II alpha 1 chain	Rattus norvegicus	85-91
27276511-0	2016	Metformin and resveratrol inhibit Drp1-mediated mitochondrial fission and prevent ER stress-associated NLRP3 inflammasome activation in the adipose tissue of diabetic mice.	Metformin	0-9	NLR family, pyrin domain containing 3	Mus musculus	103-108
27276511-1	2016	OBJECTIVE: This study was designed to investigate the hypothesis that metformin and resveratrol exhibited the same effect on inhibition of NLRP3 inflammasome activation with regulation of AMPK in adipose tissue exposed to high glucose.	Metformin	70-79	NLR family, pyrin domain containing 3	Mus musculus	139-144
27276511-6	2016	CONCLUSION: Metformin and resveratrol protected mitochondrial integrity by inhibiting Drp1 activity and prevented NLRP3 inflammasome activation by suppressing ER stress, and thereby protected adipose function from high glucose insult.	Metformin	12-21	NLR family, pyrin domain containing 3	Mus musculus	114-119
27018756-15	2016	Metformin significantly (P &lt; .05) reduced insulin, BP, CRP, and PAI-1 levels.	Metformin	0-9	serpin family E member 1	Homo sapiens	67-72
27424158-13	2016	Exenatide was more effective than metformin in reducing MCP-1 expression and JNK activity.	Metformin	34-43	C-C motif chemokine ligand 2	Homo sapiens	56-61
26960058-11	2016	Pretreatment with metformin in I/R animals significantly increased P70S6K compared with the I/R group (p &lt; 0.001).	Metformin	18-27	ribosomal protein S6 kinase B1	Rattus norvegicus	67-73
26960058-12	2016	Conclusion Short-term memory in ischaemic rats treated with metformin increased step-through latency; sensory-motor evaluation was applied and a group of ischaemia rats that were pretreated with metformin showed high levels of BDNF, P70S6K that seemed to be due to increasing AMPK.	Metformin	60-69	ribosomal protein S6 kinase B1	Rattus norvegicus	233-239
26960058-12	2016	Conclusion Short-term memory in ischaemic rats treated with metformin increased step-through latency; sensory-motor evaluation was applied and a group of ischaemia rats that were pretreated with metformin showed high levels of BDNF, P70S6K that seemed to be due to increasing AMPK.	Metformin	195-204	ribosomal protein S6 kinase B1	Rattus norvegicus	233-239
27627081-8	2016	KEY WORDS: DPP-4 inhibitors - gliflozines - GLP-1 agonists - insulin - metformin - osteoporosis - sulfonylureas - thiazolidinediones - type 2 diabetes mellitus.	Metformin	71-80	dipeptidyl peptidase 4	Homo sapiens	11-16
27688041-5	2016	In addition, an inhibitory effect of AMPK activators metformin and AICAR on BMP6-mediated hepcidin gene expression was significantly attenuated by ablation of SHP expression.	Metformin	53-62	bone morphogenetic protein 6	Mus musculus	76-80
29467552-11	2018	The inhibitory effects of metformin on activated HSCs were mediated by inhibiting the Akt/mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) pathways via the activation of adenosine monophosphate-activated protein kinase (AMPK).	Metformin	26-35	AKT serine/threonine kinase 1	Homo sapiens	86-89
29467552-11	2018	The inhibitory effects of metformin on activated HSCs were mediated by inhibiting the Akt/mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) pathways via the activation of adenosine monophosphate-activated protein kinase (AMPK).	Metformin	26-35	mechanistic target of rapamycin kinase	Homo sapiens	90-119
29467552-11	2018	The inhibitory effects of metformin on activated HSCs were mediated by inhibiting the Akt/mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) pathways via the activation of adenosine monophosphate-activated protein kinase (AMPK).	Metformin	26-35	mechanistic target of rapamycin kinase	Homo sapiens	121-125
29467552-11	2018	The inhibitory effects of metformin on activated HSCs were mediated by inhibiting the Akt/mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) pathways via the activation of adenosine monophosphate-activated protein kinase (AMPK).	Metformin	26-35	mitogen-activated protein kinase 1	Homo sapiens	131-168
29467552-11	2018	The inhibitory effects of metformin on activated HSCs were mediated by inhibiting the Akt/mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) pathways via the activation of adenosine monophosphate-activated protein kinase (AMPK).	Metformin	26-35	mitogen-activated protein kinase 1	Homo sapiens	170-173
25028601-0	2014	Effects of high-fat diet and the anti-diabetic drug metformin on circulating GLP-1 and the relative number of intestinal L-cells.	Metformin	52-61	glucagon	Mus musculus	77-82
24462945-1	2014	BACKGROUND: Metformin has been shown to have a strong anti-proliferative effect in many breast cancer cell lines, mainly due to the activation of the energy sensing kinase, AMP-activated protein kinase (AMPK).	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	173-201
24916949-2	2014	As a potent activator of AMPK, metformin has become a hot topic of discussion for its effect on cancer cell.	Metformin	31-40	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	25-29
24916949-3	2014	Here, we report that AMPK activated by metformin promotes HeLa-S3 cell survival and growth in vivo.	Metformin	39-48	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	21-25
24916949-7	2014	Our findings identify a link between AMPK activation and cell survival in HeLa-S3 cells, which demonstrates a beneficial effect of AMPK activated by metformin in cancer cell, and suggests a discrete re-evaluation on the role of metformin/AMPK activation on tumor cell growth, proliferation, and on clinical application in cancer therapy.	Metformin	149-158	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	37-41
24916949-7	2014	Our findings identify a link between AMPK activation and cell survival in HeLa-S3 cells, which demonstrates a beneficial effect of AMPK activated by metformin in cancer cell, and suggests a discrete re-evaluation on the role of metformin/AMPK activation on tumor cell growth, proliferation, and on clinical application in cancer therapy.	Metformin	149-158	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	131-135
24916949-7	2014	Our findings identify a link between AMPK activation and cell survival in HeLa-S3 cells, which demonstrates a beneficial effect of AMPK activated by metformin in cancer cell, and suggests a discrete re-evaluation on the role of metformin/AMPK activation on tumor cell growth, proliferation, and on clinical application in cancer therapy.	Metformin	149-158	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	131-135
24905518-0	2014	Metformin affects macrophages" phenotype and improves the activity of glutathione peroxidase, superoxide dismutase, catalase and decreases malondialdehyde concentration in a partially AMPK-independent manner in LPS-stimulated human monocytes/macrophages.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	184-188
24428821-6	2014	Metformin also increased PGC-1alpha in human primary hepatocytes; this effect of metformin was abolished by AMPK inhibitor compound C and sirtuin 1 siRNA.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	108-112
24428821-6	2014	Metformin also increased PGC-1alpha in human primary hepatocytes; this effect of metformin was abolished by AMPK inhibitor compound C and sirtuin 1 siRNA.	Metformin	81-90	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	108-112
24428821-8	2014	Whereas metformin increased PGC-1alpha, it down-regulated gluconeogenic genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase).	Metformin	8-17	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	28-38
24428821-8	2014	Whereas metformin increased PGC-1alpha, it down-regulated gluconeogenic genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase).	Metformin	8-17	glucose-6-phosphatase, catalytic	Mus musculus	124-145
24428821-8	2014	Whereas metformin increased PGC-1alpha, it down-regulated gluconeogenic genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase).	Metformin	8-17	glucose-6-phosphatase, catalytic	Mus musculus	147-153
24428821-9	2014	Furthermore, metformin attenuated the increase in PEPCK and G6Pase mRNAs induced by PGC-1alpha overexpression, but did not affect PGC-1alpha-mediated induction of mitochondrial genes.	Metformin	13-22	glucose-6-phosphatase, catalytic	Mus musculus	60-66
24428821-9	2014	Furthermore, metformin attenuated the increase in PEPCK and G6Pase mRNAs induced by PGC-1alpha overexpression, but did not affect PGC-1alpha-mediated induction of mitochondrial genes.	Metformin	13-22	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	84-94
24428821-10	2014	Metformin down-regulated several key transcription factors that mediate the effect of PGC-1alpha on gluconeogenic genes including Kruppel-like factor 15, forkhead box protein O1 and hepatocyte NF 4alpha, whereas it increased nuclear respiratory factor 1, which is involved in PGC-1alpha-mediated regulation of mitochondrial proteins.	Metformin	0-9	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	86-96
24428821-10	2014	Metformin down-regulated several key transcription factors that mediate the effect of PGC-1alpha on gluconeogenic genes including Kruppel-like factor 15, forkhead box protein O1 and hepatocyte NF 4alpha, whereas it increased nuclear respiratory factor 1, which is involved in PGC-1alpha-mediated regulation of mitochondrial proteins.	Metformin	0-9	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	276-286
24428821-12	2014	Importantly, metformin selectively affects hepatic PGC-1alpha-mediated gene regulation and prevents activation of gluconeogenesis, but does not influence its regulation of mitochondrial genes.	Metformin	13-22	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	51-61
24428821-13	2014	These results identify selective modulation of hepatic PGC-1alpha functions as a novel mechanism involved in the therapeutic action of metformin.	Metformin	135-144	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	55-65
24419232-5	2014	Gene expression profiling of human umbilical vein endothelial cells revealed a paradoxical modulation of several angiogenesis-associated genes and proteins by metformin, with short-term induction of vascular endothelial growth factor (VEGF), cyclooxygenase 2 and CXC chemokine receptor 4 at the messenger RNA level and downregulation of ADAMTS1.	Metformin	159-168	ADAM metallopeptidase with thrombospondin type 1 motif 1	Homo sapiens	337-344
24419232-7	2014	Endothelial cell production of the cytochrome P450 member CYP1B1 is upregulated by tumor cell supernatants in an AMPK-dependent manner, metformin blocks this effect.	Metformin	136-145	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	58-64
24509842-4	2014	A time-dependent approach was applied in the calculation of bladder cancer incidence and in the estimation of hazard ratios by Cox regression for ever-users, never-users, and subgroups of metformin exposure (using tertile cutoffs of cumulative duration of therapy and cumulative dose).	Metformin	188-197	cytochrome c oxidase subunit 8A	Homo sapiens	127-130
24931021-9	2014	CONCLUSIONS: Metformin may inhibit the proliferation of Fadu cells by inducing the cell cycle arrest in G1 phase mediated in part by AMPK and P21.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	133-137
24662793-4	2014	However, some of the biological responses to metformin (e.g. the release of cytokines and the expression of arginase I or PGC-1alpha) are not limited to AMPK activation but also are mediated by AMPK-independent mechanisms.	Metformin	45-54	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	153-157
24662793-4	2014	However, some of the biological responses to metformin (e.g. the release of cytokines and the expression of arginase I or PGC-1alpha) are not limited to AMPK activation but also are mediated by AMPK-independent mechanisms.	Metformin	45-54	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	194-198
24362725-10	2014	Of particular importance, we found that metformin treatment downregulated Srebp-1c promoter activity, decreased the specific binding of SREBP-1c to Irs-1 promoter and upregulated Irs-1 promoter activity in PA-cultured L6 cells.	Metformin	40-49	sterol regulatory element binding transcription factor 1	Rattus norvegicus	74-82
24362725-10	2014	Of particular importance, we found that metformin treatment downregulated Srebp-1c promoter activity, decreased the specific binding of SREBP-1c to Irs-1 promoter and upregulated Irs-1 promoter activity in PA-cultured L6 cells.	Metformin	40-49	sterol regulatory element binding transcription factor 1	Rattus norvegicus	136-144
24490856-6	2014	Activation of AMPK by pharmacological agents, such as metformin and thiazolidinediones, may modulate the activity of PVAT surrounding blood vessels and thereby contribute to their beneficial effect in cardiometabolic diseases.	Metformin	54-63	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	14-18
24252946-0	2014	Metformin represses drug-induced expression of CYP2B6 by modulating the constitutive androstane receptor signaling.	Metformin	0-9	cytochrome P450 family 2 subfamily B member 6	Homo sapiens	47-53
24252946-4	2014	We show that metformin could suppress drug-induced expression of CYP2B6 (a typical target gene of CAR) by modulating the phosphorylation status of CAR.	Metformin	13-22	cytochrome P450 family 2 subfamily B member 6	Homo sapiens	65-71
24252946-5	2014	In human hepatocytes, metformin robustly suppressed the expression of CYP2B6 induced by both indirect (phenobarbital) and direct CITCO [6-(4-chlorophenyl)imidazo[2,1-b]1,3thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime] activators of human CAR.	Metformin	22-31	cytochrome P450 family 2 subfamily B member 6	Homo sapiens	70-76
24252946-8	2014	Additional two-hybrid and coimmunoprecipitation assays demonstrated that metformin could also disrupt CITCO-mediated interaction between CAR and the steroid receptor coactivator 1 or the glucocorticoid receptor-interacting protein 1.	Metformin	73-82	nuclear receptor coactivator 1	Homo sapiens	149-179
24252946-8	2014	Additional two-hybrid and coimmunoprecipitation assays demonstrated that metformin could also disrupt CITCO-mediated interaction between CAR and the steroid receptor coactivator 1 or the glucocorticoid receptor-interacting protein 1.	Metformin	73-82	nuclear receptor coactivator 2	Homo sapiens	187-232
24252946-9	2014	Our results suggest that metformin is a potent repressor of drug-induced CYP2B6 expression through specific inhibition of human CAR activation.	Metformin	25-34	cytochrome P450 family 2 subfamily B member 6	Homo sapiens	73-79
24252946-10	2014	Thus, metformin may affect the metabolism and clearance of drugs that are CYP2B6 substrates.	Metformin	6-15	cytochrome P450 family 2 subfamily B member 6	Homo sapiens	74-80
24233023-1	2014	One aspect of the effects of metformin on glucagon-like peptide (GLP)-1 might be associated with the mechanism by which the cross talk between insulin and Wnt signaling enhances GLP1 secretion, due to the action of metformin as an insulin sensitizer.	Metformin	29-38	glucagon	Mus musculus	42-71
24233023-1	2014	One aspect of the effects of metformin on glucagon-like peptide (GLP)-1 might be associated with the mechanism by which the cross talk between insulin and Wnt signaling enhances GLP1 secretion, due to the action of metformin as an insulin sensitizer.	Metformin	29-38	glucagon	Mus musculus	178-182
24233023-1	2014	One aspect of the effects of metformin on glucagon-like peptide (GLP)-1 might be associated with the mechanism by which the cross talk between insulin and Wnt signaling enhances GLP1 secretion, due to the action of metformin as an insulin sensitizer.	Metformin	215-224	glucagon	Mus musculus	42-71
24233023-1	2014	One aspect of the effects of metformin on glucagon-like peptide (GLP)-1 might be associated with the mechanism by which the cross talk between insulin and Wnt signaling enhances GLP1 secretion, due to the action of metformin as an insulin sensitizer.	Metformin	215-224	glucagon	Mus musculus	178-182
24233023-4	2014	GLP1 enhancement by meformin was determined in human NCI-H716 intestinal L-cells and hyperglycemic db/db mice treated with metformin (0.25 and 0.5 mM and/or 12.5 mg/kg body weight) for 24 h and 2 months.	Metformin	123-132	glucagon like peptide 1 receptor	Homo sapiens	0-4
24233023-5	2014	Metformin increased GLP1 secretion in L-cells and db/db mice.	Metformin	0-9	glucagon	Mus musculus	20-24
24233023-6	2014	Metformin stimulated the nuclear translocation of beta-catenin and TOPflash reporter activity, and gene depletion of beta-catenin or enhancement of mutation of transcription factor 7-like 2 binding site offset GLP1.	Metformin	0-9	glucagon	Mus musculus	210-214
24603137-3	2014	The aim of this study was to evaluate gene and protein expression of an insulin receptor (IR), insulin-like growth factor-1 (IGF1) receptor (IGF1R) and aromatase in granulosa cells treated with metformin and insulin.	Metformin	194-203	insulin receptor	Homo sapiens	72-88
24603137-3	2014	The aim of this study was to evaluate gene and protein expression of an insulin receptor (IR), insulin-like growth factor-1 (IGF1) receptor (IGF1R) and aromatase in granulosa cells treated with metformin and insulin.	Metformin	194-203	insulin receptor	Homo sapiens	90-92
24603137-6	2014	RESULTS: IR and IGF1R mRNA expression was significantly enhanced by metformin but was not affected by insulin.	Metformin	68-77	insulin receptor	Homo sapiens	9-11
24603137-9	2014	CONCLUSION: A direct effect of metformin on the gene expression of IGF1R, IR and aromatase was observed.	Metformin	31-40	insulin receptor	Homo sapiens	74-76
24750786-3	2014	Metformin exerts anticancer effects by primarily blocking the pivotal LKB1/AMPK/mTOR/S6K1 pathway-dependent cell growth, induces selective lethal effects on GSC by impairing the GSC-initiating spherogenesis and inhibits the proliferation of CD133+ cells, while having a low or null effect on differentiated glioblastoma cells and normal human stem cells.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	75-79
24750786-6	2014	In this regard, metformin acts via activation of the AMPK-FOXO3 axis, whereas ATO blocks the interleukin 6-induced promotion of STAT3 phosphorylation.	Metformin	16-25	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	53-57
24243637-9	2014	Treatment of adipocyte fractions or SGBS adipocytes with metformin or acetylsalicylic acid, which target C/EBPbeta and NF-kappaB/RelA signaling, attenuated the IL-1alpha induction of 11beta-HSD1 (P&lt;=.002).	Metformin	57-66	CCAAT enhancer binding protein beta	Homo sapiens	105-114
24243637-9	2014	Treatment of adipocyte fractions or SGBS adipocytes with metformin or acetylsalicylic acid, which target C/EBPbeta and NF-kappaB/RelA signaling, attenuated the IL-1alpha induction of 11beta-HSD1 (P&lt;=.002).	Metformin	57-66	RELA proto-oncogene, NF-kB subunit	Homo sapiens	129-133
24812633-11	2014	Metformin attenuated the suppression on proliferation with increased expression of Col I, OCN, and OPG, meanwhile suppressing MMP1 and MMP2.	Metformin	0-9	TNF receptor superfamily member 11b	Homo sapiens	99-102
24812633-11	2014	Metformin attenuated the suppression on proliferation with increased expression of Col I, OCN, and OPG, meanwhile suppressing MMP1 and MMP2.	Metformin	0-9	matrix metallopeptidase 2	Homo sapiens	135-139
24190973-8	2014	The activation of p53 through AMPK-mediated MDMX phosphorylation and inactivation was further confirmed by using cell and animal model systems with two AMPK activators, metformin and salicylate (the active form of aspirin).	Metformin	169-178	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	30-34
26351208-2	2014	Adenosine 5"-monophosphate-activated protein kinase (AMPK) activators such as metformin have similar actions in keeping with the TSC2/1 pathway linking activation of AMPK to inhibition of mTOR.	Metformin	78-87	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-51
26351208-2	2014	Adenosine 5"-monophosphate-activated protein kinase (AMPK) activators such as metformin have similar actions in keeping with the TSC2/1 pathway linking activation of AMPK to inhibition of mTOR.	Metformin	78-87	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	53-57
26351208-2	2014	Adenosine 5"-monophosphate-activated protein kinase (AMPK) activators such as metformin have similar actions in keeping with the TSC2/1 pathway linking activation of AMPK to inhibition of mTOR.	Metformin	78-87	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	166-170
24357397-13	2014	Metformin inhibited TGF-beta1-induced phosphorylation of Smad2/3.	Metformin	0-9	SMAD family member 2	Homo sapiens	57-64
24357397-14	2014	CONCLUSIONS: This study showed that metformin inhibits TGF-beta1-induced myofibroblast differentiation and ECM production in NPDFs via the Smad2/3 pathway.	Metformin	36-45	SMAD family member 2	Homo sapiens	139-146
24351837-4	2013	Metformin significantly inhibited the proliferation and colony formation of 5637 and T24 cells in vitro; specifically, metformin induced an apparent cell cycle arrest in G0/G1 phases, accompanied by a strong decrease of cyclin D1, cyclin-dependent kinase 4 (CDK4), E2F1 and an increase of p21waf-1.	Metformin	0-9	cyclin dependent kinase 4	Homo sapiens	231-256
23803693-3	2013	Treatment of Panc1, L3.6pL and Panc28 pancreatic cancer cells with metformin downregulated Sp1, Sp3 and Sp4 proteins and several pro-oncogenic Sp-regulated genes including bcl-2, survivin, cyclin D1, vascular endothelial growth factor and its receptor, and fatty acid synthase.	Metformin	67-76	cyclin D1	Homo sapiens	189-198
23993965-0	2013	Tiam-1, a GEF for Rac1, plays a critical role in metformin-mediated glucose uptake in C2C12 cells.	Metformin	49-58	T cell lymphoma invasion and metastasis 1	Mus musculus	0-6
23993965-0	2013	Tiam-1, a GEF for Rac1, plays a critical role in metformin-mediated glucose uptake in C2C12 cells.	Metformin	49-58	Rac family small GTPase 1	Mus musculus	18-22
23993965-2	2013	In this study, AMPK activators (AICAR and metformin) increased the expression of T-lymphoma invasion and metastasis-inducing protein-1 (Tiam-1), a Rac1 specific guanine nucleotide exchange factor (GEF), mRNA and protein in skeletal muscle C2C12 cells.	Metformin	42-51	T cell lymphoma invasion and metastasis 1	Mus musculus	81-134
23993965-2	2013	In this study, AMPK activators (AICAR and metformin) increased the expression of T-lymphoma invasion and metastasis-inducing protein-1 (Tiam-1), a Rac1 specific guanine nucleotide exchange factor (GEF), mRNA and protein in skeletal muscle C2C12 cells.	Metformin	42-51	T cell lymphoma invasion and metastasis 1	Mus musculus	136-142
23993965-2	2013	In this study, AMPK activators (AICAR and metformin) increased the expression of T-lymphoma invasion and metastasis-inducing protein-1 (Tiam-1), a Rac1 specific guanine nucleotide exchange factor (GEF), mRNA and protein in skeletal muscle C2C12 cells.	Metformin	42-51	Rac family small GTPase 1	Mus musculus	147-151
23993965-3	2013	Metformin increases the serine-phosphorylation of Tiam-1 by AMPK and induces interaction between Tiam-1 and 14-3-3.	Metformin	0-9	T cell lymphoma invasion and metastasis 1	Mus musculus	50-56
23993965-3	2013	Metformin increases the serine-phosphorylation of Tiam-1 by AMPK and induces interaction between Tiam-1 and 14-3-3.	Metformin	0-9	T cell lymphoma invasion and metastasis 1	Mus musculus	97-114
23993965-5	2013	Metformin also increases the phosphorylation of p21-activated kinase 1 (PAK1), a direct downstream target of Rac1, dependent on AMPK.	Metformin	0-9	Rac family small GTPase 1	Mus musculus	109-113
23993965-7	2013	Furthermore, Tiam-1 knock-down blocked metformin-induced increase in glucose uptake.	Metformin	39-48	T cell lymphoma invasion and metastasis 1	Mus musculus	13-19
23993965-8	2013	These findings suggest that metformin promotes cellular glucose uptake in part through Tiam-1 induction.	Metformin	28-37	T cell lymphoma invasion and metastasis 1	Mus musculus	87-93
24403860-2	2013	Clinical trials using the United States Food and Drug Administration (FDA)-approved, AMPK-activating, antidiabetic drug metformin are promising in this regard, but the question of why metformin is protective for some women but not others still remains.	Metformin	120-129	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	85-89
24403860-2	2013	Clinical trials using the United States Food and Drug Administration (FDA)-approved, AMPK-activating, antidiabetic drug metformin are promising in this regard, but the question of why metformin is protective for some women but not others still remains.	Metformin	184-193	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	85-89
24403860-7	2013	Activation of AMPK by metformin triggered a growth inhibitory signal but also increased BCA2 protein levels, which correlated with AKT activation and could be curbed by an AMPK inhibitor, suggesting a potential feedback mechanism from pAMPKalpha1 to pAkt to BCA2.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	14-18
24403860-7	2013	Activation of AMPK by metformin triggered a growth inhibitory signal but also increased BCA2 protein levels, which correlated with AKT activation and could be curbed by an AMPK inhibitor, suggesting a potential feedback mechanism from pAMPKalpha1 to pAkt to BCA2.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	172-176
24209692-4	2013	We identified multiple rare variants in KSR2 that disrupt signaling through the Raf-MEKERK pathway and impair cellular fatty acid oxidation and glucose oxidation in transfected cells; effects that can be ameliorated by the commonly prescribed antidiabetic drug, metformin.	Metformin	262-271	zinc fingers and homeoboxes 2	Homo sapiens	80-83
24265196-8	2013	For example, the AMPK activator metformin induces apoptosis in a variety of cancer cell lines and models.	Metformin	32-41	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	17-21
24265196-9	2013	A major problem with many of the studies on metformin is that little effort has been invested in unraveling how metformin activates AMPK in the many contexts it has been tested.	Metformin	112-121	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	132-136
24265196-10	2013	This is significant because many AMPK-independent effects of metformin have been documented.	Metformin	61-70	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	33-37
23841933-6	2013	Activation of AMPK, which is induced by glucose deprivation, treatment with pharmacological agents such as 2-deoxy-D-glucose, metformin, and 5-aminoimidazole-4-carboxamide ribonucleoside or forced expression of a constitutively active AMPKalpha subunit, counteracts BDNF-induced phosphorylation of p70S6K and enhanced protein synthesis in cortical neurons.	Metformin	126-135	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	14-18
23794020-3	2013	These results have drawn attention to the mechanisms underlying metformin"s anti-cancer effects, which may include triggering of the AMP-activated protein kinase (AMPK) pathway, resulting in vulnerability to an energy crisis (leading to cell death under conditions of nutrient deprivation) and a reduction in circulating insulin/IGF-1 levels.	Metformin	64-73	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	133-161
23794020-3	2013	These results have drawn attention to the mechanisms underlying metformin"s anti-cancer effects, which may include triggering of the AMP-activated protein kinase (AMPK) pathway, resulting in vulnerability to an energy crisis (leading to cell death under conditions of nutrient deprivation) and a reduction in circulating insulin/IGF-1 levels.	Metformin	64-73	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	163-167
24009772-0	2013	Metformin induces apoptosis through AMPK-dependent inhibition of UPR signaling in ALL lymphoblasts.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	36-40
24009772-3	2013	Metformin activated AMPK, down-regulated the unfolded protein response (UPR) demonstrated by significant decrease in the main UPR regulator GRP78, and led to UPR-mediated cell death via up-regulation of the ER stress/UPR cell death mediators IRE1alpha and CHOP.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	20-24
24009772-3	2013	Metformin activated AMPK, down-regulated the unfolded protein response (UPR) demonstrated by significant decrease in the main UPR regulator GRP78, and led to UPR-mediated cell death via up-regulation of the ER stress/UPR cell death mediators IRE1alpha and CHOP.	Metformin	0-9	endoplasmic reticulum to nucleus signaling 1	Homo sapiens	242-251
24009772-4	2013	Using shRNA, we demonstrate that metformin-induced apoptosis is AMPK-dependent since AMPK knock-down rescued ALL cells, which correlated with down-regulation of IRE1alpha and CHOP and restoration of the UPR/GRP78 function.	Metformin	33-42	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	64-68
24009772-4	2013	Using shRNA, we demonstrate that metformin-induced apoptosis is AMPK-dependent since AMPK knock-down rescued ALL cells, which correlated with down-regulation of IRE1alpha and CHOP and restoration of the UPR/GRP78 function.	Metformin	33-42	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	85-89
24009772-4	2013	Using shRNA, we demonstrate that metformin-induced apoptosis is AMPK-dependent since AMPK knock-down rescued ALL cells, which correlated with down-regulation of IRE1alpha and CHOP and restoration of the UPR/GRP78 function.	Metformin	33-42	endoplasmic reticulum to nucleus signaling 1	Homo sapiens	161-170
24009772-7	2013	Similar synergism was seen with agents targeting Akt in combination with metformin, supporting our original postulate that AMPK and Akt exert opposite regulatory roles on UPR activity in ALL.	Metformin	73-82	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	123-127
23904524-0	2013	Metformin inhibits growth of eutopic stromal cells from adenomyotic endometrium via AMPK activation and subsequent inhibition of AKT phosphorylation: a possible role in the treatment of adenomyosis.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	84-88
23983487-1	2013	INTRODUCTION: Metformin is a first-line drug choice for the treatment of type 2 diabetes mellitus (DM-2).	Metformin	14-23	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	99-103
22928702-4	2013	We hypothesized that metformin alone would lead to an improvement in HbA1C and lipid levels in overweight adolescent girls with PCOS compared with meformin with EP.	Metformin	21-30	hemoglobin subunit alpha 1	Homo sapiens	69-73
23595973-0	2013	Metformin augments the levels of molecules that regulate the expression of the insulin-dependent glucose transporter GLUT4 in the endometria of hyperinsulinemic PCOS patients.	Metformin	0-9	solute carrier family 2 member 4	Homo sapiens	117-122
23595973-1	2013	STUDY QUESTION: Does treatment with the insulin sensitizer metformin modify the levels and activation of proteins related to the expression of the insulin-dependent glucose transporter (GLUT4), such as adenosine monophosphate-activated protein kinase (AMPK) and myocyte enhancer factor 2A (MEF2A), in endometria from hyperinsulinemic hyperandrogenemic polycystic ovary syndrome (PCOS h-Ins) patients?	Metformin	59-68	solute carrier family 2 member 4	Homo sapiens	186-191
23595973-1	2013	STUDY QUESTION: Does treatment with the insulin sensitizer metformin modify the levels and activation of proteins related to the expression of the insulin-dependent glucose transporter (GLUT4), such as adenosine monophosphate-activated protein kinase (AMPK) and myocyte enhancer factor 2A (MEF2A), in endometria from hyperinsulinemic hyperandrogenemic polycystic ovary syndrome (PCOS h-Ins) patients?	Metformin	59-68	myocyte enhancer factor 2A	Homo sapiens	262-288
23595973-1	2013	STUDY QUESTION: Does treatment with the insulin sensitizer metformin modify the levels and activation of proteins related to the expression of the insulin-dependent glucose transporter (GLUT4), such as adenosine monophosphate-activated protein kinase (AMPK) and myocyte enhancer factor 2A (MEF2A), in endometria from hyperinsulinemic hyperandrogenemic polycystic ovary syndrome (PCOS h-Ins) patients?	Metformin	59-68	myocyte enhancer factor 2A	Homo sapiens	290-295
23595973-2	2013	SUMMARY ANSWER: In PCOS h-Ins patients, metformin increases endometrial levels of GLUT4 mRNA and protein levels by normalizing the quantity and activation of molecules that regulate GLUT4 expression to healthy values.	Metformin	40-49	solute carrier family 2 member 4	Homo sapiens	82-87
23595973-2	2013	SUMMARY ANSWER: In PCOS h-Ins patients, metformin increases endometrial levels of GLUT4 mRNA and protein levels by normalizing the quantity and activation of molecules that regulate GLUT4 expression to healthy values.	Metformin	40-49	solute carrier family 2 member 4	Homo sapiens	182-187
23595973-18	2013	WIDER IMPLICATIONS OF THE FINDINGS: Since the insulin sensitizer metformin increases the expression of the GLUT4, it may improve endometrial physiology in PCOS patients and, therefore, promote better reproductive outcomes.	Metformin	65-74	solute carrier family 2 member 4	Homo sapiens	107-112
23595973-19	2013	These results suggest that in PCOS patients, metformin may act directly at the endometrial level and decrease insulin resistance condition by increasing the expression of GLUT4 and, in this way, indirectly restore endometrial function.	Metformin	45-54	solute carrier family 2 member 4	Homo sapiens	171-176
23562376-0	2013	Transfer of metformin across the rat placenta is mediated by organic cation transporter 3 (OCT3/SLC22A3) and multidrug and toxin extrusion 1 (MATE1/SLC47A1) protein.	Metformin	12-21	solute carrier family 22 member 3	Rattus norvegicus	61-89
23562376-0	2013	Transfer of metformin across the rat placenta is mediated by organic cation transporter 3 (OCT3/SLC22A3) and multidrug and toxin extrusion 1 (MATE1/SLC47A1) protein.	Metformin	12-21	solute carrier family 22 member 3	Rattus norvegicus	91-95
23562376-0	2013	Transfer of metformin across the rat placenta is mediated by organic cation transporter 3 (OCT3/SLC22A3) and multidrug and toxin extrusion 1 (MATE1/SLC47A1) protein.	Metformin	12-21	solute carrier family 22 member 3	Rattus norvegicus	96-103
23562376-2	2013	Since metformin is a substrate of both OCT3 and MATE1, in this study we used the model of dually perfused rat placenta to investigate the role of these transporters in metformin passage across the placenta.	Metformin	6-15	solute carrier family 22 member 3	Rattus norvegicus	39-43
23562376-6	2013	In conclusion, we suggest an important role of OCT3 and MATE1 in the transplacental transfer of metformin.	Metformin	96-105	solute carrier family 22 member 3	Rattus norvegicus	47-51
23935921-5	2013	AICAR and metformin were used to activate AMPK in the presence of the secretagogues CTX or forskolin (FSK).	Metformin	10-19	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	42-46
23935921-9	2013	The increase in chloride efflux could be offset by using the AMPK activators AICAR and metformin.	Metformin	87-96	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	61-65
23936124-9	2013	AMPK activation by metformin completely reversed the inhibitory effect of glucose on Nampt-Sirt1-PGC-1 alpha and Rev-erb alpha.	Metformin	19-28	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	97-108
23362830-0	2013	Metformin induces cytotoxicity by down-regulating thymidine phosphorylase and excision repair cross-complementation 1 expression in non-small cell lung cancer cells.	Metformin	0-9	thymidine phosphorylase	Homo sapiens	50-73
23362830-3	2013	We used A549 and H1975 human non-small cell lung cancer (NSCLC) cell lines to investigate the role of TP and ERCC1 expression in metformin-induced cytotoxicity.	Metformin	129-138	thymidine phosphorylase	Homo sapiens	102-104
23362830-4	2013	Metformin treatment decreased cellular TP and ERCC1 protein and mRNA levels by down-regulating phosphorylated MEK1/2-ERK1/2 protein levels in a dose- and time-dependent manner.	Metformin	0-9	thymidine phosphorylase	Homo sapiens	39-41
23362830-6	2013	Specific inhibition of TP and ERCC1 expression by siRNA enhanced the metformin-induced cytotoxicity and growth inhibition.	Metformin	69-78	thymidine phosphorylase	Homo sapiens	23-25
23362830-8	2013	In conclusion, metformin induces cytotoxicity by down-regulating TP and ERCC1 expression in NSCLC cells.	Metformin	15-24	thymidine phosphorylase	Homo sapiens	65-67
23801715-3	2013	Although the known metabolic effects of AMPK activation are consistent with the idea that it mediates some of the therapeutic benefits of metformin, as discussed below it now appears unlikely that AMPK is the sole target of the drug.	Metformin	138-147	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	40-44
23651427-2	2013	The goal of this study is to determine whether IRIP regulates the activities of OCT1 and MATE1, and hence the disposition in vivo of their substrate metformin, a therapeutic drug for diabetes and other obesity-related syndromes.	Metformin	149-158	yrdC domain containing (E.coli)	Mus musculus	47-51
23651427-2	2013	The goal of this study is to determine whether IRIP regulates the activities of OCT1 and MATE1, and hence the disposition in vivo of their substrate metformin, a therapeutic drug for diabetes and other obesity-related syndromes.	Metformin	149-158	solute carrier family 47, member 1	Mus musculus	89-94
23651427-6	2013	By overexpressing IRIP in mouse liver via hydrodynamic tail vein injection, we demonstrated that increased IRIP expression could cause a significant reduction in hepatic accumulation of metformin (P &lt; 0.01).	Metformin	186-195	yrdC domain containing (E.coli)	Mus musculus	18-22
23651427-6	2013	By overexpressing IRIP in mouse liver via hydrodynamic tail vein injection, we demonstrated that increased IRIP expression could cause a significant reduction in hepatic accumulation of metformin (P &lt; 0.01).	Metformin	186-195	yrdC domain containing (E.coli)	Mus musculus	107-111
23651427-7	2013	In addition, we observed that the expression of IRIP was approximately half (P &lt; 0.01) in ob/ob mice when compared to their lean littermates, with significant increases in hepatic Oct1 protein expression and metformin accumulation.	Metformin	211-220	yrdC domain containing (E.coli)	Mus musculus	48-52
22751115-7	2013	AMPK activation by its activators AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) and metformin (N",N"-dimethylbiguanide), the most widely used antidiabetic drug, increased the expression of XPC and UVB-induced DNA repair in mouse skin, normal human epidermal keratinocytes, and AMPK wild-type (WT) cells but not in AMPK-deficient cells, indicating an AMPK-dependent mechanism.	Metformin	92-101	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
22751115-7	2013	AMPK activation by its activators AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) and metformin (N",N"-dimethylbiguanide), the most widely used antidiabetic drug, increased the expression of XPC and UVB-induced DNA repair in mouse skin, normal human epidermal keratinocytes, and AMPK wild-type (WT) cells but not in AMPK-deficient cells, indicating an AMPK-dependent mechanism.	Metformin	92-101	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	285-289
22751115-7	2013	AMPK activation by its activators AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) and metformin (N",N"-dimethylbiguanide), the most widely used antidiabetic drug, increased the expression of XPC and UVB-induced DNA repair in mouse skin, normal human epidermal keratinocytes, and AMPK wild-type (WT) cells but not in AMPK-deficient cells, indicating an AMPK-dependent mechanism.	Metformin	92-101	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	285-289
22751115-7	2013	AMPK activation by its activators AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) and metformin (N",N"-dimethylbiguanide), the most widely used antidiabetic drug, increased the expression of XPC and UVB-induced DNA repair in mouse skin, normal human epidermal keratinocytes, and AMPK wild-type (WT) cells but not in AMPK-deficient cells, indicating an AMPK-dependent mechanism.	Metformin	92-101	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	285-289
22751115-7	2013	AMPK activation by its activators AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) and metformin (N",N"-dimethylbiguanide), the most widely used antidiabetic drug, increased the expression of XPC and UVB-induced DNA repair in mouse skin, normal human epidermal keratinocytes, and AMPK wild-type (WT) cells but not in AMPK-deficient cells, indicating an AMPK-dependent mechanism.	Metformin	109-126	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
22751115-7	2013	AMPK activation by its activators AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) and metformin (N",N"-dimethylbiguanide), the most widely used antidiabetic drug, increased the expression of XPC and UVB-induced DNA repair in mouse skin, normal human epidermal keratinocytes, and AMPK wild-type (WT) cells but not in AMPK-deficient cells, indicating an AMPK-dependent mechanism.	Metformin	109-126	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	285-289
22751115-7	2013	AMPK activation by its activators AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) and metformin (N",N"-dimethylbiguanide), the most widely used antidiabetic drug, increased the expression of XPC and UVB-induced DNA repair in mouse skin, normal human epidermal keratinocytes, and AMPK wild-type (WT) cells but not in AMPK-deficient cells, indicating an AMPK-dependent mechanism.	Metformin	109-126	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	285-289
22751115-7	2013	AMPK activation by its activators AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) and metformin (N",N"-dimethylbiguanide), the most widely used antidiabetic drug, increased the expression of XPC and UVB-induced DNA repair in mouse skin, normal human epidermal keratinocytes, and AMPK wild-type (WT) cells but not in AMPK-deficient cells, indicating an AMPK-dependent mechanism.	Metformin	109-126	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	285-289
22751115-9	2013	Furthermore, AMPK deletion increased extracellular signal-regulated kinase (ERK) activation and cell proliferation, whereas AICAR and metformin inhibited ERK activation and cell proliferation in keratinocytes, mouse skin, AMPK WT and AMPK-deficient cells, suggesting an AMPK-independent mechanism.	Metformin	134-143	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	222-226
22751115-9	2013	Furthermore, AMPK deletion increased extracellular signal-regulated kinase (ERK) activation and cell proliferation, whereas AICAR and metformin inhibited ERK activation and cell proliferation in keratinocytes, mouse skin, AMPK WT and AMPK-deficient cells, suggesting an AMPK-independent mechanism.	Metformin	134-143	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	222-226
22751115-9	2013	Furthermore, AMPK deletion increased extracellular signal-regulated kinase (ERK) activation and cell proliferation, whereas AICAR and metformin inhibited ERK activation and cell proliferation in keratinocytes, mouse skin, AMPK WT and AMPK-deficient cells, suggesting an AMPK-independent mechanism.	Metformin	134-143	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	222-226
23315983-0	2013	Visfatin is expressed in human granulosa cells: regulation by metformin through AMPK/SIRT1 pathways and its role in steroidogenesis.	Metformin	62-71	nicotinamide phosphoribosyltransferase	Homo sapiens	0-8
23315983-0	2013	Visfatin is expressed in human granulosa cells: regulation by metformin through AMPK/SIRT1 pathways and its role in steroidogenesis.	Metformin	62-71	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	80-84
23315983-3	2013	Here, we identified visfatin in human follicles and investigated the molecular mechanisms involved in the regulation of its expression in response to insulin sensitizers, metformin (MetF) and rosiglitazone, in primary human granulosa cells (hGCs) and in a human ovarian granulosa-like tumour cell line (KGN).	Metformin	171-180	nicotinamide phosphoribosyltransferase	Homo sapiens	20-28
23315983-3	2013	Here, we identified visfatin in human follicles and investigated the molecular mechanisms involved in the regulation of its expression in response to insulin sensitizers, metformin (MetF) and rosiglitazone, in primary human granulosa cells (hGCs) and in a human ovarian granulosa-like tumour cell line (KGN).	Metformin	182-186	nicotinamide phosphoribosyltransferase	Homo sapiens	20-28
23540700-5	2013	Alterations in metformin-induced longevity by mutation of worm methionine synthase (metr-1) and S-adenosylmethionine synthase (sams-1) imply metformin-induced methionine restriction in the host, consistent with action of this drug as a dietary restriction mimetic.	Metformin	15-24	putative methionine synthase	Caenorhabditis elegans	84-90
23540700-5	2013	Alterations in metformin-induced longevity by mutation of worm methionine synthase (metr-1) and S-adenosylmethionine synthase (sams-1) imply metformin-induced methionine restriction in the host, consistent with action of this drug as a dietary restriction mimetic.	Metformin	141-150	putative methionine synthase	Caenorhabditis elegans	84-90
23382195-5	2013	Our results show that AMPK activation with treatment of 5-aminoimidazole-4-carboxamide ribonucleotide, metformin, or pulsatile shear stress induces PARP-1 dissociation from the Bcl-6 intron 1, increases Bcl-6 expression, and inhibits expression of inflammatory mediators.	Metformin	103-112	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	22-26
23267855-0	2013	The effect of novel promoter variants in MATE1 and MATE2 on the pharmacokinetics and pharmacodynamics of metformin.	Metformin	105-114	solute carrier family 47 member 2	Homo sapiens	51-56
23103561-8	2013	The increase in angiogenesis by Metformin is abolished by pretreatment with AMPK inhibitor, Compound C. Expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor beta (PDGFbeta) are decreased in IPH-PAEC compared with control PAEC and were not altered by Metformin.	Metformin	32-41	vascular endothelial growth factor A	Ovis aries	118-152
23103561-8	2013	The increase in angiogenesis by Metformin is abolished by pretreatment with AMPK inhibitor, Compound C. Expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor beta (PDGFbeta) are decreased in IPH-PAEC compared with control PAEC and were not altered by Metformin.	Metformin	32-41	vascular endothelial growth factor A	Ovis aries	154-158
23103561-8	2013	The increase in angiogenesis by Metformin is abolished by pretreatment with AMPK inhibitor, Compound C. Expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor beta (PDGFbeta) are decreased in IPH-PAEC compared with control PAEC and were not altered by Metformin.	Metformin	288-297	vascular endothelial growth factor A	Ovis aries	118-152
23103561-8	2013	The increase in angiogenesis by Metformin is abolished by pretreatment with AMPK inhibitor, Compound C. Expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor beta (PDGFbeta) are decreased in IPH-PAEC compared with control PAEC and were not altered by Metformin.	Metformin	288-297	vascular endothelial growth factor A	Ovis aries	154-158
23621234-10	2013	In conclusion, expression changes in miRNAs of miR-146a, miR-100, miR-425, miR-193a-3p and, miR-106b in metformin-treated cells may be important.	Metformin	104-113	microRNA 425	Homo sapiens	66-73
23991948-2	2013	Besides the discovery of somatic mutations in the LKB1 gene in certain type of cancers, a critical emerging point was that the LKB1/AMPK axis remains generally functional and could be stimulated by pharmacological molecules such as metformin in cancer cells.	Metformin	232-241	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	132-136
23431246-7	2013	HE3286 HbA1c decrease correlated with weight loss and inversely with baseline monocyte chemoattractant protein-1 (MCP-1) in metformin-treated diabetics.	Metformin	124-133	hemoglobin subunit alpha 1	Homo sapiens	7-11
23301094-8	2013	In contrast, co-treatment with Compound C (AMPK inhibitor) could significantly abrogate metformin induced DVL3 reduction.	Metformin	88-97	dishevelled segment polarity protein 3	Homo sapiens	106-110
23301094-9	2013	In addition, co-treatment with AM114 or MG132 (proteosomal inhibitors) could partially restore DVL3 expression under the treatment of metformin.	Metformin	134-143	dishevelled segment polarity protein 3	Homo sapiens	95-99
23301094-10	2013	Further in vivo ubiquitination assay revealed that metformin could reduce DVL3 by ubiquitin/proteasomal degradation.	Metformin	51-60	dishevelled segment polarity protein 3	Homo sapiens	74-78
23019312-8	2012	Overall, this study indicates that exercise training and metformin have additive influences on adipose tissue secretion and plasma concentrations of leptin and IL-10.	Metformin	57-66	leptin	Rattus norvegicus	149-155
23222299-11	2012	Treatment with the antidiabetic drug metformin during ovariectomy-induced weight gain caused tumor regression and downregulation of PR expression in tumors.	Metformin	37-46	progesterone receptor	Homo sapiens	132-134
22248012-0	2012	Pigment epithelium-derived factor increases in type 2 diabetes after treatment with metformin.	Metformin	84-93	serpin family F member 1	Homo sapiens	0-33
22248012-4	2012	However, whether metformin treatment has any significant effects on PEDF levels is not known.	Metformin	17-26	serpin family F member 1	Homo sapiens	68-72
22248012-12	2012	We observed a decrease in the weight, WC, FPG, PPPG, HOMA, total and truncal fat mass of the patients while there was a significant rise in the PEDF levels (P = 0 002) after the metformin treatment.	Metformin	178-187	serpin family F member 1	Homo sapiens	144-148
22248012-14	2012	CONCLUSION: Our study is the first to identify a metformin-related increase in PEDF levels in diabetes.	Metformin	49-58	serpin family F member 1	Homo sapiens	79-83
22248012-15	2012	The increase observed in PEDF levels after the metformin treatment does not seem to be related to the changes in insulin resistance, fat mass or glycemic control.	Metformin	47-56	serpin family F member 1	Homo sapiens	25-29
22248012-16	2012	Hence, our results suggest that further investigation is necessary to determine the direct effects of metformin on PEDF gene and protein expression in vitro.	Metformin	102-111	serpin family F member 1	Homo sapiens	115-119
22968630-6	2012	Our data also showed that metformin increased the expressions of PGC1-alpha, NRF-1, and TFAM, which were reduced in the NYGGF4 overexpression adipocytes.	Metformin	26-35	nuclear respiratory factor 1	Homo sapiens	77-82
22968630-7	2012	These results suggest that NYGGF4 plays a role in IR and its effects on IR could be reversed by metformin through activating IRS-1/PI3K/Akt and AMPK-PGC1-alpha pathways.	Metformin	96-105	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	144-148
22977252-8	2012	Up-regulation of SHP by metformin-mediated activation of the ATM-AMP-activated protein kinase pathway led to inhibition of GH-mediated induction of hepatic gluconeogenesis, which was abolished by an ATM inhibitor, KU-55933.	Metformin	24-33	ataxia telangiectasia mutated	Mus musculus	61-64
22977252-8	2012	Up-regulation of SHP by metformin-mediated activation of the ATM-AMP-activated protein kinase pathway led to inhibition of GH-mediated induction of hepatic gluconeogenesis, which was abolished by an ATM inhibitor, KU-55933.	Metformin	24-33	ataxia telangiectasia mutated	Mus musculus	199-202
23102217-5	2012	Indeed, AMPK is activated by the drugs metformin and salicylate, the latter being the major breakdown product of aspirin.	Metformin	39-48	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	8-12
22821946-6	2012	Pretreatment with AICAR or metformin (AMPK activators) or compound C (an AMPK inhibitor) reduced or increased cerulein-induced zymogen activation, respectively.	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	38-42
22964327-9	2012	Suppression of AMPK by Compound C augmented RANKL expression, and AMPK activation by metformin significantly decreased RANKL expression in hPDL cells.	Metformin	85-94	programmed cell death 1	Homo sapiens	139-143
22964327-10	2012	Additionally, metformin down-regulated RANKL expression in hPDL cells exposed to high glucose via AMPK activation.	Metformin	14-23	programmed cell death 1	Homo sapiens	59-63
22778212-0	2012	Metformin inhibits human androgen production by regulating steroidogenic enzymes HSD3B2 and CYP17A1 and complex I activity of the respiratory chain.	Metformin	0-9	cytochrome P450 family 17 subfamily A member 1	Homo sapiens	92-99
22778212-6	2012	Similar to in vivo situation, metformin inhibited androgen production in NCI cells by decreasing HSD3B2 expression and CYP17A1 and HSD3B2 activities.	Metformin	30-39	cytochrome P450 family 17 subfamily A member 1	Homo sapiens	119-126
22644486-0	2012	Metformin interacts with AMPK through binding to gamma subunit.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	25-29
22644486-1	2012	Metformin acts as an energy regulator by activating 5"-adenosine monophosphate-activated protein kinase (AMPK), which is a key player in the regulation of energy homeostasis, but it is uncertain whether AMPK is its direct target.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	105-109
22644486-2	2012	This study aims to investigate the possible interaction between metformin and AMPK.	Metformin	64-73	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	78-82
22644486-3	2012	First, we verified that metformin can promote AMPK activation and induce ACC inactivation in human HepG2 cells using western blot.	Metformin	24-33	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	46-50
22644486-4	2012	Then we predicted that metformin may interact with the gamma subunit of AMPK by molecular docking analysis.	Metformin	23-32	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	72-76
22644486-5	2012	The fluorescence spectrum and ForteBio assays indicated that metformin has a stronger binding ability to the gamma subunit of AMPK than to alpha subunit.	Metformin	61-70	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	126-130
22644486-6	2012	In addition, interaction of metformin with gamma-AMPK resulted in a decrease in the alpha-helicity determined by CD spectra, but relatively little change was seen with alpha-AMPK.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	49-53
22644486-6	2012	In addition, interaction of metformin with gamma-AMPK resulted in a decrease in the alpha-helicity determined by CD spectra, but relatively little change was seen with alpha-AMPK.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	174-178
22644486-7	2012	These results demonstrate that metformin may interact with AMPK through binding to the gamma subunit.	Metformin	31-40	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	59-63
22572996-0	2012	Effects of metformin on the expression of GLUT4 in endometrium of obese women with polycystic ovary syndrome.	Metformin	11-20	solute carrier family 2 member 4	Homo sapiens	42-47
22572996-1	2012	The objective was to explore the effects of metformin on the expression of endometrial glucose transporter 4 (GLUT4) and analyze the related factors of GLUT4 in patients with polycystic ovary syndrome (PCOS).	Metformin	44-53	solute carrier family 2 member 4	Homo sapiens	87-108
22572996-1	2012	The objective was to explore the effects of metformin on the expression of endometrial glucose transporter 4 (GLUT4) and analyze the related factors of GLUT4 in patients with polycystic ovary syndrome (PCOS).	Metformin	44-53	solute carrier family 2 member 4	Homo sapiens	110-115
22572996-9	2012	The expression of protein and mRNA of endometrial GLUT4 increased after metformin treatment (P &lt; 0.001).	Metformin	72-81	solute carrier family 2 member 4	Homo sapiens	50-55
22572996-12	2012	Metformin may up-regulate endometrial GLUT4 expression to improve endometrial IR.	Metformin	0-9	solute carrier family 2 member 4	Homo sapiens	38-43
22432846-10	2012	GLP-1 receptor agonists should be considered also in patients in therapy with metformin and another agent, such as a sulfonylurea, because of the minor risk of developing hypoglycemia and the positive effect on body weight.	Metformin	78-87	glucagon like peptide 1 receptor	Homo sapiens	0-14
22694351-3	2012	Because metformin, an AMPK activator that is a favored first-line therapeutic option for type 2 diabetes, may confer benefits in chronic inflammatory diseases and cancers independent of its ability to normalize blood glucose, there is now considerable interest in identifying and exploiting AMPK"s anti-inflammatory effects.	Metformin	8-17	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	291-295
22442140-1	2012	Focus on "A novel inverse relationship between metformin-triggered AMPK-SIRT1 signaling and p53 protein abundance in high glucose-exposed HepG2 cells".	Metformin	47-56	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	67-71
22717640-3	2012	In addition, the widely used antidiabetic metformin also exerts its anti-inflammatory effects through activating AMPK.	Metformin	42-51	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	113-117
22611195-2	2012	Metformin exhibits antiproliferative and antineoplastic effects associated with inhibition of mammalian target of rapamycin complex 1 (mTORC1), but the mechanisms are poorly understood.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	135-141
22611195-4	2012	Importantly, metformin"s antiproliferative activity can be explained by selective translational suppression of mRNAs encoding cell-cycle regulators via the mTORC1/eukaryotic translation initiation factor 4E-binding protein pathway.	Metformin	13-22	CREB regulated transcription coactivator 1	Mus musculus	156-162
22492524-3	2012	We demonstrate that copper sequestration opposes known actions of metformin not only on AMP-activated protein kinase (AMPK)-dependent signaling, but also on S6 protein phosphorylation.	Metformin	66-75	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	88-116
22492524-3	2012	We demonstrate that copper sequestration opposes known actions of metformin not only on AMP-activated protein kinase (AMPK)-dependent signaling, but also on S6 protein phosphorylation.	Metformin	66-75	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	118-122
22492524-4	2012	Biguanide/metal interactions are stabilized by extensive pi-electron delocalization and by investigating analogs of metformin; we provide evidence that this intrinsic property enables biguanides to regulate AMPK, glucose production, gluconeogenic gene expression, mitochondrial respiration, and mitochondrial copper binding.	Metformin	116-125	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	207-211
22407892-11	2012	These findings challenge the presumption that systemic OCT inhibition will affect metformin pharmacology.	Metformin	82-91	plexin A2	Mus musculus	55-58
21298495-6	2012	Additionally, DM2 patients without cancer, who had parents or siblings with DM2, received biguanide metformin versus sulfonylurea derivatives more often than those with breast or endometrial cancer, either with or without family history of DM2.	Metformin	100-109	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	14-17
21298495-6	2012	Additionally, DM2 patients without cancer, who had parents or siblings with DM2, received biguanide metformin versus sulfonylurea derivatives more often than those with breast or endometrial cancer, either with or without family history of DM2.	Metformin	100-109	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	76-79
21298495-6	2012	Additionally, DM2 patients without cancer, who had parents or siblings with DM2, received biguanide metformin versus sulfonylurea derivatives more often than those with breast or endometrial cancer, either with or without family history of DM2.	Metformin	100-109	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	76-79
22389381-2	2012	Recent studies showed that the antidiabetic agent metformin decreases proliferation of cancer cells through 5"-AMP-activated protein kinase (AMPK)-dependent inhibition of mTOR.	Metformin	50-59	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	141-145
22389381-6	2012	We found that metformin inhibited growth and decreased expression of cyclin D1 in MTC cells.	Metformin	14-23	cyclin D1	Homo sapiens	69-78
22389381-9	2012	Metformin-inducible AMPK activation was noted only in TT cells.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	20-24
22593501-1	2012	BACKGROUND: In a retrospective controlled study, a tumor-protective effect, regarding breast cancer, was determined for the medicines metformin and glitazone (anti-diabetics), bisoprolol, and propranolol (cardioselective beta1 adrenoceptor antagonists).	Metformin	134-143	adrenoceptor beta 1	Homo sapiens	221-239
22266668-6	2012	These GLP-1 effects were more pronounced in the presence of an activating mutation of Kras and were inhibited by metformin.	Metformin	113-122	glucagon	Mus musculus	6-11
22576211-1	2012	UNLABELLED: The antidiabetic drug metformin has antitumor activity in a variety of cancers because it blocks cell growth by inhibiting TORC1.	Metformin	34-43	CREB regulated transcription coactivator 1	Homo sapiens	135-140
22326821-5	2012	Furthermore, the body weight, liver glycogen formation, antioxidant substance (GSH) and antioxidant enzyme (SOD and GPX) levels increased evidently in diabetic mice treated with both ASP and metformin.	Metformin	191-200	peroxiredoxin 6 pseudogene 2	Mus musculus	116-119
20560107-3	2010	The action of metformin was analyzed by dividing lipopolysaccharide signaling into the MyD88-dependent and -independent pathways.	Metformin	14-23	MYD88 innate immune signal transduction adaptor	Homo sapiens	87-92
20560107-6	2010	The expression levels of interferon-beta protein and mRNA, which is a key molecule in MyD88-independent pathway, were significantly inhibited by metformin.	Metformin	145-154	interferon beta 1	Homo sapiens	25-40
20560107-6	2010	The expression levels of interferon-beta protein and mRNA, which is a key molecule in MyD88-independent pathway, were significantly inhibited by metformin.	Metformin	145-154	MYD88 innate immune signal transduction adaptor	Homo sapiens	86-91
20560107-8	2010	Metformin was suggested to inhibit lipopolysaccharide-induced nitric oxide production via inhibition of interferon-beta production in MyD88-independent pathway.	Metformin	0-9	interferon beta 1	Homo sapiens	104-119
20560107-8	2010	Metformin was suggested to inhibit lipopolysaccharide-induced nitric oxide production via inhibition of interferon-beta production in MyD88-independent pathway.	Metformin	0-9	MYD88 innate immune signal transduction adaptor	Homo sapiens	134-139
20599746-3	2010	In studies using the AMPK activators AICAR or metformin, we found potent inhibitory effects of AMPK activity on the growth of SK-MEL-2 and SK-MEL-28 malignant melanoma cells.	Metformin	46-55	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	95-99
20583965-7	2010	Streptozotocin diabetes provoked increase of both GLUT1 gene and protein expression in kidneys, metformin treatment produced normalization of the GLUT1 expression levels.	Metformin	96-105	solute carrier family 2 member 1	Rattus norvegicus	146-151
20583965-8	2010	In the liver, diabetes triggered an increase in GLUT1 protein expression, which was normalized by metformin.	Metformin	98-107	solute carrier family 2 member 1	Rattus norvegicus	48-53
27688041-7	2016	Finally, overexpression of SHP and metformin treatment of BMP6 stimulated mice substantially restored hepcidin expression and serum iron to baseline levels.	Metformin	35-44	bone morphogenetic protein 6	Mus musculus	58-62
27177784-8	2016	In comparison with the metformin-sulphonylurea regimen, adjusted HRs were 0.78 (95% CI 0.55; 1.11) for the metformin-DPP-4 inhibitor regimen and 0.68 (95% CI 0.54; 0.85) for the metformin-thiazolidinedione regimen.	Metformin	107-116	dipeptidyl peptidase 4	Homo sapiens	117-122
28157435-0	2010	The combination of metformin and 2 deoxyglucose inhibits autophagy and induces AMPK-dependent apoptosis in prostate cancer cells.	Metformin	19-28	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	79-83
27177784-8	2016	In comparison with the metformin-sulphonylurea regimen, adjusted HRs were 0.78 (95% CI 0.55; 1.11) for the metformin-DPP-4 inhibitor regimen and 0.68 (95% CI 0.54; 0.85) for the metformin-thiazolidinedione regimen.	Metformin	107-116	dipeptidyl peptidase 4	Homo sapiens	117-122
27268470-10	2016	The significantly decreased cardiovascular risk associated with empagliflozin SGLT-2 inhibitor therapy is impressive and may change how practitioners prescribe add-on therapy to metformin.	Metformin	178-187	solute carrier family 5 member 2	Homo sapiens	78-84
27730072-13	2016	DISCUSSION: Even short-term treatment with metformin causes a decrease in serum Cbl folic acid and increase in Hcy, which leads to peripheral neuropathy in Type 2 diabetes patients.	Metformin	43-52	Cbl proto-oncogene	Homo sapiens	80-83
27643646-8	2016	Metformin reduced EMT in the cell lines and regulated the expression of the EMT-related epithelial markers, E-cadherin and Pan-keratin; the mesenchymal markers, N-cadherin, fibronectin, and vimentin; and the EMT drivers, Twist-1, snail-1, and ZEB-1.	Metformin	0-9	vimentin	Homo sapiens	190-198
27510385-11	2016	The mRNA levels of collagen, collagen-1, procollagen, fibronectin, and transforming growth factor-beta in the metformin-treated mice were lower than those in the BLM-only mice on day 21, although statistical significance was observed only in the case of procollagen due to the small number of live mice in the BLM-only group.	Metformin	110-119	fibronectin 1	Mus musculus	54-65
27517917-10	2016	Metformin treatment reduced breast cancer cell viability, increased miR-26a expression, and led to a reduction in BCL-2, EZH2, and PTEN expression.	Metformin	0-9	phosphatase and tensin homolog	Homo sapiens	131-135
27517917-12	2016	Our results indicate that metformin effectively reduces breast cancer cell viability and suggests that the effects of the drug are mediated by an increase in miR-26a expression and a reduction of its targets, PTEN and EHZ2 Thus, the use of metformin in breast cancer treatment constitutes a promising potential breast cancer therapy.	Metformin	26-35	phosphatase and tensin homolog	Homo sapiens	209-213
27391065-4	2016	Metformin also triggers the apoptotic pathway, shown by the decreased expression of Bcl-2 and HSP27, HSP60 and HSP70, and enhanced membrane exposure of annexin V, resulting in activation of caspase-3 apoptotic effector.	Metformin	0-9	heat shock protein family B (small) member 1	Homo sapiens	94-99
27391065-4	2016	Metformin also triggers the apoptotic pathway, shown by the decreased expression of Bcl-2 and HSP27, HSP60 and HSP70, and enhanced membrane exposure of annexin V, resulting in activation of caspase-3 apoptotic effector.	Metformin	0-9	annexin A5	Homo sapiens	152-161
27391065-5	2016	Metformin interferes with the proliferative autocrine loop of IGF2/IGF-1R, which supports adrenal cancer growth.	Metformin	0-9	insulin like growth factor 2	Homo sapiens	62-66
27509335-5	2016	Moreover, metformin induces mitochondrial dysfunction and cell death by affecting the level and conformation of Translocase of the Outer Membrane 40 (TOM40), voltage-dependent anion-selective channels 1 (VDAC1) and hexokinase I (HKI), proteins involved in mitochondrial transport of molecules, including Abeta.	Metformin	10-19	translocase of outer mitochondrial membrane 40	Mus musculus	150-155
27509335-5	2016	Moreover, metformin induces mitochondrial dysfunction and cell death by affecting the level and conformation of Translocase of the Outer Membrane 40 (TOM40), voltage-dependent anion-selective channels 1 (VDAC1) and hexokinase I (HKI), proteins involved in mitochondrial transport of molecules, including Abeta.	Metformin	10-19	amyloid beta (A4) precursor protein	Mus musculus	304-309
27509335-6	2016	By using biophysical techniques we found that metformin is able to directly interact with Abeta influencing its aggregation kinetics and features.	Metformin	46-55	amyloid beta (A4) precursor protein	Mus musculus	90-95
27174003-9	2016	Treatment with metformin reduced the expression of GFAP, Iba-1 (astrocyte and microglial markers) and the inflammation markers (p-IKB, IL-1 and VEGF), while enhancing p-AMPK and eNOS levels and increasing neuronal survival (Fox-1 and NeuN).	Metformin	15-24	glial fibrillary acidic protein	Mus musculus	51-55
27174003-9	2016	Treatment with metformin reduced the expression of GFAP, Iba-1 (astrocyte and microglial markers) and the inflammation markers (p-IKB, IL-1 and VEGF), while enhancing p-AMPK and eNOS levels and increasing neuronal survival (Fox-1 and NeuN).	Metformin	15-24	induction of brown adipocytes 1	Mus musculus	57-62
26974526-2	2016	This study assessed the effect of dolutegravir on the pharmacokinetics of metformin, an OCT2 substrate.	Metformin	74-83	solute carrier family 22 member 2	Homo sapiens	88-92
26974526-12	2016	CONCLUSIONS: Dolutegravir significantly increased metformin plasma exposure, which can be partially explained by OCT2 inhibition.	Metformin	50-59	solute carrier family 22 member 2	Homo sapiens	113-117
27454290-10	2016	Together, these results reveal that p53-dependent coordination of AMPK and mTORC1 signaling controls parturition timing and suggest that metformin and resveratrol have therapeutic potential to prevent PTB.	Metformin	137-146	transformation related protein 53	Mus musculus	36-39
27217019-7	2016	Furthermore, metformin recoupled eNOS through upregulating GTPCH1 and BH4 levels, and attenuated the upregulation of p47-phox in FG-treated HUVECs.	Metformin	13-22	inhibitor of growth family member 1	Homo sapiens	117-120
27297969-7	2016	Pretreatment with 2-deoxyglucose, cobalt chloride, AICAR and metformin significantly enhanced CD1d-mediated NKT-cell activation.	Metformin	61-70	CD1d molecule	Homo sapiens	94-98
27256105-6	2016	Conversely, chronic administration of metformin, which activated AMPK, markedly reduced atherosclerotic calcification and Runx2 expression in ApoE(-/-) mice but had less effects in ApoE(-/-)/AMPKalpha1(-/-) mice.	Metformin	38-47	runt related transcription factor 2	Mus musculus	122-127
27256105-10	2016	Finally, mutation of protein inhibitor of activated STAT-1 at serine 510 suppressed metformin-induced Runx2 SUMOylation and subsequently prevented metformin"s effect on reducing oxidized low-density lipoprotein-triggered Runx2 expression in VSMC.	Metformin	84-93	runt related transcription factor 2	Mus musculus	102-107
27256105-10	2016	Finally, mutation of protein inhibitor of activated STAT-1 at serine 510 suppressed metformin-induced Runx2 SUMOylation and subsequently prevented metformin"s effect on reducing oxidized low-density lipoprotein-triggered Runx2 expression in VSMC.	Metformin	84-93	runt related transcription factor 2	Mus musculus	221-226
27256105-10	2016	Finally, mutation of protein inhibitor of activated STAT-1 at serine 510 suppressed metformin-induced Runx2 SUMOylation and subsequently prevented metformin"s effect on reducing oxidized low-density lipoprotein-triggered Runx2 expression in VSMC.	Metformin	147-156	runt related transcription factor 2	Mus musculus	221-226
27478876-8	2016	Metformin increased protein abundance of inner medullary urea transporter UT-A1 by 61% and aquaporin 2 (AQP2) by 44% in tolvaptan-treated rats, and immunohistochemistry showed increased membrane accumulation of AQP2 with acute and chronic AMPK stimulation.	Metformin	0-9	aquaporin 2	Rattus norvegicus	91-102
20393151-0	2010	Role of KLF15 in regulation of hepatic gluconeogenesis and metformin action.	Metformin	59-68	Kruppel-like factor 15	Mus musculus	8-13
20393151-5	2010	Exposure of cultured hepatocytes to metformin reduced the abundance of KLF15 through acceleration of its degradation and downregulation of its mRNA.	Metformin	36-45	Kruppel-like factor 15	Mus musculus	71-76
20393151-6	2010	Metformin suppressed the expression of genes for gluconeogenic or amino acid-degrading enzymes in cultured hepatocytes, and these effects of metformin were attenuated by restoration of KLF15 expression.	Metformin	0-9	Kruppel-like factor 15	Mus musculus	185-190
20393151-6	2010	Metformin suppressed the expression of genes for gluconeogenic or amino acid-degrading enzymes in cultured hepatocytes, and these effects of metformin were attenuated by restoration of KLF15 expression.	Metformin	141-150	Kruppel-like factor 15	Mus musculus	185-190
20393151-7	2010	Administration of metformin to mice inhibited both the expression of KLF15 and glucose production in the liver, the latter effect also being attenuated by restoration of hepatic KLF15 expression.	Metformin	18-27	Kruppel-like factor 15	Mus musculus	69-74
20393151-7	2010	Administration of metformin to mice inhibited both the expression of KLF15 and glucose production in the liver, the latter effect also being attenuated by restoration of hepatic KLF15 expression.	Metformin	18-27	Kruppel-like factor 15	Mus musculus	178-183
20393151-8	2010	CONCLUSIONS: KLF15 plays an important role in regulation of the expression of genes for gluconeogenic and amino acid-degrading enzymes and that the inhibitory effect of metformin on gluconeogenesis is mediated at least in part by downregulation of KLF15 and consequent attenuation of the expression of such genes.	Metformin	169-178	Kruppel-like factor 15	Mus musculus	13-18
20393151-8	2010	CONCLUSIONS: KLF15 plays an important role in regulation of the expression of genes for gluconeogenic and amino acid-degrading enzymes and that the inhibitory effect of metformin on gluconeogenesis is mediated at least in part by downregulation of KLF15 and consequent attenuation of the expression of such genes.	Metformin	169-178	Kruppel-like factor 15	Mus musculus	248-253
20671408-0	2010	Preliminary data on effects of metformin on PED/PEA-15 cellular levels in obese women with polycystic ovary syndrome.	Metformin	31-40	OCA2 melanosomal transmembrane protein	Homo sapiens	44-47
20671408-2	2010	AIM: To investigate whether metformin (MET) has additive effects on PED/PEA-15 protein levels.	Metformin	28-37	OCA2 melanosomal transmembrane protein	Homo sapiens	68-71
19617399-3	2010	AMPK activation after overnight treatment with either metformin (2-5 mM) or AICAR (1 mM) substantially inhibited ENaC-dependent I(sc) in both CF and non-CF airway cultures.	Metformin	54-63	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
19617399-4	2010	Live-cell confocal images acquired 60 minutes after apical addition of Texas Red-dextran-containing fluid revealed significantly greater ASL heights after AICAR and metformin treatment relative to controls, suggesting that AMPK-dependent ENaC inhibition slows apical fluid reabsorption.	Metformin	165-174	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	223-227
24843413-8	2010	Furthermore, we found that metformin and pioglitazone, both of which have the ability to reduce diabetic vascular complications, could ameliorate hyperglycemia-induced mtROS production by the induction of PPARgamma coactivator-1alpha (PGC-1alpha) and MnSOD and/or activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK).	Metformin	27-36	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	205-233
24843413-8	2010	Furthermore, we found that metformin and pioglitazone, both of which have the ability to reduce diabetic vascular complications, could ameliorate hyperglycemia-induced mtROS production by the induction of PPARgamma coactivator-1alpha (PGC-1alpha) and MnSOD and/or activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK).	Metformin	27-36	peroxisome proliferative activated receptor, gamma, coactivator 1 alpha	Mus musculus	235-245
22263023-10	2010	The expressions of MMP2 and MMP9 mRNA were both up-regulated after metformin treatment, while in the 8mmol/L Group the genes changes were the most significant.	Metformin	67-76	matrix metallopeptidase 2	Homo sapiens	19-23
22263023-11	2010	CONCLUSIONS: Metformin can increase the migration speed and enhance invasion abilities of A549 cells in vitro, which may be attributed to the up-regulation of MMP2 and MMP9.	Metformin	13-22	matrix metallopeptidase 2	Homo sapiens	159-163
20363874-3	2010	The AMPK activator metformin stimulated AMPK Thr172 phosphorylation and inhibited IGF-I-stimulated phosphorylation of Akt/tuberous sclerosis 2 (TSC2)/mammalian target of rapamycin (mTOR)/p70S6 kinase (p70S6K).	Metformin	19-28	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	4-8
20363874-3	2010	The AMPK activator metformin stimulated AMPK Thr172 phosphorylation and inhibited IGF-I-stimulated phosphorylation of Akt/tuberous sclerosis 2 (TSC2)/mammalian target of rapamycin (mTOR)/p70S6 kinase (p70S6K).	Metformin	19-28	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	40-44
27478876-8	2016	Metformin increased protein abundance of inner medullary urea transporter UT-A1 by 61% and aquaporin 2 (AQP2) by 44% in tolvaptan-treated rats, and immunohistochemistry showed increased membrane accumulation of AQP2 with acute and chronic AMPK stimulation.	Metformin	0-9	aquaporin 2	Rattus norvegicus	104-108
27478876-8	2016	Metformin increased protein abundance of inner medullary urea transporter UT-A1 by 61% and aquaporin 2 (AQP2) by 44% in tolvaptan-treated rats, and immunohistochemistry showed increased membrane accumulation of AQP2 with acute and chronic AMPK stimulation.	Metformin	0-9	aquaporin 2	Rattus norvegicus	211-215
27478876-11	2016	Metformin increased AQP2 in the V2R KO mice similar to the tolvaptan-treated rats.	Metformin	0-9	aquaporin 2	Mus musculus	20-24
27334428-0	2016	Metformin and gefitinib cooperate to inhibit bladder cancer growth via both AMPK and EGFR pathways joining at Akt and Erk.	Metformin	0-9	epidermal growth factor receptor	Mus musculus	85-89
27316923-0	2016	Metformin improves the angiogenic functions of endothelial progenitor cells via activating AMPK/eNOS pathway in diabetic mice.	Metformin	0-9	nitric oxide synthase 3, endothelial cell	Mus musculus	96-100
27316923-14	2016	In vitro, metformin improved impaired BM-EPC functions, and increased phosphorylated-eNOS expression and NO production in cultured BM-EPCs caused by high glucose, which was prevented by the AMPK inhibitor compound C. CONCLUSIONS: Our results suggest that metformin could improve BM-EPC functions in STZ-induced diabetic mice, which was possibly dependent on the AMPK/eNOS pathway.	Metformin	10-19	nitric oxide synthase 3, endothelial cell	Mus musculus	85-89
27316923-14	2016	In vitro, metformin improved impaired BM-EPC functions, and increased phosphorylated-eNOS expression and NO production in cultured BM-EPCs caused by high glucose, which was prevented by the AMPK inhibitor compound C. CONCLUSIONS: Our results suggest that metformin could improve BM-EPC functions in STZ-induced diabetic mice, which was possibly dependent on the AMPK/eNOS pathway.	Metformin	10-19	nitric oxide synthase 3, endothelial cell	Mus musculus	367-371
27019345-2	2016	The aim of the current study was to investigate the ability of physiologically-based pharmacokinetic (PBPK) models to simulate the effects of OCT and MATE inhibition by cimetidine on metformin kinetics.	Metformin	183-192	plexin A2	Homo sapiens	142-145
27145454-11	2016	The impeded cancer progression was due to the inhibitory effect of metformin on STAT3-ERK-vimentin and fibronectin-integrin signaling to decrease tumor cell invasion and de-differentiation.	Metformin	67-76	fibronectin 1	Mus musculus	103-114
27326258-11	2016	Concomitantly, Metformin up-regulated pluripotency, Wnt, Notch and SHH pathways genes in LRCC vs. non-LRCC.	Metformin	15-24	sonic hedgehog signaling molecule	Homo sapiens	67-70
20498500-10	2010	These discoveries seem interesting not only due to their cognitive value, but because they may also carry significant practical aspects, both in the context of AMPK activators, such as the use of metformin in diabetes mellitus therapy, and in the recent trend to look for new ways to deal with the increase in obesity in well-developed countries.	Metformin	196-205	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	160-164
20065018-6	2010	These results not only suggest the importance of mMate1 in the efflux of organic cations into the urine and bile in mice but also the importance of canalicular efflux mediated by MATE proteins for the therapeutic efficacy of metformin.	Metformin	225-234	solute carrier family 47, member 1	Mus musculus	49-55
20080851-6	2010	The effect of metformin on adipocyte galectin-3 was analyzed by immunoblot.	Metformin	14-23	galectin 3	Homo sapiens	37-47
20080851-9	2010	Metformin treatment was associated with lower systemic galectin-3.	Metformin	0-9	galectin 3	Homo sapiens	55-65
20039777-1	2010	Telithromycin and metformin have been reported to be commonly metabolized via hepatic CYP3A1/2 in rats.	Metformin	18-27	cytochrome P450, family 3, subfamily a, polypeptide 23-polypeptide 1	Rattus norvegicus	86-92
20039777-4	2010	After the intravenous administration of both drugs together to male DMIS rats, the time-averaged non-renal clearance (CL(NR)) of metformin was significantly slower (by 33.1%; 10.3 versus 15.4 ml min(-1) kg(-1)) than metformin alone due to the inhibition of hepatic metabolism of metformin by telithromycin via CYP3A1/2.	Metformin	129-138	cytochrome P450, family 3, subfamily a, polypeptide 23-polypeptide 1	Rattus norvegicus	310-316
27355749-7	2016	Compared to I/R group, metformin restored testicular Johnsen"s scores, SOD activity, MDA and MPO levels (P &lt; 0.05).	Metformin	23-32	myeloperoxidase	Rattus norvegicus	93-96
27059094-0	2016	The role of metformin and resveratrol in the prevention of hypoxia-inducible factor 1alpha accumulation and fibrosis in hypoxic adipose tissue.	Metformin	12-21	hypoxia inducible factor 1, alpha subunit	Mus musculus	59-90
27059094-2	2016	This study was designed to investigate the effects of metformin and resveratrol on the regulation of HIF-1alpha and fibrosis in hypoxic adipose tissue.	Metformin	54-63	hypoxia inducible factor 1, alpha subunit	Mus musculus	101-111
27059094-6	2016	Metformin and resveratrol down-regulated gene expressions of Col3alpha, Col6alpha, elastin and lysyl oxidase and thereby reduced collagen deposition in adipose tissue.	Metformin	0-9	elastin	Mus musculus	83-90
27059094-9	2016	Metformin reduced ATP production and prevented the reduction in oxygen tension in 3T3-L1 cells, suggesting that it prevented hypoxia by limiting oxygen consumption, whereas resveratrol reduced HIF-1alpha accumulation by promoting its proteasomal degradation via the regulation of AMPK/SIRT1.	Metformin	0-9	sirtuin 1	Mus musculus	285-290
27059094-11	2016	Both metformin and resveratrol effectively inhibited HIF-1alpha activation-induced fibrosis and inflammation in adipose tissue, although by different mechanisms.	Metformin	5-14	hypoxia inducible factor 1, alpha subunit	Mus musculus	53-63
27082123-3	2016	The present study demonstrates the effects of metformin on KB human oral cancer cells and explores the role of myeloid cell leukaemia-1 (Mcl-1) in metformin-induced mitochondria-dependent cellular apoptosis.	Metformin	147-156	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	111-135
27082123-3	2016	The present study demonstrates the effects of metformin on KB human oral cancer cells and explores the role of myeloid cell leukaemia-1 (Mcl-1) in metformin-induced mitochondria-dependent cellular apoptosis.	Metformin	147-156	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	137-142
27082123-5	2016	Furthermore, metformin induced apoptosis through the downregulation of Mcl-1 in KB human oral cancer cells, and the overexpression of Mcl-1 in metformin-treated KB cells significantly increased cell viability.	Metformin	13-22	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	71-76
27082123-5	2016	Furthermore, metformin induced apoptosis through the downregulation of Mcl-1 in KB human oral cancer cells, and the overexpression of Mcl-1 in metformin-treated KB cells significantly increased cell viability.	Metformin	143-152	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	134-139
27082123-9	2016	These results suggest that the anti-proliferative effects of metformin in KB cells may result partly from induction of apoptosis by miR-26a-induced downregulation of Mcl-1.	Metformin	61-70	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	166-171
26987032-5	2016	Meanwhile, Metformin markedly suppressed migration and invasion and induced apoptosis of both LNCaP and PC3 cancer cells.	Metformin	11-20	chromobox 8	Homo sapiens	104-107
26784938-1	2016	PURPOSE: Human multidrug and toxin extrusion member 1 (MATE1, SLC47A1) and Organic Cation Transporter 2 (OCT2, SLC22A2) play important roles in the renal elimination of various pharmacologic agents, including the anti-diabetic drug metformin.	Metformin	232-241	solute carrier family 22 member 2	Homo sapiens	75-103
26784938-1	2016	PURPOSE: Human multidrug and toxin extrusion member 1 (MATE1, SLC47A1) and Organic Cation Transporter 2 (OCT2, SLC22A2) play important roles in the renal elimination of various pharmacologic agents, including the anti-diabetic drug metformin.	Metformin	232-241	solute carrier family 22 member 2	Homo sapiens	105-109
26784938-1	2016	PURPOSE: Human multidrug and toxin extrusion member 1 (MATE1, SLC47A1) and Organic Cation Transporter 2 (OCT2, SLC22A2) play important roles in the renal elimination of various pharmacologic agents, including the anti-diabetic drug metformin.	Metformin	232-241	solute carrier family 22 member 2	Homo sapiens	111-118
26784938-2	2016	The goal of this study was to determine the association between metformin"s pharmacokinetics and pharmacodynamics and the genetic variants of MATE1 (rs2289669) and OCT2 (rs316019) before and after treatment with the potential MATE inhibitor, ranitidine.	Metformin	64-73	solute carrier family 22 member 2	Homo sapiens	164-168
27009398-1	2016	The anti-diabetic drug, metformin, exerts its action through AMP-activated protein kinase (AMPK), and Sirtuin (Sirt1) signaling.	Metformin	24-33	sirtuin 1	Mus musculus	111-116
27009398-3	2016	In this study, we demonstrate that metformin upregulates Igfbp-2 expression through the AMPK-Sirt1-PPARalpha cascade pathway.	Metformin	35-44	sirtuin 1	Mus musculus	93-98
27009398-5	2016	Upregulation of Igfbp-2 expression by metformin administration was disrupted by gene silencing of Ampk and Sirt1, and this phenomenon was not observed in Pparalpha-null mice.	Metformin	38-47	sirtuin 1	Mus musculus	107-112
27009398-8	2016	Taken together, these findings indicate that IGFBP-2 might be a new target of metformin action in diabetes and the metformin-AMPK-Sirt1-PPARalpha-IGFBP-2 network may provide a novel pathway that could be applied to ameliorate metabolic syndromes by controlling IGF-1 bioavailability.	Metformin	78-87	sirtuin 1	Mus musculus	130-135
27009398-8	2016	Taken together, these findings indicate that IGFBP-2 might be a new target of metformin action in diabetes and the metformin-AMPK-Sirt1-PPARalpha-IGFBP-2 network may provide a novel pathway that could be applied to ameliorate metabolic syndromes by controlling IGF-1 bioavailability.	Metformin	115-124	sirtuin 1	Mus musculus	130-135
27135362-8	2016	These hypotheses were tested in vivo; as a proof-of-principle, we demonstrated that metformin inhibits the p70S6K-rpS6 axis in a PP2A-phosphatase dependent manner.	Metformin	84-93	ribosomal protein S6 kinase B1	Homo sapiens	107-113
26721779-0	2016	Metformin as a prevention and treatment for preeclampsia: effects on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion and endothelial dysfunction.	Metformin	0-9	endoglin	Homo sapiens	116-124
26721779-12	2016	RESULTS: Metformin reduced soluble fms-like tyrosine kinase 1 and soluble endoglin secretion from primary endothelial cells, villous cytotrophoblast cells, and preterm preeclamptic placental villous explants.	Metformin	9-18	endoglin	Homo sapiens	74-82
26721779-13	2016	The reduction in soluble fms-like tyrosine kinase 1 and soluble endoglin secretion was rescued by coadministration of succinate, which suggests that the effects of metformin on soluble fms-like tyrosine kinase 1 and soluble endoglin were likely to be regulated at the level of the mitochondria.	Metformin	164-173	endoglin	Homo sapiens	64-72
26721779-20	2016	CONCLUSION: Metformin reduced soluble fms-like tyrosine kinase 1 and soluble endoglin secretion from primary human tissues, possibly by inhibiting the mitochondrial electron transport chain.	Metformin	12-21	endoglin	Homo sapiens	77-85
26998282-5	2016	Furthermore, treatment with resistin decreased phosphorylation of LKB1 and AMPK, whereas pretreatment with metformin increased phosphorylation of LKB1 and AMPK that is reduced by resistin.	Metformin	107-116	serine/threonine kinase 11	Rattus norvegicus	146-150
26606753-0	2016	Recessive mutations in the cancer gene Ataxia Telangiectasia Mutated (ATM), at a locus previously associated with metformin response, cause dysglycaemia and insulin resistance.	Metformin	114-123	ATM serine/threonine kinase	Homo sapiens	39-68
26606753-0	2016	Recessive mutations in the cancer gene Ataxia Telangiectasia Mutated (ATM), at a locus previously associated with metformin response, cause dysglycaemia and insulin resistance.	Metformin	114-123	ATM serine/threonine kinase	Homo sapiens	70-73
26874027-4	2016	Metformin pretreated cells were then subjected to immunoblotting as well as real time PCR to find PI3K, Akt, mTOR and S6K concurrent transcriptional and post-transcriptional changes.	Metformin	0-9	ribosomal protein S6 kinase B1	Rattus norvegicus	118-121
26874027-5	2016	The proportions of phosphorylated to non-phosphorylated constituents of PI3K/Akt/mTOR/S6K were determined to address their activation upon metformin treatment.	Metformin	139-148	ribosomal protein S6 kinase B1	Rattus norvegicus	86-89
26874027-7	2016	Metformin induced protection concurred with elevated PI3K/Akt/mTOR/S6K activity as well as enhanced GSH levels.	Metformin	0-9	ribosomal protein S6 kinase B1	Rattus norvegicus	67-70
26874027-9	2016	SIGNIFICANCE: Taken together our experimentation supports the hypothesis that Akt/mTOR/S6K cascade may contribute to metformin alleviating effect.	Metformin	117-126	ribosomal protein S6 kinase B1	Rattus norvegicus	87-90
26824415-9	2016	In addition, brusatol and metformin overcame progestin resistance by down-regulating Nrf2/AKR1C1 expression.	Metformin	26-35	aldo-keto reductase family 1 member C1	Homo sapiens	90-96
26930651-0	2016	Metformin Changes the Relationship between Blood Monocyte Toll-Like Receptor 4 Levels and Nonalcoholic Fatty Liver Disease-Ex Vivo Studies.	Metformin	0-9	toll like receptor 4	Homo sapiens	58-78
26930651-7	2016	In ex vivo studies, 100 muM of metformin decreased the TLR4 level by 19.9% (II group) or by 35% (III group) as well as IL-1beta and TNFalpha production.	Metformin	31-40	toll like receptor 4	Homo sapiens	55-59
26930651-8	2016	A stepwise multiple regression analysis highlighted a strong effect of metformin on attenuation of the link between TLR4 and NAFLD, and TNFalpha.	Metformin	71-80	toll like receptor 4	Homo sapiens	116-120
26930651-9	2016	CONCLUSION: We concluded that, by attenuation of the blood monocyte TLR4 level, metformin reduced their inflammatory potential-critical after recruitment these cells into liver.	Metformin	80-89	toll like receptor 4	Homo sapiens	68-72
27180666-5	2016	The response to metformin treatment was associated with the genetic variants ATM and SLC47A1.	Metformin	16-25	ATM serine/threonine kinase	Homo sapiens	77-80
26708162-6	2016	In the animals treated with metformin, the preservation of left ventricular function was associated with the reduction of myeloperoxidase activity (31%, P&lt;0.01) in the heart and decrease of TNF-alpha level both in the serum and heart tissue (20%, P&lt;0.01 and 42%, P&lt;0.05, respectively).	Metformin	28-37	myeloperoxidase	Rattus norvegicus	122-137
26708162-7	2016	It was found that the level of phosphorylated AMPK in heart was significantly upregulated by 43% (P&lt;0.001) in the metformin group while the content of TLRs adapter protein of MyD88 was reduced by 45% (P&lt;0.05).	Metformin	117-126	MYD88, innate immune signal transduction adaptor	Rattus norvegicus	178-183
26717043-5	2016	Second, Metformin, a pharmacological AMPK activator and anti-diabetic drug, or ectopic expression of LKB1, diminished expression of Bmi-1 in cancer cells, an event that was reversed by silencing LKB1.	Metformin	8-17	serine/threonine kinase 11	Homo sapiens	195-199
26745759-2	2016	Besides, the C allele of a SNP in the Lkb1 gene impedes the likelihood of ovulation in polycystic ovary syndrome (PCOS) in women treated with metformin, a known LKB1-AMPK activator.	Metformin	142-151	serine/threonine kinase 11	Homo sapiens	38-42
26745759-2	2016	Besides, the C allele of a SNP in the Lkb1 gene impedes the likelihood of ovulation in polycystic ovary syndrome (PCOS) in women treated with metformin, a known LKB1-AMPK activator.	Metformin	142-151	serine/threonine kinase 11	Homo sapiens	161-165
26582729-8	2016	The presence of metformin, or the inhibition of miR-34a using an anti-miR-34a inhibitor, increases the expression of sirtuin1 and attenuates the impairment in angiogenesis in HG-exposed MMECs.	Metformin	16-25	sirtuin 1	Mus musculus	117-125
26582729-10	2016	These data indicate that miR-34a, via the regulation of sirtuin1 expression, has an anti-angiogenic action in MMECs, which can be modulated by metformin.	Metformin	143-152	sirtuin 1	Mus musculus	56-64
26211973-4	2016	Chronic treatment of db/db mice with antidiabetic drugs such as metformin, glibenclamide and insulin glargine significantly decreased Abeta influx across the BBB determined by intra-arterial infusion of (125)I-Abeta(1-40), and expression of the receptor for advanced glycation end products (RAGE) participating in Abeta influx.	Metformin	64-73	amyloid beta (A4) precursor protein	Mus musculus	134-139
26211973-4	2016	Chronic treatment of db/db mice with antidiabetic drugs such as metformin, glibenclamide and insulin glargine significantly decreased Abeta influx across the BBB determined by intra-arterial infusion of (125)I-Abeta(1-40), and expression of the receptor for advanced glycation end products (RAGE) participating in Abeta influx.	Metformin	64-73	amyloid beta (A4) precursor protein	Mus musculus	210-215
26893732-3	2016	The anticancer action of metformin involves the enhancement of phosphorylation of liver kinase B1, activation of adenosine monophosphate-activated protein kinase and inhibition of mammalian target of rapamycin, which reduces cell growth.	Metformin	25-34	serine/threonine kinase 11	Homo sapiens	82-97
26673006-0	2016	Metformin increases antitumor activity of MEK inhibitors through GLI1 downregulation in LKB1 positive human NSCLC cancer cells.	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	88-92
26673006-2	2016	Our group recently has demonstrated that metformin and gefitinib are synergistic in LKB1-wild-type NSCLC cells.	Metformin	41-50	serine/threonine kinase 11	Homo sapiens	84-88
26673006-4	2016	EXPERIMENTAL DESIGN: Since single agent metformin enhances proliferating signals through the RAS/RAF/MAPK pathway, and several MEK inhibitors (MEK-I) demonstrated clinical efficacy in combination with other agents in NSCLC, we tested the effects of metformin plus MEK-I (selumetinib or pimasertib) on proliferation, invasiveness, migration abilities in vitro and in vivo in LKB1 positive NSCLC models harboring KRAS wild type and mutated gene.	Metformin	40-49	serine/threonine kinase 11	Homo sapiens	374-378
26673006-8	2016	CONCLUSIONS: Metformin potentiates the antitumor activity of MEK-Is in human LKB1-wild-type NSCLC cell lines, independently from the KRAS mutational status, through GLI1 downregulation and by reducing the NF-jB (p65)-mediated transcription of MMP-2 and MMP-9.	Metformin	13-22	serine/threonine kinase 11	Homo sapiens	77-81
26784190-0	2016	Metformin Restores Parkin-Mediated Mitophagy, Suppressed by Cytosolic p53.	Metformin	0-9	transformation related protein 53, pseudogene	Mus musculus	70-73
26784190-1	2016	Metformin is known to alleviate hepatosteatosis by inducing 5" adenosine monophosphate (AMP)-kinase-independent, sirtuin 1 (SIRT1)-mediated autophagy.	Metformin	0-9	sirtuin 1	Mus musculus	113-122
26784190-1	2016	Metformin is known to alleviate hepatosteatosis by inducing 5" adenosine monophosphate (AMP)-kinase-independent, sirtuin 1 (SIRT1)-mediated autophagy.	Metformin	0-9	sirtuin 1	Mus musculus	124-129
26784190-9	2016	However, metformin decreased ER stress and p53 expression, resulting in induction of Parkin-mediated mitophagy.	Metformin	9-18	transformation related protein 53, pseudogene	Mus musculus	43-46
26784190-11	2016	Taken together, these results indicate that metformin treatment facilitates Parkin-mediated mitophagy rather than mitochondrial spheroid formation by decreasing the inhibitory interaction with cytosolic p53 and increasing degradation of mitofusins.	Metformin	44-53	transformation related protein 53, pseudogene	Mus musculus	203-206
27928958-9	2016	CONCLUSION: The use of either NPH insulin or a DPP-4 inhibitor as add-on treatments improves glucose control in patients with T2D failing on metformin plus glyburide therapy.	Metformin	141-150	dipeptidyl peptidase 4	Homo sapiens	47-52
28042486-2	2016	L-leucine, an allosteric Sirt1 activator, synergizes with low doses of metformin or sildenafil on the AMPK-eNOS-Sirt1 pathway to reverse mild NAFLD in preclinical mouse models.	Metformin	71-80	sirtuin 1	Mus musculus	112-117
20016398-1	2010	Multidrug and toxin extrusions (MATE1/SLC47A1 and MATE2-K/SLC47A2) play important roles in the renal excretion of metformin.	Metformin	114-123	solute carrier family 47 member 2	Homo sapiens	50-57
20016398-1	2010	Multidrug and toxin extrusions (MATE1/SLC47A1 and MATE2-K/SLC47A2) play important roles in the renal excretion of metformin.	Metformin	114-123	solute carrier family 47 member 2	Homo sapiens	58-65
20016398-4	2010	Pharmacokinetic parameters of metformin in Mate1(+ or -) heterozygous mice were comparable with those in Mate1(+ or +) wild-type mice.	Metformin	30-39	solute carrier family 47, member 1	Mus musculus	43-48
20126541-8	2010	Administration of the glycolytic inhibitor 2-deoxy-D-glucose (2DG) or the mitochondrial toxin and anti-Type II Diabetes drug, metformin, or AMP mimetic AICAR results in activation of AMPK, repression of the mTOR pathway and prevents maintenance of Late-Phase LTP (L-LTP).	Metformin	126-135	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	183-187
26608911-4	2016	Treatments of B6.Sle1Sle2.Sle3 mice with either 2-deoxy-D-glucose or metformin were sufficient to prevent autoimmune activation, whereas their combination was necessary to reverse the process.	Metformin	69-78	systemic lupus erythmatosus susceptibility 1	Mus musculus	17-25
27057099-0	2016	Metformin Prevents Fatty Liver and Improves Balance of White/Brown Adipose in an Obesity Mouse Model by Inducing FGF21.	Metformin	0-9	WD and tetratricopeptide repeats 1	Mus musculus	67-74
27195075-0	2016	Metformin Decreases Reactive Oxygen Species, Enhances Osteogenic Properties of Adipose-Derived Multipotent Mesenchymal Stem Cells In Vitro, and Increases Bone Density In Vivo.	Metformin	0-9	WD and tetratricopeptide repeats 1	Mus musculus	79-86
27069466-3	2016	Fenofibrate plus metformin generated cardioprotection in a DBI/R model, reported as decreased coronary vascular resistance, compared to DBI/R-Vehicle, smaller infarct size, and increased cardiac work.	Metformin	17-26	diazepam binding inhibitor	Rattus norvegicus	59-62
27069466-5	2016	These findings suggest that PPARalpha activation by fenofibrate + metformin, at low doses, generates cardioprotection in a rat model of T2D and AMI and may represent a novel treatment strategy to limit I/R injury in patients with T2D.	Metformin	66-75	peroxisome proliferator activated receptor alpha	Rattus norvegicus	28-37
26073221-8	2016	Dipeptidyl peptidase 4 inhibitors (iDPP4) are particularly useful in this age group, either as a second drug added to metformin monotherapy, or as first line when metformin is contraindicated or not tolerated.	Metformin	118-127	dipeptidyl peptidase 4	Homo sapiens	0-22
20522960-3	2010	In addition, metformin at a higher dose increased plasma active glucagon-like peptide-1 (GLP-1) levels at 1 h after the HFD was given.	Metformin	13-22	glucagon	Mus musculus	64-87
20522960-3	2010	In addition, metformin at a higher dose increased plasma active glucagon-like peptide-1 (GLP-1) levels at 1 h after the HFD was given.	Metformin	13-22	glucagon	Mus musculus	89-94
20332619-6	2010	We recently showed that after raising [cAMP], wt-CFTR chloride-conductance, when expressed in Xenopus oocytes, remains elevated despite the presence of metformin.	Metformin	152-161	cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)	Xenopus laevis	49-53
26073221-8	2016	Dipeptidyl peptidase 4 inhibitors (iDPP4) are particularly useful in this age group, either as a second drug added to metformin monotherapy, or as first line when metformin is contraindicated or not tolerated.	Metformin	163-172	dipeptidyl peptidase 4	Homo sapiens	0-22
26496641-0	2016	Metformin-Derived Growth Inhibition in Renal Cell Carcinoma Depends on miR-21-Mediated PTEN Expression.	Metformin	0-9	microRNA 21	Homo sapiens	71-77
26496641-0	2016	Metformin-Derived Growth Inhibition in Renal Cell Carcinoma Depends on miR-21-Mediated PTEN Expression.	Metformin	0-9	phosphatase and tensin homolog	Homo sapiens	87-91
26718286-13	2015	Metformin was also associated with a reduction of snail2, twist, and vimentin in CD44(+)CD117(+) ovarian CSCs in vivo.	Metformin	0-9	vimentin	Homo sapiens	69-77
26629827-9	2015	The reduction of cytokine level by metformin was accompanied by the decrease in toll-like receptor-4 expression.	Metformin	35-44	toll like receptor 4	Homo sapiens	80-100
26629827-12	2015	CONCLUSIONS: Metformin and phosphatidylcholine attenuated lipopolysaccharide induced toll-like receptor 4 overexpression and overproduction of pro-inflammatory cytokines; however, their efficacy depended on combined presence of non-alcoholic fatty liver disease, metabolic syndrome and obesity.	Metformin	13-22	toll like receptor 4	Homo sapiens	85-105
26629991-0	2015	Metformin and Resveratrol Inhibited High Glucose-Induced Metabolic Memory of Endothelial Senescence through SIRT1/p300/p53/p21 Pathway.	Metformin	0-9	H3 histone pseudogene 16	Homo sapiens	123-126
26616595-0	2015	Clinical Characteristics and Metabolic Predictors of Rapid Responders to Dipeptidyl Peptidase-4 Inhibitor as an Add-on Therapy to Sulfonylurea and Metformin.	Metformin	147-156	dipeptidyl peptidase 4	Homo sapiens	73-95
26616595-1	2015	BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitor add-on therapy is a new option for patients with inadequately controlled type 2 diabetes who are taking combined metformin and sulfonylurea (SU).	Metformin	166-175	dipeptidyl peptidase 4	Homo sapiens	12-34
26616595-1	2015	BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitor add-on therapy is a new option for patients with inadequately controlled type 2 diabetes who are taking combined metformin and sulfonylurea (SU).	Metformin	166-175	dipeptidyl peptidase 4	Homo sapiens	36-41
26616595-3	2015	METHODS: We included 807 patients with type 2 diabetes who were prescribed a newly added DPP-4 inhibitor to ongoing metformin and SU in 2009 to 2011.	Metformin	116-125	dipeptidyl peptidase 4	Homo sapiens	89-94
26706918-6	2015	Pro-apoptotic events (nuclear condensation, hydrolysis of intact poly ADP ribose polymerase and caspase-3) were stimulated by metformin and then suppressed by compound C. Interestingly, the formation of acidic intracellular vesicles, a marker of autophagy, was stimulated by compound C. Although the deprivation of amino acids in culture media also induced apoptosis, neither metformin nor compound C affected cell viability.	Metformin	126-135	poly (ADP-ribose) polymerase 1	Rattus norvegicus	65-91
26362676-13	2015	Thyroid cancer cell lines were characterized by over-expression of glycolytic genes, and metformin decreased the protein level of pyruvate kinase muscle 2 (PKM2).	Metformin	89-98	pyruvate kinase M1/2	Homo sapiens	130-154
19740083-2	2009	Metformin, used for treatment of type 2 diabetes, is taken up into renal tubular cells by the organic cation transporter 2 (OCT2).	Metformin	0-9	solute carrier family 22 member 2	Canis lupus familiaris	94-122
19740083-2	2009	Metformin, used for treatment of type 2 diabetes, is taken up into renal tubular cells by the organic cation transporter 2 (OCT2).	Metformin	0-9	solute carrier family 22 member 2	Canis lupus familiaris	124-128
19740083-6	2009	Moreover, all beta-blockers significantly inhibited OCT2-mediated metformin uptake (IC(50) for bisoprolol: 2.4 microM, IC(50) for carvedilol: 2.3 microM, IC(50) for metoprolol: 50.2 microM and IC(50) for propranolol: 8.3 microM).	Metformin	66-75	solute carrier family 22 member 2	Canis lupus familiaris	52-56
19579180-7	2009	In contrast, under conditions of stimulation with dexamethasone and cAMP, treatment with compound C reversed the inhibitory effect of metformin on G6Pase promoter activity to a similar extent as compared to nonstimulated conditions, whereas the effect of insulin was almost resistant to treatment with the AMPK-antagonist.	Metformin	134-143	glucose-6-phosphatase catalytic subunit 1	Homo sapiens	147-153
19579180-8	2009	These data indicate a differential AMPK-dependent regulation of G6Pase gene expression by insulin and metformin under basal and dexamethasone/cAMP-stimulated conditions.	Metformin	102-111	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	35-39
19579180-8	2009	These data indicate a differential AMPK-dependent regulation of G6Pase gene expression by insulin and metformin under basal and dexamethasone/cAMP-stimulated conditions.	Metformin	102-111	glucose-6-phosphatase catalytic subunit 1	Homo sapiens	64-70
19576170-0	2009	Attenuation of hepatic expression and secretion of selenoprotein P by metformin.	Metformin	70-79	selenoprotein P	Rattus norvegicus	51-66
19576170-3	2009	This study was undertaken to test for a hypothesized effect of hyperglycemia and the antihyperglycemic drug metformin on hepatic selenoprotein P biosynthesis.	Metformin	108-117	selenoprotein P	Rattus norvegicus	129-144
19576170-5	2009	Treatment with metformin dose-dependently downregulated SeP mRNA expression and secretion, and suppressed glucocorticoid-stimulated production of SeP.	Metformin	15-24	selenoprotein P	Rattus norvegicus	56-59
19576170-5	2009	Treatment with metformin dose-dependently downregulated SeP mRNA expression and secretion, and suppressed glucocorticoid-stimulated production of SeP.	Metformin	15-24	selenoprotein P	Rattus norvegicus	146-149
19576170-8	2009	As selenoprotein P is the major transport form of selenium, metformin treatment may thereby diminish selenium supply to extrahepatic tissues.	Metformin	60-69	selenoprotein P	Rattus norvegicus	3-18
19553503-7	2009	Finally, metformin treatment was associated with higher mRNA levels and activities for lipogenic enzymes (fatty acid synthase and glucose-6-phosphate dehydrogenase).	Metformin	9-18	glucose-6-phosphate-1-dehydrogenase	Oncorhynchus mykiss	130-163
19744424-7	2009	The unique mechanism of action of the GLP-1 receptor agonist class of medications makes these agents a desirable choice as add-on therapy to metformin.	Metformin	141-150	glucagon like peptide 1 receptor	Homo sapiens	38-52
19679549-0	2009	Metformin disrupts crosstalk between G protein-coupled receptor and insulin receptor signaling systems and inhibits pancreatic cancer growth.	Metformin	0-9	insulin receptor	Homo sapiens	68-84
19679549-4	2009	Here, we determined whether metformin disrupts the crosstalk between insulin receptor and GPCR signaling in pancreatic cancer cells.	Metformin	28-37	insulin receptor	Homo sapiens	69-85
26362676-13	2015	Thyroid cancer cell lines were characterized by over-expression of glycolytic genes, and metformin decreased the protein level of pyruvate kinase muscle 2 (PKM2).	Metformin	89-98	pyruvate kinase M1/2	Homo sapiens	156-160
26394887-0	2015	Circulating hepcidin in type 2 diabetes: A multivariate analysis and double blind evaluation of metformin effects.	Metformin	96-105	hepcidin antimicrobial peptide	Homo sapiens	12-20
26394887-9	2015	Hepcidin decreased in both arms of the trial (Placebo, p = 0.004; metformin, p = 0.022).	Metformin	66-75	hepcidin antimicrobial peptide	Homo sapiens	0-8
26424816-1	2015	AMP-activated protein kinase (AMPK), an important downstream effector of the tumor suppressor liver kinase 1 (LKB1) and pharmacologic target of metformin, is well known to exert a preventive and inhibitory effect on tumorigenesis; however, its role in cancer progression and metastasis has not been well characterized.	Metformin	144-153	serine/threonine kinase 11	Homo sapiens	110-114
26424816-4	2015	The effect of metformin is dependent on the presence of LKB1.	Metformin	14-23	serine/threonine kinase 11	Homo sapiens	56-60
26424816-6	2015	As a consequence, expression of genes downstream of Smad2/3, including plasminogen activator inhibitor-1, fibronectin, and connective tissue growth factor, was suppressed by metformin in a LKB1-dependent fashion.	Metformin	174-183	serpin family E member 1	Homo sapiens	71-104
19476473-5	2009	At end-point, vildagliptin was as effective as metformin, improving HbA1c by -0.64+/-0.07% and -0.75+/-0.07%, respectively, meeting the predefined statistical criterion for non-inferiority (upper limit of 95% confidence interval for between-treatment difference&lt;or=0.3%).	Metformin	47-56	hemoglobin subunit alpha 1	Homo sapiens	68-72
26424816-6	2015	As a consequence, expression of genes downstream of Smad2/3, including plasminogen activator inhibitor-1, fibronectin, and connective tissue growth factor, was suppressed by metformin in a LKB1-dependent fashion.	Metformin	174-183	serine/threonine kinase 11	Homo sapiens	189-193
26424816-7	2015	In addition, metformin blocked TGF-beta-induced inteleukin-6 expression through both LKB1-dependent and -independent mechanisms.	Metformin	13-22	serine/threonine kinase 11	Homo sapiens	85-89
26467463-9	2015	RESULTS: Metformin induced single-cultured RAW264.7 macrophages with an M2 phenotype but attenuated the M2 macrophage differentiation and inhibited monocyte chemoattractant protein-1 (MCP-1) secretion in a co-culture system.	Metformin	9-18	C-C motif chemokine ligand 2	Homo sapiens	148-182
26467463-9	2015	RESULTS: Metformin induced single-cultured RAW264.7 macrophages with an M2 phenotype but attenuated the M2 macrophage differentiation and inhibited monocyte chemoattractant protein-1 (MCP-1) secretion in a co-culture system.	Metformin	9-18	C-C motif chemokine ligand 2	Homo sapiens	184-189
26503124-9	2015	Ranitidine, allopurinol, and metformin together accounted for 76% of renally misprescribed medications in individuals with a CrCl of 30 to 49 mL/min.	Metformin	29-38	CRCL	Homo sapiens	125-129
19371451-2	2009	It has been reported that metformin elevates the activity of Tyrosine kinase receptors and may amplify BDNF signalling.	Metformin	26-35	brain derived neurotrophic factor	Bos taurus	103-107
19494326-2	2009	Metformin is the most widely used drug for diabetes and mediates its action via activating AMP-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	91-119
26186064-3	2015	We have also shown that metformin activates the ERK pathway in Ph+ALL cells, SUP-B15, a side effect that can be overcome by U0126 (MEK1/2 inhibitor) or imatinib.	Metformin	24-33	mitogen-activated protein kinase kinase 1	Homo sapiens	131-137
25840943-3	2015	Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models to compare the DPP-4 inhibitor-metformin combination to the sulfonylurea-metformin combination so as to study the risk for a composite endpoint consisting of myocardial infarction, stroke and all-cause mortality.	Metformin	139-148	dipeptidyl peptidase 4	Homo sapiens	123-128
25840943-6	2015	The crude incidence rates (95% CIs) of the composite endpoint were 1.2% (0.8% to 1.7%) and 2.2% (1.9% to 2.5%) per year for the DPP-4 inhibitor-metformin and sulfonylurea-metformin combinations, respectively.	Metformin	144-153	dipeptidyl peptidase 4	Homo sapiens	128-133
25840943-6	2015	The crude incidence rates (95% CIs) of the composite endpoint were 1.2% (0.8% to 1.7%) and 2.2% (1.9% to 2.5%) per year for the DPP-4 inhibitor-metformin and sulfonylurea-metformin combinations, respectively.	Metformin	171-180	dipeptidyl peptidase 4	Homo sapiens	128-133
25840943-7	2015	In the high-dimensional propensity score-adjusted model, the use of the DPP-4 inhibitor-metformin combination was associated with a 38% decreased risk for the composite endpoint (adjusted HR: 0.62; 95% CI 0.40 to 0.98), compared with the sulfonylurea-metformin combination.	Metformin	88-97	dipeptidyl peptidase 4	Homo sapiens	72-77
25840943-7	2015	In the high-dimensional propensity score-adjusted model, the use of the DPP-4 inhibitor-metformin combination was associated with a 38% decreased risk for the composite endpoint (adjusted HR: 0.62; 95% CI 0.40 to 0.98), compared with the sulfonylurea-metformin combination.	Metformin	251-260	dipeptidyl peptidase 4	Homo sapiens	72-77
25840943-8	2015	CONCLUSIONS: The use of a DPP-4 inhibitor combination with metformin, compared with a sulfonylurea-metformin combination, was associated with decreased risks for major cardiovascular events and all-cause mortality.	Metformin	59-68	dipeptidyl peptidase 4	Homo sapiens	26-31
26251408-12	2015	Variations of these three metabolites were significantly associated with 17 genes (including FADS1 and FADS2) and controlled by AMPK, a metformin target.	Metformin	136-145	fatty acid desaturase 1	Homo sapiens	93-98
26236947-5	2015	Intriguingly, AICAR or metformin treatment resulted in significant downregulation of MTDH expression via inhibiting c-Myc expression.	Metformin	23-32	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	116-121
26383681-7	2015	Interestingly, metformin may enhance radiation response specifically in certain genetic backgrounds, such as in cells with loss of the tumor suppressors p53 and LKB1, giving rise to a therapeutic ratio and potential predictive biomarkers.	Metformin	15-24	serine/threonine kinase 11	Homo sapiens	161-165
26335661-4	2015	Metformin inhibited histamine and serotonin uptake by OCT1, OCT3 and SERT in a dose-dependent manner, with OCT1-mediated amine uptake being most potently inhibited (IC50 = 1.5 mM).	Metformin	0-9	POU class 5 homeobox 1	Homo sapiens	60-64
19428322-4	2009	AMPK activators metformin and AICAR partly prevented the cell cycle block, oxidative stress and apoptosis induced by compound C. The small interfering RNA (siRNA) targeting of human AMPK mimicked compound C-induced G(2)/M cell cycle arrest, but failed to induce oxidative stress and apoptosis in U251 glioma cells.	Metformin	16-25	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
19428322-4	2009	AMPK activators metformin and AICAR partly prevented the cell cycle block, oxidative stress and apoptosis induced by compound C. The small interfering RNA (siRNA) targeting of human AMPK mimicked compound C-induced G(2)/M cell cycle arrest, but failed to induce oxidative stress and apoptosis in U251 glioma cells.	Metformin	16-25	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	182-186
26276089-7	2015	Adriamycin or metformin alone or in combination induced significant increase in the survival rate, tissue catalase, reduced glutathione and tissue caspase 3 activity with significant decrease in tumor volume, tissue malondialdehyde, tissue sphingosine kinase 1 activity and tumor necrosis factor alpha and alleviated the histopathological changes with significant increase in Trp53 expression and apoptotic index compared to SEC group.	Metformin	14-23	transformation related protein 53	Mus musculus	376-381
26815356-1	2015	OBJECTIVE: To observe the effects of metformin (MET) on podocalyxin (PCX) expression in renal tissue from type 2 diabetes mellitus (T2DM) model rats and investigate its protective effects against glomerular podocyte injury.	Metformin	37-46	podocalyxin-like	Rattus norvegicus	56-67
26265045-4	2015	The results indicated that treatment with metformin significantly suppressed the elevation of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the activation of caspase cascade and the induction of cleaved caspase-3.	Metformin	42-51	glutamic pyruvic transaminase, soluble	Mus musculus	101-125
26265045-4	2015	The results indicated that treatment with metformin significantly suppressed the elevation of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the activation of caspase cascade and the induction of cleaved caspase-3.	Metformin	42-51	glutamic pyruvic transaminase, soluble	Mus musculus	127-130
26265045-4	2015	The results indicated that treatment with metformin significantly suppressed the elevation of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the activation of caspase cascade and the induction of cleaved caspase-3.	Metformin	42-51	solute carrier family 17 (anion/sugar transporter), member 5	Mus musculus	136-162
26265045-4	2015	The results indicated that treatment with metformin significantly suppressed the elevation of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the activation of caspase cascade and the induction of cleaved caspase-3.	Metformin	42-51	solute carrier family 17 (anion/sugar transporter), member 5	Mus musculus	164-167
26391180-0	2015	Metformin Increases Sensitivity of Pancreatic Cancer Cells to Gemcitabine by Reducing CD133+ Cell Populations and Suppressing ERK/P70S6K Signaling.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	130-136
26100439-2	2015	In the following studies, we observed that metformin, one of the most widely used antidiabetic medications, induces mitochondrial stress and induces FGF21 through a PERK-eIF2alpha-ATF4 pathway, which may contribute to the antidiabetic effect of metformin.	Metformin	43-52	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	165-169
26100439-2	2015	In the following studies, we observed that metformin, one of the most widely used antidiabetic medications, induces mitochondrial stress and induces FGF21 through a PERK-eIF2alpha-ATF4 pathway, which may contribute to the antidiabetic effect of metformin.	Metformin	245-254	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	165-169
26294325-5	2015	Of the top 10 genes (fold-change &gt; 10, P &lt; 10(-10)) regulated by metformin plus aspirin, PCDH18, CCL2, RASL11A, FAM111B and BMP5 were down-regulated &gt;= 20-fold, while NGFR, NPTX1, C7orf57, MRPL23AS1 and UNC5B were up-regulated &gt;= 10-fold.	Metformin	71-80	C-C motif chemokine ligand 2	Homo sapiens	103-107
26294325-5	2015	Of the top 10 genes (fold-change &gt; 10, P &lt; 10(-10)) regulated by metformin plus aspirin, PCDH18, CCL2, RASL11A, FAM111B and BMP5 were down-regulated &gt;= 20-fold, while NGFR, NPTX1, C7orf57, MRPL23AS1 and UNC5B were up-regulated &gt;= 10-fold.	Metformin	71-80	RAS like family 11 member A	Homo sapiens	109-116
26294325-5	2015	Of the top 10 genes (fold-change &gt; 10, P &lt; 10(-10)) regulated by metformin plus aspirin, PCDH18, CCL2, RASL11A, FAM111B and BMP5 were down-regulated &gt;= 20-fold, while NGFR, NPTX1, C7orf57, MRPL23AS1 and UNC5B were up-regulated &gt;= 10-fold.	Metformin	71-80	FAM111 trypsin like peptidase B	Homo sapiens	118-125
26294325-5	2015	Of the top 10 genes (fold-change &gt; 10, P &lt; 10(-10)) regulated by metformin plus aspirin, PCDH18, CCL2, RASL11A, FAM111B and BMP5 were down-regulated &gt;= 20-fold, while NGFR, NPTX1, C7orf57, MRPL23AS1 and UNC5B were up-regulated &gt;= 10-fold.	Metformin	71-80	nerve growth factor receptor	Homo sapiens	176-180
26291325-0	2015	Metformin Induces Apoptosis and Downregulates Pyruvate Kinase M2 in Breast Cancer Cells Only When Grown in Nutrient-Poor Conditions.	Metformin	0-9	pyruvate kinase M1/2	Homo sapiens	46-64
26291325-10	2015	Finally, we showed that, in nutrient-poor conditions, metformin was able to modulate the intracellular glycolytic equilibrium by downregulating PKM2 expression and that this mechanism was mediated by AMPK activation.	Metformin	54-63	pyruvate kinase M1/2	Homo sapiens	144-148
26291325-11	2015	CONCLUSION: We demonstrated that metformin induces breast cancer cell apoptosis and PKM2 downregulation only in nutrient-poor conditions.	Metformin	33-42	pyruvate kinase M1/2	Homo sapiens	84-88
26291325-13	2015	These data demonstrate that the reduction of nutrient supply in tumors can increase metformin efficacy and that modulation of PKM2 expression/activity could be a promising strategy to boost metformin anti-cancer effect.	Metformin	190-199	pyruvate kinase M1/2	Homo sapiens	126-130
26245871-0	2015	Metformin can block precancerous progression to invasive tumors of bladder through inhibiting STAT3-mediated signaling pathways.	Metformin	0-9	signal transducer and activator of transcription 3	Rattus norvegicus	94-99
19318378-8	2009	In patients failing to sulphonylureas and/or metformin, GLP-1 receptor agonists are similarly effective as insulin.	Metformin	45-54	glucagon like peptide 1 receptor	Homo sapiens	56-70
19332510-11	2009	This is the first report to demonstrate an essential role of MATE1 in systemic clearance of metformin.	Metformin	92-101	solute carrier family 47, member 1	Mus musculus	61-66
19332510-0	2009	Targeted disruption of the multidrug and toxin extrusion 1 (mate1) gene in mice reduces renal secretion of metformin.	Metformin	107-116	solute carrier family 47, member 1	Mus musculus	27-58
19332510-0	2009	Targeted disruption of the multidrug and toxin extrusion 1 (mate1) gene in mice reduces renal secretion of metformin.	Metformin	107-116	solute carrier family 47, member 1	Mus musculus	60-65
19332510-7	2009	Pharmacokinetic characterization was carried out using metformin, a typical substrate of MATE1.	Metformin	55-64	solute carrier family 47, member 1	Mus musculus	89-94
19332510-8	2009	After a single intravenous administration of metformin (5 mg/kg), a 2-fold increase in the area under the blood concentration-time curve for 60 min (AUC(0-60)) of metformin in Mate1(-/-) mice was observed.	Metformin	45-54	solute carrier family 47, member 1	Mus musculus	176-181
19332510-8	2009	After a single intravenous administration of metformin (5 mg/kg), a 2-fold increase in the area under the blood concentration-time curve for 60 min (AUC(0-60)) of metformin in Mate1(-/-) mice was observed.	Metformin	163-172	solute carrier family 47, member 1	Mus musculus	176-181
19332510-9	2009	Urinary excretion of metformin for 60 min after the intravenous administration was significantly decreased in Mate1(-/-) mice compared with Mate1(+/+) mice.	Metformin	21-30	solute carrier family 47, member 1	Mus musculus	110-115
19332510-9	2009	Urinary excretion of metformin for 60 min after the intravenous administration was significantly decreased in Mate1(-/-) mice compared with Mate1(+/+) mice.	Metformin	21-30	solute carrier family 47, member 1	Mus musculus	140-145
19332510-10	2009	The renal clearance (CL(ren)) and renal secretory clearance (CL(sec)) of metformin in Mate1(-/-) mice were approximately 18 and 14% of those in Mate1(+/+) mice, respectively.	Metformin	73-82	solute carrier family 47, member 1	Mus musculus	86-91
26245871-12	2015	Accordingly, phosphorylation of signal transducer and activator of transcription 3 (STAT3), which is a well known oncogene, was significantly inhibited in the tumors of rats treated with metformin.	Metformin	187-196	signal transducer and activator of transcription 3	Rattus norvegicus	32-82
26245871-12	2015	Accordingly, phosphorylation of signal transducer and activator of transcription 3 (STAT3), which is a well known oncogene, was significantly inhibited in the tumors of rats treated with metformin.	Metformin	187-196	signal transducer and activator of transcription 3	Rattus norvegicus	84-89
26245871-13	2015	In vitro experiments revealed that the metformin could efficiently inhibit STAT3 activation, which was associated with the cell cycle arrest, reduction of cell proliferation, migration and invasiveness, and increase in apoptotic cell death of bladder cancer cell lines.	Metformin	39-48	signal transducer and activator of transcription 3	Rattus norvegicus	75-80
26245871-14	2015	CONCLUSIONS: These findings provide for the first time the evidence that metformin can block precancerous lesions progressing to invasive tumors through inhibiting the activation of STAT3 pathway, and may be used for treatment of the non-invasive bladder cancers to prevent them from progression to invasive tumors.	Metformin	73-82	signal transducer and activator of transcription 3	Rattus norvegicus	182-187
26962596-11	2015	Of note, the Canadian Drug Expert Committee recommendations for the existing DPP-4 inhibitors have recommended listing for patients with inadequate glycemic control on metformin and a sulfonylurea who are unable to use insulin.	Metformin	168-177	dipeptidyl peptidase 4	Homo sapiens	77-82
26962605-9	2015	DPP-4 inhibitor/metformin fixed-dose combinations (FDCs) are marketed for all four DPP-4 inhibitors.	Metformin	16-25	dipeptidyl peptidase 4	Homo sapiens	83-88
25687657-1	2015	PURPOSE: To assess the metformin effect on endometrial stromal cell decidualization, proliferation, gene and protein expression of IGFBPs, IGFs and their receptors.	Metformin	23-32	insulin like growth factor binding protein 1	Homo sapiens	131-137
25687657-9	2015	Higher concentrations of metformin lead to a significant (p &lt; 0.05) dose-dependent attenuation of the progesterone effect with regard to IGFBP-1, -3, -5, -6, as well as IGF I receptor, while it did not change the expression of IGFBP-2 and -4, IGF I and II and the IGF II receptor.	Metformin	25-34	insulin like growth factor binding protein 1	Homo sapiens	140-159
25687657-9	2015	Higher concentrations of metformin lead to a significant (p &lt; 0.05) dose-dependent attenuation of the progesterone effect with regard to IGFBP-1, -3, -5, -6, as well as IGF I receptor, while it did not change the expression of IGFBP-2 and -4, IGF I and II and the IGF II receptor.	Metformin	25-34	insulin like growth factor 2 receptor	Homo sapiens	267-282
25975389-0	2015	Metformin targets Axl and Tyro3 receptor tyrosine kinases to inhibit cell proliferation and overcome chemoresistance in ovarian cancer cells.	Metformin	0-9	AXL receptor tyrosine kinase	Homo sapiens	18-21
25975389-4	2015	We next observed the effect of metformin on expression of Axl and Tyro3 receptor tyrosine kinases (RTKs) which belong to the TAM subfamily of RTKs transducing pro-survival and anti-apoptotic signals.	Metformin	31-40	AXL receptor tyrosine kinase	Homo sapiens	58-61
25975389-5	2015	Metformin treatment of ovarian cancer cells decreased both mRNA and protein levels of Axl and Tyro3 in a dose-dependent manner.	Metformin	0-9	AXL receptor tyrosine kinase	Homo sapiens	86-89
25975389-6	2015	Axl promoter activity was also inhibited by metformin, indicating that metformin suppresses Axl and Tyro3 expression at the transcriptional level.	Metformin	44-53	AXL receptor tyrosine kinase	Homo sapiens	0-3
25975389-6	2015	Axl promoter activity was also inhibited by metformin, indicating that metformin suppresses Axl and Tyro3 expression at the transcriptional level.	Metformin	44-53	AXL receptor tyrosine kinase	Homo sapiens	92-95
25975389-6	2015	Axl promoter activity was also inhibited by metformin, indicating that metformin suppresses Axl and Tyro3 expression at the transcriptional level.	Metformin	71-80	AXL receptor tyrosine kinase	Homo sapiens	0-3
25975389-6	2015	Axl promoter activity was also inhibited by metformin, indicating that metformin suppresses Axl and Tyro3 expression at the transcriptional level.	Metformin	71-80	AXL receptor tyrosine kinase	Homo sapiens	92-95
25975389-7	2015	Metformin treatment was also found to augment its anti-proliferative effect in SKOV3 and taxol-resistant SKOV3/TR cells transfected with Axl and Tyro3 specific siRNAs, siAxl and siTyro3, respectively, suggesting that metformin might target Axl and Tyro3 RTKs to restrain cell proliferation.	Metformin	0-9	AXL receptor tyrosine kinase	Homo sapiens	137-140
25975389-7	2015	Metformin treatment was also found to augment its anti-proliferative effect in SKOV3 and taxol-resistant SKOV3/TR cells transfected with Axl and Tyro3 specific siRNAs, siAxl and siTyro3, respectively, suggesting that metformin might target Axl and Tyro3 RTKs to restrain cell proliferation.	Metformin	0-9	AXL receptor tyrosine kinase	Homo sapiens	170-173
25975389-9	2015	Collectively, our data showed that metformin caused reduction of Axl and Tyro3 RTKs" expression, inactivation of downstream effectors, and decrease of anti-apoptotic protein level, forming a potent therapeutic strategy to facilitate its anticancer activity as well as to overcome chemoresistance in human ovarian cancer cells.	Metformin	35-44	AXL receptor tyrosine kinase	Homo sapiens	65-68
25988874-0	2015	Metformin inhibits age-related centrosome amplification in Drosophila midgut stem cells through AKT/TOR pathway.	Metformin	0-9	Akt1	Drosophila melanogaster	96-99
19385979-6	2009	There is also a potential synergistic effect of vildagliptin and metformin in increasing active GLP-1 levels, and this activity may contribute to the long-term improvements in beta-cell function observed in patients with T2DM who have vildagliptin added to ongoing metformin therapy.	Metformin	65-74	glucagon like peptide 1 receptor	Homo sapiens	96-101
19385979-6	2009	There is also a potential synergistic effect of vildagliptin and metformin in increasing active GLP-1 levels, and this activity may contribute to the long-term improvements in beta-cell function observed in patients with T2DM who have vildagliptin added to ongoing metformin therapy.	Metformin	265-274	glucagon like peptide 1 receptor	Homo sapiens	96-101
19275766-7	2009	Recent mechanistic studies have shown that AMPK has an important role in the mechanism of action of MF (metformin), TDZs (thiazolinediones) and statins.	Metformin	104-113	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	43-47
19303974-5	2009	Our data showed that a therapeutically relevant concentration of metformin (5.10(-5) mol/L) was able to abolish PARP activation, to reduce poly(ribosyl)ated protein polymer accumulation, to decrease intracellular peroxynitrite anion level, and to reverse the overexpression of p47phox in bovine aortic endothelial cells stimulated by 25 mmol/L glucose in a similar manner to that of calphostin or diphenyleneiodonium chloride.	Metformin	65-74	neutrophil cytosol factor 1	Bos taurus	277-284
19221498-6	2009	At the molecular level, metformin treatment was associated with a reduction of cyclin D1 and E2F1 expression with no changes in p27(kip1) or p21(waf1).	Metformin	24-33	cyclin D1	Homo sapiens	79-88
19106626-7	2009	Mechanistically, metformin-induced suppression of HER2 overexpression appears to occur via direct (AMPK-independent) inhibition of p70S6K1 activity.	Metformin	17-26	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	99-103
18972094-8	2009	CONCLUSIONS/INTERPRETATION: Combined thiazolidinedione-metformin treatment markedly improves sub-maximal and maximal insulin signalling to IR, IRS-1/PI3K, aPKC and PKBbeta in type 2 diabetic muscle.	Metformin	55-64	insulin receptor	Homo sapiens	139-141
19084933-8	2008	The general caspase inhibitor (VAD-fmk) completely abolished metformin-induced PARP cleavage and apoptosis in ASPC-1 BxPc-3 and PANC-1, the caspase-8 specific inhibitor (IETD-fmk) and the caspase-9 specific inhibitor (LEHD-fmk) only partially abrogated metformin-induced apoptosis and PARP cleavage in BxPc-3 and PANC-1 cells.	Metformin	61-70	caspase 8	Homo sapiens	140-149
19084933-12	2008	Hence, both caspase-8 and -9-initiated apoptotic signaling pathways contribute to metformin-induced apoptosis in pancreatic cell lines.	Metformin	82-91	caspase 8	Homo sapiens	12-28
19046439-0	2008	Cell cycle arrest in Metformin treated breast cancer cells involves activation of AMPK, downregulation of cyclin D1, and requires p27Kip1 or p21Cip1.	Metformin	21-30	cyclin D1	Homo sapiens	106-115
19046439-8	2008	As in previous studies, metformin treatment led to activation of (AMPK) and downregulation of cyclin D1.	Metformin	24-33	cyclin D1	Homo sapiens	94-103
19046439-13	2008	CONCLUSION: Cell cycle arrest in response to metformin requires CDK inhibitors in addition to AMPK activation and cyclin D1 downregulation.	Metformin	45-54	cyclin D1	Homo sapiens	114-123
18778865-0	2008	The effects of pioglitazone and metformin on plasma visfatin levels in patients with treatment naive type 2 diabetes mellitus.	Metformin	32-41	nicotinamide phosphoribosyltransferase	Homo sapiens	52-60
18837086-5	2008	Compared to controls, males DM2 with HCC were more frequently treated with insulin (38.1% vs 17.6%, P = 0.009) and with sulfonylurea with or without metformin than with diet with or without metformin (84% vs 68.3%, P = 0.049).	Metformin	149-158	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	28-31
19138981-0	2008	The effects of adiponectin and metformin on prostate and colon neoplasia involve activation of AMP-activated protein kinase.	Metformin	31-40	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	95-123
19138981-6	2008	Furthermore, metformin was observed to activate AMPK and to have growth inhibitory actions on prostate and colon cancer cells, suggesting that this compound may be of particular value in attenuating the adverse effects of obesity on neoplasia.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	48-52
18678646-6	2008	Treatment of both primary cells and cancer cell lines with rapamycin, metformin, and pyrvinium resulted in an increase in p73 levels, as did RNA interference-mediated knockdown of mTOR.	Metformin	70-79	tumor protein p73	Homo sapiens	122-125
25988874-0	2015	Metformin inhibits age-related centrosome amplification in Drosophila midgut stem cells through AKT/TOR pathway.	Metformin	0-9	Target of rapamycin	Drosophila melanogaster	100-103
25988874-6	2015	Furthermore, we revealed that this effect is mediated via down-regulation of AKT/target of rapamycin (TOR) activity, suggesting that metformin prevents centrosome amplification by inhibiting the TOR signaling pathway.	Metformin	133-142	Target of rapamycin	Drosophila melanogaster	77-100
25988874-6	2015	Furthermore, we revealed that this effect is mediated via down-regulation of AKT/target of rapamycin (TOR) activity, suggesting that metformin prevents centrosome amplification by inhibiting the TOR signaling pathway.	Metformin	133-142	Target of rapamycin	Drosophila melanogaster	102-105
25988874-6	2015	Furthermore, we revealed that this effect is mediated via down-regulation of AKT/target of rapamycin (TOR) activity, suggesting that metformin prevents centrosome amplification by inhibiting the TOR signaling pathway.	Metformin	133-142	Target of rapamycin	Drosophila melanogaster	195-198
25988874-8	2015	Our study reveals the beneficial and protective effects of metformin on centrosome amplification via AKT/TOR signaling modulation.	Metformin	59-68	Akt1	Drosophila melanogaster	101-104
25988874-8	2015	Our study reveals the beneficial and protective effects of metformin on centrosome amplification via AKT/TOR signaling modulation.	Metformin	59-68	Target of rapamycin	Drosophila melanogaster	105-108
25921843-9	2015	Compared to baseline, metformin significantly improved metabolic parameters and insulin sensitivity, increased SIRT1 gene/protein expression and SIRT1 promoter chromatin accessibility, elevated mTOR gene expression with concomitant reduction in p70S6K phosphorylation in subjects" PBMCs, and modified the plasma N-glycan profile.	Metformin	22-31	ribosomal protein S6 kinase B1	Homo sapiens	245-251
25921843-10	2015	Compared to placebo, metformin increased SIRT1 protein expression and reduced p70S6K phosphorylation (a proxy of mTOR activity).	Metformin	21-30	ribosomal protein S6 kinase B1	Homo sapiens	78-84
26036314-0	2015	Axl receptor tyrosine kinase is up-regulated in metformin resistant prostate cancer cells.	Metformin	48-57	AXL receptor tyrosine kinase	Homo sapiens	0-3
26036314-8	2015	Here, we show that the metformin resistant cell line as well as castrate resistant cell lines that over express Axl were more resistant to metformin, as well as to taxotere compared to androgen sensitive LNCaP and CWR22 cells that do not overexpress Axl.	Metformin	23-32	AXL receptor tyrosine kinase	Homo sapiens	250-253
26036314-8	2015	Here, we show that the metformin resistant cell line as well as castrate resistant cell lines that over express Axl were more resistant to metformin, as well as to taxotere compared to androgen sensitive LNCaP and CWR22 cells that do not overexpress Axl.	Metformin	139-148	AXL receptor tyrosine kinase	Homo sapiens	112-115
26036314-9	2015	Forced overexpression of Axl in LNCaP cells decreased metformin and taxotere sensitivity and knockdown of Axl in resistant cells increased sensitivity to these drugs.	Metformin	54-63	AXL receptor tyrosine kinase	Homo sapiens	25-28
26036314-10	2015	Inhibition of Axl activity by R428, a small molecule Axl kinase inhibitor, sensitized metformin resistant cells that overexpressed Axl to metformin.	Metformin	86-95	AXL receptor tyrosine kinase	Homo sapiens	14-17
26036314-10	2015	Inhibition of Axl activity by R428, a small molecule Axl kinase inhibitor, sensitized metformin resistant cells that overexpressed Axl to metformin.	Metformin	138-147	AXL receptor tyrosine kinase	Homo sapiens	14-17
26036314-11	2015	Inhibitors of Axl may enhance tumor responses to metformin and other chemotherapy in cancers that over express Axl.	Metformin	49-58	AXL receptor tyrosine kinase	Homo sapiens	14-17
26036314-11	2015	Inhibitors of Axl may enhance tumor responses to metformin and other chemotherapy in cancers that over express Axl.	Metformin	49-58	AXL receptor tyrosine kinase	Homo sapiens	111-114
26091000-9	2015	In an opposite manner, incubation of MIN6 cells with AICAR or metformin activated AMPK, which suppressed C/EBPbeta expression.	Metformin	62-71	CCAAT/enhancer binding protein (C/EBP), beta	Mus musculus	105-114
26091000-10	2015	In addition, administration of the dipeptidyl peptidase-4 inhibitor vildagliptin and metformin to pancreatic beta cell-specific C/EBPbeta transgenic mice decreased C/EBPbeta expression levels and enhanced pancreatic beta cell mass in proportion to the recovery of AMPK activity.	Metformin	85-94	CCAAT/enhancer binding protein (C/EBP), beta	Mus musculus	128-137
26091000-10	2015	In addition, administration of the dipeptidyl peptidase-4 inhibitor vildagliptin and metformin to pancreatic beta cell-specific C/EBPbeta transgenic mice decreased C/EBPbeta expression levels and enhanced pancreatic beta cell mass in proportion to the recovery of AMPK activity.	Metformin	85-94	CCAAT/enhancer binding protein (C/EBP), beta	Mus musculus	164-173
26083494-10	2015	The follow-up network analyses and literature mining revealed that seven genes (CDKN1A, ESR1, MAX, MYC, PPARGC1A, SP1, and STK11) and one novel MYC-centered pathway with CDKN1A, SP1, and STK11 might play important roles in metformin"s antidiabetic and anticancer effects.	Metformin	223-232	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	144-147
25817233-11	2015	Co-treatment with metformin or AICAR decreased the TNF-alpha-induced intracellular TG, accompanied by significantly enhanced AMPK and ACC phosphorylation, suppressed mTOR and p70S6K phosphorylation, and reduced SREBP-1 and FAS expressions.	Metformin	18-27	ribosomal protein S6 kinase B1	Homo sapiens	175-181
25817233-11	2015	Co-treatment with metformin or AICAR decreased the TNF-alpha-induced intracellular TG, accompanied by significantly enhanced AMPK and ACC phosphorylation, suppressed mTOR and p70S6K phosphorylation, and reduced SREBP-1 and FAS expressions.	Metformin	18-27	sterol regulatory element binding transcription factor 1	Homo sapiens	211-218
25457473-5	2015	CONCLUSION: Both of these DPP-4 inhibitors, given as SPCs twice daily with metformin, lowered FPG after 14 days of treatment.	Metformin	75-84	dipeptidyl peptidase 4	Homo sapiens	26-31
25370454-4	2015	Meanwhile, IL-22-induced STAT3 phosphorylation and upregulation of downstream genes Bcl-2 and cyclin D1 were inhibited by metformin.	Metformin	122-131	interleukin 22	Mus musculus	11-16
25370454-0	2015	Metformin decreases IL-22 secretion to suppress tumor growth in an orthotopic mouse model of hepatocellular carcinoma.	Metformin	0-9	interleukin 22	Mus musculus	20-25
25370454-3	2015	Oral metformin administration led to a significant reduction of tumor growth, which was accompanied by decreased interleukin-22 (IL-22).	Metformin	5-14	interleukin 22	Mus musculus	113-127
25370454-3	2015	Oral metformin administration led to a significant reduction of tumor growth, which was accompanied by decreased interleukin-22 (IL-22).	Metformin	5-14	interleukin 22	Mus musculus	129-134
25370454-5	2015	At the cellular level, metformin attenuated Th1- and Th17-derived IL-22 production.	Metformin	23-32	interleukin 22	Mus musculus	66-71
25370454-7	2015	These observations were further supported by the fact that metformin treatment inhibited CD3/CD28-induced IFN-gamma and IL-17A expression along with the transcription factors that drive their expression (T-bet [Th1] and ROR-gammat [Th17], respectively).	Metformin	59-68	CD28 antigen	Mus musculus	93-97
25370454-9	2015	Notably, metformin led to a reduction in glucose transporter Glut1 expression, resulting in less glucose uptake, which is critical to regulate CD4(+) T cell fate.	Metformin	9-18	solute carrier family 2 (facilitated glucose transporter), member 1	Mus musculus	61-66
25891779-0	2015	Metformin attenuates palmitic acid-induced insulin resistance in L6 cells through the AMP-activated protein kinase/sterol regulatory element-binding protein-1c pathway.	Metformin	0-9	sterol regulatory element binding transcription factor 1	Homo sapiens	115-159
25891779-2	2015	We recently reported that metformin improved insulin receptor substrate-1 (IRS-1)-associated insulin signaling by downregulating sterol regulatory element-binding protein-1c (SREBP-1c) expression.	Metformin	26-35	insulin receptor substrate 1	Homo sapiens	45-73
25891779-2	2015	We recently reported that metformin improved insulin receptor substrate-1 (IRS-1)-associated insulin signaling by downregulating sterol regulatory element-binding protein-1c (SREBP-1c) expression.	Metformin	26-35	insulin receptor substrate 1	Homo sapiens	75-80
25891779-2	2015	We recently reported that metformin improved insulin receptor substrate-1 (IRS-1)-associated insulin signaling by downregulating sterol regulatory element-binding protein-1c (SREBP-1c) expression.	Metformin	26-35	sterol regulatory element binding transcription factor 1	Homo sapiens	129-173
25891779-2	2015	We recently reported that metformin improved insulin receptor substrate-1 (IRS-1)-associated insulin signaling by downregulating sterol regulatory element-binding protein-1c (SREBP-1c) expression.	Metformin	26-35	sterol regulatory element binding transcription factor 1	Homo sapiens	175-183
25891779-3	2015	In this study, we investigated whether AMPK activation and SREBP-1c inhibition contribute to the beneficial effects of metformin on IRS-1-associated insulin signaling in L6 myotubes.	Metformin	119-128	insulin receptor substrate 1	Homo sapiens	132-137
25407884-6	2015	Metformin inhibited TNF-alpha production with similar potency to rolipram and azithromycin (IC50 3.35 mum) but showed significantly lower efficacy (45.93%; P &lt; 0.05), and had no inhibitory effect on IL-1beta.	Metformin	0-9	interleukin-1 beta	Equus caballus	202-210
25736235-15	2015	Of the seven studies comparing DPP-4 inhibitors plus metformin with sulfonylureas plus metformin, six concluded that DPP-4 inhibitors were cost effective in patients with type 2 diabetes who were no longer adequately controlled by metformin monotherapy.	Metformin	53-62	dipeptidyl peptidase 4	Homo sapiens	117-122
18777489-4	2008	At week 52, the reduction in HbA1C with muraglitazar 5 mg plus metformin was superior (p&lt;0.0001) and with muraglitazar 2.5 mg it was non-inferior in comparison with glimepiride.	Metformin	63-72	hemoglobin subunit alpha 1	Homo sapiens	29-33
18469156-7	2008	Metformin attenuated the increased insulin receptor activation associated with the high-energy diet and also led to increased phosphorylation of AMP kinase, two actions that would be expected to decrease neoplastic proliferation.	Metformin	0-9	insulin receptor	Mus musculus	35-51
25736235-15	2015	Of the seven studies comparing DPP-4 inhibitors plus metformin with sulfonylureas plus metformin, six concluded that DPP-4 inhibitors were cost effective in patients with type 2 diabetes who were no longer adequately controlled by metformin monotherapy.	Metformin	87-96	dipeptidyl peptidase 4	Homo sapiens	117-122
25736235-15	2015	Of the seven studies comparing DPP-4 inhibitors plus metformin with sulfonylureas plus metformin, six concluded that DPP-4 inhibitors were cost effective in patients with type 2 diabetes who were no longer adequately controlled by metformin monotherapy.	Metformin	87-96	dipeptidyl peptidase 4	Homo sapiens	117-122
26030161-13	2015	The meta-analysis showed that metformin significantly inhibited the growth of HCC tumour (SMD -2.20[-2.96,-1.43]; n=16), but no significant effect on the number of tumors (SMD-1.05[-2.13,0.03]; n=5) or the incidence of HCC was observed (RR 0.62[0.33,1.16]; n=6).	Metformin	30-39	small nuclear ribonucleoprotein D2 polypeptide	Homo sapiens	90-96
26117007-5	2015	In process of inducing effect of 20 mmol/L metformin on THP-1 cells, the expressions of BCL-XL and BIM did not significantly changed, while the expressions of BAX and caspase-3 significantly increased (P&lt;0.01).	Metformin	43-52	BCL2 like 11	Homo sapiens	99-102
25736975-1	2015	Conclusions on the effect of metformin on circulating anti-Mullerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS) are ambiguous.	Metformin	29-38	anti-Mullerian hormone	Homo sapiens	78-81
18719601-8	2008	Two existing classes of antidiabetic drugs, that is, biguanides (for example, metformin) and the thiazolidinediones (for example, rosiglitazone), both act (at least in part) by activation of AMPK.	Metformin	78-87	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	191-195
18606228-0	2008	Dehydroepiandrosterone and metformin modulate progesterone-induced blocking factor (PIBF), cyclooxygenase 2 (COX2) and cytokines in early pregnant mice.	Metformin	27-36	prostaglandin-endoperoxide synthase 2	Mus musculus	91-107
18606228-0	2008	Dehydroepiandrosterone and metformin modulate progesterone-induced blocking factor (PIBF), cyclooxygenase 2 (COX2) and cytokines in early pregnant mice.	Metformin	27-36	prostaglandin-endoperoxide synthase 2	Mus musculus	109-113
18606228-4	2008	These findings prompted us to investigate the effect of DHEA and metformin on both PIBF and cyclooxygenase 2 (COX2) expressions at the implantation sites, as well as cytokine production.	Metformin	65-74	prostaglandin-endoperoxide synthase 2	Mus musculus	92-108
18606228-4	2008	These findings prompted us to investigate the effect of DHEA and metformin on both PIBF and cyclooxygenase 2 (COX2) expressions at the implantation sites, as well as cytokine production.	Metformin	65-74	prostaglandin-endoperoxide synthase 2	Mus musculus	110-114
18606228-7	2008	Embryo resorption correlates with the lack of PIBF expression, diminished IL-6 levels and increased IL-2 concentration while metformin was able to reverse the effect of DHEA on both PIBF and COX2 expression and IL-6 levels.	Metformin	125-134	prostaglandin-endoperoxide synthase 2	Mus musculus	191-195
25736975-6	2015	The decrease in AMH from a median of 49.5 to 46.9 pmol/L after 6 months on metformin was overall not significant (p = 0.81), nor were changes in obese women (from 49.5 to 38.2 pmol/L; p = 0.53).	Metformin	75-84	anti-Mullerian hormone	Homo sapiens	16-19
25736975-7	2015	Comparing individual metformin/placebo AMH values, a small absolute decrease of 9.3 pmol/L (p = 0.03) was observed in obese women after 6 months relative to baseline, suggesting a trend towards decreasing values after metformin treatment, mainly in obese women.	Metformin	21-30	anti-Mullerian hormone	Homo sapiens	39-42
23665884-1	2015	Dipeptidyl peptidase-4 (DPP-4) inhibitors have been well established as an adjunctive treatment to metformin.	Metformin	99-108	dipeptidyl peptidase 4	Homo sapiens	0-22
23665884-1	2015	Dipeptidyl peptidase-4 (DPP-4) inhibitors have been well established as an adjunctive treatment to metformin.	Metformin	99-108	dipeptidyl peptidase 4	Homo sapiens	24-29
23665884-4	2015	Our objective was to evaluate, by means of retrospective analysis, the efficacy of once-daily metformin and vildagliptin (a DPP-4 inhibitor) in reducing blood glucose for patients on combination therapy.	Metformin	94-103	dipeptidyl peptidase 4	Homo sapiens	124-129
25879666-8	2015	Furthermore, serum levels of leptin were decreased, while those of adiponectin were increased by metformin.	Metformin	97-106	adiponectin, C1Q and collagen domain containing	Mus musculus	67-78
25879666-9	2015	These findings suggest that metformin prevents liver tumorigenesis by ameliorating insulin sensitivity, inhibiting the activation of Akt/mTOR/p70S6 signaling, and improving adipokine imbalance.	Metformin	28-37	mechanistic target of rapamycin kinase	Mus musculus	137-141
25697376-0	2015	Metformin inhibits 7,12-dimethylbenz[a]anthracene-induced breast carcinogenesis and adduct formation in human breast cells by inhibiting the cytochrome P4501A1/aryl hydrocarbon receptor signaling pathway.	Metformin	0-9	cytochrome P450 family 1 subfamily A member 1	Homo sapiens	141-159
25867026-8	2015	Cell sensitivity to metformin also depends on the genetic and mutational backgrounds of the different GB cells used in this study, particularly their PTEN status.	Metformin	20-29	phosphatase and tensin homolog	Homo sapiens	150-154
25849717-9	2015	Treatment with anti-diabetic drugs metformin and glibenclamide also reduced IL-1alpha and IL-1beta secretion in infection and cytokine-primed adipose tissue.	Metformin	35-44	interleukin 1 alpha	Homo sapiens	76-85
25617357-8	2015	Coimmunoprecipitation studies revealed that metformin abolished oxidative stress-induced physical interactions between PPARalpha and cyclophilin D (CypD), and the abolishment of these interactions was associated with inhibition of permeability transition pore formation.	Metformin	44-53	peroxisome proliferator activated receptor alpha	Rattus norvegicus	119-128
25617357-10	2015	In conclusion, this study demonstrates that the protective effects of metformin-induced AMPK activation against oxidative stress converge on mitochondria and are mediated, at least in part, through the dissociation of PPARalpha-CypD interactions, independent of phosphorylation and acetylation of PPARalpha and CypD.	Metformin	70-79	peroxisome proliferator activated receptor alpha	Rattus norvegicus	218-227
25617357-10	2015	In conclusion, this study demonstrates that the protective effects of metformin-induced AMPK activation against oxidative stress converge on mitochondria and are mediated, at least in part, through the dissociation of PPARalpha-CypD interactions, independent of phosphorylation and acetylation of PPARalpha and CypD.	Metformin	70-79	peroxisome proliferator activated receptor alpha	Rattus norvegicus	297-306
25662675-0	2015	The variant organic cation transporter 2 (OCT2)-T201M contribute to changes in insulin resistance in patients with type 2 diabetes treated with metformin.	Metformin	144-153	solute carrier family 22 member 2	Homo sapiens	12-40
25662675-0	2015	The variant organic cation transporter 2 (OCT2)-T201M contribute to changes in insulin resistance in patients with type 2 diabetes treated with metformin.	Metformin	144-153	solute carrier family 22 member 2	Homo sapiens	42-46
25662675-2	2015	Organic cation transporter 2 (OCT2) is responsible for 80% metformin clearance.	Metformin	59-68	solute carrier family 22 member 2	Homo sapiens	0-28
25662675-2	2015	Organic cation transporter 2 (OCT2) is responsible for 80% metformin clearance.	Metformin	59-68	solute carrier family 22 member 2	Homo sapiens	30-34
25662675-4	2015	In this study, we examined the role of OCT2-T201M (602 C&gt;T) variant in insulin resistance in patients with type 2 diabetes (T2D) who were treated with metformin.	Metformin	154-163	solute carrier family 22 member 2	Homo sapiens	39-43
25662675-11	2015	CONCLUSIONS: Our findings suggest that the loss-of-function variant OCT2-T201M (rs145450955) contribute to changes in insulin resistance and beta cell activity in patients with T2D treated with metformin.	Metformin	194-203	solute carrier family 22 member 2	Homo sapiens	68-72
25727881-8	2015	RESULTS: Compared with men who were not on medication, the PSA level at the first PSA test was lower among men using 75 mg/dose aspirin (-3.9% change in PSA concentration; 95% confidence interval (CI): -5.8 to -2.1), statin (-4.6%; 95% CI: -6.2 to -2.9), metformin (-14%; 95% CI: -17 to -12) and insulin (-16%; 95% CI: -18 to -14).	Metformin	255-264	kallikrein related peptidase 3	Homo sapiens	59-62
25644093-8	2015	These results indicate that SGLT2 inhibitors can be successfully added to metformin plus sulfonylurea regimens.	Metformin	74-83	solute carrier family 5 member 2	Homo sapiens	28-33
18343152-5	2008	A low incidence of cancer in diabetic patients on metformin has been explained in vitro by the drug"s anti-proliferative effect through activation of AMPK.	Metformin	50-59	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	150-154
18401838-2	2008	Our first aim was to investigate the prevalence of risk determinants in subjects with type 2 diabetes mellitus (DM2) taking metformin compared to subjects with nonmetformin treatment.	Metformin	124-133	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	112-115
18401838-11	2008	Improved selection of patients can result in safe metformin utilization in one quarter of subjects on DM2 related drug treatment.	Metformin	50-59	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	102-105
26148594-8	2015	CONCLUSIONS: Metformin inhibited the expression of MMP-2, cisplatin and the combined treatment inhibited the expression of survivin, MMP-2, VEGF-C, and VEGFR-3, and the combined treatment of metformin with cisplatin resulted in enhanced anti-tumor efficacy.	Metformin	13-22	FMS-like tyrosine kinase 4	Mus musculus	152-159
25675380-11	2015	After 6 months of metformin treatment, there was a significant decrease in circulating irisin in PCOS women following improved IR.	Metformin	18-27	fibronectin type III domain containing 5	Homo sapiens	87-93
25613530-3	2015	Therefore, the present study used a PCOS rat model to test the hypotheses that HIF-1a signaling is expressed and inhibited in ovaries during PCOS formation and that the HIF-1a/ET-2 signaling pathway is a target of dimethyldiguanide (DMBG) in the clinical treatment of PCOS.	Metformin	214-231	endothelin 2	Rattus norvegicus	176-180
18405894-4	2008	Activation of AMPK by metformin or 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) increased the rates of constitutive exocytosis by about 2-fold.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	14-18
18405894-5	2008	Stimulation of exocytosis by AMPK occurred within minutes, and persisted after overnight exposure to metformin or AICAR.	Metformin	101-110	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	29-33
18375721-7	2008	The exposure of H9c2 cells to inhibitors of p38 mitogen-activated protein kinase (p38 MAPK) or protein kinase C (PKC) partially or completely abrogated metformin-induced alterations in metabolism in these cells, respectively.	Metformin	152-161	mitogen activated protein kinase 14	Rattus norvegicus	44-80
18375721-7	2008	The exposure of H9c2 cells to inhibitors of p38 mitogen-activated protein kinase (p38 MAPK) or protein kinase C (PKC) partially or completely abrogated metformin-induced alterations in metabolism in these cells, respectively.	Metformin	152-161	mitogen activated protein kinase 14	Rattus norvegicus	82-90
18375721-8	2008	Thus the metabolic actions of metformin in the heart muscle can occur independent of changes in AMPK activity and may be mediated by p38 MAPK- and PKC-dependent mechanisms.	Metformin	30-39	mitogen activated protein kinase 14	Rattus norvegicus	133-136
18322300-2	2008	This study was performed to explore whether the well-known clinical, hormonal and metabolic efficacy of metformin or rosiglitazone treatment is reflected in the modulation of adipocyte GLUT4 mRNA expression in patients with PCOS.	Metformin	104-113	solute carrier family 2 member 4	Homo sapiens	185-190
25948182-7	2015	RESULTS: The metformin lowered the OD value, and the expression levels of both adipogenic genes C/EBPalpha and FABP4 were lower than those of controls, while the expression level of PPARgamma mRNA was not significantly changed, the apoptosis rate of leukemia cells co-caltured with metformin-treated adipocytes was higher than that of co-cultured cells without metformin treatment.	Metformin	13-22	fatty acid binding protein 4	Homo sapiens	111-116
26101707-0	2015	Metformin inhibits gastric cancer via the inhibition of HIF1alpha/PKM2 signaling.	Metformin	0-9	pyruvate kinase M1/2	Homo sapiens	66-70
26101707-9	2015	Metformin downregulated PI3K, Akt, HIF1alpha, PARP, PKM2 and COX expression.	Metformin	0-9	pyruvate kinase M1/2	Homo sapiens	52-56
26101707-11	2015	In summary, metformin has profound antitumor effect for gastric cancer by inducing intrinsic apoptosis via the inhibition of HIF1alpha/PKM2 signaling pathway.	Metformin	12-21	pyruvate kinase M1/2	Homo sapiens	135-139
25382002-8	2015	Metformin, but not glibenclamide, increased intramuscular FNDC5 mRNA/protein expression and blood irisin levels.	Metformin	0-9	fibronectin type III domain containing 5	Mus musculus	58-63
25527093-9	2015	The addition of metformin or cimetidine significantly reduced the creatinine transepithelial flux, indicating active creatinine uptake in ciPTECs, most likely mediated by the organic cation transporter, OCT2 (SLC22A2).	Metformin	16-25	solute carrier family 22 member 2	Homo sapiens	203-207
25527093-9	2015	The addition of metformin or cimetidine significantly reduced the creatinine transepithelial flux, indicating active creatinine uptake in ciPTECs, most likely mediated by the organic cation transporter, OCT2 (SLC22A2).	Metformin	16-25	solute carrier family 22 member 2	Homo sapiens	209-216
25563903-6	2015	The organic cation transporter 1, plasma membrane monoamine transporter (PMAT), serotonin reuptake transporter, and choline high-affinity transporter contributed to approximately 25%, 20%, 20%, and 15%, respectively, of the AP uptake of metformin.	Metformin	237-246	solute carrier family 29 member 4	Homo sapiens	73-77
25812364-4	2015	Caution is advised to avoid use of metformin in patients at risk for lactic acidosis (e.g., in patients with advanced renal and liver insufficiency, infection, dehydration, alcoholism, or in those using diuretics or SGLT2 inhibitor).	Metformin	35-44	solute carrier family 5 member 2	Homo sapiens	216-221
26038701-8	2015	We demonstrate that (1) Metformin inhibits menadione-induced caspase-9,-6,-3 activation and PARP-cleavage in a concentration-dependent manner.	Metformin	24-33	poly (ADP-ribose) polymerase 1	Rattus norvegicus	92-96
26038701-9	2015	(2) Metformin increases menadione-induced heme oxygenase-1 (HO-1) expression and inhibits c-Jun N-terminal kinase (JNK)-phosphorylation.	Metformin	4-13	mitogen-activated protein kinase 8	Rattus norvegicus	90-113
26038701-9	2015	(2) Metformin increases menadione-induced heme oxygenase-1 (HO-1) expression and inhibits c-Jun N-terminal kinase (JNK)-phosphorylation.	Metformin	4-13	mitogen-activated protein kinase 8	Rattus norvegicus	115-118
26038701-11	2015	Metformin protects hepatocytes against oxidative stress-induced caspase activation, PARP-cleavage and apoptosis.	Metformin	0-9	poly (ADP-ribose) polymerase 1	Rattus norvegicus	84-88
26038701-12	2015	The anti-apoptotic effect of metformin is in part dependent on HO-1 and bcl-xl induction and inhibition of JNK activation and independent of insulin signaling.	Metformin	29-38	mitogen-activated protein kinase 8	Rattus norvegicus	107-110
18177481-7	2008	The importance of AMPK in cardiovascular functions is best demonstrated by recent studies showing that widely used drugs, including statins, metformin and rosiglitazone, execute cardiovascular protective effects at least partly through the activation of AMPK.	Metformin	141-150	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	18-22
18177481-7	2008	The importance of AMPK in cardiovascular functions is best demonstrated by recent studies showing that widely used drugs, including statins, metformin and rosiglitazone, execute cardiovascular protective effects at least partly through the activation of AMPK.	Metformin	141-150	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	254-258
25661368-0	2015	Metformin enhances radiation response of ECa109 cells through activation of ATM and AMPK.	Metformin	0-9	ATM serine/threonine kinase	Homo sapiens	76-79
25661368-7	2015	Furthermore, the mechanisms how metformin sensitized ECa109 cells to IR may be targeting the ATM and AMPK/mTOR/HIF-1alpha pathways.	Metformin	32-41	ATM serine/threonine kinase	Homo sapiens	93-96
25199921-2	2015	A recent in vitro study found that proton pump inhibitors (PPIs) inhibit OCT1, OCT2 and OCT3, suggesting that PPIs might reduce metformin"s effectiveness.	Metformin	128-137	ATPase H+/K+ transporting non-gastric alpha2 subunit	Homo sapiens	35-46
25377599-0	2015	The impact of metformin treatment on adiponectin and resistin levels in women with polycystic ovary syndrome: a prospective clinical study.	Metformin	14-23	resistin	Homo sapiens	53-61
24993950-0	2015	Metformin stimulates ischemia-induced revascularization through an eNOS dependent pathway in the ischemic hindlimb mice model.	Metformin	0-9	nitric oxide synthase 3, endothelial cell	Mus musculus	67-71
18079111-1	2008	AMP-activated protein kinase (AMPK) plays multiple roles in the body"s overall metabolic balance and response to exercise, nutritional stress, hormonal stimulation, and the glucose-lowering drugs metformin and rosiglitazone.	Metformin	196-205	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-28
18079111-1	2008	AMP-activated protein kinase (AMPK) plays multiple roles in the body"s overall metabolic balance and response to exercise, nutritional stress, hormonal stimulation, and the glucose-lowering drugs metformin and rosiglitazone.	Metformin	196-205	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	30-34
18250273-1	2008	BACKGROUND: Metformin, one of most commonly used antidiabetes drugs, is reported to exert its therapeutic effects by activating AMP-activated protein kinase (AMPK); however, the mechanism by which metformin activates AMPK is poorly defined.	Metformin	197-206	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	128-156
18250273-1	2008	BACKGROUND: Metformin, one of most commonly used antidiabetes drugs, is reported to exert its therapeutic effects by activating AMP-activated protein kinase (AMPK); however, the mechanism by which metformin activates AMPK is poorly defined.	Metformin	197-206	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	158-162
18250273-1	2008	BACKGROUND: Metformin, one of most commonly used antidiabetes drugs, is reported to exert its therapeutic effects by activating AMP-activated protein kinase (AMPK); however, the mechanism by which metformin activates AMPK is poorly defined.	Metformin	197-206	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	217-221
18250273-2	2008	The objective of the present study was to determine how metformin activates AMPK in endothelial cells.	Metformin	56-65	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	76-80
18250273-3	2008	METHODS AND RESULTS: Exposure of human umbilical vein endothelial cells or bovine aortic endothelial cells to metformin significantly increased AMPK activity and the phosphorylation of both AMPK at Thr172 and LKB1 at Ser428, an AMPK kinase, which was paralleled by increased activation of protein kinase C (PKC)-zeta, as evidenced by increased activity, phosphorylation (Thr410/403), and nuclear translocation of PKC-zeta.	Metformin	110-119	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	144-148
18250273-3	2008	METHODS AND RESULTS: Exposure of human umbilical vein endothelial cells or bovine aortic endothelial cells to metformin significantly increased AMPK activity and the phosphorylation of both AMPK at Thr172 and LKB1 at Ser428, an AMPK kinase, which was paralleled by increased activation of protein kinase C (PKC)-zeta, as evidenced by increased activity, phosphorylation (Thr410/403), and nuclear translocation of PKC-zeta.	Metformin	110-119	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	190-194
18250273-3	2008	METHODS AND RESULTS: Exposure of human umbilical vein endothelial cells or bovine aortic endothelial cells to metformin significantly increased AMPK activity and the phosphorylation of both AMPK at Thr172 and LKB1 at Ser428, an AMPK kinase, which was paralleled by increased activation of protein kinase C (PKC)-zeta, as evidenced by increased activity, phosphorylation (Thr410/403), and nuclear translocation of PKC-zeta.	Metformin	110-119	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	190-194
18250273-4	2008	Consistently, either pharmacological or genetic inhibition of PKC-zeta ablated metformin-enhanced phosphorylation of both AMPK-Thr172 and LKB1-Ser428, suggesting that PKC-zeta might act as an upstream kinase for LKB1.	Metformin	79-88	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	122-126
18250273-5	2008	Furthermore, adenoviral overexpression of LKB1 kinase-dead mutants abolished but LKB1 wild-type overexpression enhanced the effects of metformin on AMPK in bovine aortic endothelial cells.	Metformin	135-144	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	148-152
18250273-6	2008	In addition, metformin increased the phosphorylation and nuclear export of LKB1 into the cytosols as well as the association of AMPK with LKB1 in bovine aortic endothelial cells.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	128-132
18250273-7	2008	Similarly, overexpression of LKB1 wild-type but not LKB1 S428A mutants (serine replaced by alanine) restored the effects of metformin on AMPK in LKB1-deficient HeLa-S3 cells, suggesting that Ser428 phosphorylation of LKB1 is required for metformin-enhanced AMPK activation.	Metformin	124-133	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	137-141
18250273-9	2008	Finally, inhibition of PKC-zeta abolished metformin-enhanced coimmunoprecipitation of LKB1 with both AMPKalpha1 and AMPKalpha2.	Metformin	42-51	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	101-111
18250273-9	2008	Finally, inhibition of PKC-zeta abolished metformin-enhanced coimmunoprecipitation of LKB1 with both AMPKalpha1 and AMPKalpha2.	Metformin	42-51	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	116-126
18098312-4	2008	A time-dependent activation of AMPK was observed in response to a number of stimuli, including globular adiponectin, 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), or metformin.	Metformin	184-193	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	31-35
18220291-10	2008	AMPK activation by AICAR or metformin inhibits HSC proliferation via suppression of ROS production and subsequent inhibition of AKT pathway.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
18076373-8	2008	The two leading diabetic drugs, namely metformin and rosiglitazone, and adipokines, such as adiponectin and leptin, show their metabolic effects partially through AMPK.	Metformin	39-48	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	163-167
24993950-11	2015	Treatment with metformin significantly enhanced the increase in AMPK and eNOS phosphorylation levels of muscle tissues in WT mice induced by ischemia.	Metformin	15-24	nitric oxide synthase 3, endothelial cell	Mus musculus	73-77
24993950-12	2015	In eNOS- deficient knockout mice, there was a significant increase in ischemic tissue AMPK phosphorylation induced by metformin; however, blood flow recovery in ischemic limb after surgery was unaffected.	Metformin	118-127	nitric oxide synthase 3, endothelial cell	Mus musculus	3-7
18040888-5	2008	More importantly, metformin, together with the PTP classical inhibitor cyclosporin A (CsA), strongly mitigated the activation of this apoptotic cascade.	Metformin	18-27	ERCC excision repair 8, CSA ubiquitin ligase complex subunit	Homo sapiens	86-89
18040888-7	2008	In addition, metformin was shown to delay CsA-sensitive PTP opening in permeabilized neurons, as triggered by a calcium overload, probably through its mild inhibitory effect on the respiratory chain complex I.	Metformin	13-22	ERCC excision repair 8, CSA ubiquitin ligase complex subunit	Homo sapiens	42-45
18561513-6	2008	Sitagliptin has also been examined in initial combination therapy with metformin have; HbA1 was reduced by this combination by 2.1% (baseline HbA1C 8.8%) after 24 weeks of treatment.	Metformin	71-80	hemoglobin subunit alpha 1	Homo sapiens	87-91
18006825-3	2007	Recently, we showed that metformin inhibits the growth of breast cancer cells through the activation of AMPK.	Metformin	25-34	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	104-108
24993950-13	2015	CONCLUSIONS: Metformin promoted revascularization in the presence of tissue ischemia through an AMPK/eNOS-related mechanism.	Metformin	13-22	nitric oxide synthase 3, endothelial cell	Mus musculus	101-105
25504439-0	2015	Metformin and trametinib have synergistic effects on cell viability and tumor growth in NRAS mutant cancer.	Metformin	0-9	NRAS proto-oncogene, GTPase	Rattus norvegicus	88-92
25504439-3	2015	Here we test a novel dual therapy combination of metformin and trametinib on a panel of 16 NRAS mutant cell lines, including melanoma cells, melanoma cells with acquired trametinib resistance, lung cancer and neuroblastoma cells.	Metformin	49-58	NRAS proto-oncogene, GTPase	Rattus norvegicus	91-95
25504439-4	2015	We show that both of the main downstream cascades of NRAS can be blocked by this combination: metformin indirectly inhibits the PI3K/AKT/mTOR pathway and trametinib directly impedes the MAPK pathway.	Metformin	94-103	NRAS proto-oncogene, GTPase	Rattus norvegicus	53-57
25504439-6	2015	We conclude that metformin and trametinib combinations are effective in preclinical models and may be a possible option for treatment of NRAS mutant cancers.	Metformin	17-26	NRAS proto-oncogene, GTPase	Rattus norvegicus	137-141
25497710-10	2015	The effect of metformin reducing the tumor development in obese rats might involve increased mRNA expression of pRb and p27, increased activity of AMPK and FOXO3a and decreased expression of p-ERK1/2 (Thr202/Tyr204) in Walker-256 tumor.	Metformin	14-23	cyclin-dependent kinase inhibitor 1B	Rattus norvegicus	120-123
25179820-1	2015	The aim of this study was to elucidate whether metformin can regulate the expression of vascular endothelial growth factor (VEGF) in rat-derived uterine leiomyoma cells (ELT-3 cells).	Metformin	47-56	vascular endothelial growth factor A	Rattus norvegicus	88-122
25179820-1	2015	The aim of this study was to elucidate whether metformin can regulate the expression of vascular endothelial growth factor (VEGF) in rat-derived uterine leiomyoma cells (ELT-3 cells).	Metformin	47-56	vascular endothelial growth factor A	Rattus norvegicus	124-128
25179820-3	2015	Under normoxic conditions, metformin suppressed VEGF protein levels in the supernatant and cells in a dose-dependent manner.	Metformin	27-36	vascular endothelial growth factor A	Rattus norvegicus	48-52
25179820-4	2015	In hypoxia-mimicking conditions, VEGF and hypoxia-inducible factor-1alpha (HIF-1alpha) proteins were both highly expressed and were suppressed by the metformin treatment.	Metformin	150-159	vascular endothelial growth factor A	Rattus norvegicus	33-37
25179820-7	2015	This study revealed the anti-angiogenic activity of metformin in ELT-3 cells by suppressing the expression of VEGF via the mTORC1/HIF-1alpha pathway.	Metformin	52-61	vascular endothelial growth factor A	Rattus norvegicus	110-114
25640355-4	2015	IGF-1R was highly expressed in human endometrial carcinoma paraffin sections, but IGF-1R and phosphor-protein kinase B/protein kinase B (p-Akt/ Akt) expression was down-regulated after metformin treatment (p&lt;0.05).	Metformin	185-194	protein tyrosine kinase 2 beta	Homo sapiens	102-118
25640355-4	2015	IGF-1R was highly expressed in human endometrial carcinoma paraffin sections, but IGF-1R and phosphor-protein kinase B/protein kinase B (p-Akt/ Akt) expression was down-regulated after metformin treatment (p&lt;0.05).	Metformin	185-194	protein tyrosine kinase 2 beta	Homo sapiens	119-135
26064989-7	2015	The reduced level of OPN in the adipose tissue of metformin-treated animals strongly correlated with the lower expression of Ki67 and CD105 and increased caspase-3.	Metformin	50-59	endoglin	Mus musculus	134-139
26075281-0	2015	Metformin Ameliorates Podocyte Damage by Restoring Renal Tissue Podocalyxin Expression in Type 2 Diabetic Rats.	Metformin	0-9	podocalyxin-like	Rattus norvegicus	64-75
26075281-2	2015	The aim of this study was to observe the effect of different doses of metformin on renal tissue PCX expression in type 2 diabetic rats and clarify its protection on glomerular podocytes.	Metformin	70-79	podocalyxin-like	Rattus norvegicus	96-99
26075281-10	2015	These results suggested that metformin can ameliorate glomerular podocyte damage in type 2 diabetic rats, which may be partly associated with its role in restoring PCX expression and inhibiting urinary excretion of PCX with dose dependence.	Metformin	29-38	podocalyxin-like	Rattus norvegicus	164-167
26075281-10	2015	These results suggested that metformin can ameliorate glomerular podocyte damage in type 2 diabetic rats, which may be partly associated with its role in restoring PCX expression and inhibiting urinary excretion of PCX with dose dependence.	Metformin	29-38	podocalyxin-like	Rattus norvegicus	215-218
25861467-8	2015	Plasma TF activity was reduced by metformin and increased with rosiglitazone treatment.	Metformin	34-43	coagulation factor III, tissue factor	Homo sapiens	7-9
26688757-3	2015	In metformin-sensitive cells, autophagy was not induced but rather it blocked proliferation by means of arresting cells in the S and G2/M phases which was associated with the downregulation of cyclin A, cyclin B1, and cdc2, but not that of cyclin E. In 10E1-CEM cells that overexpress Bcl-2 and are drug-resistant, the effect of metformin on proliferation was more pronounced, also inducing the activation of the caspases 3/7 and hence apoptosis.	Metformin	3-12	cyclin B1	Homo sapiens	203-212
26688757-3	2015	In metformin-sensitive cells, autophagy was not induced but rather it blocked proliferation by means of arresting cells in the S and G2/M phases which was associated with the downregulation of cyclin A, cyclin B1, and cdc2, but not that of cyclin E. In 10E1-CEM cells that overexpress Bcl-2 and are drug-resistant, the effect of metformin on proliferation was more pronounced, also inducing the activation of the caspases 3/7 and hence apoptosis.	Metformin	3-12	cyclin dependent kinase 1	Homo sapiens	218-222
26688757-4	2015	In all sensitive cells, metformin decreased the Deltapsi m and it modified the expression of enzymes involved in energy metabolism: PKCepsilon (PKCepsilon) and PKCdelta (PKCdelta).	Metformin	24-33	protein kinase C epsilon	Homo sapiens	132-142
26688757-4	2015	In all sensitive cells, metformin decreased the Deltapsi m and it modified the expression of enzymes involved in energy metabolism: PKCepsilon (PKCepsilon) and PKCdelta (PKCdelta).	Metformin	24-33	protein kinase C epsilon	Homo sapiens	144-154
26688757-5	2015	In sensitive cells, metformin altered PKCepsilon and PKCdelta expression leading to a predominance of PKCepsilon over PKCdelta which implies a more glycolytic state.	Metformin	20-29	protein kinase C epsilon	Homo sapiens	38-48
26688757-5	2015	In sensitive cells, metformin altered PKCepsilon and PKCdelta expression leading to a predominance of PKCepsilon over PKCdelta which implies a more glycolytic state.	Metformin	20-29	protein kinase C epsilon	Homo sapiens	102-112
25815012-0	2015	Correlation of endometrial glycodelin expression and pregnancy outcome in cases with polycystic ovary syndrome treated with clomiphene citrate plus metformin: a controlled study.	Metformin	148-157	progestagen associated endometrial protein	Homo sapiens	27-37
25815012-2	2015	The purpose of this study was to evaluate the relationship between clomiphene citrate (CC) plus metformin treatment and endometrial glycodelin expression and to then correlate this relationship with pregnancy outcomes.	Metformin	96-105	progestagen associated endometrial protein	Homo sapiens	132-142
24621340-0	2015	Influence of dissolution media pH and USP1 basket speed on erosion and disintegration characteristics of immediate release metformin hydrochloride tablets.	Metformin	123-146	ubiquitin specific peptidase 1	Homo sapiens	38-42
24862830-3	2015	Metformin decreases hepatic glucose production via a mechanism requiring liver kinase B1, which controls the metabolic checkpoint, AMP-activated protein kinase-mammalian target of rapamycin and neoglucogenic genes.	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	73-88
17635921-7	2007	Conversely, activation of AMPK by pharmacologic (nicotine, ONOO(-), metformin, and AICAR) or genetic (overexpression of constitutively active AMPK) means inhibited FAS activity.	Metformin	68-77	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	26-30
17718786-2	2007	We analyzed the data from this study to determine (a) if metformin reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations during the 6-month trial, and (b) if the response to pharmacotherapy varied along gender or ethnic lines.	Metformin	57-66	glutamic--pyruvic transaminase	Homo sapiens	81-105
18038714-9	2007	After 8 months of treatment with metformin he developed DM2.	Metformin	33-42	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	56-59
18038714-17	2007	CONCLUSION: We suggest that early initiation of combined therapy comprising a high dose of metformin plus rosiglitazone may be valuable in managing insulin resistance and DM2 in children with AS.	Metformin	91-100	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	171-174
17603555-1	2007	BACKGROUND AND PURPOSE: AMP-activated protein kinase (AMPK) is activated by metformin, phenformin, and the AMP mimetic, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).	Metformin	76-85	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	54-58
17603555-7	2007	KEY RESULTS: Phenformin, AICAR and metformin increased AMPK (alpha1) activity and decreased I(amiloride).	Metformin	35-44	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	55-67
17603555-8	2007	The AMPK inhibitor Compound C prevented the action of metformin and AICAR but not phenformin.	Metformin	54-63	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	4-8
17513706-1	2007	Activation of AMP-activated protein kinase (AMPK) in rodent muscle by exercise, metformin, 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR), and adiponectin increases glucose uptake.	Metformin	80-89	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	44-48
17525164-0	2007	Activation of 5"-AMP-activated kinase with diabetes drug metformin induces casein kinase Iepsilon (CKIepsilon)-dependent degradation of clock protein mPer2.	Metformin	57-66	casein kinase 1, epsilon	Mus musculus	75-97
17525164-0	2007	Activation of 5"-AMP-activated kinase with diabetes drug metformin induces casein kinase Iepsilon (CKIepsilon)-dependent degradation of clock protein mPer2.	Metformin	57-66	casein kinase 1, epsilon	Mus musculus	99-109
17525164-5	2007	We discovered that the circadian period of Rat-1 fibroblasts treated with metformin was shortened by 1 h. One of the regulators of the period length is casein kinase Iepsilon (CKIepsilon), which by phosphorylating and inducing the degradation of the circadian clock component, mPer2, shortens the period length.	Metformin	74-83	casein kinase 1, epsilon	Mus musculus	152-174
17525164-5	2007	We discovered that the circadian period of Rat-1 fibroblasts treated with metformin was shortened by 1 h. One of the regulators of the period length is casein kinase Iepsilon (CKIepsilon), which by phosphorylating and inducing the degradation of the circadian clock component, mPer2, shortens the period length.	Metformin	74-83	casein kinase 1, epsilon	Mus musculus	176-186
17342635-3	2007	The synthetic GLP-1 agonist exenatide underlies a different metabolism and has recently been approved by the U.S. Food and Drug Administration for the adjunctive treatment of patients with type 2 diabetes who are suboptimally controlled with metformin and/or sulfonylurea.	Metformin	242-251	glucagon like peptide 1 receptor	Homo sapiens	14-19
31627625-6	2007	In patients with DM-2, metformin exerted a positive effect on fasting glycemia (p = 0.001) and postprandial hyperglycemia (absolute and relative areas under the curve in the oral glucose tolerance test (OGTT)).	Metformin	23-32	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	17-21
31627625-9	2007	In patients with DM-2, metformin therapy enhanced a low-calorie diet-induced body weight loss, most markedly within the first three months of therapy.	Metformin	23-32	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	17-21
25734181-5	2015	Metformin, an antidiabetic drug, is effective for endometrial cancer through inhibition of the PI3K-Akt-mTOR pathway by activating LKB1-AMPK and reduction of insulin and insulin-like growth factor-1 due to AMPK activation.	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	131-135
25262277-6	2015	We found that only inhibition of Wnt signaling by either metformin or IWP-2 significantly decreased the effect of MMP26 on cancer cell invasion, possibly through increasing beta-catenin phosphorylation.	Metformin	57-66	matrix metallopeptidase 26	Homo sapiens	114-119
25262277-6	2015	We found that only inhibition of Wnt signaling by either metformin or IWP-2 significantly decreased the effect of MMP26 on cancer cell invasion, possibly through increasing beta-catenin phosphorylation.	Metformin	57-66	catenin beta 1	Homo sapiens	173-185
25427448-8	2014	Metformin substantially increased radiosensitivity, intracellular ROS levels and reduced Trx expression, in luminal breast cancer cells, but had little effect on basal phenotype cells.	Metformin	0-9	thioredoxin	Homo sapiens	89-92
17095593-1	2007	The oral antidiabetic agent metformin acts at least partially via an activation of AMP-activated kinase (AMPK) in liver and muscle cells.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	83-103
17095593-1	2007	The oral antidiabetic agent metformin acts at least partially via an activation of AMP-activated kinase (AMPK) in liver and muscle cells.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	105-109
17095593-3	2007	Because metformin also exhibits anorectic effects in animal models as well as in humans, we hypothesized that AMPK may be a target of metformin in hypothalamic neurons.	Metformin	8-17	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	110-114
17095593-3	2007	Because metformin also exhibits anorectic effects in animal models as well as in humans, we hypothesized that AMPK may be a target of metformin in hypothalamic neurons.	Metformin	134-143	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	110-114
17095593-5	2007	The addition of metformin in low glucose conditions was found to block AMPK phosphorylation.	Metformin	16-25	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	71-75
17095593-8	2007	Taken together, our data demonstrate that metformin can inhibit AMPK activity in hypothalamic neurons, thus modulating the expression of the orexigenic peptide NPY.	Metformin	42-51	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	64-68
16987706-1	2006	The first antidiabetic treatment (exenatide; Byetta) based on the incretin hormone glucagon-like peptide-1 (GLP-1) was approved in 2005 as an adjunctive therapy in diabetic patients in whom sulfonylurea, metformin or both had failed.	Metformin	204-213	glucagon like peptide 1 receptor	Homo sapiens	108-113
17085580-7	2006	In culture, endogenous TAK1 was activated by oligomycin, the antidiabetic drug metformin, 5-aminoimidazole-4-carboxamide riboside (AICAR), and ischemia, well established triggers of AMPK activity.	Metformin	79-88	mitogen-activated protein kinase kinase kinase 7	Mus musculus	23-27
17026483-6	2006	Recent studies have shown that AMPK is involved in the mechanism of action of metformin and thiazolidinediones, and the adipocytokines leptin and adiponectin.	Metformin	78-87	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	31-35
16945366-8	2006	In vivo metformin lowered plasma DPP IV activity in ob/ob mice, and improved glucose-lowering and insulin-releasing effects of exogenous GLP-1 administration.	Metformin	8-17	glucagon	Mus musculus	137-142
16945366-10	2006	In contrast metformin had minor effects on in vitro GLP-1-stimulated insulin release from clonal beta cells.	Metformin	12-21	glucagon	Mus musculus	52-57
16945366-12	2006	These findings indicate that metformin decreases the plasma DPP IV activity, limiting the inactivation of exogenously administered GLP-1 and improving glycaemic control.	Metformin	29-38	glucagon	Mus musculus	131-136
16940989-2	2006	Therefore, a series of experiments using various inducers and inhibitors of CYP isozymes was conducted to find out what types of CYP isozymes are involved in the metabolism of metformin in rats.	Metformin	176-185	cytochrome P450, family 3, subfamily a, polypeptide 23-polypeptide 1	Rattus norvegicus	76-79
16940989-2	2006	Therefore, a series of experiments using various inducers and inhibitors of CYP isozymes was conducted to find out what types of CYP isozymes are involved in the metabolism of metformin in rats.	Metformin	176-185	cytochrome P450, family 3, subfamily a, polypeptide 23-polypeptide 1	Rattus norvegicus	129-132
16868748-1	2006	AIMS/HYPOTHESIS: Metformin has been shown to increase fatty acid oxidation, an effect mediated by AMP activated protein kinase (AMPK).	Metformin	17-26	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	98-126
16868748-1	2006	AIMS/HYPOTHESIS: Metformin has been shown to increase fatty acid oxidation, an effect mediated by AMP activated protein kinase (AMPK).	Metformin	17-26	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	128-132
16868748-5	2006	To investigate the mechanism of metformin"s effect on cardiomyocytes, substrate utilisation and phosphorylation of AMPK and acetyl-CoA carboxylase were measured.	Metformin	32-41	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	115-119
16868748-8	2006	This beneficial effect of metformin was associated with increased AMPK phosphorylation, palmitic acid oxidation and suppression of high-fat-induced increases in (1) long chain base biosynthesis protein 1 levels, (2) ceramide levels, and (3) caspase-3 activity.	Metformin	26-35	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	66-70
16882108-19	2006	However, long-term treatment with metformin plus pioglitazone significantly reduced Lp(a) plasma levels, whereas metformin + rosiglitazone did not.	Metformin	34-43	lipoprotein(a)	Homo sapiens	84-89
16882108-20	2006	CONCLUSION: For patients with type 2 diabetes mellitus and metabolic syndrome, combined treatment with metformin and rosiglitazone or pioglitazone is safe and effective, However, the pioglitazone combination also reduced the plasma Lp(a) levels whereas the rosiglitazone combination did not.	Metformin	103-112	lipoprotein(a)	Homo sapiens	232-237
16513829-0	2006	Long-term metformin treatment stimulates cardiomyocyte glucose transport through an AMP-activated protein kinase-dependent reduction in GLUT4 endocytosis.	Metformin	10-19	solute carrier family 2 member 4	Homo sapiens	136-141
16513829-10	2006	These data also indicate an independent point of convergence of metformin and insulin stimuli on GLUT4 regulatory processes.	Metformin	64-73	solute carrier family 2 member 4	Homo sapiens	97-102
16513829-12	2006	Metformin treatment markedly slowed endocytosis of GLUT4, but exocytosis was not increased.	Metformin	0-9	solute carrier family 2 member 4	Homo sapiens	51-56
16513829-13	2006	We conclude that metformin treatment leads to a longer residence time of GLUT4 in the plasma membrane due to an AMP-activated protein kinase-dependent reduction in endocytosis.	Metformin	17-26	solute carrier family 2 member 4	Homo sapiens	73-78
16636195-2	2006	Metformin has been shown to activate AMPK.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	37-41
16636195-4	2006	Metformin was observed to activate AMPK, as well as its downstream target, phosphoacetyl coenzyme A carboxylase, in human umbilical vein endothelial cells (HUVECs).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	35-39
16636195-9	2006	The small interfering RNA for AMPKalpha1 attenuated metformin or AICAR-induced inhibition of NF-kappaB activation by TNF-alpha, suggesting a possible role of AMPK in the regulation of cell inflammation.	Metformin	52-61	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	30-40
16636195-9	2006	The small interfering RNA for AMPKalpha1 attenuated metformin or AICAR-induced inhibition of NF-kappaB activation by TNF-alpha, suggesting a possible role of AMPK in the regulation of cell inflammation.	Metformin	52-61	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	30-34
16636195-10	2006	In light of these findings, we suggest that metformin attenuates the cytokine-induced expression of proinflammatory and adhesion molecule genes by inhibiting NF-kappaB activation via AMPK activation.	Metformin	44-53	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	183-187
16785142-15	2006	CONCLUSIONS: The use of metformin with GnRH antagonist improves the outcome of ovarian stimulation in IVF-ET cycles in PCOS patients.	Metformin	24-33	gonadotropin releasing hormone 1	Homo sapiens	39-43
16617360-18	2006	Treatment with fenofibrate or metformin ameliorated renal damage in OLETF rats through SREBP-1 and some enzyme regulated by it reduced fat deposit in kidney directly.	Metformin	30-39	sterol regulatory element binding transcription factor 1	Rattus norvegicus	87-94
16489446-4	2006	METHODS: We used reporter gene analysis to examine the effects of rosiglitazone and metformin on the activity of the proinsulin and insulin promoter factor 1 (IPF1) gene promoters in the glucose-responsive mouse beta cell line Min6.	Metformin	84-93	pancreatic and duodenal homeobox 1	Mus musculus	132-157
16489446-4	2006	METHODS: We used reporter gene analysis to examine the effects of rosiglitazone and metformin on the activity of the proinsulin and insulin promoter factor 1 (IPF1) gene promoters in the glucose-responsive mouse beta cell line Min6.	Metformin	84-93	pancreatic and duodenal homeobox 1	Mus musculus	159-163
25427448-10	2014	Metformin preferentially radiosensitises luminal breast cancer cells, potentially due to alterations to intracellular ROS levels via modulation of Trx family protein expression.	Metformin	0-9	thioredoxin	Homo sapiens	147-150
25554070-9	2014	Furthermore, the combination of SGLT-2 inhibitors with other drugs that either have anorectic effects (such as incretin-based therapies) or reduce hepatic glucose output (like metformin) and, thus, may dampen these two compensatory mechanisms appears appealing for the management of type 2 diabetes mellitus.	Metformin	176-185	solute carrier family 5 member 2	Homo sapiens	32-38
16597407-8	2006	Moreover, the AMPK system is one of the probable target for the anti-diabetic drug metformin and rosiglitazone.	Metformin	83-92	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	14-18
24903160-4	2014	Metformin enhanced basal and insulin-stimulated glucose uptake and GLUT4 translocation, reduced IRS-1 and Akt phosphorylation and ROS levels, and affected the expression of regulators of mitochondrial biogenesis in LYRM1-over-expressing adipocytes.	Metformin	0-9	insulin receptor substrate 1	Homo sapiens	96-101
25951664-8	2014	Metformin improved metabolic disorders, upregulated activity of renal AMPK, diminished the expression of renal SREBP-1c, TNF-alpha, NOX4 mRNA, decreased accumulation of renal lipids, and prevened renal injury.	Metformin	0-9	sterol regulatory element binding transcription factor 1	Mus musculus	111-119
25623461-1	2014	OBJECTIVE: To analyze the level of serum leptin and its relations with insulin resistance in patients with polycystic ovary syndrome (PCOS) so as to investigate the clinical effect of aciesis in PCOS under treatment of metformin.	Metformin	219-228	leptin	Homo sapiens	41-47
25412314-0	2014	Combination simvastatin and metformin induces G1-phase cell cycle arrest and Ripk1- and Ripk3-dependent necrosis in C4-2B osseous metastatic castration-resistant prostate cancer cells.	Metformin	28-37	receptor interacting serine/threonine kinase 1	Homo sapiens	77-82
25361177-6	2014	Combined metformin and erlotinib led to partial regression of PTEN-null and EGFR-amplified xenografted MDA-MB-468 BBC tumors with evidence of significant apoptosis, reduction of EGFR and AKT signaling, and lack of altered plasma insulin levels.	Metformin	9-18	phosphatase and tensin homolog	Homo sapiens	62-66
25248681-0	2014	Glutathione-S-transferase selective release of metformin from its sulfonamide prodrug.	Metformin	47-56	hematopoietic prostaglandin D synthase	Rattus norvegicus	0-25
25089916-12	2014	CONCLUSIONS: Despite the limitations of this observational study, diabetes patients with MS who were treated with metformin plus DPP-4 inhibitors had better compliance, greater metabolic control, and lower rates of hypoglycemia, causing lower costs for the Spanish national health system than patients receiving metformin plus other antidiabetes drugs.	Metformin	312-321	dipeptidyl peptidase 4	Homo sapiens	129-134
25127677-11	2014	These effects were markedly attenuated in K-Ras(+/LSL-G12D);Trp53(+/LSLR172H);Pdx-1-Cre mice given metformin.	Metformin	99-108	Kirsten rat sarcoma viral oncogene homolog	Mus musculus	42-47
25127677-11	2014	These effects were markedly attenuated in K-Ras(+/LSL-G12D);Trp53(+/LSLR172H);Pdx-1-Cre mice given metformin.	Metformin	99-108	transformation related protein 53	Mus musculus	60-65
25364682-1	2014	UNLABELLED: Allele and genotype frequency of a genetic variant in ATM gene affecting glycemic response to metformin in South Indian population.	Metformin	106-115	ATM serine/threonine kinase	Homo sapiens	66-69
25364682-2	2014	CONTEXT: The novel polymorphism in ATM gene (rs11212617), which is implicated to have association with metformin response, exhibits inter-ethnic variability in the allele and genotype frequency distribution.	Metformin	103-112	ATM serine/threonine kinase	Homo sapiens	35-38
24827939-6	2014	In adjusted analyses with metformin + SU as reference, metformin + DPP-4 inhibitor was associated with an RR of 0.65 (0.54-0.80) for mortality, an RR of 0.57 (0.40-0.80) for CV mortality and an RR of 0.70 (0.57-0.85) for the combined end point.	Metformin	26-35	dipeptidyl peptidase 4	Homo sapiens	67-72
24827939-6	2014	In adjusted analyses with metformin + SU as reference, metformin + DPP-4 inhibitor was associated with an RR of 0.65 (0.54-0.80) for mortality, an RR of 0.57 (0.40-0.80) for CV mortality and an RR of 0.70 (0.57-0.85) for the combined end point.	Metformin	55-64	dipeptidyl peptidase 4	Homo sapiens	67-72
25111690-6	2014	A blocker of ER stress, tauroursodeoxycholic acid (TUDCA), and an inhibitor of SREBP-1c, metformin, blocked hepatic fat accumulation, suggesting that uric acid promoted fat synthesis in hepatocytes via ER stress-induced activation of SREBP-1c.	Metformin	89-98	sterol regulatory element binding transcription factor 1	Homo sapiens	79-87
25122066-6	2014	Combination of simvastatin and metformin decreased Akt Ser-473 and Thr-308 phosphorylation and AMPKalpha Ser-485/491 phosphorylation; increased Thr-172 phosphorylation and AMPKalpha activity, as assessed by increased Ser-79 and Ser-872 phosphorylation of acetyl-CoA carboxylase and HMG-CoAR, respectively; decreased HMG-CoAR activity; and reduced total cellular cholesterol and its synthesis in both cell lines.	Metformin	31-40	3-hydroxy-3-methylglutaryl-CoA reductase	Homo sapiens	282-290
25122066-6	2014	Combination of simvastatin and metformin decreased Akt Ser-473 and Thr-308 phosphorylation and AMPKalpha Ser-485/491 phosphorylation; increased Thr-172 phosphorylation and AMPKalpha activity, as assessed by increased Ser-79 and Ser-872 phosphorylation of acetyl-CoA carboxylase and HMG-CoAR, respectively; decreased HMG-CoAR activity; and reduced total cellular cholesterol and its synthesis in both cell lines.	Metformin	31-40	3-hydroxy-3-methylglutaryl-CoA reductase	Homo sapiens	316-324
25597711-1	2014	OBJECTIVES: Determine the clinical repurcussions of adherence, metabolic control, hypoglycemia and cardiovascular events (CVE) and economics (resources and costs) in the combination therapy of metformin vs DPP-4 (dipeptidyl peptidase-4) inhibitors and sulfonylureas in patients with type 2 diabetes.	Metformin	193-202	dipeptidyl peptidase 4	Homo sapiens	213-235
25107910-0	2014	Taste of a pill: organic cation transporter-3 (OCT3) mediates metformin accumulation and secretion in salivary glands.	Metformin	62-71	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	17-45
25107910-0	2014	Taste of a pill: organic cation transporter-3 (OCT3) mediates metformin accumulation and secretion in salivary glands.	Metformin	62-71	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	47-51
25107910-5	2014	Metformin, a widely used anti-diabetic drug known to induce taste disturbance, is transported by OCT3/Oct3 in vitro.	Metformin	0-9	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	97-101
25107910-5	2014	Metformin, a widely used anti-diabetic drug known to induce taste disturbance, is transported by OCT3/Oct3 in vitro.	Metformin	0-9	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	102-106
25107910-7	2014	In contrast, active uptake and accumulation of metformin in salivary glands were abolished in Oct3(-/-) mice.	Metformin	47-56	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	94-98
25107910-8	2014	Oct3(-/-) mice also showed altered metformin pharmacokinetics and reduced drug exposure in the heart.	Metformin	35-44	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	0-4
25107910-9	2014	These results demonstrate that OCT3 is responsible for metformin accumulation and secretion in salivary glands.	Metformin	55-64	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	31-35
25108167-12	2014	Interestingly, BDNF levels were found to be significantly elevated in metformin treatment group as compared to MPTP treatment mice (P&lt;0.001).	Metformin	70-79	brain derived neurotrophic factor	Mus musculus	15-19
25125398-1	2014	A high throughput LC-MS/MS method for quantification of metformin substrate uptake enables conversion of radiometric transporter inhibition assays for multidrug and toxin extrusion transporters (MATE 1 and 2) and organic cation transporter 2 (OCT2) to a nonradioactive format.	Metformin	56-65	solute carrier family 22 member 2	Homo sapiens	213-241
16505235-0	2006	Metformin restores leptin sensitivity in high-fat-fed obese rats with leptin resistance.	Metformin	0-9	leptin	Rattus norvegicus	19-25
16505235-0	2006	Metformin restores leptin sensitivity in high-fat-fed obese rats with leptin resistance.	Metformin	0-9	leptin	Rattus norvegicus	70-76
16505235-2	2006	Anorexic and fat-losing responses after intracerebroventricular leptin infusion for 7 days (15 microg daily per rat) in standard chow rats were enhanced by metformin treatment, and these responses to leptin were attenuated in high-fat-fed obese rats compared with age-matched standard chow rats.	Metformin	156-165	leptin	Rattus norvegicus	64-70
16505235-2	2006	Anorexic and fat-losing responses after intracerebroventricular leptin infusion for 7 days (15 microg daily per rat) in standard chow rats were enhanced by metformin treatment, and these responses to leptin were attenuated in high-fat-fed obese rats compared with age-matched standard chow rats.	Metformin	156-165	leptin	Rattus norvegicus	200-206
16505235-3	2006	However, these responses to leptin were corrected by metformin treatment in high-fat-fed obese rats.	Metformin	53-62	leptin	Rattus norvegicus	28-34
16505235-4	2006	Moreover, serum concentrations of leptin and insulin were decreased dramatically by leptin in metformin-treated standard chow and high-fat-fed obese rats.	Metformin	94-103	leptin	Rattus norvegicus	34-40
16505235-4	2006	Moreover, serum concentrations of leptin and insulin were decreased dramatically by leptin in metformin-treated standard chow and high-fat-fed obese rats.	Metformin	94-103	leptin	Rattus norvegicus	84-90
16505235-5	2006	The hypothalamic phosphorylated AMP-activated protein kinase level was decreased by lower leptin dose in metformin-treated rats than in untreated rats.	Metformin	105-114	leptin	Rattus norvegicus	90-96
16505235-6	2006	In an acute study, metformin treatment also increased the anorexic effect of leptin (5 microg), and this was accompanied by an increased level of phosphorylated signal transducer and activator of transcription 3 in the hypothalamus.	Metformin	19-28	leptin	Rattus norvegicus	77-83
16505235-7	2006	These results suggest that metformin enhances leptin sensitivity and corrects leptin resistance in high-fat-fed obese rats and that a combination therapy including metformin and leptin would be helpful in the treatment of obesity.	Metformin	27-36	leptin	Rattus norvegicus	46-52
16505235-7	2006	These results suggest that metformin enhances leptin sensitivity and corrects leptin resistance in high-fat-fed obese rats and that a combination therapy including metformin and leptin would be helpful in the treatment of obesity.	Metformin	27-36	leptin	Rattus norvegicus	78-84
16505235-7	2006	These results suggest that metformin enhances leptin sensitivity and corrects leptin resistance in high-fat-fed obese rats and that a combination therapy including metformin and leptin would be helpful in the treatment of obesity.	Metformin	27-36	leptin	Rattus norvegicus	78-84
16354680-7	2006	Knockdown of Raptor as well as activators of the LKB1/AMPK pathway, such as the widely used antidiabetic compound metformin, suppress IRS-1 Ser636/639 phosphorylation and reverse mTOR-mediated inhibition on PI3-kinase/Akt signaling.	Metformin	114-123	regulatory associated protein of MTOR complex 1	Homo sapiens	13-19
17065104-7	2006	In order to clarify whether the activation of AMPK is related to apoptosis in our model, we have used another AMPK stimulator, metformin, and we have analysed its effects on cell viability, nuclear morphology and AMPK activity.	Metformin	127-136	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	46-50
17065104-7	2006	In order to clarify whether the activation of AMPK is related to apoptosis in our model, we have used another AMPK stimulator, metformin, and we have analysed its effects on cell viability, nuclear morphology and AMPK activity.	Metformin	127-136	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	110-114
17065104-7	2006	In order to clarify whether the activation of AMPK is related to apoptosis in our model, we have used another AMPK stimulator, metformin, and we have analysed its effects on cell viability, nuclear morphology and AMPK activity.	Metformin	127-136	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	110-114
17065104-8	2006	Five mM metformin increased AMPK activity, inhibited viability, and increased the number of apoptotic nuclei.	Metformin	8-17	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	28-32
16836960-5	2006	Treatment with DHEA increased ovarian oxidative stress and diminished uterine nitric oxide synthase (NOS) activity; however, when metformin was administered together with DHEA, both ovarian oxidative stress and uterine NOS activity were not different from controls.	Metformin	130-139	nitric oxide synthase 1, neuronal	Mus musculus	78-99
16930507-0	2006	Obesity is associated with altered metabolic and reproductive activity in the mare: effects of metformin on insulin sensitivity and reproductive cyclicity.	Metformin	95-104	INS	Equus caballus	108-115
16503324-1	2005	BACKGROUND: Metformin hydrochloride is widely used for the treatment of type 2 diabetes mellitus (DM-2).	Metformin	12-35	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	98-102
16503324-3	2005	OBJECTIVE: The aim of this article was to report a case of serious hepatotoxicity possibly associated with metformin use in an elderly patient with DM-2.	Metformin	107-116	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	148-152
16503324-4	2005	METHODS: After receiving metformin 500 mg/d for 3 weeks, a 73-year-old Japanese woman weighing 33.5 kg with poorly controlled DM-2 presented with fatigue, jaundice, nausea, vomiting, anorexia, and abdominal pain.	Metformin	25-34	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	126-130
16503324-9	2005	CONCLUSIONS: In this case of an elderly woman with DM-2 who presented with symptoms of hepatotoxicity after 3 weeks of metformin treatment, metformin appeared to have caused a mixed-type (hepatocellular and cholestatic) hepatic damage.	Metformin	119-128	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	51-55
16503324-9	2005	CONCLUSIONS: In this case of an elderly woman with DM-2 who presented with symptoms of hepatotoxicity after 3 weeks of metformin treatment, metformin appeared to have caused a mixed-type (hepatocellular and cholestatic) hepatic damage.	Metformin	140-149	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	51-55
15983226-10	2005	Metformin also inhibited the effect of leptin on HASMC proliferation and MMP-2 expression.	Metformin	0-9	matrix metallopeptidase 2	Homo sapiens	73-78
25125398-1	2014	A high throughput LC-MS/MS method for quantification of metformin substrate uptake enables conversion of radiometric transporter inhibition assays for multidrug and toxin extrusion transporters (MATE 1 and 2) and organic cation transporter 2 (OCT2) to a nonradioactive format.	Metformin	56-65	solute carrier family 22 member 2	Homo sapiens	243-247
25246775-9	2014	However, given current safety and efficacy data, SGLT2 inhibitors may present an attractive option for T2DM patients who are failing with metformin monotherapy, especially if weight is part of the underlying treatment consideration.	Metformin	138-147	solute carrier family 5 member 2	Homo sapiens	49-54
25026071-8	2014	Similarly, the numbers of BrdU+/DCX+ and nestin+ cells in the subventricular zone were increased in metformin treated mice compared to the control (p&lt;0.05).	Metformin	100-109	doublecortin	Mus musculus	32-35
24714080-0	2014	Metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through mTOR/S6K1-mediated downregulation of c-FLIP.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	88-92
24714080-6	2014	However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway.	Metformin	9-18	ribosomal protein S6 kinase B1	Homo sapiens	38-42
24714080-6	2014	However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway.	Metformin	9-18	ribosomal protein S6 kinase B1	Homo sapiens	142-146
24714080-6	2014	However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway.	Metformin	9-18	ribosomal protein S6 kinase B1	Homo sapiens	142-146
24714080-6	2014	However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway.	Metformin	206-215	ribosomal protein S6 kinase B1	Homo sapiens	142-146
25015317-1	2014	AIMS: In search of add-on treatments to metformin, sodium-glucose cotransporter-2 (SGLT-2) inhibitors are potential candidates.	Metformin	40-49	solute carrier family 5 member 2	Homo sapiens	83-89
15899896-3	2005	The AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme that functions as a fuel sensor to regulate energy balance at both cellular and whole body levels, and it may mediate the action of anti-diabetic drugs such as metformin and peroxisome proliferator-activated receptor gamma agonists.	Metformin	227-236	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	4-32
15899896-3	2005	The AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme that functions as a fuel sensor to regulate energy balance at both cellular and whole body levels, and it may mediate the action of anti-diabetic drugs such as metformin and peroxisome proliferator-activated receptor gamma agonists.	Metformin	227-236	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	34-38
15893879-5	2005	Furthermore, SNARK activity is downregulated by metformin in a dose- and time-dependent manner in H4IIE cells.	Metformin	48-57	NUAK family kinase 2	Rattus norvegicus	13-18
15864539-0	2005	Enhanced insulin-stimulated glycogen synthesis in response to insulin, metformin or rosiglitazone is associated with increased mRNA expression of GLUT4 and peroxisomal proliferator activator receptor gamma co-activator 1.	Metformin	71-80	solute carrier family 2 member 4	Homo sapiens	146-151
15864539-8	2005	Exposure to insulin, rosiglitazone or metformin increased mRNA expression of PGC1 and GLUT4, while AICAR or 25 mmol/l glucose treatment increased GLUT1 mRNA expression.	Metformin	38-47	solute carrier family 2 member 4	Homo sapiens	86-91
15864539-9	2005	Metformin also increased mRNA expression of the MEF2 isoforms.	Metformin	0-9	myocyte enhancer factor 2A	Homo sapiens	48-52
16006730-4	2005	With regard to the type of therapy, the BNP levels were significantly lower in the combinations of both sulfonylurea and metformin and sulfonylurea and pioglitazone than those in insulin alone.	Metformin	121-130	natriuretic peptide B	Homo sapiens	40-43
15367103-13	2005	The anti-diabetic drug metformin, a known activator of AMPK, also induced the localization of GLUT2 to the luminal surface.	Metformin	23-32	solute carrier family 2 (facilitated glucose transporter), member 2	Mus musculus	94-99
15504342-9	2004	The mechanism responsible for this action, as well as its relevance to the reported anti-atherogenic actions of exercise, metformin, thiazolidinediones, and adiponectin, all of which have been shown to activate AMPK, remains to be determined.	Metformin	122-131	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	211-215
15371448-0	2004	AMP-activated protein kinase is required for the lipid-lowering effect of metformin in insulin-resistant human HepG2 cells.	Metformin	74-83	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-28
15371448-1	2004	The antidiabetic drug metformin stimulates AMP-activated protein kinase (AMPK) activity in the liver and in skeletal muscle.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	43-71
15371448-1	2004	The antidiabetic drug metformin stimulates AMP-activated protein kinase (AMPK) activity in the liver and in skeletal muscle.	Metformin	22-31	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	73-77
15371448-2	2004	To better understand the role of AMPK in the regulation of hepatic lipids, we studied the effect of metformin on AMPK and its downstream effector, acetyl-CoA carboxylase (ACC), as well as on lipid content in cultured human hepatoma HepG2 cells.	Metformin	100-109	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	113-117
15371448-3	2004	Metformin increased Thr-172 phosphorylation of the alpha subunit of AMPK in a dose- and time-dependent manner.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	68-72
15371448-9	2004	The inhibition of AMPK and the accumulation of lipids caused by high glucose concentrations were prevented either by metformin or by expressing the constitutively active AMPKalpha.	Metformin	117-126	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	18-22
15371448-13	2004	Metformin lowers hepatic lipid content by activating AMPK, thereby mediating beneficial effects in hyperglycemia and insulin resistance.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	53-57
15464987-0	2004	Reduced serum dipeptidyl peptidase-IV after metformin and pioglitazone treatments.	Metformin	44-53	dipeptidylpeptidase 4	Rattus norvegicus	14-37
15464987-6	2004	Metformin and pioglitazone significantly (P&lt;0.05) reduced serum DPP-IV activity and glycosylated hemoglobin.	Metformin	0-9	dipeptidylpeptidase 4	Rattus norvegicus	67-73
15464987-10	2004	We propose the in vivo inhibitory effects observed with metformin and pioglitazone on serum DPP-IV activity results from reduced DPP-IV secretion.	Metformin	56-65	dipeptidylpeptidase 4	Rattus norvegicus	92-98
15464987-10	2004	We propose the in vivo inhibitory effects observed with metformin and pioglitazone on serum DPP-IV activity results from reduced DPP-IV secretion.	Metformin	56-65	dipeptidylpeptidase 4	Rattus norvegicus	129-135
15531718-7	2004	Metformin acutely stimulated p44/p42 mitogen-activated protein (MAP) kinase in a dose- (3.2-fold at 1 mmol/l, P&lt; 0.05) as well as time-dependent (3.8-fold at 5 min, P&lt; 0.05) manner.	Metformin	0-9	interferon induced protein 44	Homo sapiens	29-32
15531718-12	2004	Pharmacological inhibition of p44/p42 MAP kinase prevented the metformin-induced negative effect on leptin secretion.	Metformin	63-72	interferon induced protein 44	Homo sapiens	30-33
15472203-0	2004	Increased plasma concentration of macrophage migration inhibitory factor (MIF) and MIF mRNA in mononuclear cells in the obese and the suppressive action of metformin.	Metformin	156-165	macrophage migration inhibitory factor	Homo sapiens	34-72
15472203-0	2004	Increased plasma concentration of macrophage migration inhibitory factor (MIF) and MIF mRNA in mononuclear cells in the obese and the suppressive action of metformin.	Metformin	156-165	macrophage migration inhibitory factor	Homo sapiens	74-77
15472203-0	2004	Increased plasma concentration of macrophage migration inhibitory factor (MIF) and MIF mRNA in mononuclear cells in the obese and the suppressive action of metformin.	Metformin	156-165	macrophage migration inhibitory factor	Homo sapiens	83-86
15472203-1	2004	The objective of the study was to determine whether plasma migration inhibitor factor (MIF) concentration and mononuclear cell (MNC) mRNA are elevated in obesity and whether treatment with metformin reduces plasma MIF concentration.	Metformin	189-198	macrophage migration inhibitory factor	Homo sapiens	214-217
25015317-2	2014	This meta-analysis examines the potential use of SGLT-2 inhibitors in combination with metformin as a therapeutic option for type 2 diabetes management in patients with inadequate control with metformin.	Metformin	193-202	solute carrier family 5 member 2	Homo sapiens	49-55
15506677-10	2004	CONCLUSIONS: Metformin was often ineffective in our adolescents with DM2 and compliance was a major factor.	Metformin	13-22	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	69-72
25309796-10	2014	Knock down of Vav3 enhances metformin-mediated glucose uptake.	Metformin	28-37	vav 3 oncogene	Mus musculus	14-18
25309796-12	2014	Metformin-mediated Glut4 translocation was also increased by Vav3 knock-down, suggesting that Vav3 is involved in metformin-mediated glucose uptake.	Metformin	0-9	vav 3 oncogene	Mus musculus	61-65
25309796-12	2014	Metformin-mediated Glut4 translocation was also increased by Vav3 knock-down, suggesting that Vav3 is involved in metformin-mediated glucose uptake.	Metformin	0-9	vav 3 oncogene	Mus musculus	94-98
25309796-12	2014	Metformin-mediated Glut4 translocation was also increased by Vav3 knock-down, suggesting that Vav3 is involved in metformin-mediated glucose uptake.	Metformin	114-123	vav 3 oncogene	Mus musculus	61-65
25309796-12	2014	Metformin-mediated Glut4 translocation was also increased by Vav3 knock-down, suggesting that Vav3 is involved in metformin-mediated glucose uptake.	Metformin	114-123	vav 3 oncogene	Mus musculus	94-98
24970682-9	2014	Metformin reduced heme oxygenase-1 and superoxide dismutase 2 but upregulated catalase expression in MCF-7 cells.	Metformin	0-9	heme oxygenase 1	Homo sapiens	18-34
24970682-11	2014	Furthermore, upregulation of death receptor 5 by metformin-mediated Sirt1 downregulation enhanced the sensitivity of wild-type p53 cancer cells to TRAIL-induced apoptosis.	Metformin	49-58	TNF receptor superfamily member 10b	Homo sapiens	29-45
24127429-3	2014	A second aim was to determine whether metformin treatment could rescue the age-associated decline in adipose tissue mitochondrial proteins.	Metformin	38-47	WD and tetratricopeptide repeats 1	Mus musculus	101-108
24127429-9	2014	Our findings demonstrate a co-ordinated down regulation of lipolytic, reesterification, and mitochondrial enzymes in adipose tissue with aging that is unresponsive to metformin treatment.	Metformin	167-176	WD and tetratricopeptide repeats 1	Mus musculus	117-124
24905037-8	2014	Western blot analysis revealed an increase in p-AMPK/AMPK ratio and suppressions of mTOR and Akt expressions in metformin-treated mice compared to the results in mock-treated control mice.	Metformin	112-121	mechanistic target of rapamycin kinase	Mus musculus	84-88
24657329-7	2014	All of the nine antidepressant compounds showed moderate inhibitory effects on OCT2-mediated metformin, serotonin and/or norepinephrine uptake.	Metformin	93-102	solute carrier family 22 member 2	Homo sapiens	79-83
24943040-4	2014	Here, we identified ITLN1 in human ovarian follicles and investigated the molecular mechanisms involved in the regulation of its expression in response to the insulin sensitizers metformin and rosiglitazone, in human granulosa-lutein cells (hGLCs) and in a human ovarian granulosa-like tumor cell line (KGN).	Metformin	179-188	intelectin 1	Homo sapiens	20-25
24647737-7	2014	These observations indicate that in type 2 diabetes, 1) the capacity of endogenous GIP to lower blood glucose is impaired; 2) the effect of DPP-4 inhibition on glycemia is likely to depend on adequate endogenous GLP-1 release, requiring gastric emptying &gt;2 kcal/min; and 3) the action of metformin to lower blood glucose is not predominantly by way of the incretin axis.	Metformin	291-300	dipeptidyl peptidase 4	Homo sapiens	140-145
25056111-5	2014	Low-dose metformin or SN-38 increases FOXO3 nuclear localization as well as the amount of DNA damage markers and downregulates the expression of a cancer-stemness marker CD44 and other stemness markers, including Nanog, Oct-4, and c-Myc, in these cancer cells.	Metformin	9-18	POU class 5 homeobox 1	Homo sapiens	220-225
25056111-5	2014	Low-dose metformin or SN-38 increases FOXO3 nuclear localization as well as the amount of DNA damage markers and downregulates the expression of a cancer-stemness marker CD44 and other stemness markers, including Nanog, Oct-4, and c-Myc, in these cancer cells.	Metformin	9-18	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	231-236
24970804-5	2014	Metformin inhibited adipogenesis by inhibition of key adipogenesis regulating transcription factors (CEBPalpha, CEBPss, and SREBP1), and induced AMPK.	Metformin	0-9	sterol regulatory element binding transcription factor 1	Mus musculus	124-130
24682379-2	2014	In this work we compared RCT and real-life data on the efficacy of the dipeptidyl peptidase-IV (DPP-4) inhibitor vildagliptin or sulfonylureas when added to metformin.	Metformin	157-166	dipeptidyl peptidase 4	Homo sapiens	71-94
24682379-2	2014	In this work we compared RCT and real-life data on the efficacy of the dipeptidyl peptidase-IV (DPP-4) inhibitor vildagliptin or sulfonylureas when added to metformin.	Metformin	157-166	dipeptidyl peptidase 4	Homo sapiens	96-101
24764147-1	2014	As inhibitors of organic cation transporters (OCTs), proton pump inhibitors (PPIs) may affect the plasma levels of metformin, an OCT substrate.	Metformin	115-124	plexin A2	Homo sapiens	46-49
24844317-10	2014	In corpora cavernosa (CC) from HFD, in vivo metformin (i) normalized A3 R, ADA, and AMPD1; (ii) further decreased AMPD2; (iii) increased dimethylarginine dimethylamino-hydrolase; and (iv) partially restored impaired Ach-induced relaxation.	Metformin	44-53	AMP deaminase 2	Oryctolagus cuniculus	114-119
15068958-1	2004	Activation of AMP-activated protein kinase (AMPK) by exercise and metformin is beneficial for the treatment of type 2 diabetes.	Metformin	66-75	protein kinase AMP-activated catalytic subunit alpha 1	Rattus norvegicus	44-48
15068958-2	2004	We recently found that, in cultured cells, the LKB1 tumor suppressor protein kinase activates AMPK in response to the metformin analog phenformin and the AMP mimetic drug 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).	Metformin	118-127	protein kinase AMP-activated catalytic subunit alpha 1	Rattus norvegicus	94-98
15039452-11	2004	These results demonstrate that the combination therapy of metformin with DPPIV inhibitor leads to reduced food intake and body weight gain, most likely through the significant increase of plasma GLP-1 level.	Metformin	58-67	dipeptidylpeptidase 4	Rattus norvegicus	73-78
24451322-9	2014	Metformin, an inducer of autophagy, abolished cell death induced by Rictor siRNA and cisplatin.	Metformin	0-9	RPTOR independent companion of MTOR complex 2	Homo sapiens	68-74
24889636-0	2014	Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2.	Metformin	0-9	Thioredoxin domain-containing protein	Caenorhabditis elegans	57-70
24925061-10	2014	Combination of ciglitazone and metformin further reduced PDK1 expression and promoter activity.	Metformin	31-40	pyruvate dehydrogenase kinase 1	Homo sapiens	57-61
15135305-0	2004	Metformin (Glucophage) inhibits tyrosine phosphatase activity to stimulate the insulin receptor tyrosine kinase.	Metformin	0-9	insulin receptor	Homo sapiens	79-95
15135305-0	2004	Metformin (Glucophage) inhibits tyrosine phosphatase activity to stimulate the insulin receptor tyrosine kinase.	Metformin	11-21	insulin receptor	Homo sapiens	79-95
15135305-1	2004	Metformin is a commonly used anti-diabetic but whether its mechanism involves action on the insulin receptor or on downstream events is still controversial.	Metformin	0-9	insulin receptor	Homo sapiens	92-108
15135305-2	2004	With a time course that was slow compared with insulin action, metformin increased tyrosine phosphorylation of the regulatory domain of the insulin receptor (specifically, tyrosine residues 1150 and 1151).	Metformin	63-72	insulin receptor	Homo sapiens	140-156
15135305-3	2004	In a direct action, therapeutic levels of metformin stimulated the tyrosine kinase activity of the soluble intracellular portion of the beta subunit of the human insulin receptor toward a substrate derived from the insulin receptor regulatory domain.	Metformin	42-51	insulin receptor	Homo sapiens	162-178
15135305-3	2004	In a direct action, therapeutic levels of metformin stimulated the tyrosine kinase activity of the soluble intracellular portion of the beta subunit of the human insulin receptor toward a substrate derived from the insulin receptor regulatory domain.	Metformin	42-51	insulin receptor	Homo sapiens	215-231
15135305-6	2004	In an indirect stimulation of the insulin receptor, metformin inhibited endogenous tyrosine phosphatases and purified human protein tyrosine phosphatase 1B that dephosphorylate and inhibit the insulin receptor kinase.	Metformin	52-61	insulin receptor	Homo sapiens	34-50
15135305-6	2004	In an indirect stimulation of the insulin receptor, metformin inhibited endogenous tyrosine phosphatases and purified human protein tyrosine phosphatase 1B that dephosphorylate and inhibit the insulin receptor kinase.	Metformin	52-61	insulin receptor	Homo sapiens	193-209
15135305-7	2004	Thus, there was evidence that metformin acted directly upon the insulin receptor and indirectly through inhibition of tyrosine phosphatases.	Metformin	30-39	insulin receptor	Homo sapiens	64-80
15044053-9	2004	These results suggest that GLP-2 is co-secreted with GLP-1 flollowing biguanide stimulation, and that the combination of metformin with a DPPIV inhibitor might a useful oral treatment for gastrointestinal damage, based on GLP-2 actions.	Metformin	121-130	glucagon-like peptide 2 receptor	Mus musculus	222-227
14502098-3	2003	Experimental studies show that metformin-mediated improvements in insulin sensitivity may be associated with several mechanisms, including increased insulin receptor tyrosine kinase activity, enhanced glycogen synthesis, and an increase in the recruitment and activity of GLUT4 glucose transporters.	Metformin	31-40	solute carrier family 2 member 4	Homo sapiens	272-277
12769787-1	2003	Although a number of assessments disagree, the preponderance of the evidence indicates that the major therapeutic action of metformin in type 2 diabetes (DM2) is on the liver, and glucose production (EGP) in particular.	Metformin	124-133	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	154-157
12769787-9	2003	Sites of metformin action can therefore be considered as a compilation of valid therapeutic targets in DM2.	Metformin	9-18	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	103-106
12769787-12	2003	(iii) unifying concepts: reported actions of metformin on the mitochondrial respiratory chain, free fatty acid metabolism, AMP-activated protein kinase, and on membrane proteins directly may all explain subsets of actions that are seen, providing more integrated targets for consideration in the therapy of DM2.	Metformin	45-54	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	307-310
12803833-0	2003	Urinary PC-1 and N-acetyl-beta-D-glucosaminidase activity in patients with type 2 diabetes treated with metformin, gliclazide or glibenclamide.	Metformin	104-113	O-GlcNAcase	Homo sapiens	17-48
12419322-2	2002	There are two possible mechanisms for this effect: (1) metformin inhibits dipeptidyl peptidase IV (DPPIV), an enzyme degrading GLP-1, and (2) metformin enhances GLP-1 secretion.	Metformin	55-64	dipeptidylpeptidase 4	Rattus norvegicus	74-97
12419322-2	2002	There are two possible mechanisms for this effect: (1) metformin inhibits dipeptidyl peptidase IV (DPPIV), an enzyme degrading GLP-1, and (2) metformin enhances GLP-1 secretion.	Metformin	55-64	dipeptidylpeptidase 4	Rattus norvegicus	99-104
12419322-5	2002	Metformin treatment (30, 100, and 300mg/kg) increased plasma active GLP-1 levels dose-dependently in DPPIV-deficient F344/DuCrj rats (approximately 1.6-fold at 3 and 5h after administration of 300mg/kg).	Metformin	0-9	dipeptidylpeptidase 4	Rattus norvegicus	101-106
12419322-8	2002	In DPPIV-positive F344/Jcl rats, coadministration of metformin (300mg/kg) and valine-pyrrolidide (30mg/kg) resulted in elevation of plasma active GLP-1, but neither metformin nor valine-pyrrolidide treatment alone had any effect.	Metformin	53-62	dipeptidylpeptidase 4	Rattus norvegicus	3-8
11994296-0	2002	The Anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways.	Metformin	42-51	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	62-90
11994296-5	2002	In muscle cells, both hyperosmotic stress and the anti-diabetic agent, metformin, activate AMPK in the absence of any increase in the AMP:ATP ratio.	Metformin	71-80	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	91-95
11712407-5	2001	In clinical study, RSG, alone or in combination with other diabetic agents(metformin or sulphonylurea), produces significant improvements in HbA1c levels with type 2 diabetes mellitus.	Metformin	75-84	hemoglobin subunit alpha 1	Homo sapiens	141-145
11602624-6	2001	Activation of AMPK by metformin or an adenosine analogue suppresses expression of SREBP-1, a key lipogenic transcription factor.	Metformin	22-31	sterol regulatory element binding transcription factor 1	Rattus norvegicus	82-89
11602624-7	2001	In metformin-treated rats, hepatic expression of SREBP-1 (and other lipogenic) mRNAs and protein is reduced; activity of the AMPK target, ACC, is also reduced.	Metformin	3-12	sterol regulatory element binding transcription factor 1	Rattus norvegicus	49-56
11601679-1	2001	Metformin reduces blood glucose levels predominantly by inhibiting hepatic gluconeogenesis, although it also may enhance insulin receptor number or activity.	Metformin	0-9	insulin receptor	Homo sapiens	121-137
11525086-7	2001	Combination therapy with sulphonylurea derivatives or metformin seems to be more effective, i.e. lower dosages of either agent or both are sufficient to achieve the same reduction in plasma glucose and HbA1c as monotherapy.	Metformin	54-63	hemoglobin subunit alpha 1	Homo sapiens	202-206
24717679-3	2014	In the present study, the anti-oxidative potential of metformin and its potential mechanisms were investigated in a mouse model with carbon tetrachloride (CCl2)-induced severe oxidative liver injury.	Metformin	54-63	chemokine (C-C motif) ligand 2	Mus musculus	155-159
24717679-4	2014	Our results showed that treatment with metformin significantly attenuated CCl2-induced elevation of serum aminotransferases and hepatic histological abnormalities.	Metformin	39-48	chemokine (C-C motif) ligand 2	Mus musculus	74-78
24717679-6	2014	In addition, metformin treatment dose-dependently enhanced the activities of catalase (CAT) and decreased CCl4-induced elevation of hepatic H2O2 levels, but it had no obvious effects on the protein level of CAT.	Metformin	13-22	chemokine (C-C motif) ligand 4	Mus musculus	106-110
24717679-9	2014	These data suggested that metformin effectively alleviated CCl4-induced oxidative liver injury in mice and these hepatoprotective effects might be associated with CAT.	Metformin	26-35	chemokine (C-C motif) ligand 4	Mus musculus	59-63
24797033-14	2014	Metformin improved insulin resistance and reversed liver injury through the activation of AMPK and normalized adiponectin signaling making metformin a promising drug for the treatment of ALD.	Metformin	0-9	adiponectin, C1Q and collagen domain containing	Rattus norvegicus	110-121
24797033-14	2014	Metformin improved insulin resistance and reversed liver injury through the activation of AMPK and normalized adiponectin signaling making metformin a promising drug for the treatment of ALD.	Metformin	139-148	adiponectin, C1Q and collagen domain containing	Rattus norvegicus	110-121
26327848-9	2014	A statistically significant increase in the number of apoptotic cells after 48 and 72 hours" treatment with metformin relative to a control cells seems to be correlated with a decrease in the expression of the BIRC5 gene at the mRNA level.	Metformin	108-117	baculoviral IAP repeat containing 5	Homo sapiens	210-215
11252980-7	2001	Metformine should be prescribed if the HbA1c is above normal in order to achieve the demonstrated benefit in prevention of microangiopathy and in the hope, motivated by pathophysiology data, of preventing insulin failure.	Metformin	0-10	hemoglobin subunit alpha 1	Homo sapiens	39-43
11220991-3	2000	Clinical trial data involving over 4500 patients with type 2 diabetes suggest it is effective both as monotherapy and in combination with sulphonylureas, metformin and insulin, producing both significant falls in HbA1c and favourable improvements in lipid parameters.	Metformin	154-163	hemoglobin subunit alpha 1	Homo sapiens	213-217
11068959-0	2000	Effects of metformin and vanadium on leptin secretion from cultured rat adipocytes.	Metformin	11-20	leptin	Rattus norvegicus	37-43
24997826-1	2014	OBJECTIVE: To compare the effects of piglitazone and metformin on retinol-binding protein-4 (RBP-4) and adiponcetin (APN) in patients with type 2 diabetes mellitus (T2DM) complicated with Non alcohol fatty acid liver disease (NAFLD).	Metformin	53-62	retinol binding protein 4	Homo sapiens	66-91
24843782-0	2014	Pioglitazone and metformin are equally effective in reduction of chemerin in patients with type 2 diabetes.	Metformin	17-26	retinoic acid receptor responder 2	Homo sapiens	65-73
11068959-9	2000	Across metformin doses, leptin secretion was inversely related to the percentage of glucose taken up and released as lactate (r = -0.74; p &lt; 0.0001).	Metformin	7-16	leptin	Rattus norvegicus	24-30
11068959-12	2000	DISCUSSION: Both metformin and vanadium increase glucose uptake and inhibit leptin secretion from cultured adipocytes.	Metformin	17-26	leptin	Rattus norvegicus	76-82
11068959-13	2000	The inhibition of leptin secretion by metformin is related to an increase in the metabolism of glucose to lactate.	Metformin	38-47	leptin	Rattus norvegicus	18-24
9514089-0	1998	Stimulation of the intracellular portion of the human insulin receptor by the antidiabetic drug metformin.	Metformin	96-105	insulin receptor	Homo sapiens	54-70
9514089-2	1998	We now report that therapeutic concentrations (approximately 1 microg/mL) of metformin stimulated the tyrosine kinase activity of the intracellular portion of the beta-subunit of the human insulin receptor (IPbetaIRK), the intracellular portion of the epidermal growth factor receptor and pp60-src, but not cAMP-dependent protein kinase.	Metformin	77-86	insulin receptor	Homo sapiens	189-205
9398716-10	1997	They also indicate that decreasing serum insulin with metformin reduces ovarian cytochrome P450c17 alpha activity and ameliorates the hyperandrogenism of these women.	Metformin	54-63	cytochrome P450 family 17 subfamily A member 1	Homo sapiens	91-98
9137903-5	1997	Since both body weight and plasma glucose concentrations were similar before and after treatment, the effect of metformin on insulin-receptor binding and tyrosine kinase activity appeared to be independent of either of these variables.	Metformin	112-121	insulin receptor	Homo sapiens	125-141
9109854-6	1997	Metformin decreases Izero in hyperinsulinemic PCOS patients, reverses the hyperinsulinemia-driven endocrinopathy, decreases PAI-1, and decreases Lp(a), and should thus reduce the increased risk of atherothrombosis in PCOS.	Metformin	0-9	lipoprotein(a)	Homo sapiens	145-150
8875085-10	1996	After metformin treatment, the decrease in blood pressure after L-arginine infusion was significantly enhanced, with a maximal decrease of sBP of 12 +/- 3.4 mmHg (8 +/- 2.5 mmHg pretreatment, P &lt; 0.05) and dBP of 9.5 +/- 2.4 mmHg (4.5 +/- 1.9 mmHg pretreatment, P &lt; 0.01).	Metformin	6-15	selenium binding protein 1	Homo sapiens	139-142
8687515-11	1996	CONCLUSIONS: In obese women with the polycystic ovary syndrome, decreasing serum insulin concentrations with metformin reduces ovarian cytochrome P450c17 alpha activity and ameliorates hyperandrogenism.	Metformin	109-118	cytochrome P450 family 17 subfamily A member 1	Homo sapiens	146-153
7835271-0	1995	Action of metformin on glucose transport and glucose transporter GLUT1 and GLUT4 in heart muscle cells from healthy and diabetic rats.	Metformin	10-19	solute carrier family 2 member 1	Rattus norvegicus	65-70
7835271-6	1995	Like insulin, metformin caused an approximately 1.6-fold increase in the content of both glucose transporter isoforms GLUT1 and GLUT4 in the plasma membrane of cardiac myocytes, with a corresponding decrease in an intracellular membrane fraction.	Metformin	14-23	solute carrier family 2 member 1	Rattus norvegicus	118-123
7843470-3	1994	Metformin gave better fasting plasma glucose control compared to glipizide at 24 (p &lt; 0.01), 36 (p &lt; 0.05) and 52 weeks (p &lt; 0.05) with a lower HbA1 concentration at 52 weeks (p &lt; 0.05).	Metformin	0-9	hemoglobin subunit alpha 1	Homo sapiens	153-157
1679326-3	1991	We measured amylin secretion from HIT T15 beta-cells exposed to glucose, arginine, glucagon, somatostatin, tolbutamide, glyburide, or metformin.	Metformin	134-143	islet amyloid polypeptide	Mesocricetus auratus	12-18
1936482-2	1991	The addition of both insulin and metformin treatment significantly improved fasting plasma glucose, post-prandial plasma glucose and %HbA1.	Metformin	33-42	hemoglobin subunit alpha 1	Homo sapiens	134-138
24843782-2	2014	We investigated the effects of pioglitazone and metformin, two commonly prescribed antidiabetic agents, on the reduction of serum chemerin concentrations.	Metformin	48-57	retinoic acid receptor responder 2	Homo sapiens	130-138
24843782-9	2014	Similarly, metformin caused a significant drop in chemerin concentrations at week 12 (P = 0.015).	Metformin	11-20	retinoic acid receptor responder 2	Homo sapiens	50-58
24843782-10	2014	When compared, metformin and pioglitazone proved to be equally effective in the alleviation of chemerin concentrations (P = 0.895, effect size: 0.1%).	Metformin	15-24	retinoic acid receptor responder 2	Homo sapiens	95-103
24843782-11	2014	CONCLUSIONS: The present findings show that pioglitazone and metformin have comparable efficacy on serum chemerin concentrations, albeit through different mechanisms.	Metformin	61-70	retinoic acid receptor responder 2	Homo sapiens	105-113
24059314-7	2014	Some drug agonists of AMPK are known to mimic these effects such as metformin or resveratrol, a polyphenol extracted from plants and present in red wine, a component of the French paradox related diet.	Metformin	68-77	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	22-26
24405721-10	2014	Metformin augmented hypertonicity-induced apoptosis of RMIC, suppressed the nuclear factor-kappaB/cyclo-oxygenase-2 pathway, reduced reactive oxygen species production and inhibited transcriptional activation of tonicity-responsive enhancer binding protein (TonEBP) and its downstream osmoprotective gene expression.	Metformin	0-9	nuclear factor of activated T cells 5	Mus musculus	212-256
24405721-10	2014	Metformin augmented hypertonicity-induced apoptosis of RMIC, suppressed the nuclear factor-kappaB/cyclo-oxygenase-2 pathway, reduced reactive oxygen species production and inhibited transcriptional activation of tonicity-responsive enhancer binding protein (TonEBP) and its downstream osmoprotective gene expression.	Metformin	0-9	nuclear factor of activated T cells 5	Mus musculus	258-264
24490835-7	2014	In the 11-study saxagliptin + metformin pool, the IRR for MACE was 0.93 (0.44, 1.99).	Metformin	30-39	insulin receptor related receptor	Homo sapiens	50-53
24505341-6	2014	Importantly, metformin was preferentially cytotoxic to CD44(high)/CD24(low) cells of MCF-7 cells and, CD44(high)/CD24(high) cells of MIA PaCa-2 cells, which are known to be cancer stem cells (CSCs) of MCF-7 cells and MIA PaCa-2 cells, respectively.	Metformin	13-22	CD44 molecule (Indian blood group)	Homo sapiens	55-59
24728163-0	2014	Impact of metformin treatment and swimming exercise on visfatin levels in high-fat-induced obesity rats.	Metformin	10-19	nicotinamide phosphoribosyltransferase	Rattus norvegicus	55-63
2060439-4	1991	RESULTS: Mean HbA1 fell from 11.7 +/- 0.4 to 10.3 +/- 0.4% (means +/- SE) on metformin but rose from 11.8 +/- 0.4 to 13.3 +/- 0.4% on placebo (P less than 0.001).	Metformin	77-86	hemoglobin subunit alpha 1	Homo sapiens	14-18
2060439-9	1991	CONCLUSIONS: Metformin achieved a 23% lower mean HbA1 than placebo without weight gain or significant unwanted effects.	Metformin	13-22	hemoglobin subunit alpha 1	Homo sapiens	49-53
33797562-6	2021	In vitro studies suggest that metformin directly stimulates osteoblasts differentiation and may inhibit osteoclastogenesis by increasing osteoprotegerin expression, both through activation of the AMPK signaling pathway.	Metformin	30-39	TNF receptor superfamily member 11b	Homo sapiens	137-152
33797562-6	2021	In vitro studies suggest that metformin directly stimulates osteoblasts differentiation and may inhibit osteoclastogenesis by increasing osteoprotegerin expression, both through activation of the AMPK signaling pathway.	Metformin	30-39	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	196-200
33808727-11	2021	In chondrocytes from OA patients, metformin reduced catabolic factor gene expression and inflammatory cell death factor expression, increased LC3IIb, p62, and LAMP1 expression, and induced an autophagy-lysosome fusion phenotype.	Metformin	34-43	lysosomal associated membrane protein 1	Homo sapiens	159-164
24728163-3	2014	We aim to investigate the impact of metformin treatment and/or swimming exercise on serum visfatin and visfatin levels in subcutaneous adipose tissue (SAT), peri-renal adipose tissue (PAT) and skeletal muscle (SM) of high-fat-induced obesity rats.	Metformin	36-45	nicotinamide phosphoribosyltransferase	Rattus norvegicus	90-98
24728163-3	2014	We aim to investigate the impact of metformin treatment and/or swimming exercise on serum visfatin and visfatin levels in subcutaneous adipose tissue (SAT), peri-renal adipose tissue (PAT) and skeletal muscle (SM) of high-fat-induced obesity rats.	Metformin	36-45	nicotinamide phosphoribosyltransferase	Rattus norvegicus	103-111
24728163-9	2014	Both metformin and swimming exercise down-regulated visfatin levels in SAT and PAT, while the adjunctive therapy conferred greater benefits, but no changes of visfatin levels were observed in SM.	Metformin	5-14	nicotinamide phosphoribosyltransferase	Rattus norvegicus	52-60
24728163-10	2014	CONCLUSION: Our results indicate that visfatin down-regulation in SAT and PAT may be one of the mechanisms by which metformin and swimming exercise inhibit obesity.	Metformin	116-125	nicotinamide phosphoribosyltransferase	Rattus norvegicus	38-46
24233023-7	2014	In addition, insulin receptor substrate 2 gene depletion blocked metformin-enhanced beta-catenin translocation.	Metformin	65-74	catenin (cadherin associated protein), beta 1	Mus musculus	84-96
24196830-8	2014	Furthermore, treatment with metformin led to activation of epidermal AMP-activated protein kinase (AMPK) and attenuated signaling through mTOR complex (mTORC)-1 and p70S6K.	Metformin	28-37	ribosomal protein S6 kinase, polypeptide 1	Mus musculus	165-171
24791887-9	2014	Both genes and protein expression of NF-kappaB, MCP-1, ICAM-1, TGF-beta1 of MCs induced by high glucose were markedly reduced after metformin treatment in a dose-dependent manner (P &lt; 0.05).	Metformin	132-141	intercellular adhesion molecule 1	Rattus norvegicus	55-61
24601227-5	2014	Furthermore, western blot analysis showed that metformin suppressed the overexpression of the endoplasmic reticulum stress (ERS) markers cleaved caspase-12 and CEBP-homologous protein induced by ISO and increased the phosphorylation of AMP-activated protein kinase (AMPK).	Metformin	47-56	caspase 12	Rattus norvegicus	145-155
24026623-3	2013	However, vandetanib was an even more potent inhibitor of MATE1- and MATE2K-mediated uptake of MPP(+) (IC(50) of 1.23 +- 0.05 and 1.26 +- 0.06 microM, respectively) and metformin (IC(50) of 0.16 +- 0.05 and 0.30 +- 0.09 microM, respectively).	Metformin	168-177	solute carrier family 47 member 1	Homo sapiens	57-62
24185692-0	2013	Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin.	Metformin	112-121	acetyl-Coenzyme A carboxylase beta	Mus musculus	41-45
24466367-9	2013	These results suggest that biologic effects of metformin are mediated through decreased CSC markers cluster of differentiation 44 (CD44 and CD133), aldehyde dehydrogenase isoform 1 (ALDH1), and epithelial cell adhesion molecule (EPCAM) and modulation of the mTOR signaling pathway.	Metformin	47-56	CD44 antigen	Mus musculus	131-135
24466367-9	2013	These results suggest that biologic effects of metformin are mediated through decreased CSC markers cluster of differentiation 44 (CD44 and CD133), aldehyde dehydrogenase isoform 1 (ALDH1), and epithelial cell adhesion molecule (EPCAM) and modulation of the mTOR signaling pathway.	Metformin	47-56	prominin 1	Mus musculus	140-145
23831117-14	2013	Further, the SNARK kinase inhibitor metformin suppressed both HCV replication and SNARK-mediated enhancement of TGF-beta signaling.	Metformin	36-45	NUAK family kinase 2	Homo sapiens	13-18
23831117-14	2013	Further, the SNARK kinase inhibitor metformin suppressed both HCV replication and SNARK-mediated enhancement of TGF-beta signaling.	Metformin	36-45	NUAK family kinase 2	Homo sapiens	82-87
24041694-0	2013	Metformin-induced inhibition of the mitochondrial respiratory chain increases FGF21 expression via ATF4 activation.	Metformin	0-9	activating transcription factor 4	Homo sapiens	99-103
24041694-6	2013	Importantly, inhibition of mitochondrial complex I activity by metformin resulted in FGF21 induction through PKR-like ER kinase (PERK)-eukaryotic translation factor 2alpha (eIF2alpha)-activating transcription factor 4 (ATF4).	Metformin	63-72	activating transcription factor 4	Homo sapiens	219-223
24041694-9	2013	In conclusion, our results indicate that metformin induced expression of FGF21 through an ATF4-dependent mechanism by inhibiting mitochondrial respiration independently of AMPK.	Metformin	41-50	activating transcription factor 4	Homo sapiens	90-94
23906870-10	2013	The antidiabetic drug metformin reduces cellular and soluble chemerin in PHH as has already been described in adipose tissue.	Metformin	22-31	retinoic acid receptor responder 2	Homo sapiens	61-69
33815295-8	2021	Decreasing insulin resistance, reduction of some inflammatory cytokines like IL-6 and TNF-alpha, modulation of angiotensin-converting enzyme 2 (ACE2) receptor, and improving neutrophil to lymphocyte ratio are some of the potential mechanisms of metformin in COVID-19 patients with DM.	Metformin	245-254	angiotensin converting enzyme 2	Homo sapiens	111-142
33807522-2	2021	Metformin mainly activates adenosine monophosphate-activated protein kinase (AMPK) in the liver which leads to suppression of fatty acid synthesis and gluconeogenesis.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	27-75
33807522-2	2021	Metformin mainly activates adenosine monophosphate-activated protein kinase (AMPK) in the liver which leads to suppression of fatty acid synthesis and gluconeogenesis.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	77-81
33807522-3	2021	Metformin activates AMPK in skeletal muscle as well, which increases translocation of glucose transporter 4 to the cell membrane and thereby increases glucose uptake.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	20-24
33807522-9	2021	Metformin suppresses the mechanistic target of rapamycin (mTOR) by activating AMPK in pre-neoplastic cells, which leads to suppression of cell growth and an increase in apoptosis in pre-neoplastic cells.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	78-82
33236135-0	2021	Metformin induces apoptosis and inhibits migration by activating the AMPK/p53 axis and suppressing PI3K/AKT signaling in human cervical cancer cells.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	69-73
33236135-5	2021	Following metformin treatment, the protein expression levels of p-AMP-activated protein kinase (p-AMPK), which promotes cell death, and the tumor suppressor protein p-p53 were remarkably upregulated in CaSki and C33A cells compared with the control group.	Metformin	10-19	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	98-102
33236135-7	2021	Compound C (an AMPK inhibitor) significantly reversed the effects of metformin on CaSki, C33A and HeLa cell viability, and AMPK and p53 phosphorylation.	Metformin	69-78	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	15-19
33236135-8	2021	The results of the present study suggested that metformin induced AMPK-mediated apoptosis, thus metformin may serve as a chemotherapeutic agent for human cervical cancer.	Metformin	48-57	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	66-70
33236135-8	2021	The results of the present study suggested that metformin induced AMPK-mediated apoptosis, thus metformin may serve as a chemotherapeutic agent for human cervical cancer.	Metformin	96-105	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	66-70
33234131-4	2020	This could be due to the effects of metformin on preventing the structural and electrical remodeling of left atrium via attenuating intracellular reactive oxygen species, activating 5" adenosine monophosphate-activated protein kinase, improving calcium homeostasis, attenuating inflammation, increasing connexin-43 gap junction expression, and restoring small conductance calcium-activated potassium channels current.	Metformin	36-45	gap junction protein alpha 1	Homo sapiens	303-314
33234131-5	2020	For ventricular arrhythmias, in vivo reports demonstrated that activation of 5" adenosine monophosphate-activated protein kinase and phosphorylated connexin-43 by metformin played a key role in ischemic ventricular arrhythmias reduction.	Metformin	163-172	gap junction protein alpha 1	Homo sapiens	148-159
23873119-0	2013	A gene-gene interaction between polymorphisms in the OCT2 and MATE1 genes influences the renal clearance of metformin.	Metformin	108-117	POU class 2 homeobox 2	Homo sapiens	53-57
23873119-0	2013	A gene-gene interaction between polymorphisms in the OCT2 and MATE1 genes influences the renal clearance of metformin.	Metformin	108-117	solute carrier family 47 member 1	Homo sapiens	62-67
23873119-1	2013	OBJECTIVE: The aim of this study was to determine the association between the renal clearance (CL(renal)) of metformin in healthy Caucasian volunteers and the single-nucleotide polymorphism (SNP) c.808G&gt;T (rs316019) in OCT2 as well as the relevance of the gene-gene interactions between this SNP and (a) the promoter SNP g.-66T&gt;C (rs2252281) in MATE1 and (b) the OCT1 reduced-function diplotypes.	Metformin	109-118	POU class 2 homeobox 2	Homo sapiens	222-226
23873119-1	2013	OBJECTIVE: The aim of this study was to determine the association between the renal clearance (CL(renal)) of metformin in healthy Caucasian volunteers and the single-nucleotide polymorphism (SNP) c.808G&gt;T (rs316019) in OCT2 as well as the relevance of the gene-gene interactions between this SNP and (a) the promoter SNP g.-66T&gt;C (rs2252281) in MATE1 and (b) the OCT1 reduced-function diplotypes.	Metformin	109-118	solute carrier family 47 member 1	Homo sapiens	351-356
23824960-0	2013	Central administration of metformin into the third ventricle of C57BL/6 mice decreases meal size and number and activates hypothalamic S6 kinase.	Metformin	26-35	ribosomal protein S6 kinase, polypeptide 1	Mus musculus	135-144
25897192-0	2015	Metformin With Either Histamine H2-Receptor Antagonists or Proton Pump Inhibitors: A Polypharmacy Recipe for Neuropathy via Vitamin B12 Depletion.	Metformin	0-9	histamine receptor H2	Homo sapiens	22-43
25590243-6	2015	We found that metformin was able to restore the increased levels of vascular endothelial growth factor, angiopoietin (ANGPT)1, and ANGPT1/ANGPT2 ratio and the decreased levels of platelet-derived growth factor B and platelet-derived growth factor D observed in the dehydroepiandrosterone-treated rats.	Metformin	14-23	angiopoietin 2	Rattus norvegicus	138-144
20668229-2	2010	We show in our current study that the LKB1/AMPK/TSC tumor suppressor axis is functional in AML and can be activated by the biguanide molecule metformin, resulting in a specific inhibition of mammalian target of rapamycin (mTOR) catalytic activity.	Metformin	142-151	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	43-47
34309806-7	2022	RESULTS: A single passive transport coefficient, k = 0.044 +- 0.014 (h-1), can be applied, describing the uptake and release transport rate versus the linear equation v = k x (Mpl - MRBC), where Mpl is the metformin concentration in plasma and MRBC is the metformin concentration in RBCs.	Metformin	256-265	MRBC	Homo sapiens	244-248
34718940-5	2022	METHODS AND RESULTS: In this context, we created a full-thickness excisional wound model in Wistar albino rats and, investigated NF-kappaB p65 DNA-binding activity and expression levels of RELA (p65), MMP2 and MMP9 in wound samples taken on days 0, 3, 7, and 14 from diabetic/non-diabetic rats treated with metformin and saline.	Metformin	307-316	matrix metallopeptidase 2	Rattus norvegicus	201-205
34718940-6	2022	As a result of our study, we showed that topically applied metformin accelerates wound healing by suppressing NF-kappaB p65 activity and diminishing the expression of MMP2 and MMP9.	Metformin	59-68	matrix metallopeptidase 2	Rattus norvegicus	167-171
34910358-9	2022	Metformin upregulated CD31 expression and suppressed inflammation in the lung of mice exposed to hyperoxia on postnatal days 7 and 14.	Metformin	0-9	platelet/endothelial cell adhesion molecule 1	Mus musculus	22-26
34910358-10	2022	Metformin downregulated Gli1 expression in macrophages in the lung after exposure to hyperoxia on postnatal day 14.	Metformin	0-9	GLI-Kruppel family member GLI1	Mus musculus	24-28
34910358-11	2022	In vitro studies showed that metformin inhibited Gli1 expression in RAW264.7 macrophages exposed to 90% oxygen, which was reversed after purmorphamine pretreatment.	Metformin	29-38	GLI-Kruppel family member GLI1	Mus musculus	49-53
23824960-8	2013	Compared with the control, I3V administration of metformin significantly increased phosphorylation of S6K at Thr(389) and AMPK at Ser(485/491) in the mediobasal hypothalamus, while AMPK phosphorylation at Thr(172) was not significantly altered.	Metformin	49-58	ribosomal protein S6 kinase, polypeptide 1	Mus musculus	102-105
23824960-10	2013	These results suggest that the reduction in food intake induced by the central administration of metformin in the mice may be mediated by activation of S6K pathway.	Metformin	97-106	ribosomal protein S6 kinase, polypeptide 1	Mus musculus	152-155
23786968-10	2013	CONCLUSION: Intolerance to metformin represents an unforeseen phenotype in T2DM patients characterized by a low rate of ischaemic heart disease, left-handedness, ABO group imbalance and an iron load.	Metformin	27-36	ABO, alpha 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase	Homo sapiens	162-165
23666872-5	2013	OCTN1-mediated uptake of metformin was observed in human embryonic kidney 293 cells transfected with mouse OCTN1 gene, but much lower than the uptake of the typical substrate [(3) H]ergothioneine (ERGO).	Metformin	25-34	solute carrier family 22 member 4	Homo sapiens	0-5
23464532-0	2013	Dose-ranging study with the glucokinase activator AZD1656 in patients with type 2 diabetes mellitus on metformin.	Metformin	103-112	glucokinase	Homo sapiens	28-39
34887495-7	2021	Gene augmentation of L-ORD-iRPE with WT CTRP5 or modulation of AMPK, by metformin, re-sensitize L-ORD-iRPE to changes in cellular energy status alleviating the disease cellular phenotypes.	Metformin	72-81	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	63-67
34851228-7	2021	Metformin could restore the isoflurane- and STZ-induced hippocampal tissue damage, cognitive and memory impairment in exposed space via improving the oxidative stress, upregulating the contents of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in the hippocampus tissues of diabetic mice.	Metformin	0-9	glucagon	Mus musculus	197-220
34851228-7	2021	Metformin could restore the isoflurane- and STZ-induced hippocampal tissue damage, cognitive and memory impairment in exposed space via improving the oxidative stress, upregulating the contents of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in the hippocampus tissues of diabetic mice.	Metformin	0-9	glucagon	Mus musculus	222-227
34851228-8	2021	Furthermore, chronic treatment of metformin significantly down-regulated the expression of AGEs, RAGE, pNF-kappaB, iNOS, and COX-2.	Metformin	34-43	cytochrome c oxidase II, mitochondrial	Mus musculus	125-130
34530523-7	2021	The I/R group had significantly higher JNK, p38 MAPK, Bax, caspase-3, and NF-kappaB levels, and lower ERK and Bcl-2 levels in the bladder than the sham-operated group; these changes were significantly ameliorated by metformin and/or sildenafil treatment.	Metformin	216-225	caspase 3	Rattus norvegicus	59-68
34850372-3	2022	Metformin activates AMP-activated kinase (AMPK), which inhibits mechanistic target of rapamycin complex 1 (mTORC1) signaling.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	107-113
34850372-5	2022	Thus, we hypothesized that metformin may attenuate ketamine- or scopolamine-induced antidepressant efficacies by blocking their mTORC1 activation.	Metformin	27-36	CREB regulated transcription coactivator 1	Mus musculus	128-134
34850372-9	2022	Although metformin reduced mTORC1 downstream activated P70S6K, it did not significantly alter mTORser2448 activation and even increased BDNF expression.	Metformin	9-18	CREB regulated transcription coactivator 1	Mus musculus	27-33
34881181-7	2021	PD-L1 expression in ESCC cell lines was significantly inhibited by metformin via the IL-6/JAK2/STAT3 signaling pathway but was not correlated with the canonical AMPK pathway.	Metformin	67-76	Janus kinase 2	Homo sapiens	90-94
34881181-9	2021	Animal experiments confirmed that metformin downregulated PD-L1 expression and that combination treatment with metformin and PD-1 inhibitors synergistically enhanced the antitumor response.	Metformin	34-43	programmed cell death 1	Homo sapiens	125-129
34881181-10	2021	Conclusions: Metformin downregulated PD-L1 expression by blocking the IL-6/JAK2/STAT3 signaling pathway in ESCC, which enhanced the antitumor immune response.	Metformin	13-22	Janus kinase 2	Homo sapiens	75-79
34761355-1	2022	PURPOSE: Metformin induces GLUT-4 mRNA expression in insulin target tissues in PCOS.	Metformin	9-18	solute carrier family 2 member 4	Homo sapiens	27-33
34761355-3	2022	We aimed to compare the effect of metformin withdrawal on GLUT-4 mRNA expression in subcutaneous adipose tissue after prior short (ST, 1 year, N = 11) and long term (LT, at least 3 years, N = 13) treatment in obese PCOS women.	Metformin	34-43	solute carrier family 2 member 4	Homo sapiens	58-64
34975134-6	2021	Hypoglycemic activity of a combination of glimepiride + metformin was enhanced when losartan was co-administered as a single dosage schedule as well as a multiple dose schedule as indicated by a reduced blood glucose level and enhanced levels of insulin in rats as well as in rabbits.	Metformin	56-65	insulin	Oryctolagus cuniculus	246-253
6350337-7	1983	It is suggested, therefore, that the action of metformin on the insulin receptor may be one of the mechanisms of the antidiabetic effect of this drug.	Metformin	47-56	insulin receptor	Homo sapiens	64-80
23827952-1	2013	Metformin has been reported to increase the expression of the glucagon-like peptide-1 (GLP-1) receptor in pancreatic beta cells in a peroxisome proliferator-activated receptor (PPAR)-alpha-dependent manner.	Metformin	0-9	glucagon	Rattus norvegicus	62-85
23827952-1	2013	Metformin has been reported to increase the expression of the glucagon-like peptide-1 (GLP-1) receptor in pancreatic beta cells in a peroxisome proliferator-activated receptor (PPAR)-alpha-dependent manner.	Metformin	0-9	glucagon-like peptide 1 receptor	Rattus norvegicus	87-102
23827952-6	2013	Metformin increased the expression of the GLP-1 receptor in pancreatic islets, whereas fenofibrate did not.	Metformin	0-9	glucagon-like peptide 1 receptor	Rattus norvegicus	42-56
23819460-5	2013	METHODS: Effect of the activation of AMPK on FOXM1 expression was examined by hypoxia and glucose deprivation, as well as pharmacological AMPK activators such as A23187, AICAR and metformin.	Metformin	180-189	forkhead box M1	Homo sapiens	45-50
23500454-9	2013	Treatment with the insulin-sensitizing drug metformin attenuated estrogen-dependent proliferative expression of c-myc and c-fos in the obese rat endometrium compared to untreated controls and was accompanied by inhibition of phosphorylation of the insulin and IGF1 receptors (IRbeta/IGF1R) and ERK1/2.	Metformin	44-53	Fos proto-oncogene, AP-1 transcription factor subunit	Rattus norvegicus	122-127
23612973-2	2013	In a previous study, we demonstrated that phosphorylation of Ser-428/431 (in LKB1(L)) by protein kinase Czeta (PKCzeta) was essential for LKB1-mediated activation of AMP-activated protein kinase (AMPK) in response to oxidants or metformin.	Metformin	229-238	protein kinase C zeta	Homo sapiens	89-109
23620395-6	2013	In addition, we treated Ins2(+/Akita) mice with metformin, which activates AMP-activated protein kinase (AMPK) and thereby slows the degradation of GTPCH I; despite blood glucose levels that were similar to untreated mice, those treated with metformin had significantly less albuminuria.	Metformin	242-251	insulin II	Mus musculus	24-28
23228442-8	2013	Surprisingly, the expression of the organic cation transporters Slc22a1, Slc22a2 and Slc22a3 essential for the cellular uptake of metformin was highly suppressed in renal tumours.	Metformin	130-139	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	64-71
23111552-0	2013	Gemfibrozil and its combination with metformin on pleiotropic effect on IL-10 and adiponectin and anti-atherogenic treatment in insulin resistant type 2 diabetes mellitus rats.	Metformin	37-46	adiponectin, C1Q and collagen domain containing	Rattus norvegicus	82-93
23111552-8	2013	OVERALL CONCLUSIONS: Gemfibrozil plus metformin decrease MMP-9, increase IL-10 and adiponectin acting as anti-atherogenic, anti-inflammatory and immunomodulatory in IR type 2 DM.	Metformin	38-47	matrix metallopeptidase 9	Rattus norvegicus	57-62
23111552-8	2013	OVERALL CONCLUSIONS: Gemfibrozil plus metformin decrease MMP-9, increase IL-10 and adiponectin acting as anti-atherogenic, anti-inflammatory and immunomodulatory in IR type 2 DM.	Metformin	38-47	adiponectin, C1Q and collagen domain containing	Rattus norvegicus	83-94
23497197-13	2013	CONCLUSIONS: An antidiabetic treatment with either insulin or metformin in ZDF rats inhibits the development of hypoadiponectinemia and downregulation of APPL1 in mesenteric resistance arteries, but is not able to improve adiponectin induced vasodilation and endothelial dysfunction.	Metformin	62-71	adiponectin, C1Q and collagen domain containing	Rattus norvegicus	116-127
22861817-0	2013	Differential expression of organic cation transporter OCT-3 in oral premalignant and malignant lesions: potential implications in the antineoplastic effects of metformin.	Metformin	160-169	solute carrier family 22 member 3	Homo sapiens	54-59
22861817-3	2013	As organic cation transporters (OCT) belonging to the solute carrier 22A gene family, including OCT-1, OCT-2, and OCT-3, mediate metformin uptake and activity, it is critical to define what role they play in the antineoplastic activity of metformin.	Metformin	129-138	solute carrier family 22 member 3	Homo sapiens	114-119
22861817-6	2013	Indeed, inhibition of OCT-3 expression and activity in HNSCC cells prevented metformin-induced AMP-activated protein kinase activation and mTORC1 pathway inhibition.	Metformin	77-86	solute carrier family 22 member 3	Homo sapiens	22-27
22861817-7	2013	Moreover, in oral dysplasias, high OCT-3 expression localized to epithelial compartments where mTORC1 signaling was also upregulated suggestive of a potential local effect of metformin.	Metformin	175-184	solute carrier family 22 member 3	Homo sapiens	35-40
23280877-5	2013	In vivo kidney uptake clearances of benzylpenicillin and metformin, which are typical substrates for renal organic anion transporters Oat1 and Oat3 and organic cation transporters Oct1 and Oct2, respectively, were evaluated.	Metformin	57-66	solute carrier family 22 member 6	Rattus norvegicus	134-138
23280877-5	2013	In vivo kidney uptake clearances of benzylpenicillin and metformin, which are typical substrates for renal organic anion transporters Oat1 and Oat3 and organic cation transporters Oct1 and Oct2, respectively, were evaluated.	Metformin	57-66	solute carrier family 22 member 1	Rattus norvegicus	180-184
23287468-8	2013	The AMPK agonist metformin, which endows somatic cells with a bioenergetic infrastructure that is protected against reprogramming, was found to drastically elongate fibroblast mitochondria, fully reverse the high IF1/beta-F1-ATPase ratio and downregulate the ACACA/FASN lipogenic enzymes in iPS cells.	Metformin	17-26	acetyl-CoA carboxylase alpha	Homo sapiens	259-264
23287468-8	2013	The AMPK agonist metformin, which endows somatic cells with a bioenergetic infrastructure that is protected against reprogramming, was found to drastically elongate fibroblast mitochondria, fully reverse the high IF1/beta-F1-ATPase ratio and downregulate the ACACA/FASN lipogenic enzymes in iPS cells.	Metformin	17-26	fatty acid synthase	Homo sapiens	265-269
24335168-0	2013	Metformin inhibits esophagus cancer proliferation through upregulation of USP7.	Metformin	0-9	ubiquitin specific peptidase 7	Homo sapiens	74-78
23378779-13	2013	Similarly, a fall in C-reactive protein and adenosine deaminase levels was greater in patients taking metformin with garlic than in patients taking only metformin.	Metformin	102-111	adenosine deaminase	Homo sapiens	44-63
23378779-13	2013	Similarly, a fall in C-reactive protein and adenosine deaminase levels was greater in patients taking metformin with garlic than in patients taking only metformin.	Metformin	153-162	adenosine deaminase	Homo sapiens	44-63
24324494-5	2013	SLC22A1, SLC47A1, and ATM gene variants were repeatedly associated with the response to metformin.	Metformin	88-97	solute carrier family 47 member 1	Homo sapiens	9-16
22960565-10	2012	Up-regulation of GNMT may represent an important mechanism of beneficial action of metformin in NAFLD treatment.	Metformin	83-92	glycine N-methyltransferase	Mus musculus	17-21
23141431-6	2012	Metformin with insulin significantly increased mRNA expressions of INSR, IGF-1R, and IRS-1, while metformin alone had no significant effect.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	73-79
23061989-6	2012	Regarding adipocytokines, sitagliptin + metformin better reduced RBP-4, visfatin and chemerin levels, compared to placebo + metformin.	Metformin	40-49	retinol binding protein 4	Homo sapiens	65-70
23061989-6	2012	Regarding adipocytokines, sitagliptin + metformin better reduced RBP-4, visfatin and chemerin levels, compared to placebo + metformin.	Metformin	40-49	retinoic acid receptor responder 2	Homo sapiens	85-93
22698918-5	2012	Metformin inhibited the induction of PDK4 expression by GH via a pathway dependent on AMP-activated protein kinase (AMPK) and SHP induction.	Metformin	0-9	nuclear receptor subfamily 0, group B, member 2	Mus musculus	126-129
22735389-2	2012	So far, the number of polymorphisms in SLC22A1, SLC22A2, and SLC47A1 genes coding for organic cation transporter 1 (OCT1), OCT2, and multidrug and toxin extrusion transporter 1 (MATE1) metformin transporters have been described in association with the efficacy of metformin.	Metformin	185-194	solute carrier family 47 member 1	Homo sapiens	61-68
22735389-2	2012	So far, the number of polymorphisms in SLC22A1, SLC22A2, and SLC47A1 genes coding for organic cation transporter 1 (OCT1), OCT2, and multidrug and toxin extrusion transporter 1 (MATE1) metformin transporters have been described in association with the efficacy of metformin.	Metformin	185-194	solute carrier family 47 member 1	Homo sapiens	133-176
22378745-0	2012	A novel inverse relationship between metformin-triggered AMPK-SIRT1 signaling and p53 protein abundance in high glucose-exposed HepG2 cells.	Metformin	37-46	sirtuin 1	Homo sapiens	62-67
22378745-5	2012	Metformin induced activation of AMPK and SIRT1 and decreased p53 protein abundance.	Metformin	0-9	sirtuin 1	Homo sapiens	41-46
22378745-9	2012	It also diminished the triglyceride-lowering action of metformin, an effect that was rescued by incubation with the SIRT1 activator SRT2183.	Metformin	55-64	sirtuin 1	Homo sapiens	116-121
22703658-7	2012	RESULTS: The number of RANKL-positive and tartrate-resistant acid phosphatase (TRAP)-positive cells in the metformin-treated groups decreased on day 14, whereas the number of OPG-positive cells increased on day 28.	Metformin	107-116	acid phosphatase 5, tartrate resistant	Rattus norvegicus	42-77
22703658-7	2012	RESULTS: The number of RANKL-positive and tartrate-resistant acid phosphatase (TRAP)-positive cells in the metformin-treated groups decreased on day 14, whereas the number of OPG-positive cells increased on day 28.	Metformin	107-116	acid phosphatase 5, tartrate resistant	Rattus norvegicus	79-83
22493491-12	2012	Inhibition of PTP-1B activity with pervanadate and metformin or knocking down PTP-1B reestablishes IFNalpha response.	Metformin	51-60	protein tyrosine phosphatase non-receptor type 1	Homo sapiens	14-20
22493491-13	2012	Likewise, metformin decreases PTP-1B activity and improves response to IFNalpha in insulin-resistant obese mice.	Metformin	10-19	protein tyrosine phosphatase, non-receptor type 1	Mus musculus	30-36
22565037-0	2012	Metformin-induced preferential killing of breast cancer initiating CD44+CD24-/low cells is sufficient to overcome primary resistance to trastuzumab in HER2+ human breast cancer xenografts.	Metformin	0-9	CD44 molecule (Indian blood group)	Homo sapiens	67-71
22565037-4	2012	Because recent studies have shown that the anti-diabetic biguanide metformin can exert antitumor effects by targeted killing of CSC-like cells, we explored whether metformin"s ability to preferentially kill breast cancer initiating CD44+CD24-/low cells may have the potential to sensitize JIMT-1 xenograft mouse models to trastuzumab.	Metformin	164-173	CD44 antigen	Mus musculus	232-236
22565037-5	2012	Upon isolation for breast cancer initiating CD44+CD24-/low cells by employing magnetic activated cell sorting, we observed the kinetics of metformin-induced killing drastically varied among CSC and non-CSC subpopulations.	Metformin	139-148	CD44 molecule (Indian blood group)	Homo sapiens	44-48
22565037-6	2012	Metformin"s cell killing effect increased dramatically by more than 10-fold in CD44+CD24-/low breast CSC cells compared to non-CD44+CD24-/low immunophenotypes.	Metformin	0-9	CD44 molecule (Indian blood group)	Homo sapiens	79-83
22565037-6	2012	Metformin"s cell killing effect increased dramatically by more than 10-fold in CD44+CD24-/low breast CSC cells compared to non-CD44+CD24-/low immunophenotypes.	Metformin	0-9	CD44 molecule (Indian blood group)	Homo sapiens	127-131
22565037-9	2012	Given that metformin-induced preferential killing of breast cancer initiating CD44+CD24-/low subpopulations is sufficient to overcome in vivo primary resistance to trastuzumab, the incorporation of metformin into trastuzumab-based regimens may provide a valuable strategy for treatment of HER2+ breast cancer patients.	Metformin	11-20	CD44 molecule (Indian blood group)	Homo sapiens	78-82
22107872-5	2012	We found that metformin activates the PERK-ATF4 but not the ATF6 or IRE1-XBP1 branch in ERSS and leads to a strong upregulation of CHOP mRNA and protein.	Metformin	14-23	activating transcription factor 4	Homo sapiens	43-47
22108913-0	2012	Rosiglitazone and metformin have opposite effects on intestinal absorption of oligopeptides via the proton-dependent PepT1 transporter.	Metformin	18-27	solute carrier family 15 (oligopeptide transporter), member 1	Mus musculus	117-122
22108913-3	2012	This prompted us to investigate the effects of two antidiabetic drugs, rosiglitazone and metformin, on PepT1 activity/expression in a murine diet-induced obesity model.	Metformin	89-98	solute carrier family 15 (oligopeptide transporter), member 1	Mus musculus	103-108
22108913-7	2012	Metformin alone did not modify PepT1 activity but counteracted rosiglitazone-induced PepT1-mediated transport.	Metformin	0-9	solute carrier family 15 (oligopeptide transporter), member 1	Mus musculus	85-90
22108913-9	2012	Furthermore, metformin decreased PepT1 expression (mRNA and protein) and its transport activity.	Metformin	13-22	solute carrier family 15 (oligopeptide transporter), member 1	Mus musculus	33-38
22038047-4	2012	In Calu-1, but not in Calu-6 cells, metformin reduced phosphorylation of type 1 insulin-like growth factor receptor (IGF-IR) substrates Akt and Forkhead transcription factor 3a (FOXO3a), inhibited IGF1-dependent FOXO3a nuclear exit, and decreased IGF1-dependent cell proliferation.	Metformin	36-45	insulin like growth factor 1 receptor	Homo sapiens	117-123
22223580-1	2012	Independently, metformin (MET) and the prebiotic, oligofructose (OFS), have been shown to increase glucagon-like peptide (GLP-1) secretion.	Metformin	15-24	glucagon	Rattus norvegicus	122-127
22117073-12	2012	Induction of IL1Rn by PGC-1alpha and AMPK may be involved in the beneficial effects of exercise and caloric restriction and putative anti-inflammatory effects of metformin.	Metformin	162-171	interleukin 1 receptor antagonist	Mus musculus	13-18
21769504-5	2012	In this study, we demonstrate significant up-regulation of Hsp60 at both mRNA and protein levels when these cells were exposed to metformin at therapeutic dosage levels.	Metformin	130-139	heat shock protein family D (Hsp60) member 1	Homo sapiens	59-64
22615536-7	2012	Serum RBP4 levels were normalized in obese/diabetic subjects treated with diet or metformin (P &lt; 0.05).	Metformin	82-91	retinol binding protein 4	Homo sapiens	6-10
21424914-9	2011	In the metformin group, body mass index, PPG, HbA1c, IL-6, ICAM-1, and TNF-alpha levels were significantly decreased after 12 weeks compared with the basal levels.	Metformin	7-16	intercellular adhesion molecule 1	Homo sapiens	59-65
6354812-1	1983	The effect of metformin on hepatocyte insulin receptor binding was examined in normal, streptozotocin diabetic and genetically obese diabetic (ob/ob) mice.	Metformin	14-23	insulin receptor	Mus musculus	38-54
6405894-0	1983	Effect of metformin on insulin receptor binding and diabetic control.	Metformin	10-19	insulin receptor	Homo sapiens	23-39
21971158-11	2011	In contrast, pretreatment with the gastrin-releasing peptide antagonist, RC-3095 (100 mug/kg, sc), reduced the GLP-1 response to metformin, by 55 +- 6% (P &lt; 0.01) at 30 min.	Metformin	129-138	gastrin releasing peptide	Homo sapiens	35-60
21923552-3	2011	Two isoforms, MATE1 and 2, have been identified, and, so far, only a limited number of substrates, including clinically used drugs such as metformin and cimetidine, are known.	Metformin	139-148	solute carrier family 47 member 1	Homo sapiens	14-25
21839072-6	2011	After monotherapy with metformin, with the exception of PPARgamma expression which was blunted, all of the above parameters were significantly increased (compared to untreated controls).	Metformin	23-32	peroxisome proliferator-activated receptor gamma	Rattus norvegicus	56-65
6403102-0	1983	Effect of metformin on insulin receptor binding and glycaemic control in type II diabetes.	Metformin	10-19	insulin receptor	Homo sapiens	23-39
6403102-5	1983	Diabetic control as assessed by urinary glucose, glycosylated haemoglobin (HbA1), and glucose tolerance values was significantly improved during metformin treatment, while plasma insulin concentrations were not altered.	Metformin	145-154	hemoglobin subunit alpha 1	Homo sapiens	75-79
21839072-7	2011	Metformin/rosiglitazone co-treatment prevented all the in vivo and ex vivo anti-osteogenic effects of rosiglitazone monotherapy, with a reversion back to control levels of PPARgamma, Runx2/Cbfa1 and AMP-kinase phosphorylation of BMPC.	Metformin	0-9	peroxisome proliferator-activated receptor gamma	Rattus norvegicus	172-181
21700905-5	2011	Similar effects on PPAR-gamma were seen, with both AICAR and metformin inhibiting PPRE reporter activity.	Metformin	61-70	peroxisome proliferator-activated receptor gamma	Rattus norvegicus	19-29
21700905-11	2011	We concluded that the AMPK activators AICAR and metformin inhibited transcriptional activities of PPAR-alpha and PPAR-gamma, whereas inhibition of AMPK with compound C activated both PPARs.	Metformin	48-57	peroxisome proliferator-activated receptor gamma	Rattus norvegicus	113-123
21338323-0	2011	Metformin counters both lipolytic/inflammatory agents-decreased hormone sensitive lipase phosphorylation at Ser-554 and -induced lipolysis in human adipocytes.	Metformin	0-9	lipase E, hormone sensitive type	Homo sapiens	64-88
21338323-5	2011	Pre-incubation with metformin (24 h, 1 mM) inhibited forskolin-, isoproterenol-, IBMX-, LPS-, IL-1beta- and TNF-alpha-induced glycerol release and prevented p(Ser554)HSL decrease and p(Ser-552)HSL increase due to lipolytic and inflammatory agents.	Metformin	20-29	lipase E, hormone sensitive type	Homo sapiens	166-169
21338323-5	2011	Pre-incubation with metformin (24 h, 1 mM) inhibited forskolin-, isoproterenol-, IBMX-, LPS-, IL-1beta- and TNF-alpha-induced glycerol release and prevented p(Ser554)HSL decrease and p(Ser-552)HSL increase due to lipolytic and inflammatory agents.	Metformin	20-29	lipase E, hormone sensitive type	Homo sapiens	193-196
21835890-5	2011	Interestingly, we found that metformin also induces LKB1 cytosolic translocation, but the stimulation is independent of APPL1 and the PP2A-PKCzeta pathway.	Metformin	29-38	protein kinase C zeta	Homo sapiens	139-146
21803292-6	2011	CBP(DeltaCH1/DeltaCH1) mice remain metformin responsive.	Metformin	35-44	CREB binding protein	Mus musculus	0-3
21655990-11	2011	Messenger RNA expression was significantly downregulated by metformin for PDE3B (phosphodiesterase 3B, cGMP-inhibited; a critical regulator of cAMP levels that affect activation of AMP-activated protein kinase, AMPK), confirmed by immunohistochemistry, SSR3, TP53 and CCDC14.	Metformin	60-69	phosphodiesterase 3B	Homo sapiens	74-79
21655990-11	2011	Messenger RNA expression was significantly downregulated by metformin for PDE3B (phosphodiesterase 3B, cGMP-inhibited; a critical regulator of cAMP levels that affect activation of AMP-activated protein kinase, AMPK), confirmed by immunohistochemistry, SSR3, TP53 and CCDC14.	Metformin	60-69	phosphodiesterase 3B	Homo sapiens	81-117
21655990-11	2011	Messenger RNA expression was significantly downregulated by metformin for PDE3B (phosphodiesterase 3B, cGMP-inhibited; a critical regulator of cAMP levels that affect activation of AMP-activated protein kinase, AMPK), confirmed by immunohistochemistry, SSR3, TP53 and CCDC14.	Metformin	60-69	signal sequence receptor subunit 3	Homo sapiens	253-257
21655990-13	2011	Gene set analysis additionally revealed that p53, BRCA1 and cell cycle pathways also had reduced expression following metformin.	Metformin	118-127	BRCA1 DNA repair associated	Homo sapiens	50-55
21518836-5	2011	In HEK293-MATE1 cells, chloroquine competitively inhibited MATE1-mediated metformin uptake (K(i) = 2.8 muM).	Metformin	74-83	solute carrier family 47 member 1	Canis lupus familiaris	10-15
433615-0	1979	The effect of metformin on the arginine induced insulin- and glucagon release in pigs.	Metformin	14-23	insulin	Sus scrofa	48-55
33714764-2	2021	In this study metformin derived carbon dots (Met-CDs) were synthesized using a microwave assisted method.	Metformin	14-23	MET proto-oncogene, receptor tyrosine kinase	Danio rerio	45-48
33915432-0	2021	Metformin attenuates atherosclerosis and plaque vulnerability by upregulating KLF2-mediated autophagy in apoE-/- mice.	Metformin	0-9	Kruppel-like factor 2 (lung)	Mus musculus	78-82
33915432-10	2021	Subsequently, we further determined the molecular mechanism that whether metformin could inhibit foam cell formation by activating KLF2-mediated autophagy.	Metformin	73-82	Kruppel-like factor 2 (lung)	Mus musculus	131-135
33915432-13	2021	Mechanistically, metformin promotes autophagy via modulating KLF2 expression.	Metformin	17-26	Kruppel-like factor 2 (lung)	Mus musculus	61-65
33915432-14	2021	Taken together, our study demonstrates a novel antiatherogenic mechanism of metformin by upregulating KLF2-mediated autophagy.	Metformin	76-85	Kruppel-like factor 2 (lung)	Mus musculus	102-106
33714781-1	2021	Metformin is an oral antihyperglycemic drug widely used to treat type 2 diabetes mellitus (T2DM), acting via indirect activation of 5" Adenosine monophosphate-activated Protein Kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	135-183
33714781-1	2021	Metformin is an oral antihyperglycemic drug widely used to treat type 2 diabetes mellitus (T2DM), acting via indirect activation of 5" Adenosine monophosphate-activated Protein Kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	185-189
33714781-3	2021	In various acute kidney diseases (AKI) animal models, metformin protects renal tubular cells from inflammation, apoptosis, reactive oxygen stress (ROS), endoplasmic reticulum (ER) stress, epithelial-mesenchymal transition (EMT) via AMPK activation.	Metformin	54-63	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	232-236
33714781-4	2021	In diabetic kidney disease (DKD), metformin also alleviates podocyte loss, mesangial cells apoptosis, and tubular cells senescence through AMPK-mediated signaling pathways.	Metformin	34-43	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	139-143
33714781-5	2021	Besides, metformin inhibits cystic fibrosis transmembrane conductance regulator (CFTR)-mediated fluids secretion and the mammalian target of rapamycin (mTOR)-involved cyst formation negatively regulated by AMPK in autosomal dominant polycystic kidney disease (APDKD).	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	206-210
33714781-7	2021	As the common pathway for chronic kidney disease (CKD) progressing towards end-stage renal disease (ESRD), renal fibrosis is ameliorated by metformin, to a great extent dependent on AMPK activation.	Metformin	140-149	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	182-186
33859820-15	2021	The ratio of leptin to adiponectin was increased in obese compared with the lean rats in both the control and metformin treatment groups (P<0.0001).	Metformin	110-119	leptin	Rattus norvegicus	13-19
33355497-5	2021	Moreover, metformin furtherly promoted autophagy by increasing the protein expression of LC3-II, ATG5, ATG7 and Beclin1, and by involving AMPK pathway during MI.	Metformin	10-19	beclin 1	Rattus norvegicus	112-119
33355497-9	2021	In addition, metformin augmented the protein level of Bcl-2 and diminished the protein levels of Bax and cleaved caspase-3.	Metformin	13-22	caspase 3	Rattus norvegicus	113-122
33838154-3	2021	Here we provide evidence that metformin induces accumulation of ROS by inhibiting the expression of a core antioxidant transcription factor nuclear factor erythroid 2 like 1 (NFE2L1/Nrf1) in human hepatocellular carcinoma HepG2 cells.	Metformin	30-39	nuclear respiratory factor 1	Homo sapiens	182-186
34053455-0	2021	Metformin reduces androgen receptor and upregulates homeobox A10 expression in uterine endometrium in women with polycystic ovary syndrome.	Metformin	0-9	homeobox A10	Homo sapiens	52-64
34053455-5	2021	METHODS: In this study, we examined whether metformin affects androgen receptor (AR) and HOXA10 expression in PCOS endometrium in vivo and in human endometrial cell lines in vitro.	Metformin	44-53	homeobox A10	Homo sapiens	89-95
34053455-9	2021	In contrast, HOXA10 expression in the stromal cells with metformin treatment increased in comparison to its level before treatment.	Metformin	57-66	homeobox A10	Homo sapiens	13-19
34053455-10	2021	Further, we showed that metformin counteracted the testosterone-induced AR expression in both Ishikawa cells and human endometrial stromal cells (HESCs); whereas, metformin partly restored the testosterone-reduced HOXA10 expression in HESCs in vitro.	Metformin	163-172	homeobox A10	Homo sapiens	214-220
34042039-6	2021	More specifically, we review the neuroprotective or neurodegenerative effects of AMPK or AMPK activators like metformin, resveratrol, and 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside on neurological diseases and dementia, which exert through the intracellular molecules involved in neuronal survival or death.	Metformin	110-119	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	81-85
34042039-6	2021	More specifically, we review the neuroprotective or neurodegenerative effects of AMPK or AMPK activators like metformin, resveratrol, and 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside on neurological diseases and dementia, which exert through the intracellular molecules involved in neuronal survival or death.	Metformin	110-119	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	89-93
34041677-10	2021	Vildagliptin and metformin not only restored the above but also decreased the expression of IL-6, NFkappaB, SOCS-3 along with lipid accumulation.	Metformin	17-26	suppressor of cytokine signaling 3	Rattus norvegicus	108-114
34033525-2	2021	Metformin is beneficial against aging-related diseases, and we hypothesized that it may ameliorate CS-induced pathologies of emphysematous COPD.	Metformin	0-9	citrate synthase	Homo sapiens	99-101
34033525-7	2021	RESULTS: Metformin protected against CS-induced pulmonary inflammation, airspace enlargement, and small airway remodeling, glomerular shrinkage, oxidative stress, apoptosis, telomere damage, aging, dysmetabolism in vivo and in vitro, and ER stress.	Metformin	9-18	citrate synthase	Homo sapiens	37-39
34033525-8	2021	The AMPK pathway was central to metformin protective action.	Metformin	32-41	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	4-8
21518836-5	2011	In HEK293-MATE1 cells, chloroquine competitively inhibited MATE1-mediated metformin uptake (K(i) = 2.8 muM).	Metformin	74-83	solute carrier family 47 member 1	Canis lupus familiaris	59-64
20883471-3	2011	However, the functional interaction of OCTs and MATE1 for uptake and transcellular transport of the oral antidiabetic drug metformin or of the cation 1-methyl-4-phenylpyridinium (MPP(+)) has not fully been characterized.	Metformin	123-132	solute carrier family 47 member 1	Canis lupus familiaris	48-53
20883471-5	2011	KEY RESULTS: Cellular accumulation of MPP(+) and metformin was significantly reduced by 31% and 46% in MDCK-MATE1 single-transfected cells compared with MDCK control cells (10 microM; P &lt; 0.01).	Metformin	49-58	solute carrier family 47 member 1	Canis lupus familiaris	108-113
20883471-6	2011	Over a wide concentration range (10-2500 microM) metformin transcellular transport from the basal into the apical compartment was significantly higher in the double-transfected cells compared with the MDCK control and MDCK-MATE1 monolayers.	Metformin	49-58	solute carrier family 47 member 1	Homo sapiens	223-228
20883471-8	2011	In MDCK-OCT2-MATE1 cells basal to apical MPP(+) and metformin transcellular translocation decreased with increasing pH from 6.0 to 7.5.	Metformin	52-61	solute carrier family 47 member 1	Homo sapiens	13-18
21597332-4	2011	Understanding how the IR/IGF-1R pathway functions in tumors is increasing in importance as the efficacy of drugs that target metabolic pathways, such as metformin, are investigated in prospective clinical trials.	Metformin	153-162	insulin like growth factor 1 receptor	Homo sapiens	25-31
21552023-0	2011	Increased F-18 FDG intestinal uptake in diabetic patients on metformin: a matched case-control analysis.	Metformin	61-70	mastermind like domain containing 1	Homo sapiens	10-14
21552023-1	2011	PURPOSE: A matched case-control study was performed to assess the relationship between metformin use and the degree of F-18 fluorodeoxyglucose (FDG) bowel activity in diabetic patients.	Metformin	87-96	mastermind like domain containing 1	Homo sapiens	119-123
21552023-5	2011	RESULTS: F-18 FDG uptake in small and large bowel was significantly increased in metformin patients compared with nondiabetic controls both visually and quantitatively (all P &lt; 0.0001), as well as compared with nonmetformin patients with diabetes.	Metformin	81-90	mastermind like domain containing 1	Homo sapiens	9-13
21552023-8	2011	CONCLUSION: Physiologic accumulation of F-18 FDG in bowel is increased in diabetic patients maintained on metformin.	Metformin	106-115	mastermind like domain containing 1	Homo sapiens	40-44
21677353-9	2011	However, MATE1 transporter (multidrug and toxin extrusion 1 protein) is encoded by the SLC47A1 gene and facilitates metformin excretion from these cells into bile and urine.	Metformin	116-125	solute carrier family 47 member 1	Homo sapiens	9-14
21677353-9	2011	However, MATE1 transporter (multidrug and toxin extrusion 1 protein) is encoded by the SLC47A1 gene and facilitates metformin excretion from these cells into bile and urine.	Metformin	116-125	solute carrier family 47 member 1	Homo sapiens	87-94
21465524-7	2011	Metformin also increased the phosphorylation of c-Jun N-terminal kinase (JNK)-c-Jun and mammalian target of rapamycin (mTOR)-p70S6 kinase pathways.	Metformin	0-9	Jun proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	48-53
21465524-8	2011	Both pharmacologic inhibition and knock-down of AMPK blocked metformin-induced phosphorylation of JNK and mTOR.	Metformin	61-70	mitogen-activated protein kinase 8	Mus musculus	98-101
21465524-10	2011	PTEN promoter activity was suppressed by metformin and inhibition of mTOR and JNK by pharmacologic inhibitors blocked metformin-induced PTEN promoter activity suppression.	Metformin	118-127	mitogen-activated protein kinase 8	Mus musculus	78-81
21091653-6	2011	KEY RESULTS: Both pre- and post-treatment with metformin significantly improved survival of animals during lethal endotoxaemia (survival rate was monitored up to 2 weeks), decreased serum levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta, HMGB1 expression and myeloperoxidase activity in lungs.	Metformin	47-56	myeloperoxidase	Mus musculus	280-295
21738897-8	2011	T2DM patients on metformin monotherapy showed a lower ADA activity (20.9+-1.0 U/L vs. 28.1+-2.8 U/L; P&lt;0.05) compared with that of those on sulfonylurea monotherapy.	Metformin	17-26	adenosine deaminase	Homo sapiens	54-57
33975892-3	2021	SGLT-2 inhibitors and GLP-1 receptor agonists are traditionally used in people with elevated glucose level after metformin treatment.	Metformin	113-122	glucagon like peptide 1 receptor	Homo sapiens	22-36
21054339-11	2011	Furthermore, the inhibitory effects of metformin on MDR1 expression and cAMP-responsive element binding protein (CREB) phosphorylation were reversed by overexpression of a dominant-negative mutant of AMPK.	Metformin	39-48	cAMP responsive element binding protein 1	Homo sapiens	72-111
21054339-11	2011	Furthermore, the inhibitory effects of metformin on MDR1 expression and cAMP-responsive element binding protein (CREB) phosphorylation were reversed by overexpression of a dominant-negative mutant of AMPK.	Metformin	39-48	cAMP responsive element binding protein 1	Homo sapiens	113-117
21054339-12	2011	CONCLUSIONS AND IMPLICATIONS: These results suggest that metformin activates AMPK and suppresses MDR1 expression in MCF-7/adr cells by inhibiting the activation of NF-kappaB and CREB.	Metformin	57-66	cAMP responsive element binding protein 1	Homo sapiens	178-182
21282369-2	2011	We assess here the effects of the biguanide, metformin, on the expression of HIF-1alpha in diabetic nephropathy using renal proximal tubular cells and type 2 diabetic rats.	Metformin	45-54	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	77-87
21282369-11	2011	Finally, metformin, but not insulin, attenuated tubular HIF-1alpha expression and pimonidazole staining and ameliorated tubular injury in ZDF rats.	Metformin	9-18	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	56-66
21241070-15	2011	An intron variant of multidrug and toxin extrusion transporter [MATE1] (G&gt;A, SNP rs2289669) has also been associated with a small increase in antihyperglycaemic effect of metformin.	Metformin	174-183	solute carrier family 47 member 1	Homo sapiens	64-69
21241070-17	2011	However, intersubject differences in the levels of expression of OCT1 and OCT3 in the liver are very large and may contribute more to the variations in the hepatic uptake and clinical effect of metformin.	Metformin	194-203	solute carrier family 22 member 3	Homo sapiens	74-78
20972533-4	2011	METHODS: Metformin action was assessed in Glp1r(-/-), Gipr(-/-), Glp1r:Gipr(-/-), Pparalpha (also known as Ppara)(-/-) and hyperglycaemic obese wild-type mice with or without the GLP-1 receptor (GLP1R) antagonist exendin(9-39).	Metformin	9-18	glucagon-like peptide 1 receptor	Mus musculus	42-47
20972533-4	2011	METHODS: Metformin action was assessed in Glp1r(-/-), Gipr(-/-), Glp1r:Gipr(-/-), Pparalpha (also known as Ppara)(-/-) and hyperglycaemic obese wild-type mice with or without the GLP-1 receptor (GLP1R) antagonist exendin(9-39).	Metformin	9-18	gastric inhibitory polypeptide receptor	Mus musculus	54-58
20972533-4	2011	METHODS: Metformin action was assessed in Glp1r(-/-), Gipr(-/-), Glp1r:Gipr(-/-), Pparalpha (also known as Ppara)(-/-) and hyperglycaemic obese wild-type mice with or without the GLP-1 receptor (GLP1R) antagonist exendin(9-39).	Metformin	9-18	glucagon-like peptide 1 receptor	Mus musculus	65-70
20972533-4	2011	METHODS: Metformin action was assessed in Glp1r(-/-), Gipr(-/-), Glp1r:Gipr(-/-), Pparalpha (also known as Ppara)(-/-) and hyperglycaemic obese wild-type mice with or without the GLP-1 receptor (GLP1R) antagonist exendin(9-39).	Metformin	9-18	gastric inhibitory polypeptide receptor	Mus musculus	71-75
20972533-8	2011	Metformin significantly improved oral glucose tolerance despite loss of incretin action in Glp1r(-/-), Gipr(-/-) and Glp1r(-/-) :Gipr(-/-) mice, and in wild-type mice fed a high-fat diet and treated with exendin(9-39).	Metformin	0-9	glucagon-like peptide 1 receptor	Mus musculus	117-122
20972533-8	2011	Metformin significantly improved oral glucose tolerance despite loss of incretin action in Glp1r(-/-), Gipr(-/-) and Glp1r(-/-) :Gipr(-/-) mice, and in wild-type mice fed a high-fat diet and treated with exendin(9-39).	Metformin	0-9	gastric inhibitory polypeptide receptor	Mus musculus	129-133
20972533-9	2011	Levels of mRNA transcripts for Glp1r, Gipr and Pparalpha were significantly increased in islets from metformin-treated mice.	Metformin	101-110	glucagon-like peptide 1 receptor	Mus musculus	31-36
20972533-9	2011	Levels of mRNA transcripts for Glp1r, Gipr and Pparalpha were significantly increased in islets from metformin-treated mice.	Metformin	101-110	gastric inhibitory polypeptide receptor	Mus musculus	38-42
20972533-10	2011	Metformin directly increased Glp1r expression in INS-1 beta cells via a PPAR-alpha-dependent, AMPK-independent mechanism.	Metformin	0-9	glucagon-like peptide 1 receptor	Rattus norvegicus	29-34
20972533-12	2011	CONCLUSIONS/INTERPRETATION: As metformin modulates multiple components of the incretin axis, and enhances expression of the Glp1r and related insulinotropic islet receptors through a mechanism requiring PPAR-alpha, metformin may be mechanistically well suited for combination with incretin-based therapies.	Metformin	31-40	glucagon-like peptide 1 receptor	Mus musculus	124-129
20972533-12	2011	CONCLUSIONS/INTERPRETATION: As metformin modulates multiple components of the incretin axis, and enhances expression of the Glp1r and related insulinotropic islet receptors through a mechanism requiring PPAR-alpha, metformin may be mechanistically well suited for combination with incretin-based therapies.	Metformin	215-224	glucagon-like peptide 1 receptor	Mus musculus	124-129
21084384-9	2011	In conclusion, metformin activates AMPK in beta cells leading to suppression of protein translation through mTOR-dependent and -independent signaling.	Metformin	15-24	mechanistic target of rapamycin kinase	Rattus norvegicus	108-112
21084384-10	2011	Glibenclamide antagonizes these metformin effects through activation of mTOR- and PKA-dependent signaling pathways.	Metformin	32-41	mechanistic target of rapamycin kinase	Rattus norvegicus	72-76
21647332-7	2011	When endogenous LXR ligand production was blocked by the potent HMG CoA reductase inhibitor compactin, T0901317-induced Srebp-1c promoter activity was decreased by AICAR or metformin treatment.	Metformin	173-182	3-hydroxy-3-methylglutaryl-CoA reductase	Rattus norvegicus	64-81
20869956-7	2010	Mice receiving UA or metformin supplementation had increased CD4(+)CD8(+) subpopulations in the thymus compared to the untreated diabetic mice.	Metformin	21-30	CD4 antigen	Mus musculus	61-64
20977577-9	2010	Beneficial effects of metformin were also observed in cells exposed to glibenclamide for 18 h with significant improvements in the insulin secretory responsiveness to alanine, GLP-1 and sulphonylureas.	Metformin	22-31	glucagon	Rattus norvegicus	176-181
20863201-3	2010	The K(i) values of sitagliptin for OCT1- and OCT2-mediated metformin uptake were 34.9 and 40.8 muM, respectively.	Metformin	59-68	POU class 2 homeobox 2	Homo sapiens	45-49
20682687-6	2010	RESULTS: We replicated the association of variants in the metformin transporter gene SLC47A1 with metformin response and detected nominal interactions in the AMP kinase (AMPK) gene STK11, the AMPK subunit genes PRKAA1 and PRKAA2, and a missense SNP in SLC22A1, which encodes another metformin transporter.	Metformin	58-67	solute carrier family 47 member 1	Homo sapiens	85-92
33984637-5	2021	Metformin enhances EVs production via an autophagy-related pathway, concomitantly with the phosphorylation of synaptosome-associated protein 29.	Metformin	0-9	synaptosome associated protein 29	Homo sapiens	110-143
33609563-2	2021	Direct/indirect activation of Adenosine Monophosphate-activated protein kinase (AMPK) and non-AMPK pathways, amongst others, are deemed to explain the molecular mechanisms of action of metformin.	Metformin	185-194	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	30-78
33609563-2	2021	Direct/indirect activation of Adenosine Monophosphate-activated protein kinase (AMPK) and non-AMPK pathways, amongst others, are deemed to explain the molecular mechanisms of action of metformin.	Metformin	185-194	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	80-84
33609563-2	2021	Direct/indirect activation of Adenosine Monophosphate-activated protein kinase (AMPK) and non-AMPK pathways, amongst others, are deemed to explain the molecular mechanisms of action of metformin.	Metformin	185-194	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	94-98
33609563-3	2021	Metformin is an established insulin receptor sensitizing antihyperglycemic agent, is highly affordable, and has superior safety and efficacy profiles.	Metformin	0-9	insulin receptor	Homo sapiens	28-44
33377575-7	2021	In addition, we demonstrated metformin could protect MLE-12 cells from LPS-induced senescence via increasing the expression of ATG5 and augmenting autophagy activity.	Metformin	29-38	autophagy related 5	Mus musculus	127-131
33856655-2	2021	Recently, clinical guidelines have focussed on patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) and recommend a sodium-glucose co-transporter 2 (SGLT2) inhibitor or a glucagon-like peptide 1 (GLP-1) receptor agonist as second-line treatment after metformin or independently of baseline glycated haemogloblin A1c (HbA1c).	Metformin	279-288	glucagon like peptide 1 receptor	Homo sapiens	224-239
32791889-13	2021	Metformin treatment decreased the FRO- or SW1736-CM-induced STAT3 phosphorylation by AMPK phosphorylation.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	85-89
34007848-5	2021	Metformin, which is a potent AMPK activator and is the only recommended first-line drug for the treatment of type 2 diabetes, has emerged as a promising method of fibrosis reduction or reversion.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	29-33
33852202-5	2021	After 36 months, all combinations showed similar reductions in HbA1c (0.8-1.0%), however, metformin plus a DPP-4 inhibitor, an SGLT-2 inhibitor, or a GLP-1 receptor agonist were associated with greater weight loss (1.9, 2.9, and 5.0 kg, respectively) than metformin plus an SU (1.3 kg, P < 0.0001).	Metformin	256-265	glucagon like peptide 1 receptor	Homo sapiens	150-164
33924306-7	2021	Importantly, Cd2+ and candesartan treatments could lead to an enhanced accumulation of metformin, which is a well-characterized substrate of OCTs/MATEs, in mouse kidney and liver, respectively.	Metformin	87-96	CD2 antigen	Mus musculus	13-16
33918222-7	2021	Unexpectedly, Wnt/beta-catenin signaling remained activated in chronic HCV-infected cells after HCV eradication by DAA, but metformin reversed it through PKA/GSK-3beta-mediated beta-catenin degradation, inhibited colony-forming ability and proliferation, and increased apoptosis, suggesting that DAA therapy in combination with metformin may be a novel therapy to treat HCV-associated HCC where metformin suppresses Wnt/beta-catenin signaling for HCV-infected patients.	Metformin	124-133	glycogen synthase kinase 3 alpha	Homo sapiens	158-167
33504231-7	2021	Metformin also induced a significant decrease in Plasma SIP, SPHK1 activity, inflammatory, oxidative stress markers, ICAM-1 and Caspase-3 genes expression compared to oxazolone group.	Metformin	0-9	caspase 3	Rattus norvegicus	128-137
33687163-2	2021	The study aims to evaluate metformin"s efficacy in preventing PL in fresh GnRH antagonist intracytoplasmic sperm injection (ICSI) cycles with cleavage-stage embryo transfer.	Metformin	27-36	gonadotropin releasing hormone 1	Homo sapiens	74-78
20730705-2	2010	We aimed to study if the changes observed in the insulin sensitivity of PCOS patients during treatment with oral contraceptives or metformin associate changes in the serum inflammatory markers interleukin-6 (IL-6) and interleukin-18 (IL-18).	Metformin	131-140	interleukin 18	Homo sapiens	218-232
20730705-2	2010	We aimed to study if the changes observed in the insulin sensitivity of PCOS patients during treatment with oral contraceptives or metformin associate changes in the serum inflammatory markers interleukin-6 (IL-6) and interleukin-18 (IL-18).	Metformin	131-140	interleukin 18	Homo sapiens	234-239
21047255-6	2010	By following this methodological approach, we recently obtained data fitting a model in which, in response to chronic impairment of cellular bioenergetics imposed by metformin-induced mitochondrial uncoupling as assessed by the phosphorylation state of cAMP-response element binding protein (CREB), tumor cells can retrogress from a differentiated state to a more CD44(+) stem-like primitive state epigenetically governed by the Polycomb-group suppressor BMI1-a crucial "stemness" gene involved in the epigenetic maintenance of adult stem cells.	Metformin	166-175	cAMP responsive element binding protein 1	Homo sapiens	253-290
32989831-4	2021	In vitro, tucatinib inhibited OCT2-, MATE1-, and MATE2-K-mediated transport of metformin, with IC50 values of 14.7, 0.340, and 0.135 microM, respectively.	Metformin	79-88	solute carrier family 47 member 2	Homo sapiens	49-56
33642112-11	2021	Metformin alleviated transcription and secretion of IL-1beta, Tumor Necrosis Factor-alpha, and Fibroblast Growth Factor 2, expression and nuclear translocation of C/EBPbeta in this model.	Metformin	0-9	fibroblast growth factor 2	Mus musculus	95-121
33642112-11	2021	Metformin alleviated transcription and secretion of IL-1beta, Tumor Necrosis Factor-alpha, and Fibroblast Growth Factor 2, expression and nuclear translocation of C/EBPbeta in this model.	Metformin	0-9	CCAAT/enhancer binding protein (C/EBP), alpha	Mus musculus	163-172
33625942-0	2021	Metformin Alleviates Cisplatin-Induced Ototoxicity by Autophagy Induction Possibly via the AMPK/FOXO3a Pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	91-95
33625942-10	2021	Notably, metformin activated autophagy and increased the expression levels of the adenosine monophosphate-activated protein kinase (AMPK) and the transcription factor Forkhead box protein O3 (FOXO3a), while cells with AMPK silencing displayed otherwise.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	82-130
33625942-10	2021	Notably, metformin activated autophagy and increased the expression levels of the adenosine monophosphate-activated protein kinase (AMPK) and the transcription factor Forkhead box protein O3 (FOXO3a), while cells with AMPK silencing displayed otherwise.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	132-136
33625942-10	2021	Notably, metformin activated autophagy and increased the expression levels of the adenosine monophosphate-activated protein kinase (AMPK) and the transcription factor Forkhead box protein O3 (FOXO3a), while cells with AMPK silencing displayed otherwise.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	218-222
33625942-11	2021	Our findings indicate that metformin alleviates cisplatin-induced ototoxicity possibly through AMPK/FOXO3a-mediated autophagy machinery.	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	95-99
33915902-9	2021	In addition, metformin treatment increased the expression of monophosphate (AMP)-activated protein kinase (AMPK) and p53 in both HCT116 xenografts and colorectal cancer cell lines and decreased the expression of the urea cycle enzymes, including carbamoyl phosphate synthase 1 (CPS1), arginase 1 (ARG1), ornithine trans-carbamylase (OTC), and ODC.	Metformin	13-22	carbamoyl-phosphate synthase 1	Homo sapiens	246-276
33915902-9	2021	In addition, metformin treatment increased the expression of monophosphate (AMP)-activated protein kinase (AMPK) and p53 in both HCT116 xenografts and colorectal cancer cell lines and decreased the expression of the urea cycle enzymes, including carbamoyl phosphate synthase 1 (CPS1), arginase 1 (ARG1), ornithine trans-carbamylase (OTC), and ODC.	Metformin	13-22	carbamoyl-phosphate synthase 1	Homo sapiens	278-282
33915902-9	2021	In addition, metformin treatment increased the expression of monophosphate (AMP)-activated protein kinase (AMPK) and p53 in both HCT116 xenografts and colorectal cancer cell lines and decreased the expression of the urea cycle enzymes, including carbamoyl phosphate synthase 1 (CPS1), arginase 1 (ARG1), ornithine trans-carbamylase (OTC), and ODC.	Metformin	13-22	arginase 1	Homo sapiens	285-295
33915902-9	2021	In addition, metformin treatment increased the expression of monophosphate (AMP)-activated protein kinase (AMPK) and p53 in both HCT116 xenografts and colorectal cancer cell lines and decreased the expression of the urea cycle enzymes, including carbamoyl phosphate synthase 1 (CPS1), arginase 1 (ARG1), ornithine trans-carbamylase (OTC), and ODC.	Metformin	13-22	arginase 1	Homo sapiens	297-301
33915902-9	2021	In addition, metformin treatment increased the expression of monophosphate (AMP)-activated protein kinase (AMPK) and p53 in both HCT116 xenografts and colorectal cancer cell lines and decreased the expression of the urea cycle enzymes, including carbamoyl phosphate synthase 1 (CPS1), arginase 1 (ARG1), ornithine trans-carbamylase (OTC), and ODC.	Metformin	13-22	ornithine decarboxylase 1	Homo sapiens	343-346
33784336-0	2021	Profiling immuno-metabolic mediators of vitamin B12 deficiency among metformin-treated type 2 diabetic patients in Ghana.	Metformin	69-78	TNF alpha induced protein 1	Homo sapiens	48-51
33784336-1	2021	BACKGROUND: The association between prolong metformin usage and B12 deficiency has been documented.	Metformin	44-53	TNF alpha induced protein 1	Homo sapiens	64-67
33784336-2	2021	However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed substantial disparity among studies due to varied study definitions of vitamin B12 deficiency.	Metformin	37-46	TNF alpha induced protein 1	Homo sapiens	63-66
33784336-2	2021	However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed substantial disparity among studies due to varied study definitions of vitamin B12 deficiency.	Metformin	37-46	TNF alpha induced protein 1	Homo sapiens	164-167
33784336-3	2021	Metformin blocks the calcium dependent absorption of the vitamin B12-Intrinsic Factor complex at the terminal ileum.	Metformin	0-9	TNF alpha induced protein 1	Homo sapiens	65-68
33784336-11	2021	RESULTS: Using the combined indicator (4cB12), the prevalence of metformin induced vitamin B12 deficiency was 40.5% whilst the prevalence of MNSI-Q and MNSI-PE diabetic neuropathy was 32.5% and 6.5% respectively.	Metformin	65-74	TNF alpha induced protein 1	Homo sapiens	41-44
33784336-15	2021	CONCLUSION: Vitamin B12 deficiency and diabetic neuropathy are very high among metformin-treated T2DM patients and it is associated with increased GPA, IFA, TNF-alpha and cardiometabolic risk factors (higher LDL and TC and lower HDL).	Metformin	79-88	TNF alpha induced protein 1	Homo sapiens	20-23
33784336-16	2021	Upon verification of these findings in a prospective case-control study, it may be beneficial to include periodic measurement of Vitamin B12 using the more sensitive combined indicators (4cB 12) in the management of patients with T2DM treated with metformin in Ghana.	Metformin	248-257	TNF alpha induced protein 1	Homo sapiens	137-140
33395696-8	2021	These abnormalities were ameliorated by pharmacological activation of UNC-51/ATG1, a FEZ1-activating kinase, with rapamycin and metformin.	Metformin	128-137	unc-51 like autophagy activating kinase 1	Homo sapiens	70-76
33395696-8	2021	These abnormalities were ameliorated by pharmacological activation of UNC-51/ATG1, a FEZ1-activating kinase, with rapamycin and metformin.	Metformin	128-137	unc-51 like autophagy activating kinase 1	Homo sapiens	77-81
33796404-9	2021	Metabolic modulation with metformin modifies the acetylation pattern in the B7-H6 promoter, impairing BRD4 binding, thereby inhibiting B7-H6 expression.	Metformin	26-35	natural killer cell cytotoxicity receptor 3 ligand 1	Homo sapiens	76-81
33796404-9	2021	Metabolic modulation with metformin modifies the acetylation pattern in the B7-H6 promoter, impairing BRD4 binding, thereby inhibiting B7-H6 expression.	Metformin	26-35	natural killer cell cytotoxicity receptor 3 ligand 1	Homo sapiens	135-140
33841337-7	2021	GLP1 RAs and metformin also had better therapeutic effects than other drugs as measured by the levels of ALT (liraglutide: -9.36 (95% Cl -18 to -0.34), metformin: -2.84 (95% CI -11.09 to 5.28)) and AST (liraglutide: -5.14 (95% CI -10.69 to 0.37), metformin: -2.39 (95% CI -7.55, 2.49)) and other biological indicators.	Metformin	152-161	glucagon like peptide 1 receptor	Homo sapiens	0-4
33841337-7	2021	GLP1 RAs and metformin also had better therapeutic effects than other drugs as measured by the levels of ALT (liraglutide: -9.36 (95% Cl -18 to -0.34), metformin: -2.84 (95% CI -11.09 to 5.28)) and AST (liraglutide: -5.14 (95% CI -10.69 to 0.37), metformin: -2.39 (95% CI -7.55, 2.49)) and other biological indicators.	Metformin	152-161	glucagon like peptide 1 receptor	Homo sapiens	0-4
33606884-1	2021	AIMS: To evaluate the effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) on major cardiovascular events (MACE) in metformin-naive patients with type 2 diabetes (T2D).	Metformin	181-190	glucagon like peptide 1 receptor	Homo sapiens	87-119
33752282-8	2021	The cell growth and Bcl-2 expression level suppressed under hypoxia were reversed with a decrease of the induced Hif-1alpha and Cav-1 levels after AMPK activation with metformin (1 mM) or phenformin (0.1 microM).	Metformin	168-177	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	147-151
33746115-13	2021	The contents of CHOP and cleaved ATF6 were decreased in metformin-treated 24 mo.	Metformin	56-65	activating transcription factor 6	Mus musculus	33-37
21047255-6	2010	By following this methodological approach, we recently obtained data fitting a model in which, in response to chronic impairment of cellular bioenergetics imposed by metformin-induced mitochondrial uncoupling as assessed by the phosphorylation state of cAMP-response element binding protein (CREB), tumor cells can retrogress from a differentiated state to a more CD44(+) stem-like primitive state epigenetically governed by the Polycomb-group suppressor BMI1-a crucial "stemness" gene involved in the epigenetic maintenance of adult stem cells.	Metformin	166-175	cAMP responsive element binding protein 1	Homo sapiens	292-296
21047255-6	2010	By following this methodological approach, we recently obtained data fitting a model in which, in response to chronic impairment of cellular bioenergetics imposed by metformin-induced mitochondrial uncoupling as assessed by the phosphorylation state of cAMP-response element binding protein (CREB), tumor cells can retrogress from a differentiated state to a more CD44(+) stem-like primitive state epigenetically governed by the Polycomb-group suppressor BMI1-a crucial "stemness" gene involved in the epigenetic maintenance of adult stem cells.	Metformin	166-175	CD44 molecule (Indian blood group)	Homo sapiens	364-368
20300828-7	2010	Furthermore, metformin inhibits the nuclear translocation of CRTC2, a CREB-coactivator known to increase aromatase expression which is also a direct downstream target of AMPK.	Metformin	13-22	CREB regulated transcription coactivator 2	Homo sapiens	61-66
20300828-7	2010	Furthermore, metformin inhibits the nuclear translocation of CRTC2, a CREB-coactivator known to increase aromatase expression which is also a direct downstream target of AMPK.	Metformin	13-22	cAMP responsive element binding protein 1	Homo sapiens	70-74
20559023-5	2010	Furthermore, we showed that metformin inhibits 2DG-induced autophagy, decreases beclin 1 expression and triggers a switch from a survival process to cell death.	Metformin	28-37	beclin 1	Homo sapiens	80-88
20228137-7	2010	Furthermore, the administration of metformin led to the activation of AMPK, the inhibitory phosphorylation of acetyl-CoA carboxylase, the upregulation of BNIP3 and increased apoptosis as estimated by poly (ADP-ribose) polymerase (PARP) cleavage.	Metformin	35-44	poly (ADP-ribose) polymerase family, member 1	Mus musculus	200-228
20228137-7	2010	Furthermore, the administration of metformin led to the activation of AMPK, the inhibitory phosphorylation of acetyl-CoA carboxylase, the upregulation of BNIP3 and increased apoptosis as estimated by poly (ADP-ribose) polymerase (PARP) cleavage.	Metformin	35-44	poly (ADP-ribose) polymerase family, member 1	Mus musculus	230-234
20610860-9	2010	In addition, metformin reduced the glucose-induced abundance of SGLT-1 in BBM and increased those of GLUT2, concomitantly increasing the phosphorylation of intracellular AMPKalpha2.	Metformin	13-22	solute carrier family 2 member 2	Homo sapiens	101-106
20363874-3	2010	The AMPK activator metformin stimulated AMPK Thr172 phosphorylation and inhibited IGF-I-stimulated phosphorylation of Akt/tuberous sclerosis 2 (TSC2)/mammalian target of rapamycin (mTOR)/p70S6 kinase (p70S6K).	Metformin	19-28	TSC complex subunit 2	Homo sapiens	118-142
20363874-3	2010	The AMPK activator metformin stimulated AMPK Thr172 phosphorylation and inhibited IGF-I-stimulated phosphorylation of Akt/tuberous sclerosis 2 (TSC2)/mammalian target of rapamycin (mTOR)/p70S6 kinase (p70S6K).	Metformin	19-28	TSC complex subunit 2	Homo sapiens	144-148
20363874-6	2010	Both metformin and constitutively activated AMPK enhanced phosphorylation of IRS-1 Ser794, which led to decreased IRS-1 tyrosine phosphorylation and recruitment of the p85 subunit of PI3K.	Metformin	5-14	phosphoinositide-3-kinase regulatory subunit 2	Homo sapiens	168-171
20363874-9	2010	Cells overexpressing TSC2/S1345A (the site of AMPK phosphorylation) were less responsive to metformin-induced inhibition of p70S6 kinase.	Metformin	92-101	TSC complex subunit 2	Homo sapiens	21-25
20363874-10	2010	These findings are relevant to whole animal physiology because administration of metformin to mice resulted in inhibition of IGF-I-stimulated phosphorylation of Akt/mTOR/p70S6K.	Metformin	81-90	ribosomal protein S6 kinase, polypeptide 1	Mus musculus	170-176
20035912-0	2010	Metformin regresses endometriotic implants in rats by improving implant levels of superoxide dismutase, vascular endothelial growth factor, tissue inhibitor of metalloproteinase-2, and matrix metalloproteinase-9.	Metformin	0-9	matrix metallopeptidase 9	Rattus norvegicus	185-211
20093281-0	2010	Metformin suppresses hepatic gluconeogenesis through induction of SIRT1 and GCN5.	Metformin	0-9	K(lysine) acetyltransferase 2A	Mus musculus	76-80
20093281-4	2010	We report that in db/db mice, metformin (250 mg/kg per day; 7 days) increases hepatic levels of GCN5 protein and mRNA compared with the untreated db/db mice, as well as increases levels of SIRT1 protein and activity relative to controls and untreated db/db mice.	Metformin	30-39	K(lysine) acetyltransferase 2A	Mus musculus	96-100
20093281-10	2010	In conclusion, induction of GCN5 and SIRT1 potentially represents a critical mechanism of action of metformin.	Metformin	100-109	K(lysine) acetyltransferase 2A	Mus musculus	28-32
20069360-6	2010	In the metformin-treated ZDF group, Ki67- and DCX-immunoreactive cells were significantly increased in the SZDG compared to those in the vehicle-treated ZDF group.	Metformin	7-16	doublecortin	Rattus norvegicus	46-49
33757860-3	2021	Preclinical studies have shown that metformin downregulates the insulin/IGF-1 signaling pathway, corrects dendritic defects, and improves repetitive behavior in Fmr1 knockout mice.	Metformin	36-45	insulin-like growth factor 1	Mus musculus	72-77
33758522-8	2021	Metformin treatment significantly inhibited the expression of Bcl-10, Bid, and caspase-3 and upregulated Bad/Bax/caspase-7 pathway suggesting the activation of Bad/Bax/caspase-7 apoptotic pathway.	Metformin	0-9	BCL10 immune signaling adaptor	Homo sapiens	62-68
33997458-6	2021	Six months later, individuals who have not lost at least 5% of their bodyweight or continue to have an HbA1c of 6% or higher are prescribed metformin medication.	Metformin	140-149	hemoglobin subunit alpha 1	Homo sapiens	103-107
33690729-18	2021	However, further investigations are necessary to confirm the observations and conclusions drawn from the presented data after metformin administration, especially for proteins that were regulated in a favorable way, i.e. AKT3, CCND2, CD63, CD81, GFAP, IL5, IL17A, IRF4, PI3, and VTCN1.	Metformin	126-135	interleukin 5	Homo sapiens	252-255
33690729-18	2021	However, further investigations are necessary to confirm the observations and conclusions drawn from the presented data after metformin administration, especially for proteins that were regulated in a favorable way, i.e. AKT3, CCND2, CD63, CD81, GFAP, IL5, IL17A, IRF4, PI3, and VTCN1.	Metformin	126-135	interferon regulatory factor 4	Homo sapiens	264-268
33690729-18	2021	However, further investigations are necessary to confirm the observations and conclusions drawn from the presented data after metformin administration, especially for proteins that were regulated in a favorable way, i.e. AKT3, CCND2, CD63, CD81, GFAP, IL5, IL17A, IRF4, PI3, and VTCN1.	Metformin	126-135	peptidase inhibitor 3	Homo sapiens	270-273
33665728-5	2021	Based on our established IVIVC and in vitro dissolution profiles of generic metformin ER products, we were able to predict their in vivo pharmacokinetic profiles and quantitatively compare the differences in AUC and Cmax to ensure the correct selection of BE product.	Metformin	76-85	epiregulin	Homo sapiens	86-88
33665728-8	2021	Our novel integrative approach of PCA with a convolution-based IVIVC was successfully adopted for the screening of the BE metformin ER formulation and such an approach could be further utilized for the effective selection of BE formulation for other drugs/formulations with complex in vivo absorption processes.	Metformin	122-131	epiregulin	Homo sapiens	132-134
33648513-11	2021	Compared with the LPS group, phosphorylation of p65 and IkappaBalpha in the ML group were decreased and accumulation of NF-kappaB in the nucleus was significantly reduced by pretreatment with metformin.	Metformin	192-201	synaptotagmin 1	Bos taurus	48-51
33648513-12	2021	Metformin protects the cells from the increase of LPS-induced binding activity of NF-kappaB on both TNFA and IL1B promoters.	Metformin	0-9	interleukin 1 beta	Bos taurus	109-113
33648513-15	2021	CONCLUSION: Altogether, our results indicated that pretreatment with metformin dampens LPS-induced inflammatory responses mediated in part by AMPK/NF-kappaB/NLRP3 signaling and modification of histone H3K14 deacetylation and metabolic changes.	Metformin	69-78	NLR family pyrin domain containing 3	Bos taurus	157-162
33368612-9	2021	CONCLUSIONS: SGLT2 inhibitors and GLP1-RAs provided without metformin at baseline may reduce the risk of MACE in comparison with placebo in T2D patients at increased risk of cardiovascular events.	Metformin	60-69	glucagon like peptide 1 receptor	Homo sapiens	34-38
33453674-2	2021	Hence, the study aimed to inspect the ability of the combination therapy of metformin and omega-3 to modulate different signaling pathways and micro RNAs such as (miR-155, miR-146a and miR-34) as new targets in order to mitigate adjuvant-induced arthritis and compare their effect to that of methotrexate.	Metformin	76-85	microRNA 34a	Homo sapiens	185-191
33538080-7	2021	In accordance, deletion of the putative binding site of Smad3 in the TGF-beta1 promoter region severely impaired the promoter activity and response to metformin.	Metformin	151-160	SMAD family member 3	Homo sapiens	56-61
33603170-0	2021	Repurposing dextromethorphan and metformin for treating nicotine-induced cancer by directly targeting CHRNA7 to inhibit JAK2/STAT3/SOX2 signaling.	Metformin	33-42	Janus kinase 2	Homo sapiens	120-124
32897388-5	2021	Widely studied mechanisms of action, such as complex I inhibition leading to AMPK activation, have only been observed in the context of supra-pharmacological (> 1mM) metformin concentrations which do not occur in the clinical setting.	Metformin	166-175	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	77-81
33510179-7	2021	Metformin increased the AMPK and FOXO3 and induced phosphorylation of activating FOXO3 in iCCA cells.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	24-28
33510179-11	2021	In conclusion, Metformin reverts the mesenchymal and EMT traits in iCCA by activating AMPK-FOXO3 related pathways suggesting it might have therapeutic implications.	Metformin	15-24	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	86-90
33507658-4	2021	Currently, the best classes to add after metformin seem to be SGLT2 inhibitors and GLP-1 receptor agonists, as these molecules showed some cardiovascular and renal beneficial effects in dedicated studies.	Metformin	41-50	glucagon like peptide 1 receptor	Homo sapiens	83-97
33575255-6	2020	Interestingly, we discovered that the activation of ECE1, ABCA12, BPY2, EEF1A1, RAD9A, and NIPSNAP1 contributed to in vitro resistance to metformin in DU145 and PC3 cell lines.	Metformin	138-147	ATP binding cassette subfamily A member 12	Homo sapiens	58-64
33575255-6	2020	Interestingly, we discovered that the activation of ECE1, ABCA12, BPY2, EEF1A1, RAD9A, and NIPSNAP1 contributed to in vitro resistance to metformin in DU145 and PC3 cell lines.	Metformin	138-147	eukaryotic translation elongation factor 1 alpha 1	Homo sapiens	72-78
33575255-6	2020	Interestingly, we discovered that the activation of ECE1, ABCA12, BPY2, EEF1A1, RAD9A, and NIPSNAP1 contributed to in vitro resistance to metformin in DU145 and PC3 cell lines.	Metformin	138-147	RAD9 checkpoint clamp component A	Homo sapiens	80-85
33575255-9	2020	These results suggested that a high level of RAD9A may upregulate regulatory T cells to counterbalance metformin in the tumor immune microenvironment.	Metformin	103-112	RAD9 checkpoint clamp component A	Homo sapiens	45-50
33569379-12	2020	Metformin normalized the SR/ER-mitochondria interaction, decreased MICU1 expression and mitochondrial Ca2+ content, and enhanced complex I-driven respiration.	Metformin	0-9	mitochondrial calcium uptake 1	Mus musculus	67-72
33543290-7	2021	CP + metformin treatment also tended to increase antral follicular count (5.4 +- 1.1 versus 2.5 +- 1.6 follicles/section), serum AMH levels (4.6 +- 1.2 versus 2.0 +- 0.8 ng/ml) and the litter size (4.2 +- 1.3 versus 1.5 +- 1.0 mice per pregnancy), compared with CP-alone group.	Metformin	5-14	anti-Mullerian hormone	Mus musculus	129-132
19887597-0	2010	AICAR and metformin, but not exercise, increase muscle glucose transport through AMPK-, ERK-, and PDK1-dependent activation of atypical PKC.	Metformin	10-19	protein kinase C, iota	Mus musculus	136-139
19566821-11	2010	Both rosiglitazone and metformin exhibited gastroprotective effects, as evidenced by significant decreases in the ulcer index, free and total acid output in gastric juice and gastric mucosal malondialdehyde concentrations, with concomitant increases in gastric juice pH (only with rosiglitazone), mucin concentrations, gastric mucosal concentrations of nitric oxide and catalase activity compared with untreated diabetic rats.	Metformin	23-32	solute carrier family 13 member 2	Rattus norvegicus	297-302
20814161-8	2010	In conclusion, our results suggest, at least in part, that obesity might have an effect on the absorption or distribution pharmacokinetics of metformin through an increase in hepatic OCT1 expression.	Metformin	142-151	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	183-187
19858375-0	2009	If mammalian target of metformin indirectly is mammalian target of rapamycin, then the insulin-like growth factor-1 receptor axis will audit the efficacy of metformin in cancer clinical trials.	Metformin	23-32	insulin like growth factor 1 receptor	Homo sapiens	87-124
19858375-0	2009	If mammalian target of metformin indirectly is mammalian target of rapamycin, then the insulin-like growth factor-1 receptor axis will audit the efficacy of metformin in cancer clinical trials.	Metformin	157-166	insulin like growth factor 1 receptor	Homo sapiens	87-124
19502420-0	2009	Insulin and metformin regulate circulating and adipose tissue chemerin.	Metformin	12-21	retinoic acid receptor responder 2	Homo sapiens	62-70
19502420-5	2009	Ex vivo effects of insulin, metformin, and steroid hormones on adipose tissue chemerin protein production and secretion into conditioned media were assessed by Western blotting and enzyme-linked immunosorbent assay, respectively.	Metformin	28-37	retinoic acid receptor responder 2	Homo sapiens	78-86
19502420-9	2009	After 6 months of metformin treatment, there was a significant decrease in serum chemerin (n = 21; P &lt; 0.01).	Metformin	18-27	retinoic acid receptor responder 2	Homo sapiens	81-89
19502420-12	2009	Metformin treatment decreases serum chemerin in these women.	Metformin	0-9	retinoic acid receptor responder 2	Homo sapiens	36-44
19490068-3	2009	Adiponectin, 5-aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR) and metformin activate the AMP-kinase that exerts anti-inflammatory effects, and the influence of adiponectin and these drugs on monocytic CD163 was analysed, and cellular and sCD163 were determined in obesity and type 2 diabetes.	Metformin	75-84	CD163 molecule	Homo sapiens	210-215
19490068-8	2009	Further, metformin and AICAR downregulated CD163.	Metformin	9-18	CD163 molecule	Homo sapiens	43-48
19501448-1	2009	OBJECTIVE: The effects of metformin on S6K1, which is a crucial effector of mTOR signaling, and on endometrium were studied in a mouse model of endometrial hyperplasia induced by unopposed estradiol or tamoxifen.	Metformin	26-35	ribosomal protein S6 kinase, polypeptide 1	Mus musculus	39-43
19501448-9	2009	Addition of metformin to tamoxifen significantly decreased the H-score of S6K1 (p&lt;0.05) and the immunohistochemical expression of PCNA (p&lt;0.05) in uterine lining epithelium, glandular and stromal cells.	Metformin	12-21	ribosomal protein S6 kinase, polypeptide 1	Mus musculus	74-78
19501448-9	2009	Addition of metformin to tamoxifen significantly decreased the H-score of S6K1 (p&lt;0.05) and the immunohistochemical expression of PCNA (p&lt;0.05) in uterine lining epithelium, glandular and stromal cells.	Metformin	12-21	proliferating cell nuclear antigen	Mus musculus	133-137
19501448-10	2009	Addition of metformin to estradiol significantly decreased the H-score of S6K1 (p&lt;0.05) and the immunohistochemical expression of PCNA (p&lt;0.05) in uterine lining epithelium, glandular and stromal cells.	Metformin	12-21	ribosomal protein S6 kinase, polypeptide 1	Mus musculus	74-78
19501448-10	2009	Addition of metformin to estradiol significantly decreased the H-score of S6K1 (p&lt;0.05) and the immunohistochemical expression of PCNA (p&lt;0.05) in uterine lining epithelium, glandular and stromal cells.	Metformin	12-21	proliferating cell nuclear antigen	Mus musculus	133-137
19501448-11	2009	CONCLUSION: Metformin seems to have possible antiproliferative effects on the endometrium of estradiol or tamoxifen treated mice via inhibiting the mTOR mediated S6K1 activation.	Metformin	12-21	ribosomal protein S6 kinase, polypeptide 1	Mus musculus	162-166
19619327-18	2009	Current data indicate that the combined glibenclamide/metformin therapy seems to present special risk and should be avoided in the long-term management of T2DM with proven CAD; 4.	Metformin	54-63	cadherin 4	Homo sapiens	172-178
19494812-7	2009	Administration of the anti-diabetic drug metformin restored FAO and CD8 T(M)-cell generation in the absence of TRAF6.	Metformin	41-50	TNF receptor associated factor 6	Rattus norvegicus	111-116
19494326-3	2009	We provide evidence that metformin attenuates the induction of EAE by restricting the infiltration of mononuclear cells into the CNS, down-regulating the expression of proinflammatory cytokines (IFN-gamma, TNF-alpha, IL-6, IL-17, and inducible NO synthase (iNOS)), cell adhesion molecules, matrix metalloproteinase 9, and chemokine (RANTES).	Metformin	25-34	interleukin 17A	Homo sapiens	223-228
19494326-3	2009	We provide evidence that metformin attenuates the induction of EAE by restricting the infiltration of mononuclear cells into the CNS, down-regulating the expression of proinflammatory cytokines (IFN-gamma, TNF-alpha, IL-6, IL-17, and inducible NO synthase (iNOS)), cell adhesion molecules, matrix metalloproteinase 9, and chemokine (RANTES).	Metformin	25-34	matrix metallopeptidase 9	Homo sapiens	290-331
19494326-3	2009	We provide evidence that metformin attenuates the induction of EAE by restricting the infiltration of mononuclear cells into the CNS, down-regulating the expression of proinflammatory cytokines (IFN-gamma, TNF-alpha, IL-6, IL-17, and inducible NO synthase (iNOS)), cell adhesion molecules, matrix metalloproteinase 9, and chemokine (RANTES).	Metformin	25-34	C-C motif chemokine ligand 5	Homo sapiens	333-339
19494326-7	2009	Metformin inhibited T cell-mediated immune responses including Ag-specific recall responses and production of Th1 or Th17 cytokines, while it induced the generation of IL-10 in spleen cells of treated EAE animals.	Metformin	0-9	negative elongation factor complex member C/D	Homo sapiens	110-113
19494326-7	2009	Metformin inhibited T cell-mediated immune responses including Ag-specific recall responses and production of Th1 or Th17 cytokines, while it induced the generation of IL-10 in spleen cells of treated EAE animals.	Metformin	0-9	interleukin 10	Homo sapiens	168-173
19450513-0	2009	Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of CREB binding protein.	Metformin	0-9	CREB binding protein	Mus musculus	82-102
19450513-3	2009	Here, we show that both the antidiabetic agent metformin and insulin phosphorylate the transcriptional coactivator CREB binding protein (CBP) at serine 436 via PKC iota/lambda.	Metformin	47-56	CREB binding protein	Mus musculus	115-135
19450513-3	2009	Here, we show that both the antidiabetic agent metformin and insulin phosphorylate the transcriptional coactivator CREB binding protein (CBP) at serine 436 via PKC iota/lambda.	Metformin	47-56	CREB binding protein	Mus musculus	137-140
19450513-5	2009	Mice carrying a germline mutation of this CBP phosphorylation site (S436A) demonstrate resistance to the hypoglycemic effect of both insulin and metformin.	Metformin	145-154	CREB binding protein	Mus musculus	42-45
19450513-6	2009	Obese, hyperglycemic mice display hepatic insulin resistance, but metformin is still effective in treating the hyperglycemia of these mice since it stimulates CBP phosphorylation by bypassing the block in insulin signaling.	Metformin	66-75	CREB binding protein	Mus musculus	159-162
33469052-0	2021	Boosting anti-PD-1 therapy with metformin-loaded macrophage-derived microparticles.	Metformin	32-41	programmed cell death 1	Homo sapiens	14-18
33430391-5	2021	While the inhibition of miR-378a-3p was shown to impair metformin"s effect in ATP production, PEPCK activity and the expression of Tfam.	Metformin	56-65	transcription factor A, mitochondrial	Mus musculus	131-135
32940848-12	2021	CONCLUSIONS: We conclude that the combination of metformin and BMS-754807 is more effective than either drug alone in inhibiting cell proliferation in the majority of TNBC cell lines, and that one important mechanism may be suppression of SCFSkp2 and subsequent stabilization of the cell cycle inhibitor p27Kip1.	Metformin	49-58	S-phase kinase associated protein 2	Homo sapiens	239-246
33426334-0	2020	PSTi8 with metformin ameliorates perimenopause induced steatohepatitis associated ER stress by regulating SIRT-1/SREBP-1c axis.	Metformin	11-20	sterol regulatory element binding transcription factor 1	Rattus norvegicus	113-121
19450513-7	2009	Our findings point to CBP phosphorylation at Ser436 by metformin as critical for its therapeutic effect, and as a potential target for pharmaceutical intervention.	Metformin	55-64	CREB binding protein	Mus musculus	22-25
19164462-0	2009	Involvement of human multidrug and toxin extrusion 1 in the drug interaction between cimetidine and metformin in renal epithelial cells.	Metformin	100-109	solute carrier family 47 member 1	Homo sapiens	21-52
32951228-2	2020	The purpose was to study the effect of four-week metformin treatment (120 mg kg-1  day-1 ) of male Wistar rats with high-fat diet/low-dose streptozotocin-induced type 2 diabetes on basal and gonadotropin-stimulated steroidogenesis, intratesticular content of leptin and the leptin and luteinising hormone receptors and on spermatogenesis.	Metformin	49-58	leptin	Rattus norvegicus	259-265
32951228-2	2020	The purpose was to study the effect of four-week metformin treatment (120 mg kg-1  day-1 ) of male Wistar rats with high-fat diet/low-dose streptozotocin-induced type 2 diabetes on basal and gonadotropin-stimulated steroidogenesis, intratesticular content of leptin and the leptin and luteinising hormone receptors and on spermatogenesis.	Metformin	49-58	leptin	Rattus norvegicus	274-280
32951228-8	2020	We concluded that metformin treatment normalises the testicular steroidogenesis in diabetic rats, which is due to restoration of the gonadotropin and leptin systems in the testes and is associated with an improvement in spermatogenesis.	Metformin	18-27	leptin	Rattus norvegicus	150-156
33180557-3	2020	Metformin (Met), a drug approved by the Food and Drug Administration used for the treatment of type 2 diabetes, specifically inhibits HMGB1.	Metformin	0-9	high mobility group box 1	Mus musculus	134-139
33180557-3	2020	Metformin (Met), a drug approved by the Food and Drug Administration used for the treatment of type 2 diabetes, specifically inhibits HMGB1.	Metformin	0-3	high mobility group box 1	Mus musculus	134-139
33126079-4	2020	In addition, activation of AMPK by metformin inhibited S1P-induced ASMCs proliferation by suppressing STAT3 phosphorylation and therefore suppression of PLK1 and ID2 protein expression.	Metformin	35-44	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	27-31
33304158-14	2020	The different treatments decreased caspase 3 and increased insulin gene expression, and the effect was superior in the Ella NPs and metformin group.	Metformin	132-141	caspase 3	Rattus norvegicus	35-44
31851866-0	2020	Metformin promotes innate immunity through a conserved PMK-1/p38 MAPK pathway.	Metformin	0-9	mitogen-activated protein kinase 14	Mus musculus	61-64
31851866-5	2020	Through the screening of classical immune pathways in C. elegans, we find metformin enhances innate immunity through p38 MAPK pathway.	Metformin	74-83	mitogen-activated protein kinase 14	Mus musculus	117-120
31851866-6	2020	Furthermore, activated p38/PMK-1 by metformin acts on the intestine for innate immune response.	Metformin	36-45	mitogen-activated protein kinase 14	Mus musculus	23-26
31851866-8	2020	Therefore, promoted p38/PMK-1-mediated innate immunity by metformin is conserved from worms to mammals.	Metformin	58-67	mitogen-activated protein kinase 14	Mus musculus	20-23
19237574-4	2009	We demonstrate that metformin, at doses that lead to activation of the AMP-activated protein kinase (AMPK), significantly increases the generation of both intracellular and extracellular Abeta species.	Metformin	20-29	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	71-99
19237574-4	2009	We demonstrate that metformin, at doses that lead to activation of the AMP-activated protein kinase (AMPK), significantly increases the generation of both intracellular and extracellular Abeta species.	Metformin	20-29	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	101-105
18393297-1	2008	It has been reported that metformin was primarily metabolized via hepatic CYP2C11, 2D1, and 3A1/2 in rats, and the expression and mRNA levels of hepatic CYP2C11 and 3A1 decreased and increased, respectively, whereas the expression of CYP2D1 was not changed in rat model of diabetes induced by streptozotocin (DMIS).	Metformin	26-35	cytochrome P450, family 2, subfamily d, polypeptide 1	Rattus norvegicus	234-240
19000376-6	2008	The reciprocal relationship between osteoblastic and adipogenic differentiation suggests that metformin may regulate osteoblastic and adipogenic differentiation through inhibition of PPARgamma.	Metformin	94-103	peroxisome proliferator-activated receptor gamma	Rattus norvegicus	183-192
18673148-8	2008	We observed that metformin, besides its antihyperglycemic action, induces a significant decrease in TBARS and MDA levels, GPx and GRed activities and a significant increase in GSH levels and MnSOD activity.	Metformin	17-26	superoxide dismutase 2	Rattus norvegicus	191-196
32911202-0	2020	Effect of metformin and insulin combination on monocyte chemoattractant protein-1 and cathepsin-D in type 2 diabetes mellitus.	Metformin	10-19	cathepsin D	Homo sapiens	86-97
32911202-7	2020	CONCLUSION: Patients treated with metformin and insulin combination had lower serum MCP-1 and cathepsin-D levels which suggests that this combination may be more effective in reducing the progression of diabetic retinopathy.	Metformin	34-43	cathepsin D	Homo sapiens	94-105
33112812-0	2020	Metformin decreases miR-122, miR-223 and miR-29a in women with polycystic ovary syndrome.	Metformin	0-9	microRNA 223	Homo sapiens	29-36
32870322-6	2020	We further found that metformin significantly suppressed NLRP3 inflammasome activation, subsequent caspase-1 cleavage, and interleukin-1beta secretion in both peripheral macrophages and central hippocampus.	Metformin	22-31	caspase 1	Mus musculus	99-108
32239671-0	2020	Metformin inhibition of colorectal cancer cell migration is associated with rebuilt adherens junctions and FAK downregulation.	Metformin	0-9	protein tyrosine kinase 2	Homo sapiens	107-110
32239671-4	2020	Metformin also promoted translocation from the cytosol to the plasma membrane of p120-catenin, another core component of the AJs.	Metformin	0-9	catenin delta 1	Homo sapiens	81-93
32239671-6	2020	Western blot analysis of lysates of CRC-derived cells revealed a substantial metformin-induced increase in the level of p120-catenin as well as E-cadherin phosphorylation on Ser838/840 , a modification associated with beta-catenin/E-cadherin interaction.	Metformin	77-86	catenin delta 1	Homo sapiens	120-132
32239671-7	2020	These modifications in E-cadherin, p120-catenin and beta-catenin localization suggest that metformin induces rebuilding of AJs in CRC-derived cells.	Metformin	91-100	catenin delta 1	Homo sapiens	35-47
33065544-9	2020	The expression of genes related to steroidogenesis such as FSHR, STAR, CYP11A1, HSD3B, and progesterone secretion was significantly decreased in response to metformin treatment in a dose-dependent manner.	Metformin	157-166	steroidogenic acute regulatory protein	Gallus gallus	65-69
18555836-0	2008	Adiponectin receptors: expression in Zucker diabetic rats and effects of fenofibrate and metformin.	Metformin	89-98	adiponectin, C1Q and collagen domain containing	Rattus norvegicus	0-11
18555836-3	2008	We determined if the expression of adiponectin receptors is decreased in an experimental model, the Zucker diabetic rat (ZDF), and if a peroxisome proliferator-activated receptor alpha agonist, fenofibrate, and metformin could increase these expressions.	Metformin	211-220	adiponectin, C1Q and collagen domain containing	Rattus norvegicus	35-46
18514142-0	2008	Thiazolidinedione addition reduces the serum retinol-binding protein 4 in type 2 diabetic patients treated with metformin and sulfonylurea.	Metformin	112-121	retinol binding protein 4	Homo sapiens	45-70
32781368-4	2020	Thus, the aim of the present work was to investigate whether the pharmacological inhibition of G6PDH, the first and rate-limiting enzyme of the PPP, by 6-amino nicotinamide (6-AN) potentiates the antitumoral activity of metformin on different human melanoma cell lines.	Metformin	220-229	hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase	Homo sapiens	95-100
32829010-5	2020	We identified and selected metformin, simvastatin and digoxin (C3) as a novel combination of FDA approved drugs, which were shown to effectively target PDX1 and BIRC5 in human PDAC tumors in mice with no toxicity.	Metformin	27-36	pancreatic and duodenal homeobox 1	Homo sapiens	152-156
33116117-0	2020	Metformin as a senostatic drug enhances the anticancer efficacy of CDK4/6 inhibitor in head and neck squamous cell carcinoma.	Metformin	0-9	cyclin dependent kinase 4	Homo sapiens	67-73
33116117-4	2020	We investigated whether metformin can act as a senostatic drug to modulate the SASP and enhance the anticancer efficacy of CDK4/6 inhibitors in HNSCC.	Metformin	24-33	cyclin dependent kinase 4	Homo sapiens	123-129
33116117-12	2020	Collectively, our data suggest that metformin can act as a senostatic drug to enhance the anticancer efficacy of CDK4/6 inhibitors by reprogramming the profiles of the SASP.	Metformin	36-45	cyclin dependent kinase 4	Homo sapiens	113-119
33108409-0	2020	Metformin partially reverses the inhibitory effect of co-culture with ER-/PR-/HER2+ breast cancer cells on biomarkers of monocyte antitumor activity.	Metformin	0-9	epiregulin	Homo sapiens	70-72
32800853-0	2020	Activation of AMPK/aPKCzeta/CREB pathway by metformin is associated with upregulation of GDNF and dopamine.	Metformin	44-53	glial cell line derived neurotrophic factor	Mus musculus	89-93
32800853-5	2020	Herein, we found that metformin enhanced the phosphorylation of tyrosine hydroxylase (TH) which was accompanied by increase in brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and activation of their downstream signaling pathways in the mouse brain and SH-SY5Y cells.	Metformin	22-31	glial cell line derived neurotrophic factor	Mus musculus	169-212
32800853-5	2020	Herein, we found that metformin enhanced the phosphorylation of tyrosine hydroxylase (TH) which was accompanied by increase in brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and activation of their downstream signaling pathways in the mouse brain and SH-SY5Y cells.	Metformin	22-31	glial cell line derived neurotrophic factor	Mus musculus	214-218
32861747-5	2020	Transfection of mir-181c, one of the positive regulators of Akt and mTOR, lead to an increase in the cell resistance to both mTOR inhibitors, rapamycin, and metformin, which correlated with Raptor overexpression and activation of Akt/AP-1 signaling.	Metformin	157-166	microRNA 181c	Homo sapiens	16-24
32861747-5	2020	Transfection of mir-181c, one of the positive regulators of Akt and mTOR, lead to an increase in the cell resistance to both mTOR inhibitors, rapamycin, and metformin, which correlated with Raptor overexpression and activation of Akt/AP-1 signaling.	Metformin	157-166	regulatory associated protein of MTOR complex 1	Homo sapiens	190-196
32861747-5	2020	Transfection of mir-181c, one of the positive regulators of Akt and mTOR, lead to an increase in the cell resistance to both mTOR inhibitors, rapamycin, and metformin, which correlated with Raptor overexpression and activation of Akt/AP-1 signaling.	Metformin	157-166	JunD proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	234-238
32728891-13	2020	Post metformin iGLP-1 and PYY concentrations in youth with type 2 diabetes were comparable to levels in youth with NGT.	Metformin	5-14	Immune response to synthetic polypeptides-1	Homo sapiens	15-21
33471718-2	2020	Metformin increases the expression of angiotensin converting enzyme 2, a known receptor for severe acute respiratory syndrome coronavirus 2.	Metformin	0-9	angiotensin converting enzyme 2	Homo sapiens	38-69
32912901-2	2020	In particular, the detailed molecular interplays between the AMPK and the mTORC1 pathway in the hepatic benefits of metformin are still ill defined.	Metformin	116-125	CREB regulated transcription coactivator 1	Mus musculus	74-80
32912901-3	2020	Metformin-dependent activation of AMPK classically inhibits mTORC1 via TSC/RHEB, but several lines of evidence suggest additional mechanisms at play in metformin inhibition of mTORC1.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	60-66
32912901-3	2020	Metformin-dependent activation of AMPK classically inhibits mTORC1 via TSC/RHEB, but several lines of evidence suggest additional mechanisms at play in metformin inhibition of mTORC1.	Metformin	0-9	Ras homolog enriched in brain	Mus musculus	75-79
32912901-3	2020	Metformin-dependent activation of AMPK classically inhibits mTORC1 via TSC/RHEB, but several lines of evidence suggest additional mechanisms at play in metformin inhibition of mTORC1.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	176-182
32912901-3	2020	Metformin-dependent activation of AMPK classically inhibits mTORC1 via TSC/RHEB, but several lines of evidence suggest additional mechanisms at play in metformin inhibition of mTORC1.	Metformin	152-161	CREB regulated transcription coactivator 1	Mus musculus	176-182
32912901-5	2020	Metformin treatment of primary hepatocytes and intact murine liver requires AMPK regulation of both RAPTOR and TSC2 to fully inhibit mTORC1, and this regulation is critical for both the translational and transcriptional response to metformin.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	133-139
32912901-6	2020	Transcriptionally, AMPK and mTORC1 were both important for regulation of anabolic metabolism and inflammatory programs triggered by metformin treatment.	Metformin	132-141	CREB regulated transcription coactivator 1	Mus musculus	28-34
32800550-0	2020	Metformin, resveratrol, and exendin-4 inhibit high phosphate-induced vascular calcification via AMPK-RANKL signaling.	Metformin	0-9	TNF superfamily member 11	Rattus norvegicus	101-106
32800550-5	2020	Metformin, resveratrol, and exendin-4 reduced the expression of osteoblast differentiation-associated factors, such as runt-related transcription factor 2, bone morphogenic protein-2, p-small mothers against decapentaplegic 1/5/8, and Rankl.	Metformin	0-9	TNF superfamily member 11	Rattus norvegicus	235-240
33014814-0	2020	Metformin Overcomes Acquired Resistance to EGFR TKIs in EGFR-Mutant Lung Cancer via AMPK/ERK/NF-kappaB Signaling Pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	84-88
33014814-11	2020	Mechanistically, those effects of metformin were associated with activation of AMPK, resulting in the inhibition of downstream ERK/NF-kappaB signaling.	Metformin	34-43	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	79-83
31720741-9	2020	Genetic or pharmacological AMPK activation by AMPK overexpression or metformin, as well as genetic or pharmacological autophagy induction by TFEB overexpression or lithium chloride, reduced the sensitivity of nutrient-deprived SH-SY5Y cells to glutamate excitotoxicity.	Metformin	69-78	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	27-31
32700188-1	2020	INTRODUCTION: International guidelines recommend treatment with a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist for treatment intensification in type 2 diabetes mellitus (T2DM) patients with progression on metformin.	Metformin	262-271	glucagon like peptide 1 receptor	Homo sapiens	144-159
32841254-8	2020	Lower OPG/RANKL, increased OCN and TRAP expression were observed in hyperglycemic animals, and treatment with metformin partially reversed hyperglycemia on the OPG/RANKL, OPN and TRAP expression in the periodontitis.	Metformin	110-119	TNF superfamily member 11	Rattus norvegicus	10-15
32841254-8	2020	Lower OPG/RANKL, increased OCN and TRAP expression were observed in hyperglycemic animals, and treatment with metformin partially reversed hyperglycemia on the OPG/RANKL, OPN and TRAP expression in the periodontitis.	Metformin	110-119	TNF superfamily member 11	Rattus norvegicus	164-169
32470453-8	2020	As a plausible mechanism to mediate T-cell function, metformin showed enhanced potential to regulate mechanistic targets of rapamycin (mTOR), STAT5 and adenosine-monophosphate-activated protein kinase (AMPK) signalling pathways.	Metformin	53-62	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	152-200
32470453-8	2020	As a plausible mechanism to mediate T-cell function, metformin showed enhanced potential to regulate mechanistic targets of rapamycin (mTOR), STAT5 and adenosine-monophosphate-activated protein kinase (AMPK) signalling pathways.	Metformin	53-62	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	202-206
32473247-2	2020	Co-delivery of metformin (MET) with phosphatidylserine liposomes neuroprotectant may be beneficial in ameliorating AD-related symptoms like memory impairment and inflammation.	Metformin	15-24	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	26-29
32473247-3	2020	Therefore, we aimed to prepare metformin containing phosphatidylserine nanoliposomes formulation (MET-PSL) and to evaluate its effect on rats subjected to AD.	Metformin	31-40	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	98-101
18514142-3	2008	Therefore, we investigated whether TZD could affect serum RBP4 level in type 2 diabetes already treated with MF and/or SU.	Metformin	109-111	retinol binding protein 4	Homo sapiens	58-62
18384255-6	2008	Metformin is not metabolized but is transported by at least two organic cation transporters (OCT), OCT1 and OCT2.	Metformin	0-9	POU class 2 homeobox 2	Homo sapiens	108-112
18055057-6	2008	Knockdown of organic cation transporter 1 (OCT1), which is thought to be the gene that influences metformin action, was shown to successfully diminish the ability of metformin to inhibit gluconeogenesis in H4IIEC3 cells.	Metformin	98-107	solute carrier family 22 member 1	Rattus norvegicus	13-41
18055057-6	2008	Knockdown of organic cation transporter 1 (OCT1), which is thought to be the gene that influences metformin action, was shown to successfully diminish the ability of metformin to inhibit gluconeogenesis in H4IIEC3 cells.	Metformin	98-107	solute carrier family 22 member 1	Rattus norvegicus	43-47
18055057-6	2008	Knockdown of organic cation transporter 1 (OCT1), which is thought to be the gene that influences metformin action, was shown to successfully diminish the ability of metformin to inhibit gluconeogenesis in H4IIEC3 cells.	Metformin	166-175	solute carrier family 22 member 1	Rattus norvegicus	13-41
18055057-6	2008	Knockdown of organic cation transporter 1 (OCT1), which is thought to be the gene that influences metformin action, was shown to successfully diminish the ability of metformin to inhibit gluconeogenesis in H4IIEC3 cells.	Metformin	166-175	solute carrier family 22 member 1	Rattus norvegicus	43-47
17609683-5	2008	The effect of OCT1 on metformin pharmacokinetics in mice was less than in humans possibly reflecting species differences in hepatic expression level of the transporter.	Metformin	22-31	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	14-18
17909097-0	2008	Metformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent regulation of the orphan nuclear receptor SHP.	Metformin	0-9	nuclear receptor subfamily 0, group B, member 2	Mus musculus	132-135
17909097-2	2008	The aim of the study was to determine whether metformin regulates hepatic gluconeogenesis through the orphan nuclear receptor small heterodimer partner (SHP; NR0B2).	Metformin	46-55	nuclear receptor subfamily 0, group B, member 2	Mus musculus	153-156
17909097-2	2008	The aim of the study was to determine whether metformin regulates hepatic gluconeogenesis through the orphan nuclear receptor small heterodimer partner (SHP; NR0B2).	Metformin	46-55	nuclear receptor subfamily 0, group B, member 2	Mus musculus	158-163
17909097-3	2008	RESEARCH DESIGN AND METHODS: We assessed the regulation of hepatic SHP gene expression by Northern blot analysis with metformin and adenovirus containing a constitutive active form of AMP-activated protein kinase (AMPK) (Ad-AMPK) and evaluated SHP, PEPCK, and G6Pase promoter activities via transient transfection assays in hepatocytes.	Metformin	118-127	nuclear receptor subfamily 0, group B, member 2	Mus musculus	67-70
17909097-4	2008	Knockdown of SHP using siRNA SHP was conducted to characterize the metformin-induced inhibition of hepatic gluconeogenic gene expression in hepatocytes, and metformin-and adenovirus SHP (Ad-SHP)-mediated hepatic glucose production was measured in B6-Lep(ob/ob) mice.	Metformin	67-76	nuclear receptor subfamily 0, group B, member 2	Mus musculus	13-16
17909097-6	2008	Metformin-induced SHP gene expression was abolished by adenovirus containing the dominant negative form of AMPK (Ad-DN-AMPK), as well as by compound C. Metformin inhibited hepatocyte nuclear factor-4alpha-or FoxA2-mediated promoter activity of PEPCK and G6Pase, and the inhibition was blocked with siRNA SHP.	Metformin	0-9	nuclear receptor subfamily 0, group B, member 2	Mus musculus	18-21
17909097-6	2008	Metformin-induced SHP gene expression was abolished by adenovirus containing the dominant negative form of AMPK (Ad-DN-AMPK), as well as by compound C. Metformin inhibited hepatocyte nuclear factor-4alpha-or FoxA2-mediated promoter activity of PEPCK and G6Pase, and the inhibition was blocked with siRNA SHP.	Metformin	0-9	phosphoenolpyruvate carboxykinase 1, cytosolic	Mus musculus	244-249
17909097-6	2008	Metformin-induced SHP gene expression was abolished by adenovirus containing the dominant negative form of AMPK (Ad-DN-AMPK), as well as by compound C. Metformin inhibited hepatocyte nuclear factor-4alpha-or FoxA2-mediated promoter activity of PEPCK and G6Pase, and the inhibition was blocked with siRNA SHP.	Metformin	0-9	nuclear receptor subfamily 0, group B, member 2	Mus musculus	304-307
17909097-6	2008	Metformin-induced SHP gene expression was abolished by adenovirus containing the dominant negative form of AMPK (Ad-DN-AMPK), as well as by compound C. Metformin inhibited hepatocyte nuclear factor-4alpha-or FoxA2-mediated promoter activity of PEPCK and G6Pase, and the inhibition was blocked with siRNA SHP.	Metformin	152-161	nuclear receptor subfamily 0, group B, member 2	Mus musculus	18-21
17909097-6	2008	Metformin-induced SHP gene expression was abolished by adenovirus containing the dominant negative form of AMPK (Ad-DN-AMPK), as well as by compound C. Metformin inhibited hepatocyte nuclear factor-4alpha-or FoxA2-mediated promoter activity of PEPCK and G6Pase, and the inhibition was blocked with siRNA SHP.	Metformin	152-161	phosphoenolpyruvate carboxykinase 1, cytosolic	Mus musculus	244-249
17909097-6	2008	Metformin-induced SHP gene expression was abolished by adenovirus containing the dominant negative form of AMPK (Ad-DN-AMPK), as well as by compound C. Metformin inhibited hepatocyte nuclear factor-4alpha-or FoxA2-mediated promoter activity of PEPCK and G6Pase, and the inhibition was blocked with siRNA SHP.	Metformin	152-161	nuclear receptor subfamily 0, group B, member 2	Mus musculus	304-307
17909097-7	2008	Additionally, SHP knockdown by adenovirus containing siRNA SHP inhibited metformin-mediated repression of cAMP/dexamethasone-induced hepatic gluconeogenic gene expression.	Metformin	73-82	nuclear receptor subfamily 0, group B, member 2	Mus musculus	14-17
17909097-7	2008	Additionally, SHP knockdown by adenovirus containing siRNA SHP inhibited metformin-mediated repression of cAMP/dexamethasone-induced hepatic gluconeogenic gene expression.	Metformin	73-82	nuclear receptor subfamily 0, group B, member 2	Mus musculus	59-62
17909097-8	2008	Furthermore, oral administration of metformin increased SHP mRNA levels in B6-Lep(ob/ob) mice.	Metformin	36-45	nuclear receptor subfamily 0, group B, member 2	Mus musculus	56-59
17909097-10	2008	CONCLUSIONS: We have concluded that metformin inhibits hepatic gluconeogenesis through AMPK-dependent regulation of SHP.	Metformin	36-45	nuclear receptor subfamily 0, group B, member 2	Mus musculus	116-119
18237462-1	2008	Metformin is metabolized primarily via hepatic microsomal cytochrome P450 (CYP)2C11, CYP2D1 and CYP3A1/2 in rats.	Metformin	0-9	cytochrome P450, family 2, subfamily d, polypeptide 1	Rattus norvegicus	85-91
17876861-3	2007	Uptake of metformin was facilitated by over-expression of hOCT1 and hOCT2 and showed saturable processes, indicating that metformin is a substrate of hOCT1 and hOCT2.	Metformin	10-19	POU class 2 homeobox 2	Homo sapiens	68-73
17876861-3	2007	Uptake of metformin was facilitated by over-expression of hOCT1 and hOCT2 and showed saturable processes, indicating that metformin is a substrate of hOCT1 and hOCT2.	Metformin	10-19	POU class 2 homeobox 2	Homo sapiens	160-165
17876861-3	2007	Uptake of metformin was facilitated by over-expression of hOCT1 and hOCT2 and showed saturable processes, indicating that metformin is a substrate of hOCT1 and hOCT2.	Metformin	122-131	POU class 2 homeobox 2	Homo sapiens	68-73
17876861-3	2007	Uptake of metformin was facilitated by over-expression of hOCT1 and hOCT2 and showed saturable processes, indicating that metformin is a substrate of hOCT1 and hOCT2.	Metformin	122-131	POU class 2 homeobox 2	Homo sapiens	160-165
17876861-4	2007	The IC(50) values of TAAs for hOCT2 were lower than hOCT1 and decreased with increasing alkyl chain length, indicating that the inhibitory potential of TAAs on metformin uptake was greater in hOCT2 than in hOCT1 and increased with increasing alkyl chain length.	Metformin	160-169	POU class 2 homeobox 2	Homo sapiens	30-35
17876861-4	2007	The IC(50) values of TAAs for hOCT2 were lower than hOCT1 and decreased with increasing alkyl chain length, indicating that the inhibitory potential of TAAs on metformin uptake was greater in hOCT2 than in hOCT1 and increased with increasing alkyl chain length.	Metformin	160-169	POU class 2 homeobox 2	Homo sapiens	192-197
18075846-7	2007	CONCLUSIONS: The major novel information of the present study is that ASP and C3 values are markedly increased in non-obese patients with PCOS, with a decrease evidenced with metformin treatment.	Metformin	175-184	complement C3	Homo sapiens	78-80
17701831-2	2007	Transfection of rOct1 resulted in a considerable increase in the uptake of metformin, whereas that of hOCT1 resulted in only a slight increase.	Metformin	75-84	solute carrier family 22 member 1	Rattus norvegicus	16-21
32690681-0	2020	Metformin inhibits RAN translation through PKR pathway and mitigates disease in C9orf72 ALS/FTD mice.	Metformin	0-9	C9orf72-SMCR8 complex subunit	Homo sapiens	80-87
32690681-6	2020	In summary, targeting PKR, including by use of metformin, is a promising therapeutic approach for C9orf72 ALS/FTD and other expansion diseases.	Metformin	47-56	C9orf72-SMCR8 complex subunit	Homo sapiens	98-105
32792943-10	2020	In addition, either celecoxib alone or in combination with metformin suppressed NSCLC cell migration and invasion by inhibiting FAK, N-cadherin, and matrix metalloproteinase-9 activities.	Metformin	59-68	protein tyrosine kinase 2	Homo sapiens	128-131
32679729-3	2020	Pharmacological reagents, including statins, metformin, berberine, polyphenol, and resveratrol, all of which are widely used therapeutics for cardiovascular disorders, appear to deliver their protective/therapeutic effects partially via AMPK signaling modulation.	Metformin	45-54	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	237-241
32631421-12	2020	Furthermore, metformin also regulated the mRNA and protein expression of MICA and HSP70 on the surface of human cervical cancer cells via the PI3K/Akt pathway, enhancing NK cell cytotoxicity.	Metformin	13-22	MHC class I polypeptide-related sequence A	Homo sapiens	73-77
32072735-0	2020	Dapagliflozin plus saxagliptin add-on to metformin reduces liver fat and adipose tissue volume in patients with type 2 diabetes.	Metformin	41-50	FAT atypical cadherin 1	Homo sapiens	65-68
32072735-6	2020	In the full-study population, dapagliflozin plus saxagliptin plus metformin decreased body weight and serum alanine aminotransferase and aspartate aminotransferase levels over 52 weeks.	Metformin	66-75	glutamic--pyruvic transaminase	Homo sapiens	108-132
17167165-9	2007	Other known PRKA activators, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) and metformin, also blocked meiotic resumption in COC.	Metformin	96-105	A kinase (PRKA) anchor protein 6	Mus musculus	12-16
17123942-10	2007	Metformin decreased phosphorylation levels of MAPK3/MAPK1 and MAPK14 in a dose- and time-dependent manner.	Metformin	0-9	mitogen-activated protein kinase 14	Bos taurus	62-68
19888409-10	2007	Significant increases demonstrated for RBP4 in both treatment arms were more pronounced in the metformin group (metformin: +66%, rosiglitazone: +33%).	Metformin	95-104	retinol binding protein 4	Homo sapiens	39-43
19888409-10	2007	Significant increases demonstrated for RBP4 in both treatment arms were more pronounced in the metformin group (metformin: +66%, rosiglitazone: +33%).	Metformin	112-121	retinol binding protein 4	Homo sapiens	39-43
17135357-4	2007	We report that when S122 on NDPK-A is phosphorylated by AMPK alpha1 in vivo, (i.e., stimulation of AMPK using either metformin or phenformin) initiating the substrate channeling mechanism, the catalytic subunit of CK2 (CK2alpha) is expelled from the complex and translocates to bind NDPK-B, a closely related but independent isoform of NDPK.	Metformin	117-126	casein kinase 2 alpha 2	Homo sapiens	219-227
16760380-6	2006	Metformin treatment (10 mM, 24 h) also reduced cell proliferation and the levels of CCND2 and CCNE proteins without affecting cell viability, both in the basal state and in response to FSH.	Metformin	0-9	cyclin D2	Rattus norvegicus	84-89
16859126-7	2006	After treatment with rosiglitazone and metformin, IMTc and serum MMP-9 levels decreased significantly (P &lt; 0.05).	Metformin	39-48	matrix metallopeptidase 9	Homo sapiens	65-70
16514202-8	2006	However, when metformin was administered together with DHEA, the percentages of CD4 + and CD8 + T lymphocyte populations from both ovarian tissue and retroperitoneal lymph nodes were similar to those observed in controls.	Metformin	14-23	CD4 antigen	Mus musculus	80-83
16443786-3	2006	Exposure of cultured bovine aortic endothelial cells (BAECs) to clinically relevant concentrations of metformin (50-500 micromol/l) dose-dependently increased serine-1179 (Ser1179) phosphorylation (equal to human Ser1179) of endothelial nitric oxide (NO) synthase (eNOS) as well as its association with heat shock protein (hsp)-90, resulting in increased activation of eNOS and NO bioactivity (cyclic GMP).	Metformin	102-111	5'-nucleotidase, cytosolic II	Homo sapiens	401-404
16272756-0	2005	Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1.	Metformin	0-9	POU class 2 homeobox 2	Homo sapiens	71-75
16272756-5	2005	A kinetic analysis of metformin transport demonstrated that the amount of plasmid cDNA for transfection was also important parameter to the quantitative elucidation of functional characteristics of transporters, and both human and rat OCT2 had about a 10- and 100-fold greater capacity to transport metformin than did OCT1, respectively.	Metformin	22-31	solute carrier family 22 member 1	Rattus norvegicus	318-322
16272756-8	2005	These findings suggest that metformin is a superior substrate for renal OCT2 rather than hepatic OCT1, and renal OCT2 plays a dominant role for metformin pharmacokinetics.	Metformin	28-37	POU class 2 homeobox 2	Homo sapiens	72-76
16272756-8	2005	These findings suggest that metformin is a superior substrate for renal OCT2 rather than hepatic OCT1, and renal OCT2 plays a dominant role for metformin pharmacokinetics.	Metformin	144-153	POU class 2 homeobox 2	Homo sapiens	113-117
16372821-15	2005	The biguanide metformin is not significantly metabolised but polymorphisms in the organic cation transporter (OCT) 1 and OCT2 may determine its pharmacokinetic variability.	Metformin	14-23	POU class 2 homeobox 2	Homo sapiens	121-125
15039452-2	2004	We previously found that the biguanide metformin, an antidiabetic agent, causes a significant increase of plasma active GLP-1 level in the presence of dipeptidyl peptidase IV (DPPIV) inhibitor in normal rats.	Metformin	39-48	glucagon	Rattus norvegicus	120-125
14605997-2	2003	METHODS: rGLP-1 was administered s. c. to 40 type 2 diabetics currently treated by diet, sulfonylurea (SU), metformin, or insulin in a double-blind, placebo-controlled, cross-over trial; preexisting treatments were continued during the study.	Metformin	108-117	glucagon	Rattus norvegicus	9-15
14605997-6	2003	RESULTS: In the diet, SU, and metformin cohorts, bolus rGLP-1 injections produced modest reductions in mean FSG levels, averaging 17.4 mg/dl (7.3-27.5; 95 % CI) at the highest dose (p &lt; 0.001 vs. placebo).	Metformin	30-39	glucagon	Rattus norvegicus	55-61
12644585-0	2003	Involvement of organic cation transporter 1 in the lactic acidosis caused by metformin.	Metformin	77-86	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	15-43
32278655-8	2020	Doses of metformin sufficient to lower glucose and increase GLP-1 levels in GcgGut+/+ mice retained their glucoregulatory activity, yet failed to increase GLP-1 levels in GcgGut-/- mice.	Metformin	9-18	glucagon	Mus musculus	60-65
32278655-9	2020	Surprisingly, the actions of metformin to increase plasma GLP-1 levels were substantially attenuated in GcgDistalGut-/- mice.	Metformin	29-38	glucagon	Mus musculus	58-63
32535544-7	2020	Specifically, we describe the molecular mechanisms involved in metformin"s effect on gluconeogenesis, its capacity to interfere with major metabolic pathways (AMPK and mTORC1), its action on mitochondria and its antioxidant effects.	Metformin	63-72	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	159-163
32535544-7	2020	Specifically, we describe the molecular mechanisms involved in metformin"s effect on gluconeogenesis, its capacity to interfere with major metabolic pathways (AMPK and mTORC1), its action on mitochondria and its antioxidant effects.	Metformin	63-72	CREB regulated transcription coactivator 1	Mus musculus	168-174
32556103-6	2020	Moreover, lowering UA using benzbromarone (a uricosuric agent) or metformin-induced activation of AMPK expression significantly attenuated UA-induced FFA metabolism impairment and adipose beiging suppression, which subsequently alleviated serum FFA elevation and insulin resistance in HUA mice.	Metformin	66-75	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	98-102
32566257-0	2020	Metformin effectively treats Tsc1 deletion-caused kidney pathology by upregulating AMPK phosphorylation.	Metformin	0-9	TSC complex subunit 1	Mus musculus	29-33
32566257-5	2020	We therefore treated Tsc1 ptKO mice with the AMPK activator, metformin, by daily intraperitoneal injection.	Metformin	61-70	TSC complex subunit 1	Mus musculus	21-25
32626781-11	2020	Finally, the levels of IL-1beta, TNF-alpha, Bax, and caspase-3 were also decreased in both treated groups (metformin and green coffee) when compared to the diabetic group.	Metformin	107-116	caspase 3	Rattus norvegicus	53-62
32545395-9	2020	In contrast, metformin, an AMPK activator, suppressed H. pylori-induced apoptosis, showing that AMPK activation inhibits H. pylori-induced apoptosis.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	27-31
32545395-9	2020	In contrast, metformin, an AMPK activator, suppressed H. pylori-induced apoptosis, showing that AMPK activation inhibits H. pylori-induced apoptosis.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	96-100
32596370-7	2020	Subsequently, metformin, a first-line clinical drug for T2DM treatment, was found to improve the osteogenic differentiation potential of BMSCs from T2DM patients via the BMP-4/Smad/Runx2 signaling pathway.	Metformin	14-23	bone morphogenetic protein 4	Homo sapiens	170-175
32243780-3	2020	Administering the AMPK activator metformin decreases epithelial progenitor proliferation and increases acid-secreting parietal cells (PCs) in mice and organoids.	Metformin	33-42	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	18-22
32243780-7	2020	Thus, AMPK activates KLF4 in progenitors to reduce self-renewal and promote PC fate, whereas AMPK-PGC1alpha activation within the PC lineage promotes maturation, providing a potential suggestion for why metformin increases acid secretion and reduces gastric cancer risk in humans.	Metformin	203-212	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	6-10
32243780-7	2020	Thus, AMPK activates KLF4 in progenitors to reduce self-renewal and promote PC fate, whereas AMPK-PGC1alpha activation within the PC lineage promotes maturation, providing a potential suggestion for why metformin increases acid secretion and reduces gastric cancer risk in humans.	Metformin	203-212	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	93-97
32369446-10	2020	Tumors treated with metformin had a 2.4-fold decrease in ALDH+/CD133+ CSC and increased sensitivity to cisplatin ex vivo.	Metformin	20-29	prominin 1	Homo sapiens	63-68
32493421-17	2020	The mechanistic studies indicated that the therapeutic effects of Diane-35 plus metformin treatment in the PCOS rats may be associated with the regulation of glycolysis-related mediators including PKM2, LDH-A and SIRT1.	Metformin	80-89	pyruvate kinase M1/2	Rattus norvegicus	197-201
32493421-17	2020	The mechanistic studies indicated that the therapeutic effects of Diane-35 plus metformin treatment in the PCOS rats may be associated with the regulation of glycolysis-related mediators including PKM2, LDH-A and SIRT1.	Metformin	80-89	lactate dehydrogenase A	Rattus norvegicus	203-208
32572457-0	2020	Metformin Corrects Abnormal Circadian Rhythm and Kir4.1 Channels in Diabetes.	Metformin	0-9	potassium inwardly-rectifying channel, subfamily J, member 10	Mus musculus	49-55
32572457-3	2020	Metformin, a commonly used oral antidiabetic drug, is known to elicit its action through 5" adenosine monophosphate-activated protein kinase (AMPK), a cellular metabolic regulator; however, its effect on Kir4.1 channels is unknown.	Metformin	0-9	potassium inwardly-rectifying channel, subfamily J, member 10	Mus musculus	204-210
32572457-4	2020	For this study, we hypothesized that metformin treatment would correct circadian rhythm disruption and Kir4.1 channel dysfunction in db/db mice.	Metformin	37-46	potassium inwardly-rectifying channel, subfamily J, member 10	Mus musculus	103-109
32572457-9	2020	The Kir4.1 level in Muller cells was corrected after metformin treatment.	Metformin	53-62	potassium inwardly-rectifying channel, subfamily J, member 10	Mus musculus	4-10
32572457-13	2020	Conclusions: Our findings demonstrate that metformin corrects abnormal circadian rhythm and Kir4.1 channels in db/db mouse a model of type 2 diabetes.	Metformin	43-52	potassium inwardly-rectifying channel, subfamily J, member 10	Mus musculus	92-98
32550106-0	2020	Metformin attenuates TGF-beta1-induced pulmonary fibrosis through inhibition of transglutaminase 2 and subsequent TGF-beta pathways.	Metformin	0-9	transforming growth factor alpha	Homo sapiens	21-29
32550106-1	2020	The purpose of this study was to confirm whether metformin can attenuate TGF-beta1-induced pulmonary fibrosis through inhibition of transglutaminase 2 (TG2) and subsequent TGF-beta pathways.	Metformin	49-58	transforming growth factor alpha	Homo sapiens	73-81
32550106-11	2020	Taken together, our results demonstrated that metformin can attenuate TGF-beta1-induced pulmonary fibrosis, at least partly, through inhibition of TG2 and subsequent TGF-beta pathways.	Metformin	46-55	transforming growth factor alpha	Homo sapiens	70-78
32048878-12	2020	AMPK agonists, A769662 and metformin increased the mitochondrial complex proteins and number, in vitro angiogenesis and Jag1 levels and decreased DLL4 levels in PPHN PAEC.	Metformin	27-36	delta-like protein 4	Ovis aries	146-150
31840936-10	2020	Decreased GLUT1 protein expression was observed in parallel with increased P-AMPK protein expression in SFC in the presence of metformin (n=4).	Metformin	127-136	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	75-81
31840936-14	2020	Furthermore the effect of metformin on pro-inflammatory mechanisms suggests a role for AMPK modifying compounds for treatment of RA.	Metformin	26-35	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	87-91
32270948-9	2020	In addition, metformin significantly attenuated IL-6, IL-1beta, and TNF-alpha production and increased the expression of active caspase-3 and Bax in the liver (p<0.05).	Metformin	13-22	caspase 3	Rattus norvegicus	128-137
32179514-0	2020	GPD1 Enhances the Anticancer Effects of Metformin by Synergistically Increasing Total Cellular Glycerol-3-Phosphate.	Metformin	40-49	glycerol-3-phosphate dehydrogenase 1	Homo sapiens	0-4
32179514-4	2020	Here, we found that low mRNA expression of glycerol-3-phosphate dehydrogenase 1 (GPD1) may predict a poor response to metformin treatment in 15 cancer cell lines.	Metformin	118-127	glycerol-3-phosphate dehydrogenase 1	Homo sapiens	43-79
32179514-4	2020	Here, we found that low mRNA expression of glycerol-3-phosphate dehydrogenase 1 (GPD1) may predict a poor response to metformin treatment in 15 cancer cell lines.	Metformin	118-127	glycerol-3-phosphate dehydrogenase 1	Homo sapiens	81-85
32179514-5	2020	In vitro and in vivo, metformin treatment alone significantly suppressed cancer cell proliferation, a phenotype enhanced by GPD1 overexpression.	Metformin	22-31	glycerol-3-phosphate dehydrogenase 1	Homo sapiens	124-128
32179514-7	2020	Eventually, increased reactive oxygen species and mitochondrial structural damage was observed in GPD1-overexpressing cell lines treated with metformin, which may contribute to cell death.	Metformin	142-151	glycerol-3-phosphate dehydrogenase 1	Homo sapiens	98-102
32179514-8	2020	In summary, this study demonstrates that GPD1 overexpression enhances the anticancer activity of metformin and that patients with increased GPD1 expression in tumor cells may respond better to metformin therapy.	Metformin	97-106	glycerol-3-phosphate dehydrogenase 1	Homo sapiens	41-45
32179514-8	2020	In summary, this study demonstrates that GPD1 overexpression enhances the anticancer activity of metformin and that patients with increased GPD1 expression in tumor cells may respond better to metformin therapy.	Metformin	193-202	glycerol-3-phosphate dehydrogenase 1	Homo sapiens	140-144
32179514-9	2020	SIGNIFICANCE: GPD1 overexpression enhances the anticancer effect of metformin through synergistic inhibition of mitochondrial function, thereby providing new insight into metformin-mediated cancer therapy.	Metformin	68-77	glycerol-3-phosphate dehydrogenase 1	Homo sapiens	14-18
32179514-9	2020	SIGNIFICANCE: GPD1 overexpression enhances the anticancer effect of metformin through synergistic inhibition of mitochondrial function, thereby providing new insight into metformin-mediated cancer therapy.	Metformin	171-180	glycerol-3-phosphate dehydrogenase 1	Homo sapiens	14-18
32248666-13	2020	The AMPK/Erk signaling pathway experiments revealed that the upregulation of Bcl-2 induced by insulin through Erk phosphorylation was inhibited by metformin and that such inhibition could be mitigated by the inhibition of AMPK.	Metformin	147-156	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	4-8
32248666-13	2020	The AMPK/Erk signaling pathway experiments revealed that the upregulation of Bcl-2 induced by insulin through Erk phosphorylation was inhibited by metformin and that such inhibition could be mitigated by the inhibition of AMPK.	Metformin	147-156	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	222-226
32248666-14	2020	CONCLUSIONS: Insulin-induced oxaliplatin resistance was reversed by metformin-mediated AMPK activation.	Metformin	68-77	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	87-91
32360359-19	2020	However, a log shift of EC50 of ACTH stimulation on MC3R was observed with metformin treatment.	Metformin	75-84	melanocortin 3 receptor	Homo sapiens	52-56
32360359-20	2020	Metformin also inhibited melanocortin stimulating hormone (alphaMSH) induced MC3R activity.	Metformin	0-9	melanocortin 3 receptor	Homo sapiens	77-81
32360359-21	2020	In conclusion, we show that metformin acts on MC2R and MC3R signaling directly.	Metformin	28-37	melanocortin 3 receptor	Homo sapiens	55-59
32251713-7	2020	Moreover, metformin decreased HSP70, increased Zac1 and AhR expression; these effects were abolished in AIP silenced QGP-1 cells.	Metformin	10-19	aryl hydrocarbon receptor	Homo sapiens	56-59
12644585-4	2003	When mice were given metformin, the blood lactate concentration significantly increased in the wild-type mice, whereas only a slight increase was observed in Oct1(-/-) mice.	Metformin	21-30	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	158-162
12629126-7	2003	Metformin (1 micro g/ml) increased IR tyrosine phosphorylation by 78% (P = 0.0007) in 30 min in human hepatocytes and Huh7 cells and increased IRS-2 but not IRS-1 activation, and the downstream increase in deoxyglucose uptake was mediated via increased translocation of GLUT-1 to the plasma membrane.	Metformin	0-9	solute carrier family 2 member 1	Homo sapiens	270-276
12629126-11	2003	This study demonstrates that the mechanism of action of metformin in liver involves IR activation, followed by selective IRS-2 activation, and increased glucose uptake via increased GLUT-1 translocation.	Metformin	56-65	solute carrier family 2 member 1	Homo sapiens	182-188
12724019-11	2003	The effect of metformin on subjects with elevated DHEAS levels was different to that on individuals with normal DHEAS levels.	Metformin	14-23	sulfotransferase family 2A member 1	Homo sapiens	50-55
32139384-9	2020	CONCLUSIONS: Optimizing metformin to 2,000 mg/day or a maximally tolerated lower dose combined with emphasis on medication adherence and lifestyle can improve glycemia in type 2 diabetes and HbA1c values >=6.8% (51 mmol/mol).	Metformin	24-33	hemoglobin subunit alpha 1	Homo sapiens	191-195
32330868-0	2020	Metformin protects against intestinal ischemia-reperfusion injury and cell pyroptosis via TXNIP-NLRP3-GSDMD pathway.	Metformin	0-9	gasdermin D	Homo sapiens	102-107
32330868-11	2020	Importantly, Metformin reduced pyroptosis-related proteins, including NLRP3, cleaved caspase-1, and the N-terminus of GSDMD.	Metformin	13-22	gasdermin D	Homo sapiens	118-123
32330868-12	2020	Knocking down the GSDMD could reversed the protective effects of Metformin, which showed pyroptosis was one of the major cell death pathways controlled by Metformin treatment in setting of intestinal I/R injury.	Metformin	65-74	gasdermin D	Homo sapiens	18-23
32330868-12	2020	Knocking down the GSDMD could reversed the protective effects of Metformin, which showed pyroptosis was one of the major cell death pathways controlled by Metformin treatment in setting of intestinal I/R injury.	Metformin	155-164	gasdermin D	Homo sapiens	18-23
32330868-15	2020	In conclusion, we believe that Metformin protects against intestinal I/R injury in a TXNIP-NLRP3-GSDMD-dependent manner.	Metformin	31-40	gasdermin D	Homo sapiens	97-102
32276645-2	2020	Metformin is used for the treatment of type 2 diabetes and was reported to exert therapeutic effects against rheumatoid arthritis and obesity by improving mitochondrial dysfunction via the activation of fibroblast growth factor 21.	Metformin	0-9	fibroblast growth factor 21	Mus musculus	203-230
32047109-6	2020	Intriguingly, we found that metformin- or rapamycin-induced activation of autophagy significantly lessened the size and levels of CCFs and repressed the activation of the cGAS-STING-NF-kappaB-SASP cascade and cellular senescence.	Metformin	28-37	stimulator of interferon response cGAMP interactor 1	Mus musculus	176-181
32308645-17	2020	Among patients with preexisting CVD, GLP-1 receptor agonists with a proven cardiovascular benefit are indicated as add-on to metformin therapy.	Metformin	125-134	glucagon like peptide 1 receptor	Homo sapiens	37-51
31731885-5	2020	However, metformin over 24 weeks led to decreases compared to OBS in single PD1+ (percent decrease: -9.6% vs 7.5%, p=0.015), in dual PD1+TIGIT+ (-15.0% vs 10.4%, p=0.002) and in triple PD1+TIGIT+TIM3+ (-24.0% vs 8.1%, p=0.041) CD4 T-cells.	Metformin	9-18	programmed cell death 1	Sus scrofa	76-79
31731885-5	2020	However, metformin over 24 weeks led to decreases compared to OBS in single PD1+ (percent decrease: -9.6% vs 7.5%, p=0.015), in dual PD1+TIGIT+ (-15.0% vs 10.4%, p=0.002) and in triple PD1+TIGIT+TIM3+ (-24.0% vs 8.1%, p=0.041) CD4 T-cells.	Metformin	9-18	programmed cell death 1	Sus scrofa	133-136
31731885-5	2020	However, metformin over 24 weeks led to decreases compared to OBS in single PD1+ (percent decrease: -9.6% vs 7.5%, p=0.015), in dual PD1+TIGIT+ (-15.0% vs 10.4%, p=0.002) and in triple PD1+TIGIT+TIM3+ (-24.0% vs 8.1%, p=0.041) CD4 T-cells.	Metformin	9-18	programmed cell death 1	Sus scrofa	133-136
31731885-7	2020	CONCLUSIONS: Metformin decreases the frequency of PD1+, PD1+TIGIT+ and PD1+TIGIT+TIM3+ expressing CD4 T-cells.	Metformin	13-22	programmed cell death 1	Sus scrofa	50-53
31731885-7	2020	CONCLUSIONS: Metformin decreases the frequency of PD1+, PD1+TIGIT+ and PD1+TIGIT+TIM3+ expressing CD4 T-cells.	Metformin	13-22	programmed cell death 1	Sus scrofa	56-59
31731885-7	2020	CONCLUSIONS: Metformin decreases the frequency of PD1+, PD1+TIGIT+ and PD1+TIGIT+TIM3+ expressing CD4 T-cells.	Metformin	13-22	programmed cell death 1	Sus scrofa	56-59
32020647-7	2020	Metformin and ginger reduced the degenerative changes observed in the testes of diabetic rats, significantly reduced (p < .001) caspase-3 immunoexpression, and significantly increased (p < .001) the immune-expression of androgen receptors and proliferating cell nuclear antigen.	Metformin	0-9	caspase 3	Rattus norvegicus	128-137
31789625-7	2020	We found that microRNA-7 was dramatically upregulated by metformin via AMPK in a dose- and time-dependent manner.	Metformin	57-66	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	71-75
31789625-9	2020	Metformin downregulated the levels of p-NF-kappaB p65, p-Erk1/2, p-AKT, and p-mTOR proteins.	Metformin	0-9	RELA proto-oncogene, NF-kB subunit	Homo sapiens	40-53
31789625-12	2020	Our discovery revealed that metformin, via increasing the expression of microRNA-7 mediated by AMPK, regulates the AKT/mTOR, MAPK/Erk, and NF-kappaB signaling pathways, thereby suppressing A549 cell growth, migration, and invasion.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	95-99
31884044-3	2020	Metformin can affect metabolic pathways within cells mainly through activation of AMPK.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	82-86
31884044-9	2020	Here we represent metformin, an AMPK activator, as a new candidate drug for metabolic reprogramming of tumor-specific T cells to increase the efficacy and accountability of cancer immunotherapy.	Metformin	18-27	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	32-36
32014566-0	2020	Metformin Attenuates Sevoflurane-induced Neurocognitive Impairment Through AMPK-ULK1-dependent Autophagy in Aged Mice.	Metformin	0-9	unc-51 like kinase 1	Mus musculus	80-84
32014566-12	2020	The AMPK inhibitor compound C abolished metformin-induced ULK1 phosphorylation and autophagy activation after anaesthesia.	Metformin	40-49	unc-51 like kinase 1	Mus musculus	58-62
32014566-13	2020	These results suggest that metformin attenuates sevoflurane-induced neurocognitive impairment through AMPK-ULK1-dependent autophagy in aged mice.	Metformin	27-36	unc-51 like kinase 1	Mus musculus	107-111
12622936-0	2002	Inhibition of phosphoenolpyruvate carboxykinase gene expression by metformin in cultured hepatocytes.	Metformin	67-76	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	14-47
32034646-9	2020	In this review, we introduce different agents known to activate AMPK (metformin, statins, resveratrol, thiazolidinediones, AICAR, specific AMPK activators) as well as exercise and dietary restriction, and we discuss the existing evidence for their potential role in cardioprotection from doxorubicin cardiotoxicity.	Metformin	70-79	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	64-68
31821581-0	2020	Metformin alleviates renal injury in diabetic rats by inducing Sirt1/FoxO1 autophagic signal axis.	Metformin	0-9	forkhead box O1	Rattus norvegicus	69-74
31821581-6	2020	Sirt1 inhibitor EX527 and metformin were used to observe whether the protective effect of metformin on DN kidney was achieved through Sirt1/FoxO1 autophagic signaling pathway.	Metformin	90-99	forkhead box O1	Rattus norvegicus	140-145
31821581-8	2020	Sirt1 inhibitor could block the protective effect of metformin on kidney of diabetic rats, suggesting that metformin could alleviate kidney injury in diabetic rats by inducing Sirt1/FoxO1 autophagy signal axis.	Metformin	53-62	forkhead box O1	Rattus norvegicus	182-187
31821581-8	2020	Sirt1 inhibitor could block the protective effect of metformin on kidney of diabetic rats, suggesting that metformin could alleviate kidney injury in diabetic rats by inducing Sirt1/FoxO1 autophagy signal axis.	Metformin	107-116	forkhead box O1	Rattus norvegicus	182-187
31821581-9	2020	So metformin could alleviate renal injury in diabetic rats, which may be achieved by regulating Sirt1/FoxO1 autophagic signaling pathway and inducing renal autophagy.	Metformin	3-12	forkhead box O1	Rattus norvegicus	102-107
30669167-4	2020	The primary objective was to report, after 9 months of metformin treatment, the percentage of patients with baseline glycated haemoglobin (HbA1c) levels &gt;=6.5% (&gt;=48 mmol/mol) achieving HbA1c&lt;6.5%.	Metformin	55-64	hemoglobin subunit alpha 1	Homo sapiens	139-143
32208365-4	2020	Correlations between metformin concentration and high-mobility group box 1 (HMGB1) and miR-142-3p levels were assessed.	Metformin	21-30	high mobility group box 1	Homo sapiens	76-81
32208365-7	2020	HMGB1 gene expression correlated negatively with metformin concentration, whereas miR-142-3p expression correlated positively with metformin concentration.	Metformin	49-58	high mobility group box 1	Homo sapiens	0-5
32208365-9	2020	Metformin inhibits high glucose-induced VSMC hyperproliferation and increased migration by inducing miR-142-3p-mediated inhibition of HMGB1 expression via the HMGB1-autophagy related pathway.	Metformin	0-9	high mobility group box 1	Homo sapiens	134-139
32208365-9	2020	Metformin inhibits high glucose-induced VSMC hyperproliferation and increased migration by inducing miR-142-3p-mediated inhibition of HMGB1 expression via the HMGB1-autophagy related pathway.	Metformin	0-9	high mobility group box 1	Homo sapiens	159-164
32269725-9	2020	Our results show that metformin attenuates bleomycin-induced pulmonary fibrosis via IGF-1 pathway.	Metformin	22-31	insulin-like growth factor 1	Mus musculus	84-89
12622936-1	2002	OBJECTIVE: To investigate the effect and mechanism of the antihyperglycemic agent metformin on the expression of phosphoenolpyruvate carboxykinase (PEPCK) gene in hepatocytes and to determine whether the effects of metformin in hepatocytes are transmitted throughout the known insulin signaling pathways.	Metformin	82-91	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	113-146
12622936-1	2002	OBJECTIVE: To investigate the effect and mechanism of the antihyperglycemic agent metformin on the expression of phosphoenolpyruvate carboxykinase (PEPCK) gene in hepatocytes and to determine whether the effects of metformin in hepatocytes are transmitted throughout the known insulin signaling pathways.	Metformin	82-91	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	148-153
12622936-1	2002	OBJECTIVE: To investigate the effect and mechanism of the antihyperglycemic agent metformin on the expression of phosphoenolpyruvate carboxykinase (PEPCK) gene in hepatocytes and to determine whether the effects of metformin in hepatocytes are transmitted throughout the known insulin signaling pathways.	Metformin	215-224	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	148-153
12622936-4	2002	RESULTS: Therapeutic concentrations of metformin significantly inhibited basal PEPCK mRNA expression and also decreased cAMP and dexamethasone induced PEPCK gene expression through interaction with insulin.	Metformin	39-48	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	79-84
12622936-4	2002	RESULTS: Therapeutic concentrations of metformin significantly inhibited basal PEPCK mRNA expression and also decreased cAMP and dexamethasone induced PEPCK gene expression through interaction with insulin.	Metformin	39-48	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	151-156
12622936-5	2002	In the presence of insulin signaling pathway inhibitors wortmannin and UO126, metformin reduced PEPCK mRNA levels, but wortmannin blocked inhibitory regulation of insulin on PEPCK gene expression.	Metformin	78-87	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	96-101
12622936-6	2002	CONCLUSION: Metformin inhibits PEPCK gene expression via either an insulin-independent or an interacting-with-insulin manner.	Metformin	12-21	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	31-36
12622936-7	2002	The results suggest that a possible mechanism by which metformin reduces gluconeogenesis could be associated with the inhibition of PEPCK gene expression.	Metformin	55-64	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	132-137
12485530-1	2002	OBJECTIVE: To investigate the effect and mechanism of antihyperglycemic agent metformin on the gene expression of phosphoenolpyruvate carboxykinase (PEPCK)-a key enzyme within the regulation of gluconeogenesis in hepatocytes and to determine whether the effects of metformin on hepatocytes are transmitted throughout the known insulin signaling pathways.	Metformin	78-87	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	114-147
12485530-1	2002	OBJECTIVE: To investigate the effect and mechanism of antihyperglycemic agent metformin on the gene expression of phosphoenolpyruvate carboxykinase (PEPCK)-a key enzyme within the regulation of gluconeogenesis in hepatocytes and to determine whether the effects of metformin on hepatocytes are transmitted throughout the known insulin signaling pathways.	Metformin	78-87	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	149-154
12485530-1	2002	OBJECTIVE: To investigate the effect and mechanism of antihyperglycemic agent metformin on the gene expression of phosphoenolpyruvate carboxykinase (PEPCK)-a key enzyme within the regulation of gluconeogenesis in hepatocytes and to determine whether the effects of metformin on hepatocytes are transmitted throughout the known insulin signaling pathways.	Metformin	265-274	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	114-147
12485530-1	2002	OBJECTIVE: To investigate the effect and mechanism of antihyperglycemic agent metformin on the gene expression of phosphoenolpyruvate carboxykinase (PEPCK)-a key enzyme within the regulation of gluconeogenesis in hepatocytes and to determine whether the effects of metformin on hepatocytes are transmitted throughout the known insulin signaling pathways.	Metformin	265-274	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	149-154
12485530-4	2002	RESULTS: Metformin significantly decreased basal PEPCK mRNA levels by 75% (P &lt; 0.01).	Metformin	9-18	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	49-54
12485530-6	2002	In contrast, insulin 0.1 nmol/L significantly inhibited cAMP/dexamethasone stimulated PEPCK gene expression by 67% (P &lt; 0.01), when insulin 0.1 nmol/L was present together with metformin, cAMP/dexamethasone induced PEPCK gene expression was decreased by 94% (P &lt; 0.01).	Metformin	180-189	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	86-91
12485530-8	2002	CONCLUSION: Metformin can inhibit the PEPCK gene expression via either an insulin-independent or interaction with insulin manner.	Metformin	12-21	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	38-43
12130709-0	2002	Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin.	Metformin	86-95	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	15-43
12130709-2	2002	The purpose of the present study was to investigate the role of organic cation transporter 1 (Oct1) in the disposition of metformin.	Metformin	122-131	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	64-92
12130709-2	2002	The purpose of the present study was to investigate the role of organic cation transporter 1 (Oct1) in the disposition of metformin.	Metformin	122-131	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	94-98
12130709-3	2002	Transfection of rat Oct1 cDNA results in the time-dependent and saturable uptake of metformin by the Chinese hamster ovary cell line with K(m) and V(max) values of 377 microM and 1386 pmol/min/mg of protein, respectively.	Metformin	84-93	solute carrier family 22 member 1	Rattus norvegicus	20-24
12130709-4	2002	Buformin and phenformin, two other biguanides, were also transported by rOct1 with a higher affinity than metformin: their K(m) values were 49 and 16 microM, respectively.	Metformin	106-115	solute carrier family 22 member 1	Rattus norvegicus	72-77
11753758-9	2001	This is consistent with findings that metformin restored the increased gene expression of PEPCK in liver from STZ-diabetic rats.	Metformin	38-47	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	90-95
10856473-11	2000	Subjects with elevated DHEAS differed from those with normal DHEAS in their responses to metformin treatment.	Metformin	89-98	sulfotransferase family 2A member 1	Homo sapiens	23-28
10856473-11	2000	Subjects with elevated DHEAS differed from those with normal DHEAS in their responses to metformin treatment.	Metformin	89-98	sulfotransferase family 2A member 1	Homo sapiens	61-66
8626883-4	1995	In healthy elderly individuals, the plasma and whole blood clearance/absolute bioavailability values [CL/F and (CL/F)b], and corresponding renal clearance values (CLR and CLR,b) of metformin were 35-40% lower than the respective values in healthy young individuals.	Metformin	181-190	crooked neck pre-mRNA splicing factor 1	Homo sapiens	112-118
8216316-2	1993	Metformin caused a dose and time dependent increase in GLUT1 number with a maximum at a concentration of 10 micrograms metformin given over 4 days.	Metformin	0-9	solute carrier family 2 member 1	Homo sapiens	55-60
8216316-2	1993	Metformin caused a dose and time dependent increase in GLUT1 number with a maximum at a concentration of 10 micrograms metformin given over 4 days.	Metformin	119-128	solute carrier family 2 member 1	Homo sapiens	55-60
8216316-3	1993	This was accompanied by an increase in GLUT1 mRNA, suggesting that metformin has a stimulating effect on glucose transporter gene expression.	Metformin	67-76	solute carrier family 2 member 1	Homo sapiens	39-44
8216316-5	1993	We conclude that in human fibroblasts GLUT1 de novo synthesis is involved in the long term effect of metformin on glucose transport.	Metformin	101-110	solute carrier family 2 member 1	Homo sapiens	38-43
8412779-0	1993	The impact of metformin therapy on hepatic glucose production and skeletal muscle glycogen synthase activity in overweight type II diabetic patients.	Metformin	14-23	glycogen synthase 1	Homo sapiens	66-99
33798646-4	2021	Of these, repurposing of tideglusib, mexiletine, or metformin appear to be therapies with the most potential to receive marketing authorization for DM1.	Metformin	52-61	DM1 protein kinase	Homo sapiens	148-151
34890997-13	2022	Both metformin and fluoxetine increased neurogenesis by increasing KI67, but only the combined treatment increased neuronal survival by NeuN positive cells in the hippocampus.	Metformin	5-14	antigen identified by monoclonal antibody Ki 67	Mus musculus	67-71
34826740-11	2022	In vitro, overexpression of INSM1 decreased AMPK-alpha expression as well as glucose intake, promoted tumor cell migration, and limited the apoptosis induced by Cisplatin, which all could be reversed by Metformin.	Metformin	203-212	INSM transcriptional repressor 1	Homo sapiens	28-33
34808525-0	2021	Sex-specific effects of metformin and liraglutide on renal pathology and expression of connexin 45 and pannexin 1 following long-term high-fat high-sugar diet.	Metformin	24-33	Pannexin 1	Rattus norvegicus	103-113
34424816-13	2021	Metformin also reduced the expression of CXCL12 and CXCR4 in mdx mice.	Metformin	0-9	chemokine (C-X-C motif) receptor 4	Mus musculus	52-57
34665880-5	2021	A subsequent GWAS of metformin response identifies a robust variant that alters GLUT2 expression - which may support increasing evidence that metformin works primarily in the gut.	Metformin	21-30	solute carrier family 2 member 2	Homo sapiens	80-85
34665880-5	2021	A subsequent GWAS of metformin response identifies a robust variant that alters GLUT2 expression - which may support increasing evidence that metformin works primarily in the gut.	Metformin	142-151	solute carrier family 2 member 2	Homo sapiens	80-85
34551339-8	2021	Metformin treated hUC-MSCs up-regulated the expression of osteogenic marker ALP, OCN and RUNX2, but down-regulated the expression of adipogenic markers PPARgamma and LPL.	Metformin	0-9	ATHS	Homo sapiens	76-79
34551339-11	2021	The results of RT-qPCR revealed that the SCF and VEGFR2 were raised in metformin treatment.	Metformin	71-80	KIT ligand	Homo sapiens	41-44
34551339-11	2021	The results of RT-qPCR revealed that the SCF and VEGFR2 were raised in metformin treatment.	Metformin	71-80	kinase insert domain receptor	Homo sapiens	49-55
34432321-10	2021	Consistent with this, metformin directly inhibited LATS1/2 and activated Mst1/2, phosphorylated YAP1 in vitro.	Metformin	22-31	macrophage stimulating 1 (hepatocyte growth factor-like)	Mus musculus	73-79
34432321-11	2021	After blocking the Hippo pathway by XMU-MP-1, the inhibitor of MST1/2, the inhibitory effects by metformin were dramatically attenuated as shown by in vitro study.	Metformin	97-106	macrophage stimulating 1 (hepatocyte growth factor-like)	Mus musculus	63-69
34570348-7	2021	Moreover, metformin treatment significantly downregulated the expression of pro-inflammatory associated genes (iNOS, H2-Aa, and TNF-alpha) in the corpus callosum, whereas expression of anti-inflammatory markers (Arg1, Mrc1, and IL10) was not promoted, compared to CPZ mice.	Metformin	10-19	mannose receptor, C type 1	Mus musculus	218-222
34733370-0	2021	Metformin inhibits the proliferation of canine mammary gland tumor cells through the AMPK/AKT/mTOR signaling pathway in vitro.	Metformin	0-9	mechanistic target of rapamycin kinase	Canis lupus familiaris	94-98
34733370-11	2021	The expression of associated signaling molecules revealed that metformin markedly increased the phosphorylation of AMPK in CHMm cells, and decreased the levels of phosphorylated (p-)AKT, p-mTOR and p-4E-BP1, while Compound C reversed these changes.	Metformin	63-72	mechanistic target of rapamycin kinase	Canis lupus familiaris	189-193
34733370-12	2021	These findings demonstrated that metformin may be a potential therapeutic agent for CMGTs, acting via the AMPK/AKT/mTOR signaling pathway.	Metformin	33-42	mechanistic target of rapamycin kinase	Canis lupus familiaris	115-119
34825068-9	2021	Gene expression analysis demonestrated that metformin treatment was associated with an enhanced expression of antioxidant genes such as Nrf-2, HO-1, SOD and catalase in liver of HFD fed rats.	Metformin	44-53	heme oxygenase 1	Rattus norvegicus	143-147
34825068-10	2021	Metformin treatment also found to modulate the expression of fat metabolizing and anti-inflammatory genes including PPAR--gamma, C/EBP-alpha, SREBP1c, FAS, AMPK and GLUT-4.	Metformin	0-9	peroxisome proliferator-activated receptor gamma	Rattus norvegicus	116-127
34738906-6	2021	The AMPK activators metformin or AICAR-two compounds that mimic fasting-elevate hepatic gluconeogenic gene expression dependent on in turn activation of the AMPK-TET1-SIRT1 axis.	Metformin	20-29	tet methylcytosine dioxygenase 1	Mus musculus	162-166
34725961-0	2022	Metformin induces muscle atrophy by transcriptional regulation of myostatin via HDAC6 and FoxO3a.	Metformin	0-9	forkhead box O3	Mus musculus	90-96
34725961-10	2022	Metformin induced the interaction between AMPK and FoxO3a, a key transcription factor of myostatin.	Metformin	0-9	forkhead box O3	Mus musculus	51-57
34725961-12	2022	The interaction between HDAC6 and FoxO3a induced after metformin treatment.	Metformin	55-64	forkhead box O3	Mus musculus	34-40
34725961-13	2022	Confocal microscopy revealed that metformin increased the nuclear localization of FoxO3a (>3.3-fold, P < 0.001).	Metformin	34-43	forkhead box O3	Mus musculus	82-88
34725961-14	2022	Chromatin immunoprecipitation revealed that metformin induced the binding of FoxO3a to the myostatin promoter.	Metformin	44-53	forkhead box O3	Mus musculus	77-83
34725961-17	2022	The serum myoglobin level was significantly decreased in metformin-treated WT mice (-66.6 +- 9.03%, P < 0.01).	Metformin	57-66	myoglobin	Mus musculus	10-19
34725961-18	2022	CONCLUSIONS: Our results demonstrate that metformin treatment impairs muscle function through the regulation of myostatin in skeletal muscle cells via AMPK-FoxO3a-HDAC6 axis.	Metformin	42-51	forkhead box O3	Mus musculus	156-162
34986539-4	2021	After metformin treatment, the apoptosis rate of Caco-2 cells was decreased from (14.22+-2.34)% to 0.61)% (=3.119, <0.05), and the expression levels of tight junction protein-1 and claudin-1 increased (=5.172 and 3.546, both <0.05).	Metformin	6-15	claudin 1	Homo sapiens	181-190
34486387-8	2021	While 0.1mM/L metformin upregulated the expression of BECLIN1 and LC3 I/II gene and inhibited the expression of mTOR and GSK3beta, contribute to reverse the osteogenesis inhibition of ASCs caused by high glucose.	Metformin	14-23	beclin 1	Homo sapiens	54-61
34642298-0	2021	Metformin alleviates inflammation through suppressing FASN-dependent palmitoylation of Akt.	Metformin	0-9	fatty acid synthase	Homo sapiens	54-58
34642298-4	2021	We further show that metformin could suppress such elevation of FASN as well as proinflammatory activation in macrophages.	Metformin	21-30	fatty acid synthase	Homo sapiens	64-68
34642298-6	2021	The reduction of FASN by metformin hinders Akt palmitoylation, which further disturbs Akt membrane attachment and its phosphorylation.	Metformin	25-34	fatty acid synthase	Homo sapiens	17-21
34642298-7	2021	Metformin-mediated suppression of FASN/Akt pathway and its downstream MAPK signaling contributes to its anti-inflammatory role in macrophages.	Metformin	0-9	fatty acid synthase	Homo sapiens	34-38
34626114-8	2022	Expression of AMPK and SIRT1 was reduced in gut of 6-month-old fish with poly I:C-treatment, and feeding metformin reversed these declines.	Metformin	105-114	sirtuin 1	Homo sapiens	23-28
34626114-9	2022	Taken together, the present study suggested that poly I:C-injection led to aging-like phenomena in gut and metformin activated AMPK and SIRT1 to reduce NF-kappaB mediated inflammation and resist oxidative stress via enhanced expression of FoxO3a and PGC-1alpha, and finally delayed gut aging in vertebrates.	Metformin	107-116	sirtuin 1	Homo sapiens	136-141
34375763-0	2021	ATXN7L3B promotes hepatocellular carcinoma stemness and is downregulated by metformin.	Metformin	76-85	ataxin 7 like 3B	Homo sapiens	0-8
34375763-7	2021	We observed that metformin reduced ATXN7L3B level in HCC cells.	Metformin	17-26	ataxin 7 like 3B	Homo sapiens	35-43
34790753-0	2021	Metformin alleviates bevacizumab-induced vascular endothelial injury by up-regulating GDF15 and activating the PI3K/AKT/FOXO/PPARgamma signaling pathway.	Metformin	0-9	growth differentiation factor 15	Homo sapiens	86-91
34790753-8	2021	Subsequently, GDF15 siRNA reduced the effects of metformin on the bevacizumab-induced vascular endothelial injury (as described above) in HUEVCs.	Metformin	49-58	growth differentiation factor 15	Homo sapiens	14-19
34790753-10	2021	Conclusions: Metformin protected against bevacizumab-induced vascular endothelial injury via activation of GDF15 and the PI3K/AKT/FOXO/PPARgamma signaling pathway.	Metformin	13-22	growth differentiation factor 15	Homo sapiens	107-112
34388523-0	2021	The L125F MATE1 variant enriched in populations of Amerindian origin is associated with increased plasma levels of metformin and lactate.	Metformin	115-124	solute carrier family 47 member 1	Homo sapiens	10-15
34388523-2	2021	Metformin pharmacokinetics is carried out by members of the membrane transporters superfamily (SLCs), being the multidrug and toxin extrusion protein 1 (MATE1), one of the most studied.	Metformin	0-9	solute carrier family 47 member 1	Homo sapiens	112-151
34388523-2	2021	Metformin pharmacokinetics is carried out by members of the membrane transporters superfamily (SLCs), being the multidrug and toxin extrusion protein 1 (MATE1), one of the most studied.	Metformin	0-9	solute carrier family 47 member 1	Homo sapiens	153-158
34388523-3	2021	Some genetic variants in MATE1 have been associated with reduced in vitro metformin transport.	Metformin	74-83	solute carrier family 47 member 1	Homo sapiens	25-30
34388523-6	2021	To elucidate the metformin pharmacogenetics, a children cohort was genotyped, allowing us to describe, for the first time, a MATE1 rs77474263 TT homozygous individual.	Metformin	17-26	solute carrier family 47 member 1	Homo sapiens	125-130
34396446-0	2021	Metformin inhibits cholesterol-induced adhesion molecule expression via activating the AMPK signaling pathway in vascular smooth muscle cells.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	87-91
34396446-10	2021	Metformin decreased cholesterol-induced VSMC damage by activating the AMPK signaling pathway, and suppressing p38 MAPK and NF-kappaB signaling.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	70-74
34396450-0	2021	Protective effects of metformin against myocardial ischemia-reperfusion injury via AMPK-dependent suppression of NOX4.	Metformin	22-31	NADPH oxidase 4	Rattus norvegicus	113-117
34396450-10	2021	Furthermore, NADPH oxidase 4 (NOX4) was downregulated by metformin at both the mRNA and protein levels, and adenosine 5"-monophosphate-activated protein kinase (AMPK) phosphorylation was increased by metformin.	Metformin	57-66	NADPH oxidase 4	Rattus norvegicus	13-28
34396450-10	2021	Furthermore, NADPH oxidase 4 (NOX4) was downregulated by metformin at both the mRNA and protein levels, and adenosine 5"-monophosphate-activated protein kinase (AMPK) phosphorylation was increased by metformin.	Metformin	57-66	NADPH oxidase 4	Rattus norvegicus	30-34
34396450-10	2021	Furthermore, NADPH oxidase 4 (NOX4) was downregulated by metformin at both the mRNA and protein levels, and adenosine 5"-monophosphate-activated protein kinase (AMPK) phosphorylation was increased by metformin.	Metformin	200-209	NADPH oxidase 4	Rattus norvegicus	13-28
34396450-12	2021	It was also found that metformin upregulated the phosphorylation of AMPK and decreased the expression of NOX4.	Metformin	23-32	NADPH oxidase 4	Rattus norvegicus	105-109
34396450-13	2021	Furthermore, pre-treatment with AMPK inhibitor compound-C could block the effect of metformin, indicated by increased NOX4 compared with metformin treatment alone.	Metformin	84-93	NADPH oxidase 4	Rattus norvegicus	118-122
34396450-13	2021	Furthermore, pre-treatment with AMPK inhibitor compound-C could block the effect of metformin, indicated by increased NOX4 compared with metformin treatment alone.	Metformin	137-146	NADPH oxidase 4	Rattus norvegicus	118-122
34396450-15	2021	In conclusion, the present study indicated that metformin activated AMPK to inhibit the expression of NOX4, leading to a decrease in myocardial oxidative damage and apoptosis, thus alleviating reperfusion injury.	Metformin	48-57	NADPH oxidase 4	Rattus norvegicus	102-106
34584129-8	2021	Weight loss couldn"t be achieved with lifestyle changes, metformin and orlistat treatments In genetic examination, a sporadic heterozygous c.206T>G(p.I69R) variant (reported previously) was found in the MC4R gene.	Metformin	57-66	melanocortin 4 receptor	Homo sapiens	203-207
34684418-7	2021	Maternal metformin increased MyoD expression but decreased Ppargc1a, Drp1 and Mfn2 expression in SM of adult male and female offspring.	Metformin	9-18	mitofusin 2	Rattus norvegicus	78-82
34684418-10	2021	Our data demonstrate that maternal metformin during gestation and lactation can potentially overcome the negative effects of perinatal exposure to HF diet in offspring, by altering their myogenesis, mitochondrial biogenesis and dynamics through AMPK/mTOR pathways in SM.	Metformin	35-44	mechanistic target of rapamycin kinase	Rattus norvegicus	250-254
34588803-3	2021	Among these, in this review, we will examine above all the role of metformin, hypothesized to be able to activate the AMP-activated protein kinase (AMPK) pathway and potentially modulate some mechanisms implicated in the onset and the growth of the cysts.	Metformin	67-76	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	118-146
34588803-3	2021	Among these, in this review, we will examine above all the role of metformin, hypothesized to be able to activate the AMP-activated protein kinase (AMPK) pathway and potentially modulate some mechanisms implicated in the onset and the growth of the cysts.	Metformin	67-76	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	148-152
34572586-0	2021	Dual Blockade of Lactate/GPR81 and PD-1/PD-L1 Pathways Enhances the Anti-Tumor Effects of Metformin.	Metformin	90-99	hydroxycarboxylic acid receptor 1	Homo sapiens	25-30
34572586-6	2021	In addition, considering that 3-OBA could recover the inhibitory effects of metformin on PD-1 expression, we further determined the dual blockade effects of PD-1/PD-L1 and lactate/GPR81 on the antitumor activity of metformin.	Metformin	76-85	hydroxycarboxylic acid receptor 1	Homo sapiens	180-185
34572586-6	2021	In addition, considering that 3-OBA could recover the inhibitory effects of metformin on PD-1 expression, we further determined the dual blockade effects of PD-1/PD-L1 and lactate/GPR81 on the antitumor activity of metformin.	Metformin	215-224	hydroxycarboxylic acid receptor 1	Homo sapiens	180-185
34576192-11	2021	Metformin and DCA inhibited mTOR complex I signaling through upregulated AMPK-independent REDD1.	Metformin	0-9	DNA damage inducible transcript 4	Homo sapiens	90-95
34630909-15	2021	However, metformin performed poorly according to most indicators (SUCRA = 54.5%, 0.3%, 19.5%, 33.7%, 57.7% and 44.3% for HFC, NAS, ALT, AST, GGT and body weight, respectively).	Metformin	9-18	gamma-glutamyltransferase 1	Homo sapiens	141-144
34505146-0	2022	Genomic editing of metformin efficacy-associated genetic variants in SLC47A1 does not alter SLC47A1 expression.	Metformin	19-28	solute carrier family 47 member 1	Homo sapiens	69-76
34505146-1	2022	Several pharmacogenetics studies have identified an association between a greater metformin-dependent reduction in HbA1c levels and the minor A allele at rs2289669 in intron 10 of SLC47A1, encoding multidrug and toxin extrusion 1 (MATE1), a presumed metformin transporter.	Metformin	82-91	solute carrier family 47 member 1	Homo sapiens	180-187
34505146-1	2022	Several pharmacogenetics studies have identified an association between a greater metformin-dependent reduction in HbA1c levels and the minor A allele at rs2289669 in intron 10 of SLC47A1, encoding multidrug and toxin extrusion 1 (MATE1), a presumed metformin transporter.	Metformin	82-91	solute carrier family 47 member 1	Homo sapiens	198-229
34505146-1	2022	Several pharmacogenetics studies have identified an association between a greater metformin-dependent reduction in HbA1c levels and the minor A allele at rs2289669 in intron 10 of SLC47A1, encoding multidrug and toxin extrusion 1 (MATE1), a presumed metformin transporter.	Metformin	82-91	solute carrier family 47 member 1	Homo sapiens	231-236
34505146-3	2022	We looked at association between common genetic variants in the SLC47A1 gene region and HbA1c reduction after metformin treatment using locus-wise meta-analysis from the MetGen consortium.	Metformin	110-119	solute carrier family 47 member 1	Homo sapiens	64-71
34480113-8	2021	Using co-immunofluorescence of IBa-1 and MBP, and luxol fasting blue (LFB) staining, we demonstrated that metformin promoted the transformation of M1 to M2 phenotype polarization of microglial cells, then greatly facilitated myelin debris clearance and protected the myelin in SCI rats.	Metformin	106-115	myelin basic protein	Rattus norvegicus	41-44
34480113-9	2021	Furthermore, metformin ameliorated SCI-induced blockade of autophagic flux in the spinal cord, and enhanced the fusion of autophagosome and lysosome by inhibiting the AMPK-mTOR signaling pathway.	Metformin	13-22	mechanistic target of rapamycin kinase	Rattus norvegicus	172-176
34557403-11	2021	Finally, we showed that metformin can induce cell death in BL cells by stressing cellular metabolism through the induction of GLUT1, PKM2, and LDHA.	Metformin	24-33	solute carrier family 2 member 1	Homo sapiens	126-131
34399755-10	2021	Metformin also induced the activation of AMPK, markedly promoted expression of LC3II, and down-regulated the expression of p62/SQSTM1.	Metformin	0-9	sequestosome 1	Homo sapiens	123-126
34399755-10	2021	Metformin also induced the activation of AMPK, markedly promoted expression of LC3II, and down-regulated the expression of p62/SQSTM1.	Metformin	0-9	sequestosome 1	Homo sapiens	127-133
34489707-5	2021	The modulating effects of empagliflozin and metformin on the AMPK/mTOR/NLRP3 axis and T cell polarization were delineated.	Metformin	44-53	mechanistic target of rapamycin kinase	Rattus norvegicus	66-70
34489707-9	2021	Interestingly, empagliflozin/metformin combination significantly enhanced AMPK phosphorylation and depressed mTOR and NLRP3 expression leading to a subsequent reduction in caspase-1 cleavage and inhibition of several inflammatory cytokines, including IL-1beta, and IL-18.	Metformin	29-38	mechanistic target of rapamycin kinase	Rattus norvegicus	109-113
34489707-9	2021	Interestingly, empagliflozin/metformin combination significantly enhanced AMPK phosphorylation and depressed mTOR and NLRP3 expression leading to a subsequent reduction in caspase-1 cleavage and inhibition of several inflammatory cytokines, including IL-1beta, and IL-18.	Metformin	29-38	caspase 1	Rattus norvegicus	172-181
34434111-0	2021	Metformin Attenuates Silica-Induced Pulmonary Fibrosis by Activating Autophagy via the AMPK-mTOR Signaling Pathway.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	87-91
34434111-7	2021	Besides, metformin increased the expression levels of phosphorylated adenosine 5"-monophosphate (AMP)-activated protein kinase (p-AMPK), microtubule-associated protein (MAP) light chain 3B (LC3B) and Beclin1 proteins, and reduced levels of phosphorylated mammalian target of rapamycin (p-mTOR) and p62 proteins in vivo and in vitro.	Metformin	9-18	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	130-134
34434111-7	2021	Besides, metformin increased the expression levels of phosphorylated adenosine 5"-monophosphate (AMP)-activated protein kinase (p-AMPK), microtubule-associated protein (MAP) light chain 3B (LC3B) and Beclin1 proteins, and reduced levels of phosphorylated mammalian target of rapamycin (p-mTOR) and p62 proteins in vivo and in vitro.	Metformin	9-18	beclin 1	Homo sapiens	200-207
34439169-0	2021	Metformin Is a Pyridoxal-5"-phosphate (PLP)-Competitive Inhibitor of SHMT2.	Metformin	0-9	serine hydroxymethyltransferase 2	Homo sapiens	69-74
34439169-2	2021	We report that metformin directly and specifically targets the enzymatic activity of mitochondrial serine hydroxymethyltransferase (SHMT2).	Metformin	15-24	serine hydroxymethyltransferase 2	Homo sapiens	85-130
34439169-2	2021	We report that metformin directly and specifically targets the enzymatic activity of mitochondrial serine hydroxymethyltransferase (SHMT2).	Metformin	15-24	serine hydroxymethyltransferase 2	Homo sapiens	132-137
34439169-3	2021	In vitro competitive binding assays with human recombinant SHMT1 and SHMT2 isoforms revealed that metformin preferentially inhibits SHMT2 activity by a non-catalytic mechanism.	Metformin	98-107	serine hydroxymethyltransferase 2	Homo sapiens	69-74
34439169-3	2021	In vitro competitive binding assays with human recombinant SHMT1 and SHMT2 isoforms revealed that metformin preferentially inhibits SHMT2 activity by a non-catalytic mechanism.	Metformin	98-107	serine hydroxymethyltransferase 2	Homo sapiens	132-137
34439169-4	2021	Computational docking coupled with molecular dynamics simulation predicted that metformin could occupy the cofactor pyridoxal-5"-phosphate (PLP) cavity and destabilize the formation of catalytically active SHMT2 oligomers.	Metformin	80-89	serine hydroxymethyltransferase 2	Homo sapiens	206-211
34439169-5	2021	Differential scanning fluorimetry-based biophysical screening confirmed that metformin diminishes the capacity of PLP to promote the conversion of SHMT2 from an inactive, open state to a highly ordered, catalytically competent closed state.	Metformin	77-86	serine hydroxymethyltransferase 2	Homo sapiens	147-152
34439169-6	2021	CRISPR/Cas9-based disruption of SHMT2, but not of SHMT1, prevented metformin from inhibiting total SHMT activity in cancer cell lines.	Metformin	67-76	serine hydroxymethyltransferase 2	Homo sapiens	32-37
34439169-7	2021	Isotope tracing studies in SHMT1 knock-out cells confirmed that metformin decreased the SHMT2-channeled serine-to-formate flux and restricted the formate utilization in thymidylate synthesis upon overexpression of the metformin-unresponsive yeast equivalent of mitochondrial complex I (mCI).	Metformin	64-73	glycine hydroxymethyltransferase SHM2	Saccharomyces cerevisiae S288C	88-93
34439169-8	2021	While maintaining its capacity to inhibit mitochondrial oxidative phosphorylation, metformin lost its cytotoxic and antiproliferative activity in SHMT2-null cancer cells unable to produce energy-rich NADH or FADH2 molecules from tricarboxylic acid cycle (TCA) metabolites.	Metformin	83-92	glycine hydroxymethyltransferase SHM2	Saccharomyces cerevisiae S288C	146-151
34439169-9	2021	As currently available SHMT2 inhibitors have not yet reached the clinic, our current data establishing the structural and mechanistic bases of metformin as a small-molecule, PLP-competitive inhibitor of the SHMT2 activating oligomerization should benefit future discovery of biguanide skeleton-based novel SHMT2 inhibitors in cancer prevention and treatment.	Metformin	143-152	glycine hydroxymethyltransferase SHM2	Saccharomyces cerevisiae S288C	207-212
34421608-0	2021	Metformin Potentiates the Effects of Anlotinib in NSCLC via AMPK/mTOR and ROS-Mediated Signaling Pathways.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	60-64
34421608-4	2021	Interesting, metformin also exerts broad anticancer effects through the activation of AMP-activated protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR).	Metformin	13-22	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	86-114
34421608-4	2021	Interesting, metformin also exerts broad anticancer effects through the activation of AMP-activated protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR).	Metformin	13-22	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	116-120
34421608-7	2021	Moreover, anlotinib combined with metformin induced apoptosis and oxidative stress, which was associated with the activation of AMPK and inhibition of mTOR.	Metformin	34-43	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	128-132
34129225-7	2021	The proliferation of HDFs was decreased significantly (P < 0.01) and expression of COL1A1 was downregulated by HG without metformin, whereas proliferation was elevated and expression was upregulated with 500 muM metformin + HG compared to 5.5 mM glucose (P < 0.05).	Metformin	212-221	collagen type I alpha 1 chain	Homo sapiens	83-89
34129225-9	2021	Metformin not only significantly downregulated RELA/p65 expression, but also inhibited the apoptosis of HDFs from aged human skin at toxic glucose concentrations which could be inversely mediated via COL1A1 and COL3A1 expression.	Metformin	0-9	collagen type I alpha 1 chain	Homo sapiens	200-206
34302119-0	2021	Correction: Repurposing dextromethorphan and metformin for treating nicotine-induced cancer by directly targeting CHRNA7 to inhibit JAK2/STAT3/SOX2 signaling.	Metformin	45-54	SRY-box transcription factor 2	Homo sapiens	143-147
34389700-7	2021	Metformin was positively correlated with the enrichment of different intestinal bacteria such as Bifidobacterium and Akkermansia and a lower cutC (a choline utilization gene) abundance.	Metformin	0-9	cutC copper transporter	Mus musculus	141-145
34354368-11	2021	Ten hub genes identified using PPI network analysis were screened for interactions with metformin target gene INS using cytoHubba based on maximal clique centrality (MCC) score.	Metformin	88-97	ELAV like RNA binding protein 2	Homo sapiens	4-7
34354368-14	2021	Notably, six hub genes (STAT1, IFIT3, RSAD2, ISG15, IFI44, IFI6) were down-regulated in cells exposed to both metformin and Mycobacterium tuberculosis antigens.	Metformin	110-119	ELAV like RNA binding protein 2	Homo sapiens	13-16
34354368-14	2021	Notably, six hub genes (STAT1, IFIT3, RSAD2, ISG15, IFI44, IFI6) were down-regulated in cells exposed to both metformin and Mycobacterium tuberculosis antigens.	Metformin	110-119	signal transducer and activator of transcription 1	Homo sapiens	24-29
34354368-15	2021	Conclusion: Network hub genes hold promise as disease status biomarkers and as metformin treatment targets for alleviating TB and DM.	Metformin	79-88	ELAV like RNA binding protein 2	Homo sapiens	20-23
34326272-11	2021	For the mechanisms, activating AMPK with metformin (obese CCD rats) or AICAR (DRG neurons in a high-fat environment) not only inhibited the ERK-NOX4 pathway, but also improved oxidative stress and inflammation caused by high-fat.	Metformin	41-50	NADPH oxidase 4	Rattus norvegicus	144-148
34366846-0	2021	Metformin Alleviates Hepatic Steatosis and Insulin Resistance in a Mouse Model of High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Promoting Transcription Factor EB-Dependent Autophagy.	Metformin	0-9	transcription factor EB	Mus musculus	150-173
34366846-7	2021	Metformin treatment significantly reverses the activity of TFEB, and the protective effect of metformin against hepatic steatosis and insulin resistance is dependent on TFEB.	Metformin	0-9	transcription factor EB	Mus musculus	59-63
34366846-7	2021	Metformin treatment significantly reverses the activity of TFEB, and the protective effect of metformin against hepatic steatosis and insulin resistance is dependent on TFEB.	Metformin	0-9	transcription factor EB	Mus musculus	169-173
34366846-7	2021	Metformin treatment significantly reverses the activity of TFEB, and the protective effect of metformin against hepatic steatosis and insulin resistance is dependent on TFEB.	Metformin	94-103	transcription factor EB	Mus musculus	169-173
34366846-8	2021	We show that metformin-induced autophagy is regulated by TFEB, and our findings reveal that TFEB acts as a mediator, linking metformin with autophagy to reverse NAFLD, and highlight that TFEB may be a promising molecular target for the treatment of NAFLD.	Metformin	13-22	transcription factor EB	Mus musculus	57-61
34366846-8	2021	We show that metformin-induced autophagy is regulated by TFEB, and our findings reveal that TFEB acts as a mediator, linking metformin with autophagy to reverse NAFLD, and highlight that TFEB may be a promising molecular target for the treatment of NAFLD.	Metformin	13-22	transcription factor EB	Mus musculus	92-96
34366846-8	2021	We show that metformin-induced autophagy is regulated by TFEB, and our findings reveal that TFEB acts as a mediator, linking metformin with autophagy to reverse NAFLD, and highlight that TFEB may be a promising molecular target for the treatment of NAFLD.	Metformin	13-22	transcription factor EB	Mus musculus	187-191
34366846-8	2021	We show that metformin-induced autophagy is regulated by TFEB, and our findings reveal that TFEB acts as a mediator, linking metformin with autophagy to reverse NAFLD, and highlight that TFEB may be a promising molecular target for the treatment of NAFLD.	Metformin	125-134	transcription factor EB	Mus musculus	57-61
34366846-8	2021	We show that metformin-induced autophagy is regulated by TFEB, and our findings reveal that TFEB acts as a mediator, linking metformin with autophagy to reverse NAFLD, and highlight that TFEB may be a promising molecular target for the treatment of NAFLD.	Metformin	125-134	transcription factor EB	Mus musculus	92-96
34253170-0	2021	Inhibition of mTORC1 through ATF4-induced REDD1 and Sestrin2 expression by Metformin.	Metformin	75-84	activating transcription factor 4	Homo sapiens	29-33
34253170-0	2021	Inhibition of mTORC1 through ATF4-induced REDD1 and Sestrin2 expression by Metformin.	Metformin	75-84	DNA damage inducible transcript 4	Homo sapiens	42-47
34253170-3	2021	RESULTS: Metformin induced the expression of ATF4, REDD1, and Sestrin2 concomitant with its inhibition of mTORC1 activity.	Metformin	9-18	activating transcription factor 4	Homo sapiens	45-49
34253170-3	2021	RESULTS: Metformin induced the expression of ATF4, REDD1, and Sestrin2 concomitant with its inhibition of mTORC1 activity.	Metformin	9-18	DNA damage inducible transcript 4	Homo sapiens	51-56
34253170-4	2021	Treatment with REDD1 or Sestrin2 siRNA reversed the mTORC1 inhibition induced by metformin, indicating that REDD1 and Sestrin2 are important for the inhibition of mTORC1 triggered by metformin treatment.	Metformin	81-90	DNA damage inducible transcript 4	Homo sapiens	15-20
34253170-4	2021	Treatment with REDD1 or Sestrin2 siRNA reversed the mTORC1 inhibition induced by metformin, indicating that REDD1 and Sestrin2 are important for the inhibition of mTORC1 triggered by metformin treatment.	Metformin	81-90	DNA damage inducible transcript 4	Homo sapiens	108-113
34253170-4	2021	Treatment with REDD1 or Sestrin2 siRNA reversed the mTORC1 inhibition induced by metformin, indicating that REDD1 and Sestrin2 are important for the inhibition of mTORC1 triggered by metformin treatment.	Metformin	183-192	DNA damage inducible transcript 4	Homo sapiens	15-20
34253170-4	2021	Treatment with REDD1 or Sestrin2 siRNA reversed the mTORC1 inhibition induced by metformin, indicating that REDD1 and Sestrin2 are important for the inhibition of mTORC1 triggered by metformin treatment.	Metformin	183-192	DNA damage inducible transcript 4	Homo sapiens	108-113
34253170-5	2021	Moreover, REDD1- and Sestrin2-mediated mTORC1 inhibition in response to metformin was independent of AMPK activation.	Metformin	72-81	DNA damage inducible transcript 4	Homo sapiens	10-15
34253170-6	2021	Additionally, lapatinib enhances cell sensitivity to metformin, and knockdown of REDD1 and Sestrin2 decreased cell sensitivity to metformin and lapatinib.	Metformin	130-139	DNA damage inducible transcript 4	Homo sapiens	81-86
34253170-7	2021	CONCLUSIONS: ATF4-induced REDD1 and Sestrin2 expression in response to metformin plays an important role in mTORC1 inhibition independent of AMPK activation, and this signalling pathway could have therapeutic value.	Metformin	71-80	activating transcription factor 4	Homo sapiens	13-17
34253170-7	2021	CONCLUSIONS: ATF4-induced REDD1 and Sestrin2 expression in response to metformin plays an important role in mTORC1 inhibition independent of AMPK activation, and this signalling pathway could have therapeutic value.	Metformin	71-80	DNA damage inducible transcript 4	Homo sapiens	26-31
34230143-5	2021	Metformin-induced AKT activation was markedly suppressed by siRNA targeting activating transcription factor 4 (ATF4) but not AMP-activated protein kinase alpha.	Metformin	0-9	activating transcription factor 4	Homo sapiens	76-109
34230143-5	2021	Metformin-induced AKT activation was markedly suppressed by siRNA targeting activating transcription factor 4 (ATF4) but not AMP-activated protein kinase alpha.	Metformin	0-9	activating transcription factor 4	Homo sapiens	111-115
34230143-6	2021	These results indicate that AKT activation by metformin was induced in an ATF4-dependent and AMPKalpha-independent manner.	Metformin	46-55	activating transcription factor 4	Homo sapiens	74-78
34097256-0	2021	Effect of Omecamtiv Mecarbil on the Pharmacokinetics of Metformin, a Probe Substrate for MATE1/MATE2-K, in Healthy Subjects.	Metformin	56-65	solute carrier family 47 member 1	Homo sapiens	89-94
34156429-6	2021	Aside from this, drugs that have been the subject of multiple clinical trials such as metformin, which targets AMPK signalling and somatostatins, which target cAMP signalling have shown great promise in reducing cyst formation and cellular proliferation.	Metformin	86-95	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	111-115
34211461-7	2021	Metformin increased the levels of SMILE, AMPK, and Foxp3 but decreased the number of interleukin (IL)-17-producing T cells among PBMCs from patients with UC.	Metformin	0-9	interleukin 17A	Homo sapiens	85-104
34163481-3	2021	The mechanisms by which metformin regulates the function of macrophages include AMPK, AMPK independent targets, NF-kappaB, ABCG5/8, Sirt1, FOXO1/FABP4 and HMGB1.	Metformin	24-33	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	80-84
34163481-3	2021	The mechanisms by which metformin regulates the function of macrophages include AMPK, AMPK independent targets, NF-kappaB, ABCG5/8, Sirt1, FOXO1/FABP4 and HMGB1.	Metformin	24-33	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	86-90
34163481-3	2021	The mechanisms by which metformin regulates the function of macrophages include AMPK, AMPK independent targets, NF-kappaB, ABCG5/8, Sirt1, FOXO1/FABP4 and HMGB1.	Metformin	24-33	sirtuin 1	Homo sapiens	132-137
34087084-4	2021	However, the effect of metformin administration on hsa-miR-21-5p and MMP9 has not been evaluated in T2DM and DN patients.	Metformin	23-32	matrix metallopeptidase 9	Homo sapiens	69-73
34087084-10	2021	However, in metformin-treated group, a downregulation of hsa-miR-21-5p and upregulation of MMP9 was observed.	Metformin	12-21	matrix metallopeptidase 9	Homo sapiens	91-95
34087084-12	2021	Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.	Metformin	0-9	matrix metallopeptidase 9	Homo sapiens	48-52
34087084-12	2021	Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.	Metformin	0-9	matrix metallopeptidase 9	Homo sapiens	349-353
34087084-12	2021	Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.	Metformin	0-9	matrix metallopeptidase 9	Homo sapiens	382-387
34087084-12	2021	Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.	Metformin	0-9	matrix metallopeptidase 9	Homo sapiens	455-459
34087084-12	2021	Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.	Metformin	280-289	matrix metallopeptidase 9	Homo sapiens	48-52
34087084-12	2021	Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.	Metformin	280-289	matrix metallopeptidase 9	Homo sapiens	349-353
34087084-12	2021	Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.	Metformin	280-289	matrix metallopeptidase 9	Homo sapiens	382-387
34087084-12	2021	Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.	Metformin	280-289	matrix metallopeptidase 9	Homo sapiens	455-459
34149615-14	2021	The activation of this pathway is reduced by treatment with 2DG and metformin, which also reverted imbalances in CD4+ T cell differentiation.	Metformin	68-77	CD4 antigen	Mus musculus	113-116
34151116-4	2021	To find a potential explanation for this practice, we employed atomistic-level computer simulations to simulate the transport of metformin through multidrug and toxin extrusion 1 (MATE1), a protein known to play a key role in the expulsion of metformin into urine.	Metformin	129-138	solute carrier family 47 member 1	Homo sapiens	147-178
34151116-4	2021	To find a potential explanation for this practice, we employed atomistic-level computer simulations to simulate the transport of metformin through multidrug and toxin extrusion 1 (MATE1), a protein known to play a key role in the expulsion of metformin into urine.	Metformin	129-138	solute carrier family 47 member 1	Homo sapiens	180-185
34151116-4	2021	To find a potential explanation for this practice, we employed atomistic-level computer simulations to simulate the transport of metformin through multidrug and toxin extrusion 1 (MATE1), a protein known to play a key role in the expulsion of metformin into urine.	Metformin	243-252	solute carrier family 47 member 1	Homo sapiens	147-178
34151116-4	2021	To find a potential explanation for this practice, we employed atomistic-level computer simulations to simulate the transport of metformin through multidrug and toxin extrusion 1 (MATE1), a protein known to play a key role in the expulsion of metformin into urine.	Metformin	243-252	solute carrier family 47 member 1	Homo sapiens	180-185
34151116-5	2021	Herein, we examine the hydrogen bonding between MATE1 and one or more metformin molecules.	Metformin	70-79	solute carrier family 47 member 1	Homo sapiens	48-53
34151116-6	2021	The simulation results indicate that metformin continuously forms and breaks off hydrogen bonds with MATE1 residues.	Metformin	37-46	solute carrier family 47 member 1	Homo sapiens	101-106
34386644-9	2021	Metformin, on the contrary, suppressed the expression of sparc, integrin alphaV, fibronectin and N-cadherin with the reduced cell motility.	Metformin	0-9	integrin subunit alpha V	Homo sapiens	64-79
34386644-9	2021	Metformin, on the contrary, suppressed the expression of sparc, integrin alphaV, fibronectin and N-cadherin with the reduced cell motility.	Metformin	0-9	cadherin 2	Homo sapiens	97-107
34064886-2	2021	Hepatic OCT1, intestinal OCT3, renal OCT2 on tubule basolateral membrane, and MATE1/2-K on tubule apical membrane coordinately work to control metformin disposition.	Metformin	143-152	solute carrier family 22 member 3	Homo sapiens	25-29
34064886-7	2021	Individual contributions of transporters to metformin disposition are renal OCT2   renal MATEs > intestinal OCT3 > hepatic OCT1 > intestinal PMAT.	Metformin	44-53	solute carrier family 22 member 3	Homo sapiens	108-112
34277866-12	2021	Results: Photobiomodulation at 1, 2, and 3 J/cm2 combined with metformin significantly promoted diabetic cell lines of HPDLSCs viability (in MTT assay and ELISA reader of ROS, TNF-alpha, IL-10 results) and gene expression of Nrf2, Keap1, PIK3, and HO-1 levels (p< 0.05).	Metformin	63-72	interleukin 10	Homo sapiens	187-192
34265779-7	2021	Variants on SLC47A1, SLC28A1, and ABCG2 likely impact the pharmacokinetics (PK) of metformin, while the role of the two latter can be related to insulin resistance and regulation of adipogenesis.	Metformin	83-92	solute carrier family 47 member 1	Homo sapiens	12-19
34265779-7	2021	Variants on SLC47A1, SLC28A1, and ABCG2 likely impact the pharmacokinetics (PK) of metformin, while the role of the two latter can be related to insulin resistance and regulation of adipogenesis.	Metformin	83-92	solute carrier family 28 member 1	Homo sapiens	21-28
35286779-10	2022	Immunostaining of active caspase3 and BAX were intense in the endometrium of aging model compare to CN- and metformin-treated groups.	Metformin	108-117	caspase 3	Mus musculus	25-33
35286779-10	2022	Immunostaining of active caspase3 and BAX were intense in the endometrium of aging model compare to CN- and metformin-treated groups.	Metformin	108-117	BCL2-associated X protein	Mus musculus	38-41
35421356-9	2022	Furthermore, we identified that metformin could reverse FAM98A-mediated 5-FU resistance in CRC cells.	Metformin	32-41	family with sequence similarity 98 member A	Homo sapiens	56-62
35398171-6	2022	Some markers of senescent cells (p21WAF1/Cip1, p16INK4A, and gammaH2AX) were also significantly upregulated by doxorubicin and then counteracted by metformin treatment.	Metformin	148-157	cyclin-dependent kinase inhibitor 1A (P21)	Mus musculus	33-45
35396800-5	2022	An ecto-enzyme (CD39) antagonist POM1 and AMP-activated protein kinase (AMPK) agonist metformin are both encapsulated into cancer cell-derived exosomes and used as nanocarriers for tumor targeting delivery.	Metformin	86-95	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	42-70
35396800-5	2022	An ecto-enzyme (CD39) antagonist POM1 and AMP-activated protein kinase (AMPK) agonist metformin are both encapsulated into cancer cell-derived exosomes and used as nanocarriers for tumor targeting delivery.	Metformin	86-95	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	72-76
35418220-0	2022	PEN2: Metformin"s new partner at lysosome.	Metformin	6-15	presenilin enhancer, gamma-secretase subunit	Homo sapiens	0-4
35481401-4	2022	Mechanically, we revealed that metformin could inhibit protein expression of FTO, leading to increased m6A methylation levels of cyclin D1 (Ccnd1) and cyclin dependent kinase 2 (Cdk2), two crucial regulators in cell cycle.	Metformin	31-40	cyclin D1	Mus musculus	129-138
35481401-4	2022	Mechanically, we revealed that metformin could inhibit protein expression of FTO, leading to increased m6A methylation levels of cyclin D1 (Ccnd1) and cyclin dependent kinase 2 (Cdk2), two crucial regulators in cell cycle.	Metformin	31-40	cyclin D1	Mus musculus	140-145
35481401-4	2022	Mechanically, we revealed that metformin could inhibit protein expression of FTO, leading to increased m6A methylation levels of cyclin D1 (Ccnd1) and cyclin dependent kinase 2 (Cdk2), two crucial regulators in cell cycle.	Metformin	31-40	cyclin-dependent kinase 2	Mus musculus	151-176
35481401-4	2022	Mechanically, we revealed that metformin could inhibit protein expression of FTO, leading to increased m6A methylation levels of cyclin D1 (Ccnd1) and cyclin dependent kinase 2 (Cdk2), two crucial regulators in cell cycle.	Metformin	31-40	cyclin-dependent kinase 2	Mus musculus	178-182
35143930-0	2022	Numb/Notch/PLK1 signaling pathway mediated hyperglycemic memory in pancreatic cancer cell radioresistance and the therapeutic effects of metformin.	Metformin	137-146	NUMB endocytic adaptor protein	Homo sapiens	0-4
35143930-0	2022	Numb/Notch/PLK1 signaling pathway mediated hyperglycemic memory in pancreatic cancer cell radioresistance and the therapeutic effects of metformin.	Metformin	137-146	polo like kinase 1	Homo sapiens	11-15
35143930-7	2022	The therapeutic effect of metformin was revealed by detecting the level of Numb / Notch /PLK1 through Western blot and real-time PCR.	Metformin	26-35	NUMB endocytic adaptor protein	Homo sapiens	75-79
35143930-7	2022	The therapeutic effect of metformin was revealed by detecting the level of Numb / Notch /PLK1 through Western blot and real-time PCR.	Metformin	26-35	polo like kinase 1	Homo sapiens	89-93
35143930-8	2022	RESULTS: Inactivation of Numb promotes the pancreatic cancer radio-resistance through hyperglycemic memory and metformin could suppress the radio-resistance by activating Numb in vitro and in vivo.	Metformin	111-120	NUMB endocytic adaptor protein	Homo sapiens	171-175
35143930-11	2022	CONCLUSIONS: Our data demonstrated that Numb might be a promising target for the improvement of hyperglycemic memory damage and the effect of metformin deserved urgent attention on pancreatic cancer radio-resistance therapy.	Metformin	142-151	NUMB endocytic adaptor protein	Homo sapiens	40-44
35090865-1	2022	The aim of this study was to investigate the contributions of multiple transport mechanisms to the intestinal absorption of metformin, focusing on OCT3, PMAT, THTR2, SERT and OCTN2.	Metformin	124-133	solute carrier family 22 member 3	Homo sapiens	147-151
35090865-3	2022	Uptake studies with MDCKII cells expressing OCT3, PMAT, THTR2 or SERT confirmed that metformin is a substrate of these transporters.	Metformin	85-94	solute carrier family 22 member 3	Homo sapiens	44-48
35090865-5	2022	7-Cyclopentyl inhibited OCT3- and THTR2-mediated uptake of metformin.	Metformin	59-68	solute carrier family 22 member 3	Homo sapiens	24-28
35090865-7	2022	Using these inhibitors, the relative contributions of OCT3, PMAT, THTR2, SERT, OCTN2 and others to the intestinal permeation of metformin across Caco-2 cells were estimated to be 9.77%, 9.68%, 22.2%, 1.52%, 0% and 0.66%, respectively.	Metformin	128-137	solute carrier family 22 member 3	Homo sapiens	54-58
35557626-9	2022	mRS shift analysis showed a significantly better outcome in metformin-treated patients (p < 0.001) and lower mortality (8.1 vs. 4.6% p < 0.001).	Metformin	60-69	sterile alpha motif domain containing 11	Mus musculus	0-3
35557626-11	2022	In diabetic patients, pre-stroke treatment with metformin improved the outcome (90-day mRS) by factor 0.14 (IRR 0.86 (CI 0.75-0.97) p = 0.006).	Metformin	48-57	sterile alpha motif domain containing 11	Mus musculus	87-90
35557626-11	2022	In diabetic patients, pre-stroke treatment with metformin improved the outcome (90-day mRS) by factor 0.14 (IRR 0.86 (CI 0.75-0.97) p = 0.006).	Metformin	48-57	insulin receptor related receptor	Homo sapiens	108-111
35454162-1	2022	Dual Blockade of Lactate/GPR81 and PD-1/PD-L1 Pathways Enhances the Anti-Tumor Effects of Metformin.	Metformin	90-99	hydroxycarboxylic acid receptor 1	Homo sapiens	25-30
35300794-7	2022	We discovered that metformin treatment was associated with the downregulation of lipids and fatty acids, potentially through the inhibition of fatty acid synthase (FASN).	Metformin	19-28	fatty acid synthase	Homo sapiens	143-162
35300794-7	2022	We discovered that metformin treatment was associated with the downregulation of lipids and fatty acids, potentially through the inhibition of fatty acid synthase (FASN).	Metformin	19-28	fatty acid synthase	Homo sapiens	164-168
35300794-10	2022	Using enzymatic activity assay, we determined that the co-treatment exhibit the highest FASN inhibition compared with the mono-treatment of IRI or metformin.	Metformin	147-156	fatty acid synthase	Homo sapiens	88-92
35344434-5	2022	Our results thus reveal an important role of the hepatic let-7/TET3/HNF4alpha axis in mediating the therapeutic effects of metformin and suggest that targeting this axis may be a potential therapeutic for diabetes.	Metformin	123-132	hepatic nuclear factor 4, alpha	Mus musculus	68-77
35444557-13	2022	Silencing of Nedd4-2 mitigated NHE3 inhibition and ubiquitination by metformin.	Metformin	69-78	NEDD4 like E3 ubiquitin protein ligase	Homo sapiens	13-20
35444557-13	2022	Silencing of Nedd4-2 mitigated NHE3 inhibition and ubiquitination by metformin.	Metformin	69-78	solute carrier family 9 member A3	Homo sapiens	31-35
35444557-14	2022	Our findings suggest that metformin-induced diarrhea in type 2 diabetes is in part caused by reduced Na+ and water absorption that is associated with NHE3 inhibition, probably by AMPK.	Metformin	26-35	solute carrier family 9 member A3	Homo sapiens	150-154
34990285-9	2022	Furthermore, metformin decreased mRNA and protein expression of components of the Shh pathway including Shh, Ptch, Smo and Gli-1.	Metformin	13-22	GLI family zinc finger 1	Homo sapiens	123-128
35390228-19	2022	We found that degradation of cardiac GATA4 by Bmi-1 was mainly dependent on autophagy rather than proteasome, and autophagy agonists metformin and rapamycin could ameliorate the SA-PCH, suggesting that activation of autophagy with metformin or rapamycin could also be a promising method to prevent SA-PCH.	Metformin	133-142	GATA binding protein 4	Homo sapiens	37-42
35390228-19	2022	We found that degradation of cardiac GATA4 by Bmi-1 was mainly dependent on autophagy rather than proteasome, and autophagy agonists metformin and rapamycin could ameliorate the SA-PCH, suggesting that activation of autophagy with metformin or rapamycin could also be a promising method to prevent SA-PCH.	Metformin	231-240	GATA binding protein 4	Homo sapiens	37-42
35147202-0	2022	Metformin inhibits pulmonary artery smooth muscle cell proliferation by upregulating p21 via NONRATT015587.2.	Metformin	0-9	KRAS proto-oncogene, GTPase	Rattus norvegicus	85-88
35344814-4	2022	Metformin upregulated BAX activation with facilitation of BIM, BAD and PUMA; downregulated Bcl-2 and Bcl-xl, but did not affect Mcl-1.	Metformin	0-9	BCL2-associated X protein	Mus musculus	22-25
35344814-4	2022	Metformin upregulated BAX activation with facilitation of BIM, BAD and PUMA; downregulated Bcl-2 and Bcl-xl, but did not affect Mcl-1.	Metformin	0-9	BCL2-like 11 (apoptosis facilitator)	Mus musculus	58-61
35270043-7	2022	In DM1, different studies revealed that metformin rescues multiple phenotypes of the disease.	Metformin	40-49	DM1 protein kinase	Homo sapiens	3-6
35270043-8	2022	This review provides an overview of recent findings describing metformin as a novel therapy to combat DM1 and their link with aging.	Metformin	63-72	DM1 protein kinase	Homo sapiens	102-105
35131865-3	2022	Among them, metformin is an activator of the adenosine 5"-monophosphate protein kinase (AMPK) that can in turn modulate the activity of the E3 ubiquitin ligase NEDD4-2 and thus posttranslational expression of voltage gated sodium channels (Navs).	Metformin	12-21	NEDD4 like E3 ubiquitin protein ligase	Homo sapiens	160-167
35131865-4	2022	In this study, we found that the bulk of the effect of metformin on Na1.7 is dependent on NEDD4-2.	Metformin	55-64	NEDD4 like E3 ubiquitin protein ligase	Homo sapiens	90-97
35131865-5	2022	In HEK cells, the expression of Nav1.7 at the membrane fraction, obtained by a biotinylation approach, is only reduced by metformin when co-transfected with NEDD4-2.	Metformin	122-131	sodium voltage-gated channel alpha subunit 9	Homo sapiens	32-38
35131865-5	2022	In HEK cells, the expression of Nav1.7 at the membrane fraction, obtained by a biotinylation approach, is only reduced by metformin when co-transfected with NEDD4-2.	Metformin	122-131	NEDD4 like E3 ubiquitin protein ligase	Homo sapiens	157-164
35131865-6	2022	Similarly, in voltage clamp recordings, metformin significantly reduced Nav1.7 current density when co-transfected with NEDD4-2.	Metformin	40-49	sodium voltage-gated channel alpha subunit 9	Homo sapiens	72-78
35131865-6	2022	Similarly, in voltage clamp recordings, metformin significantly reduced Nav1.7 current density when co-transfected with NEDD4-2.	Metformin	40-49	NEDD4 like E3 ubiquitin protein ligase	Homo sapiens	120-127
35434034-0	2022	Metformin reverses tamoxifen resistance through the lncRNA GAS5-medicated mTOR pathway in breast cancer.	Metformin	0-9	growth arrest specific 5	Homo sapiens	59-63
35434034-10	2022	Conclusions: Metformin can inhibit overactivation of the mTOR signaling pathway through upregulating lncRNA GAS5 expression, thereby inhibiting the growth and inducing the apoptosis of BC cells, providing a new clinical treatment for BC.	Metformin	13-22	growth arrest specific 5	Homo sapiens	108-112
35190587-6	2022	Among eight metformin sensitizing miRNAs identified by functional screening, miR-676-3p had both pro-apoptotic and cell cycle arrest activity in combination with metformin, whereas other miRNAs (miR-18b-5p, miR-145-3p miR-376b-5p, and miR-718) resulted primarily in cell cycle arrest when combined with metformin.	Metformin	12-21	microRNA 18b	Homo sapiens	195-202
35190587-6	2022	Among eight metformin sensitizing miRNAs identified by functional screening, miR-676-3p had both pro-apoptotic and cell cycle arrest activity in combination with metformin, whereas other miRNAs (miR-18b-5p, miR-145-3p miR-376b-5p, and miR-718) resulted primarily in cell cycle arrest when combined with metformin.	Metformin	12-21	microRNA 718	Homo sapiens	235-242
35190587-6	2022	Among eight metformin sensitizing miRNAs identified by functional screening, miR-676-3p had both pro-apoptotic and cell cycle arrest activity in combination with metformin, whereas other miRNAs (miR-18b-5p, miR-145-3p miR-376b-5p, and miR-718) resulted primarily in cell cycle arrest when combined with metformin.	Metformin	162-171	microRNA 718	Homo sapiens	235-242
35190587-7	2022	Investigation of the combined effect of miRNAs and metformin on CRC cell metabolism showed that miR-18b-5p, miR-145-3p, miR-376b-5p, miR-676-3p and miR-718 affected glycolysis only, while miR-1181 only regulated CRC respiration.	Metformin	51-60	microRNA 18b	Homo sapiens	96-103
35190587-7	2022	Investigation of the combined effect of miRNAs and metformin on CRC cell metabolism showed that miR-18b-5p, miR-145-3p, miR-376b-5p, miR-676-3p and miR-718 affected glycolysis only, while miR-1181 only regulated CRC respiration.	Metformin	51-60	microRNA 376b	Homo sapiens	120-128
35190587-7	2022	Investigation of the combined effect of miRNAs and metformin on CRC cell metabolism showed that miR-18b-5p, miR-145-3p, miR-376b-5p, miR-676-3p and miR-718 affected glycolysis only, while miR-1181 only regulated CRC respiration.	Metformin	51-60	microRNA 718	Homo sapiens	148-155
35190587-7	2022	Investigation of the combined effect of miRNAs and metformin on CRC cell metabolism showed that miR-18b-5p, miR-145-3p, miR-376b-5p, miR-676-3p and miR-718 affected glycolysis only, while miR-1181 only regulated CRC respiration.	Metformin	51-60	microRNA 1181	Homo sapiens	188-196
35169250-5	2022	We aimed to investigate the therapeutic efficacy of tofacitinib and metformin on IL-17 and TGF-beta cytokines, skin fibrosis and inflammation in mouse model of systemic sclerosis (SSc).	Metformin	68-77	interleukin 17A	Mus musculus	81-86
35042121-10	2022	The inhibitor sensitivity of MATE1-facilitated amiloride transport was similar to those of known substrates, such as tetraethylammonium and metformin.	Metformin	140-149	solute carrier family 47 member 1	Homo sapiens	29-34
35134125-7	2022	Finally, systemic administration of metformin, an AMPK agonist and common diabetes treatment, profoundly increased spike-wave seizures.	Metformin	36-45	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	50-54
35044756-5	2022	Additionally, combined metformin and anthocyanin treatment suppressed protein tyrosine phosphatase 1B expression and regulated the PI3K/AKT/GSK3beta pathway.	Metformin	23-32	protein tyrosine phosphatase non-receptor type 1	Homo sapiens	70-101
35129424-7	2022	Metformin mainly affected the AMPK and FOXO signaling pathways, whereas vildagliptin affected insulin secretion and the HIF-1 signaling pathway.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	30-34
35096812-11	2021	Metformin inhibited osteoclast formation and accordingly downregulated the genes involved in osteoclastogenesis: RANKL, macrophage colony stimulating factor (M-CSF) and osteoclast fusion gene DC-STAMP.	Metformin	0-9	TNF superfamily member 11	Homo sapiens	113-118
34994666-0	2022	AMPK/mTOR-mediated therapeutic effect of metformin on myocardial ischaemia reperfusion injury in diabetic rat.	Metformin	41-50	mechanistic target of rapamycin kinase	Rattus norvegicus	5-9
34994666-9	2022	Furthermore, the increasing protein levels of LC3-II, BECLIN 1, autophagy related 5 (ATG5) and AMP-activated protein kinase suggested activated autophagy-associated intracellular signalling AMPK and mTOR pathways upon DMBG treated.	Metformin	218-222	mechanistic target of rapamycin kinase	Rattus norvegicus	199-203
35070958-0	2021	Stimulation of Let-7 Maturation by Metformin Improved the Response to Tyrosine Kinase Inhibitor Therapy in an m6A Dependent Manner.	Metformin	35-44	TXK tyrosine kinase	Homo sapiens	70-85
35070958-4	2021	Let-7b expression was stimulated when adding Metformin and then increasing the therapy sensitivity by decreasing the stem cell groups expanding.	Metformin	45-54	microRNA let-7b	Homo sapiens	0-6
34375188-11	2022	RESULTS: Astaxanthin and metformin have anti-obesity and antioxidant actions and significantly decreased the weight of the body, glucose, insulin, triglycerides, total cholesterol, triglycerides and leptin, as well as plasma calprotectin & IL-6 and increased HDL-C and adiponectin.	Metformin	25-34	adiponectin, C1Q and collagen domain containing	Rattus norvegicus	269-280
33711726-11	2021	Metformin may have an essential antitumor role in the invasion and metastasis pathways of PBCCs by downregulating the MMP-9 expression blocking both the activity and nuclear translocation of NF-kB.	Metformin	0-9	matrix metallopeptidase 9	Homo sapiens	118-123
33524789-6	2021	First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3.	Metformin	32-41	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	111-115
33524789-6	2021	First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3.	Metformin	32-41	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	149-153
33524789-6	2021	First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3.	Metformin	32-41	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	149-153
33524789-6	2021	First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3.	Metformin	32-41	CCAAT enhancer binding protein delta	Homo sapiens	165-170
33524789-6	2021	First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3.	Metformin	32-41	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	149-153
33524789-6	2021	First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3.	Metformin	32-41	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	149-153
33524789-6	2021	First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3.	Metformin	32-41	DNA damage inducible transcript 4	Homo sapiens	212-217
33524789-6	2021	First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3.	Metformin	32-41	prokineticin 2	Homo sapiens	265-268
33524789-6	2021	First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3.	Metformin	32-41	tribbles pseudokinase 3	Homo sapiens	292-297
33524789-7	2021	Secondly, some signaling pathways were involved in the process of metformin inhibiting autophagy, such as AMPK-related signaling pathways (AMPK/NF-kappaB and other undetermined AMPK-related signaling pathways), Hedgehog, miR-570-3p, miR-142-3p, and MiR-3127-5p.	Metformin	66-75	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	106-110
33524789-7	2021	Secondly, some signaling pathways were involved in the process of metformin inhibiting autophagy, such as AMPK-related signaling pathways (AMPK/NF-kappaB and other undetermined AMPK-related signaling pathways), Hedgehog, miR-570-3p, miR-142-3p, and MiR-3127-5p.	Metformin	66-75	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	139-143
33524789-7	2021	Secondly, some signaling pathways were involved in the process of metformin inhibiting autophagy, such as AMPK-related signaling pathways (AMPK/NF-kappaB and other undetermined AMPK-related signaling pathways), Hedgehog, miR-570-3p, miR-142-3p, and MiR-3127-5p.	Metformin	66-75	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	139-143
33524789-7	2021	Secondly, some signaling pathways were involved in the process of metformin inhibiting autophagy, such as AMPK-related signaling pathways (AMPK/NF-kappaB and other undetermined AMPK-related signaling pathways), Hedgehog, miR-570-3p, miR-142-3p, and MiR-3127-5p.	Metformin	66-75	microRNA 3127	Homo sapiens	249-257
33946426-0	2021	Metformin Dysregulates the Unfolded Protein Response and the WNT/beta-Catenin Pathway in Endometrial Cancer Cells through an AMPK-Independent Mechanism.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	125-129
33946426-2	2021	Metformin has been reported to affect cancer cells" metabolism and proliferation mainly through the activation of AMP-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	114-142
33946426-2	2021	Metformin has been reported to affect cancer cells" metabolism and proliferation mainly through the activation of AMP-activated protein kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	144-148
33929675-0	2021	Crocin and Metformin suppress metastatic breast cancer progression via VEGF and MMP9 downregulations: in vitro and in vivo studies.	Metformin	11-20	vascular endothelial growth factor A	Mus musculus	71-75
33929675-9	2021	While crocin alone restored the mice"s weight reduction, crocin, metformin, and their combination significantly reduced the tumor volume size and enhanced animal survival rate in murine breast cancer model, responses that were associated with VEGF and MMP9 down-regulation.	Metformin	65-74	vascular endothelial growth factor A	Mus musculus	243-247
33903987-4	2021	In the current research, the pharmacokinetics of OCT1 substrates (sumatriptan and metformin) were assessed in Oct knockout rats for comparison with previous Oct1/2-/- mice data and OCT1 pharmacogenetics in humans.	Metformin	82-91	solute carrier family 22 member 1	Rattus norvegicus	49-53
32667970-5	2021	METHODS AND RESULTS: Normoglycemic Ldlr-/- hyperlipidemic mice were treated with oral metformin, which profoundly suppressed atherosclerotic lesion development (p < 5x10-11).	Metformin	86-95	low density lipoprotein receptor	Mus musculus	35-39
32667970-7	2021	Metformin at a clinically relevant concentration (10muM) evoked AMPK-dependent and ATF1-dependent increases in Hmox1, Nr1h2 (Lxrb), Abca1, Apoe, Igf1 and Pdgf, increases in several M2-markers and decreases in Nos2, in murine bone marrow macrophages.	Metformin	0-9	ATP-binding cassette, sub-family A (ABC1), member 1	Mus musculus	132-137
33953705-9	2021	Our results suggest that FOXO3 can be activated by metformin leading to reduced ROS/RNS level in immune cells.	Metformin	51-60	forkhead box O3	Mus musculus	25-30
33643408-0	2021	Constitutive Androstane Receptor-Mediated Inhibition of Metformin on Phase II Metabolic Enzyme SULT2A1.	Metformin	56-65	nuclear receptor subfamily 1 group I member 3	Homo sapiens	0-32
33643408-0	2021	Constitutive Androstane Receptor-Mediated Inhibition of Metformin on Phase II Metabolic Enzyme SULT2A1.	Metformin	56-65	sulfotransferase family 2A member 1	Homo sapiens	95-102
33643408-3	2021	Herein, we designed experiments to investigate the effects and mechanisms of metformin on SULT2A1 expression in vitro.	Metformin	77-86	sulfotransferase family 2A member 1	Homo sapiens	90-97
33643408-8	2021	Results: We showed that metformin did not affect the basic expression of SULT2A1 but could suppress the expression of SULT2A1 induced by the activator of human CAR.	Metformin	24-33	sulfotransferase family 2A member 1	Homo sapiens	118-125
33643408-8	2021	Results: We showed that metformin did not affect the basic expression of SULT2A1 but could suppress the expression of SULT2A1 induced by the activator of human CAR.	Metformin	24-33	nuclear receptor subfamily 1 group I member 3	Homo sapiens	160-163
33643408-9	2021	Investigations revealed that metformin which could block CAR nuclear translocation further suppress SULT2A1.	Metformin	29-38	nuclear receptor subfamily 1 group I member 3	Homo sapiens	57-60
33643408-9	2021	Investigations revealed that metformin which could block CAR nuclear translocation further suppress SULT2A1.	Metformin	29-38	sulfotransferase family 2A member 1	Homo sapiens	100-107
33643408-10	2021	In addition, we found that the prevented CAR transfer into the nucleus by metformin was partially an AMPK-dependent event.	Metformin	74-83	nuclear receptor subfamily 1 group I member 3	Homo sapiens	41-44
33643408-11	2021	Conclusion: The present study indicated that the activation of AMPK-CAR pathway mediated the suppression of SULT2A1 by metformin.	Metformin	119-128	nuclear receptor subfamily 1 group I member 3	Homo sapiens	68-71
33643408-11	2021	Conclusion: The present study indicated that the activation of AMPK-CAR pathway mediated the suppression of SULT2A1 by metformin.	Metformin	119-128	sulfotransferase family 2A member 1	Homo sapiens	108-115
33643408-12	2021	Metformin may affect the metabolism and clearance of drugs which are SULT2A1 substrates.	Metformin	0-9	sulfotransferase family 2A member 1	Homo sapiens	69-76
33112382-5	2021	Consistent with reduced HIF1A transcriptional activity, SIRT1 activators, resveratrol, SRT2104, and metformin, each acting via different mechanisms, significantly inhibited EDN2.	Metformin	100-109	endothelin 2	Homo sapiens	173-177
33578894-2	2021	Metformin significantly reduced H3K4me3 level at the promoters of positive cell cycle regulatory genes such as CCNB2, CDK1, CDK6, and E2F8.	Metformin	0-9	cyclin B2	Mus musculus	111-116
33578894-2	2021	Metformin significantly reduced H3K4me3 level at the promoters of positive cell cycle regulatory genes such as CCNB2, CDK1, CDK6, and E2F8.	Metformin	0-9	E2F transcription factor 8	Mus musculus	134-138
33561991-1	2021	AIMS: To examine the association of polymorphisms belonging to SLC22A1, SP1, PRPF31, NBEA, SCNN1B, CPA6 and CAPN10 genes with glycaemic response to metformin and sulphonylureas (SU) combination therapy among South African adults with diabetes mellitus type 2 (T2DM).	Metformin	148-157	pre-mRNA processing factor 31	Homo sapiens	77-83
33059952-11	2021	RESULTS: Data showed that metformin decreased cell survival and expression of miRNA-21, miRNA-155, and miRNA-182 (p <0.05).	Metformin	26-35	microRNA 155	Homo sapiens	88-97
33059952-11	2021	RESULTS: Data showed that metformin decreased cell survival and expression of miRNA-21, miRNA-155, and miRNA-182 (p <0.05).	Metformin	26-35	microRNA 182	Homo sapiens	103-112
33262224-3	2021	In order to address if IC50 values of MATE1 inhibitors with regard to their extracellular concentrations are affected by the direction of MATE1-mediated transport, we established an efflux assay of 1-methyl-4-phenylpyridinium (MPP+) and metformin using the HEK293 model transiently expressing human MATE1.	Metformin	237-246	solute carrier family 47 member 1	Homo sapiens	38-43
33262224-13	2021	This study supports the rationale for commonly accepted uptake assay with metformin as an in vitro probe substrate for MATE1-mediated DDI risk assessment in drug development.	Metformin	74-83	solute carrier family 47 member 1	Homo sapiens	119-124
33523504-1	2021	Organic cation transporter (OCT) 3 (SLC22A3) is a widely-expressed drug transporter, handling notably metformin and platinum derivatives, as well as endogenous compounds like monoamine neurotransmitters.	Metformin	102-111	solute carrier family 22 member 3	Homo sapiens	0-34
33523504-1	2021	Organic cation transporter (OCT) 3 (SLC22A3) is a widely-expressed drug transporter, handling notably metformin and platinum derivatives, as well as endogenous compounds like monoamine neurotransmitters.	Metformin	102-111	solute carrier family 22 member 3	Homo sapiens	36-43
33386490-0	2021	Metformin ameliorates the status epilepticus- induced hippocampal pathology through possible mTOR modulation.	Metformin	0-9	mechanistic target of rapamycin kinase	Rattus norvegicus	93-97
33386490-10	2021	Metformin significantly inhibited phosphorylated S6 ribosomal protein (phospho-S6rp) (p < 0.05), thus demonstrating that the beneficial effects might be partly mediated by the mTOR pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Rattus norvegicus	176-180
32737864-0	2021	Metformin inhibits pancreatic cancer metastasis caused by SMAD4 deficiency and consequent HNF4G upregulation.	Metformin	0-9	hepatocyte nuclear factor 4 gamma	Homo sapiens	90-95
32737864-6	2021	We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency.	Metformin	19-28	hepatocyte nuclear factor 4 gamma	Homo sapiens	40-45
32737864-9	2021	These results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.	Metformin	180-189	hepatocyte nuclear factor 4 gamma	Homo sapiens	71-76
33510216-5	2021	Metformin increased expression of Slc2a1 (GLUT1), decreased expression of Slc2a2 (GLUT2) and Slc5a1 (SGLT1) whilst increasing GLUT-dependent glucose uptake and glycolytic rate as observed by live cell imaging of genetically encoded metabolite sensors and measurement of oxygen consumption and extracellular acidification rates.	Metformin	0-9	solute carrier family 5 (sodium/glucose cotransporter), member 1	Mus musculus	93-99
33510216-5	2021	Metformin increased expression of Slc2a1 (GLUT1), decreased expression of Slc2a2 (GLUT2) and Slc5a1 (SGLT1) whilst increasing GLUT-dependent glucose uptake and glycolytic rate as observed by live cell imaging of genetically encoded metabolite sensors and measurement of oxygen consumption and extracellular acidification rates.	Metformin	0-9	solute carrier family 5 (sodium/glucose cotransporter), member 1	Mus musculus	101-106
33019813-0	2021	Effects of Brief Adjunctive Metformin Therapy in Virologically Suppressed HIV-Infected Adults on Polyfunctional HIV-Specific CD8 T cell Responses to PD-L1 Blockade.	Metformin	28-37	CD8a molecule	Homo sapiens	125-128
33019813-8	2021	Ex vivo polyfunctional HIV-Gag-specific CD8 T cell responses to anti-PD-L1 mAb significantly improved (p < 0.05) over the 8-week course of metformin therapy.	Metformin	139-148	CD8a molecule	Homo sapiens	40-43
33019813-10	2021	Collectively, these findings highlight that 8-week course of metformin increases the polyfunctionality of CD8 T cells and that baseline monocyte subset frequencies may be a potential determinant of PD-L1 blockade efficacy.	Metformin	61-70	CD8a molecule	Homo sapiens	106-109
33227290-4	2021	We also reassessed the effect of metformin on EML4-ALK positive lung cancer (H3122) cell viability.	Metformin	33-42	EMAP like 4	Homo sapiens	46-50
33227290-4	2021	We also reassessed the effect of metformin on EML4-ALK positive lung cancer (H3122) cell viability.	Metformin	33-42	ALK receptor tyrosine kinase	Homo sapiens	51-54
33227290-11	2021	We further hypothesised that the effect of metformin could be due to modulation of thrombospondin 1 (TSP-1), which metformin has been proposed to regulatein vivo, but again we found no difference between the experimental groups.	Metformin	43-52	thrombospondin 1	Mus musculus	83-99
33227290-11	2021	We further hypothesised that the effect of metformin could be due to modulation of thrombospondin 1 (TSP-1), which metformin has been proposed to regulatein vivo, but again we found no difference between the experimental groups.	Metformin	43-52	thrombospondin 1	Mus musculus	101-106
33227290-11	2021	We further hypothesised that the effect of metformin could be due to modulation of thrombospondin 1 (TSP-1), which metformin has been proposed to regulatein vivo, but again we found no difference between the experimental groups.	Metformin	115-124	thrombospondin 1	Mus musculus	83-99
33227290-11	2021	We further hypothesised that the effect of metformin could be due to modulation of thrombospondin 1 (TSP-1), which metformin has been proposed to regulatein vivo, but again we found no difference between the experimental groups.	Metformin	115-124	thrombospondin 1	Mus musculus	101-106
32386485-4	2021	Clinical data suggest the direct effects of this drug on cardiac metabolism and studies in animal models showed that metformin activates the classical pathway of AMP-activated protein kinase (AMPK), generating cardioprotective effects during cardiac remodeling, hypertrophy and fibrosis.	Metformin	117-126	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	162-190
32386485-4	2021	Clinical data suggest the direct effects of this drug on cardiac metabolism and studies in animal models showed that metformin activates the classical pathway of AMP-activated protein kinase (AMPK), generating cardioprotective effects during cardiac remodeling, hypertrophy and fibrosis.	Metformin	117-126	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	192-196
32987433-0	2021	Efficacy of Metformin and Chemotherapeutic Agents on the Inhibition of Colony Formation and Shh/Gli1 Pathway: Metformin/Docetaxel Versus Metformin/5-Fluorouracil.	Metformin	12-21	GLI family zinc finger 1	Homo sapiens	96-100
32987433-0	2021	Efficacy of Metformin and Chemotherapeutic Agents on the Inhibition of Colony Formation and Shh/Gli1 Pathway: Metformin/Docetaxel Versus Metformin/5-Fluorouracil.	Metformin	110-119	GLI family zinc finger 1	Homo sapiens	96-100
32987433-0	2021	Efficacy of Metformin and Chemotherapeutic Agents on the Inhibition of Colony Formation and Shh/Gli1 Pathway: Metformin/Docetaxel Versus Metformin/5-Fluorouracil.	Metformin	110-119	GLI family zinc finger 1	Homo sapiens	96-100
32987433-12	2021	Interestingly, we found that the combination of metformin with docetaxel significantly down-regulated the mRNA levels of Gli1, Gli2, and TWIST1 in the AGS gastric cancer cell line compared to docetaxel alone.	Metformin	48-57	GLI family zinc finger 1	Homo sapiens	121-125
33601368-0	2021	Metformin Inhibits Abdominal Aortic Aneurysm Formation through the Activation of the AMPK/mTOR Signaling Pathway.	Metformin	0-9	mechanistic target of rapamycin kinase	Rattus norvegicus	90-94
32994182-9	2021	Immunostaining of primary tumors indicated that DPP-4 suppression promoted the expression of EMT-inducing transcription factor Snail through activation of the CXCR4-mediated mTOR/p70S6K pathway in an allograft breast cancer model; metformin abolished this alteration.	Metformin	231-240	snail family zinc finger 1	Mus musculus	127-132
33311640-8	2020	Pathway enrichment analysis suggested that pathways associated with proliferation and nutrient sensing are modulated by metformin-regulated miRNAs and that some of the regulated isomiRs (e.g. the 5" miR-217 isomiR) are endowed with alternative seed sequences and share less than half of the predicted targets with the canonical form.	Metformin	120-129	microRNA 217	Homo sapiens	199-206
30513216-7	2020	Treatment with metformin up-regulated antioxidant enzymes, down-regulated inflammation, and apoptosis and increased PCNA immunoexpression in the testes.	Metformin	15-24	proliferating cell nuclear antigen	Rattus norvegicus	116-120
33221742-7	2020	In addition, according to immunofluorescence staining of MTs, metformin, a medicine for the treatment of diabetes mellitus, rescued the reduced length of neurites detected in NEAT1 silencing cells.	Metformin	62-71	nuclear paraspeckle assembly transcript 1	Homo sapiens	175-180
33221742-8	2020	We suspected that metformin may play a neuroprotective role in early AD by increasing NEAT1 expression and through FZD3/GSK3beta/p-tau pathway.	Metformin	18-27	nuclear paraspeckle assembly transcript 1	Homo sapiens	86-91
32713735-10	2020	Finally, we found that the anti-diabetic and potential anti-aging drug metformin strongly induced G6PD activity throughout reconstructed epidermis.	Metformin	71-80	glucose-6-phosphate dehydrogenase	Homo sapiens	98-102
32312181-7	2020	Addition of metformin increased transport, in the context of a transient effect on AMPK phosphorylation.	Metformin	12-21	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	83-87
33062917-4	2020	Objective: To assess the endometrial expression changes of vascular endothelial growth factor A (VEGFA) and leukemia inhibitory factor (LIF), at the time of implantation in diabetic rats following treatment with Metformin and Pioglitazone.	Metformin	212-221	LIF, interleukin 6 family cytokine	Rattus norvegicus	136-139
33062917-10	2020	LIF expression was elevated in the Metformin- and the Pioglitazone-treated rats and reduced in the diabetic group in comparison with the control group.	Metformin	35-44	LIF, interleukin 6 family cytokine	Rattus norvegicus	0-3
33062917-11	2020	Compared to the diabetic rats, the expression of LIF was significantly elevated in the Metformin- (p = 0.01) and Pioglitazone-treated (p = 0.03) groups.	Metformin	87-96	LIF, interleukin 6 family cytokine	Rattus norvegicus	49-52
32738111-3	2020	Metformin can activate 5"-AMP-activated protein kinase (AMPK) to improve metabolic flexibility and maintain energy homeostasis.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	56-60
32738111-4	2020	Thus, the aim of the present study was to investigate whether metformin can improve boar sperm quality through AMPK mediation of energy metabolism.	Metformin	62-71	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	111-115
32738111-7	2020	We found that metformin treatment significantly increased sperm motility parameters, mitochondrial membrane potential, and ATP content during storage at 17  C. Moreover, results showed that AMPK was localized at the acrosomal region, connecting piece, and midpiece of sperm and p-AMPK was distributed at the post-acrosomal region, connecting piece, and midpiece.	Metformin	14-23	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	190-194
32738111-7	2020	We found that metformin treatment significantly increased sperm motility parameters, mitochondrial membrane potential, and ATP content during storage at 17  C. Moreover, results showed that AMPK was localized at the acrosomal region, connecting piece, and midpiece of sperm and p-AMPK was distributed at the post-acrosomal region, connecting piece, and midpiece.	Metformin	14-23	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	280-284
32738111-8	2020	When sperm were incubated with metformin for 4 h at 37  C, sperm motility parameters, mitochondrial membrane potential, ATP content, p-AMPK, glucose uptake, and lactate efflux all significantly increased, whereas the addition of Compound C treatment, an inhibitor of AMPK, counteracted these positive effects.	Metformin	31-40	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	135-139
32738111-8	2020	When sperm were incubated with metformin for 4 h at 37  C, sperm motility parameters, mitochondrial membrane potential, ATP content, p-AMPK, glucose uptake, and lactate efflux all significantly increased, whereas the addition of Compound C treatment, an inhibitor of AMPK, counteracted these positive effects.	Metformin	31-40	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	267-271
32738111-9	2020	Together, our results suggest that metformin promotes AMPK activation, which contributes to the maintenance of energy hemostasis and mitochondrial activity, thereby maintaining boar sperm functionality and improving the efficacy of semen preservation.	Metformin	35-44	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	54-58
32911743-11	2020	Metformin treatment increased p-AMPK and decreased mTOR (pS6) expression; these effects were reversed by addition of mevalonate.	Metformin	0-9	taste 2 receptor member 63 pseudogene	Homo sapiens	57-60
33042621-0	2020	Metformin activates the STING/IRF3/IFN-beta pathway by inhibiting AKT phosphorylation in pancreatic cancer.	Metformin	0-9	interferon alpha	Mus musculus	35-43
33042621-4	2020	Metformin also activated the STING/IRF3/IFN-beta pathway by inhibiting AKT signaling in PDAC cells.	Metformin	0-9	interferon alpha	Mus musculus	40-48
32718270-7	2020	Metformin significantly inhibited the expression of phosphorylation-PFKFB2(p-PFKFB2) in the low-glucose group and inhibited the LDH activity both in the low and high glucose groups, thus inhibiting anaerobic glycolysis and inducing energy stress.	Metformin	0-9	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2	Homo sapiens	68-74
32718270-7	2020	Metformin significantly inhibited the expression of phosphorylation-PFKFB2(p-PFKFB2) in the low-glucose group and inhibited the LDH activity both in the low and high glucose groups, thus inhibiting anaerobic glycolysis and inducing energy stress.	Metformin	0-9	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2	Homo sapiens	77-83
32718270-11	2020	In conclusion, the enhanced inhibitory effect of metformin on PANC-1 cells cultured in low glucose may be due to the up-regulation of the expression of miR-210-5p, then inhibiting anaerobic glycolytic flux and inducing energy stress via repressing the expression of p-PFKFB2 and activity of LDH.	Metformin	49-58	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2	Homo sapiens	268-274
31593308-8	2020	RESULTS: Metformin treatment was associated with a 41.4% decrease in FOXP3+ T cells in intratumor regions of interest (P = .004) and a 66.5% increase in stromal CD8+ T cells at the leading edge of the tumor (P = .021) when compared to pretreatment biopsies.	Metformin	9-18	CD8a molecule	Homo sapiens	161-164
32959498-7	2020	Metformin increased the levels of p-AMPK and PGC-1alpha, a downstream AMPK target which regulates mitochondrial biogenesis, at P4, P10, and P21 in hyperoxia pups.	Metformin	0-9	KRAS proto-oncogene, GTPase	Rattus norvegicus	140-143
32959498-9	2020	Radial alveolar count and alveolar septal tips were decreased and mean linear intercept increased in hyperoxia-exposed pups at P10 and the changes persisted at P21; these were improved by metformin.	Metformin	188-197	KRAS proto-oncogene, GTPase	Rattus norvegicus	160-163
32863218-0	2020	Metformin alleviates lead-induced mitochondrial fragmentation via AMPK/Nrf2 activation in SH-SY5Y cells.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	66-70
32863218-5	2020	By applying metformin, an AMP-activated protein kinase (AMPK) activator, these impairments could be alleviated via activation of AMPK, validated by experiments of pharmacological inhibition of AMPK.	Metformin	12-21	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	26-54
32863218-5	2020	By applying metformin, an AMP-activated protein kinase (AMPK) activator, these impairments could be alleviated via activation of AMPK, validated by experiments of pharmacological inhibition of AMPK.	Metformin	12-21	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	56-60
32863218-5	2020	By applying metformin, an AMP-activated protein kinase (AMPK) activator, these impairments could be alleviated via activation of AMPK, validated by experiments of pharmacological inhibition of AMPK.	Metformin	12-21	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	129-133
32863218-5	2020	By applying metformin, an AMP-activated protein kinase (AMPK) activator, these impairments could be alleviated via activation of AMPK, validated by experiments of pharmacological inhibition of AMPK.	Metformin	12-21	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	129-133
32863218-9	2020	To conclude, metformin could ameliorate Pb-induced mitochondrial fragmentation via antioxidative effects originated from AMPK/Nrf2 pathway activation, promoting energy supply and cell survival.	Metformin	13-22	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	121-125
32190918-6	2020	We also found that metformin increased the immunoreactivity of synaptophysin, sirtuin-1, AMP-activated protein kinase (AMPK) and brain-derived neuronal factor (BDNF), which are important plasticity markers.	Metformin	19-28	synaptophysin	Rattus norvegicus	63-76
32190918-6	2020	We also found that metformin increased the immunoreactivity of synaptophysin, sirtuin-1, AMP-activated protein kinase (AMPK) and brain-derived neuronal factor (BDNF), which are important plasticity markers.	Metformin	19-28	brain-derived neurotrophic factor	Rattus norvegicus	129-158
32190918-6	2020	We also found that metformin increased the immunoreactivity of synaptophysin, sirtuin-1, AMP-activated protein kinase (AMPK) and brain-derived neuronal factor (BDNF), which are important plasticity markers.	Metformin	19-28	brain-derived neurotrophic factor	Rattus norvegicus	160-164
32879653-11	2020	Both diabetic groups treated with CNME or metformin significantly improved the impairment in endothelium-dependent vasorelaxation; this was associated with increased expression of aortic eNOS protein.	Metformin	42-51	nitric oxide synthase 3	Rattus norvegicus	187-191
32806648-6	2020	We, thus, developed a new therapeutic approach to inhibit EGFR and hypoxia by combination treatment with metformin and gefitinib that sensitized TNBC cells to cisplatin and led to the inhibition of both CD44+/CD24- and ALDH+ CSCs.	Metformin	105-114	CD44 molecule (Indian blood group)	Homo sapiens	203-207
32780768-4	2020	The longitudinal blood-derived transcriptome analysis revealed metformin-induced differential expression of novel and previously described genes involved in cholesterol homeostasis (SLC46A1 and LRP1), cancer development (CYP1B1, STAB1, CCR2, TMEM176B), and immune responses (CD14, CD163) after administration of metformin for three months.	Metformin	63-72	stabilin 1	Homo sapiens	229-234
32780768-4	2020	The longitudinal blood-derived transcriptome analysis revealed metformin-induced differential expression of novel and previously described genes involved in cholesterol homeostasis (SLC46A1 and LRP1), cancer development (CYP1B1, STAB1, CCR2, TMEM176B), and immune responses (CD14, CD163) after administration of metformin for three months.	Metformin	63-72	transmembrane protein 176B	Homo sapiens	242-250
32780768-4	2020	The longitudinal blood-derived transcriptome analysis revealed metformin-induced differential expression of novel and previously described genes involved in cholesterol homeostasis (SLC46A1 and LRP1), cancer development (CYP1B1, STAB1, CCR2, TMEM176B), and immune responses (CD14, CD163) after administration of metformin for three months.	Metformin	63-72	CD163 molecule	Homo sapiens	281-286
32568826-11	2020	In conclusion, these results indicate that metformin-induced apoptosis was mediated through AIF-promoted caspase-independent pathways as well as caspase-dependent pathways in T24 cells.	Metformin	43-52	apoptosis inducing factor mitochondria associated 1	Homo sapiens	92-95
32409919-0	2020	Characterization of Huh7 cells after the induction of insulin resistance and post-treatment with metformin.	Metformin	97-106	MIR7-3 host gene	Homo sapiens	20-24
32472157-0	2020	A drug-drug interaction study to evaluate the impact of peficitinib on OCT1- and MATE1-mediated transport of metformin in healthy volunteers.	Metformin	109-118	solute carrier family 47 member 1	Homo sapiens	81-86
32472157-3	2020	Hepatic and renal uptake of metformin is mediated by organic cation transporter 1 (OCT1) and OCT2, respectively, and its renal excretion by multidrug and toxin extrusion 1 (MATE1) and MATE2-K.	Metformin	28-37	solute carrier family 47 member 1	Homo sapiens	140-171
32472157-3	2020	Hepatic and renal uptake of metformin is mediated by organic cation transporter 1 (OCT1) and OCT2, respectively, and its renal excretion by multidrug and toxin extrusion 1 (MATE1) and MATE2-K.	Metformin	28-37	solute carrier family 47 member 1	Homo sapiens	173-178
32551505-5	2020	The assay is capable of simultaneously quantifying multiple endogenous compounds, including IBC, thiamine, N1-methylnicotinamide (1-NMN), creatinine, carnitine, and metformin, a substrate for OCT1/2 and MATE1/2K in clinical studies.	Metformin	165-174	solute carrier family 47 member 1	Homo sapiens	203-210
32765083-7	2020	MHCC97H cells were transfected with a EGFP-LC3 plasmid and treatment with metformin could lead to the increased level of LC3-II and decreased level of p62.	Metformin	74-83	nucleoporin 62	Homo sapiens	151-154
32443237-6	2020	Metformin significantly attenuated the production of IL-6, mitochondrial damage, cell viability and LDH activity by limiting TLRs/MyD88/NF-kappaB pathway.	Metformin	0-9	myeloid differentiation primary response gene 88	Mus musculus	130-135
32443237-8	2020	Pretreatment with metformin significantly attenuated PM2.5 induced decreasing of cell viability and increased LDH activity, as well as inhibited the TLRs/MyD88/NF-kappaB pathway in both siControl or siAMPKalpha2 cells.	Metformin	18-27	myeloid differentiation primary response gene 88	Mus musculus	154-159
32443237-9	2020	Taken together, our results indicate that metformin protects against PM2.5-induced mitochondrial damage and cell cytotoxicity by inhibiting TLRs/MyD88/NF-kappaB signaling pathway in an AMPKalpha2 independent manner.	Metformin	42-51	myeloid differentiation primary response gene 88	Mus musculus	145-150
32187752-7	2020	Currently, the most promising potential drug candidate to slow AAA growth is metformin, and RCTs to verify or reject this hypothesis are warranted.	Metformin	77-86	AAA1	Homo sapiens	63-66
32453427-2	2020	Recent studies have demonstrated that metformin, which is an AMPK activator, modifies alternative precursor mRNA (pre-mRNA) splicing.	Metformin	38-47	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	61-65
32591547-0	2020	The importance of the AMPK gamma 1 subunit in metformin suppression of liver glucose production.	Metformin	46-55	protein kinase, AMP-activated, gamma 1 non-catalytic subunit	Mus musculus	22-34
32670025-0	2020	Metformin Ameliorates Synaptic Defects in a Mouse Model of AD by Inhibiting Cdk5 Activity.	Metformin	0-9	cyclin-dependent kinase 5	Mus musculus	76-80
32670025-4	2020	Here in the present study, we showed that metformin, the most widely used drug for type 2 diabetes, suppressed Cdk5 hyper-activation and Cdk5-dependent tau hyper-phosphorylation in the APP/PS1 mouse hippocampus.	Metformin	42-51	cyclin-dependent kinase 5	Mus musculus	111-115
32670025-4	2020	Here in the present study, we showed that metformin, the most widely used drug for type 2 diabetes, suppressed Cdk5 hyper-activation and Cdk5-dependent tau hyper-phosphorylation in the APP/PS1 mouse hippocampus.	Metformin	42-51	cyclin-dependent kinase 5	Mus musculus	137-141
32670025-5	2020	We also identified the underlying molecular and cellular mechanism that metformin prevented Cdk5 hyper-activation by inhibiting the calpain-dependent cleavage of p35 into p25.	Metformin	72-81	cyclin-dependent kinase 5	Mus musculus	92-96
32670025-7	2020	Altogether our study discovered an unidentified role of metformin in suppressing Cdk5 hyper-activation and thus preventing AD pathogenesis and suggested that metformin is a potential promising AD therapeutic drug.	Metformin	56-65	cyclin-dependent kinase 5	Mus musculus	81-85
32670025-7	2020	Altogether our study discovered an unidentified role of metformin in suppressing Cdk5 hyper-activation and thus preventing AD pathogenesis and suggested that metformin is a potential promising AD therapeutic drug.	Metformin	158-167	cyclin-dependent kinase 5	Mus musculus	81-85
32625061-0	2020	Metformin Protects From Rotenone-Induced Nigrostriatal Neuronal Death in Adult Mice by Activating AMPK-FOXO3 Signaling and Mitigation of Angiogenesis.	Metformin	0-9	forkhead box O3	Mus musculus	103-108
32625104-8	2020	AMPK knockdown blocked the inhibitory functions of JMJD1C knockdown on Ang II-induced hypertrophic response, whereas metformin reduced the functions of JMJD1C and repressed the hypertrophic response in cardiomyocytes.	Metformin	117-126	jumonji domain containing 1C	Mus musculus	152-158
32399705-14	2020	Furthermore, insulin showed more beneficial effects than metformin in hindering these complications by modifying the expression of VEGF and TGF-beta.	Metformin	57-66	transforming growth factor alpha	Rattus norvegicus	140-148
32360359-12	2020	We found a significant inhibition of ACTH induced MC2R activation and signaling with 10 mM metformin.	Metformin	91-100	melanocortin 2 receptor	Mus musculus	50-54
32427048-1	2020	Aim: GDF15 levels are a biomarker for metformin use.	Metformin	38-47	growth differentiation factor 15	Homo sapiens	5-10
32427048-5	2020	Conclusion: Noncoding variation within a metformin-activated enhancer may increase GDF15 expression and help to predict GDF15 levels.	Metformin	41-50	growth differentiation factor 15	Homo sapiens	83-88
32427048-5	2020	Conclusion: Noncoding variation within a metformin-activated enhancer may increase GDF15 expression and help to predict GDF15 levels.	Metformin	41-50	growth differentiation factor 15	Homo sapiens	120-125
31904843-0	2020	Metformin enhances the immunomodulatory potential of adipose-derived mesenchymal stem cells through STAT1 in an animal model of lupus.	Metformin	0-9	signal transducer and activator of transcription 1	Mus musculus	100-105
31904843-9	2020	Metformin upregulated the expression of p-AMPK, p-STAT1 and inhibited the expression of p-STAT3, p-mTOR in Ad-MSCs.	Metformin	0-9	signal transducer and activator of transcription 1	Mus musculus	50-55
31904843-10	2020	STAT1 inhibition by siRNA strongly diminished IDO, IL-10, TGF-beta in metformin-treated Ad-MSCs.	Metformin	70-79	signal transducer and activator of transcription 1	Mus musculus	0-5
31904843-11	2020	As a result, metformin promoted the immunoregulatory effect of Ad-MSCs by enhancing STAT1 expression, which was dependent on the AMPK/mTOR pathway.	Metformin	13-22	signal transducer and activator of transcription 1	Mus musculus	84-89
31904843-13	2020	Moreover, metformin-treated Ad-MSCs inhibited CD4-CD8- T-cell expansion and Th17/Treg cell ratio.	Metformin	10-19	CD4 antigen	Mus musculus	46-49
32444674-11	2020	The transcription factor downstream of AMPK that is relevant to cAMP signaling is CREB; decreased levels of phospho-CREB seem to mediate the observed effects of metformin on NaCT.	Metformin	161-170	cAMP responsive element binding protein 1	Homo sapiens	116-120
32508669-0	2020	Metformin Ameliorates Diabetic Cardiomyopathy by Activating the PK2/PKR Pathway.	Metformin	0-9	eukaryotic translation initiation factor 2-alpha kinase 2	Mus musculus	68-71
32547075-0	2020	Metformin Promotes Beclin1-Dependent Autophagy to Inhibit the Progression of Gastric Cancer.	Metformin	0-9	beclin 1	Homo sapiens	19-26
32547075-4	2020	Transmission electron microscopy, confocal microscopy and Western blotting confirmed that metformin enhanced beclin1-dependent autophagy in gastric cancer cells.	Metformin	90-99	beclin 1	Homo sapiens	109-116
32547075-10	2020	Metformin could also promote beclin1-dependent autophagy in GC cells.	Metformin	0-9	beclin 1	Homo sapiens	29-36
32547075-13	2020	Furthermore, we verified that metformin can upregulate beclin1-mediated autophagy to inhibit GC cells through the AMPK-mTOR signalling pathway.	Metformin	30-39	beclin 1	Homo sapiens	55-62
32547075-14	2020	Conclusion: In summary, the results revealed the role of autophagy in metformin inhibition of gastric cancer and suggest that beclin1 may be a potential target for gastric cancer therapy.	Metformin	70-79	beclin 1	Homo sapiens	126-133
32550202-10	2020	Results: Treatment with metformin/donepezil combination significantly reduced the activities of AchE, BchE as well as levels of malondialdehyde, TNF-alpha and IL-6, while the activities of SOD, GPx and catalase were significantly increased in the brain.	Metformin	24-33	butyrylcholinesterase	Rattus norvegicus	102-106
32202622-10	2020	While in-vitro treatment with metformin alone increased Snail and decreased Claudin 1, N-cadherin and alpha-SMA proteins, concomitant treatment with metformin and E2 increased the expression of CK 8 and Snail proteins and decreased the expression of Claudin 1, ZO-1, Slug and alpha-SMA proteins.	Metformin	30-39	claudin 1	Homo sapiens	76-85
32202622-10	2020	While in-vitro treatment with metformin alone increased Snail and decreased Claudin 1, N-cadherin and alpha-SMA proteins, concomitant treatment with metformin and E2 increased the expression of CK 8 and Snail proteins and decreased the expression of Claudin 1, ZO-1, Slug and alpha-SMA proteins.	Metformin	30-39	cadherin 2	Homo sapiens	87-97
32202622-10	2020	While in-vitro treatment with metformin alone increased Snail and decreased Claudin 1, N-cadherin and alpha-SMA proteins, concomitant treatment with metformin and E2 increased the expression of CK 8 and Snail proteins and decreased the expression of Claudin 1, ZO-1, Slug and alpha-SMA proteins.	Metformin	30-39	keratin 8	Homo sapiens	194-198
32202622-10	2020	While in-vitro treatment with metformin alone increased Snail and decreased Claudin 1, N-cadherin and alpha-SMA proteins, concomitant treatment with metformin and E2 increased the expression of CK 8 and Snail proteins and decreased the expression of Claudin 1, ZO-1, Slug and alpha-SMA proteins.	Metformin	30-39	claudin 1	Homo sapiens	250-259
32202622-10	2020	While in-vitro treatment with metformin alone increased Snail and decreased Claudin 1, N-cadherin and alpha-SMA proteins, concomitant treatment with metformin and E2 increased the expression of CK 8 and Snail proteins and decreased the expression of Claudin 1, ZO-1, Slug and alpha-SMA proteins.	Metformin	30-39	snail family transcriptional repressor 2	Homo sapiens	267-271
32202622-10	2020	While in-vitro treatment with metformin alone increased Snail and decreased Claudin 1, N-cadherin and alpha-SMA proteins, concomitant treatment with metformin and E2 increased the expression of CK 8 and Snail proteins and decreased the expression of Claudin 1, ZO-1, Slug and alpha-SMA proteins.	Metformin	149-158	claudin 1	Homo sapiens	76-85
32202622-10	2020	While in-vitro treatment with metformin alone increased Snail and decreased Claudin 1, N-cadherin and alpha-SMA proteins, concomitant treatment with metformin and E2 increased the expression of CK 8 and Snail proteins and decreased the expression of Claudin 1, ZO-1, Slug and alpha-SMA proteins.	Metformin	149-158	cadherin 2	Homo sapiens	87-97
32202622-10	2020	While in-vitro treatment with metformin alone increased Snail and decreased Claudin 1, N-cadherin and alpha-SMA proteins, concomitant treatment with metformin and E2 increased the expression of CK 8 and Snail proteins and decreased the expression of Claudin 1, ZO-1, Slug and alpha-SMA proteins.	Metformin	149-158	keratin 8	Homo sapiens	194-198
32202622-10	2020	While in-vitro treatment with metformin alone increased Snail and decreased Claudin 1, N-cadherin and alpha-SMA proteins, concomitant treatment with metformin and E2 increased the expression of CK 8 and Snail proteins and decreased the expression of Claudin 1, ZO-1, Slug and alpha-SMA proteins.	Metformin	149-158	claudin 1	Homo sapiens	250-259
32202622-10	2020	While in-vitro treatment with metformin alone increased Snail and decreased Claudin 1, N-cadherin and alpha-SMA proteins, concomitant treatment with metformin and E2 increased the expression of CK 8 and Snail proteins and decreased the expression of Claudin 1, ZO-1, Slug and alpha-SMA proteins.	Metformin	149-158	snail family transcriptional repressor 2	Homo sapiens	267-271
32415061-6	2020	Notably, the metastatic potential in PDAC could be reversely regulated by metformin, a drug was found accelerating the degradation of COX6B2 mRNA in this study.	Metformin	74-83	cytochrome c oxidase subunit 6B2	Mus musculus	134-140
32483456-0	2020	Dysregulated expression of monoacylglycerol lipase is a marker for anti-diabetic drug metformin-targeted therapy to correct impaired neurogenesis and spatial memory in Alzheimer"s disease.	Metformin	86-95	monoglyceride lipase	Homo sapiens	27-50
32483456-4	2020	Here, we identify Mgll as an aging-induced factor that impairs adult neurogenesis and spatial memory in AD, and show that metformin, an FDA-approved anti-diabetic drug, can reduce the expression of Mgll to reverse impaired adult neurogenesis, prevent spatial memory decline and reduce beta-amyloid accumulation.	Metformin	122-131	monoglyceride lipase	Homo sapiens	18-22
32483456-4	2020	Here, we identify Mgll as an aging-induced factor that impairs adult neurogenesis and spatial memory in AD, and show that metformin, an FDA-approved anti-diabetic drug, can reduce the expression of Mgll to reverse impaired adult neurogenesis, prevent spatial memory decline and reduce beta-amyloid accumulation.	Metformin	122-131	monoglyceride lipase	Homo sapiens	198-202
32483456-12	2020	However, we find that metformin-stimulated aPKC-CBP pathway decreases Mgll expression to recover these deficits in 3xTg-AD.	Metformin	22-31	CREB binding protein	Mus musculus	48-51
32483456-14	2020	Conclusion: Our findings set the stage for development of a clinical protocol where Mgll would serve as a biomarker in early stages of AD to identify potential metformin-responsive AD patients to restore their neurogenesis and spatial memory.	Metformin	160-169	monoglyceride lipase	Homo sapiens	84-88
32404204-6	2020	In contrast, metformin and SGLT2 inhibitors activate SIRT1 and/or AMPK and promote autophagic flux to varying degrees in cardiomyocytes, which may explain their benefits in experimental cardiomyopathy.	Metformin	13-22	sirtuin 1	Homo sapiens	53-58
32467714-0	2020	High fat-induced inflammation in vascular endothelium can be improved by Abelmoschus esculentus and metformin via increasing the expressions of miR-146a and miR-155.	Metformin	100-109	microRNA 155	Rattus norvegicus	157-164
32467714-9	2020	While AE and metformin could ameliorate the endothelial inflammation by increasing miR-146a and miR-155.	Metformin	13-22	microRNA 155	Rattus norvegicus	96-103
32467714-11	2020	AE and metformin can attenuate endothelial inflammation through regulating miR-146a and miR-155.	Metformin	7-16	microRNA 155	Rattus norvegicus	88-95
32518807-0	2020	Metformin, an AMPK Activator, Inhibits Activation of FLSs but Promotes HAPLN1 Secretion.	Metformin	0-9	hyaluronan and proteoglycan link protein 1	Homo sapiens	71-77
32518807-9	2020	After metformin treatment, expression of interleukin 6 (IL-6), TNF-alpha, and IL-1beta were significantly downregulated in RA-FLSs; however, increased expression of p-AMPK-alpha1, protein kinase A (PKA)-alpha1, and HAPLN1 (hyaluronan and proteoglycan link protein 1) was observed.	Metformin	6-15	hyaluronan and proteoglycan link protein 1	Homo sapiens	215-221
32518807-9	2020	After metformin treatment, expression of interleukin 6 (IL-6), TNF-alpha, and IL-1beta were significantly downregulated in RA-FLSs; however, increased expression of p-AMPK-alpha1, protein kinase A (PKA)-alpha1, and HAPLN1 (hyaluronan and proteoglycan link protein 1) was observed.	Metformin	6-15	hyaluronan and proteoglycan link protein 1	Homo sapiens	223-265
32375255-6	2020	In conditions of either glucose excess or gluconeogenic substrate excess, metformin lowers hexose monophosphates by mechanisms that are independent of AMPK-activation and most likely mediated by allosteric activation of phosphofructokinase-1 and/or inhibition of fructose bisphosphatase-1.	Metformin	74-83	fructose-bisphosphatase 1	Homo sapiens	263-288
32364526-4	2020	Metformin may interfere with these pathways by orchestrating AMPK signaling and AMPK-independent pathways to protect the kidneys from injury.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	61-65
32364526-4	2020	Metformin may interfere with these pathways by orchestrating AMPK signaling and AMPK-independent pathways to protect the kidneys from injury.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	80-84
32208194-0	2020	Metformin treatment decreases the expression of cancer stem cell marker CD44 and stemness related gene expression in primary oral cancer cells.	Metformin	0-9	CD44 molecule (Indian blood group)	Homo sapiens	72-76
32208194-3	2020	Here, we attempt to find out the effect of metformin on cancer stem cell marker CD44 and stemness related transcription factors including OCT4, SOX2, NANOG, c-Myc and KLF4.	Metformin	43-52	CD44 molecule (Indian blood group)	Homo sapiens	80-84
32208194-3	2020	Here, we attempt to find out the effect of metformin on cancer stem cell marker CD44 and stemness related transcription factors including OCT4, SOX2, NANOG, c-Myc and KLF4.	Metformin	43-52	SRY-box transcription factor 2	Homo sapiens	144-148
32208194-3	2020	Here, we attempt to find out the effect of metformin on cancer stem cell marker CD44 and stemness related transcription factors including OCT4, SOX2, NANOG, c-Myc and KLF4.	Metformin	43-52	Nanog homeobox	Homo sapiens	150-155
32208194-3	2020	Here, we attempt to find out the effect of metformin on cancer stem cell marker CD44 and stemness related transcription factors including OCT4, SOX2, NANOG, c-Myc and KLF4.	Metformin	43-52	Kruppel like factor 4	Homo sapiens	167-171
32208194-7	2020	RESULTS: Metformin showed downregulation in the gene expressions of stemness related transcription factors OCT4, SOX2, NANOG, c-Myc, and KLF4 in a dose-dependent as well as time-dependent manner.	Metformin	9-18	SRY-box transcription factor 2	Homo sapiens	113-117
32208194-7	2020	RESULTS: Metformin showed downregulation in the gene expressions of stemness related transcription factors OCT4, SOX2, NANOG, c-Myc, and KLF4 in a dose-dependent as well as time-dependent manner.	Metformin	9-18	Nanog homeobox	Homo sapiens	119-124
32208194-7	2020	RESULTS: Metformin showed downregulation in the gene expressions of stemness related transcription factors OCT4, SOX2, NANOG, c-Myc, and KLF4 in a dose-dependent as well as time-dependent manner.	Metformin	9-18	Kruppel like factor 4	Homo sapiens	137-141
32208194-8	2020	Also, the most effective concentration of metformin at 25 muM was found to decrease the expression of CD44 in the primary tumor cells in a time-dependent manner.	Metformin	42-51	CD44 molecule (Indian blood group)	Homo sapiens	102-106
32208194-9	2020	CONCLUSION: Continuous treatment of lower concentrations of metformin decreases the expression of cancer stem cell markers at the transcription level and cancer stem cell-surface marker CD44 in primary oral cancer cells.	Metformin	60-69	CD44 molecule (Indian blood group)	Homo sapiens	186-190
32246808-5	2020	Pharmacologic activation of AMPK with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) or metformin during sepsis improved the survival, while AMPK inhibition with Compound C increased mortality, impaired mitochondrial respiration, decreased OCR, and disrupted TEC metabolic fitness.	Metformin	95-104	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	28-32
32281270-3	2020	Metformin (MET), a first-line diabetes medication that also has anti-tumour activities, induces AMP-activated protein kinase (AMPK), directly phosphorylates YAP and inhibits YAP transcriptional activity.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	96-124
32281270-3	2020	Metformin (MET), a first-line diabetes medication that also has anti-tumour activities, induces AMP-activated protein kinase (AMPK), directly phosphorylates YAP and inhibits YAP transcriptional activity.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	126-130
32092034-7	2020	We observed that dapagliflozin or metformin mitigated the enhanced expression of renal gluconeogenic enzymes, PEPCK, G6Pase and FBPase, as well as improved glucose tolerance and renal function in obese rats.	Metformin	34-43	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	110-115
32221038-0	2020	Metformin Enhances the Antitumor Activity of CD8+ T Lymphocytes via the AMPK-miR-107-Eomes-PD-1 Pathway.	Metformin	0-9	CD8a molecule	Homo sapiens	45-48
32221038-3	2020	We found that the frequencies of memory stem and central memory T cells increased for both in peripheral and tumor-infiltrating CD8+ T cells in metformin-treated lung cancer patients compared with those not taking the medication.	Metformin	144-153	CD8a molecule	Homo sapiens	128-131
32221038-4	2020	An in vitro assay showed that metformin promoted the formation of memory CD8+ T cells and enhanced their antiapoptotic abilities.	Metformin	30-39	CD8a molecule	Homo sapiens	73-76
32221038-5	2020	In addition, AMP-activated protein kinase (AMPK) activation decreased microRNA-107 expression, thus enhancing Eomesodermin expression, which suppressed the transcription of PDCD1 in metformin-treated CD8+ T cells.	Metformin	182-191	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	13-41
32221038-5	2020	In addition, AMP-activated protein kinase (AMPK) activation decreased microRNA-107 expression, thus enhancing Eomesodermin expression, which suppressed the transcription of PDCD1 in metformin-treated CD8+ T cells.	Metformin	182-191	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	43-47
32221038-5	2020	In addition, AMP-activated protein kinase (AMPK) activation decreased microRNA-107 expression, thus enhancing Eomesodermin expression, which suppressed the transcription of PDCD1 in metformin-treated CD8+ T cells.	Metformin	182-191	CD8a molecule	Homo sapiens	200-203
32221038-7	2020	Metformin could reprogram the differentiation of CD8+ T cells, which may benefit the clinical therapy of cancer patients by facilitating long-lasting cytotoxic functions.	Metformin	0-9	CD8a molecule	Homo sapiens	49-52
32249489-3	2020	Metformin is an anti-hyperglycemic drug which is beneficial for treating the both DM2 and DM1.	Metformin	0-9	DM1 protein kinase	Homo sapiens	90-93
32249489-6	2020	Metformin also restored the expression of the steroidogenic transport protein steroidogenic acute regulatory protein reduced in DM1.	Metformin	0-9	DM1 protein kinase	Homo sapiens	128-131
32114843-2	2020	The purpose of the present study was to assess the possible modulatory effect of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor lovastatin on therapeutic efficiency of traditional antidiabetics, as metformin and gliclazide, regarding hepatic complications in streptozotocin (STZ)-induced diabetes in rats.Methods: Animals were divided into seven groups; normal control group, STZ control group (50 mg/kg, i.p., single dose), lovastatin group, metformin group, gliclazide group, lovastatin plus metformin group and lovastatin plus gliclazide group.	Metformin	223-232	3-hydroxy-3-methylglutaryl-CoA reductase	Rattus norvegicus	85-142
32114843-2	2020	The purpose of the present study was to assess the possible modulatory effect of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor lovastatin on therapeutic efficiency of traditional antidiabetics, as metformin and gliclazide, regarding hepatic complications in streptozotocin (STZ)-induced diabetes in rats.Methods: Animals were divided into seven groups; normal control group, STZ control group (50 mg/kg, i.p., single dose), lovastatin group, metformin group, gliclazide group, lovastatin plus metformin group and lovastatin plus gliclazide group.	Metformin	468-477	3-hydroxy-3-methylglutaryl-CoA reductase	Rattus norvegicus	85-142
32114843-2	2020	The purpose of the present study was to assess the possible modulatory effect of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor lovastatin on therapeutic efficiency of traditional antidiabetics, as metformin and gliclazide, regarding hepatic complications in streptozotocin (STZ)-induced diabetes in rats.Methods: Animals were divided into seven groups; normal control group, STZ control group (50 mg/kg, i.p., single dose), lovastatin group, metformin group, gliclazide group, lovastatin plus metformin group and lovastatin plus gliclazide group.	Metformin	468-477	3-hydroxy-3-methylglutaryl-CoA reductase	Rattus norvegicus	85-142
31689532-5	2020	Our results showed that metformin reduces bacillary loads in macrophages and lung epithelial cells which correlates with higher production of beta-defensin-2, -3 and -4.	Metformin	24-33	defensin beta 4B	Homo sapiens	142-168
31874168-6	2020	We further indicated that treatment with the FDA-approved drug metformin normalized the hyperactive Akt-mTOR signaling, and attenuated pain-related hypersensitivity in Cntnap2-/- mice.	Metformin	63-72	contactin associated protein-like 2	Mus musculus	168-175
31974165-4	2020	The G6P lowering by metformin was mimicked by a complex 1 inhibitor (rotenone) and an uncoupler (dinitrophenol) and by overexpression of mGPDH, which lowers glycerol 3-phosphate and G6P and also mimics the G6pc repression by metformin.	Metformin	20-29	glycerol phosphate dehydrogenase 2, mitochondrial	Mus musculus	137-142
31974165-4	2020	The G6P lowering by metformin was mimicked by a complex 1 inhibitor (rotenone) and an uncoupler (dinitrophenol) and by overexpression of mGPDH, which lowers glycerol 3-phosphate and G6P and also mimics the G6pc repression by metformin.	Metformin	225-234	glycerol phosphate dehydrogenase 2, mitochondrial	Mus musculus	137-142
31225649-4	2020	Metformin treatment increased the formation of acidic vesicles and mitophagosomes, upregulated mitophagy markers, and enhanced mitophagic flux, as indicated by increased LC3-II expression and reduced p62 protein levels.	Metformin	0-9	nucleoporin 62	Homo sapiens	200-203
32355824-9	2020	All of the 10 hub genes (CCNA2, CCNB1, MAD2L1, BU1B, RACGAP1, CHEK1, BUB1, ASPM, NCAPG and TTK) have a strong association with lower overall survival in liver cancer patients and four genes (CCNA2, CCNB1, CHEK1 and BUB1) have reduced expression in metformin-treated samples.	Metformin	248-257	BUB1 mitotic checkpoint serine/threonine kinase	Homo sapiens	215-219
31801667-0	2020	KLF4/Ch25h axis activated by metformin suppresses EndoMT in human umbilical vein endothelial cells.	Metformin	29-38	Kruppel like factor 4	Homo sapiens	0-4
31801667-0	2020	KLF4/Ch25h axis activated by metformin suppresses EndoMT in human umbilical vein endothelial cells.	Metformin	29-38	cholesterol 25-hydroxylase	Homo sapiens	5-10
31801667-4	2020	In this study, we found that metformin increased the expression of kruppel-like factor 4 (KLF4) and cholesterol-25-hydroxylase (Ch25h) while HG decreased the expression of KLF4 and Ch25h.	Metformin	29-38	Kruppel like factor 4	Homo sapiens	67-88
31801667-4	2020	In this study, we found that metformin increased the expression of kruppel-like factor 4 (KLF4) and cholesterol-25-hydroxylase (Ch25h) while HG decreased the expression of KLF4 and Ch25h.	Metformin	29-38	Kruppel like factor 4	Homo sapiens	90-94
31801667-4	2020	In this study, we found that metformin increased the expression of kruppel-like factor 4 (KLF4) and cholesterol-25-hydroxylase (Ch25h) while HG decreased the expression of KLF4 and Ch25h.	Metformin	29-38	cholesterol 25-hydroxylase	Homo sapiens	100-126
31801667-4	2020	In this study, we found that metformin increased the expression of kruppel-like factor 4 (KLF4) and cholesterol-25-hydroxylase (Ch25h) while HG decreased the expression of KLF4 and Ch25h.	Metformin	29-38	cholesterol 25-hydroxylase	Homo sapiens	128-133
31801667-7	2020	Moreover, we proved that metformin increased Ch25h expression through not only KLF4 but also epigenetic modification including DNA methylation and active histone modification.	Metformin	25-34	cholesterol 25-hydroxylase	Homo sapiens	45-50
31801667-7	2020	Moreover, we proved that metformin increased Ch25h expression through not only KLF4 but also epigenetic modification including DNA methylation and active histone modification.	Metformin	25-34	Kruppel like factor 4	Homo sapiens	79-83
31801667-9	2020	Altogether, our study demonstrated that KLF4/Ch25h/axis activated by metformin suppressed EndoMT.	Metformin	69-78	Kruppel like factor 4	Homo sapiens	40-44
31801667-9	2020	Altogether, our study demonstrated that KLF4/Ch25h/axis activated by metformin suppressed EndoMT.	Metformin	69-78	cholesterol 25-hydroxylase	Homo sapiens	45-50
32041944-0	2020	Metformin reduces HGF-induced resistance to alectinib via the inhibition of Gab1.	Metformin	0-9	GRB2 associated binding protein 1	Homo sapiens	76-80
32041944-7	2020	The antidiabetic drug metformin combined with alectinib overcame alectinib resistance triggered by HGF/MET through disrupting the complex between MET and Gab1, thereby inhibiting Gab1 phosphorylation and the activation of downstream signal transduction pathways.	Metformin	22-31	GRB2 associated binding protein 1	Homo sapiens	154-158
32041944-7	2020	The antidiabetic drug metformin combined with alectinib overcame alectinib resistance triggered by HGF/MET through disrupting the complex between MET and Gab1, thereby inhibiting Gab1 phosphorylation and the activation of downstream signal transduction pathways.	Metformin	22-31	GRB2 associated binding protein 1	Homo sapiens	179-183
31944526-11	2020	Notably, metformin treatment disrupted p62-RIP1-RIP3 complexes and effectively repressed I/R-induced necroptosis in aged hearts, ultimately reducing mortality in this model.	Metformin	9-18	nucleoporin 62	Mus musculus	39-42
31944526-11	2020	Notably, metformin treatment disrupted p62-RIP1-RIP3 complexes and effectively repressed I/R-induced necroptosis in aged hearts, ultimately reducing mortality in this model.	Metformin	9-18	receptor-interacting serine-threonine kinase 3	Mus musculus	48-52
31989218-8	2020	In contrast, in the celastrol and celastrol + metformin groups, the apoptotic potential was amplified, as revealed by the increase in the caspase-9 and caspase-3 levels and Bax:BCL-2 ratio.	Metformin	46-55	caspase 3	Mus musculus	152-161
31989218-8	2020	In contrast, in the celastrol and celastrol + metformin groups, the apoptotic potential was amplified, as revealed by the increase in the caspase-9 and caspase-3 levels and Bax:BCL-2 ratio.	Metformin	46-55	BCL2-associated X protein	Mus musculus	173-176
31989218-9	2020	In addition to their repressive effect on the gene expression of NFkappaBp65, TNFR and TLR4, metformin and celastrol inhibited phosphorylation-induced activation of IkappaBkappaB and NFkappaBp65 and decreased IkappaBalpha degradation.	Metformin	93-102	tumor necrosis factor receptor superfamily, member 1a	Mus musculus	78-82
31989218-10	2020	Combination therapy with metformin and celastrol repressed markers of angiogenesis, metastasis and tumour proliferation, as revealed by the decreased hepatic levels of VEGF, MMP-2/9 and cyclin D1 mRNA, respectively.	Metformin	25-34	vascular endothelial growth factor A	Mus musculus	168-172
31989218-10	2020	Combination therapy with metformin and celastrol repressed markers of angiogenesis, metastasis and tumour proliferation, as revealed by the decreased hepatic levels of VEGF, MMP-2/9 and cyclin D1 mRNA, respectively.	Metformin	25-34	matrix metallopeptidase 2	Mus musculus	174-181
31989218-10	2020	Combination therapy with metformin and celastrol repressed markers of angiogenesis, metastasis and tumour proliferation, as revealed by the decreased hepatic levels of VEGF, MMP-2/9 and cyclin D1 mRNA, respectively.	Metformin	25-34	cyclin D1	Mus musculus	186-195
32405365-3	2020	We aimed to investigate the combination therapeutic effect of these cells with insulin and metformin on neuropeptide Y, melanocortin-4 receptor, and leptin receptor genes expression in TID.	Metformin	91-100	melanocortin 4 receptor	Rattus norvegicus	120-143
31875646-4	2020	Here we show-in two independent randomized controlled clinical trials-that metformin increases circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15), which has been shown to reduce food intake and lower body weight through a brain-stem-restricted receptor.	Metformin	75-84	growth differentiation factor 15	Homo sapiens	171-176
32051582-0	2020	Publisher Correction: GDF15 mediates the effects of metformin on body weight and energy balance.	Metformin	52-61	growth differentiation factor 15	Homo sapiens	22-27
31915055-0	2020	Metformin alleviates muscle wasting post-thermal injury by increasing Pax7-positive muscle progenitor cells.	Metformin	0-9	paired box 7	Homo sapiens	70-74
31915055-10	2020	Burned animals treated with metformin had a significant increase in Pax7 protein level and the number of Pax7-positive cells at 7 days post-burn, p < 0.05.	Metformin	28-37	paired box 7	Homo sapiens	68-72
31915055-10	2020	Burned animals treated with metformin had a significant increase in Pax7 protein level and the number of Pax7-positive cells at 7 days post-burn, p < 0.05.	Metformin	28-37	paired box 7	Homo sapiens	105-109
31907698-0	2020	Metformin Disrupts Bile Acid Efflux by Repressing Bile Salt Export Pump Expression.	Metformin	0-9	ATP binding cassette subfamily B member 11	Homo sapiens	50-71
31907698-6	2020	RESULTS: Metformin concentration-dependently repressed BSEP expression in HPH.	Metformin	9-18	ATP binding cassette subfamily B member 11	Homo sapiens	55-59
31907698-7	2020	Although metformin did not directly inhibit BSEP activity, longer metformin exposure reduced BSEP transport function in HPH by down-regulating BSEP expression.	Metformin	66-75	ATP binding cassette subfamily B member 11	Homo sapiens	93-97
31907698-7	2020	Although metformin did not directly inhibit BSEP activity, longer metformin exposure reduced BSEP transport function in HPH by down-regulating BSEP expression.	Metformin	66-75	ATP binding cassette subfamily B member 11	Homo sapiens	93-97
31907698-8	2020	BSEP repression by metformin was found to be AMP-activated protein kinase-independent.	Metformin	19-28	ATP binding cassette subfamily B member 11	Homo sapiens	0-4
31907698-11	2020	Metformin and tamoxifen appear to be prototypes of a class of BSEP repressors that may cause drug-induced cholestasis through gene repression instead of direct BSEP inhibition.	Metformin	0-9	ATP binding cassette subfamily B member 11	Homo sapiens	62-66
31907698-11	2020	Metformin and tamoxifen appear to be prototypes of a class of BSEP repressors that may cause drug-induced cholestasis through gene repression instead of direct BSEP inhibition.	Metformin	0-9	ATP binding cassette subfamily B member 11	Homo sapiens	160-164
31950065-5	2019	GPR40 was involved in metformin reversing metabolic inflammation key marker TLR4 activation-mediated beta-cell injury.	Metformin	22-31	free fatty acid receptor 1	Rattus norvegicus	0-5
31950065-6	2019	Furthermore, downstream signaling protein PLC-IP3 of GPR40 was involved in the protective effect of metformin on meta-inflammation, and the above process of metformin was partially regulated by AMPK activity.	Metformin	100-109	free fatty acid receptor 1	Rattus norvegicus	53-58
31950065-6	2019	Furthermore, downstream signaling protein PLC-IP3 of GPR40 was involved in the protective effect of metformin on meta-inflammation, and the above process of metformin was partially regulated by AMPK activity.	Metformin	157-166	free fatty acid receptor 1	Rattus norvegicus	53-58
31950065-8	2019	Conclusion: Metformin can reduce lipotoxicity-induced meta-inflammation in beta-cells through the regulation of the GPR40-PLC-IP3 pathway and partially via the regulation of AMPK activity.	Metformin	12-21	free fatty acid receptor 1	Rattus norvegicus	116-121
31818258-0	2019	Systemic RAGE ligands are upregulated in tuberculosis individuals with diabetes co-morbidity and modulated by anti-tuberculosis treatment and metformin therapy.	Metformin	142-151	advanced glycosylation end-product specific receptor	Homo sapiens	9-13
31818258-9	2019	CONCLUSIONS: Our data demonstrate that RAGE ligand levels reflect disease severity and extent in TB-DM, distinguish KDM from NDM and are modulated by metformin therapy.	Metformin	150-159	advanced glycosylation end-product specific receptor	Homo sapiens	39-43
31801093-7	2019	Beyond AMPK, metformin activates protein kinase D and MAPKAPK2 in an LKB1-independent manner, revealing additional kinases that may mediate aspects of metformin response.	Metformin	13-22	protein kinase D1	Mus musculus	33-49
31870092-7	2019	The suppression of migration mediated through the regulatory proteins such as focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (Akt), Rac1 and RhoA after metformin treatment.	Metformin	164-173	Rac family small GTPase 1	Homo sapiens	144-148
31870092-8	2019	CONCLUSION: Metformin displays antimigration effects in cervical cancer cells by inhibiting filopodia and lamellipodia formation through the suppression of FAK, Akt and its downstream Rac1 and RhoA protein.	Metformin	12-21	Rac family small GTPase 1	Homo sapiens	184-188
31678476-9	2019	Furthermore, the metformin + osteogenic group had 3-fold to 4-fold increases over those of the osteogenic group in osteogenic gene expressions, ALP activity and mineral synthesis.	Metformin	17-26	ATHS	Homo sapiens	144-147
31427432-3	2019	Following a 30 minute preincubation with an inhibitor, approximately 50-fold higher inhibition potency was observed for Cyclosporine (CsA) against OCT1-mediated uptake of metformin as compared to coincubation, with IC50 values of 0.43 +- 0.12 and 21.6 +- 4.5 muM, respectively.	Metformin	171-180	chorionic somatomammotropin hormone 1	Homo sapiens	134-137
31427432-8	2019	A short (30 min) exposure to 10 muM CsA produced long-lasting (at least 120 min) inhibition of the OCT1-mediated uptake of metformin in OCT1-HEK293 cells, which was likely attributable to the retention of CsA in the cells, as shown by the fact that inhibitory cellular concentrations of CsA are maintained long after the removal of the compound from incubation buffer.	Metformin	123-132	chorionic somatomammotropin hormone 1	Homo sapiens	36-39
31427432-8	2019	A short (30 min) exposure to 10 muM CsA produced long-lasting (at least 120 min) inhibition of the OCT1-mediated uptake of metformin in OCT1-HEK293 cells, which was likely attributable to the retention of CsA in the cells, as shown by the fact that inhibitory cellular concentrations of CsA are maintained long after the removal of the compound from incubation buffer.	Metformin	123-132	chorionic somatomammotropin hormone 1	Homo sapiens	205-208
31427432-8	2019	A short (30 min) exposure to 10 muM CsA produced long-lasting (at least 120 min) inhibition of the OCT1-mediated uptake of metformin in OCT1-HEK293 cells, which was likely attributable to the retention of CsA in the cells, as shown by the fact that inhibitory cellular concentrations of CsA are maintained long after the removal of the compound from incubation buffer.	Metformin	123-132	chorionic somatomammotropin hormone 1	Homo sapiens	205-208
31427432-12	2019	For the first time, we observed a 50-fold increase in CsA inhibitory potency against OCT1-mediated transport of metformin following a preincubation step.	Metformin	112-121	chorionic somatomammotropin hormone 1	Homo sapiens	54-57
31687710-7	2019	Moreover, treatment with honey or combination of honey and metformin significantly enhanced glucokinase (GK) activity (p < 0.05), and meanwhile suppressed the activities of glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), pyruvate carboxylase (PC) and pyruvate dehydrogenase kinases (PDK) (p < 0.05) in diabetic mice.	Metformin	59-68	phosphoenolpyruvate carboxykinase 1, cytosolic	Mus musculus	205-238
31687710-7	2019	Moreover, treatment with honey or combination of honey and metformin significantly enhanced glucokinase (GK) activity (p < 0.05), and meanwhile suppressed the activities of glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), pyruvate carboxylase (PC) and pyruvate dehydrogenase kinases (PDK) (p < 0.05) in diabetic mice.	Metformin	59-68	phosphoenolpyruvate carboxykinase 1, cytosolic	Mus musculus	240-245
30989649-0	2019	Metformin treatment alleviates polycystic ovary syndrome by decreasing the expression of MMP-2 and MMP-9 via H19/miR-29b-3p and AKT/mTOR/autophagy signaling pathways.	Metformin	0-9	matrix metallopeptidase 9	Rattus norvegicus	99-104
30989649-0	2019	Metformin treatment alleviates polycystic ovary syndrome by decreasing the expression of MMP-2 and MMP-9 via H19/miR-29b-3p and AKT/mTOR/autophagy signaling pathways.	Metformin	0-9	H19, imprinted maternally expressed transcript (non-protein coding)	Rattus norvegicus	109-112
30989649-0	2019	Metformin treatment alleviates polycystic ovary syndrome by decreasing the expression of MMP-2 and MMP-9 via H19/miR-29b-3p and AKT/mTOR/autophagy signaling pathways.	Metformin	0-9	microRNA mir-29b-3	Rattus norvegicus	113-123
30989649-0	2019	Metformin treatment alleviates polycystic ovary syndrome by decreasing the expression of MMP-2 and MMP-9 via H19/miR-29b-3p and AKT/mTOR/autophagy signaling pathways.	Metformin	0-9	mechanistic target of rapamycin kinase	Rattus norvegicus	132-136
30989649-1	2019	In this study, we aimed to investigate the molecular pathway(s) underlying the effect of metformin (MET) on the expression of matrix metalloproteinase (MMP)-2 and MMP-9.	Metformin	89-98	matrix metallopeptidase 9	Rattus norvegicus	163-168
31640742-0	2019	Metformin overcomes resistance to cisplatin in triple-negative breast cancer (TNBC) cells by targeting RAD51.	Metformin	0-9	RAD51 recombinase	Homo sapiens	103-108
31640742-8	2019	Metformin suppressed cisplatin-mediated RAD51 upregulation by decreasing RAD51 protein stability and increasing its ubiquitination.	Metformin	0-9	RAD51 recombinase	Homo sapiens	40-45
31640742-8	2019	Metformin suppressed cisplatin-mediated RAD51 upregulation by decreasing RAD51 protein stability and increasing its ubiquitination.	Metformin	0-9	RAD51 recombinase	Homo sapiens	73-78
31640742-11	2019	Overexpression of RAD51 blocked the metformin-induced inhibition of cell migration and invasion, while RAD51 knockdown enhanced cisplatin activity.	Metformin	36-45	RAD51 recombinase	Homo sapiens	18-23
31640742-13	2019	CONCLUSIONS: Metformin enhances anticancer effect of cisplatin by downregulating RAD51 expression, which represents a novel therapeutic target in TNBC management.	Metformin	13-22	RAD51 recombinase	Homo sapiens	81-86
31595194-8	2019	Metformin inhibited oxidative phosphorylation and elevated glycolysis by inhibiting mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) in vitro at therapeutic doses.	Metformin	0-9	glycerol phosphate dehydrogenase 2, mitochondrial	Mus musculus	134-139
31405334-0	2019	Metformin and sitagliptin combination therapy ameliorates polycystic ovary syndrome with insulin resistance through upregulation of lncRNA H19.	Metformin	0-9	H19, imprinted maternally expressed transcript (non-protein coding)	Rattus norvegicus	139-142
31405334-8	2019	Furthermore, co-treatment with TECOS and DMBG induced H19 expression via suppressing the PI3K/AKT-DNMT1 pathway.	Metformin	41-45	H19, imprinted maternally expressed transcript (non-protein coding)	Rattus norvegicus	54-57
31405334-9	2019	Collectively, these findings demonstrate that combination treatment with TECOS and DMBG ameliorates PCOS with IR, at least partially, through upregulation of lncRNA H19.	Metformin	83-87	H19, imprinted maternally expressed transcript (non-protein coding)	Rattus norvegicus	165-168
31012983-1	2019	The organic cation transporters OCT1 and OCT2 and the multidrug and toxin extrusion transporter MATE1, encoded by the SLC22A1, SLC22A2, and SLC47A1 genes, respectively, are responsible for the absorption of metformin in enterocytes, hepatocytes, and kidney cells.	Metformin	207-216	solute carrier family 47 member 1	Homo sapiens	96-101
31012983-1	2019	The organic cation transporters OCT1 and OCT2 and the multidrug and toxin extrusion transporter MATE1, encoded by the SLC22A1, SLC22A2, and SLC47A1 genes, respectively, are responsible for the absorption of metformin in enterocytes, hepatocytes, and kidney cells.	Metformin	207-216	solute carrier family 47 member 1	Homo sapiens	140-147
31012983-2	2019	The aim of this study was to evaluate whether genetic variations in the SLC22A1, SLC22A2, and SLC47A1 genes could be associated with an altered response to metformin in patients with type 2 diabetes mellitus.	Metformin	156-165	solute carrier family 47 member 1	Homo sapiens	94-101
31439934-3	2019	In addition, the discovery that metformin inhibits the mitochondrial respiratory chain complex 1 has placed energy metabolism and activation of AMP-activated protein kinase (AMPK) at the centre of its proposed mechanism of action.	Metformin	32-41	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	144-172
31439934-3	2019	In addition, the discovery that metformin inhibits the mitochondrial respiratory chain complex 1 has placed energy metabolism and activation of AMP-activated protein kinase (AMPK) at the centre of its proposed mechanism of action.	Metformin	32-41	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	174-178
31541100-7	2019	The anti-diabetic drug metformin and ginsenoside Rb1 lower blood glucose at least in part by inhibiting p52 activation.	Metformin	23-32	nuclear factor of kappa light polypeptide gene enhancer in B cells 2, p49/p100	Mus musculus	104-107
31527397-8	2019	Although no association remained statistically significant after multiple-test correction, our findings support previously reported variants in metformin transporters or targets as well as identify novel and promising loci, such as the ADYC3 and the BDNF genes, with plausible biological relation to the metformin"s action mechanism.	Metformin	144-153	brain derived neurotrophic factor	Homo sapiens	250-254
31645842-0	2019	Metformin restores the mitochondrial membrane potentials in association with a reduction in TIMM23 and NDUFS3 in MPP+-induced neurotoxicity in SH-SY5Y cells.	Metformin	0-9	translocase of inner mitochondrial membrane 23	Homo sapiens	92-98
31645842-7	2019	Pretreatment with metformin decreased the expression of TIMM23 and NDUFS3 in MPP+-treated SH-SY5Y cells.	Metformin	18-27	translocase of inner mitochondrial membrane 23	Homo sapiens	56-62
31125865-4	2019	As for now, natural agents and antidiabetic drug - metformin, have been found to activate sirtuin 1.	Metformin	51-60	sirtuin 1	Homo sapiens	90-99
31581911-4	2019	Metformin increased p27 and LC3II expression and AMP-activated protein kinase (AMPK) phosphorylation, and decreased p62 expression, while miR-221 overexpression reversed the effects of metformin.	Metformin	0-9	nucleoporin 62	Homo sapiens	116-119
31339921-4	2019	The previously reported lipid metabolism-related axis, Acyl-CoA synthetases/ Stearoyl-CoA desaturase (ACSLs/SCD), stimulates colon cancer progression and metformin is able to rescue the invasive and migratory phenotype conferred to cancer cells upon this axis overexpression.	Metformin	154-163	stearoyl-CoA desaturase	Homo sapiens	77-100
31339921-4	2019	The previously reported lipid metabolism-related axis, Acyl-CoA synthetases/ Stearoyl-CoA desaturase (ACSLs/SCD), stimulates colon cancer progression and metformin is able to rescue the invasive and migratory phenotype conferred to cancer cells upon this axis overexpression.	Metformin	154-163	stearoyl-CoA desaturase	Homo sapiens	102-111
31028998-0	2019	Metformin inhibits the proliferation of rheumatoid arthritis fibroblast-like synoviocytes through IGF-IR/PI3K/AKT/m-TOR pathway.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	98-104
31028998-6	2019	More importantly, metformin induced G2/M cell cycle phase arrest in RA-FLS via the IGF-IR/PI3K/AKT/ m-TOR pathway and inhibited m-TOR phosphorylation through both the IGF-IR/PI3K/AKT signaling pathways thereby further upregulating and down-regulating p70s6k and 4E-BP1 phosphorylation, respectively; however, metformin was found not to induce apoptosis in RA-FLSs.	Metformin	18-27	insulin like growth factor 1 receptor	Homo sapiens	83-89
31028998-6	2019	More importantly, metformin induced G2/M cell cycle phase arrest in RA-FLS via the IGF-IR/PI3K/AKT/ m-TOR pathway and inhibited m-TOR phosphorylation through both the IGF-IR/PI3K/AKT signaling pathways thereby further upregulating and down-regulating p70s6k and 4E-BP1 phosphorylation, respectively; however, metformin was found not to induce apoptosis in RA-FLSs.	Metformin	18-27	insulin like growth factor 1 receptor	Homo sapiens	167-173
31028998-8	2019	Moreover, IGF-IR/PI3K/AKT m-TOR signaling pathway can be regulated by metformin.	Metformin	70-79	insulin like growth factor 1 receptor	Homo sapiens	10-16
30760033-3	2019	Results: We showed that metformin can improve the depression-like behavior in spatial restraint stress model; then we found that metformin through AMPK/Tet2 pathway increasing the expression of BDNF to antidepression.	Metformin	24-33	brain derived neurotrophic factor	Homo sapiens	194-198
30760033-3	2019	Results: We showed that metformin can improve the depression-like behavior in spatial restraint stress model; then we found that metformin through AMPK/Tet2 pathway increasing the expression of BDNF to antidepression.	Metformin	129-138	brain derived neurotrophic factor	Homo sapiens	194-198
30760033-4	2019	Conclusion: Our study provided evidences that metformin plays a role of antidepressant effects through the AMPK/Tet2/BDNF pathway.	Metformin	46-55	brain derived neurotrophic factor	Homo sapiens	117-121
30032440-4	2019	Metformin (50 muM) significantly decreased SOST and DKK1 mRNA expression, stimulating alkaline phosphatase activity and proliferation of osteoblast, and increased OPG secretion and the ratio of OPG/RANKL, inhibiting osteoclastogenesis.	Metformin	0-9	tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)	Mus musculus	163-166
30032440-4	2019	Metformin (50 muM) significantly decreased SOST and DKK1 mRNA expression, stimulating alkaline phosphatase activity and proliferation of osteoblast, and increased OPG secretion and the ratio of OPG/RANKL, inhibiting osteoclastogenesis.	Metformin	0-9	tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)	Mus musculus	194-197
30032440-5	2019	Moreover, the effect on OPG was reversed by adenosine 5"-monophosphate-activated protein kinase inhibitor, Compound C. Our finding suggests that metformin induces differentiation and mineralization of osteoblasts, while inhibits osteoclastogenesis via mature osteocytes secretion.	Metformin	145-154	tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)	Mus musculus	24-27
30998979-8	2019	The anti-remodeling effects of metformin were also associated with a decrease in the transcription factor Yy1 intranuclear level and lower levels of phosphorylated HDAC4 within the cytoplasmic space.	Metformin	31-40	YY1 transcription factor	Rattus norvegicus	106-109
30998979-12	2019	CONCLUSION: The transcription factor Yy1 regulates sST2 expression, and repression of Yy1 by metformin results in lower levels of sST2 that are associated with favorable myocardial remodeling.	Metformin	93-102	YY1 transcription factor	Rattus norvegicus	86-89
30742852-11	2019	Also Metformin could activate CREB (both forms), BDNF and Akt (both forms) proteins" expression and inhibited GSK3 (both forms) protein expression in methamphetamine treated rats.	Metformin	5-14	brain-derived neurotrophic factor	Rattus norvegicus	49-53
30742852-12	2019	SIGNIFICANCE: According to obtained data, metformin could protect the brain against methamphetamine-induced neurodegeneration probably by mediation of CREB/BDNF or Akt/GSK3 signaling pathways.	Metformin	42-51	brain-derived neurotrophic factor	Rattus norvegicus	156-160
30742852-13	2019	These data suggested that CREB/BDNF or Akt/GSK3 signaling pathways may have a critical role in methamphetamine induced neurotoxicity and/or neuroprotective effects of metformin.	Metformin	167-176	brain-derived neurotrophic factor	Rattus norvegicus	31-35
31061679-7	2019	Results: Treatment of diabetic rats with curcumin or metformin alone decreased the plasma levels of glucose, triacylglycerol, cholesterol, TBARS, and fluorescent AGEs, as well as increased the activity of PON 1.	Metformin	53-62	paraoxonase 1	Rattus norvegicus	205-210
31061679-8	2019	The combination of metformin with curcumin further decreased dyslipidemia and TBARS levels in diabetic rats, indicating synergy, and maintained the high levels of PON 1.	Metformin	19-28	paraoxonase 1	Rattus norvegicus	163-168
31061679-9	2019	Conclusion: These findings indicated that curcumin combined with metformin may act synergistically on dyslipidemia and oxidative stress, as well as increased PON 1 levels.	Metformin	65-74	paraoxonase 1	Rattus norvegicus	158-163
31249600-7	2019	We report that satellite cells, when treated with metformin in vitro, ex vivo, or in vivo, delay activation, Pax7 downregulation, and terminal myogenic differentiation.	Metformin	50-59	paired box 7	Homo sapiens	109-113
31014052-7	2019	Moreover, treatment with metformin increased the protein expression of LC3II/I ratio, and decreased the expression of p62, while treatment with aspirin decreased the expression of LC3II/I ratio and increased the expression of p62.	Metformin	25-34	nucleoporin 62	Homo sapiens	118-121
30992489-6	2019	[18F]-FDG/PET revealed a slower intestinal transit of labeled glucose after metformin as compared to vehicle administration.	Metformin	76-85	thyroid stimulating hormone receptor	Mus musculus	10-13
30710424-0	2019	Metformin and tenovin-6 synergistically induces apoptosis through LKB1-independent SIRT1 down-regulation in non-small cell lung cancer cells.	Metformin	0-9	sirtuin 1	Homo sapiens	83-88
30710424-2	2019	This study was designed to scrutinize clinicopathological significance of SIRT1 in NSCLC and investigate effects of metformin on SIRT1 inhibition.	Metformin	116-125	sirtuin 1	Homo sapiens	129-134
30710424-8	2019	In addition, metformin and tenovin-6 synergistically suppressed SIRT1 expression in NSCLC cells regardless of LKB1 status.	Metformin	13-22	sirtuin 1	Homo sapiens	64-69
30710424-9	2019	The marked reduction in SIRT1 expression by combination of metformin and tenovin-6 increased acetylation of p53 at lysine 382 and enhanced p53 stability in LKB1-deficient A549 cells.	Metformin	59-68	sirtuin 1	Homo sapiens	24-29
30710424-12	2019	The study concluded that metformin with tenovin-6 may enhance antitumour effects through LKB1-independent SIRT1 down-regulation in NSCLC cells.	Metformin	25-34	sirtuin 1	Homo sapiens	106-111
30508092-0	2019	Metformin induces CD11b+-cell-mediated growth inhibition of an osteosarcoma: implications for metabolic reprogramming of myeloid cells and anti-tumor effects.	Metformin	0-9	integrin subunit alpha M	Homo sapiens	18-23
30508092-3	2019	We found that metformin (Met) induces CD11b+-cell-mediated growth inhibition of a K7M2neo osteosarcoma independent of T cells, as growth inhibition of K7M2neo was still observed in wild-type (WT) mice depleted of T cells by antibodies and in SCID; this contrasted with the effect of Met on Meth A fibrosarcoma, which was entirely T-cell-dependent.	Metformin	14-23	integrin subunit alpha M	Homo sapiens	38-43
30944551-0	2019	Role of IRF4 in the Protection of Metformin-Mediated Sepsis Myocarditis.	Metformin	34-43	interferon regulatory factor 4	Rattus norvegicus	8-12
30944551-5	2019	So we sought to determine whether metformin promotes PKCepsilon/IRF4 activation by FRET.	Metformin	34-43	interferon regulatory factor 4	Rattus norvegicus	64-68
30944551-11	2019	Conclusion: We demonstrate that metformin promotes rapid association of PKCepsilon with IRF4 at mitochondrial microdomain of cardiac myocytes and PKCepsilon via direct molecular interaction with IRF4.	Metformin	32-41	interferon regulatory factor 4	Rattus norvegicus	88-92
30944551-11	2019	Conclusion: We demonstrate that metformin promotes rapid association of PKCepsilon with IRF4 at mitochondrial microdomain of cardiac myocytes and PKCepsilon via direct molecular interaction with IRF4.	Metformin	32-41	interferon regulatory factor 4	Rattus norvegicus	195-199
30918838-10	2019	Recently, drugs belonging to the biguanide class (including metformin) were reported to selectively inhibit CLIC1 activity in CSCs, impairing their viability and invasiveness, but sparing normal stem cells, thus representing potential novel antitumor drugs with a safe toxicological profile.	Metformin	60-69	chloride intracellular channel 1	Homo sapiens	108-113
30866414-0	2019	Integrin beta1-Mediated Cell-Cell Adhesion Augments Metformin-Induced Anoikis.	Metformin	52-61	integrin subunit beta 1	Homo sapiens	0-14
30866414-5	2019	Furthermore, western blot and QPCR analyses revealed that metformin dramatically upregulated integrin beta1 expression.	Metformin	58-67	integrin subunit beta 1	Homo sapiens	93-107
30866414-6	2019	Silencing of integrin beta1 significantly disrupted cell aggregation and reduced anoikis induced by metformin.	Metformin	100-109	integrin subunit beta 1	Homo sapiens	13-27
30866414-7	2019	Moreover, we showed that p53 family member DeltaNp63alpha transcriptionally suppressed integrin beta1 expression and is responsible for metformin-mediated upregulation of integrin beta1.	Metformin	136-145	integrin subunit beta 1	Homo sapiens	171-185
30866414-8	2019	In summary, this study reveals a novel mechanism for metformin anticancer activity and demonstrates that cell-cell adhesion mediated by integrin beta1 plays a critical role in metformin-induced anoikis.	Metformin	53-62	integrin subunit beta 1	Homo sapiens	136-150
30866414-8	2019	In summary, this study reveals a novel mechanism for metformin anticancer activity and demonstrates that cell-cell adhesion mediated by integrin beta1 plays a critical role in metformin-induced anoikis.	Metformin	176-185	integrin subunit beta 1	Homo sapiens	136-150
30841429-7	2019	Metformin led to a more massive BAT in both groups CM and FM, associated with a higher adipocyte proliferation (beta1-adrenergic receptor, proliferating cell nuclear antigen, and vascular endothelial growth factor), and differentiation (PR domain containing 16, bone morphogenetic protein 7), in part by activating 5" adenosine monophosphate-activated protein kinase.	Metformin	0-9	adrenergic receptor, beta 1	Mus musculus	112-137
30841429-7	2019	Metformin led to a more massive BAT in both groups CM and FM, associated with a higher adipocyte proliferation (beta1-adrenergic receptor, proliferating cell nuclear antigen, and vascular endothelial growth factor), and differentiation (PR domain containing 16, bone morphogenetic protein 7), in part by activating 5" adenosine monophosphate-activated protein kinase.	Metformin	0-9	proliferating cell nuclear antigen	Mus musculus	139-173
30841429-7	2019	Metformin led to a more massive BAT in both groups CM and FM, associated with a higher adipocyte proliferation (beta1-adrenergic receptor, proliferating cell nuclear antigen, and vascular endothelial growth factor), and differentiation (PR domain containing 16, bone morphogenetic protein 7), in part by activating 5" adenosine monophosphate-activated protein kinase.	Metformin	0-9	bone morphogenetic protein 7	Mus musculus	262-290
30599373-13	2019	CONCLUSIONS: Our findings have demonstrated that protein levels of pERK and BAX may be relevant to the role of GLP-1 in antidepressant effects of metformin and exercise, which may provide a novel topic for future clinical research.	Metformin	146-155	eukaryotic translation initiation factor 2 alpha kinase 3	Mus musculus	67-71
30599373-13	2019	CONCLUSIONS: Our findings have demonstrated that protein levels of pERK and BAX may be relevant to the role of GLP-1 in antidepressant effects of metformin and exercise, which may provide a novel topic for future clinical research.	Metformin	146-155	BCL2-associated X protein	Mus musculus	76-79
30628691-10	2019	Furthermore, it was confirmed that metformin suppressed the LPS-induced secretion of TNF-alpha, IL-6, ICAM-1 and VCAM-1.	Metformin	35-44	intercellular adhesion molecule 1	Homo sapiens	102-108
30584213-0	2019	Protective effects of metformin against osteoarthritis through upregulation of SIRT3-mediated PINK1/Parkin-dependent mitophagy in primary chondrocytes.	Metformin	22-31	PTEN induced kinase 1	Homo sapiens	94-99
30584213-9	2019	Overall, our findings provide evidence that metformin suppresses IL-1beta-induced oxidative and osteoarthritis-like inflammatory changes by enhancing the SIRT3/PINK1/Parkin signaling pathway, thereby indicating metformin"s potential in prevention and treatment of osteoarthritic joint disease.	Metformin	44-53	PTEN induced kinase 1	Homo sapiens	160-165
30584213-9	2019	Overall, our findings provide evidence that metformin suppresses IL-1beta-induced oxidative and osteoarthritis-like inflammatory changes by enhancing the SIRT3/PINK1/Parkin signaling pathway, thereby indicating metformin"s potential in prevention and treatment of osteoarthritic joint disease.	Metformin	211-220	PTEN induced kinase 1	Homo sapiens	160-165
30375695-0	2019	Retardation of Trap-Assisted Recombination in Lead Halide Perovskite Solar Cells by a Dimethylbiguanide Anchor Layer.	Metformin	86-103	TRAP	Homo sapiens	15-19
30428337-7	2019	Metformin (&gt;=1 or &gt;=0.3 mM) decreased berberine transport in MDCK-rOCT1, MDCK-rOCT2, and MDCK-rMATE1 cells.	Metformin	0-9	solute carrier family 22 member 1	Rattus norvegicus	72-77
30666163-0	2019	Metformin induces apoptotic cytotoxicity depending on AMPK/PKA/GSK-3beta-mediated c-FLIPL degradation in non-small cell lung cancer.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	54-58
30666163-10	2019	Furthermore, metformin significantly activated Adenosine 5"-monophosphate (AMP)-activated protein kinase (AMPK) and its downstream glycogen synthase kinase 3beta (GSK-3beta), block the expression of AMPK, and GSK-3beta with siRNA partially reversed metformin-induced cytotoxicity and restored the expression of c-FLIPL in lung cancer cells.	Metformin	13-22	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	106-110
30666163-10	2019	Furthermore, metformin significantly activated Adenosine 5"-monophosphate (AMP)-activated protein kinase (AMPK) and its downstream glycogen synthase kinase 3beta (GSK-3beta), block the expression of AMPK, and GSK-3beta with siRNA partially reversed metformin-induced cytotoxicity and restored the expression of c-FLIPL in lung cancer cells.	Metformin	13-22	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	199-203
30666163-10	2019	Furthermore, metformin significantly activated Adenosine 5"-monophosphate (AMP)-activated protein kinase (AMPK) and its downstream glycogen synthase kinase 3beta (GSK-3beta), block the expression of AMPK, and GSK-3beta with siRNA partially reversed metformin-induced cytotoxicity and restored the expression of c-FLIPL in lung cancer cells.	Metformin	249-258	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	106-110
30666163-10	2019	Furthermore, metformin significantly activated Adenosine 5"-monophosphate (AMP)-activated protein kinase (AMPK) and its downstream glycogen synthase kinase 3beta (GSK-3beta), block the expression of AMPK, and GSK-3beta with siRNA partially reversed metformin-induced cytotoxicity and restored the expression of c-FLIPL in lung cancer cells.	Metformin	249-258	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	199-203
30666163-11	2019	Metformin also suppressed the activity of AMPK downstream protein kinase A (PKA), PKA activators, both 8-Br-cAMP and forskolin, greatly increased c-FLIPL expression in NSCLC cells.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	42-46
30666163-12	2019	Conclusion: This study provided evidence that metformin killed NSCLC cells through AMPK/PKA/GSK-3beta axis-mediated c-FLIPL degradation.	Metformin	46-55	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	83-87
30774659-0	2019	Metformin Counteracts HCC Progression and Metastasis Enhancing KLF6/p21 Expression and Downregulating the IGF Axis.	Metformin	0-9	Kruppel like factor 6	Homo sapiens	63-67
30625181-6	2019	Similarly, metformin treatment suppressed expressions of anti-apoptotic genes BCL2 and Bcl-xL, and mesenchymal genes vimentin, N-cadherin, Zeb1 and Zeb2 with simultaneous enhancement of apoptotic caspase 3 and Bax, and epithelial genes E-cadherin and keratin 19 expressions, confirming an inhibitory effect of metformin in tumorigenesis.	Metformin	11-20	cadherin 2	Homo sapiens	127-137
30625181-6	2019	Similarly, metformin treatment suppressed expressions of anti-apoptotic genes BCL2 and Bcl-xL, and mesenchymal genes vimentin, N-cadherin, Zeb1 and Zeb2 with simultaneous enhancement of apoptotic caspase 3 and Bax, and epithelial genes E-cadherin and keratin 19 expressions, confirming an inhibitory effect of metformin in tumorigenesis.	Metformin	11-20	zinc finger E-box binding homeobox 1	Homo sapiens	139-143
30625181-9	2019	Similarly, cholesterol treatment inverted metformin-reduced several gene expressions (e.g., Bcl-xL, BCL2, Zeb1, vimentin, and BMI-1).	Metformin	42-51	zinc finger E-box binding homeobox 1	Homo sapiens	106-110
30621095-7	2019	Treatment with metformin resulted in a dose-dependent induction of the stem cell genes CD44, BMI-1, OCT-4, and NANOG.	Metformin	15-24	CD44 molecule (Indian blood group)	Homo sapiens	87-91
30621095-7	2019	Treatment with metformin resulted in a dose-dependent induction of the stem cell genes CD44, BMI-1, OCT-4, and NANOG.	Metformin	15-24	Nanog homeobox	Homo sapiens	111-116
30569877-2	2019	Metformin has demonstrated its ability to inhibit cell growth and the LY294002 is the major inhibitor of PI3K/AKT/mTOR pathway that has antiangiogenic properties.	Metformin	0-9	mechanistic target of rapamycin kinase	Canis lupus familiaris	114-118
30569877-8	2019	The protein and gene expression of HIF-1 and VEGF decreased after treatment with metformin and LY294002.	Metformin	81-90	vascular endothelial growth factor A	Canis lupus familiaris	45-49
30569877-10	2019	CONCLUSION: Our results demonstrate the effectiveness of metformin and LY294002 in controlling the angiogenesis process in mammary tumors by VEGF and HIF-1, the most important angiogenic markers.	Metformin	57-66	vascular endothelial growth factor A	Canis lupus familiaris	141-145
30551411-11	2019	Metformin suppressed EP-induced MMP-2 and MMP-9 upregulation.	Metformin	0-9	matrix metallopeptidase 9	Homo sapiens	42-47
30551411-14	2019	CONCLUSION: Metformin alleviated EP-induced decidualization of endometrial stromal cells by modulating secretion of multiple cytokines, inhibiting expression of MMP-2 and MMP-9, activating p38-MAPK signaling and reducing PGR expression, providing a deep insight into the molecular basis of metfromin therapy for PCOS patients.	Metformin	12-21	matrix metallopeptidase 9	Homo sapiens	171-176
30551471-10	2019	Inhibition of JAK/STAT pathway and activation of Nrf2/HO-1 pathway seems to be among the mechanisms mediating the effects of curcumin and metformin.	Metformin	138-147	heme oxygenase 1	Rattus norvegicus	54-58
30097812-0	2018	Anti-inflammatory Action of Metformin with Respect to CX3CL1/CX3CR1 Signaling in Human Placental Circulation in Normal-Glucose Versus High-Glucose Environments.	Metformin	28-37	C-X3-C motif chemokine receptor 1	Homo sapiens	61-67
30097812-11	2018	Increased CX3CR1 protein content in the placental lysates was observed in subgroups B and C. The two higher metformin concentrations significantly decreased the levels of NF-kappaBp65 protein content in both groups.	Metformin	108-117	C-X3-C motif chemokine receptor 1	Homo sapiens	10-16
30469399-8	2018	At 100 microM, however, metformin reduced ICAM1 and COX2 expression, as well as reduced PGE2 production and endogenous mitochondrial ROS production while failing to significantly impact cell viability.	Metformin	24-33	intercellular adhesion molecule 1	Homo sapiens	42-47
30459620-7	2018	However, the metformin effect on BDNF levels in HG-incubated HUVECs was blocked by a CREB inhibitor, which indicated that BDNF expression is regulated by metformin through CREB activation.	Metformin	154-163	brain derived neurotrophic factor	Homo sapiens	122-126
30459620-7	2018	However, the metformin effect on BDNF levels in HG-incubated HUVECs was blocked by a CREB inhibitor, which indicated that BDNF expression is regulated by metformin through CREB activation.	Metformin	154-163	cAMP responsive element binding protein 1	Homo sapiens	172-176
30459620-8	2018	In addition, we found that adenosine monophosphate-activated protein kinase (AMPK) activation is involved in CREB/BDNF regulation in HG-incubated HUVECs treated with metformin and that an AMPK inhibitor impaired the protective effects of metformin on HG-treated HUVECs.	Metformin	166-175	cAMP responsive element binding protein 1	Homo sapiens	109-113
30459620-8	2018	In addition, we found that adenosine monophosphate-activated protein kinase (AMPK) activation is involved in CREB/BDNF regulation in HG-incubated HUVECs treated with metformin and that an AMPK inhibitor impaired the protective effects of metformin on HG-treated HUVECs.	Metformin	166-175	brain derived neurotrophic factor	Homo sapiens	114-118
30459620-8	2018	In addition, we found that adenosine monophosphate-activated protein kinase (AMPK) activation is involved in CREB/BDNF regulation in HG-incubated HUVECs treated with metformin and that an AMPK inhibitor impaired the protective effects of metformin on HG-treated HUVECs.	Metformin	238-247	cAMP responsive element binding protein 1	Homo sapiens	109-113
30459620-8	2018	In addition, we found that adenosine monophosphate-activated protein kinase (AMPK) activation is involved in CREB/BDNF regulation in HG-incubated HUVECs treated with metformin and that an AMPK inhibitor impaired the protective effects of metformin on HG-treated HUVECs.	Metformin	238-247	brain derived neurotrophic factor	Homo sapiens	114-118
30459620-9	2018	In conclusion, this study demonstrated that metformin affects cell proliferation and apoptosis via the AMPK/CREB/BDNF pathway in HG-incubated HUVECs.	Metformin	44-53	cAMP responsive element binding protein 1	Homo sapiens	108-112
30459620-9	2018	In conclusion, this study demonstrated that metformin affects cell proliferation and apoptosis via the AMPK/CREB/BDNF pathway in HG-incubated HUVECs.	Metformin	44-53	brain derived neurotrophic factor	Homo sapiens	113-117
30098371-10	2018	Although the increase in DNA pol beta was not significant, XRCC1 and p53 levels were significantly upregulated with metformin treatment in type 2 diabetes patients.	Metformin	116-125	X-ray repair cross complementing 1	Homo sapiens	59-64
30294927-0	2018	Co-administration of nuciferine reduces the concentration of metformin in liver via differential inhibition of hepatic drug transporter OCT1 and MATE1.	Metformin	61-70	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	136-140
30294927-3	2018	Since nuciferine and metformin are likely to be co-administered, the aim of the present study was to evaluate whether co-administration of nuciferine would influence the liver (target tissue) distribution and the anti-diabetic effect of metformin by inhibiting hepatic organic cation transporter 1 (OCT1) and multidrug and toxin extrusion 1 (MATE1).	Metformin	237-246	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	269-297
30294927-3	2018	Since nuciferine and metformin are likely to be co-administered, the aim of the present study was to evaluate whether co-administration of nuciferine would influence the liver (target tissue) distribution and the anti-diabetic effect of metformin by inhibiting hepatic organic cation transporter 1 (OCT1) and multidrug and toxin extrusion 1 (MATE1).	Metformin	237-246	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	299-303
30294927-5	2018	Furthermore, the presence of nuciferine in the basal compartment caused a concentration-dependent reduction of intracellular metformin accumulation in MDCK-hOCT1/hMATE1 cell monolayers.	Metformin	125-134	solute carrier family 47 member 1	Homo sapiens	162-168
30294927-7	2018	Therefore, nuciferine influenced the liver concentration and glucose-lowering effect of metformin only for a period of time after dose, administration of nuciferine and metformin with an interval might prevent the drug-drug interaction mediated by OCT1 and MATE1.	Metformin	88-97	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	248-252
30294927-7	2018	Therefore, nuciferine influenced the liver concentration and glucose-lowering effect of metformin only for a period of time after dose, administration of nuciferine and metformin with an interval might prevent the drug-drug interaction mediated by OCT1 and MATE1.	Metformin	169-178	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	248-252
30070925-3	2018	This study aims to assess the effectiveness of metformin in the management of obesity among 8- to 16-year-old children in Gampaha District of Sri Lanka.	Metformin	47-56	sorcin	Homo sapiens	142-145
29630425-8	2018	RESULTS: Metformin suppressed LPS-induced IP-10 and MCP-1 production as well as LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38, extracellular signal-regulated kinase (ERK), and nuclear factor-kappa B (NF-kappaB).	Metformin	9-18	C-X-C motif chemokine ligand 10	Homo sapiens	42-47
29630425-9	2018	Moreover, metformin suppressed LPS-induced acetylation of histones H3 and H4 at the IP-10 promoter.	Metformin	10-19	C-X-C motif chemokine ligand 10	Homo sapiens	84-89
29630425-10	2018	CONCLUSIONS: Metformin suppressed the production of Th1-related chemokines IP-10 and MCP-1 in THP-1 cells.	Metformin	13-22	chemokine (C-C motif) ligand 2	Mus musculus	85-90
29630425-11	2018	Suppressive effects of metformin on IP-10 production might be attributed at least partially to the JNK, p38, ERK, and NF-kappaB pathways as well as to epigenetic regulation through the acetylation of histones H3 and H4.	Metformin	23-32	C-X-C motif chemokine ligand 10	Homo sapiens	36-41
30536344-12	2018	Additionally, we also found that AMPK plays an essential role in the inhibition of GSK3beta by metformin.	Metformin	95-104	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	33-37
29380373-10	2018	Folic acid induced nephropathy was associated with the overexpression of inflammatory markers MCP-1, F4/80, type IV collagen, fibronectin and TGF-beta1 compared to control groups, which were partially attenuated by metformin treatment.	Metformin	215-224	adhesion G protein-coupled receptor E1	Mus musculus	101-124
29753686-6	2018	Long-term metformin treatment after MIwas associated with (1) a reduction in myocardial fibrosis and Gal-3 levels; (2) an increase in adenosine monophosphate-activated protein kinase (AMPK) alpha1/alpha2 levels; and (3) an inhibition of both mRNA expression and enzymatic activities of mitoNox and PKCalpha.	Metformin	10-19	protein kinase C, alpha	Rattus norvegicus	298-306
29753686-9	2018	In conclusion, a metformin-induced increase in AMPK improves myocardial remodeling post-MI, which is related to the inhibition of the mitoNox/PKCalpha/Gal-3 pathway.	Metformin	17-26	protein kinase C, alpha	Rattus norvegicus	142-150
30186163-4	2018	Although several cell-specific intracellular mechanisms contribute to the anti-tumor activity of metformin, the inhibition of the chloride intracellular channel 1 activity (CLIC1) at G1/S transition is a key events in metformin antiproliferative effect in glioblastoma stem cells (GSCs).	Metformin	97-106	chloride intracellular channel 1	Homo sapiens	130-162
30186163-4	2018	Although several cell-specific intracellular mechanisms contribute to the anti-tumor activity of metformin, the inhibition of the chloride intracellular channel 1 activity (CLIC1) at G1/S transition is a key events in metformin antiproliferative effect in glioblastoma stem cells (GSCs).	Metformin	97-106	chloride intracellular channel 1	Homo sapiens	173-178
30186163-4	2018	Although several cell-specific intracellular mechanisms contribute to the anti-tumor activity of metformin, the inhibition of the chloride intracellular channel 1 activity (CLIC1) at G1/S transition is a key events in metformin antiproliferative effect in glioblastoma stem cells (GSCs).	Metformin	218-227	chloride intracellular channel 1	Homo sapiens	130-162
30186163-4	2018	Although several cell-specific intracellular mechanisms contribute to the anti-tumor activity of metformin, the inhibition of the chloride intracellular channel 1 activity (CLIC1) at G1/S transition is a key events in metformin antiproliferative effect in glioblastoma stem cells (GSCs).	Metformin	218-227	chloride intracellular channel 1	Homo sapiens	173-178
29865970-5	2018	In addition to apoptosis, we showed that metformin increased autophagic flux in MCF-7 cells, as evidenced by the upregulation of LC3-II and downregulation of P62/SQSTM1.	Metformin	41-50	sequestosome 1	Homo sapiens	158-161
29865970-5	2018	In addition to apoptosis, we showed that metformin increased autophagic flux in MCF-7 cells, as evidenced by the upregulation of LC3-II and downregulation of P62/SQSTM1.	Metformin	41-50	sequestosome 1	Homo sapiens	162-168
29865970-9	2018	Furthermore, N-acetyl-l-cysteine (NAC), a ROS scavenger, abrogated the effects of metformin on TFE3-dependent autophagy.	Metformin	82-91	X-linked Kx blood group	Homo sapiens	34-37
29655834-0	2018	Metformin Use Is Associated With Longer Progression-Free Survival of Patients With Diabetes and Pancreatic Neuroendocrine Tumors Receiving Everolimus and/or Somatostatin Analogues.	Metformin	0-9	somatostatin	Homo sapiens	157-169
29655834-14	2018	Metformin was associated with increased PFS of patients receiving somatostatin analogues and in those receiving everolimus, with or without somatostatin analogues.	Metformin	0-9	somatostatin	Homo sapiens	66-78
29922884-0	2018	Comment on "Targeting AMPK, mTOR and beta-Catenin by Combined Metformin and Aspirin Therapy in HCC: An Appraisal in Egyptian HCC Patients".	Metformin	62-71	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	22-26
29977599-2	2018	Studying the molecular changes associated with the tumor-suppressive action of Metformin we found that the oncogene SOX4, which is upregulated in solid tumors and associated with poor prognosis, was induced by Wnt/beta-catenin signaling and blocked by Metformin.	Metformin	79-88	catenin (cadherin associated protein), beta 1	Mus musculus	214-226
29864938-9	2018	Real-time polymerase chain reaction (PCR) analysis showed that T. polium and metformin significantly increased eNOS expression, while it decreased VCAM-1 expressions in aortic tissue of diabetic rats.	Metformin	77-86	nitric oxide synthase 3	Rattus norvegicus	111-115
29457866-6	2018	Metformin has also been reported to decrease expression of multiple histone methyltransferases, to increase the activity of the class III HDAC SIRT1 and to decrease the influence of DNMT inhibitors.	Metformin	0-9	sirtuin 1	Homo sapiens	143-148
29457866-6	2018	Metformin has also been reported to decrease expression of multiple histone methyltransferases, to increase the activity of the class III HDAC SIRT1 and to decrease the influence of DNMT inhibitors.	Metformin	0-9	DNA methyltransferase 1	Homo sapiens	182-186
29650774-0	2018	Genetic Variants in CPA6 and PRPF31 Are Associated With Variation in Response to Metformin in Individuals With Type 2 Diabetes.	Metformin	81-90	carboxypeptidase A6	Mus musculus	20-24
29650774-4	2018	Common variants in PRPF31 and CPA6 were associated with worse and better metformin response, respectively (P &lt; 5 x 10-6), and meta-analysis in independent cohorts displayed similar associations with metformin response (P = 1.2 x 10-8 and P = 0.005, respectively).	Metformin	73-82	carboxypeptidase A6	Mus musculus	30-34
29650774-8	2018	Here, we provide novel evidence for associations of common and rare variants in PRPF31, CPA6, and STAT3 with metformin response that may provide insight into mechanisms important for metformin efficacy in T2D.	Metformin	109-118	carboxypeptidase A6	Mus musculus	88-92
29650774-8	2018	Here, we provide novel evidence for associations of common and rare variants in PRPF31, CPA6, and STAT3 with metformin response that may provide insight into mechanisms important for metformin efficacy in T2D.	Metformin	183-192	carboxypeptidase A6	Mus musculus	88-92
29369427-0	2018	Pioglitazone/metformin adduct regulates insulin secretion and inhibits high glucose-induced apoptosis via p21-p53-MDM2 signaling in INS-1 cells.	Metformin	13-22	KRAS proto-oncogene, GTPase	Rattus norvegicus	106-109
29369427-0	2018	Pioglitazone/metformin adduct regulates insulin secretion and inhibits high glucose-induced apoptosis via p21-p53-MDM2 signaling in INS-1 cells.	Metformin	13-22	MDM2 proto-oncogene	Rattus norvegicus	114-118
28727687-5	2018	Both T4 and metformin alleviated contextual fear memory deficit induced by FAE, and reversed the hippocampal expression changes in the thyroid hormone-inactivating enzyme, deiodinase-III (Dio3) and insulin-like growth factor 2 (Igf2), genes that are known to modulate memory processes.	Metformin	12-21	iodothyronine deiodinase 3	Rattus norvegicus	188-192
28727687-5	2018	Both T4 and metformin alleviated contextual fear memory deficit induced by FAE, and reversed the hippocampal expression changes in the thyroid hormone-inactivating enzyme, deiodinase-III (Dio3) and insulin-like growth factor 2 (Igf2), genes that are known to modulate memory processes.	Metformin	12-21	insulin-like growth factor 2	Rattus norvegicus	198-226
28727687-5	2018	Both T4 and metformin alleviated contextual fear memory deficit induced by FAE, and reversed the hippocampal expression changes in the thyroid hormone-inactivating enzyme, deiodinase-III (Dio3) and insulin-like growth factor 2 (Igf2), genes that are known to modulate memory processes.	Metformin	12-21	insulin-like growth factor 2	Rattus norvegicus	228-232
28727687-6	2018	Neonatal T4 restored maternal allelic expressions of the imprinted Dio3 and Igf2 in the adult male hippocampus, while metformin restored FAE-caused changes in Igf2 expression only.	Metformin	118-127	insulin-like growth factor 2	Rattus norvegicus	159-163
28727687-8	2018	Administering Dnmt1 inhibitor to control neonates resulted in FAE-like deficits in fear memory and hippocampal allele-specific expression of Igf2, which were reversed by metformin.	Metformin	170-179	insulin-like growth factor 2	Rattus norvegicus	141-145
28727687-9	2018	We propose that neonatal administration of T4 and metformin post FAE affect memory via elevating Dnmt1 and consequently normalizing hippocampal Dio3 and Igf2 expressions in the adult offspring.	Metformin	50-59	iodothyronine deiodinase 3	Rattus norvegicus	144-148
28727687-9	2018	We propose that neonatal administration of T4 and metformin post FAE affect memory via elevating Dnmt1 and consequently normalizing hippocampal Dio3 and Igf2 expressions in the adult offspring.	Metformin	50-59	insulin-like growth factor 2	Rattus norvegicus	153-157
29542325-9	2018	Metformin use reduced MYC levels in Caco2 and consequently, SLC1A5 and GLS expression, with a greater effect in cells dependent on glutaminolytic metabolism.	Metformin	0-9	glutaminase 2	Rattus norvegicus	71-74
29915999-4	2018	The inhibition potential of fampridine on the renal transporters was evaluated by determining the uptake of TEA and Metformin, the probe substrates of the transporters of OCT2 and MATEs, respectively, in the absence or presence of fampridine.	Metformin	116-125	POU class 2 homeobox 2	Homo sapiens	171-175
29915999-7	2018	Fampridine also inhibited OCT2 mediated uptake of Metformin with estimated IC50 of 66.8 muM.	Metformin	50-59	POU class 2 homeobox 2	Homo sapiens	26-30
29789508-6	2018	Furthermore, only the higher concentrations of metformin induced the phosphorylation of adenosine 5"-monophosphate (AMP)-activated protein kinase (AMPK), p38, and c-Jun N-terminal kinase (JNK) and reduced the phosphorylation of extracellular regulated protein kinases (ERK) and Akt.	Metformin	47-56	mitogen-activated protein kinase 8	Mus musculus	163-186
29789508-6	2018	Furthermore, only the higher concentrations of metformin induced the phosphorylation of adenosine 5"-monophosphate (AMP)-activated protein kinase (AMPK), p38, and c-Jun N-terminal kinase (JNK) and reduced the phosphorylation of extracellular regulated protein kinases (ERK) and Akt.	Metformin	47-56	mitogen-activated protein kinase 8	Mus musculus	188-191
29759071-15	2018	CONCLUSIONS: Together, these results reveal that metformin reduces TG accumulation in HepG2 cells via inhibiting the expression of SCD1.	Metformin	49-58	stearoyl-CoA desaturase	Homo sapiens	131-135
29662316-3	2018	However, no report has revealed the direct effect of metformin on CD19-CAR T cell biological function and its underling mechanisms.	Metformin	53-62	nuclear receptor subfamily 1 group I member 3	Homo sapiens	71-74
29662316-4	2018	Purpose: The purpose of this research was to explore the effect of metformin on CD19-CAR T cell biological function and the mechanisms involved.	Metformin	67-76	nuclear receptor subfamily 1 group I member 3	Homo sapiens	85-88
29662316-8	2018	Results: In the current study, it was found that metformin inhibited CD19-CAR T cell proliferation and cytotoxicity and induced apoptosis.	Metformin	49-58	nuclear receptor subfamily 1 group I member 3	Homo sapiens	74-77
29662316-10	2018	By using an AMPK inhibitor, compound C, we demonstrated the crucial roles of AMPK in CD19-CAR T cells when they were treated with metformin.	Metformin	130-139	nuclear receptor subfamily 1 group I member 3	Homo sapiens	90-93
29662316-11	2018	Finally, we verified that metformin suppressed the cytotoxicity of CD19-CAR T cell in vivo.	Metformin	26-35	nuclear receptor subfamily 1 group I member 3	Homo sapiens	72-75
29662316-12	2018	Conclusion: Taken together, these results indicated that metformin may play an important role in modulating CD19-CAR T cell biological functions in an AMPK-dependent and mTOR/HIF1alpha-independent manner.	Metformin	57-66	nuclear receptor subfamily 1 group I member 3	Homo sapiens	113-116
29253574-8	2018	Meanwhile, metformin notably suppressed the activation of P65 NF-kappaB, mTOR and S6K, reduced Bace1 protein expression.	Metformin	11-20	ribosomal protein S6 kinase, polypeptide 1	Mus musculus	82-85
29253574-9	2018	Our data suggest that metformin can exert functional recovery of memory deficits and neuroprotective effect on APP/PS1 mice via triggering neurogenesis and anti-inflammation mediated by regulating AMPK/mTOR/S6K/Bace1 and AMPK/P65 NF-kappaB signaling pathways in the hippocampus, which may contribute to improvement in neurological deficits.	Metformin	22-31	ribosomal protein S6 kinase, polypeptide 1	Mus musculus	207-210
29253762-2	2018	In addition to its effect on glucose control, metformin, may also directly benefit in the restoration of the function of eNOS and EC.	Metformin	46-55	nitric oxide synthase 3	Rattus norvegicus	121-125
29080083-5	2018	We show that metformin potently reduces the progression of seizures and blocks seizure-induced over-expression of brain-derived neurotropic factor (BDNF) and its receptor, Tropomyosin receptor kinase B (TrkB).	Metformin	13-22	brain-derived neurotrophic factor	Rattus norvegicus	114-146
29080083-5	2018	We show that metformin potently reduces the progression of seizures and blocks seizure-induced over-expression of brain-derived neurotropic factor (BDNF) and its receptor, Tropomyosin receptor kinase B (TrkB).	Metformin	13-22	brain-derived neurotrophic factor	Rattus norvegicus	148-152
29080083-7	2018	Moreover, metformin decreased mechanistic target of rapamycin (mTOR) activation through activation of AMP-activated protein kinase (AMPK) signaling pathway.	Metformin	10-19	mechanistic target of rapamycin kinase	Rattus norvegicus	30-61
29080083-7	2018	Moreover, metformin decreased mechanistic target of rapamycin (mTOR) activation through activation of AMP-activated protein kinase (AMPK) signaling pathway.	Metformin	10-19	mechanistic target of rapamycin kinase	Rattus norvegicus	63-67
29094287-0	2018	Targeting AMPK, mTOR and beta-Catenin by Combined Metformin and Aspirin Therapy in HCC: An Appraisal in Egyptian HCC Patients.	Metformin	50-59	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	10-14
29094287-3	2018	OBJECTIVE: The current work aimed to investigate the possibility of targeting AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and beta-catenin proteins through combined metformin/aspirin treatment in the HepG2 cell line, and to explore such molecular targets in Egyptian HCC patients.	Metformin	196-205	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	78-106
29094287-3	2018	OBJECTIVE: The current work aimed to investigate the possibility of targeting AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and beta-catenin proteins through combined metformin/aspirin treatment in the HepG2 cell line, and to explore such molecular targets in Egyptian HCC patients.	Metformin	196-205	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	108-112
29094287-10	2018	CONCLUSIONS: Targeting AMPK, mTOR and beta-catenin by combined metformin/aspirin treatment could be a promising therapeutic strategy for Egyptian HCC patients, and possibly other HCC patients.	Metformin	63-72	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	23-27
29929422-0	2018	Metformin reduces TRIB3 expression and restores autophagy flux: an alternative antitumor action.	Metformin	0-9	tribbles pseudokinase 3	Mus musculus	18-23
29929422-4	2018	Here, we discuss our recent findings regarding how metformin reduces TRIB3 expression to restore autophagic flux and suppress melanoma progression in non-diabetic and diabetic mice.	Metformin	51-60	tribbles pseudokinase 3	Mus musculus	69-74
29929422-5	2018	We found that overexpression of TRIB3 reverses the metformin-activated autophagic flux, clearance of accumulated tumor-promoting factors and inhibition of tumor progression.	Metformin	51-60	tribbles pseudokinase 3	Mus musculus	32-37
29929422-7	2018	Metformin inhibits SMAD3 phosphorylation and impedes the KAT5-SMAD3 interaction, which attenuates the KAT5-mediated K333 acetylation of SMAD3 to suppress SMAD3 transcriptional activity and TRIB3 expression.	Metformin	0-9	tribbles pseudokinase 3	Mus musculus	189-194
29929422-8	2018	Our finding defines a molecular mechanism by which metformin targets TRIB3 expression to induce autophagy and protect against melanoma progression.	Metformin	51-60	tribbles pseudokinase 3	Mus musculus	69-74
30032136-14	2018	The metformin/FTY720 regimen markedly induced ROS generation; moreover, apoptosis, ER stress and inhibition of PI3K/AKT/ mTOR were attenuated by the ROS scavenger NAC.	Metformin	4-13	X-linked Kx blood group	Homo sapiens	163-166
30481793-9	2018	mRNA and protein levels of MMP-2 and MMP-9 decreased significantly upon treatment with metformin of 10mM for 12, 24 and 48h in a time-dependent manner (p &lt; 0.05).	Metformin	87-96	matrix metallopeptidase 9	Homo sapiens	37-42
30481793-10	2018	In line with in vitro results, in vivo experiments demonstrated that metformin inhibited tumorigenicity, inhibited lung metastasis and down-regulated the expression of MMP-2 and MMP-9.	Metformin	69-78	matrix metallopeptidase 9	Homo sapiens	178-183
30481793-12	2018	CONCLUSION: Our study for the first time demonstrated the anti-invasive and anti-metastatic effects of metformin on human ESCC cells both in vitro and in vivo, which might be associated with the down-regulation of MMP-2 and MMP-9.	Metformin	103-112	matrix metallopeptidase 9	Homo sapiens	224-229
29110598-12	2018	Similarly, Sirtuin1 level increases after treatment with standard antihyperglycemic (metformin, exenatide, liraglutide), antihypertensive (sartans), lipid-lowering (fibrates, statins) and anticoagulant (fidarestat) drugs.	Metformin	85-94	sirtuin 1	Homo sapiens	11-19
29025860-4	2018	Treatment with two AMPK activators, metformin or AICAR, inhibited TRPA1 activity in DRG neurons by decreasing the amount of membrane-associated TRPA1.	Metformin	36-45	transient receptor potential cation channel, subfamily A, member 1	Mus musculus	66-71
29025860-4	2018	Treatment with two AMPK activators, metformin or AICAR, inhibited TRPA1 activity in DRG neurons by decreasing the amount of membrane-associated TRPA1.	Metformin	36-45	transient receptor potential cation channel, subfamily A, member 1	Mus musculus	144-149
29025860-5	2018	Metformin induced a dose-dependent inhibition of TRPA1-mediated calcium influx.	Metformin	0-9	transient receptor potential cation channel, subfamily A, member 1	Mus musculus	49-54
28696014-6	2018	Osteogenic specific makers (Alp, Bglap, Runx2, Bmp2, and Col1) in fibroblasts administered with metformin (20 mug/mL) were detected by ALP staining, alizarin red staining, qPCR, and Western blotting after 7 and 14 days of culture.	Metformin	96-105	ATHS	Homo sapiens	135-138
28722177-5	2018	Metformin treatment also increases deoxycytidine kinase (dCK) expression and, as the chemotherapeutic agent gemcitabine relies on dCK for its efficient activity, we speculated that metformin would enhance the sensitivity of OSCC cells to gemcitabine.	Metformin	0-9	Calcium/calmodulin-dependent protein kinase II	Drosophila melanogaster	57-60
28722177-5	2018	Metformin treatment also increases deoxycytidine kinase (dCK) expression and, as the chemotherapeutic agent gemcitabine relies on dCK for its efficient activity, we speculated that metformin would enhance the sensitivity of OSCC cells to gemcitabine.	Metformin	181-190	Calcium/calmodulin-dependent protein kinase II	Drosophila melanogaster	57-60
28722177-5	2018	Metformin treatment also increases deoxycytidine kinase (dCK) expression and, as the chemotherapeutic agent gemcitabine relies on dCK for its efficient activity, we speculated that metformin would enhance the sensitivity of OSCC cells to gemcitabine.	Metformin	181-190	Calcium/calmodulin-dependent protein kinase II	Drosophila melanogaster	130-133
29312507-8	2017	Further analysis showed that metformin may inhibit the VEGF-A protein translation through inducing a VEGF-A-targeting microRNA, microRNA-497a-5p, resulting in reduced retina neovascularization.	Metformin	29-38	vascular endothelial growth factor A	Mus musculus	55-61
29312507-8	2017	Further analysis showed that metformin may inhibit the VEGF-A protein translation through inducing a VEGF-A-targeting microRNA, microRNA-497a-5p, resulting in reduced retina neovascularization.	Metformin	29-38	vascular endothelial growth factor A	Mus musculus	101-107
29467947-0	2018	Metformin inhibits TGF-beta1-induced epithelial-to-mesenchymal transition-like process and stem-like properties in GBM via AKT/mTOR/ZEB1 pathway.	Metformin	0-9	zinc finger E-box binding homeobox 1	Homo sapiens	132-136
29467947-7	2018	Our results also showed that metformin significantly suppressed self-renewal capacity of glioblastoma stem cells (GSCs), and expression of stem cell markers Bmi1, Sox2 and Musashi1, indicating that metformin can inhibit cancer stem-like properties of GBM cells.	Metformin	29-38	SRY-box transcription factor 2	Homo sapiens	163-167
29467947-7	2018	Our results also showed that metformin significantly suppressed self-renewal capacity of glioblastoma stem cells (GSCs), and expression of stem cell markers Bmi1, Sox2 and Musashi1, indicating that metformin can inhibit cancer stem-like properties of GBM cells.	Metformin	198-207	SRY-box transcription factor 2	Homo sapiens	163-167
29467947-8	2018	We further clarified that metformin specifically inhibited TGF-beta1 activated AKT, the downstream molecular mTOR and the leading transcription factor ZEB1.	Metformin	26-35	zinc finger E-box binding homeobox 1	Homo sapiens	151-155
29467947-9	2018	Taken together, our data demonstrate that metformin inhibits TGF-beta1-induced EMT-like process and cancer stem-like properties in GBM cells via AKT/mTOR/ZEB1 pathway and provide evidence of metformin for further clinical investigation targeted GBM.	Metformin	42-51	zinc finger E-box binding homeobox 1	Homo sapiens	154-158
28990070-13	2017	In addition, TSP-1 expression was markedly attenuated by treatment with metformin in cultured BM-EPCs.	Metformin	72-81	thrombospondin 1	Mus musculus	13-18
28990070-14	2017	Metformin contributed to wound healing and improved angiogenesis in T2DM mice, which was, in part, associated with stimulation of NO, and inhibition of O2- and TSP-1 in EPCs from db/db mice.	Metformin	0-9	thrombospondin 1	Mus musculus	160-165
29344202-8	2017	The present study demonstrated that expression of p-ERK1/2, VEGF, VEGFR2 and Bcl-2 was downregulated by treatment with increasing concentrations of metformin, whereas expression of Bax and caspase-3 was evidently upregulated.	Metformin	148-157	kinase insert domain receptor	Homo sapiens	66-72
29230104-9	2017	Mechanistically, metformin modulated the EGCG-activated Nrf2/HO-1 pathway through Sirtuin 1 (SIRT1)-dependent deacetylation of Nrf2.	Metformin	17-26	sirtuin 1	Homo sapiens	82-91
29230104-9	2017	Mechanistically, metformin modulated the EGCG-activated Nrf2/HO-1 pathway through Sirtuin 1 (SIRT1)-dependent deacetylation of Nrf2.	Metformin	17-26	sirtuin 1	Homo sapiens	93-98
29230104-10	2017	Moreover, metformin upregulated SIRT1 expression partially through the NF-kB pathway.	Metformin	10-19	sirtuin 1	Homo sapiens	32-37
28921708-5	2017	Scopoletin or metformin down-regulated hepatic gene expression of triglyceride (Pparg, Plpp2, and Dgat2) and cholesterol (Hmgcr) synthesis as well as inflammation (Tlr4, Myd88, Nfkb1, Tnfa, and Il6), while it up-regulated Cyp7a1 gene.	Metformin	14-23	myeloid differentiation primary response gene 88	Mus musculus	170-175
29254182-0	2017	Metformin induces cell cycle arrest at the G1 phase through E2F8 suppression in lung cancer cells.	Metformin	0-9	E2F transcription factor 8	Mus musculus	60-64
29254182-1	2017	A target molecule responsible for cell cycle arrest by metformin was discovered using a gene chip array in lung cancer cells and the effect of metformin on E2F8 was assessed.	Metformin	143-152	E2F transcription factor 8	Mus musculus	156-160
29254182-2	2017	The siRNA-mediated knockdown of E2F8 significantly suppressed G1-S progression while ectopic expression of E2F8 relieved metformin-induced G1 arrest.	Metformin	121-130	E2F transcription factor 8	Mus musculus	107-111
29254182-9	2017	The present study suggests that metformin may induce cell cycle arrest at the G1 phase by suppressing E2F8 expression in lung cancer cells.	Metformin	32-41	E2F transcription factor 8	Mus musculus	102-106
28978947-4	2017	Given the conflicting results on the effects of metformin we sought, using our genetic mouse models deficient in the catalytic subunits of AMPK, to determine whether this kinase is involved in the effects of metformin on the expression of the iron-regulatory hormone hepcidin, as recently proposed.	Metformin	208-217	hepcidin antimicrobial peptide	Mus musculus	267-275
28975647-0	2017	Effect of metformin and celecoxib on cytotoxicity and release of GDF-15 from human mesenchymal stem cells in high glucose condition.	Metformin	10-19	growth differentiation factor 15	Homo sapiens	65-71
28975647-5	2017	The cytotoxicity and secretion of GDF-15 were further tested in MSCs treated with metformin and celecoxib in various glucose concentrations.	Metformin	82-91	growth differentiation factor 15	Homo sapiens	34-40
28975647-9	2017	Metformin and celecoxib induced release from MSCs; however, high glucose inhibited the metformin-induced GDF-15 release.	Metformin	87-96	growth differentiation factor 15	Homo sapiens	105-111
28807678-8	2017	Western blot analysis revealed that metformin ameliorated MPTP-induced alpha-synuclein phosphorylation which was accompanied by increased methylation of protein phosphatase 2A (PP2A), a phosphatase related to alpha-synuclein dephosphorylation.	Metformin	36-45	protein phosphatase 2, regulatory subunit A, alpha	Mus musculus	177-181
29085506-6	2017	Metformin significantly decreased E2-stimulated cell proliferation; an effect that was rescued in the presence of compound C. Metformin treatment markedly increased the phosphorylation of AMPK while decreasing p70S6K phosphorylation, indicating that metformin exerts its effects through stimulation of AMPK and subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	188-192
29085506-6	2017	Metformin significantly decreased E2-stimulated cell proliferation; an effect that was rescued in the presence of compound C. Metformin treatment markedly increased the phosphorylation of AMPK while decreasing p70S6K phosphorylation, indicating that metformin exerts its effects through stimulation of AMPK and subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	302-306
29085506-6	2017	Metformin significantly decreased E2-stimulated cell proliferation; an effect that was rescued in the presence of compound C. Metformin treatment markedly increased the phosphorylation of AMPK while decreasing p70S6K phosphorylation, indicating that metformin exerts its effects through stimulation of AMPK and subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway.	Metformin	126-135	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	188-192
29085506-6	2017	Metformin significantly decreased E2-stimulated cell proliferation; an effect that was rescued in the presence of compound C. Metformin treatment markedly increased the phosphorylation of AMPK while decreasing p70S6K phosphorylation, indicating that metformin exerts its effects through stimulation of AMPK and subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway.	Metformin	126-135	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	302-306
29085506-8	2017	Reverse transcription-quantitative polymerase chain reaction analysis demonstrated that c-fos and c-myc expression were attenuated by metformin, an effect that was rescued in the presence of compound C. Therefore, metformin regulates the expression of ERs, and inhibits estrogen-mediated proliferation of human EC cells through the activation of AMPK and subsequent inhibition of the mTOR signaling pathway.	Metformin	134-143	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	346-350
29085506-8	2017	Reverse transcription-quantitative polymerase chain reaction analysis demonstrated that c-fos and c-myc expression were attenuated by metformin, an effect that was rescued in the presence of compound C. Therefore, metformin regulates the expression of ERs, and inhibits estrogen-mediated proliferation of human EC cells through the activation of AMPK and subsequent inhibition of the mTOR signaling pathway.	Metformin	214-223	Fos proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	88-93
29085506-8	2017	Reverse transcription-quantitative polymerase chain reaction analysis demonstrated that c-fos and c-myc expression were attenuated by metformin, an effect that was rescued in the presence of compound C. Therefore, metformin regulates the expression of ERs, and inhibits estrogen-mediated proliferation of human EC cells through the activation of AMPK and subsequent inhibition of the mTOR signaling pathway.	Metformin	214-223	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	346-350
28971610-0	2017	Mechanistic in vitro studies confirm that inhibition of the renal apical efflux transporter multidrug and toxin extrusion (MATE) 1, and not altered absorption, underlies the increased metformin exposure observed in clinical interactions with cimetidine, trimethoprim or pyrimethamine.	Metformin	184-193	solute carrier family 47 member 1	Homo sapiens	106-130
28971610-4	2017	Subsequently, to understand whether inhibition of renal transporters are responsible for AUC increases, in vitro inhibitory potencies against metformin transport by human OCT2, multidrug and toxin extrusion (MATE) 1 and MATE2-K were determined.	Metformin	142-151	POU class 2 homeobox 2	Homo sapiens	171-175
28971610-4	2017	Subsequently, to understand whether inhibition of renal transporters are responsible for AUC increases, in vitro inhibitory potencies against metformin transport by human OCT2, multidrug and toxin extrusion (MATE) 1 and MATE2-K were determined.	Metformin	142-151	solute carrier family 47 member 1	Homo sapiens	191-215
28971610-6	2017	Calculated theoretical fold-increases in metformin exposure confirmed solitary inhibition of renal MATE1 to be the likely mechanism underlying the observed exposure changes in clinical DDIs.	Metformin	41-50	solute carrier family 47 member 1	Homo sapiens	99-104
28709912-6	2017	Inhibition of P-gp by oral pre-treatment with cyclosporine A increased the bioavailability of the P-gp substrates (ampicillin and ranitidine) in males and females (p&lt;0.05), and to a greater extent in males, but had no influence on the bioavailability of metformin in either male or female rats.	Metformin	257-266	ATP-binding cassette, subfamily B (MDR/TAP), member 1B	Rattus norvegicus	14-18
28709912-6	2017	Inhibition of P-gp by oral pre-treatment with cyclosporine A increased the bioavailability of the P-gp substrates (ampicillin and ranitidine) in males and females (p&lt;0.05), and to a greater extent in males, but had no influence on the bioavailability of metformin in either male or female rats.	Metformin	257-266	ATP-binding cassette, subfamily B (MDR/TAP), member 1B	Rattus norvegicus	98-102
28862982-7	2017	RESULTS: Results showed that volunteers with SLC22A3 rs8187722 variant had higher (chi2, p&lt;0.05) metformin Cmax and AUC values than the wild SLC22A3 volunteers, whereas T1/2 and Kel were not affected.	Metformin	100-109	solute carrier family 22 member 3	Homo sapiens	45-52
28862982-8	2017	In addition, volunteers with the heterozygote SLC22A3 rs2292334 variant had significantly higher (chi2, p&lt;0.05) metformin Cmax and AUC and lower Kel values than the wild-type SLC22A3 genotype.	Metformin	115-124	solute carrier family 22 member 3	Homo sapiens	46-53
28862982-9	2017	CONCLUSIONS: The SLC22A3 rs8187722 and rs2292334 genetic variants affected metformin pharmacokinetics among a clinical sample of Jordanians.	Metformin	75-84	solute carrier family 22 member 3	Homo sapiens	17-24
28947922-6	2017	Lower average and promoter DNA methylation of SLC22A1, SLC22A3, and SLC47A1 was found in diabetic subjects receiving just metformin, compared to those who took insulin plus metformin or no diabetes medication.	Metformin	122-131	solute carrier family 22 member 3	Homo sapiens	55-62
28947922-6	2017	Lower average and promoter DNA methylation of SLC22A1, SLC22A3, and SLC47A1 was found in diabetic subjects receiving just metformin, compared to those who took insulin plus metformin or no diabetes medication.	Metformin	122-131	solute carrier family 47 member 1	Homo sapiens	68-75
28947922-6	2017	Lower average and promoter DNA methylation of SLC22A1, SLC22A3, and SLC47A1 was found in diabetic subjects receiving just metformin, compared to those who took insulin plus metformin or no diabetes medication.	Metformin	173-182	solute carrier family 47 member 1	Homo sapiens	68-75
28947922-8	2017	Notably, DNA methylation was also associated with gene expression, glucose levels, and body mass index, i.e., higher SLC22A3 methylation was related to lower SLC22A3 expression and to insulin plus metformin treatment, higher fasting glucose levels and higher body mass index.	Metformin	197-206	solute carrier family 22 member 3	Homo sapiens	117-124
29050400-0	2017	Metformin reverses TRAP1 mutation-associated alterations in mitochondrial function in Parkinson"s disease.	Metformin	0-9	TNF receptor associated protein 1	Homo sapiens	19-24
28930827-14	2017	Ranking results showed that glyburide might be the optimum treatment regarding average glucose control, and metformin is the fastest in glucose control for GDM patients; glyburide have the highest incidence of macrosomia, preeclampsia, hyperbilirubinemia, neonatal hypoglycemia, shortest gestational age at delivery, and lowest mean birth weight; metformin (plus insulin when required) have the lowest incidence of macrosomia, PIH, LGA, RDS, low gestational age at delivery, and low birth weight.	Metformin	108-117	peripherin 2	Homo sapiens	437-440
29190886-6	2017	Immunoblotting data showed that metformin activated the phosphorylation of STAT-1 and STAT-2 in OR-6 and JFH-1 infected Huh 7.5.1 cells.	Metformin	32-41	signal transducer and activator of transcription 1	Homo sapiens	75-81
29190886-6	2017	Immunoblotting data showed that metformin activated the phosphorylation of STAT-1 and STAT-2 in OR-6 and JFH-1 infected Huh 7.5.1 cells.	Metformin	32-41	signal transducer and activator of transcription 2	Homo sapiens	86-92
28801594-6	2017	Metformin restored liver COMT protein levels, and metformin-induced liver AMPK phosphorylation was abolished by COMT inhibition.	Metformin	0-9	catechol-O-methyltransferase	Mus musculus	25-29
28801594-6	2017	Metformin restored liver COMT protein levels, and metformin-induced liver AMPK phosphorylation was abolished by COMT inhibition.	Metformin	50-59	catechol-O-methyltransferase	Mus musculus	112-116
28789657-0	2017	Neutrophil gelatinase associated lipocalin (NGAL) is elevated in type 2 diabetics with carotid artery stenosis and reduced under metformin treatment.	Metformin	129-138	lipocalin 2	Homo sapiens	0-42
28789657-0	2017	Neutrophil gelatinase associated lipocalin (NGAL) is elevated in type 2 diabetics with carotid artery stenosis and reduced under metformin treatment.	Metformin	129-138	lipocalin 2	Homo sapiens	44-48
28789657-4	2017	Moreover, the potential anti-inflammatory effect of metformin on NGAL was addressed in diabetics.	Metformin	52-61	lipocalin 2	Homo sapiens	65-69
28789657-13	2017	Metformin treatment was associated with decreased NGAL [60.7 ng/ml (51.9-69.2) vs. 121.7 (103.7-169.9), p &lt; 0.0001] and MMP-9/NGAL [20.8 ng/ml (12.1-26.5) vs. 53.7 (27.4-73.4), p = 0.007] in diabetics and reduced leukocyte infiltration in carotid lesions of diabetics.	Metformin	0-9	lipocalin 2	Homo sapiens	50-54
28789657-13	2017	Metformin treatment was associated with decreased NGAL [60.7 ng/ml (51.9-69.2) vs. 121.7 (103.7-169.9), p &lt; 0.0001] and MMP-9/NGAL [20.8 ng/ml (12.1-26.5) vs. 53.7 (27.4-73.4), p = 0.007] in diabetics and reduced leukocyte infiltration in carotid lesions of diabetics.	Metformin	0-9	matrix metallopeptidase 9	Homo sapiens	123-128
28789657-13	2017	Metformin treatment was associated with decreased NGAL [60.7 ng/ml (51.9-69.2) vs. 121.7 (103.7-169.9), p &lt; 0.0001] and MMP-9/NGAL [20.8 ng/ml (12.1-26.5) vs. 53.7 (27.4-73.4), p = 0.007] in diabetics and reduced leukocyte infiltration in carotid lesions of diabetics.	Metformin	0-9	lipocalin 2	Homo sapiens	129-133
28789657-15	2017	Metformin significantly reduced the inflammatory burden including NGAL in diabetics.	Metformin	0-9	lipocalin 2	Homo sapiens	66-70
28206714-9	2017	Metformin counteracted the effect of high glucose on the elevated G6P and fructose 2,6-bisphosphate and on Gck repression, recruitment of Mlx-ChREBP to the G6pc and Pklr promoters and induction of these genes.	Metformin	0-9	glucokinase	Homo sapiens	107-110
28695314-14	2017	Interestingly, reconstituted SlCAT2 showed competence for acetylcholine transport, which was also inhibited by metformin.	Metformin	111-120	catalase isozyme 2	Solanum lycopersicum	29-35
28611284-0	2017	Activation of the ATF2/CREB-PGC-1alpha pathway by metformin leads to dopaminergic neuroprotection.	Metformin	50-59	activating transcription factor 2	Homo sapiens	18-22
28611284-0	2017	Activation of the ATF2/CREB-PGC-1alpha pathway by metformin leads to dopaminergic neuroprotection.	Metformin	50-59	cAMP responsive element binding protein 1	Homo sapiens	23-27
28611284-5	2017	As a potential upstream regulator of mitochondria gene transcription by metformin, PGC-1alpha promoter activity was stimulated by metformin via CREB and ATF2 pathways.	Metformin	72-81	cAMP responsive element binding protein 1	Homo sapiens	144-148
28611284-5	2017	As a potential upstream regulator of mitochondria gene transcription by metformin, PGC-1alpha promoter activity was stimulated by metformin via CREB and ATF2 pathways.	Metformin	72-81	activating transcription factor 2	Homo sapiens	153-157
28611284-5	2017	As a potential upstream regulator of mitochondria gene transcription by metformin, PGC-1alpha promoter activity was stimulated by metformin via CREB and ATF2 pathways.	Metformin	130-139	cAMP responsive element binding protein 1	Homo sapiens	144-148
28611284-5	2017	As a potential upstream regulator of mitochondria gene transcription by metformin, PGC-1alpha promoter activity was stimulated by metformin via CREB and ATF2 pathways.	Metformin	130-139	activating transcription factor 2	Homo sapiens	153-157
28611284-6	2017	PGC-1alpha and phosphorylation of ATF2 and CREB by metformin were selectively increased in the SN and the striatum, but not the cortex.	Metformin	51-60	activating transcription factor 2	Homo sapiens	34-38
28611284-6	2017	PGC-1alpha and phosphorylation of ATF2 and CREB by metformin were selectively increased in the SN and the striatum, but not the cortex.	Metformin	51-60	cAMP responsive element binding protein 1	Homo sapiens	43-47
28611284-8	2017	Together these results suggest that the metformin-ATF2/CREB-PGC-1alpha pathway might be promising therapeutic target for PD.	Metformin	40-49	activating transcription factor 2	Homo sapiens	50-54
28611284-8	2017	Together these results suggest that the metformin-ATF2/CREB-PGC-1alpha pathway might be promising therapeutic target for PD.	Metformin	40-49	cAMP responsive element binding protein 1	Homo sapiens	55-59
28698800-0	2017	Metformin-induced ablation of microRNA 21-5p releases Sestrin-1 and CAB39L antitumoral activities.	Metformin	0-9	microRNA 215	Homo sapiens	30-44
28698800-4	2017	Our analysis here revealed that the expression of miR-21-5p was downregulated in multiple breast cancer cell lines treated with pharmacologically relevant doses of metformin.	Metformin	164-173	microRNA 215	Homo sapiens	50-59
28698800-7	2017	Antagomir-mediated ablation of miR-21-5p phenocopied the effects of metformin on both the clonogenicity and migration of the treated cells, while ectopic expression of miR-21-5p had the opposite effect.	Metformin	68-77	microRNA 215	Homo sapiens	31-40
28675758-7	2017	Furthermore, metformin exposure led to an increased apoptosis rate and cell-cycle arrest accompanied with downregulation of Ccna2 and Ccnb2.	Metformin	13-22	cyclin B2	Rattus norvegicus	134-139
28675758-8	2017	At the molecular level, the AMPK signaling pathway was activated, whereas the mTOR and ERK1/2 signaling pathways were inhibited by metformin.	Metformin	131-140	mechanistic target of rapamycin kinase	Rattus norvegicus	78-82
28380462-5	2017	ATF3 was upregulated by metformin, and its knockdown significantly reduced metformin-induced apoptosis.	Metformin	24-33	activating transcription factor 3	Rattus norvegicus	0-4
28380462-5	2017	ATF3 was upregulated by metformin, and its knockdown significantly reduced metformin-induced apoptosis.	Metformin	75-84	activating transcription factor 3	Rattus norvegicus	0-4
28387573-0	2017	Metformin inhibits RANKL and sensitizes cancer stem cells to denosumab.	Metformin	0-9	TNF superfamily member 11	Homo sapiens	19-24
28387573-3	2017	Here we report that the biguanide metformin prevents BRCA1 haploinsufficiency-driven RANKL gene overexpression, thereby disrupting an auto-regulatory feedback control of RANKL-addicted cancer stem cell-like states within BRCA1mut/- cell populations.	Metformin	34-43	BRCA1 DNA repair associated	Homo sapiens	53-58
28387573-3	2017	Here we report that the biguanide metformin prevents BRCA1 haploinsufficiency-driven RANKL gene overexpression, thereby disrupting an auto-regulatory feedback control of RANKL-addicted cancer stem cell-like states within BRCA1mut/- cell populations.	Metformin	34-43	TNF superfamily member 11	Homo sapiens	85-90
28387573-3	2017	Here we report that the biguanide metformin prevents BRCA1 haploinsufficiency-driven RANKL gene overexpression, thereby disrupting an auto-regulatory feedback control of RANKL-addicted cancer stem cell-like states within BRCA1mut/- cell populations.	Metformin	34-43	BRCA1 DNA repair associated	Homo sapiens	221-226
28387573-4	2017	Moreover, metformin treatment elicits a synergistic decline in the breast cancer-initiating cell population and its self-renewal capacity in BRCA1-mutated basal-like breast cancer cells with bone metastasis-initiation capacity that exhibit primary resistance to denosumab in mammosphere assays.	Metformin	10-19	BRCA1 DNA repair associated	Homo sapiens	141-146
28387573-6	2017	Our findings provide a rationale for new denosumab/metformin combinatorial strategies to clinically manage RANKL-related breast oncogenesis and metastatic progression.	Metformin	51-60	TNF superfamily member 11	Homo sapiens	107-112
28324269-0	2017	Metformin sensitizes triple-negative breast cancer to proapoptotic TRAIL receptor agonists by suppressing XIAP expression.	Metformin	0-9	X-linked inhibitor of apoptosis	Homo sapiens	106-110
28324269-9	2017	These effects of metformin were accompanied by robust reductions in the protein levels of XIAP, a negative regulator of TRAIL-induced apoptosis.	Metformin	17-26	X-linked inhibitor of apoptosis	Homo sapiens	90-94
28324269-10	2017	Silencing XIAP in TNBC cells mimicked the TRAIL-sensitizing effects of metformin.	Metformin	71-80	X-linked inhibitor of apoptosis	Homo sapiens	10-14
28324269-11	2017	Metformin also enhanced the antitumor effects of TRAIL in a metastatic murine TNBC model.	Metformin	0-9	tumor necrosis factor (ligand) superfamily, member 10	Mus musculus	49-54
28378944-0	2017	Chloride intracellular channel 1 regulates the antineoplastic effects of metformin in gallbladder cancer cells.	Metformin	73-82	chloride intracellular channel 1	Homo sapiens	0-32
28378944-6	2017	Of note, inhibition, knockdown and upregulation of the membrane protein Chloride intracellular channel 1 (CLIC1) can affect GBC resistance in the presence of metformin.	Metformin	158-167	chloride intracellular channel 1	Homo sapiens	72-104
28378944-6	2017	Of note, inhibition, knockdown and upregulation of the membrane protein Chloride intracellular channel 1 (CLIC1) can affect GBC resistance in the presence of metformin.	Metformin	158-167	chloride intracellular channel 1	Homo sapiens	106-111
28378944-10	2017	Notably, either dysfunction or downregulation of CLIC1 can partially decrease the antineoplastic effects of metformin while upregulation of CLIC1 can increase drug sensitivity.	Metformin	108-117	chloride intracellular channel 1	Homo sapiens	49-54
28233033-11	2017	Interestingly, metformin reduced Dhh and Ihh expression in mouse adipose tissue explants.	Metformin	15-24	Indian hedgehog	Mus musculus	41-44
28179448-11	2017	Levels of NT- and CT-IGFBP-4 were reduced in T2D patients receiving metformin compared to those in controls and patients not receiving metformin.	Metformin	68-77	insulin like growth factor binding protein 4	Homo sapiens	21-28
28179448-11	2017	Levels of NT- and CT-IGFBP-4 were reduced in T2D patients receiving metformin compared to those in controls and patients not receiving metformin.	Metformin	135-144	insulin like growth factor binding protein 4	Homo sapiens	21-28
28238946-4	2017	In the present study, experiments are designed to investigate the effects and mechanisms of metformin on Ces1d and Ces1e in vivo and in vitro.	Metformin	92-101	carboxylesterase 1E	Mus musculus	115-120
28238946-5	2017	In results, metformin suppresses the expression and activity of Ces1d and Ces1e in a dose- and time-dependent manner.	Metformin	12-21	carboxylesterase 1E	Mus musculus	74-79
28260041-7	2017	The results revealed that the protein and mRNA levels of Shh and Gli-1 were decreased by metformin treatment in the two cell lines in a dose- and time-dependent manner.	Metformin	89-98	GLI family zinc finger 1	Homo sapiens	65-70
28260041-9	2017	The small interfering RNA-induced depletion of AMPK reversed the suppressive effect of metformin on recombinant human Shh-induced expression of Gli-1 in HGC-27 gastric cancer cells.	Metformin	87-96	GLI family zinc finger 1	Homo sapiens	144-149
28043910-3	2017	In this study, we demonstrated that metformin is capable of inhibiting prostate cancer cell migration and invasion by repressing EMT evidenced by downregulating the mesenchymal markers N-cadherin, Vimentin, and Twist and upregulating the epithelium E-cadherin.	Metformin	36-45	cadherin 2	Homo sapiens	185-195
28087733-9	2017	We finally demonstrated that the expression of genes of the fission/fusion machinery, namely OPA1 and MFN2, was reduced in trisomic cells and increased by metformin treatment.	Metformin	155-164	mitofusin 2	Homo sapiens	102-106
28069720-2	2017	As pregnancy increased the renal secretion of metformin, a substrate for OCT2, MATE1, and MATE2-K, we hypothesized that the renal secretion of 1-NMN would be similarly affected.	Metformin	46-55	solute carrier family 47 member 1	Homo sapiens	79-84
28231061-0	2017	Role of treatment-modifying MTHFR677C&gt;T and 1298A&gt;C polymorphisms in metformin-treated Puerto Rican patients with type-2 diabetes mellitus and peripheral neuropathy.	Metformin	75-84	methylenetetrahydrofolate reductase	Homo sapiens	28-33
28231061-3	2017	METHODS: DNAs from 89 metformin-treated patients with T2DM and DPN were genotyped using the PCR-based RFLP assay for MTHFR677C&gt;T and 1298A&gt;C polymorphisms.	Metformin	22-31	methylenetetrahydrofolate reductase	Homo sapiens	117-122
28392895-0	2017	Association between the synonymous variant organic cation transporter 3 (OCT3)-1233G&gt;A and the glycemic response following metformin therapy in patients with type 2 diabetes.	Metformin	126-135	OCTN3	Homo sapiens	43-71
28392895-0	2017	Association between the synonymous variant organic cation transporter 3 (OCT3)-1233G&gt;A and the glycemic response following metformin therapy in patients with type 2 diabetes.	Metformin	126-135	OCTN3	Homo sapiens	73-77
28392895-1	2017	OBJECTIVES: Organic cation transporter 3 (OCT3) as a high-capacity transporter contribute to the metabolism of metformin.	Metformin	111-120	OCTN3	Homo sapiens	12-40
28392895-1	2017	OBJECTIVES: Organic cation transporter 3 (OCT3) as a high-capacity transporter contribute to the metabolism of metformin.	Metformin	111-120	OCTN3	Homo sapiens	42-46
28392895-2	2017	The present study was conducted to determine the genotype frequencies of the variant OCT3-1233G&gt;A (rs2292334) in patients with newly diagnosed type 2 diabetes (T2D) and its relationship with response to metformin.	Metformin	206-215	OCTN3	Homo sapiens	85-89
27974345-0	2017	Growth Differentiation Factor 15 as a Novel Biomarker for Metformin.	Metformin	58-67	growth differentiation factor 15	Homo sapiens	0-32
27974345-5	2017	RESULTS: Growth differentiation factor 15 (GDF15) was strongly linked to metformin, such that the odds of metformin use per SD increase in level varied from 3.73 (95% CI 3.40, 4.09) to 3.94 (95% CI 3.59, 4.33) depending on the other included variables.	Metformin	73-82	growth differentiation factor 15	Homo sapiens	9-41
27974345-5	2017	RESULTS: Growth differentiation factor 15 (GDF15) was strongly linked to metformin, such that the odds of metformin use per SD increase in level varied from 3.73 (95% CI 3.40, 4.09) to 3.94 (95% CI 3.59, 4.33) depending on the other included variables.	Metformin	73-82	growth differentiation factor 15	Homo sapiens	43-48
27974345-5	2017	RESULTS: Growth differentiation factor 15 (GDF15) was strongly linked to metformin, such that the odds of metformin use per SD increase in level varied from 3.73 (95% CI 3.40, 4.09) to 3.94 (95% CI 3.59, 4.33) depending on the other included variables.	Metformin	106-115	growth differentiation factor 15	Homo sapiens	9-41
27974345-5	2017	RESULTS: Growth differentiation factor 15 (GDF15) was strongly linked to metformin, such that the odds of metformin use per SD increase in level varied from 3.73 (95% CI 3.40, 4.09) to 3.94 (95% CI 3.59, 4.33) depending on the other included variables.	Metformin	106-115	growth differentiation factor 15	Homo sapiens	43-48
27974345-7	2017	A 1.64 ng/mL higher GDF15 level predicted a 188-mg higher metformin dose (P &lt; 0.0001).	Metformin	58-67	growth differentiation factor 15	Homo sapiens	20-25
27974345-8	2017	CONCLUSIONS: GDF15 levels are a biomarker for the use of metformin in people with dysglycemia, and its concentration reflects the dose of metformin.	Metformin	57-66	growth differentiation factor 15	Homo sapiens	13-18
27974345-8	2017	CONCLUSIONS: GDF15 levels are a biomarker for the use of metformin in people with dysglycemia, and its concentration reflects the dose of metformin.	Metformin	138-147	growth differentiation factor 15	Homo sapiens	13-18
28093504-8	2017	This insulin-independent state was confirmed by response to oral antihyperglycemic drugs, metformin and glipizide, which resolved glucose intolerance and extended survival compared with guinea pigs with uncontrolled diabetes.	Metformin	90-99	insulin	Cavia porcellus	5-12
27743302-0	2017	Effect of lifestyle interventions with or without metformin therapy on serum levels of osteoprotegerin and receptor activator of nuclear factor kappa B ligand in patients with prediabetes.	Metformin	50-59	TNF superfamily member 11	Homo sapiens	107-158
27128966-0	2017	Metformin induces degradation of cyclin D1 via AMPK/GSK3beta axis in ovarian cancer.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	47-51
27128966-3	2017	Here, we first describe that the anti-cancer effect of metformin is mediated by cyclin D1 deregulation via AMPK/GSK3beta axis in ovarian cancer cells.	Metformin	55-64	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	107-111
27128966-8	2017	The activation of GSK3beta correlated with the inhibitory phosphorylation by Akt as well as p70S6K through AMPK activation in response to metformin.	Metformin	138-147	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	107-111
27128966-9	2017	These findings suggested that the anticancer effects of metformin was induced due to cyclin D1 degradation via AMPK/GSK3beta signaling axis that involved the ubiquitin/proteasome pathway specifically in ovarian cancer cells.	Metformin	56-65	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	111-115
30562872-5	2017	Metformin increases the glycolysis efficiency, resulting in the conversion of CD8TIL to more active effector memory to fight against cancers.	Metformin	0-9	CD8a molecule	Homo sapiens	78-81
28145471-0	2017	Synergistic effects of metformin with liraglutide against endothelial dysfunction through GLP-1 receptor and PKA signalling pathway.	Metformin	23-32	glucagon-like peptide 1 receptor	Mus musculus	90-104
28145471-6	2017	Metformin upregulated GLP-1 receptor (GLP-1R) level and protein kinase A (PKA) phosphorylation.	Metformin	0-9	glucagon-like peptide 1 receptor	Mus musculus	22-36
28145471-6	2017	Metformin upregulated GLP-1 receptor (GLP-1R) level and protein kinase A (PKA) phosphorylation.	Metformin	0-9	glucagon-like peptide 1 receptor	Mus musculus	38-44
28145471-8	2017	Furthermore, AMPK inhibitor compound C abolished the metformin-mediated upregulation of GLP-1R level and PKA phosphorylation.	Metformin	53-62	glucagon-like peptide 1 receptor	Mus musculus	88-94
28145471-10	2017	Moreover, metformin stimulates GLP-1R and PKA signalling via AMPK-dependent pathway, which may account for its synergistic protective effects with liraglutide.	Metformin	10-19	glucagon-like peptide 1 receptor	Mus musculus	31-37
28249909-6	2017	Data mining of the National Library of Medicine"s MEDLINE Database and Ingenuity Pathway analysis revealed agents of relatively low toxicity-melatonin, metformin, curcumin and sulforaphane-that are capable of inhibiting directly or pharmacogenomically one or both of the SIRT1 and EZH2 pathways and should, in a combinatorial fashion, remove the block in differentiation and decrease the proliferation of the B-cell ALL lymphoblasts.	Metformin	152-161	sirtuin 1	Homo sapiens	271-276
28042775-6	2017	RESULTS: There was a lower protein expression of ROCK-1, vimentin, CD44 and CD24 in both cell lines after treatment with metformin and Y27632.	Metformin	121-130	CD44 molecule (Indian blood group)	Homo sapiens	67-71
28546950-2	2017	SLC47A1 (MATE1) and SLC47A2 (MATE2) are major efflux transporters involved in the hepatic and renal excretion of many cationic drugs including metformin.	Metformin	143-152	solute carrier family 47 member 1	Homo sapiens	0-7
28546950-2	2017	SLC47A1 (MATE1) and SLC47A2 (MATE2) are major efflux transporters involved in the hepatic and renal excretion of many cationic drugs including metformin.	Metformin	143-152	solute carrier family 47 member 1	Homo sapiens	9-14
27803295-10	2017	In ex vivo tumour slices, metformin treatment led to increased necrosis, decreased cyclin D1 and increased carbonic anhydrase-9 (CA-9).	Metformin	26-35	cyclin D1	Mus musculus	83-92
28002460-12	2016	Consistently, in Caco-2 cells, metformin promoted claudin-3 and E-cadherin assembly and mitigated TNF-alpha-induced fragmentation of tight junction proteins.	Metformin	31-40	claudin 3	Homo sapiens	50-59
27613809-8	2016	Our results suggest that targeting Mfn1 could provide novel avenues to ameliorate glucose homeostasis in obese patients and improve the effectiveness of metformin.	Metformin	153-162	mitofusin 1	Homo sapiens	35-39
27562556-3	2016	(2015, Metformin ameliorates acetaminophen hepatotoxicity via Gadd45beta-dependent regulation of JNK signaling in mice.	Metformin	7-16	mitogen-activated protein kinase 8	Mus musculus	97-100
27791206-5	2016	We further identified that metformin down-regulates SOX2 expression in TMZ-resistant glioma cells, reduces neurosphere formation capacity of glioblastoma cells, and inhibits GBM xenograft growth in vivo.	Metformin	27-36	SRY-box transcription factor 2	Homo sapiens	52-56
27893782-8	2016	We determined co-treatment with metformin or sodium salicylate alone was successful in alleviating changes observed in feeding peptide mRNA regulation, whereas a preventative pre-treatment with metformin and sodium salicylate together was able to alleviate palmitate- and TNFalpha-induced induction of NPY and/or AgRP mRNA levels.	Metformin	194-203	agouti related neuropeptide	Homo sapiens	313-317
27904436-6	2016	RESULTS: We found that metformin reduced the levels of IL-6 in blood and MCP-1 in urine, but increased IL-10 levels in blood of patients with type 2 diabetes.	Metformin	23-32	interleukin 10	Homo sapiens	103-108
27904436-9	2016	When the patients were stratified based on the durations and doses of metformin, we found that there was only change (i.e., increase) in serum IL-10 levels in patients with metformin for more than 1 year compared to treatment for less than 1 year.	Metformin	70-79	interleukin 10	Homo sapiens	143-148
27904436-9	2016	When the patients were stratified based on the durations and doses of metformin, we found that there was only change (i.e., increase) in serum IL-10 levels in patients with metformin for more than 1 year compared to treatment for less than 1 year.	Metformin	173-182	interleukin 10	Homo sapiens	143-148
27760406-7	2016	The combination of 6-BT with metformin resulted in significant cytotoxicity (60-70%) in monocytic AML cell lines and was associated with inhibition of FLT3-ITD activated STAT5 and reduced c-Myc and GLUT-1 expression.	Metformin	29-38	solute carrier family 2 member 1	Homo sapiens	198-204
27787519-8	2016	In addition, metformin was shown to promote the expression of anabolic genes such as Col2a1 and Acan expression while inhibiting the expression of catabolic genes such as Mmp3 and Adamts5 in nucleus pulposus cells.	Metformin	13-22	matrix metallopeptidase 3	Rattus norvegicus	171-175
27782167-7	2016	Even though exposure of metformin in the kidney was severely decreased in OCT1/2-/- mice when evaluated with [11C]-Metformin and PET/MRI, we found that the protective effects of metformin were OCT1/2 independent when tested in this model.	Metformin	24-33	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	74-78
27782167-7	2016	Even though exposure of metformin in the kidney was severely decreased in OCT1/2-/- mice when evaluated with [11C]-Metformin and PET/MRI, we found that the protective effects of metformin were OCT1/2 independent when tested in this model.	Metformin	24-33	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	74-80
27782167-7	2016	Even though exposure of metformin in the kidney was severely decreased in OCT1/2-/- mice when evaluated with [11C]-Metformin and PET/MRI, we found that the protective effects of metformin were OCT1/2 independent when tested in this model.	Metformin	178-187	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	74-78
27782167-7	2016	Even though exposure of metformin in the kidney was severely decreased in OCT1/2-/- mice when evaluated with [11C]-Metformin and PET/MRI, we found that the protective effects of metformin were OCT1/2 independent when tested in this model.	Metformin	178-187	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	74-80
28163738-0	2016	Allele frequency and genotype distribution of a common variant in the 3 -untranslated region of the SLC22A3 gene in patients with type 2 diabetes: Association with response to metformin.	Metformin	176-185	solute carrier family 22 member 3	Homo sapiens	100-107
28163738-1	2016	BACKGROUND: Organic cation transporter 3 (OCT3) is an excellent transporter for metformin, which is used as first-line therapy for type 2 diabetes (T2D).	Metformin	80-89	OCTN3	Homo sapiens	12-40
28163738-1	2016	BACKGROUND: Organic cation transporter 3 (OCT3) is an excellent transporter for metformin, which is used as first-line therapy for type 2 diabetes (T2D).	Metformin	80-89	OCTN3	Homo sapiens	42-46
28163738-2	2016	OCT3 genetic variants may influence the clinical response to metformin.	Metformin	61-70	OCTN3	Homo sapiens	0-4
28163738-3	2016	This study aimed to determine the genotype and allele frequency of OCT3-564G&gt;A (rs3088442) variant and its role in the glycemic response to metformin in patients with newly diagnosed T2D.	Metformin	143-152	OCTN3	Homo sapiens	67-71
27450486-0	2016	The paraoxonase 1 (PON1), platelet-activating factor acetylohydrolase (PAF-AH) and dimethylarginine dimethylaminohydrolase (DDAH) activity in the metformin treated normal and diabetic rats.	Metformin	146-155	paraoxonase 1	Rattus norvegicus	4-17
27450486-0	2016	The paraoxonase 1 (PON1), platelet-activating factor acetylohydrolase (PAF-AH) and dimethylarginine dimethylaminohydrolase (DDAH) activity in the metformin treated normal and diabetic rats.	Metformin	146-155	paraoxonase 1	Rattus norvegicus	19-23
27450486-2	2016	The present study was undertaken to determine whether the known cardio-protective effects of metformin are linked to its potential ability to affect activities of HDL"s paraoxonase (PON1) and platelet activating factor acetylohydrolase (PAF-AH) or via its interaction with the asymmetric dimethylarginine (ADMA)- dimethylarginine dimethylaminohydrolase (DDAH) axis.	Metformin	93-102	paraoxonase 1	Rattus norvegicus	182-186
27450486-6	2016	In STZ-induced diabetic rats the long-term administration of metformin normalized reduced PON1 activity assayed toward paraoxon (+42.5%, P&lt;0.05), phenyl acetate (+22.35%, P&lt;0.05) and gamma-decanolactone (+108.0%, P&lt;0.01), without affecting elevated PAF-AH activity in the plasma.	Metformin	61-70	paraoxonase 1	Rattus norvegicus	90-94
27450486-8	2016	Additionally metformin administration caused the increase in PON1 activity in the liver (+29.2%, P&lt;0.01) accompanied by the reduction in the lipid peroxidation (-59.8%, P&lt;0.001).	Metformin	13-22	paraoxonase 1	Rattus norvegicus	61-65
27450486-11	2016	Metformin might also exert its effect against diabetic complications by improving DDAH activity in the kidney and increasing PON1 activity in the liver.	Metformin	0-9	paraoxonase 1	Rattus norvegicus	125-129
27276511-0	2016	Metformin and resveratrol inhibit Drp1-mediated mitochondrial fission and prevent ER stress-associated NLRP3 inflammasome activation in the adipose tissue of diabetic mice.	Metformin	0-9	collapsin response mediator protein 1	Mus musculus	34-38
27276511-4	2016	RESULTS: Metformin and resveratrol inhibited ROS-associated mitochondrial fission by upregulating Drp1 phosphorylation (Ser 637) in an AMPK-dependent manner, and then suppressed ER stress indicated by dephosphorylation of IRE1alpha and eIF2alpha in the adipose tissue.	Metformin	9-18	collapsin response mediator protein 1	Mus musculus	98-102
27276511-6	2016	CONCLUSION: Metformin and resveratrol protected mitochondrial integrity by inhibiting Drp1 activity and prevented NLRP3 inflammasome activation by suppressing ER stress, and thereby protected adipose function from high glucose insult.	Metformin	12-21	collapsin response mediator protein 1	Mus musculus	86-90
26960058-0	2016	Metformin pretreatment enhanced learning and memory in cerebral forebrain ischaemia: the role of the AMPK/BDNF/P70SK signalling pathway.	Metformin	0-9	brain-derived neurotrophic factor	Rattus norvegicus	106-110
26960058-9	2016	Pretreatment with metformin in I/R animals reduced levels of pro-BDNF compared with the I/R group (p &lt; 0.001) but increased that compared with the sham group (p &lt; 0.001).	Metformin	18-27	brain-derived neurotrophic factor	Rattus norvegicus	65-69
26960058-12	2016	Conclusion Short-term memory in ischaemic rats treated with metformin increased step-through latency; sensory-motor evaluation was applied and a group of ischaemia rats that were pretreated with metformin showed high levels of BDNF, P70S6K that seemed to be due to increasing AMPK.	Metformin	60-69	brain-derived neurotrophic factor	Rattus norvegicus	227-231
26960058-12	2016	Conclusion Short-term memory in ischaemic rats treated with metformin increased step-through latency; sensory-motor evaluation was applied and a group of ischaemia rats that were pretreated with metformin showed high levels of BDNF, P70S6K that seemed to be due to increasing AMPK.	Metformin	195-204	brain-derived neurotrophic factor	Rattus norvegicus	227-231
27688041-5	2016	In addition, an inhibitory effect of AMPK activators metformin and AICAR on BMP6-mediated hepcidin gene expression was significantly attenuated by ablation of SHP expression.	Metformin	53-62	hepcidin antimicrobial peptide	Mus musculus	90-98
27688041-7	2016	Finally, overexpression of SHP and metformin treatment of BMP6 stimulated mice substantially restored hepcidin expression and serum iron to baseline levels.	Metformin	35-44	hepcidin antimicrobial peptide	Mus musculus	102-110
27643646-8	2016	Metformin reduced EMT in the cell lines and regulated the expression of the EMT-related epithelial markers, E-cadherin and Pan-keratin; the mesenchymal markers, N-cadherin, fibronectin, and vimentin; and the EMT drivers, Twist-1, snail-1, and ZEB-1.	Metformin	0-9	cadherin 2	Homo sapiens	161-171
27643646-8	2016	Metformin reduced EMT in the cell lines and regulated the expression of the EMT-related epithelial markers, E-cadherin and Pan-keratin; the mesenchymal markers, N-cadherin, fibronectin, and vimentin; and the EMT drivers, Twist-1, snail-1, and ZEB-1.	Metformin	0-9	zinc finger E-box binding homeobox 1	Homo sapiens	243-248
27350110-0	2016	L503F variant of carnitine/organic cation transporter 1 efficiently transports metformin and other biguanides.	Metformin	79-88	solute carrier family 22 member 4	Homo sapiens	17-55
27350110-2	2016	The purpose of this study was to clarify the transport activities of two major OCTN1 variants, L503F and I306T, for gabapentin and three biguanide drugs, metformin, buformin and phenformin.	Metformin	154-163	solute carrier family 22 member 4	Homo sapiens	79-84
27350110-5	2016	Uptake of biguanides, especially metformin, mediated by OCTN1 variant L503F, which is commonly found in Caucasians, was much higher than that by the wild-type transporter (WT-OCTN1).	Metformin	33-42	solute carrier family 22 member 4	Homo sapiens	56-61
27350110-5	2016	Uptake of biguanides, especially metformin, mediated by OCTN1 variant L503F, which is commonly found in Caucasians, was much higher than that by the wild-type transporter (WT-OCTN1).	Metformin	33-42	solute carrier family 22 member 4	Homo sapiens	175-180
27350110-6	2016	Cytotoxicity of metformin was also greater in HEK293 cells expressing the L503F variant, compared with WT-OCTN1.	Metformin	16-25	solute carrier family 22 member 4	Homo sapiens	106-111
30645839-1	2016	Objective To observe the effect and clinical efficacy of Qilin Pill (QP) combined met- formin on matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF) , hepatocyte growth factor (HGF) , sex hormones, insulin resistance (IR) related indicators in polycystic ovaries induced infertility women.	Metformin	82-93	matrix metallopeptidase 9	Homo sapiens	97-123
27259235-0	2016	Germline BRCA1 mutation reprograms breast epithelial cell metabolism towards mitochondrial-dependent biosynthesis: evidence for metformin-based "starvation" strategies in BRCA1 carriers.	Metformin	128-137	BRCA1 DNA repair associated	Homo sapiens	9-14
27259235-0	2016	Germline BRCA1 mutation reprograms breast epithelial cell metabolism towards mitochondrial-dependent biosynthesis: evidence for metformin-based "starvation" strategies in BRCA1 carriers.	Metformin	128-137	BRCA1 DNA repair associated	Homo sapiens	171-176
27259235-6	2016	The anti-diabetic biguanide metformin "reversed" the metabolomic signature and anabolic phenotype of BRCA1 one-hit cells by shutting down mitochondria-driven generation of precursors for lipogenic pathways and reducing the BCAA pool for protein synthesis and TCA fueling.	Metformin	28-37	BRCA1 DNA repair associated	Homo sapiens	101-106
27648126-4	2016	However, 0.5 mM metformin treatment protected bEnd3 endothelial cell monolayer from hypoxia or VEGF-induced permeability, which was correlated with increased expression of tight junction proteins.	Metformin	16-25	BEN domain containing 3	Mus musculus	46-51
27648126-4	2016	However, 0.5 mM metformin treatment protected bEnd3 endothelial cell monolayer from hypoxia or VEGF-induced permeability, which was correlated with increased expression of tight junction proteins.	Metformin	16-25	vascular endothelial growth factor A	Mus musculus	95-99
27648126-5	2016	Furthermore, metformin treatment attenuated AQP4 protein expression in cultured astrocytes.	Metformin	13-22	aquaporin 4	Mus musculus	44-48
27648126-9	2016	Furthermore, since the formation of cytotoxic edema and AQP4 expression was positively correlated, our results indicated that metformin may reduce the formation of cytotoxic edema.	Metformin	126-135	aquaporin 4	Mus musculus	56-60
27648126-10	2016	However, given that AQP4 plays a key role in the elimination of cerebral edema, attenuation of AQP4 expression by metformin may reduce the elimination of cerebral edema.	Metformin	114-123	aquaporin 4	Mus musculus	95-99
27488947-0	2016	Metformin Enhances the Therapy Effects of Anti-IGF-1R mAb Figitumumab to NSCLC.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	47-53
27488947-7	2016	Metformin could target IGF-1R signaling pathway by attenuating PI3K/AKT and MEK/ERK signaling pathways and down-regulating IGF-1R.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	23-29
27488947-7	2016	Metformin could target IGF-1R signaling pathway by attenuating PI3K/AKT and MEK/ERK signaling pathways and down-regulating IGF-1R.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	123-129
27488947-8	2016	Finally, we found that combining metformin with CP could further induce IGF-1R down-regulation and was more effective to target NSCLC cells.	Metformin	33-42	insulin like growth factor 1 receptor	Homo sapiens	72-78
27391065-4	2016	Metformin also triggers the apoptotic pathway, shown by the decreased expression of Bcl-2 and HSP27, HSP60 and HSP70, and enhanced membrane exposure of annexin V, resulting in activation of caspase-3 apoptotic effector.	Metformin	0-9	heat shock protein family D (Hsp60) member 1	Homo sapiens	101-106
27391065-4	2016	Metformin also triggers the apoptotic pathway, shown by the decreased expression of Bcl-2 and HSP27, HSP60 and HSP70, and enhanced membrane exposure of annexin V, resulting in activation of caspase-3 apoptotic effector.	Metformin	0-9	heat shock protein family A (Hsp70) member 4	Homo sapiens	111-116
27391065-5	2016	Metformin interferes with the proliferative autocrine loop of IGF2/IGF-1R, which supports adrenal cancer growth.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	67-73
27509335-5	2016	Moreover, metformin induces mitochondrial dysfunction and cell death by affecting the level and conformation of Translocase of the Outer Membrane 40 (TOM40), voltage-dependent anion-selective channels 1 (VDAC1) and hexokinase I (HKI), proteins involved in mitochondrial transport of molecules, including Abeta.	Metformin	10-19	hexokinase 1	Mus musculus	215-227
27509335-5	2016	Moreover, metformin induces mitochondrial dysfunction and cell death by affecting the level and conformation of Translocase of the Outer Membrane 40 (TOM40), voltage-dependent anion-selective channels 1 (VDAC1) and hexokinase I (HKI), proteins involved in mitochondrial transport of molecules, including Abeta.	Metformin	10-19	hexokinase 1	Mus musculus	229-232
27174003-9	2016	Treatment with metformin reduced the expression of GFAP, Iba-1 (astrocyte and microglial markers) and the inflammation markers (p-IKB, IL-1 and VEGF), while enhancing p-AMPK and eNOS levels and increasing neuronal survival (Fox-1 and NeuN).	Metformin	15-24	nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, beta	Mus musculus	130-133
27174003-9	2016	Treatment with metformin reduced the expression of GFAP, Iba-1 (astrocyte and microglial markers) and the inflammation markers (p-IKB, IL-1 and VEGF), while enhancing p-AMPK and eNOS levels and increasing neuronal survival (Fox-1 and NeuN).	Metformin	15-24	vascular endothelial growth factor A	Mus musculus	144-148
27282964-14	2016	CONCLUSION: Combining PARP inhibitors with metformin enhances its anti-proliferative activity in BRCA mutant ovarian cancer cells.	Metformin	43-52	BRCA1 DNA repair associated	Homo sapiens	97-101
27296990-7	2016	Furthermore, metformin increased rat lung AMP-activated protein kinase signaling, decreased lung and circulating estrogen levels, levels of aromatase, the estrogen metabolizing enzyme; cytochrome P450 1B1 and its transcription factor; the aryl hydrocarbon receptor.	Metformin	13-22	cytochrome P450, family 1, subfamily b, polypeptide 1	Rattus norvegicus	185-204
27296990-7	2016	Furthermore, metformin increased rat lung AMP-activated protein kinase signaling, decreased lung and circulating estrogen levels, levels of aromatase, the estrogen metabolizing enzyme; cytochrome P450 1B1 and its transcription factor; the aryl hydrocarbon receptor.	Metformin	13-22	aryl hydrocarbon receptor	Rattus norvegicus	239-264
26939902-0	2016	Metformin and AICAR regulate NANOG expression via the JNK pathway in HepG2 cells independently of AMPK.	Metformin	0-9	Nanog homeobox	Homo sapiens	29-34
26939902-5	2016	In this study, we used the HepG2 cell line and found that metformin/AICAR downregulated NANOG expression with decreased cell viability and enhanced chemosensitivity to 5-fluorouracil (5-FU).	Metformin	58-67	Nanog homeobox	Homo sapiens	88-93
26939902-6	2016	Moreover, metformin/AICAR inhibited c-Jun N-terminal kinase (JNK) activity, and blockade of either the JNK MAPK pathway or knockdown of JNK1 gene expression reduced NANOG levels.	Metformin	10-19	Nanog homeobox	Homo sapiens	165-170
26939902-7	2016	The upregulation of NANOG and phospho-JNK by basic fibroblast growth factor (bFGF) was abrogated by metformin/AICAR.	Metformin	100-109	Nanog homeobox	Homo sapiens	20-25
26939902-8	2016	Additionally, although transient upregulation of NANOG within 2 h of treatment with metformin/AICAR was concordant with both JNK and AMPK activation, increased NANOG expression with activation of JNK was also observed following AMPK inhibition with compound C. Taken together, our data suggest that metformin/AICAR regulate NANOG expression via the JNK MAPK pathway in HepG2 cells independently of AMPK, and that this JNK/NANOG signaling pathway may offer new therapeutic strategies for the treatment of HCC.	Metformin	84-93	Nanog homeobox	Homo sapiens	49-54
26939902-8	2016	Additionally, although transient upregulation of NANOG within 2 h of treatment with metformin/AICAR was concordant with both JNK and AMPK activation, increased NANOG expression with activation of JNK was also observed following AMPK inhibition with compound C. Taken together, our data suggest that metformin/AICAR regulate NANOG expression via the JNK MAPK pathway in HepG2 cells independently of AMPK, and that this JNK/NANOG signaling pathway may offer new therapeutic strategies for the treatment of HCC.	Metformin	84-93	Nanog homeobox	Homo sapiens	160-165
26939902-8	2016	Additionally, although transient upregulation of NANOG within 2 h of treatment with metformin/AICAR was concordant with both JNK and AMPK activation, increased NANOG expression with activation of JNK was also observed following AMPK inhibition with compound C. Taken together, our data suggest that metformin/AICAR regulate NANOG expression via the JNK MAPK pathway in HepG2 cells independently of AMPK, and that this JNK/NANOG signaling pathway may offer new therapeutic strategies for the treatment of HCC.	Metformin	84-93	Nanog homeobox	Homo sapiens	160-165
26939902-8	2016	Additionally, although transient upregulation of NANOG within 2 h of treatment with metformin/AICAR was concordant with both JNK and AMPK activation, increased NANOG expression with activation of JNK was also observed following AMPK inhibition with compound C. Taken together, our data suggest that metformin/AICAR regulate NANOG expression via the JNK MAPK pathway in HepG2 cells independently of AMPK, and that this JNK/NANOG signaling pathway may offer new therapeutic strategies for the treatment of HCC.	Metformin	84-93	Nanog homeobox	Homo sapiens	160-165
26939902-8	2016	Additionally, although transient upregulation of NANOG within 2 h of treatment with metformin/AICAR was concordant with both JNK and AMPK activation, increased NANOG expression with activation of JNK was also observed following AMPK inhibition with compound C. Taken together, our data suggest that metformin/AICAR regulate NANOG expression via the JNK MAPK pathway in HepG2 cells independently of AMPK, and that this JNK/NANOG signaling pathway may offer new therapeutic strategies for the treatment of HCC.	Metformin	299-308	Nanog homeobox	Homo sapiens	49-54
27467571-2	2016	Animal and retrospective human studies indicate that Metformin treatment is neuroprotective in Parkinson"s Disease (PD), although the neuroprotective mechanism is unknown, numerous studies suggest the beneficial effects on glucose homeostasis may be through AMPK activation.	Metformin	53-62	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	258-262
26849413-12	2016	In vivo metformin (100 mg/Kg) in drinking water for 60 days induced Abcd2 levels and mitochondrial oxidative phosphorylation protein levels in the brain and spinal cord of Abcd1-KO mice.	Metformin	8-17	ATP-binding cassette, sub-family D (ALD), member 1	Mus musculus	172-177
27019345-1	2016	Metformin is used as a probe for OCT2 mediated transport when investigating possible DDIs with new chemical entities.	Metformin	0-9	POU class 2 homeobox 2	Homo sapiens	33-37
27019345-4	2016	The models were used to simulate inhibition of the MATE1, MATE2-K, OCT1 and OCT2 mediated transport of metformin by cimetidine.	Metformin	103-112	solute carrier family 47 member 1	Homo sapiens	51-56
27019345-4	2016	The models were used to simulate inhibition of the MATE1, MATE2-K, OCT1 and OCT2 mediated transport of metformin by cimetidine.	Metformin	103-112	POU class 2 homeobox 2	Homo sapiens	76-80
27019345-7	2016	An alternative description of metformin renal transport by OCT1 and OCT2, incorporating electrochemical modulation of the rate of metformin uptake together with 8-18-fold decreases in cimetidine Ki"s for OCTs and MATEs, allowed recovery of the extent of the observed effect of cimetidine on metformin AUC.	Metformin	30-39	POU class 2 homeobox 2	Homo sapiens	68-72
27144340-3	2016	Metformin, a widely used antidiabetic agent, may reverse crizotinib resistance through inhibition of IGF-1R signaling.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	101-107
27144340-5	2016	Metformin reduced IGF-1R signaling activation in crizotinib-resistant cells.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	18-24
27145454-11	2016	The impeded cancer progression was due to the inhibitory effect of metformin on STAT3-ERK-vimentin and fibronectin-integrin signaling to decrease tumor cell invasion and de-differentiation.	Metformin	67-76	vimentin	Mus musculus	90-98
27326258-4	2016	It"s important to know if LRCC, a novel class of CSC, are relatively resistant to metformin, unlike other types of CSC.	Metformin	82-91	fumarate hydratase	Homo sapiens	26-30
27326258-5	2016	As metformin inhibits the Sorafenib-Target-Protein (STP) PI3K, and LRCC are newly described CSC, we undertook this study to test the effects of Metformin on Sorafenib-treated HCC and HCC-derived-LRCC.	Metformin	3-12	thyroid hormone receptor interactor 10	Homo sapiens	26-50
27326258-5	2016	As metformin inhibits the Sorafenib-Target-Protein (STP) PI3K, and LRCC are newly described CSC, we undertook this study to test the effects of Metformin on Sorafenib-treated HCC and HCC-derived-LRCC.	Metformin	3-12	thyroid hormone receptor interactor 10	Homo sapiens	52-55
27326258-11	2016	Concomitantly, Metformin up-regulated pluripotency, Wnt, Notch and SHH pathways genes in LRCC vs. non-LRCC.	Metformin	15-24	fumarate hydratase	Homo sapiens	89-93
27326258-11	2016	Concomitantly, Metformin up-regulated pluripotency, Wnt, Notch and SHH pathways genes in LRCC vs. non-LRCC.	Metformin	15-24	fumarate hydratase	Homo sapiens	102-106
27326258-13	2016	However, in contradistinction to reports on other types of CSC, Metformin is less effective against HCC-derived-CSC LRCC.	Metformin	64-73	fumarate hydratase	Homo sapiens	116-120
27326258-18	2016	These may significantly contribute to the understanding of Metformin"s anti-cancer effects and the development of novel drugs targeting the relatively resistant LRCC.	Metformin	59-68	fumarate hydratase	Homo sapiens	161-165
26990999-0	2016	Metformin-mediated increase in DICER1 regulates microRNA expression and cellular senescence.	Metformin	0-9	dicer 1, ribonuclease type III	Mus musculus	31-37
26990999-4	2016	Here, we show that metformin treatment increases the levels of the microRNA-processing protein DICER1 in mice and in humans with diabetes mellitus.	Metformin	19-28	dicer 1, ribonuclease type III	Mus musculus	95-101
26990999-5	2016	Our results indicate that metformin upregulates DICER1 through a post-transcriptional mechanism involving the RNA-binding protein AUF1.	Metformin	26-35	dicer 1, ribonuclease type III	Mus musculus	48-54
26990999-5	2016	Our results indicate that metformin upregulates DICER1 through a post-transcriptional mechanism involving the RNA-binding protein AUF1.	Metformin	26-35	heterogeneous nuclear ribonucleoprotein D	Mus musculus	130-134
26990999-6	2016	Treatment with metformin altered the subcellular localization of AUF1, disrupting its interaction with DICER1 mRNA and rendering DICER1 mRNA stable, allowing DICER1 to accumulate.	Metformin	15-24	heterogeneous nuclear ribonucleoprotein D	Mus musculus	65-69
26990999-6	2016	Treatment with metformin altered the subcellular localization of AUF1, disrupting its interaction with DICER1 mRNA and rendering DICER1 mRNA stable, allowing DICER1 to accumulate.	Metformin	15-24	dicer 1, ribonuclease type III	Mus musculus	103-109
26990999-6	2016	Treatment with metformin altered the subcellular localization of AUF1, disrupting its interaction with DICER1 mRNA and rendering DICER1 mRNA stable, allowing DICER1 to accumulate.	Metformin	15-24	dicer 1, ribonuclease type III	Mus musculus	129-135
26990999-6	2016	Treatment with metformin altered the subcellular localization of AUF1, disrupting its interaction with DICER1 mRNA and rendering DICER1 mRNA stable, allowing DICER1 to accumulate.	Metformin	15-24	dicer 1, ribonuclease type III	Mus musculus	129-135
26990999-7	2016	Consistent with the role of DICER1 in the biogenesis of microRNAs, we found differential patterns of microRNA expression in mice treated with metformin or caloric restriction, two proven life-extending interventions.	Metformin	142-151	dicer 1, ribonuclease type III	Mus musculus	28-34
26990999-9	2016	In agreement with these findings, treatment with metformin decreased cellular senescence in several senescence models in a DICER1-dependent manner.	Metformin	49-58	dicer 1, ribonuclease type III	Mus musculus	123-129
26990999-10	2016	Metformin lowered p16 and p21 protein levels and the abundance of inflammatory cytokines and oncogenes that are hallmarks of the senescence-associated secretory phenotype (SASP).	Metformin	0-9	cyclin-dependent kinase inhibitor 1A (P21)	Mus musculus	26-29
26990999-11	2016	These data lead us to hypothesize that changes in DICER1 levels may be important for organismal aging and to propose that interventions that upregulate DICER1 expression (e.g., metformin) may offer new pharmacotherapeutic approaches for age-related disease.	Metformin	177-186	dicer 1, ribonuclease type III	Mus musculus	152-158
27059094-7	2016	The increased gene expressions of TNF-alpha, IL-6, monocyte chemoattractant protein 1 and F4/80 were also down-regulated by metformin and resveratrol.	Metformin	124-133	chemokine (C-C motif) ligand 2	Mus musculus	51-85
27059094-7	2016	The increased gene expressions of TNF-alpha, IL-6, monocyte chemoattractant protein 1 and F4/80 were also down-regulated by metformin and resveratrol.	Metformin	124-133	adhesion G protein-coupled receptor E1	Mus musculus	90-95
27013659-12	2016	Using metformin, an activator of AMPK, we showed that AMPK activation-induced inhibition of hepatic lipid accumulation was accompanied by reduced expression of miR-291b-3p in the liver.	Metformin	6-15	microRNA 291b	Mus musculus	160-168
25994759-3	2016	RESULTS: Both metformin and ionizing radiation inhibited the expression of ME2, but not ME1, in HNSCC.	Metformin	14-23	malic enzyme 1	Homo sapiens	88-91
26784938-0	2016	The MATE1 rs2289669 polymorphism affects the renal clearance of metformin following ranitidine treatment.	Metformin	64-73	solute carrier family 47 member 1	Homo sapiens	4-9
26784938-1	2016	PURPOSE: Human multidrug and toxin extrusion member 1 (MATE1, SLC47A1) and Organic Cation Transporter 2 (OCT2, SLC22A2) play important roles in the renal elimination of various pharmacologic agents, including the anti-diabetic drug metformin.	Metformin	232-241	solute carrier family 47 member 1	Homo sapiens	15-53
26784938-1	2016	PURPOSE: Human multidrug and toxin extrusion member 1 (MATE1, SLC47A1) and Organic Cation Transporter 2 (OCT2, SLC22A2) play important roles in the renal elimination of various pharmacologic agents, including the anti-diabetic drug metformin.	Metformin	232-241	solute carrier family 47 member 1	Homo sapiens	55-60
26784938-1	2016	PURPOSE: Human multidrug and toxin extrusion member 1 (MATE1, SLC47A1) and Organic Cation Transporter 2 (OCT2, SLC22A2) play important roles in the renal elimination of various pharmacologic agents, including the anti-diabetic drug metformin.	Metformin	232-241	solute carrier family 47 member 1	Homo sapiens	62-69
26784938-2	2016	The goal of this study was to determine the association between metformin"s pharmacokinetics and pharmacodynamics and the genetic variants of MATE1 (rs2289669) and OCT2 (rs316019) before and after treatment with the potential MATE inhibitor, ranitidine.	Metformin	64-73	solute carrier family 47 member 1	Homo sapiens	142-147
26784938-5	2016	However, the renal clearance of metformin was significantly higher (15.2%) after ranitidine treatment in the MATE1 GG group compared with the MATE1 GA + AA group.	Metformin	32-41	solute carrier family 47 member 1	Homo sapiens	109-114
26784938-5	2016	However, the renal clearance of metformin was significantly higher (15.2%) after ranitidine treatment in the MATE1 GG group compared with the MATE1 GA + AA group.	Metformin	32-41	solute carrier family 47 member 1	Homo sapiens	142-147
26784938-6	2016	Only the effect of MATE1 on the renal clearance of metformin after ranitidine treatment was significant (b = -0.465, p &lt;= 0.05) after including demographic data and the OCT2 genotype in the model.	Metformin	51-60	solute carrier family 47 member 1	Homo sapiens	19-24
26784938-7	2016	CONCLUSION: Our study suggests that MATE1 rs2289669 may be a significant determinant in the renal clearance of metformin in the case of transporter-mediated drug interactions.	Metformin	111-120	solute carrier family 47 member 1	Homo sapiens	36-41
26706833-4	2016	Additionally, we assessed the added value of metformin as this drug may lower IGF1R stimulation.	Metformin	45-54	insulin like growth factor 1 receptor	Homo sapiens	78-83
27009398-0	2016	Metformin stimulates IGFBP-2 gene expression through PPARalpha in diabetic states.	Metformin	0-9	insulin-like growth factor binding protein 2	Mus musculus	21-28
27009398-3	2016	In this study, we demonstrate that metformin upregulates Igfbp-2 expression through the AMPK-Sirt1-PPARalpha cascade pathway.	Metformin	35-44	insulin-like growth factor binding protein 2	Mus musculus	57-64
27009398-5	2016	Upregulation of Igfbp-2 expression by metformin administration was disrupted by gene silencing of Ampk and Sirt1, and this phenomenon was not observed in Pparalpha-null mice.	Metformin	38-47	insulin-like growth factor binding protein 2	Mus musculus	16-23
27009398-8	2016	Taken together, these findings indicate that IGFBP-2 might be a new target of metformin action in diabetes and the metformin-AMPK-Sirt1-PPARalpha-IGFBP-2 network may provide a novel pathway that could be applied to ameliorate metabolic syndromes by controlling IGF-1 bioavailability.	Metformin	78-87	insulin-like growth factor binding protein 2	Mus musculus	45-52
27009398-8	2016	Taken together, these findings indicate that IGFBP-2 might be a new target of metformin action in diabetes and the metformin-AMPK-Sirt1-PPARalpha-IGFBP-2 network may provide a novel pathway that could be applied to ameliorate metabolic syndromes by controlling IGF-1 bioavailability.	Metformin	78-87	insulin-like growth factor binding protein 2	Mus musculus	146-153
27009398-8	2016	Taken together, these findings indicate that IGFBP-2 might be a new target of metformin action in diabetes and the metformin-AMPK-Sirt1-PPARalpha-IGFBP-2 network may provide a novel pathway that could be applied to ameliorate metabolic syndromes by controlling IGF-1 bioavailability.	Metformin	115-124	insulin-like growth factor binding protein 2	Mus musculus	146-153
26986624-0	2016	Cardiovascular Protective Effect of Metformin and Telmisartan: Reduction of PARP1 Activity via the AMPK-PARP1 Cascade.	Metformin	36-45	poly (ADP-ribose) polymerase family, member 1	Mus musculus	76-81
26986624-0	2016	Cardiovascular Protective Effect of Metformin and Telmisartan: Reduction of PARP1 Activity via the AMPK-PARP1 Cascade.	Metformin	36-45	poly (ADP-ribose) polymerase family, member 1	Mus musculus	104-109
26986624-4	2016	The results showed that metformin and telmisartan, but not glipizide and metoprolol, activated AMPK, which phosphorylated PARP1 Ser-177 in cultured ECs and the vascular wall of rodent models.	Metformin	24-33	poly (ADP-ribose) polymerase family, member 1	Mus musculus	122-127
27247792-8	2016	RESULTS: The data showed metformin, acarbose, and acarbose + metformin downregulated visfatin levels in diabetic rats, but only the reduction in metformin-treated rats was significant (162 +- 21.7, 195.66 +- 6.45 (ng/l), P = 0.001).	Metformin	25-34	nicotinamide phosphoribosyltransferase	Rattus norvegicus	85-93
27247792-8	2016	RESULTS: The data showed metformin, acarbose, and acarbose + metformin downregulated visfatin levels in diabetic rats, but only the reduction in metformin-treated rats was significant (162 +- 21.7, 195.66 +- 6.45 (ng/l), P = 0.001).	Metformin	61-70	nicotinamide phosphoribosyltransferase	Rattus norvegicus	85-93
27247792-8	2016	RESULTS: The data showed metformin, acarbose, and acarbose + metformin downregulated visfatin levels in diabetic rats, but only the reduction in metformin-treated rats was significant (162 +- 21.7, 195.66 +- 6.45 (ng/l), P = 0.001).	Metformin	61-70	nicotinamide phosphoribosyltransferase	Rattus norvegicus	85-93
26874027-0	2016	Metformin-induced protection against oxidative stress is associated with AKT/mTOR restoration in PC12 cells.	Metformin	0-9	mechanistic target of rapamycin kinase	Rattus norvegicus	77-81
26874027-2	2016	Pile of concrete evidence imply metformin as an Insulin sensitizer may enhance Akt/mTOR activity however the significance of Akt/mTOR recruitment has not yet been revealed in metformin induced neuroprotection against oxidative stress.	Metformin	32-41	mechanistic target of rapamycin kinase	Rattus norvegicus	83-87
26874027-4	2016	Metformin pretreated cells were then subjected to immunoblotting as well as real time PCR to find PI3K, Akt, mTOR and S6K concurrent transcriptional and post-transcriptional changes.	Metformin	0-9	mechanistic target of rapamycin kinase	Rattus norvegicus	109-113
26874027-5	2016	The proportions of phosphorylated to non-phosphorylated constituents of PI3K/Akt/mTOR/S6K were determined to address their activation upon metformin treatment.	Metformin	139-148	mechanistic target of rapamycin kinase	Rattus norvegicus	81-85
26874027-7	2016	Metformin induced protection concurred with elevated PI3K/Akt/mTOR/S6K activity as well as enhanced GSH levels.	Metformin	0-9	mechanistic target of rapamycin kinase	Rattus norvegicus	62-66
26874027-9	2016	SIGNIFICANCE: Taken together our experimentation supports the hypothesis that Akt/mTOR/S6K cascade may contribute to metformin alleviating effect.	Metformin	117-126	mechanistic target of rapamycin kinase	Rattus norvegicus	82-86
26874027-10	2016	The present work while highlighting metformin anti-oxidant characteristics, concludes that Akt/mTOR signaling might be central to the drug"s alleviating effects.	Metformin	36-45	mechanistic target of rapamycin kinase	Rattus norvegicus	95-99
26835874-0	2016	Trigonella foenum-graecum Seed Extract, 4-Hydroxyisoleucine, and Metformin Stimulate Proximal Insulin Signaling and Increase Expression of Glycogenic Enzymes and GLUT2 in HepG2 Cells.	Metformin	65-74	solute carrier family 2 member 2	Homo sapiens	162-167
26835874-8	2016	RESULTS: Under normo- and hyperglycemic conditions, FSE, 4-OH-Ile, insulin (100 ng/mL), and metformin (2 mM) caused a significant increase in phosphorylation of IR-beta, Akt, GSK-3alpha/beta, and GLUT2.	Metformin	92-101	solute carrier family 2 member 2	Homo sapiens	196-201
26708419-7	2016	Metformin inhibited the proliferation of Panc1, PK1 and PK9 cells in vitro.	Metformin	0-9	prokineticin 1	Homo sapiens	48-51
26708419-9	2016	In addition, metformin reduced the phosphorylation of epidermal growth factor receptor (EGFR), particularly the phosphorylation of EGFR at Tyr845, and insulin-like growth factor 1 receptor (IGF-1R) in vitro and in vivo.	Metformin	13-22	insulin like growth factor 1 receptor	Homo sapiens	151-188
26708419-9	2016	In addition, metformin reduced the phosphorylation of epidermal growth factor receptor (EGFR), particularly the phosphorylation of EGFR at Tyr845, and insulin-like growth factor 1 receptor (IGF-1R) in vitro and in vivo.	Metformin	13-22	insulin like growth factor 1 receptor	Homo sapiens	190-196
27180666-5	2016	The response to metformin treatment was associated with the genetic variants ATM and SLC47A1.	Metformin	16-25	solute carrier family 47 member 1	Homo sapiens	85-92
26887416-0	2016	Erratum to: NLK functions to maintain proliferation and stemness of NSCLC and is a target of metformin.	Metformin	93-102	nemo like kinase	Homo sapiens	12-15
26861446-0	2016	Metformin improves the angiogenic potential of human CD34+ cells co-incident with downregulating CXCL10 and TIMP1 gene expression and increasing VEGFA under hyperglycemia and hypoxia within a therapeutic window for myocardial infarction.	Metformin	0-9	C-X-C motif chemokine ligand 10	Homo sapiens	97-103
26861446-11	2016	In addition metformin, increased expression of STEAP family member 4 (STEAP4) under euglycemia, indicating an anti-inflammatory effect.	Metformin	12-21	STEAP4 metalloreductase	Homo sapiens	47-68
26861446-11	2016	In addition metformin, increased expression of STEAP family member 4 (STEAP4) under euglycemia, indicating an anti-inflammatory effect.	Metformin	12-21	STEAP4 metalloreductase	Homo sapiens	70-76
26861446-12	2016	CONCLUSIONS: Metformin has a dual effect by simultaneously increasing VEGFA and reducing CXCL10 and TIMP1 in CD34(+) cells in a model of the diabetic state combined with hypoxia.	Metformin	13-22	C-X-C motif chemokine ligand 10	Homo sapiens	89-95
26673006-0	2016	Metformin increases antitumor activity of MEK inhibitors through GLI1 downregulation in LKB1 positive human NSCLC cancer cells.	Metformin	0-9	GLI family zinc finger 1	Homo sapiens	65-69
26673006-4	2016	EXPERIMENTAL DESIGN: Since single agent metformin enhances proliferating signals through the RAS/RAF/MAPK pathway, and several MEK inhibitors (MEK-I) demonstrated clinical efficacy in combination with other agents in NSCLC, we tested the effects of metformin plus MEK-I (selumetinib or pimasertib) on proliferation, invasiveness, migration abilities in vitro and in vivo in LKB1 positive NSCLC models harboring KRAS wild type and mutated gene.	Metformin	40-49	KRAS proto-oncogene, GTPase	Homo sapiens	411-415
26673006-5	2016	RESULTS: The combination of metformin with MEK-I showed a strong anti-proliferative and proapoptotic effect in Calu-3, H1299, H358 and H1975 human NSCLC cell lines, independently from the KRAS mutational status.	Metformin	28-37	KRAS proto-oncogene, GTPase	Homo sapiens	188-192
26673006-7	2016	Metformin and MEK-Is combinations also decreased the production and activity of MMP-2 and MMP-9 by reducing the NF-jB (p65) binding to MMP-2 and MMP-9 promoters.	Metformin	0-9	matrix metallopeptidase 9	Homo sapiens	90-95
26673006-7	2016	Metformin and MEK-Is combinations also decreased the production and activity of MMP-2 and MMP-9 by reducing the NF-jB (p65) binding to MMP-2 and MMP-9 promoters.	Metformin	0-9	matrix metallopeptidase 9	Homo sapiens	145-150
26673006-8	2016	CONCLUSIONS: Metformin potentiates the antitumor activity of MEK-Is in human LKB1-wild-type NSCLC cell lines, independently from the KRAS mutational status, through GLI1 downregulation and by reducing the NF-jB (p65)-mediated transcription of MMP-2 and MMP-9.	Metformin	13-22	GLI family zinc finger 1	Homo sapiens	165-169
26673006-8	2016	CONCLUSIONS: Metformin potentiates the antitumor activity of MEK-Is in human LKB1-wild-type NSCLC cell lines, independently from the KRAS mutational status, through GLI1 downregulation and by reducing the NF-jB (p65)-mediated transcription of MMP-2 and MMP-9.	Metformin	13-22	matrix metallopeptidase 9	Homo sapiens	253-258
26608911-1	2016	We have previously shown that CD4(+) T cells from B6.Sle1Sle2.Sle3 lupus mice and patients present a high cellular metabolism, and a treatment combining 2-deoxy-D-glucose, which inhibits glucose metabolism, and metformin, which inhibits oxygen consumption, normalized lupus T cell functions in vitro and reverted disease in mice.	Metformin	211-220	CD4 antigen	Mus musculus	30-33
32309575-3	2015	Indirect AMPK activators, such as resveratrol, metformin and exercise, are currently in clinical trials for studying their impact on human aging-related characteristics, tissue homeostasis and metabolic dysfunctions.	Metformin	47-56	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	9-13
26718286-0	2015	Inhibitory effects of metformin at low concentration on epithelial-mesenchymal transition of CD44(+)CD117(+) ovarian cancer stem cells.	Metformin	22-31	CD44 molecule (Indian blood group)	Homo sapiens	93-97
26718286-12	2015	Low concentrations of metformin inhibited the secondary and the tertiary tumor sphere formation, decreased SKOV3 and primary ovarian tumor xenograft growth, enhanced the anticancer effect of cisplatin, and lowered the proportion of CD44(+)CD117(+) CSCs in the xenograft tissue.	Metformin	22-31	CD44 molecule (Indian blood group)	Homo sapiens	232-236
26718286-13	2015	Metformin was also associated with a reduction of snail2, twist, and vimentin in CD44(+)CD117(+) ovarian CSCs in vivo.	Metformin	0-9	snail family transcriptional repressor 2	Homo sapiens	50-56
26718286-13	2015	Metformin was also associated with a reduction of snail2, twist, and vimentin in CD44(+)CD117(+) ovarian CSCs in vivo.	Metformin	0-9	CD44 molecule (Indian blood group)	Homo sapiens	81-85
26718286-14	2015	CONCLUSIONS: Our results implicate that metformin at low dose inhibits selectively CD44(+)CD117(+) ovarian CSCs through inhibition of EMT and potentiates the effect of cisplatin.	Metformin	40-49	CD44 molecule (Indian blood group)	Homo sapiens	83-87
26497205-6	2015	The effect of metformin on EGFR-TKI-induced exacerbation of pulmonary fibrosis was examined in vitro and in vivo using MTT, Ki67 incorporation assay, flow cytometry, immunostaining, Western blot analysis, and a bleomycin-induced pulmonary fibrosis rat model.	Metformin	14-23	epidermal growth factor receptor	Rattus norvegicus	27-31
26629991-0	2015	Metformin and Resveratrol Inhibited High Glucose-Induced Metabolic Memory of Endothelial Senescence through SIRT1/p300/p53/p21 Pathway.	Metformin	0-9	sirtuin 1	Homo sapiens	108-113
26505133-5	2015	Mechanistically, in the presence of metformin, the anticancer potential of sorafenib, accompanying with increased LC3 levels, is found to be synergistically enhanced with the remarkably reduced protein expression of the mTOR/p70S6K/4EBP1 pathway, while not appreciably altering cell cycle.	Metformin	36-45	microtubule associated protein 1 light chain 3 alpha	Homo sapiens	114-117
26271466-6	2015	Metformin affects mainly the early phases of thymic export, increasing CD127(+) CD132(-) and CD127(+) CD132(+) cell populations in naive T cells and the CD127(+) CD132(-) population in CD4(+) T lymphocytes.	Metformin	0-9	CD4-1 molecule	Oncorhynchus mykiss	185-188
26303871-5	2015	The leucine-metformin combinations reduced fat pad mass, normalized liver weight, liver and plasma lipids and inflammatory markers (interleukin 6, interleukin 1 beta, tumor necrosis factor alpha, monocyte chemotactic protein-1, C-reactive protein) comparable to the effects of therapeutic metformin.	Metformin	12-21	chemokine (C-C motif) ligand 2	Mus musculus	196-226
26303871-5	2015	The leucine-metformin combinations reduced fat pad mass, normalized liver weight, liver and plasma lipids and inflammatory markers (interleukin 6, interleukin 1 beta, tumor necrosis factor alpha, monocyte chemotactic protein-1, C-reactive protein) comparable to the effects of therapeutic metformin.	Metformin	12-21	C-reactive protein, pentraxin-related	Mus musculus	228-246
26606013-16	2015	The CCI-induced marked increase of GFAP immunoexpression has been reduced to moderate with fluoxetine (40) and pioglitazone, and to mild with metformin and the combination groups.	Metformin	142-151	glial fibrillary acidic protein	Rattus norvegicus	35-39
26359363-8	2015	Ectopic expression of N-cadherin makes cancer more resistant to metformin.	Metformin	64-73	cadherin 2	Homo sapiens	22-32
26263223-8	2015	A significantly higher proportion of TMEM18 and GNPDA2 minor allele carriers (60% and 40%) lost more than 7% of their body weight after metformin treatment as compared with their homozygous counterparts (21.7% and 15.4%, P = 0.02 and 0.004, respectively).There were trends toward favorable metabolic changes in minor allele carrier groups.	Metformin	136-145	glucosamine-6-phosphate deaminase 2	Homo sapiens	48-54
26276089-7	2015	Adriamycin or metformin alone or in combination induced significant increase in the survival rate, tissue catalase, reduced glutathione and tissue caspase 3 activity with significant decrease in tumor volume, tissue malondialdehyde, tissue sphingosine kinase 1 activity and tumor necrosis factor alpha and alleviated the histopathological changes with significant increase in Trp53 expression and apoptotic index compared to SEC group.	Metformin	14-23	caspase 3	Mus musculus	147-156
26815356-1	2015	OBJECTIVE: To observe the effects of metformin (MET) on podocalyxin (PCX) expression in renal tissue from type 2 diabetes mellitus (T2DM) model rats and investigate its protective effects against glomerular podocyte injury.	Metformin	37-46	pyruvate carboxylase	Rattus norvegicus	69-72
26815356-12	2015	CONCLUSION: Metformin has protective effect on glomerular podocytes by regulating the expression of PCX in renal tissue, independent of its hypoglycemic effect.	Metformin	12-21	pyruvate carboxylase	Rattus norvegicus	100-103
26100439-2	2015	In the following studies, we observed that metformin, one of the most widely used antidiabetic medications, induces mitochondrial stress and induces FGF21 through a PERK-eIF2alpha-ATF4 pathway, which may contribute to the antidiabetic effect of metformin.	Metformin	43-52	activating transcription factor 4	Homo sapiens	180-184
26016715-3	2015	Metformin is almost exclusively eliminated through the kidney primarily through active secretion mediated by Oct1, Oct2, and Mate1.	Metformin	0-9	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	109-113
26294325-5	2015	Of the top 10 genes (fold-change &gt; 10, P &lt; 10(-10)) regulated by metformin plus aspirin, PCDH18, CCL2, RASL11A, FAM111B and BMP5 were down-regulated &gt;= 20-fold, while NGFR, NPTX1, C7orf57, MRPL23AS1 and UNC5B were up-regulated &gt;= 10-fold.	Metformin	71-80	chromosome 7 open reading frame 57	Homo sapiens	189-196
26294325-5	2015	Of the top 10 genes (fold-change &gt; 10, P &lt; 10(-10)) regulated by metformin plus aspirin, PCDH18, CCL2, RASL11A, FAM111B and BMP5 were down-regulated &gt;= 20-fold, while NGFR, NPTX1, C7orf57, MRPL23AS1 and UNC5B were up-regulated &gt;= 10-fold.	Metformin	71-80	unc-5 netrin receptor B	Homo sapiens	212-217
26287334-9	2015	We further illustrated the additive effect of metformin was likely through promoting further IGF-1R down-regulation.	Metformin	46-55	insulin like growth factor 1 receptor	Homo sapiens	93-99
26152715-0	2015	Metformin Inhibits the Production of Reactive Oxygen Species from NADH:Ubiquinone Oxidoreductase to Limit Induction of Interleukin-1beta (IL-1beta) and Boosts Interleukin-10 (IL-10) in Lipopolysaccharide (LPS)-activated Macrophages.	Metformin	0-9	interleukin 10	Homo sapiens	159-173
26152715-0	2015	Metformin Inhibits the Production of Reactive Oxygen Species from NADH:Ubiquinone Oxidoreductase to Limit Induction of Interleukin-1beta (IL-1beta) and Boosts Interleukin-10 (IL-10) in Lipopolysaccharide (LPS)-activated Macrophages.	Metformin	0-9	interleukin 10	Homo sapiens	175-180
26152715-3	2015	Furthermore, metformin boosted induction of the anti-inflammatory cytokine IL-10 in response to LPS.	Metformin	13-22	interleukin 10	Homo sapiens	75-80
26152715-7	2015	Another complex I inhibitor, rotenone, mimicked the effect of metformin on pro-IL-1beta and IL-10.	Metformin	62-71	interleukin 10	Homo sapiens	92-97
25687657-9	2015	Higher concentrations of metformin lead to a significant (p &lt; 0.05) dose-dependent attenuation of the progesterone effect with regard to IGFBP-1, -3, -5, -6, as well as IGF I receptor, while it did not change the expression of IGFBP-2 and -4, IGF I and II and the IGF II receptor.	Metformin	25-34	insulin like growth factor 1 receptor	Homo sapiens	172-186
25975389-8	2015	In parallel, the level of X-linked inhibitor of apoptosis protein (XIAP), an anti-apoptotic molecule, was reduced in the metformin-treated cells.	Metformin	121-130	X-linked inhibitor of apoptosis	Homo sapiens	26-65
25975389-8	2015	In parallel, the level of X-linked inhibitor of apoptosis protein (XIAP), an anti-apoptotic molecule, was reduced in the metformin-treated cells.	Metformin	121-130	X-linked inhibitor of apoptosis	Homo sapiens	67-71
25921843-9	2015	Compared to baseline, metformin significantly improved metabolic parameters and insulin sensitivity, increased SIRT1 gene/protein expression and SIRT1 promoter chromatin accessibility, elevated mTOR gene expression with concomitant reduction in p70S6K phosphorylation in subjects" PBMCs, and modified the plasma N-glycan profile.	Metformin	22-31	sirtuin 1	Homo sapiens	111-116
25921843-10	2015	Compared to placebo, metformin increased SIRT1 protein expression and reduced p70S6K phosphorylation (a proxy of mTOR activity).	Metformin	21-30	sirtuin 1	Homo sapiens	41-46
26552145-6	2015	The cellular accumulation of metformin in MDCK-hMATE1 was 17.6 folds of the control cell, which was significantly inhibited by 100 micromol   L(-1) cimetidine.	Metformin	29-38	solute carrier family 47 member 1	Homo sapiens	47-53
26075749-0	2015	Metformin induces ER stress-dependent apoptosis through miR-708-5p/NNAT pathway in prostate cancer.	Metformin	0-9	neuronatin	Homo sapiens	67-71
26075749-3	2015	Metformin promotes increased expression of miR-708-5p, leading to suppression of endoplasmic reticulum (ER) membrane protein neuronatin (NNAT) expression and subsequently induces apoptosis of prostate cancer cells through the ER stress pathway.	Metformin	0-9	neuronatin	Homo sapiens	125-135
26075749-3	2015	Metformin promotes increased expression of miR-708-5p, leading to suppression of endoplasmic reticulum (ER) membrane protein neuronatin (NNAT) expression and subsequently induces apoptosis of prostate cancer cells through the ER stress pathway.	Metformin	0-9	neuronatin	Homo sapiens	137-141
26075749-6	2015	Taken together, our findings clearly demonstrate that metformin stimulates increased expression of miR-708-5p to target the NNAT-mediated response to ER stress and apoptosis.	Metformin	54-63	neuronatin	Homo sapiens	124-128
26075749-7	2015	This novel regulatory mechanism of metformin in prostate cancer cells not only advances our knowledge on the molecular mechanism of metformin but also provides a promising therapeutic strategy by targeting miR-708-5p and NNAT for prostate cancer treatment.	Metformin	35-44	neuronatin	Homo sapiens	221-225
26040000-4	2015	This reduction in PLN levels was functionally correlated with an increased rate of SERCA2a activity, accounting for an inotropic effect of metformin.	Metformin	139-148	ATPase, Ca++ transporting, cardiac muscle, slow twitch 2	Mus musculus	83-90
25370454-4	2015	Meanwhile, IL-22-induced STAT3 phosphorylation and upregulation of downstream genes Bcl-2 and cyclin D1 were inhibited by metformin.	Metformin	122-131	cyclin D1	Mus musculus	94-103
25370454-6	2015	Furthermore, metformin inhibited de novo generation of Th1 and Th17 cells from naive CD4(+) cells.	Metformin	13-22	CD4 antigen	Mus musculus	85-88
25370454-7	2015	These observations were further supported by the fact that metformin treatment inhibited CD3/CD28-induced IFN-gamma and IL-17A expression along with the transcription factors that drive their expression (T-bet [Th1] and ROR-gammat [Th17], respectively).	Metformin	59-68	interleukin 17A	Mus musculus	120-126
25370454-7	2015	These observations were further supported by the fact that metformin treatment inhibited CD3/CD28-induced IFN-gamma and IL-17A expression along with the transcription factors that drive their expression (T-bet [Th1] and ROR-gammat [Th17], respectively).	Metformin	59-68	T-box 21	Mus musculus	204-209
25370454-8	2015	The effects of metformin on T cell differentiation were mediated by downregulated STAT3 and STAT4 phosphorylation via the AMP-activated kinase-mammalian target of rapamycin complex 1 pathway.	Metformin	15-24	signal transducer and activator of transcription 4	Homo sapiens	92-97
25370454-9	2015	Notably, metformin led to a reduction in glucose transporter Glut1 expression, resulting in less glucose uptake, which is critical to regulate CD4(+) T cell fate.	Metformin	9-18	CD4 antigen	Mus musculus	143-146
25753371-0	2015	Multidrug and toxin extrusion 1 and human organic cation transporter 1 polymorphisms in patients with castration-resistant prostate cancer receiving metformin (SAKK 08/09).	Metformin	149-158	solute carrier family 47 member 1	Homo sapiens	0-31
25753371-1	2015	BACKGROUND: This study was initiated to explore the impact of organic cation transporter 1 (OCT1) and multidrug and toxin extrusion transporter 1 (MATE1) genetic polymorphisms on toxicity, and clinical activity of metformin in patients with castration-resistant prostate cancer (CRPC).	Metformin	214-223	solute carrier family 47 member 1	Homo sapiens	147-152
26117007-4	2015	After treated with 20 mmol/L metformin for 24 h, the expressions of CD14 and CD11b in THP-1 cells didn"t change much (P&gt;0.05), the early apoptosis rates in exprimental and control groups were (2.02+-0.85)% and (4.46+-1.33)% respectively, the late apoptosis rates in experimental and control groups were (1.43+-0.83)% and (3.31+-0.59)% respectively.	Metformin	29-38	integrin subunit alpha M	Homo sapiens	77-82
26359040-1	2015	OBJECTIVE: To investigate the effect of metformin on the proliferation and cell apoptosis of oral squamous cell carcinoma (OSCC) (HSC-3, HSC-4) in vitro and in vivo.	Metformin	40-49	DnaJ heat shock protein family (Hsp40) member B7	Homo sapiens	130-135
26359040-2	2015	METHODS: HSC-3, HSC-4 cells were treated with metformin at different concentration (2-50 mmol/L) for 24, 48 or 72 hours.	Metformin	46-55	DnaJ heat shock protein family (Hsp40) member B7	Homo sapiens	9-14
26359040-12	2015	RESULTS: Metformin inhibited proliferation and colony formation of HSC-3, HSC-4 in a time- and dose-dependent manner.	Metformin	9-18	DnaJ heat shock protein family (Hsp40) member B7	Homo sapiens	67-72
26359040-19	2015	CONCLUSIONS: Metformin could inhibit the growth of OSCC cell line (HSC-3, HSC-4) by reducing cell proliferation and increasing cell apoptosis in vitro and in vivo.	Metformin	13-22	DnaJ heat shock protein family (Hsp40) member B7	Homo sapiens	67-72
25862373-0	2015	Metformin inhibits the proliferation of human prostate cancer PC-3 cells via the downregulation of insulin-like growth factor 1 receptor.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	99-136
25862373-6	2015	Accordingly, we examined the effects of metformin on IGF-1R signaling in prostate cancer cells.	Metformin	40-49	insulin like growth factor 1 receptor	Homo sapiens	53-59
25862373-11	2015	In addition, intraperitoneal treatment with metformin significantly reduced tumor growth and IGF-1R mRNA expression in PC-3 xenografts.	Metformin	44-53	insulin like growth factor 1 receptor	Homo sapiens	93-99
25862373-12	2015	Our results suggest that metformin is a potent inhibitor of the IGF-1/IGF-1R system and may be beneficial in prostate cancer treatment.	Metformin	25-34	insulin like growth factor 1 receptor	Homo sapiens	70-76
26081514-7	2015	RESULTS: At the concentrations of 0-10 mmol/L for 0-48 h, metformin in concentration and time-dependent ways promoted the expression of IL-10 mRNA and inhibited the mRNA expression of IL-1beta in RAW264.7 macrophages (both P &lt; 0.05).	Metformin	58-67	interleukin 10	Homo sapiens	136-141
26081514-8	2015	In metformin-treated cells, the expressions of Arg1 (P = 0.009), IL-10 (P = 0.015) and IL-4 (P = 0.001) mRNA increased while the expressions of IL-1beta (P = 0.001) and IL-6 (P = 0.032) mRNA decreased.	Metformin	3-12	interleukin 10	Homo sapiens	65-70
25867026-7	2015	We show that metformin induces decreased proliferation, cell cycle arrest, autophagy, apoptosis and cell death in vitro with a concomitant activation of AMPK, Redd1 and inhibition of the mTOR pathway.	Metformin	13-22	DNA damage inducible transcript 4	Homo sapiens	159-164
25867026-9	2015	Interestingly, knockdown of AMPK and Redd1 with siRNA partially, but incompletely, abrogates the induction of apoptosis by metformin suggesting both AMPK/Redd1-dependent and -independent effects.	Metformin	123-132	DNA damage inducible transcript 4	Homo sapiens	37-42
25867026-9	2015	Interestingly, knockdown of AMPK and Redd1 with siRNA partially, but incompletely, abrogates the induction of apoptosis by metformin suggesting both AMPK/Redd1-dependent and -independent effects.	Metformin	123-132	DNA damage inducible transcript 4	Homo sapiens	154-159
25617357-8	2015	Coimmunoprecipitation studies revealed that metformin abolished oxidative stress-induced physical interactions between PPARalpha and cyclophilin D (CypD), and the abolishment of these interactions was associated with inhibition of permeability transition pore formation.	Metformin	44-53	peptidylprolyl isomerase D	Rattus norvegicus	133-146
25617357-8	2015	Coimmunoprecipitation studies revealed that metformin abolished oxidative stress-induced physical interactions between PPARalpha and cyclophilin D (CypD), and the abolishment of these interactions was associated with inhibition of permeability transition pore formation.	Metformin	44-53	peptidylprolyl isomerase D	Rattus norvegicus	148-152
25617357-10	2015	In conclusion, this study demonstrates that the protective effects of metformin-induced AMPK activation against oxidative stress converge on mitochondria and are mediated, at least in part, through the dissociation of PPARalpha-CypD interactions, independent of phosphorylation and acetylation of PPARalpha and CypD.	Metformin	70-79	peptidylprolyl isomerase D	Rattus norvegicus	228-232
25617357-10	2015	In conclusion, this study demonstrates that the protective effects of metformin-induced AMPK activation against oxidative stress converge on mitochondria and are mediated, at least in part, through the dissociation of PPARalpha-CypD interactions, independent of phosphorylation and acetylation of PPARalpha and CypD.	Metformin	70-79	peptidylprolyl isomerase D	Rattus norvegicus	311-315
26148594-6	2015	In the metformin group, the expression of MMP-2 protein and mRNA was lower than that in the control group (P &lt; 0.05).	Metformin	7-16	matrix metallopeptidase 2	Mus musculus	42-47
26148594-8	2015	CONCLUSIONS: Metformin inhibited the expression of MMP-2, cisplatin and the combined treatment inhibited the expression of survivin, MMP-2, VEGF-C, and VEGFR-3, and the combined treatment of metformin with cisplatin resulted in enhanced anti-tumor efficacy.	Metformin	13-22	matrix metallopeptidase 2	Mus musculus	51-56
26148594-8	2015	CONCLUSIONS: Metformin inhibited the expression of MMP-2, cisplatin and the combined treatment inhibited the expression of survivin, MMP-2, VEGF-C, and VEGFR-3, and the combined treatment of metformin with cisplatin resulted in enhanced anti-tumor efficacy.	Metformin	13-22	matrix metallopeptidase 2	Mus musculus	133-138
26148594-8	2015	CONCLUSIONS: Metformin inhibited the expression of MMP-2, cisplatin and the combined treatment inhibited the expression of survivin, MMP-2, VEGF-C, and VEGFR-3, and the combined treatment of metformin with cisplatin resulted in enhanced anti-tumor efficacy.	Metformin	191-200	matrix metallopeptidase 2	Mus musculus	51-56
25613530-3	2015	Therefore, the present study used a PCOS rat model to test the hypotheses that HIF-1a signaling is expressed and inhibited in ovaries during PCOS formation and that the HIF-1a/ET-2 signaling pathway is a target of dimethyldiguanide (DMBG) in the clinical treatment of PCOS.	Metformin	214-231	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	169-175
25613530-11	2015	DMBG-treated PCOS may further activate HIF-1a signaling at least partly through inhibiting PHD activity.	Metformin	0-4	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	39-45
25613530-13	2015	DMBG treatment improved PCOS by rescuing this pathway, suggesting that HIF-1a signaling plays an important role in the development and treatment of PCOS.	Metformin	0-4	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	71-77
25601987-10	2015	A compromised insulin or metformin response on the Akt/eNOS and AMP-activated protein kinase/eNOS pathway was observed in aortic rings of OA-fed rats.	Metformin	25-34	nitric oxide synthase 3	Rattus norvegicus	55-59
25601987-10	2015	A compromised insulin or metformin response on the Akt/eNOS and AMP-activated protein kinase/eNOS pathway was observed in aortic rings of OA-fed rats.	Metformin	25-34	nitric oxide synthase 3	Rattus norvegicus	93-97
25894929-8	2015	Both wild-type and BSG-null cells were extremely sensitive to the mitochondria inhibitor metformin/phenformin in normoxia.	Metformin	89-98	basigin	Mus musculus	19-22
25080865-4	2015	We further show in a phase II clinical trial in KRAS mutant advanced non-small cell lung cancer (NSCLC) with single agent sorafenib an improved disease control rate in patients using the antidiabetic drug metformin.	Metformin	205-214	KRAS proto-oncogene, GTPase	Homo sapiens	48-52
25294945-6	2015	Four weeks of therapy with CD44 mAb suppressed visceral adipose tissue inflammation compared with controls and reduced fasting blood glucose levels, weight gain, liver steatosis, and insulin resistance to levels comparable to or better than therapy with the drugs metformin and pioglitazone.	Metformin	264-273	CD44 antigen	Mus musculus	27-31
26038701-9	2015	(2) Metformin increases menadione-induced heme oxygenase-1 (HO-1) expression and inhibits c-Jun N-terminal kinase (JNK)-phosphorylation.	Metformin	4-13	heme oxygenase 1	Rattus norvegicus	42-58
26038701-9	2015	(2) Metformin increases menadione-induced heme oxygenase-1 (HO-1) expression and inhibits c-Jun N-terminal kinase (JNK)-phosphorylation.	Metformin	4-13	heme oxygenase 1	Rattus norvegicus	60-64
26038701-12	2015	The anti-apoptotic effect of metformin is in part dependent on HO-1 and bcl-xl induction and inhibition of JNK activation and independent of insulin signaling.	Metformin	29-38	heme oxygenase 1	Rattus norvegicus	63-67
25605008-4	2015	We explored that the expression of six miRNAs (mir124, 182, 27b, let7b, 221 and 181a), which could directly target cell-cycle-regulatory genes, was altered by metformin in vitro and in vivo.	Metformin	159-168	microRNA let-7b	Homo sapiens	65-70
25605008-7	2015	Further we confirmed that metformin upregulated Drosha to modulate these miRNAs expression.	Metformin	26-35	drosha ribonuclease III	Homo sapiens	48-54
25605008-8	2015	Our results elucidated that metformin inhibited CCA tumor growth via the regulation of Drosha-mediated multiple carcinogenic miRNAs expression and comprehensive evaluation of these miRNAs expression could be more efficient to predict the prognosis.	Metformin	28-37	drosha ribonuclease III	Homo sapiens	87-93
25199921-2	2015	A recent in vitro study found that proton pump inhibitors (PPIs) inhibit OCT1, OCT2 and OCT3, suggesting that PPIs might reduce metformin"s effectiveness.	Metformin	128-137	POU class 2 homeobox 2	Homo sapiens	79-83
25199921-2	2015	A recent in vitro study found that proton pump inhibitors (PPIs) inhibit OCT1, OCT2 and OCT3, suggesting that PPIs might reduce metformin"s effectiveness.	Metformin	128-137	solute carrier family 22 member 3	Homo sapiens	88-92
25416412-6	2015	Furthermore, our results showed that enhancement of metformin"s chemopreventive effects by vitamin D3 was associated with downregulation of S6P expression, via the AMPK (IGFI)/mTOR pathway.	Metformin	52-61	mechanistic target of rapamycin kinase	Rattus norvegicus	176-180
25417601-7	2015	Metformin decreased expression of phosphorylated (p)-AMPK (P = 0.00001), p-Akt (P = 0.0002), p-S6 (51.2%, P = 0.0002), p-4E-BP-1 (P = 0.001), and ER (P = 0.0002) but not PR expression.	Metformin	0-9	taste 2 receptor member 63 pseudogene	Homo sapiens	93-97
25505174-0	2015	Inhibition of polo-like kinase 1 (Plk1) enhances the antineoplastic activity of metformin in prostate cancer.	Metformin	80-89	polo like kinase 1	Homo sapiens	14-32
25505174-0	2015	Inhibition of polo-like kinase 1 (Plk1) enhances the antineoplastic activity of metformin in prostate cancer.	Metformin	80-89	polo like kinase 1	Homo sapiens	34-38
25505174-3	2015	Furthermore, we also provide evidence that Plk1 inhibition makes PCa cells carrying WT p53 much more sensitive to low-dose metformin treatment.	Metformin	123-132	polo like kinase 1	Homo sapiens	43-47
25505174-4	2015	Mechanistically, we found that co-treatment with BI2536 and metformin induced p53-dependent apoptosis and further activated the p53/Redd-1 pathway.	Metformin	60-69	DNA damage inducible transcript 4	Homo sapiens	132-138
25504439-4	2015	We show that both of the main downstream cascades of NRAS can be blocked by this combination: metformin indirectly inhibits the PI3K/AKT/mTOR pathway and trametinib directly impedes the MAPK pathway.	Metformin	94-103	mechanistic target of rapamycin kinase	Rattus norvegicus	137-141
25497710-10	2015	The effect of metformin reducing the tumor development in obese rats might involve increased mRNA expression of pRb and p27, increased activity of AMPK and FOXO3a and decreased expression of p-ERK1/2 (Thr202/Tyr204) in Walker-256 tumor.	Metformin	14-23	RB transcriptional corepressor 1	Rattus norvegicus	112-115
25179820-0	2015	The anti-diabetic drug metformin inhibits vascular endothelial growth factor expression via the mammalian target of rapamycin complex 1/hypoxia-inducible factor-1alpha signaling pathway in ELT-3 cells.	Metformin	23-32	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	136-167
25179820-4	2015	In hypoxia-mimicking conditions, VEGF and hypoxia-inducible factor-1alpha (HIF-1alpha) proteins were both highly expressed and were suppressed by the metformin treatment.	Metformin	150-159	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	42-73
25179820-4	2015	In hypoxia-mimicking conditions, VEGF and hypoxia-inducible factor-1alpha (HIF-1alpha) proteins were both highly expressed and were suppressed by the metformin treatment.	Metformin	150-159	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	75-85
25179820-7	2015	This study revealed the anti-angiogenic activity of metformin in ELT-3 cells by suppressing the expression of VEGF via the mTORC1/HIF-1alpha pathway.	Metformin	52-61	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	130-140
25640355-0	2015	Metformin down-regulates endometrial carcinoma cell secretion of IGF-1 and expression of IGF-1R.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	89-95
25640355-4	2015	IGF-1R was highly expressed in human endometrial carcinoma paraffin sections, but IGF-1R and phosphor-protein kinase B/protein kinase B (p-Akt/ Akt) expression was down-regulated after metformin treatment (p&lt;0.05).	Metformin	185-194	insulin like growth factor 1 receptor	Homo sapiens	82-88
25640355-5	2015	In summary, metformin can reduce the secretion of IGF-1 by Ishikawa and JEC EC cell lines and their expression of IGF-1R to deactivate downstream signaling involving the PI-3K/Akt pathway to inhibit endometrial carcinoma cell growth.	Metformin	12-21	insulin like growth factor 1 receptor	Homo sapiens	114-120
25790097-7	2015	Metformin inhibited HK2, GLUT1, HIF-1alpha expression and glucose consumption.	Metformin	0-9	solute carrier family 2 member 1	Homo sapiens	25-30
26642701-0	2015	Therapeutic Effect of Metformin on Chemerin in Non-Obese Patients with Non-Alcoholic Fatty Liver Disease (NAFLD).	Metformin	22-31	retinoic acid receptor responder 2	Homo sapiens	35-43
26642701-8	2015	After 24 weeks of metformin treatment, the levels of WHR, AST, ALT, TG, chemerin and HOMA-IR were significantly reduced (p &lt; 0.05) and other indexes were not changed significantly.	Metformin	18-27	retinoic acid receptor responder 2	Homo sapiens	72-80
26642701-12	2015	Metformin treatment can improve NAFLD and decrease the level of chemerin.	Metformin	0-9	retinoic acid receptor responder 2	Homo sapiens	64-72
25071027-0	2015	Metformin supports the antidiabetic effect of a sodium glucose cotransporter 2 inhibitor by suppressing endogenous glucose production in diabetic mice.	Metformin	0-9	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	48-78
25755715-3	2015	Herein, we report that metformin derivative, HL010183 significantly inhibited human epidermoid A431 tumor xenograft growth in nu/nu mice, which in turn is associated with a significant reduction in proliferative biomarkers PCNA and cyclins D1/B1.	Metformin	23-32	cyclin D1	Mus musculus	232-245
26064989-7	2015	The reduced level of OPN in the adipose tissue of metformin-treated animals strongly correlated with the lower expression of Ki67 and CD105 and increased caspase-3.	Metformin	50-59	antigen identified by monoclonal antibody Ki 67	Mus musculus	125-129
26064989-7	2015	The reduced level of OPN in the adipose tissue of metformin-treated animals strongly correlated with the lower expression of Ki67 and CD105 and increased caspase-3.	Metformin	50-59	caspase 3	Mus musculus	154-163
25131770-11	2015	Metformin, an AMPK activator, more strongly suppressed cell growth in p53-mutant cell lines with inactive SIRT1 than in p53-mutant cell lines with active SIRT1.	Metformin	0-9	sirtuin 1	Homo sapiens	106-111
25131770-11	2015	Metformin, an AMPK activator, more strongly suppressed cell growth in p53-mutant cell lines with inactive SIRT1 than in p53-mutant cell lines with active SIRT1.	Metformin	0-9	sirtuin 1	Homo sapiens	154-159
25131770-13	2015	Metformin could be a therapeutic drug for HCC in patients with mutated p53, inactivated SIRT1, and AMPK expression.	Metformin	0-9	sirtuin 1	Homo sapiens	88-93
25245054-9	2014	In conclusion, metformin inhibits the migration and invasion of HCC cells by suppressing the ERK/JNK-mediated NF-kappaB-dependent pathway, and thereby reducing uPA and MMP-9 expression.	Metformin	15-24	matrix metallopeptidase 9	Homo sapiens	168-173
24612181-0	2014	Circulatory changes of the novel adipokine adipolin/CTRP12 in response to metformin treatment and an oral glucose challenge in humans.	Metformin	74-83	C1q and TNF related 12	Homo sapiens	43-51
24612181-0	2014	Circulatory changes of the novel adipokine adipolin/CTRP12 in response to metformin treatment and an oral glucose challenge in humans.	Metformin	74-83	C1q and TNF related 12	Homo sapiens	52-58
24612181-2	2014	We sought to investigate the effects of metformin treatment (850 mg twice daily for 6 months) and a 2 h 75 g oral glucose tolerance test (OGTT) on serum adipolin concentrations in humans.	Metformin	40-49	C1q and TNF related 12	Homo sapiens	153-161
24612181-7	2014	RESULTS: Metformin treatment (850 mg twice daily for 6 months) substantially increased serum adipolin concentrations (P &lt; 0 05) in women with polycystic ovary syndrome (PCOS), a pro-inflammatory state associated with obesity, diabetes, dyslipidaemia and atherosclerosis.	Metformin	9-18	C1q and TNF related 12	Homo sapiens	93-101
24903160-0	2014	Metformin prevents LYRM1-induced insulin resistance in 3T3-L1 adipocytes via a mitochondrial-dependent mechanism.	Metformin	0-9	LYR motif containing 1	Homo sapiens	19-24
24903160-4	2014	Metformin enhanced basal and insulin-stimulated glucose uptake and GLUT4 translocation, reduced IRS-1 and Akt phosphorylation and ROS levels, and affected the expression of regulators of mitochondrial biogenesis in LYRM1-over-expressing adipocytes.	Metformin	0-9	LYR motif containing 1	Homo sapiens	215-220
25213330-0	2014	Metformin-induced killing of triple-negative breast cancer cells is mediated by reduction in fatty acid synthase via miRNA-193b.	Metformin	0-9	fatty acid synthase	Homo sapiens	93-112
25213330-4	2014	Expression profiling of metformin-treated TNBC lines revealed fatty acid synthase (FASN) as one of the genes most significantly downregulated following 24 h of treatment, and a decrease in FASN protein was also observed.	Metformin	24-33	fatty acid synthase	Homo sapiens	62-81
25310131-0	2014	Effects of metformin on FOXM1 expression and on the biological behavior of acute leukemia cell lines.	Metformin	11-20	forkhead box M1	Homo sapiens	24-29
25310131-7	2014	Thus, metformin may be involved in the downregulation of FOXM1.	Metformin	6-15	forkhead box M1	Homo sapiens	57-62
25361004-0	2014	Metformin repositioning as antitumoral agent: selective antiproliferative effects in human glioblastoma stem cells, via inhibition of CLIC1-mediated ion current.	Metformin	0-9	chloride intracellular channel 1	Homo sapiens	134-139
25361004-3	2014	Here we show that chloride intracellular channel-1 (CLIC1) is a direct target of metformin in human glioblastoma cells.	Metformin	81-90	chloride intracellular channel 1	Homo sapiens	18-50
25361004-3	2014	Here we show that chloride intracellular channel-1 (CLIC1) is a direct target of metformin in human glioblastoma cells.	Metformin	81-90	chloride intracellular channel 1	Homo sapiens	52-57
25361004-5	2014	These effects phenocopy metformin-mediated inhibition of a chloride current specifically dependent on CLIC1 functional activity.	Metformin	24-33	chloride intracellular channel 1	Homo sapiens	102-107
25361004-7	2014	Metformin inhibition of CLIC1 activity induces G1 arrest of glioblastoma stem cells.	Metformin	0-9	chloride intracellular channel 1	Homo sapiens	24-29
25361004-9	2014	Furthermore, substitution of Arg29 in the putative CLIC1 pore region impairs metformin modulation of channel activity.	Metformin	77-86	chloride intracellular channel 1	Homo sapiens	51-56
25361004-11	2014	We identified CLIC1 not only as a modulator of cell cycle progression in human glioblastoma stem cells but also as the main target of metformin"s antiproliferative activity, paving the way for novel and needed pharmacological approaches to glioblastoma treatment.	Metformin	134-143	chloride intracellular channel 1	Homo sapiens	14-19
25412314-0	2014	Combination simvastatin and metformin induces G1-phase cell cycle arrest and Ripk1- and Ripk3-dependent necrosis in C4-2B osseous metastatic castration-resistant prostate cancer cells.	Metformin	28-37	receptor interacting serine/threonine kinase 3	Homo sapiens	88-93
25240593-4	2014	We confirmed in organ culture that metformin blocks the gentamicin-induced translocation of endonuclease G into the nucleus of outer hair cells and attenuates hair cell loss.	Metformin	35-44	endonuclease G	Homo sapiens	92-106
25106415-8	2014	By contrast relative to wild-type mice, in Oatp1a/1b- and Oct1/2-knockout mice, atorvastatin and metformin oral exposure was significantly increased, and liver Kp was significantly decreased.	Metformin	97-106	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	58-62
25460146-0	2014	Coencapsulation of epirubicin and metformin in PEGylated liposomes inhibits the recurrence of murine sarcoma S180 existing CD133+ cancer stem-like cells.	Metformin	34-43	prominin 1	Mus musculus	123-128
25460146-4	2014	Furthermore, a procedure for the coencapsulation of epirubicin (EPI) and metformin (MET) was developed with the primary goal of eradicating the bulk population of CD133- cells and the rare population of CD133+ cancer stem-like cells, thus ultimately preventing tumor relapse.	Metformin	73-82	prominin 1	Mus musculus	163-168
25460146-4	2014	Furthermore, a procedure for the coencapsulation of epirubicin (EPI) and metformin (MET) was developed with the primary goal of eradicating the bulk population of CD133- cells and the rare population of CD133+ cancer stem-like cells, thus ultimately preventing tumor relapse.	Metformin	73-82	prominin 1	Mus musculus	203-208
25125398-1	2014	A high throughput LC-MS/MS method for quantification of metformin substrate uptake enables conversion of radiometric transporter inhibition assays for multidrug and toxin extrusion transporters (MATE 1 and 2) and organic cation transporter 2 (OCT2) to a nonradioactive format.	Metformin	56-65	solute carrier family 47 member 1	Homo sapiens	195-207
24970682-11	2014	Furthermore, upregulation of death receptor 5 by metformin-mediated Sirt1 downregulation enhanced the sensitivity of wild-type p53 cancer cells to TRAIL-induced apoptosis.	Metformin	49-58	sirtuin 1	Homo sapiens	68-73
24970682-12	2014	Our results demonstrated that metformin induces miR-34a to suppress the Sirt1/Pgc-1alpha/Nrf2 pathway and increases susceptibility of wild-type p53 cancer cells to oxidative stress and TRAIL-induced apoptosis.	Metformin	30-39	sirtuin 1	Homo sapiens	72-77
25015078-9	2014	Metformin, an antidiabetic agent, induced SHP and suppressed cardiac hypertrophy.	Metformin	0-9	nuclear receptor subfamily 0, group B, member 2	Mus musculus	42-45
25015078-10	2014	The metformin-induced antihypertrophic effect was attenuated either by SHP small interfering RNA in cardiomyocytes or in SHP-null mice.	Metformin	4-13	nuclear receptor subfamily 0, group B, member 2	Mus musculus	71-74
25015078-10	2014	The metformin-induced antihypertrophic effect was attenuated either by SHP small interfering RNA in cardiomyocytes or in SHP-null mice.	Metformin	4-13	nuclear receptor subfamily 0, group B, member 2	Mus musculus	121-124
25015078-12	2014	SHP may participate in the metformin-induced antihypertrophic response.	Metformin	27-36	nuclear receptor subfamily 0, group B, member 2	Mus musculus	0-3
25075039-0	2014	Metformin inhibits tumor cell migration via down-regulation of MMP9 in tamoxifen-resistant breast cancer cells.	Metformin	0-9	matrix metallopeptidase 9	Homo sapiens	63-67
25075039-5	2014	These results indicate that metformin leads to the suppression of migration and invasion through regulation of MMP9 and it may have potential as an anticancer drug for therapy in human breast cancer, especially of chemoresistant cancer cells.	Metformin	28-37	matrix metallopeptidase 9	Homo sapiens	111-115
24627035-1	2014	OBJECTIVE: To assess the effect of metformin on gene and protein expression of insulin receptor (IR) and IGF-1 (IGF-1R) receptor in human endometrial stromal cells after stimulation with androgen and insulin.	Metformin	35-44	insulin like growth factor 1 receptor	Homo sapiens	105-110
24627035-1	2014	OBJECTIVE: To assess the effect of metformin on gene and protein expression of insulin receptor (IR) and IGF-1 (IGF-1R) receptor in human endometrial stromal cells after stimulation with androgen and insulin.	Metformin	35-44	insulin like growth factor 1 receptor	Homo sapiens	112-118
24824548-0	2014	Lifestyle and metformin interventions have a durable effect to lower CRP and tPA levels in the diabetes prevention program except in those who develop diabetes.	Metformin	14-23	chromosome 20 open reading frame 181	Homo sapiens	77-80
24824548-10	2014	CONCLUSIONS: Lifestyle and metformin interventions have durable effects to lower hs-CRP and tPA.	Metformin	27-36	chromosome 20 open reading frame 181	Homo sapiens	92-95
25056111-5	2014	Low-dose metformin or SN-38 increases FOXO3 nuclear localization as well as the amount of DNA damage markers and downregulates the expression of a cancer-stemness marker CD44 and other stemness markers, including Nanog, Oct-4, and c-Myc, in these cancer cells.	Metformin	9-18	CD44 molecule (Indian blood group)	Homo sapiens	170-174
25056111-5	2014	Low-dose metformin or SN-38 increases FOXO3 nuclear localization as well as the amount of DNA damage markers and downregulates the expression of a cancer-stemness marker CD44 and other stemness markers, including Nanog, Oct-4, and c-Myc, in these cancer cells.	Metformin	9-18	Nanog homeobox	Homo sapiens	213-218
24844317-10	2014	In corpora cavernosa (CC) from HFD, in vivo metformin (i) normalized A3 R, ADA, and AMPD1; (ii) further decreased AMPD2; (iii) increased dimethylarginine dimethylamino-hydrolase; and (iv) partially restored impaired Ach-induced relaxation.	Metformin	44-53	AMP deaminase 1	Oryctolagus cuniculus	84-89
24874591-9	2014	Resistin, RBP-4, vaspin and visfatin were decreased by vildagliptin + metformin, but in group to group comparison, only vaspin reduction resulted statistically significant.	Metformin	70-79	retinol binding protein 4	Homo sapiens	10-15
24966801-10	2014	Inhibition of autophagy, either by Beclin1 knockdown or by 3-methyladenine-mediated inhibition of caspase-3/7, suppressed the anti-proliferative effects of metformin on endometrial cancer cells.	Metformin	156-165	beclin 1	Homo sapiens	35-42
24748590-8	2014	However, when combined with classical AMPK activators, such as metformin, phenformin, oligomycin, or hypoxia, which impact AMPK heterotrimers more broadly via elevation of cellular AMP levels, A-769662 induced more profound AMPK phosphorylation and subsequent glucose uptake stimulation.	Metformin	63-72	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	38-42
24748590-8	2014	However, when combined with classical AMPK activators, such as metformin, phenformin, oligomycin, or hypoxia, which impact AMPK heterotrimers more broadly via elevation of cellular AMP levels, A-769662 induced more profound AMPK phosphorylation and subsequent glucose uptake stimulation.	Metformin	63-72	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	123-127
24748590-8	2014	However, when combined with classical AMPK activators, such as metformin, phenformin, oligomycin, or hypoxia, which impact AMPK heterotrimers more broadly via elevation of cellular AMP levels, A-769662 induced more profound AMPK phosphorylation and subsequent glucose uptake stimulation.	Metformin	63-72	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	123-127
32069041-3	2020	In this sequential strategy, metformin (MET) was firstly administrated to disrupt the dense stroma, based on the fact that MET down-regulated the expression of fibrogenic cytokine TGF-beta to suppress the activity of pancreatic stellate cells (PSCs), through the AMP-activated protein kinase (AMPK) path-way of PANC-1 pancreatic cancer cells.	Metformin	29-38	transforming growth factor alpha	Homo sapiens	180-188
32069041-3	2020	In this sequential strategy, metformin (MET) was firstly administrated to disrupt the dense stroma, based on the fact that MET down-regulated the expression of fibrogenic cytokine TGF-beta to suppress the activity of pancreatic stellate cells (PSCs), through the AMP-activated protein kinase (AMPK) path-way of PANC-1 pancreatic cancer cells.	Metformin	40-43	transforming growth factor alpha	Homo sapiens	180-188
32069041-3	2020	In this sequential strategy, metformin (MET) was firstly administrated to disrupt the dense stroma, based on the fact that MET down-regulated the expression of fibrogenic cytokine TGF-beta to suppress the activity of pancreatic stellate cells (PSCs), through the AMP-activated protein kinase (AMPK) path-way of PANC-1 pancreatic cancer cells.	Metformin	123-126	transforming growth factor alpha	Homo sapiens	180-188
31974165-7	2020	We conclude that therapeutically relevant doses of metformin lower G6P in hepatocytes challenged with high glucose by stimulation of glycolysis by an AMP-activated protein kinase-independent mechanism through changes in allosteric effectors of phosphofructokinase-1 and fructose bisphosphatase-1, including AMP, Pi, and glycerol 3-phosphate.	Metformin	51-60	phosphofructokinase, liver, B-type	Mus musculus	244-265
31974165-7	2020	We conclude that therapeutically relevant doses of metformin lower G6P in hepatocytes challenged with high glucose by stimulation of glycolysis by an AMP-activated protein kinase-independent mechanism through changes in allosteric effectors of phosphofructokinase-1 and fructose bisphosphatase-1, including AMP, Pi, and glycerol 3-phosphate.	Metformin	51-60	fructose bisphosphatase 1	Mus musculus	270-295
32194991-10	2020	Metformin treatment inhibited upregulation of IL-36gamma, CXCL1, CXCL2, CCL20, S100A7, S100A8 and S100A9 mRNA and protein levels induced by TNF-alpha and IL-17A stimulation.	Metformin	0-9	C-C motif chemokine ligand 20	Homo sapiens	72-77
31815765-7	2020	In addition, metformin reduced the phosphorylation of receptor tyrosine kinases, especially Tie-2, ALK, PYK, EphA4, and EphA10, as well as angiogenesis-related proteins, including RANTES, TGF-beta, and TIMP-1.	Metformin	13-22	TEK receptor tyrosine kinase	Homo sapiens	92-97
32355773-6	2020	Restoration of TET2 by chemicals including 5-Aza-2"-deoxycytidine (5-AZA), metformin or Vitamin C (VC) to inhibit tumor growth was determined in vitro and in a xenograft animal model.	Metformin	75-84	tet methylcytosine dioxygenase 2	Homo sapiens	15-19
31778750-0	2020	Metformin reduces TRPC6 expression through AMPK activation and modulates cytoskeleton dynamics in podocytes under diabetic conditions.	Metformin	0-9	transient receptor potential cation channel subfamily C member 6	Homo sapiens	18-23
31778750-0	2020	Metformin reduces TRPC6 expression through AMPK activation and modulates cytoskeleton dynamics in podocytes under diabetic conditions.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	43-47
31778750-6	2020	Recent studies have suggested that the therapeutic effect of metformin might be mediated by AMPK.	Metformin	61-70	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	92-96
31778750-8	2020	In this study, we demonstrated that metformin normalized TRPC6 expression via AMPKalpha1 activation in podocytes exposed to high glucose concentrations.	Metformin	36-45	transient receptor potential cation channel subfamily C member 6	Homo sapiens	57-62
31778750-8	2020	In this study, we demonstrated that metformin normalized TRPC6 expression via AMPKalpha1 activation in podocytes exposed to high glucose concentrations.	Metformin	36-45	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	78-88
31778750-9	2020	A quantitative analysis showed that metformin increased the colocalization of TRPC6 and AMPKalpha1 subunits from 42% to 61% in standard glucose (SG) medium and from 29% to 52% in high glucose (HG) medium.	Metformin	36-45	transient receptor potential cation channel subfamily C member 6	Homo sapiens	78-83
31778750-9	2020	A quantitative analysis showed that metformin increased the colocalization of TRPC6 and AMPKalpha1 subunits from 42% to 61% in standard glucose (SG) medium and from 29% to 52% in high glucose (HG) medium.	Metformin	36-45	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	88-98
31778750-11	2020	Moreover, metformin through AMPK activation remodeled cytoskeleton dynamics, and consequently, reduced filtration barrier permeability in diabetic conditions.	Metformin	10-19	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	28-32
31338841-0	2020	Administration of metformin alleviates atherosclerosis by promoting H2S production via regulating CSE expression.	Metformin	18-27	cystathionase (cystathionine gamma-lyase)	Mus musculus	98-101
32094377-0	2020	Metformin-induced suppression of IFN-alpha via mTORC1 signalling following seasonal vaccination is associated with impaired antibody responses in type 2 diabetes.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	47-53
32087740-9	2020	In vitro experiments showed that metformin not only decreased the level of matrix metalloproteinase 13, but also elevated type II collagen production through activating AMPK pathway.	Metformin	33-42	matrix metallopeptidase 13	Mus musculus	75-102
31846659-8	2020	The CS-TPF-drug membranes showed an acceptable control of the growth of all the microbial species compared to CS, CS-drug and the standard metformin drug.	Metformin	139-148	citrate synthase	Homo sapiens	4-6
31926250-8	2020	SIGNIFICANCE: We firstly found the synergistic anti-tumor effect of Ara-C/metformin in AML through inhibiting mTORC1/P70S6K pathway.	Metformin	74-83	CREB regulated transcription coactivator 1	Mus musculus	110-116
31653514-12	2020	Metformin reduced plasma TNFalpha levels and decreased tissue expression of COX2 and NOX2 (which were positively correlated), without affecting SOD1 and SOD2.	Metformin	0-9	cytochrome c oxidase II, mitochondrial	Rattus norvegicus	76-80
32099330-0	2020	Metformin Activates the AMPK-mTOR Pathway by Modulating lncRNA TUG1 to Induce Autophagy and Inhibit Atherosclerosis.	Metformin	0-9	taurine up-regulated 1	Homo sapiens	63-67
32099330-2	2020	However, the mechanism through which metformin acts on atherosclerosis (AS) via the long non-coding RNA taurine up-regulated gene 1 (lncRNA TUG1) is still unknown.	Metformin	37-46	taurine up-regulated 1	Homo sapiens	140-144
32099330-8	2020	In vitro experiments indicated that after metformin administration, the expression of lncRNA TUG1 decreased in a time-dependent manner.	Metformin	42-51	taurine up-regulated 1	Homo sapiens	93-97
31672491-3	2020	Metformin has long been an attractive therapeutic option for EwS, but hypoxia limits its efficacy.	Metformin	0-9	EWS RNA binding protein 1	Homo sapiens	61-64
31672491-7	2020	This suggests a potential clinical benefit of the metformin/imatinib combination by allowing the reduction in dose intensity of standard chemotherapy without compromising survival outcome and represents a potential faster track application for EwS patients.	Metformin	50-59	EWS RNA binding protein 1	Homo sapiens	244-247
31963528-0	2020	PPARalpha-Dependent Modulation by Metformin of the Expression of OCT-2 and MATE-1 in the Kidney of Mice.	Metformin	34-43	solute carrier family 47, member 1	Mus musculus	75-81
31963528-3	2020	Hereby, we provide evidence that points towards the metformin-dependent upregulation of OCT-2 and MATE-1 in the kidney via the transcription factor proliferator-activated receptor alpha (PPARalpha).	Metformin	52-61	solute carrier family 47, member 1	Mus musculus	98-104
31963528-4	2020	Treatment of wild type mice with metformin led to the upregulation of the expression of OCT-2 and MATE-1 by 34% and 157%, respectively.	Metformin	33-42	solute carrier family 47, member 1	Mus musculus	98-104
31969821-8	2019	Meanwhile, the AMPK activator metformin significantly enhanced Eth-induced autophagy and inhibited proliferation.	Metformin	30-39	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	15-19
31936169-0	2020	Metformin Inhibits Tumor Metastasis through Suppressing Hsp90alpha Secretion in an AMPKalpha1-PKCgamma Dependent Manner.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	83-93
31936169-6	2020	Moreover, we find that metformin inhibits Hsp90alpha secretion in an AMPKalpha1 dependent manner.	Metformin	23-32	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	69-79
31936169-8	2020	Collectively, our results illuminate that metformin inhibits tumor metastasis by suppressing Hsp90alpha secretion in an AMPKalpha1 dependent manner.	Metformin	42-51	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	120-130
31906986-0	2020	Metformin-repressed miR-381-YAP-snail axis activity disrupts NSCLC growth and metastasis.	Metformin	0-9	Yes1 associated transcriptional regulator	Homo sapiens	28-31
31906986-4	2020	However, the molecular mechanism underpinning how metformin-induced upregulation of miR-381 directly targets YAP or its interactions with the epithelial-mesenchymal transition (EMT) marker protein Snail in NSCLC is still unknown.	Metformin	50-59	Yes1 associated transcriptional regulator	Homo sapiens	109-112
31906986-16	2020	Furthermore, miR-381, YAP, and Snail constitute the miR-381-YAP-Snail signal axis, which is repressed by metformin, and enhances cancer cell invasiveness by directly regulating EMT.	Metformin	105-114	Yes1 associated transcriptional regulator	Homo sapiens	22-25
31906986-16	2020	Furthermore, miR-381, YAP, and Snail constitute the miR-381-YAP-Snail signal axis, which is repressed by metformin, and enhances cancer cell invasiveness by directly regulating EMT.	Metformin	105-114	Yes1 associated transcriptional regulator	Homo sapiens	60-63
31906986-17	2020	CONCLUSIONS: Metformin-induced repression of miR-381-YAP-Snail axis activity disrupts NSCLC growth and metastasis.	Metformin	13-22	Yes1 associated transcriptional regulator	Homo sapiens	53-56
32021253-0	2020	Metformin Inhibits Proliferation of Human Thyroid Cancer TPC-1 Cells by Decreasing LRP2 to Suppress the JNK Pathway.	Metformin	0-9	LDL receptor related protein 2	Homo sapiens	83-87
32021253-2	2020	Methods: Viability, apoptosis and LRP2 level in TPC-1 cells treated with different doses of metformin for different time points were determined.	Metformin	92-101	LDL receptor related protein 2	Homo sapiens	34-38
32021253-4	2020	Regulatory effects of LRP2 on the JNK pathway and cell viability in metformin-treated TPC-1 cells were assessed.	Metformin	68-77	LDL receptor related protein 2	Homo sapiens	22-26
32021253-6	2020	Relative levels of LRP2 and p-JNK1 were concentration-dependently downregulated by metformin treatment.	Metformin	83-92	LDL receptor related protein 2	Homo sapiens	19-23
32021253-7	2020	In addition, overexpression of LRP2 partially abolished the inhibitory effect of metformin on the viability of TPC-1 cells.	Metformin	81-90	LDL receptor related protein 2	Homo sapiens	31-35
32021253-8	2020	Conclusion: Metformin treatment suppresses the proliferative ability and induces apoptosis of TPC-1 cells by downregulating LRP2 to block the JNK pathway.	Metformin	12-21	LDL receptor related protein 2	Homo sapiens	124-128
32304040-7	2020	Moreover, metformin induces autophagy by activation of AMPK and can thus be potentially used to promote heathspan by hormesis-like mechanisms.	Metformin	10-19	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	55-59
32407269-10	2020	CONCLUSION: The interaction between rs72552763 and rs622342 in OCT1, and rs12943590 in MATE2 suggested an important role of these polymorphisms in metformin response in T2D Mexican Mestizo population.	Metformin	147-156	solute carrier family 47 member 2	Homo sapiens	87-92
32538851-8	2020	DNLA and metformin treatments decreased amyloid-beta1-42, AbetaPP, PS1, and BACE1, while increasing IDE and neprilysin for Abeta clearance.	Metformin	9-18	membrane metallo endopeptidase	Mus musculus	108-118
31897243-0	2020	Metformin and LW6 impairs pancreatic cancer cells and reduces nuclear localization of YAP1.	Metformin	0-9	Yes1 associated transcriptional regulator	Homo sapiens	86-90
31897243-4	2020	In addition, we found that the combination of metformin and LW6 increased the phosphorylation of yes-associated protein 1 at serine 127 and attenuated the nuclear localization of this transcription factor.	Metformin	46-55	Yes1 associated transcriptional regulator	Homo sapiens	97-121
31897243-6	2020	This suggests that metformin in combination with LW6 impairs pancreatic cancer cells and reduces nuclear localization of yes-associated protein 1.	Metformin	19-28	Yes1 associated transcriptional regulator	Homo sapiens	121-145
33184242-12	2020	Metformin reduced the upregulation of PP2Ac pY307 and the PP2Ac-a4 association, which was not affected by okadaic acid treatment.	Metformin	0-9	immunoglobulin kappa variable 1D-27 (pseudogene)	Homo sapiens	64-66
31385363-10	2020	Supraphysiological metformin also suppressed branched-chain aminotransferase 2 (BCAT2) and branched-chain-alpha-keto acid dehydrogenase E1a (BCKDHa) mRNA expression as well as BCAT2 protein expression and BCKDHa activity, which was accompanied by decreased Kruppel-like factor 15 protein expression.	Metformin	19-28	branched chain keto acid dehydrogenase E1 subunit alpha	Homo sapiens	141-147
31385363-10	2020	Supraphysiological metformin also suppressed branched-chain aminotransferase 2 (BCAT2) and branched-chain-alpha-keto acid dehydrogenase E1a (BCKDHa) mRNA expression as well as BCAT2 protein expression and BCKDHa activity, which was accompanied by decreased Kruppel-like factor 15 protein expression.	Metformin	19-28	branched chain keto acid dehydrogenase E1 subunit alpha	Homo sapiens	205-211
31385363-11	2020	Physiological levels of metformin suppressed BCKDHa and cytochrome c oxidase mRNA expression at early time points (4-12 hours) but had no effect on any other outcomes.	Metformin	24-33	branched chain keto acid dehydrogenase E1 subunit alpha	Homo sapiens	45-51
32601620-0	2020	Prospective Evaluation of Effect of Metformin on Activation of AMP-activated Protein Kinase (AMPK) and Disease Control in a Sub-group Analysis of Patients with GI Malignancies.	Metformin	36-45	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	63-91
32601620-0	2020	Prospective Evaluation of Effect of Metformin on Activation of AMP-activated Protein Kinase (AMPK) and Disease Control in a Sub-group Analysis of Patients with GI Malignancies.	Metformin	36-45	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	93-97
32601620-2	2020	Anti-neoplastic effects of metformin are believed through many mechanisms including activation of AMP-activated protein kinase, which controls mammalian target of rapamycin (mTOR) growth regulatory pathway.	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	98-126
31711841-8	2020	CONCLUSION AND RELEVANCE: Type 2 diabetes patients treated with sulfonylurea, basal insulin and GLP-1 agonist as an add on to metformin had significant reductions in HbA1c.	Metformin	126-135	glucagon like peptide 1 receptor	Homo sapiens	96-101
31098946-7	2020	Metformin mainly through AMPK axis can protect different organs against toxicities.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	25-29
32341701-7	2020	The intervention with metformin in diabetic rats inhibited the mammalian target of rapamycin mRNA expression and caused an increase in the transcriptional activity of the Foxp3 gene in parapancreatic adipose tissue.	Metformin	22-31	forkhead box P3	Homo sapiens	171-176
31669973-2	2020	Although metformin is a well-known antidiabetic drug, it also confers protection against a series of diseases through the activation of AMP-activated protein kinase (AMPK).	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	166-170
31669973-7	2020	Moreover, pretreatment with metformin significantly attenuated PM2.5-induced cell death and oxidative stress in control and AMPKalpha2-depleted BEAS-2B and H9C2 cells, and was associated with preserved expression of mitochondrial antioxidant enzymes.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	124-134
31822720-10	2019	Metformin reduced succinate even in the conditions suppressing AMPK activity.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	63-67
31822720-11	2019	These results indicate that metformin activates AMPK and reduces the intracellular succinate level, both of which are required for the activation of KDM2A to reduce rRNA transcription.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	48-52
31583436-9	2019	Translational correlates included effects of metformin on expression and phosphorylation of 5" adenosine monophosphate-activated protein kinase (AMPK) by western blot in PBMCs.	Metformin	45-54	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	95-143
31583436-9	2019	Translational correlates included effects of metformin on expression and phosphorylation of 5" adenosine monophosphate-activated protein kinase (AMPK) by western blot in PBMCs.	Metformin	45-54	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	145-149
31583436-16	2019	AMPK phosphorylation showed a four- to sixfold increase in AMPK phosphorylation after metformin.	Metformin	86-95	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	0-4
31583436-16	2019	AMPK phosphorylation showed a four- to sixfold increase in AMPK phosphorylation after metformin.	Metformin	86-95	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	59-63
31583436-18	2019	Post-metformin increase in AMPK phosphorylation may potentially explain lack of disease progression in nearly half of our patients.	Metformin	5-14	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	27-31
31357226-7	2019	Consequently, metformin reduced E-selectin as well ICAM and VCAM-1.	Metformin	14-23	vascular cell adhesion molecule 1	Rattus norvegicus	60-66
31562701-0	2019	Metformin-sensitized NSCLC cells to osimertinib via AMPK-dependent autophagy inhibition.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	52-56
31562701-6	2019	The potential mechanism was that the continual activation of AMPK induced by metformin could inhibit autophagy in a time-dependent manner.	Metformin	77-86	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	61-65
31562701-7	2019	CONCLUSION: Metformin inhibited autophagy and enhanced osimertinib sensitivity via inducing AMPK activation in a time-dependent manner.	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	92-96
31766918-4	2019	These findings have been integrated in recent guidelines which now recommend prescribing (when initial metformin monotherapy fails) a glucagon-like peptide-1 receptor agonist or a sodium/glucose co-transporter-2 inhibitor with clinical trial-confirmed benefit in patients with diabetes and atherosclerotic cardiovascular disease, and a sodium/glucose co-transporter-2 inhibitor in such patients with heart failure or chronic kidney disease at initial stages.	Metformin	103-112	glucagon like peptide 1 receptor	Homo sapiens	134-166
31852646-12	2019	CONCLUSIONS: Short-term intensive oral hypoglycemic therapy with metformin combined with sagliptin and dapagliflozin is effective for treatment of patients with newly diagnosed type 2 diabetes with HbA1c of 9%-12% and shows a good weight-reducing effect with a low risk of hypoglycemia.	Metformin	65-74	hemoglobin subunit alpha 1	Homo sapiens	198-202
31582211-0	2019	Treatment with metformin prevents pre-eclampsia by suppressing migration of trophoblast cells via modulating the signaling pathway of UCA1/miR-204/MMP-9.	Metformin	15-24	urothelial cancer associated 1	Homo sapiens	134-138
31582211-2	2019	This study aims to investigate the molecular mechanism of how UCA1 interferes with MMP9 expression under the influence of metformin, which contributes to the development of pre-eclampsia.	Metformin	122-131	urothelial cancer associated 1	Homo sapiens	62-66
31886264-7	2019	Metformin phosphorylates extracellular signal-regulated kinase (ERK), stimulates endothelial and inducible nitric oxide synthases (e/iNOS), inhibits the GSK3beta/Wnt/beta-catenin pathway, and promotes osteogenic differentiation of osteoblasts.	Metformin	0-9	glycogen synthase kinase 3 beta	Homo sapiens	153-161
31814900-5	2019	Here, we showed that metformin decreases PD-L1 and YAP1 expression in vitro and in vivo.	Metformin	21-30	Yes1 associated transcriptional regulator	Homo sapiens	51-55
31814900-7	2019	Furthermore, metformin directly phosphorylated YAP1 and restricted YAP1 to entry in the nucleus, so that PD-L1 was reduced via western blot and immunofluorescence assays in SW480 and HCT116 cells.	Metformin	13-22	Yes1 associated transcriptional regulator	Homo sapiens	47-51
31814900-7	2019	Furthermore, metformin directly phosphorylated YAP1 and restricted YAP1 to entry in the nucleus, so that PD-L1 was reduced via western blot and immunofluorescence assays in SW480 and HCT116 cells.	Metformin	13-22	Yes1 associated transcriptional regulator	Homo sapiens	67-71
31814900-9	2019	Compared with the control group, PD-L1 and YAP1 expressions in tumor tissues, detected by immunohistochemistry, were reduced in the group of metformin treatment.	Metformin	141-150	Yes1 associated transcriptional regulator	Homo sapiens	43-47
31433832-7	2019	Further, we demonstrate that metformin can suppress CD54 expression on CD4+ T cells by inhibiting NF-kappaB/p65 phosphorylation.	Metformin	29-38	RELA proto-oncogene, NF-kB subunit	Homo sapiens	108-111
31220411-3	2019	We found that metformin decreased the cell apoptosis rate and death, ratio of Bcl-2/Bax, and expression of NR2A and NR2B, and increased the expression of LC3 in Abeta25-35 -treated SH-SY5Y cells.	Metformin	14-23	glutamate ionotropic receptor NMDA type subunit 2B	Homo sapiens	116-120
31614147-0	2019	Dreh, a long noncoding RNA repressed by metformin, regulates glucose transport in C2C12 skeletal muscle cells.	Metformin	40-49	down-regulated in hepatocellular carcinoma	Mus musculus	0-4
31614147-10	2019	Metformin reduced medium glucose concentration and repressed lncRNA Dreh expression in the myotubes.	Metformin	0-9	down-regulated in hepatocellular carcinoma	Mus musculus	68-72
31614147-12	2019	Overexpression of Dreh attenuated the glucose-lowering effect of metformin in myotubes.	Metformin	65-74	down-regulated in hepatocellular carcinoma	Mus musculus	18-22
31614147-13	2019	SIGNIFICANCE: The glucoregulatory actions of metformin are mediated in part by a lncRNA, Dreh, in the skeletal muscle cells.	Metformin	45-54	down-regulated in hepatocellular carcinoma	Mus musculus	89-93
31416838-5	2019	Treatment of CDX1-expressing cells with metformin, an antidiabetic drug known to decrease the risk of gastric cancer, decreased expression of EMT and stemness markers, and reduced spheroid formation.	Metformin	40-49	caudal type homeobox 1	Homo sapiens	13-17
31486135-10	2019	Finally, we demonstrated that the clinically approved drug metformin sensitizes chemoresistant OVCA cells to CDDP via PDK1-HKII pathway.	Metformin	59-68	hexokinase 2	Homo sapiens	123-127
30599813-3	2019	The endometrium of metformin-treated group (metformin-treated patients with PCOS) and the control group (non-metformin-treated patients with PCOS) were analyzed for the expression of homeobox A10 (HOXA10) and integrin beta-3 (ITGB3) and differential micro RNA (miRNA) expression profiles.	Metformin	19-28	homeobox A10	Homo sapiens	183-195
30599813-3	2019	The endometrium of metformin-treated group (metformin-treated patients with PCOS) and the control group (non-metformin-treated patients with PCOS) were analyzed for the expression of homeobox A10 (HOXA10) and integrin beta-3 (ITGB3) and differential micro RNA (miRNA) expression profiles.	Metformin	19-28	homeobox A10	Homo sapiens	197-203
30599813-3	2019	The endometrium of metformin-treated group (metformin-treated patients with PCOS) and the control group (non-metformin-treated patients with PCOS) were analyzed for the expression of homeobox A10 (HOXA10) and integrin beta-3 (ITGB3) and differential micro RNA (miRNA) expression profiles.	Metformin	44-53	homeobox A10	Homo sapiens	183-195
30599813-3	2019	The endometrium of metformin-treated group (metformin-treated patients with PCOS) and the control group (non-metformin-treated patients with PCOS) were analyzed for the expression of homeobox A10 (HOXA10) and integrin beta-3 (ITGB3) and differential micro RNA (miRNA) expression profiles.	Metformin	44-53	homeobox A10	Homo sapiens	183-195
30599813-6	2019	Metformin induced a significant dose-dependent upregulation of HOXA10 and ITGB3.	Metformin	0-9	homeobox A10	Homo sapiens	63-69
30599813-13	2019	Metformin likely improves endometrial receptivity through downregulating the expression of miR-491-3p and miR-1910-3p, thereby increasing the expression of HOXA10 and ITGB3 in the endometrium of PCOS women.	Metformin	0-9	homeobox A10	Homo sapiens	156-162
31781371-5	2019	Cox regression analyses were used to estimate hazard ratios (HRs) for AMD development associated with metformin use.	Metformin	102-111	cytochrome c oxidase subunit 8A	Homo sapiens	0-3
31269196-0	2019	Metformin Treatment and Cancer Risk: Cox Regression Analysis with Time-Dependent Covariates of 320,000 Individuals with Incident Diabetes Mellitus.	Metformin	0-9	cytochrome c oxidase subunit 8A	Homo sapiens	37-40
31408377-7	2019	In patients with T2D enrolled in the intervention trial, antidiabetic treatment with either glyburide, metformin or pioglitazone resulted in significant reduction of circulating OPG (P=0.001), without changes in the other biomarkers and vasodilator responses (all P&gt;0.05).	Metformin	103-112	TNF receptor superfamily member 11b	Homo sapiens	178-181
31491730-8	2019	After adjustment for age, stage at diagnosis and metformin usage, significant difference in colorectal CS between metformin users in diabetic patient population compared to non-diabetics and metformin non-users in diabetic patient population was found (0.80 (0.72-0.89) vs 1.00 and vs 1.05 (0.91-1.23)).	Metformin	114-123	citrate synthase	Homo sapiens	103-105
31491730-8	2019	After adjustment for age, stage at diagnosis and metformin usage, significant difference in colorectal CS between metformin users in diabetic patient population compared to non-diabetics and metformin non-users in diabetic patient population was found (0.80 (0.72-0.89) vs 1.00 and vs 1.05 (0.91-1.23)).	Metformin	114-123	citrate synthase	Homo sapiens	103-105
31491730-10	2019	CONCLUSIONS: Colorectal cancer patients with T2DM treated with metformin as part of their diabetic therapy appear to have a superior OS and CS.	Metformin	63-72	citrate synthase	Homo sapiens	140-142
31440988-3	2019	Given the results from recent studies, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) recommend that patients with T2D and clinical cardiovascular disease (CVD) with inadequate glucose control despite treatment with metformin should receive an SGLT2 inhibitor or GLP-1 receptor agonist.	Metformin	271-280	glucagon like peptide 1 receptor	Homo sapiens	318-332
31607288-7	2019	Metformin inhibited the expression of GLUT1, LDHA, ALDOA, PDK1, and PGK1 genes of K562 cells (P&lt;0.05) showing a dose-dependent manner(r=0.83,r=0.80,r=0.72,r=0.76,r=0.73,respectively).	Metformin	0-9	aldolase, fructose-bisphosphate A	Homo sapiens	51-56
31348945-9	2019	Metformin also reduced collagen VI in both gene and protein expression level, MMP2 and MMP9 in gene expression, and also the expression of apoptosis and necrosis gene.	Metformin	0-9	matrix metallopeptidase 2	Homo sapiens	78-82
31348946-7	2019	However, there is a growing understanding that Metformin demonstrates its anti-epileptic effect mainly via ameliorating brain oxidative damage, activation of AMPK, inhibition of mTOR pathway, downregulation of alpha-synuclein, reducing apoptosis, downregulation of BDNF and TrkB level.	Metformin	47-56	neurotrophic receptor tyrosine kinase 2	Homo sapiens	274-278
31233747-4	2019	Experimental data describes potential mechanisms of metformin, including activation of AMPK, an energy sensing kinase with many downstream effects.	Metformin	52-61	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	87-91
31001733-14	2019	In addition, we found that metformin not only inhibited CCL15 expression in M2-type TAMs enhanced by hypoxia, but also suppressed CCR1 surface expression in HNSCC cells.	Metformin	27-36	C-C motif chemokine receptor 1	Homo sapiens	130-134
31173255-8	2019	In addition, compared with the control group, metformin significantly enhanced the activity of caspase-3, increased the expression of AMPK/pAMPK/Bax proteins and reduced the expression of mTOR/Bcl-2 proteins (P&lt;0.05).	Metformin	46-55	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	134-138
31173255-10	2019	Metformin may inhibit glioma cell proliferation, migration and invasion, and promote its apoptosis; the effects may be associated with the AMPK/mTOR signaling pathway and oxidative stress.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	139-143
31229399-6	2019	GLP-1 receptor agonists were associated with a higher incidence of nausea and headache than metformin, but there were no significant differences in other data.	Metformin	92-101	glucagon like peptide 1 receptor	Homo sapiens	0-14
31268904-0	2019	Metformin improved oxidized low-density lipoprotein-impaired mitochondrial function and increased glucose uptake involving Akt-AS160 pathway in raw264.7 macrophages.	Metformin	0-9	TBC1 domain family, member 4	Mus musculus	127-132
31268904-11	2019	Moreover, metformin-mediated Akt activation increased Akt substrate of 160 kDa (AS160) phosphorylation (0.51 +- 0.04 vs. 1.03 +- 0.03, P = 0.0041), promoted membrane translocation of glucose transporter 1, and increased glucose influx into the cells (4.78 +- 0.04 vs. 5.47 +- 0.01, P &lt; 0.001).	Metformin	10-19	TBC1 domain family, member 4	Mus musculus	54-78
31268904-11	2019	Moreover, metformin-mediated Akt activation increased Akt substrate of 160 kDa (AS160) phosphorylation (0.51 +- 0.04 vs. 1.03 +- 0.03, P = 0.0041), promoted membrane translocation of glucose transporter 1, and increased glucose influx into the cells (4.78 +- 0.04 vs. 5.47 +- 0.01, P &lt; 0.001).	Metformin	10-19	TBC1 domain family, member 4	Mus musculus	80-85
30759215-10	2019	Metformin-dependent PYY secretion was blocked by inhibitors of the plasma membrane monoamine transporter (PMAT) and the serotonin reuptake transporter (SERT), as well as by an inhibitor of AMP kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	189-199
30759215-10	2019	Metformin-dependent PYY secretion was blocked by inhibitors of the plasma membrane monoamine transporter (PMAT) and the serotonin reuptake transporter (SERT), as well as by an inhibitor of AMP kinase (AMPK).	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	201-205
30759215-11	2019	CONCLUSIONS: This is a report of a direct action of metformin on the gut epithelium to trigger PYY secretion in humans, occurring via cell internalization through PMAT and SERT and intracellular activation of AMPK.	Metformin	52-61	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	209-213
31237921-1	2019	BACKGROUND: The last international consensus on the management of type 2 diabetes (T2D) recommends SGLT-2 inhibitors or GLP-1 agonists for patients with clinical cardiovascular (CV) disease; metformin remains the first-line glucose lowering medication.	Metformin	191-200	glucagon like peptide 1 receptor	Homo sapiens	120-125
31186373-3	2019	Activation of AMPK with the type 2 diabetes drug metformin (GlucoPhage) also increased mTORC2 signaling in liver in vivo and in primary hepatocytes in an AMPK-dependent manner.	Metformin	49-58	CREB regulated transcription coactivator 2	Mus musculus	87-93
31186373-3	2019	Activation of AMPK with the type 2 diabetes drug metformin (GlucoPhage) also increased mTORC2 signaling in liver in vivo and in primary hepatocytes in an AMPK-dependent manner.	Metformin	60-70	CREB regulated transcription coactivator 2	Mus musculus	87-93
30851273-13	2019	PP2A catalytic activity was required for NF-kappaB inhibition and Tristetraprolin activation induced by metformin in ox-LDL-stimulated macrophages.	Metformin	104-113	ZFP36 ring finger protein	Homo sapiens	66-81
30851273-14	2019	Our data showed Metformin reduced NLRP3 protein expression and NLRP3 inflammasome activation in ox-LDL-stimulated macrophages through AMPK and PP2A.	Metformin	16-25	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	134-138
31244286-0	2019	Metformin Modulates Cyclin D1 and P53 Expression to Inhibit Cell Proliferation and to Induce Apoptosis in Cervical Cancer Cell Lines.	Metformin	0-9	cyclin D1	Homo sapiens	20-29
31244286-3	2019	Recent studies have found that metformin has a potential anticancer effect mostlythrough reduction of cyclin expression and activation of Activated Adenosine Monophosphate Kinase (AMPK).	Metformin	31-40	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	148-178
31244286-3	2019	Recent studies have found that metformin has a potential anticancer effect mostlythrough reduction of cyclin expression and activation of Activated Adenosine Monophosphate Kinase (AMPK).	Metformin	31-40	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	180-184
31244286-14	2019	Conclusion: Metformin can modulate cyclin D1 and p53 expression in HeLa cancer cell line, leadingto inhibition of cell proliferation and induction of apoptosis.	Metformin	12-21	cyclin D1	Homo sapiens	35-44
31020710-3	2019	Metformin has been demonstrated to activate the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, which induces autophagy and decreases ROS production to prevent apoptosis.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	48-96
31020710-3	2019	Metformin has been demonstrated to activate the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, which induces autophagy and decreases ROS production to prevent apoptosis.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	98-102
31020710-9	2019	Expression of phosphorylated AMPK was increased and that of phosphorylated mammalian target of rapamycin (mTOR) was decreased after exposure to tHA plus metformin.	Metformin	153-162	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	29-33
30903363-4	2019	The major molecular targets of metformin include complex I of the mitochondrial electron transport chain, adenosine monophosphate (AMP)-activated protein kinase (AMPK), and mechanistic target of rapamycin complex 1 (mTORC1), but AMPK-independent effects of metformin have also been described.	Metformin	31-40	CREB regulated transcription coactivator 1	Mus musculus	216-222
31489252-0	2019	Metformin inhibits cervical cancer cell proliferation via decreased AMPK O-GlcNAcylation.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	68-72
31489252-6	2019	Immunoprecipitation analysis was used to examine the interplay between O-GlcNAcylation and phosphorylation in HeLa cells, revealing that metformin decreased O-GlcNAcylated AMP-activated protein kinase (AMPK) and increased levels of phospho-AMPK compared to untreated cells.	Metformin	137-146	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	172-200
31489252-6	2019	Immunoprecipitation analysis was used to examine the interplay between O-GlcNAcylation and phosphorylation in HeLa cells, revealing that metformin decreased O-GlcNAcylated AMP-activated protein kinase (AMPK) and increased levels of phospho-AMPK compared to untreated cells.	Metformin	137-146	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	202-206
31489252-6	2019	Immunoprecipitation analysis was used to examine the interplay between O-GlcNAcylation and phosphorylation in HeLa cells, revealing that metformin decreased O-GlcNAcylated AMP-activated protein kinase (AMPK) and increased levels of phospho-AMPK compared to untreated cells.	Metformin	137-146	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	240-244
31489252-9	2019	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.	Metformin	23-32	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	104-108
30653446-8	2019	Furthermore, GLI-family (transcription factors of the Hh pathway) knockdown in HUVECs and retinal vasculature revealed that downregulation of hyperglycemia-activated autophagy by the metformin-mediated Hh pathway activation was GLI1 dependent.	Metformin	183-192	GLI-Kruppel family member GLI1	Mus musculus	228-232
31014173-0	2019	Fibroblasts rescue oral squamous cancer cell from metformin-induced apoptosis via alleviating metabolic disbalance and inhibiting AMPK pathway.	Metformin	50-59	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	130-134
31014173-6	2019	Here we show that while metformin can significantly inhibit cell growth and induce apoptosis of OSCC cultured alone in a dose-dependent manner through activating p-AMPKT172 and modulating Bcl-2, Bax, and cleaved PARP.	Metformin	24-33	collagen type XI alpha 2 chain	Homo sapiens	212-216
31014173-8	2019	NOFs are rescuing OSCC from metformin - induced apoptosis, at least partially, through inhibiting the activity of AMPK and PARP, maintaining mitochondrial membrane potential and increasing the oxidative stress.	Metformin	28-37	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	114-118
31014173-8	2019	NOFs are rescuing OSCC from metformin - induced apoptosis, at least partially, through inhibiting the activity of AMPK and PARP, maintaining mitochondrial membrane potential and increasing the oxidative stress.	Metformin	28-37	collagen type XI alpha 2 chain	Homo sapiens	123-127
31151499-2	2019	Nowadays metformin is also use for efficacy in diabetes mellitus-tuberculosis coinfection patients through several mechanisms, such increasing superoxide production therefore activation isoniazid is increasing; inducing adeno-monophosphate kinase (AMPK) associated autophagy process; and regulating inflammation cytokines.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	220-246
31151499-2	2019	Nowadays metformin is also use for efficacy in diabetes mellitus-tuberculosis coinfection patients through several mechanisms, such increasing superoxide production therefore activation isoniazid is increasing; inducing adeno-monophosphate kinase (AMPK) associated autophagy process; and regulating inflammation cytokines.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	248-252
30720053-0	2019	Metformin prevents nephrolithiasis formation by inhibiting the expression of OPN and MCP-1 in vitro and in vivo.	Metformin	0-9	secreted phosphoprotein 1	Rattus norvegicus	77-80
30720053-7	2019	In vitro, metformin significantly inhibited the production of MCP-1 and OPN induced by oxalate at the mRNA and protein expression levels.	Metformin	10-19	secreted phosphoprotein 1	Rattus norvegicus	72-75
30720053-8	2019	In vivo, increased expression levels of MCP-1 and OPN were detected in the EG group compared with the controls, and this upregulation was reversed in the EG + metformin group.	Metformin	159-168	secreted phosphoprotein 1	Rattus norvegicus	50-53
30720053-10	2019	Therefore, the results of the study suggest that metformin suppressed urinary crystal deposit formation, possibly by mediating the expression of inflammatory mediators OPN and MCP-1.	Metformin	49-58	secreted phosphoprotein 1	Rattus norvegicus	168-171
30720062-0	2019	Metformin triggers the intrinsic apoptotic response in human AGS gastric adenocarcinoma cells by activating AMPK and suppressing mTOR/AKT signaling.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	108-112
30720062-2	2019	Previous studies have demonstrated that metformin can act alone or in synergy with certain anticancer agents to achieve anti-neoplastic effects on various types of tumors via adenosine monophosphate-activated protein kinase (AMPK) signaling.	Metformin	40-49	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	175-223
30720062-2	2019	Previous studies have demonstrated that metformin can act alone or in synergy with certain anticancer agents to achieve anti-neoplastic effects on various types of tumors via adenosine monophosphate-activated protein kinase (AMPK) signaling.	Metformin	40-49	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	225-229
30720062-3	2019	However, the role of metformin in AMPK-mediated apoptosis of human gastric cancer cells is poorly understood.	Metformin	21-30	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	34-38
30720062-5	2019	Western blot analysis demonstrated that treatment with metformin increased the phosphorylation of AMPK, and decreased the phosphorylation of AKT, mTOR and p70S6k.	Metformin	55-64	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	98-102
30720062-6	2019	Compound C (an AMPK inhibitor) suppressed AMPK phosphorylation and significantly abrogated the effects of metformin on AGS cell viability.	Metformin	106-115	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	15-19
30720062-11	2019	The findings demonstrated that metformin induced AMPK-mediated apoptosis, making it appealing for development as a novel anticancer drug for the treating gastric cancer.	Metformin	31-40	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	49-53
29934960-13	2019	Pretreatment with metformin suppressed upregulation of MCP-1 and downregulation of BAMBI, as well as phosphorylation of ERK1/2 induced by TGF-beta1.	Metformin	18-27	mitogen activated protein kinase 3	Rattus norvegicus	120-126
30932012-3	2019	Clinically relevant conditions that lead to AMPK activation include metformin use and hypocaloric conditions.	Metformin	68-77	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	44-48
31091948-3	2019	In context of individual approach, therapy with GLP1 receptors agonists should be preferably used in early stages of type 2 diabetes mellitus, as second choice treatment after metformin, mainly in more obese patients with subclinical or clinical manifestations of atherosclerosis, but without symptoms of heart failure.	Metformin	176-185	glucagon like peptide 1 receptor	Homo sapiens	48-52
30934600-0	2019	Metformin Pharmacogenetics: Effects of SLC22A1, SLC22A2, and SLC22A3 Polymorphisms on Glycemic Control and HbA1c Levels.	Metformin	0-9	hemoglobin subunit alpha 1	Homo sapiens	107-111
30845774-5	2019	Of note, abdominal fat tissue of obese pre-DM patients treated with metformin therapy presented higher SIRT6 expression and lower NF-kappaB, PPAR-gamma, and SREBP-1 expression levels compared to pre-DM control group.	Metformin	68-77	sirtuin 6	Homo sapiens	103-108
30845774-6	2019	Collectively, results show that SIRT6 is involved in the inflammatory pathway of subcutaneous abdominal fat of obese pre-DM patients and its expression responds to metformin therapy.	Metformin	164-173	sirtuin 6	Homo sapiens	32-37
30370686-2	2019	We evaluated whether administration of metformin into the distal, vs the proximal, small intestine would be more effective in lowering plasma glucose by stimulating glucagon-like pepetide-1 (GLP-1) and/or slowing gastric emptying (GE) in type 2 diabetes (T2DM).	Metformin	39-48	glucagon like peptide 1 receptor	Homo sapiens	165-189
30370686-2	2019	We evaluated whether administration of metformin into the distal, vs the proximal, small intestine would be more effective in lowering plasma glucose by stimulating glucagon-like pepetide-1 (GLP-1) and/or slowing gastric emptying (GE) in type 2 diabetes (T2DM).	Metformin	39-48	glucagon like peptide 1 receptor	Homo sapiens	191-196
30370686-7	2019	RESULTS: Compared with control, both proximal and distal metformin reduced plasma glucose and augmented GLP-1 responses to oral glucose comparably (P &lt; 0.05 each), without affecting plasma insulin or glucagon.	Metformin	57-66	glucagon like peptide 1 receptor	Homo sapiens	104-109
30370686-9	2019	CONCLUSIONS: In diet-controlled T2DM patients, glucose-lowering via a single dose of metformin administered to the upper and lower gut was comparable and was associated with stimulation of GLP-1 and slowing of GE.	Metformin	85-94	glucagon like peptide 1 receptor	Homo sapiens	189-194
30099845-7	2019	GLP-1 receptor agonists are positioned as add-ons to metformin alone or in combination with oral agents in the clinical paradigm.	Metformin	53-62	glucagon like peptide 1 receptor	Homo sapiens	0-14
30798915-0	2019	Cellular stress and AMPK links metformin and diverse compounds with accelerated emergence from anesthesia and potential recovery from disorders of consciousness.	Metformin	31-40	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	20-24
30798915-14	2019	Because AMPK activators including metformin and nicotine promote proliferation and differentiation of neural stem cells located in the subventricular zone and the dentate gyrus, AMPK activation may also enhance brain repair and promote potential recovery from disorders of consciousness (i.e. minimally conscious state, vegetative state, coma).	Metformin	34-43	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	8-12
30890498-10	2019	The results of ELISA and qRT-PCR revealed that metformin treatment obviously increased Foxp3 and TGF-beta expressions at both the protein and mRNA levels and significantly decreased the levels of ROR-gammat, IL-17 and TNF-alpha as well as IL-35 level in these patients.	Metformin	47-56	forkhead box P3	Homo sapiens	87-92
30890498-10	2019	The results of ELISA and qRT-PCR revealed that metformin treatment obviously increased Foxp3 and TGF-beta expressions at both the protein and mRNA levels and significantly decreased the levels of ROR-gammat, IL-17 and TNF-alpha as well as IL-35 level in these patients.	Metformin	47-56	long intergenic non-protein coding RNA, regulator of reprogramming	Homo sapiens	196-199
30873028-4	2019	Here, we report that metformin represses cardiac apoptosis at least in part through inhibition of Forkhead box O1 (FoxO1) pathway.	Metformin	21-30	forkhead box O1	Rattus norvegicus	98-113
30873028-4	2019	Here, we report that metformin represses cardiac apoptosis at least in part through inhibition of Forkhead box O1 (FoxO1) pathway.	Metformin	21-30	forkhead box O1	Rattus norvegicus	115-120
30873028-8	2019	FoxO1 silencing by siRNA abolished anti-apoptotic effect of metformin under hypoxic stress in H9C2 cells.	Metformin	60-69	forkhead box O1	Rattus norvegicus	0-5
30809021-0	2019	Metformin and glucose starvation decrease the migratory ability of hepatocellular carcinoma cells: targeting AMPK activation to control migration.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	109-113
30809021-5	2019	Correspondingly, metformin activates AMPK and inhibits HCC cell proliferation.	Metformin	17-26	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	37-41
30809021-12	2019	Metformin activated AMPK at the same time that inhibited PKA, and both effects were enhanced by glucose starvation.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	20-24
30809021-13	2019	Given that AMPKalpha(S173) phosphorylation by PKA decreases AMPK activation, we hypothesized that the reduction of PKA inhibitory effect by metformin could explain the increased antitumor effects observed.	Metformin	140-149	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	11-15
30591586-6	2019	We conclude that at a low pharmacological load, the metformin effects on the lactate/pyruvate ratio and glucose production are explained by attenuation of transmitochondrial electrogenic transport mechanisms with consequent compromised malate-aspartate shuttle and changes in allosteric effectors of PFK1 and FBP1.	Metformin	52-61	phosphofructokinase, liver, B-type	Mus musculus	300-304
30591586-6	2019	We conclude that at a low pharmacological load, the metformin effects on the lactate/pyruvate ratio and glucose production are explained by attenuation of transmitochondrial electrogenic transport mechanisms with consequent compromised malate-aspartate shuttle and changes in allosteric effectors of PFK1 and FBP1.	Metformin	52-61	fructose bisphosphatase 1	Mus musculus	309-313
30793366-0	2019	Metformin promotes survivin degradation through AMPK/PKA/GSK-3beta-axis in non-small cell lung cancer.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	48-52
30793366-0	2019	Metformin promotes survivin degradation through AMPK/PKA/GSK-3beta-axis in non-small cell lung cancer.	Metformin	0-9	glycogen synthase kinase 3 beta	Homo sapiens	57-66
30793366-7	2019	Moreover, metformin greatly suppressed protein kinase A (PKA) activity and induced its downstream glycogen synthase kinase 3beta (GSK-3beta) activation.	Metformin	10-19	glycogen synthase kinase 3 beta	Homo sapiens	98-128
30793366-7	2019	Moreover, metformin greatly suppressed protein kinase A (PKA) activity and induced its downstream glycogen synthase kinase 3beta (GSK-3beta) activation.	Metformin	10-19	glycogen synthase kinase 3 beta	Homo sapiens	130-139
30793366-10	2019	Furthermore, metformin induced adenosine 5"-monophosphate-activated protein kinase (AMPK) activation.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	31-82
30793366-10	2019	Furthermore, metformin induced adenosine 5"-monophosphate-activated protein kinase (AMPK) activation.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	84-88
30793366-11	2019	Suppression of the activity of AMPK with Compound C reversed the degradation of survivin induced by metformin, and meanwhile, restored the activity of PKA and GSK-3beta.	Metformin	100-109	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	31-35
30793366-12	2019	These results suggest that metformin kills lung cancer cells through AMPK/PKA/GSK-3beta-axis-mediated survivin degradation, providing novel insights into the anticancer effects of metformin.	Metformin	27-36	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	69-73
30793366-12	2019	These results suggest that metformin kills lung cancer cells through AMPK/PKA/GSK-3beta-axis-mediated survivin degradation, providing novel insights into the anticancer effects of metformin.	Metformin	27-36	glycogen synthase kinase 3 beta	Homo sapiens	78-87
30793366-12	2019	These results suggest that metformin kills lung cancer cells through AMPK/PKA/GSK-3beta-axis-mediated survivin degradation, providing novel insights into the anticancer effects of metformin.	Metformin	180-189	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	69-73
30793366-12	2019	These results suggest that metformin kills lung cancer cells through AMPK/PKA/GSK-3beta-axis-mediated survivin degradation, providing novel insights into the anticancer effects of metformin.	Metformin	180-189	glycogen synthase kinase 3 beta	Homo sapiens	78-87
30911317-0	2019	Metformin Promotes Neuronal Differentiation via Crosstalk between Cdk5 and Sox6 in Neuroblastoma Cells.	Metformin	0-9	SRY-box transcription factor 6	Homo sapiens	75-79
30911317-7	2019	Further investigation found that metformin significantly decreased Cdk5 but increased Sox6 during cell differentiation.	Metformin	33-42	SRY-box transcription factor 6	Homo sapiens	86-90
30911317-8	2019	Analysis of the mechanism underlying these changes using Cdk5 inhibitor, roscovitine, indicated that expressions of Cdk5 and Sox6 corresponded to metformin treatment.	Metformin	146-155	SRY-box transcription factor 6	Homo sapiens	125-129
30911317-9	2019	These results suggested that metformin produces neuronal differentiation via Cdk5 and Sox6.	Metformin	29-38	SRY-box transcription factor 6	Homo sapiens	86-90
30911317-11	2019	Taken together, these findings suggest that metformin promotes neuronal differentiation via ROS activation through Cdk5/Sox6 crosstalk, relating to Erk1/2 and Akt signaling.	Metformin	44-53	SRY-box transcription factor 6	Homo sapiens	120-124
30779140-3	2019	Herein, we investigated the anti-inflammatory effects of metformin on the NIMA-related kinase 7(Nek7)/NOD-like receptor family pyrin domain containing 3 (NLRP3) pathway both in vivo and in vitro in experimental diabetic periodontitis.	Metformin	57-66	NIMA (never in mitosis gene a)-related expressed kinase 7	Mus musculus	96-100
30779140-13	2019	Furthermore, after stimulation with the mTOR inhibitor rapamycin, additional metformin treatment could still downregulate Nek7/NLRP3.	Metformin	77-86	NIMA (never in mitosis gene a)-related expressed kinase 7	Mus musculus	122-126
30779140-15	2019	Metformin suppressed the inflammatory state by inhibiting Nek7 expression to decrease NLRP3 inflammasome activity.	Metformin	0-9	NIMA (never in mitosis gene a)-related expressed kinase 7	Mus musculus	58-62
30779140-17	2019	The observed Nek7 reduction could be related to metformin-mediated cell cycle arrest.	Metformin	48-57	NIMA (never in mitosis gene a)-related expressed kinase 7	Mus musculus	13-17
30710062-6	2019	Metformin has displayed definite CV benefits related to AMPK.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	56-60
30899369-0	2019	Metformin induces the M2 macrophage polarization to accelerate the wound healing via regulating AMPK/mTOR/NLRP3 inflammasome singling pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	96-100
30899369-10	2019	Furthermore, blockage of AMPK or activation of mTOR abolished the effects of metformin treatment on depressing NLRP3 inflammasome activation, M2 polarization and improving wound healing.	Metformin	77-86	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	25-29
30899369-11	2019	It suggested that the treatment effects of metformin on wound healing were through regulating AMPK/mTOR/NLRP3 inflammasome signaling axis.	Metformin	43-52	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	94-98
30899369-12	2019	CONCLUSION: Metformin regulated AMPK/mTOR singling pathway to inhibit NLRP3 inflammasome activation, which boosted M2 macrophage polarization to accelerate the wound healing.	Metformin	12-21	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	32-36
30625338-9	2019	Moreover, metformin ameliorates FASN-mediated aberrant lipogenesis and HK2/PKM2-driven ATP generation in vivo.	Metformin	10-19	pyruvate kinase, muscle	Mus musculus	75-79
30625338-11	2019	In addition, metformin is effective at inhibiting PKM2 expression in the presence of an AMPK inhibitor compound C, suggesting that its functioning in PKM2 is AMPK-independent.	Metformin	13-22	pyruvate kinase, muscle	Mus musculus	50-54
30625338-11	2019	In addition, metformin is effective at inhibiting PKM2 expression in the presence of an AMPK inhibitor compound C, suggesting that its functioning in PKM2 is AMPK-independent.	Metformin	13-22	pyruvate kinase, muscle	Mus musculus	150-154
30717766-10	2019	In addition, the AMPK activator metformin remarkably suppressed the growth of PCK1-knockout PLC/PRF/5 cells and inhibited tumor growth in an orthotropic HCC mouse model.	Metformin	32-41	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	17-21
30717766-11	2019	CONCLUSION: This study revealed that PCK1 negatively regulates cell cycle progression and hepatoma cell proliferation via the AMPK/p27Kip1 axis and supports a potential therapeutic and protective effect of metformin on HCC.	Metformin	206-215	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	126-130
30787638-9	2019	Patients treated with metformin after cancer diagnosis were significantly associated more with an increased risk of mortality (aHR =6.78, 95% CI =2.45-18.77) compared to patients who did not use metformin during the study period.	Metformin	22-31	aryl hydrocarbon receptor	Homo sapiens	127-130
30394576-9	2019	Long-acting GLP-1r appears to be more useful for T2DM patients inadequately controlled with metformin monotherapy.	Metformin	92-101	glucagon like peptide 1 receptor	Homo sapiens	12-18
30465181-8	2019	DSPP, ALP, and DMP-1 gene expressions of DPSCs on metformin resin were much higher than DPSCs on control resin without metformin (p &lt; 0.05).	Metformin	50-59	dentin sialophosphoprotein	Homo sapiens	0-4
30804576-0	2019	Effects of SLC22A2 (rs201919874) and SLC47A2 (rs138244461) genetic variants on Metformin Pharmacokinetics in Pakistani T2DM patients.	Metformin	79-88	solute carrier family 47 member 2	Homo sapiens	37-44
30804576-1	2019	OBJECTIVE: To determine the frequencies of single nucleotide polymorphisms rs201919874 and rs138244461 in genes SLC22A2 and SLC47A2 respectively in Pakistani diabetes patients in order to characterise the genetic variants and determine their association with the pharmacokinetics of metformin.	Metformin	283-292	solute carrier family 47 member 2	Homo sapiens	124-131
30468782-3	2019	However, whether AMP activated protein kinase (AMPK) contributes to such effects of metformin remains controversial.	Metformin	84-93	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	47-51
30468782-5	2019	RESULTS: Metformin treatment induced metabolic reprogramming and reduced the energy state of both Prkaa1 WT and KO MEF cells, as evidenced by suppressed tricarboxylic acid (TCA) cycle, elevated lactate production as well as decreased NAD+/NADH ratio.	Metformin	9-18	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	98-104
30569135-0	2019	Metformin attenuates cells stemness and epithelial-mesenchymal transition in colorectal cancer cells by inhibiting the Wnt3a/beta-catenin pathway.	Metformin	0-9	Wnt family member 3A	Homo sapiens	119-124
30569135-4	2019	Mechanistically, metformin inactivated the Wnt3a/beta-catenin signaling pathway, and reactivation of Wnt3a/beta-catenin signaling attenuated the inhibition of metformin on the stemness of HCT116 colorectal cancer cells and EMT.	Metformin	17-26	Wnt family member 3A	Homo sapiens	43-48
30569135-4	2019	Mechanistically, metformin inactivated the Wnt3a/beta-catenin signaling pathway, and reactivation of Wnt3a/beta-catenin signaling attenuated the inhibition of metformin on the stemness of HCT116 colorectal cancer cells and EMT.	Metformin	159-168	Wnt family member 3A	Homo sapiens	101-106
29079305-11	2019	As the transcriptional activator YAP plays a critical role in the network, we conclude that the rationale for targeting the network (at different points), e.g. with FDA approved drugs such as statins and metformin, is therefore compelling.	Metformin	204-213	yes-associated protein 1	Mus musculus	33-36
31122183-7	2019	RESULTS: SLCs and AMPK variations are considered for metformin, CYP2C9, KATP channel, CDKAL1, CDKN2A/2B and KCNQ1 for sulphonylureas, OATP1B, and KCNQ1 for repaglinide and the last but not the least ADIPOQ, PPAR-gamma, SLC, CYP2C8, and SLCO1B1 for thiazolidinediones response prediction.	Metformin	53-62	C-C motif chemokine ligand 21	Homo sapiens	9-12
30745824-0	2019	Metformin Promotes the Survival of Random-Pattern Skin Flaps by Inducing Autophagy via the AMPK-mTOR-TFEB signaling pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	91-95
30745824-0	2019	Metformin Promotes the Survival of Random-Pattern Skin Flaps by Inducing Autophagy via the AMPK-mTOR-TFEB signaling pathway.	Metformin	0-9	transcription factor EB	Homo sapiens	101-105
30745824-6	2019	Moreover, metformin also activated the AMPK-mTOR-TFEB signaling pathway in ischemic areas.	Metformin	10-19	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	39-43
30745824-6	2019	Moreover, metformin also activated the AMPK-mTOR-TFEB signaling pathway in ischemic areas.	Metformin	10-19	transcription factor EB	Homo sapiens	49-53
30745824-7	2019	Inhibitions of AMPK via Compound C (CC) or AMPK shRNA adeno-associated virus (AAV) vector resulted in the downregulation of the AMPK-mTOR-TFEB signaling pathway and autophagy level in metformin-treated flaps.	Metformin	184-193	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	15-19
30745824-7	2019	Inhibitions of AMPK via Compound C (CC) or AMPK shRNA adeno-associated virus (AAV) vector resulted in the downregulation of the AMPK-mTOR-TFEB signaling pathway and autophagy level in metformin-treated flaps.	Metformin	184-193	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	43-47
30745824-7	2019	Inhibitions of AMPK via Compound C (CC) or AMPK shRNA adeno-associated virus (AAV) vector resulted in the downregulation of the AMPK-mTOR-TFEB signaling pathway and autophagy level in metformin-treated flaps.	Metformin	184-193	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	43-47
30291688-0	2019	Evaluation of Osteopontin Gene Expression in Endometrium of Diabetic Rat Models Treated with Metformin and Pioglitazone.	Metformin	93-102	secreted phosphoprotein 1	Rattus norvegicus	14-25
30291688-4	2019	We, therefore, designed a study to evaluate the effects of diabetes on Opn expression at implantation time after treatment with metformin and pioglitazone.	Metformin	128-137	secreted phosphoprotein 1	Rattus norvegicus	71-74
30909226-4	2019	In addition, it is known that metformin upregulates Fgf21, which in turn activates the AMPK/mTOR pathway and mediates neuroprotection.	Metformin	30-39	fibroblast growth factor 21	Mus musculus	52-57
30909226-5	2019	Thus, metformin-induced Fgf21 release may be involved in AMPK/mTOR activation.	Metformin	6-15	fibroblast growth factor 21	Mus musculus	24-29
30909226-11	2019	Further, metformin-treated mice showed increased tau phosphorylation and reduced numbers of NeuN-and PSD95-positive cells.	Metformin	9-18	RNA binding protein, fox-1 homolog (C. elegans) 3	Mus musculus	92-96
30191664-0	2019	Metformin administration attenuates dipeptidyl peptidase-4 inhibitor-induced increases in Krebs von den Lungen-6 (KL-6) levels.	Metformin	0-9	mucin 1, cell surface associated	Homo sapiens	114-118
30414431-9	2019	Metformin increased ALP and OCN secretion, enhanced BMP-2 expression, improved bone mineral density (BMD), and decreased TLR4, MyD88 and NF-kappaB levels in the femur tissues of diabetic rats.	Metformin	0-9	bone morphogenetic protein 2	Rattus norvegicus	52-57
28688035-8	2019	In contrast, rabeprazole, an inhibitor of the organic cation transporter 3, completely prevented metformin-mediated stimulation of neuronal lactate production.	Metformin	97-106	solute carrier family 22 member 3	Rattus norvegicus	46-74
28688035-9	2019	In summary, the data presented identify metformin as a potent stimulator of glycolytic lactate production in viable cultured neurons and suggest that organic cation transporter 3 mediates the uptake of metformin into neurons.	Metformin	202-211	solute carrier family 22 member 3	Rattus norvegicus	150-178
30746502-8	2019	Results: Levels of serum adipsin were higher in subjects with normal glucose tolerance (4.0 +- 1.1 microg/mL) or prediabetes (4.0 +- 1.5 microg/mL) compared with subjects with newly diagnosed diabetes (3.8 +- 1.1 microg/mL) or with known T2D on diet control (3.4 +- 1.0 microg/mL) or metformin monotherapy (3.0 +- 1.0 microg/mL, P &lt; 0.001).	Metformin	284-293	complement factor D	Homo sapiens	25-32
30433870-1	2018	Background This work aimed to evaluate the influence of single nucleotide polymorphisms (SNPs) in the SLC47A1 (922-158G&gt;A; rs2289669) and SLC47A2 (-130G&gt;A; rs12943590) genes on the relative change in HbA1c in type 2 diabetes mellitus (T2DM) patients of South India who are taking metformin as monotherapy.	Metformin	286-295	solute carrier family 47 member 2	Homo sapiens	141-148
30619366-8	2018	To test a clinically relevant way to modulate these pathways, we examined the effects of the FDA-approved drug metformin on IL-33 activation.	Metformin	111-120	interleukin 33	Homo sapiens	124-129
30619366-9	2018	Metformin activates AMPK, which suppresses glycolysis in immune cells.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	20-24
30204458-12	2018	The absolute changes in HMGB1 showed a positive correlation with the changes in testosterone (p&lt;0.05) and negative correlation with the changes in FMD (p&lt;0.05) in patients with PCOS during the course of metformin therapy.	Metformin	209-218	high mobility group box 1	Homo sapiens	24-29
30025915-0	2018	Metformin suppresses growth and adrenocorticotrophic hormone secretion in mouse pituitary corticotroph tumor AtT20 cells.	Metformin	0-9	pro-opiomelanocortin-alpha	Mus musculus	32-60
30025915-11	2018	Using the mouse corticotroph tumor cells, AtT20 cells, we report that metformin inhibited cell proliferation, promoted cell apoptosis and decreased ACTH secretion but did not block the cell cycle in cells.	Metformin	70-79	pro-opiomelanocortin-alpha	Mus musculus	148-152
30545309-2	2018	This study aimed to investigate whether metformin regulates atrial SK2 and SK3 protein expression in T2DM rats though the protein kinase C (PKC)/extracellular signal-regulated kinase (ERK) signaling pathway.	Metformin	40-49	potassium calcium-activated channel subfamily N member 3	Rattus norvegicus	75-78
30545309-0	2018	Metformin regulates atrial SK2 and SK3 expression through inhibiting the PKC/ERK signaling pathway in type 2 diabetic rats.	Metformin	0-9	potassium calcium-activated channel subfamily N member 3	Rattus norvegicus	35-38
30545309-1	2018	BACKGROUND: Our previous study showed that metformin regulates the mRNA and protein levels of type 2 small conductance calcium-activated potassium channel (SK2) and type 3 small conductance calcium-activated potassium channels (SK3) in atrial tissue as well as the ion current of atrial myocytes in rats with type 2 diabetes mellitus (T2DM), but the underlying signaling mechanism is unknown.	Metformin	43-52	potassium calcium-activated channel subfamily N member 3	Rattus norvegicus	228-231
30545309-8	2018	Eight weeks of metformin treatment inhibited the PKC activity and pERK and SK3 expression, and elevated SK2 expression compared with the T2DM group.	Metformin	15-24	potassium calcium-activated channel subfamily N member 3	Rattus norvegicus	75-78
30545309-9	2018	Compared with the metformin-treated only group, the injection of rh-EGF increased pERK and SK3 expression, and decreased SK2 expression; the injection of PMA increased PKC activity and SK3 expression, and decreased SK2 expression.	Metformin	18-27	potassium calcium-activated channel subfamily N member 3	Rattus norvegicus	91-94
30545309-9	2018	Compared with the metformin-treated only group, the injection of rh-EGF increased pERK and SK3 expression, and decreased SK2 expression; the injection of PMA increased PKC activity and SK3 expression, and decreased SK2 expression.	Metformin	18-27	potassium calcium-activated channel subfamily N member 3	Rattus norvegicus	185-188
30545309-12	2018	Long-term metformin treatment prevents the SK2 downregulation and the SK3 upregulation through inhibiting the PKC/ERK signaling pathway.	Metformin	10-19	potassium calcium-activated channel subfamily N member 3	Rattus norvegicus	70-73
30646315-18	2018	Clinicians may consider prescribing GLP-1 receptor agonists, SGLT-2 inhibitors, or DPP-4 inhibitors more routinely after metformin rather than sulfonylureas or basal insulin.	Metformin	121-130	glucagon like peptide 1 receptor	Homo sapiens	36-50
30584280-6	2018	Results: We found that metformin significantly stimulated AMPK activity and decreased intracellular total cholesterol contents in HepG2 cells.	Metformin	23-32	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	58-62
30584280-8	2018	Conclusion: Our preliminary results demonstrate that metformin as a first-line and initial medication suppresses the synthesis of SREBP-2 and upregulates LDLR, and consequently decreases cholesterol production via activation of AMPK, at least partly.	Metformin	53-62	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	228-232
30226474-10	2018	Furthermore, treatment with metformin, the most widely used antidiabetes drug, reduced hepatic lipid accumulation by inactivating ROCK1, resulting in activation of AMPK downstream signaling.	Metformin	28-37	Rho-associated coiled-coil containing protein kinase 1	Mus musculus	130-135
29847739-6	2018	In line with these findings, differentiated glucose transporter 4 (GLUT4)-overexpressing myotubes treated with 2 mmol/L glutamate displayed significantly increased GLUT4 translocation when compared with the control condition (159% +- 8% of control, P &lt; 0.001) and to an extent similar to that of insulin and metformin (181% +- 7% and 159% +- 12%, respectively).	Metformin	311-320	solute carrier family 2 member 4	Homo sapiens	44-65
29847739-6	2018	In line with these findings, differentiated glucose transporter 4 (GLUT4)-overexpressing myotubes treated with 2 mmol/L glutamate displayed significantly increased GLUT4 translocation when compared with the control condition (159% +- 8% of control, P &lt; 0.001) and to an extent similar to that of insulin and metformin (181% +- 7% and 159% +- 12%, respectively).	Metformin	311-320	solute carrier family 2 member 4	Homo sapiens	67-72
30372835-8	2018	CD133+ and VEGFR-2+ cells were detected in blood samples of non-diabetic control, diabetic subjects and diabetics received Metformin.	Metformin	123-132	prominin 1	Homo sapiens	0-5
30372835-11	2018	Metformin decreased the angiogenic potential of cells by decreasing VEGFR-2 and Tie-2 expression (p &lt; 0.05).	Metformin	0-9	TEK receptor tyrosine kinase	Homo sapiens	80-85
30372835-13	2018	Compared to the control, Metformin blunted the expression of VEGF subtypes and directed cells to energy status by induction of PRKAA1, PRKAB2, and PRKAG1 genes (p &lt; 0.05).	Metformin	25-34	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	127-133
30088260-9	2018	In metastatic MDA-MB-231 cells, migration was found to be suppressed by metformin through deregulation of the matrix metalloproteinases MMP-2 and MMP-9.	Metformin	72-81	matrix metallopeptidase 2	Homo sapiens	136-141
30088260-14	2018	Finally, we found that metformin may modulate the pro-apoptotic Bax, anti-apoptotic Bcl-2, MMP-2, MMP-9, miR-21 and miR-155 expression levels.	Metformin	23-32	matrix metallopeptidase 2	Homo sapiens	91-96
30307719-12	2018	Metformin combined with CO-1686 synergistically inhibited the p-IKBalpha, p-IKKalpha/beta, p50, and p65.	Metformin	0-9	RELA proto-oncogene, NF-kB subunit	Homo sapiens	100-103
29920623-0	2018	Synergistic Anti-proliferative Effects of Metformin and Silibinin Combination on T47D Breast Cancer Cells via hTERT and Cyclin D1 Inhibition.	Metformin	42-51	cyclin D1	Homo sapiens	120-129
29961975-6	2018	Mean (+-standard deviation) change in HbA1c from baseline to endpoint was -1.74 +- 1.64% and -1.32 +- 2.05% with BIAsp 30 plus metformin and BIAsp 30, respectively.	Metformin	127-136	hemoglobin subunit alpha 1	Homo sapiens	38-42
30242842-0	2018	Metformin inhibits IgE- and aryl hydrocarbon receptor-mediated mast cell activation in vitro and in vivo.	Metformin	0-9	aryl hydrocarbon receptor	Homo sapiens	28-53
30242842-1	2018	Metformin, an anti-diabetic drug, possesses anti-inflammatory property beyond its glucose-lowering activity, but its regulatory effect on mast cells and allergic responses remains unknown, wherein the aryl hydrocarbon receptor (AhR)-ligand axis is critical in controlling mast cell activation.	Metformin	0-9	aryl hydrocarbon receptor	Homo sapiens	201-226
30242842-1	2018	Metformin, an anti-diabetic drug, possesses anti-inflammatory property beyond its glucose-lowering activity, but its regulatory effect on mast cells and allergic responses remains unknown, wherein the aryl hydrocarbon receptor (AhR)-ligand axis is critical in controlling mast cell activation.	Metformin	0-9	aryl hydrocarbon receptor	Homo sapiens	228-231
30242842-2	2018	Herein, we provide evidence supporting the role of metformin in modulating mast cell activation by FcepsilonR1-, AhR-mediated signaling or their combination.	Metformin	51-60	aryl hydrocarbon receptor	Homo sapiens	113-116
30242842-4	2018	In contrast, metformin at the same doses potently inhibited all parameters in mast cells stimulated with an AhR ligand, 5,11-dihydroindolo[3,2-b]carbazole-6-carbaldehyde (FICZ).	Metformin	13-22	aryl hydrocarbon receptor	Homo sapiens	108-111
30242842-5	2018	Further, metformin was shown to inhibit FcepsilonR1- and AhR-mediated passive cutaneous anaphylaxis (PCA) in vivo, reversible by a S1P receptor 2 antagonist, JTE-013.	Metformin	9-18	aryl hydrocarbon receptor	Homo sapiens	57-60
30242842-6	2018	Using AhR reporter cells, Huh7-DRE-Luc cells, a human mast cell line, HMC-1, and BMMCs, metformin"s inhibitory effect was mediated through the suppression of FICZ-induced AhR activity, calcium mobilization and ROS generation.	Metformin	88-97	aryl hydrocarbon receptor	Homo sapiens	6-9
30242842-6	2018	Using AhR reporter cells, Huh7-DRE-Luc cells, a human mast cell line, HMC-1, and BMMCs, metformin"s inhibitory effect was mediated through the suppression of FICZ-induced AhR activity, calcium mobilization and ROS generation.	Metformin	88-97	aryl hydrocarbon receptor	Homo sapiens	171-174
30242842-7	2018	Notably, FICZ-mediated oxidation of S1P lyase (S1PL) and its reduced activity were reversed by metformin, resulting in decreased levels of S1P.	Metformin	95-104	sphingosine-1-phosphate lyase 1	Homo sapiens	36-45
30242842-7	2018	Notably, FICZ-mediated oxidation of S1P lyase (S1PL) and its reduced activity were reversed by metformin, resulting in decreased levels of S1P.	Metformin	95-104	sphingosine-1-phosphate lyase 1	Homo sapiens	47-51
30334444-4	2018	We found that metformin prevented an increase in serum estradiol levels at postnatal day 14 in female offspring of obese mothers, which was associated with a restoration of hepatic cytochrome P450 3A2 levels to control values.	Metformin	14-23	cytochrome P450, family 3, subfamily a, polypeptide 2	Rattus norvegicus	181-200
30054562-6	2018	LKB1-AMPK activation in GC cell lines was tumor suppressive, as metformin (an AMPK activator) inhibited GC cell growth in the CAB39L-silenced cells.	Metformin	64-73	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	78-82
30555309-0	2018	Metformin Administration During Early Postnatal Life Rescues Autistic-Like Behaviors in the BTBR T+ Itpr3tf/J Mouse Model of Autism.	Metformin	0-9	inositol 1,4,5-triphosphate receptor 3	Mus musculus	100-105
30012567-4	2018	Mechanistically, metformin represses inflammatory infiltration by downregulating both COX2 and PGE2 in tumor cells.Conclusions: Metformin is capable of repressing prostate cancer progression by inhibiting infiltration of tumor-associated macrophages, especially those induced by ADT, by inhibiting the COX2/PGE2 axis, suggesting that a combination of ADT with metformin could be a more efficient therapeutic strategy for prostate cancer treatment.	Metformin	17-26	cytochrome c oxidase II, mitochondrial	Mus musculus	86-90
30012567-4	2018	Mechanistically, metformin represses inflammatory infiltration by downregulating both COX2 and PGE2 in tumor cells.Conclusions: Metformin is capable of repressing prostate cancer progression by inhibiting infiltration of tumor-associated macrophages, especially those induced by ADT, by inhibiting the COX2/PGE2 axis, suggesting that a combination of ADT with metformin could be a more efficient therapeutic strategy for prostate cancer treatment.	Metformin	17-26	cytochrome c oxidase II, mitochondrial	Mus musculus	302-306
30012567-4	2018	Mechanistically, metformin represses inflammatory infiltration by downregulating both COX2 and PGE2 in tumor cells.Conclusions: Metformin is capable of repressing prostate cancer progression by inhibiting infiltration of tumor-associated macrophages, especially those induced by ADT, by inhibiting the COX2/PGE2 axis, suggesting that a combination of ADT with metformin could be a more efficient therapeutic strategy for prostate cancer treatment.	Metformin	128-137	cytochrome c oxidase II, mitochondrial	Mus musculus	86-90
30012567-4	2018	Mechanistically, metformin represses inflammatory infiltration by downregulating both COX2 and PGE2 in tumor cells.Conclusions: Metformin is capable of repressing prostate cancer progression by inhibiting infiltration of tumor-associated macrophages, especially those induced by ADT, by inhibiting the COX2/PGE2 axis, suggesting that a combination of ADT with metformin could be a more efficient therapeutic strategy for prostate cancer treatment.	Metformin	128-137	cytochrome c oxidase II, mitochondrial	Mus musculus	302-306
30459620-0	2018	Metformin Modulates High Glucose-Incubated Human Umbilical Vein Endothelial Cells Proliferation and Apoptosis Through AMPK/CREB/BDNF Pathway.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	118-122
29999521-6	2018	Numerous anti-obesity and/or antidiabetic agents, such as nicotine, metformin and liraglutide, are known to induce their effects through a modulation of AMPK pathway, either at central or at peripheral levels.	Metformin	68-77	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	153-157
30037614-11	2018	Metformin promotes AMPK-dependent telomerase activation (critical for telomere maintenance) and induces activation of the endonuclease RAG1 (promotes DNA cleavage and transposition) via AMPK.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	19-23
30037614-11	2018	Metformin promotes AMPK-dependent telomerase activation (critical for telomere maintenance) and induces activation of the endonuclease RAG1 (promotes DNA cleavage and transposition) via AMPK.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	186-190
30114293-4	2018	Accumulation and transport assays showed that efavirenz inhibits the uptake of metformin by OCT1-, OCT2- and MATE1-expressing MDCK cells and reduces transcellular transport of lamivudine across OCT1/OCT2- and MATE1-expressing MDCK monolayers.	Metformin	79-88	solute carrier family 22 member 2	Canis lupus familiaris	99-103
33435021-10	2018	Metformin treatment of the TEF liver model caused reduced cellular triglycerides, activated AMPK molecule, inhibited mTORC1 signaling pathway, which thus affected the synthesis and metabolism of FFAs.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	92-96
33435021-10	2018	Metformin treatment of the TEF liver model caused reduced cellular triglycerides, activated AMPK molecule, inhibited mTORC1 signaling pathway, which thus affected the synthesis and metabolism of FFAs.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	117-123
29969038-5	2018	We found that metformin improved the expression of intestinal tight junction proteins (ZO1, occludin, and Claudin1) that were reduced by LPS stimulation.	Metformin	14-23	occludin	Homo sapiens	92-100
29975542-0	2018	Importance of OCT2 and MATE1 for the Cimetidine-Metformin Interaction: Insights from Investigations of Polarized Transport in Single- And Double-Transfected MDCK Cells with a Focus on Perpetrator Disposition.	Metformin	48-57	solute carrier family 22 member 2	Canis lupus familiaris	14-18
29684379-5	2018	Metformin significantly ameliorated histopathology in mdx gastrocnemius muscle, in parallel reducing TGF-beta1 with a recovery score (r.s) of 106%; this was accompanied by a decreased plasma matrix-metalloproteinase-9 (r.s.	Metformin	0-9	transforming growth factor, beta 1	Mus musculus	101-110
29684379-5	2018	Metformin significantly ameliorated histopathology in mdx gastrocnemius muscle, in parallel reducing TGF-beta1 with a recovery score (r.s) of 106%; this was accompanied by a decreased plasma matrix-metalloproteinase-9 (r.s.	Metformin	0-9	matrix metallopeptidase 9	Mus musculus	191-217
29660403-10	2018	In contrast, both metformin and fulvene-5, inhibitors of NOX4, facilitated the reversal of TP53 WT and Mut adaptive responses from pro-survival to radio-sensitization and vice versa, respectively.	Metformin	18-27	NADPH oxidase 4	Homo sapiens	57-61
29660403-13	2018	Under these conditions NOX4 expression was inhibited by about 50%, resulting in a reversal in the expression of the TP53 WT and Mut survivin-associated adaptive responses as was observed following metformin and fulvene-5 treatment.	Metformin	197-206	NADPH oxidase 4	Homo sapiens	23-27
29967351-7	2018	In a bleomycin model of lung fibrosis in mice, metformin therapeutically accelerates the resolution of well-established fibrosis in an AMPK-dependent manner.	Metformin	47-56	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	135-139
30008897-0	2018	Metformin-induced apoptosis facilitates degradation of the cellular caspase 8 (FLICE)-like inhibitory protein through a caspase-dependent pathway in human renal cell carcinoma A498 cells.	Metformin	0-9	caspase 8	Homo sapiens	68-77
30008897-0	2018	Metformin-induced apoptosis facilitates degradation of the cellular caspase 8 (FLICE)-like inhibitory protein through a caspase-dependent pathway in human renal cell carcinoma A498 cells.	Metformin	0-9	caspase 8	Homo sapiens	79-84
30008897-0	2018	Metformin-induced apoptosis facilitates degradation of the cellular caspase 8 (FLICE)-like inhibitory protein through a caspase-dependent pathway in human renal cell carcinoma A498 cells.	Metformin	0-9	caspase 8	Homo sapiens	68-75
30008897-7	2018	It was revealed that degradation of cellular caspase 8 (FLICE)-like inhibitory protein (c-FLIP) and activation of procaspase-8 were associated with metformin-mediated apoptosis.	Metformin	148-157	caspase 8	Homo sapiens	45-54
30008897-7	2018	It was revealed that degradation of cellular caspase 8 (FLICE)-like inhibitory protein (c-FLIP) and activation of procaspase-8 were associated with metformin-mediated apoptosis.	Metformin	148-157	caspase 8	Homo sapiens	56-61
30008897-9	2018	Treatment with benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD-fmk, a pan-caspase inhibitor) almost completely blocked metformin-induced apoptosis and degradation of c-FLIPL protein.	Metformin	128-137	caspase 8	Homo sapiens	83-90
30008897-11	2018	Taken together, the results of the present study demonstrated that metformin-induced apoptosis involved degradation of the c-FLIPL protein and activation of caspase-8 in human renal cell carcinoma A498 cells and suggested that metformin could be potentially used for the treatment of renal cancer.	Metformin	67-76	caspase 8	Homo sapiens	157-166
29760016-7	2018	When applied to cultured cardiomyocytes, insulin and metformin increased titin phosphorylation at S4010, S4099, and S11878 via enhanced ERK1/2 (extracellular signal regulated kinase 1/2) and PKCalpha (protein kinase Calpha) activity; NRG-1 application enhanced ERK1/2 activity but reduced PKCalpha activity.	Metformin	53-62	titin	Homo sapiens	73-78
29760016-7	2018	When applied to cultured cardiomyocytes, insulin and metformin increased titin phosphorylation at S4010, S4099, and S11878 via enhanced ERK1/2 (extracellular signal regulated kinase 1/2) and PKCalpha (protein kinase Calpha) activity; NRG-1 application enhanced ERK1/2 activity but reduced PKCalpha activity.	Metformin	53-62	neuregulin 1	Homo sapiens	234-239
29704494-0	2018	Metformin, a first-line drug for type 2 diabetes mellitus, disrupts the MALAT1/miR-142-3p sponge to decrease invasion and migration in cervical cancer cells.	Metformin	0-9	metastasis associated lung adenocarcinoma transcript 1 (non-coding RNA)	Mus musculus	72-78
29994716-5	2018	Among the identified small set of genes associated with reduced breast cancer incidence, laboratory experiments on one of the genes, CDC42, showed that its downregulation by metformin inhibited cancer cell migration and proliferation, thus validating the ability of machine learning approaches to identify biologically relevant candidates for laboratory experiments.	Metformin	174-183	cell division cycle 42	Homo sapiens	133-138
29659176-9	2018	A specific AMPK activator metformin increased Wnt3a, beta-catenin, Nrf2 phosphorylation and activation but reduced the levels of IL-6 and IL-8 in NHBE cells and mouse lungs exposed to CSE.	Metformin	26-35	chemokine (C-X-C motif) ligand 15	Mus musculus	138-142
29659176-10	2018	Furthermore, Nrf2 deficiency abolished the protection of metformin against CSE-induced increase in IL-6 and IL-8 in NHBE cells.	Metformin	57-66	chemokine (C-X-C motif) ligand 15	Mus musculus	108-112
29895790-6	2018	This will be followed by studies targeting AMPK activators like metformin, resveratrol, thiazolidinediones, and polyphenols as reprogramming strategies to prevent hypertension and kidney disease.	Metformin	64-73	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	43-47
29679571-7	2018	Smad2/3 and JNK were phosphorylated to promote the TGF-beta1-induced activation of beta-catenin and osteoblastic differentiation of AVICs, and metformin also alleviated TGF-beta1-induced activation of Smad2/3 and JNK.	Metformin	143-152	SMAD family member 2	Homo sapiens	201-208
29550639-0	2018	Effect of metformin on estrogen and progesterone receptor-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer cells.	Metformin	10-19	progesterone receptor	Homo sapiens	36-57
29377408-5	2018	Baseline-adjusted HbA1c at 2 years (secondary outcome) was lower in the metformin arm (6.0 +- 0.2% vs 7.3 +- 0.2%; P = .0006) (42 +- 2.2 vs 56 +- 2.2mmol/mol).	Metformin	72-81	hemoglobin subunit alpha 1	Homo sapiens	18-22
29377408-6	2018	At study completion, 66.7% of participants randomized to metformin had an HbA1c concentration &lt;= 6.0% (&lt;=42mmol/mol), compared with 8.3% of those on intermittent IIT (P = .009).	Metformin	57-66	hemoglobin subunit alpha 1	Homo sapiens	74-78
29256045-0	2018	Metformin Promotes 2-Deoxy-2-[18F]Fluoro-D-Glucose Uptake in Hepatocellular Carcinoma Cells Through FoxO1-Mediated Downregulation of Glucose-6-Phosphatase.	Metformin	0-9	glucose-6-phosphatase catalytic subunit 1	Homo sapiens	133-154
29397517-8	2018	The proliferation detected in low glucose medium following metformin at doses &lt; 20 mM was found significantly decreased when compared to high glucose medium at 48 h. In terms of galectin-3 levels, the increase in high glucose medium treated with metformin and the decrease in low glucose medium were found statistically significant when compared to control.	Metformin	59-68	galectin 3	Homo sapiens	181-191
29579593-8	2018	The AMPK agonist metformin ameliorated myocardial ischemia and reperfusion (IR) injury and reduced necroptosis through down-regulating the expression of PGAM5 in the Langendorff-perfused rat hearts.	Metformin	17-26	PGAM family member 5, mitochondrial serine/threonine protein phosphatase	Rattus norvegicus	153-158
29760945-11	2018	Conclusion: In this retrospective study in Indian type 2 diabetic patients poorly controlled with metformin and SGLT-2 inhibitor we found a meaningful impact of adding a GLP-1 RA on all metabolic parameters.	Metformin	98-107	glucagon like peptide 1 receptor	Homo sapiens	170-175
29482945-5	2018	Metformin acts in part by stimulating AMP-kinase (AMPK) and results in the suppression of mTORC1 activity and the induction of autophagy.	Metformin	0-9	CREB regulated transcription coactivator 1	Mus musculus	90-96
29482945-8	2018	Furthermore, metformin could increase anti-proliferative effects of mTORC1 and PI3K/mTOR inhibitors as well as natural products such as berberine and the anti-malarial drug chloroquine in certain PDAC lines.	Metformin	13-22	CREB regulated transcription coactivator 1	Mus musculus	68-74
29535146-6	2018	Additionally, we documented how metformin contributes to the regulation of the PGR-associated MAPK/ERK/p38 signaling pathway in the PCOS-like rat uterus.	Metformin	32-41	mitogen activated protein kinase 14	Rattus norvegicus	103-106
29502204-8	2018	Administration of metformin enhanced pAP-2alpha level, reduced miR-124 expression, and increased P4Halpha1 and collagens in carotid atherosclerotic plaque in diabetic Apoe-/- mice.	Metformin	18-27	phospholipid phosphatase 1	Mus musculus	37-47
28230250-0	2018	Metformin attenuates angiotensin II-induced TGFbeta1 expression by targeting hepatocyte nuclear factor-4-alpha.	Metformin	0-9	transforming growth factor, beta 1	Mus musculus	44-52
28230250-4	2018	Here, we investigated the effects of metformin on TGFbeta1 production induced by angiotensin II (AngII) and the underlying mechanisms.	Metformin	37-46	transforming growth factor, beta 1	Mus musculus	50-58
28230250-7	2018	KEY RESULTS: In CFs, metformin inhibited AngII-induced TGFbeta1 expression via AMPK activation.	Metformin	21-30	transforming growth factor, beta 1	Mus musculus	55-63
28230250-11	2018	Metformin inhibited the AngII-induced increases in HNF4alpha protein expression and binding to the Tgfb1 promoter in CFs.	Metformin	0-9	transforming growth factor, beta 1	Mus musculus	99-104
28230250-13	2018	Consequently, metformin inhibited AngII-induced TGFbeta1 production and cardiac fibrosis in wild-type mice but not in AMPKalpha2-/- mice.	Metformin	14-23	transforming growth factor, beta 1	Mus musculus	48-56
28230250-15	2018	Metformin inhibits AngII-induced HNF4alpha expression via AMPK activation, thus decreasing TGFbeta1 transcription and cardiac fibrosis.	Metformin	0-9	transforming growth factor, beta 1	Mus musculus	91-99
29460133-9	2018	The application of metformin can suppress the expression of IGF-1 and IGF-1R, thus preventing the promotive effect of IR on prostate tissue in animal model of MetS.	Metformin	19-28	insulin-like growth factor 1 receptor	Rattus norvegicus	70-76
29484415-5	2018	The purpose of our study was to explore the role of metformin in regulating the metabolism of CCA, as well as to investigate whether metformin could act as a chemosensitizer of the HDAC3 inhibitor BG45, and therefore have potential for the treatment of CCA.	Metformin	133-142	histone deacetylase 3	Homo sapiens	181-186
29484415-10	2018	According to our previous research, which showed that an HDAC3 inhibitor (MI192) was involved in CCA apoptosis, we observed that metformin combined with BG45 (a novel specific HDAC3 inhibitor) effectively induced the apoptosis of CCA cells in vitro.	Metformin	129-138	histone deacetylase 3	Homo sapiens	57-62
29484415-10	2018	According to our previous research, which showed that an HDAC3 inhibitor (MI192) was involved in CCA apoptosis, we observed that metformin combined with BG45 (a novel specific HDAC3 inhibitor) effectively induced the apoptosis of CCA cells in vitro.	Metformin	129-138	histone deacetylase 3	Homo sapiens	176-181
29484415-12	2018	Our data revealed that reversing the Warburg effect with metformin sensitizes cells to the antitumor effects of HDAC3 inhibitors.	Metformin	57-66	histone deacetylase 3	Homo sapiens	112-117
29540614-9	2018	Similarly, in a second mouse model, where obesity was associated with increased FGF-2, normalization of FGF-2 expression by metformin or specific FGF receptor inhibition decreased vessel density and restored tumor sensitivity to anti-VEGF therapy in obese mice.	Metformin	124-133	fibroblast growth factor 2	Mus musculus	104-109
29348175-6	2018	Under high-glucose conditions, pharmacological activation of AMPK in isolated mouse islets or MIN6 cells by metformin or 5-aminoimidazole-4-carboxamide riboside decreased MafA protein levels and mRNA expression of insulin and GSIS-related genes (i.e. glut2 and sur1).	Metformin	108-117	v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (avian)	Mus musculus	171-175
29348175-6	2018	Under high-glucose conditions, pharmacological activation of AMPK in isolated mouse islets or MIN6 cells by metformin or 5-aminoimidazole-4-carboxamide riboside decreased MafA protein levels and mRNA expression of insulin and GSIS-related genes (i.e. glut2 and sur1).	Metformin	108-117	solute carrier family 2 (facilitated glucose transporter), member 2	Mus musculus	251-256
29541475-0	2018	Metformin normalizes the structural changes in glycogen preceding prediabetes in mice overexpressing neuropeptide Y in noradrenergic neurons.	Metformin	0-9	neuropeptide Y	Mus musculus	101-115
31938219-5	2018	Metformin prevented high glucose or hyperglycemia-induced MVED by inhibition of HIF-1alpha/PFN1 signaling in cultured HRMECs and in SD rats with DR.	Metformin	0-9	profilin 1	Rattus norvegicus	91-95
31938219-6	2018	CONCLUSION: Our results indicate that activation of HIF-1alpha/PFN1 by high glucose mediates permeability, apoptosis, and angiogenesis and that metformin alleviates MVED by suppressing HIF-1alpha/PFN1 signaling during DR.	Metformin	144-153	profilin 1	Rattus norvegicus	196-200
29286156-0	2018	Metformin-induced activation of AMPK inhibits the proliferation and migration of human aortic smooth muscle cells through upregulation of p53 and IFI16.	Metformin	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	32-36
29286156-3	2018	The antiproliferative and antimigratory effects of metformin have been attributed to 5" adenosine monophosphate-activated protein kinase (AMPK) activation.	Metformin	51-60	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	88-136
29286156-3	2018	The antiproliferative and antimigratory effects of metformin have been attributed to 5" adenosine monophosphate-activated protein kinase (AMPK) activation.	Metformin	51-60	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	138-142
29286156-8	2018	In addition, metformin was able to activate p53, IFI16 and AMPK, in order to inhibit proliferation and migration of HASMCs.	Metformin	13-22	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	59-63
29286156-10	2018	Notably, in response to metformin, the activation of AMPK was not observed in p53- and IFI16-silenced HASMCs.	Metformin	24-33	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	53-57
29286156-11	2018	These results indicated that metformin-induced activation of AMPK suppresses the proliferation and migration of HASMCs by upregulating p53 and IFI16.	Metformin	29-38	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	61-65
29117515-6	2018	Compared to either drug alone, combination of epothilone A and metformin was more potent; decreased Akt level; and elevated percentage of apoptotic cells, induced cell cycle arrest at G1 phase and elevated the sub-G1 cell population by increasing the mRNA level of caspase-3, poly (ADP-ribose) polymerase-1 and H2AX.	Metformin	63-72	H2A.X variant histone	Homo sapiens	311-315
24916949-5	2014	Re-expression of LKB-1 in HeLa-S3 cells restored the growth inhibitory effect of metformin, indicating a requirement for LKB-1 in metformin-induced growth inhibition.	Metformin	81-90	serine/threonine kinase 11	Homo sapiens	17-22
24916949-5	2014	Re-expression of LKB-1 in HeLa-S3 cells restored the growth inhibitory effect of metformin, indicating a requirement for LKB-1 in metformin-induced growth inhibition.	Metformin	130-139	serine/threonine kinase 11	Homo sapiens	17-22
24504677-3	2014	The biomolecular characteristics of tumors, such as appropriate expression of organic cation transporters or genetic alterations including p53, K-ras, LKB1, and PI3K may impact metformin"s anticancer efficiency.	Metformin	177-186	serine/threonine kinase 11	Homo sapiens	151-155
24530383-4	2014	CPC (100 muM) reduced the uptake of MPP(+) and metformin mediated by OCT2 in MDCK-hOCT2 cells to 60.8% and 33.6% of the control, CPC (500 muM) decreased the uptake of 6-carboxyfluorescein (6-CFL) and para-aminohippuric acid (PAH), substrates of OAT1, in MDCK-hOAT1 cells to 64.6% and 79.4% of the control.	Metformin	47-56	solute carrier family 22 member 2	Rattus norvegicus	69-73
24931021-9	2014	CONCLUSIONS: Metformin may inhibit the proliferation of Fadu cells by inducing the cell cycle arrest in G1 phase mediated in part by AMPK and P21.	Metformin	13-22	H3 histone pseudogene 16	Homo sapiens	142-145
24638078-10	2014	Additionally, in bone marrow-derived macrophages, metformin treatment partially blunted the effects of lipopolysaccharide on inducing the phosphorylation of JNK1 and nuclear factor kappa B (NF-kappaB) p65 and on increasing the mRNA levels of proinflammatory cytokines.	Metformin	50-59	v-rel reticuloendotheliosis viral oncogene homolog A (avian)	Mus musculus	201-204
23949159-3	2014	Metformin also inhibits mTOR signaling but by activating the upstream kinase AMPK.	Metformin	0-9	mechanistic target of rapamycin kinase	Mus musculus	24-28
23949159-4	2014	Here we report the effects of chronic and systemic administration of the two mTOR inhibitors, rapamycin and metformin, on adult neural stem cells of the subventricular region and the dendate gyrus of the mouse hippocampus.	Metformin	108-117	mechanistic target of rapamycin kinase	Mus musculus	77-81
23949159-5	2014	While rapamycin decreased the number of neural progenitors, metformin-mediated inhibition of mTOR had no such effect.	Metformin	60-69	mechanistic target of rapamycin kinase	Mus musculus	93-97
24285728-5	2014	Finally, forcing glycolysis by metformin treatment augments this response and the efficacy of MCT1 inhibitors, suggesting an attractive combination therapy for MYC/MCT1-expressing malignancies.	Metformin	31-40	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	160-163
24186866-1	2014	Dipeptidyl peptidase-4 (DPP-4) inhibitors prevent degradation of incretin hormones (glucagon-like peptide 1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]), whereas metformin may increase GLP-1 levels.	Metformin	181-190	dipeptidyl peptidase 4	Homo sapiens	24-29
24281385-10	2014	Aortic eNOS, AMPK, and sGC were in cav-1(-/-) &gt; WT, and metformin decreased total and phosphorylated eNOS and AMPK in cav-1(-/-).	Metformin	59-68	caveolin 1, caveolae protein	Mus musculus	121-126
24233023-7	2014	In addition, insulin receptor substrate 2 gene depletion blocked metformin-enhanced beta-catenin translocation.	Metformin	65-74	insulin receptor substrate 2	Mus musculus	13-41
24762600-11	2014	CONCLUSIONS: Upregulated SIRT3 is involved in the pharmacological mechanism by which metformin promotes glucose uptake.	Metformin	85-94	sirtuin 3	Rattus norvegicus	25-30
24791887-11	2014	Conlusion Metformin can suppress the expression of NF-kappaB, MCP-1, ICAM-1 and TGF-beta1 of glomerular MCs induced by high glucose via AMPK activation, which may partly contribute to its reno-protection.	Metformin	10-19	C-C motif chemokine ligand 2	Rattus norvegicus	62-67
24750786-3	2014	Metformin exerts anticancer effects by primarily blocking the pivotal LKB1/AMPK/mTOR/S6K1 pathway-dependent cell growth, induces selective lethal effects on GSC by impairing the GSC-initiating spherogenesis and inhibits the proliferation of CD133+ cells, while having a low or null effect on differentiated glioblastoma cells and normal human stem cells.	Metformin	0-9	serine/threonine kinase 11	Homo sapiens	70-74
24750786-3	2014	Metformin exerts anticancer effects by primarily blocking the pivotal LKB1/AMPK/mTOR/S6K1 pathway-dependent cell growth, induces selective lethal effects on GSC by impairing the GSC-initiating spherogenesis and inhibits the proliferation of CD133+ cells, while having a low or null effect on differentiated glioblastoma cells and normal human stem cells.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	85-89
24243637-9	2014	Treatment of adipocyte fractions or SGBS adipocytes with metformin or acetylsalicylic acid, which target C/EBPbeta and NF-kappaB/RelA signaling, attenuated the IL-1alpha induction of 11beta-HSD1 (P&lt;=.002).	Metformin	57-66	interleukin 1 alpha	Homo sapiens	160-169
24812633-11	2014	Metformin attenuated the suppression on proliferation with increased expression of Col I, OCN, and OPG, meanwhile suppressing MMP1 and MMP2.	Metformin	0-9	matrix metallopeptidase 1	Homo sapiens	126-130
24190973-8	2014	The activation of p53 through AMPK-mediated MDMX phosphorylation and inactivation was further confirmed by using cell and animal model systems with two AMPK activators, metformin and salicylate (the active form of aspirin).	Metformin	169-178	MDM4 regulator of p53	Homo sapiens	44-48
23974492-5	2013	Metformin treatment reduced expression of miR-222 in these cells (p &lt; 0.05).	Metformin	0-9	microRNA 222	Homo sapiens	42-49
23974492-6	2013	As a result, protein abundance of p27, p57 and PTEN were increased in cells exposed to metformin.	Metformin	87-96	interferon alpha inducible protein 27	Homo sapiens	34-37
23974492-6	2013	As a result, protein abundance of p27, p57 and PTEN were increased in cells exposed to metformin.	Metformin	87-96	phosphatase and tensin homolog	Homo sapiens	47-51
23803693-4	2013	Metformin induced proteasome-dependent degradation of Sps in L3.6pL and Panc28 cells, whereas in Panc1 cells metformin decreased microRNA-27a and induced the Sp repressor, ZBTB10, and disruption of miR-27a:ZBTB10 by metformin was phosphatase dependent.	Metformin	0-9	zinc finger and BTB domain containing 10	Homo sapiens	206-212
23803693-4	2013	Metformin induced proteasome-dependent degradation of Sps in L3.6pL and Panc28 cells, whereas in Panc1 cells metformin decreased microRNA-27a and induced the Sp repressor, ZBTB10, and disruption of miR-27a:ZBTB10 by metformin was phosphatase dependent.	Metformin	109-118	zinc finger and BTB domain containing 10	Homo sapiens	172-178
23803693-4	2013	Metformin induced proteasome-dependent degradation of Sps in L3.6pL and Panc28 cells, whereas in Panc1 cells metformin decreased microRNA-27a and induced the Sp repressor, ZBTB10, and disruption of miR-27a:ZBTB10 by metformin was phosphatase dependent.	Metformin	109-118	zinc finger and BTB domain containing 10	Homo sapiens	206-212
23993965-0	2013	Tiam-1, a GEF for Rac1, plays a critical role in metformin-mediated glucose uptake in C2C12 cells.	Metformin	49-58	rho/rac guanine nucleotide exchange factor (GEF) 2	Mus musculus	10-13
23993965-2	2013	In this study, AMPK activators (AICAR and metformin) increased the expression of T-lymphoma invasion and metastasis-inducing protein-1 (Tiam-1), a Rac1 specific guanine nucleotide exchange factor (GEF), mRNA and protein in skeletal muscle C2C12 cells.	Metformin	42-51	rho/rac guanine nucleotide exchange factor (GEF) 2	Mus musculus	161-195
23993965-2	2013	In this study, AMPK activators (AICAR and metformin) increased the expression of T-lymphoma invasion and metastasis-inducing protein-1 (Tiam-1), a Rac1 specific guanine nucleotide exchange factor (GEF), mRNA and protein in skeletal muscle C2C12 cells.	Metformin	42-51	rho/rac guanine nucleotide exchange factor (GEF) 2	Mus musculus	197-200
23875783-1	2013	AIMS: The aim of this study was to examine the effect of metformin on serum adiponectin and adiponectin receptor-1 (AdipoR1) and evaluate their role in prediction of ovulation in patients with polycystic ovarian syndrome (PCOS).	Metformin	57-66	adiponectin receptor 1	Homo sapiens	92-114
23875783-1	2013	AIMS: The aim of this study was to examine the effect of metformin on serum adiponectin and adiponectin receptor-1 (AdipoR1) and evaluate their role in prediction of ovulation in patients with polycystic ovarian syndrome (PCOS).	Metformin	57-66	adiponectin receptor 1	Homo sapiens	116-123
24094981-0	2013	Resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin.	Metformin	121-130	resistin	Homo sapiens	0-8
24094981-7	2013	Though there were conflicting findings of resistin in metabolic syndrome or type 2 diabetes mellitus in different studies, resistin was significant decreased in the rosiglitazone treated patients than in the metformin-treated patients in most of studies.	Metformin	208-217	resistin	Homo sapiens	123-131
24094981-8	2013	Here, we hypothesized that resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin.	Metformin	148-157	resistin	Homo sapiens	27-35
24403860-4	2013	Herein, we report that BCA2 is an endogenous inhibitor of AMPK activation in breast cancer cells and that BCA2 inhibition increases the efficacy of metformin.	Metformin	148-157	ring finger protein 115	Homo sapiens	23-27
24403860-4	2013	Herein, we report that BCA2 is an endogenous inhibitor of AMPK activation in breast cancer cells and that BCA2 inhibition increases the efficacy of metformin.	Metformin	148-157	ring finger protein 115	Homo sapiens	106-110
24403860-7	2013	Activation of AMPK by metformin triggered a growth inhibitory signal but also increased BCA2 protein levels, which correlated with AKT activation and could be curbed by an AMPK inhibitor, suggesting a potential feedback mechanism from pAMPKalpha1 to pAkt to BCA2.	Metformin	22-31	ring finger protein 115	Homo sapiens	88-92
24403860-7	2013	Activation of AMPK by metformin triggered a growth inhibitory signal but also increased BCA2 protein levels, which correlated with AKT activation and could be curbed by an AMPK inhibitor, suggesting a potential feedback mechanism from pAMPKalpha1 to pAkt to BCA2.	Metformin	22-31	ring finger protein 115	Homo sapiens	258-262
24403860-8	2013	Finally, BCA2 siRNA, or inhibition of its upstream stabilizing kinase AKT, increased the growth inhibitory effect of metformin in multiple breast cancer cell lines, supporting the conclusion that BCA2 weakens metformin"s efficacy.	Metformin	117-126	ring finger protein 115	Homo sapiens	9-13
24403860-8	2013	Finally, BCA2 siRNA, or inhibition of its upstream stabilizing kinase AKT, increased the growth inhibitory effect of metformin in multiple breast cancer cell lines, supporting the conclusion that BCA2 weakens metformin"s efficacy.	Metformin	117-126	ring finger protein 115	Homo sapiens	196-200
24403860-8	2013	Finally, BCA2 siRNA, or inhibition of its upstream stabilizing kinase AKT, increased the growth inhibitory effect of metformin in multiple breast cancer cell lines, supporting the conclusion that BCA2 weakens metformin"s efficacy.	Metformin	209-218	ring finger protein 115	Homo sapiens	9-13
24403860-8	2013	Finally, BCA2 siRNA, or inhibition of its upstream stabilizing kinase AKT, increased the growth inhibitory effect of metformin in multiple breast cancer cell lines, supporting the conclusion that BCA2 weakens metformin"s efficacy.	Metformin	209-218	ring finger protein 115	Homo sapiens	196-200
24403860-9	2013	Our data suggest that metformin in combination with a BCA2 inhibitor may be a more effective breast cancer treatment strategy than metformin alone.	Metformin	131-140	ring finger protein 115	Homo sapiens	54-58
24001450-4	2013	The inhibitory potencies of ondansetron on metformin accumulation mediated by OCT2 and MATEs were determined in the stable HEK-293 cells expressing these transporters.	Metformin	43-52	solute carrier family 22 member 2	Homo sapiens	78-82
24051143-0	2013	5"-AMP-activated protein kinase-activating transcription factor 1 cascade modulates human monocyte-derived macrophages to atheroprotective functions in response to heme or metformin.	Metformin	172-181	activating transcription factor 1	Homo sapiens	32-65
24051143-8	2013	The AMPK-activating oral hypoglycemic agent metformin also induced and phosphorylated ATF1 at a clinically relevant concentration (10 mumol/L).	Metformin	44-53	activating transcription factor 1	Homo sapiens	86-90
23305245-2	2013	The aim of this study was to investigate the effects of trimethoprim on metformin pharmacokinetics and genetic modulation by organic cation transporter 2 (OCT2) and multidrug and toxin extrusion 1 (MATE1) polymorphisms.	Metformin	72-81	solute carrier family 22 member 2	Homo sapiens	155-159
23980058-17	2013	Treatment with either metformin or simvastatin attenuated the fibrosis progression induced by DHEA exposure, as evidenced by a reduction of TGF-beta, plus CTGF or not, in both ovarian and uterine tissues.	Metformin	22-31	cellular communication network factor 2	Rattus norvegicus	155-159
24204674-11	2013	In addition, metformin nearly abrogated the binding of NF-kappaB subunit p65 to the iNOS promoter gene in lung tissue of obese mice.	Metformin	13-22	v-rel reticuloendotheliosis viral oncogene homolog A (avian)	Mus musculus	73-76
24227948-0	2013	The Effect of Metformin Treatment on CRBP-I Level and Cancer Development in the Liver of HBx Transgenic Mice.	Metformin	14-23	X protein	Hepatitis B virus	89-92
24227948-6	2013	Chronic treatment of HBx Tg mice with metformin did not affect the incidence of HCC, but slightly increased hepatic CRBP-I level.	Metformin	38-47	X protein	Hepatitis B virus	21-24
24227948-6	2013	Chronic treatment of HBx Tg mice with metformin did not affect the incidence of HCC, but slightly increased hepatic CRBP-I level.	Metformin	38-47	retinol binding protein 1, cellular	Mus musculus	116-122
24023727-6	2013	Ang II stimulation induced the differentiation of cardiac fibroblasts into myofibroblasts, as indicated by increased expression of alpha-smooth muscle actin (alpha-SMA) and collagen types I and III, and this effect of Ang II was inhibited by pretreatment of cardiac fibroblasts with metformin.	Metformin	283-292	actin gamma 2, smooth muscle	Rattus norvegicus	131-156
23852330-7	2013	The pivotal role of hOCT2 for renal secretion of creatinine and metformin was confirmed in clinical studies.	Metformin	64-73	solute carrier family 22 member 2	Homo sapiens	20-25
24009772-6	2013	Finally, metformin induced PIM-2 kinase activity and co-treatment of ALL cells with a PIM-1/2 kinase inhibitor plus metformin synergistically increased cell death, suggesting a buffering role for PIM-2 in metformin"s cytotoxicity.	Metformin	9-18	Pim-2 proto-oncogene, serine/threonine kinase	Homo sapiens	27-32
24009772-6	2013	Finally, metformin induced PIM-2 kinase activity and co-treatment of ALL cells with a PIM-1/2 kinase inhibitor plus metformin synergistically increased cell death, suggesting a buffering role for PIM-2 in metformin"s cytotoxicity.	Metformin	9-18	Pim-2 proto-oncogene, serine/threonine kinase	Homo sapiens	196-201
24009772-6	2013	Finally, metformin induced PIM-2 kinase activity and co-treatment of ALL cells with a PIM-1/2 kinase inhibitor plus metformin synergistically increased cell death, suggesting a buffering role for PIM-2 in metformin"s cytotoxicity.	Metformin	116-125	Pim-2 proto-oncogene, serine/threonine kinase	Homo sapiens	196-201
24009772-6	2013	Finally, metformin induced PIM-2 kinase activity and co-treatment of ALL cells with a PIM-1/2 kinase inhibitor plus metformin synergistically increased cell death, suggesting a buffering role for PIM-2 in metformin"s cytotoxicity.	Metformin	116-125	Pim-2 proto-oncogene, serine/threonine kinase	Homo sapiens	196-201
23659985-11	2013	Maternal metformin did not impact maternal markers but significantly decreased diet-induced TNF-alpha and chemokine (C-C motif) ligand 2 in the fetal plasma.	Metformin	9-18	C-C motif chemokine ligand 2	Rattus norvegicus	106-136
23709654-9	2013	In vitro data revealed that metformin inhibited cancer cell growth, activated cAMP-inducible protein kinase (5"-AMP-activated protein kinase [AMPK]), and down-regulated p70S6K/pS6.	Metformin	28-37	ribosomal protein S6 kinase B1	Homo sapiens	169-175
23709654-10	2013	Metformin potentiated H2O2-inducible activation of AMPK but attenuated pERK and p70S6K.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	80-86
23709654-14	2013	In vitro data suggest that p70S6K/pS6 is likely a molecular target of metformin in DTC cells.	Metformin	70-79	ribosomal protein S6 kinase B1	Homo sapiens	27-33
23709117-5	2013	Here we compared the IC50 values obtained for a set of structurally distinct inhibitors against OCT2-mediated transport of three structurally distinct substrates: 1-methyl-4-phenylpyridinium (MPP); metformin; and a novel fluorescent substrate, N,N,N-trimethyl-2-[methyl(7-nitrobenzo[c][l,2,5]oxadiazol-4-yl)amino]ethanaminium iodide (NBD-MTMA).	Metformin	198-207	solute carrier family 22 member 2	Homo sapiens	96-100
23741061-0	2013	Metformin blocks melanoma invasion and metastasis development in AMPK/p53-dependent manner.	Metformin	0-9	transformation related protein 53, pseudogene	Mus musculus	70-73
23936124-9	2013	AMPK activation by metformin completely reversed the inhibitory effect of glucose on Nampt-Sirt1-PGC-1 alpha and Rev-erb alpha.	Metformin	19-28	sirtuin 1	Mus musculus	91-96
23362830-0	2013	Metformin induces cytotoxicity by down-regulating thymidine phosphorylase and excision repair cross-complementation 1 expression in non-small cell lung cancer cells.	Metformin	0-9	ERCC excision repair 1, endonuclease non-catalytic subunit	Homo sapiens	78-117
23362830-3	2013	We used A549 and H1975 human non-small cell lung cancer (NSCLC) cell lines to investigate the role of TP and ERCC1 expression in metformin-induced cytotoxicity.	Metformin	129-138	ERCC excision repair 1, endonuclease non-catalytic subunit	Homo sapiens	109-114
23362830-4	2013	Metformin treatment decreased cellular TP and ERCC1 protein and mRNA levels by down-regulating phosphorylated MEK1/2-ERK1/2 protein levels in a dose- and time-dependent manner.	Metformin	0-9	ERCC excision repair 1, endonuclease non-catalytic subunit	Homo sapiens	46-51
23362830-4	2013	Metformin treatment decreased cellular TP and ERCC1 protein and mRNA levels by down-regulating phosphorylated MEK1/2-ERK1/2 protein levels in a dose- and time-dependent manner.	Metformin	0-9	mitogen-activated protein kinase kinase 1	Homo sapiens	110-116
23362830-6	2013	Specific inhibition of TP and ERCC1 expression by siRNA enhanced the metformin-induced cytotoxicity and growth inhibition.	Metformin	69-78	ERCC excision repair 1, endonuclease non-catalytic subunit	Homo sapiens	30-35
23362830-7	2013	Arachidin-1, an antioxidant stilbenoid, further decreased TP and ERCC1 expression and augmented metformin"s cytotoxic effect, which was abrogated in lung cancer cells transfected with MEK1/2-CA expression vector.	Metformin	96-105	mitogen-activated protein kinase kinase 1	Homo sapiens	184-190
23362830-8	2013	In conclusion, metformin induces cytotoxicity by down-regulating TP and ERCC1 expression in NSCLC cells.	Metformin	15-24	ERCC excision repair 1, endonuclease non-catalytic subunit	Homo sapiens	72-77
23462329-3	2013	Here, we determined whether metformin administration inhibits the growth of PANC-1 and MiaPaCa-2 tumor xenografts in vivo.	Metformin	28-37	pancreas protein 1	Mus musculus	76-82
23462329-5	2013	RESULTS: We demonstrate that metformin given once daily intraperitoneally at various doses (50-250 mg/kg) to nude mice inhibited the growth of PANC-1 xenografts in a dose-dependent manner.	Metformin	29-38	pancreas protein 1	Mus musculus	143-149
23663483-9	2013	The anti-proliferative actions of metformin were associated with an activation of AMP-activated protein kinase AMPKThr172 together with an inhibition of the insulin/insulin-like growth factor-I (IGF-I) receptor activation and downstream signalling mediators IRS-1 and phosphorylated Akt.	Metformin	34-43	insulin receptor substrate 1	Homo sapiens	258-263
23480783-0	2013	Free fatty acid binding protein-4 and retinol binding protein-4 in polycystic ovary syndrome: response to simvastatin and metformin therapies.	Metformin	122-131	fatty acid binding protein 4	Homo sapiens	5-33
23577667-9	2013	Treatment of HTLV-1 transformed cells with metformin led to LKB1/SIK1 activation, reduction in Tax expression, and inhibition of cell proliferation.	Metformin	43-52	serine/threonine kinase 11	Homo sapiens	60-64
23223177-4	2013	Conversely, activation of AMPK by metformin stimulated JNK1-Bcl-2 signaling and disrupted the Beclin1-Bcl-2 complex.	Metformin	34-43	beclin 1, autophagy related	Mus musculus	94-101
23223177-7	2013	Finally, chronic administration of metformin in diabetic mice restored cardiac autophagy by activating JNK1-Bcl-2 pathways and dissociating Beclin1 and Bcl-2.	Metformin	35-44	beclin 1, autophagy related	Mus musculus	140-147
23171036-2	2013	We have explored the effectiveness of metformin for alleviating insulin resistance in HIV-infected patients and assessed the relevance of the ataxia-telangiectasia mutated (ATM) rs11212617 variant in the clinical response with the rationale that metformin modulates cellular bioenergetics in an ATM-dependent process.	Metformin	246-255	ATM serine/threonine kinase	Homo sapiens	142-171
23171036-2	2013	We have explored the effectiveness of metformin for alleviating insulin resistance in HIV-infected patients and assessed the relevance of the ataxia-telangiectasia mutated (ATM) rs11212617 variant in the clinical response with the rationale that metformin modulates cellular bioenergetics in an ATM-dependent process.	Metformin	246-255	ATM serine/threonine kinase	Homo sapiens	173-176
23171036-10	2013	CONCLUSIONS: We provide novel data suggesting that identification of the ATM rs11212617 variant may be important in assessing the glycaemic response to metformin treatment for insulin resistance in HIV-infected patients.	Metformin	152-161	ATM serine/threonine kinase	Homo sapiens	73-76
23621234-10	2013	In conclusion, expression changes in miRNAs of miR-146a, miR-100, miR-425, miR-193a-3p and, miR-106b in metformin-treated cells may be important.	Metformin	104-113	microRNA 146a	Homo sapiens	47-55
23621234-10	2013	In conclusion, expression changes in miRNAs of miR-146a, miR-100, miR-425, miR-193a-3p and, miR-106b in metformin-treated cells may be important.	Metformin	104-113	microRNA 100	Homo sapiens	57-64
23991948-2	2013	Besides the discovery of somatic mutations in the LKB1 gene in certain type of cancers, a critical emerging point was that the LKB1/AMPK axis remains generally functional and could be stimulated by pharmacological molecules such as metformin in cancer cells.	Metformin	232-241	serine/threonine kinase 11	Homo sapiens	50-54
23991948-2	2013	Besides the discovery of somatic mutations in the LKB1 gene in certain type of cancers, a critical emerging point was that the LKB1/AMPK axis remains generally functional and could be stimulated by pharmacological molecules such as metformin in cancer cells.	Metformin	232-241	serine/threonine kinase 11	Homo sapiens	127-131
23431246-7	2013	HE3286 HbA1c decrease correlated with weight loss and inversely with baseline monocyte chemoattractant protein-1 (MCP-1) in metformin-treated diabetics.	Metformin	124-133	C-C motif chemokine ligand 2	Homo sapiens	78-112
23431246-7	2013	HE3286 HbA1c decrease correlated with weight loss and inversely with baseline monocyte chemoattractant protein-1 (MCP-1) in metformin-treated diabetics.	Metformin	124-133	C-C motif chemokine ligand 2	Homo sapiens	114-119
22841520-5	2013	RESULTS: Compared to placebo, metformin reduced monocyte release of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, monocyte chemoattractant protein-1 and interleukin-8, as well as decreased plasma C-reactive protein levels, which were accompanied by an improvement in insulin sensitivity.	Metformin	30-39	C-C motif chemokine ligand 2	Homo sapiens	131-165
24399727-6	2013	RESULTS: Metformin treatment reduced plasma C-reactive protein levels and monocyte release of tumor necrosis factor-alpha and interleukin-6, as well as tended to reduce monocyte release of interleukin-1beta and monocyte chemoattractant protein-1, which was accompanied by an improvement in insulin sensitivity.	Metformin	9-18	C-C motif chemokine ligand 2	Homo sapiens	211-245
23135276-9	2012	Moreover, AMPK knockdown attenuated metformin-induced Cbl/CAP multicomplex formation, which is critical for GLUT4 translocation.	Metformin	36-45	Casitas B-lineage lymphoma	Mus musculus	54-57
23135276-10	2012	A colorimetric absorbance assay demonstrated that metformin-induced translocation of GLUT4 was suppressed in CAP or Cbl knockdown cells.	Metformin	50-59	Casitas B-lineage lymphoma	Mus musculus	116-119
23135276-12	2012	In summary, these results demonstrate that metformin modulates GLUT4 translocation by regulating Cbl and CAP signals via AMPK.	Metformin	43-52	Casitas B-lineage lymphoma	Mus musculus	97-100
23019312-8	2012	Overall, this study indicates that exercise training and metformin have additive influences on adipose tissue secretion and plasma concentrations of leptin and IL-10.	Metformin	57-66	interleukin 10	Rattus norvegicus	160-165
23346251-5	2012	The aim of our study is to assess AMH as a prognostic marker for metformin therapy efficiency in the treatment of women with infertility and polycystic ovary syndrome (PCOS).	Metformin	65-74	anti-Mullerian hormone	Homo sapiens	34-37
23346251-10	2012	After 2 months of treatment with metformin ovulation was restored in all the patients and the serum AMH levels were significantly decreased.	Metformin	33-42	anti-Mullerian hormone	Homo sapiens	100-103
23346251-11	2012	CONCLUSIONS: In clinical practice, serum AMH levels of women with infertility and PCOS receiving metformin are a useful predictive marker for the treatment efficiency.	Metformin	97-106	anti-Mullerian hormone	Homo sapiens	41-44
20455069-8	2012	Metformin at 48 h only in microvascular endothelial cells is able to reduce in a significant manner (p = 0.01) the activity of DPP-4 but not its expression.	Metformin	0-9	dipeptidyl peptidase 4	Homo sapiens	127-132
22968630-5	2012	The reactive oxygen species (ROS) levels in NYGGF4 overexpression adipocytes were strikingly enhanced, which could be decreased by the metformin pretreatment.	Metformin	135-144	phosphotyrosine interaction domain containing 1	Homo sapiens	44-50
22968630-6	2012	Our data also showed that metformin increased the expressions of PGC1-alpha, NRF-1, and TFAM, which were reduced in the NYGGF4 overexpression adipocytes.	Metformin	26-35	phosphotyrosine interaction domain containing 1	Homo sapiens	120-126
22968630-7	2012	These results suggest that NYGGF4 plays a role in IR and its effects on IR could be reversed by metformin through activating IRS-1/PI3K/Akt and AMPK-PGC1-alpha pathways.	Metformin	96-105	phosphotyrosine interaction domain containing 1	Homo sapiens	27-33
22968630-7	2012	These results suggest that NYGGF4 plays a role in IR and its effects on IR could be reversed by metformin through activating IRS-1/PI3K/Akt and AMPK-PGC1-alpha pathways.	Metformin	96-105	insulin receptor substrate 1	Homo sapiens	125-130
23173578-9	2012	Various drugs have been reported to induce FGF21, including peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists such as fenofibrate, the histone deacetylase inhibitor sodium butyrate, and adenosine monophosphate (AMP) kinase activators metformin and 5-amino-1-beta-D-ribofuranosyl-imidazole-4-carboxamide (AICAR).	Metformin	254-263	peroxisome proliferator activated receptor alpha	Homo sapiens	60-108
23173578-9	2012	Various drugs have been reported to induce FGF21, including peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists such as fenofibrate, the histone deacetylase inhibitor sodium butyrate, and adenosine monophosphate (AMP) kinase activators metformin and 5-amino-1-beta-D-ribofuranosyl-imidazole-4-carboxamide (AICAR).	Metformin	254-263	peroxisome proliferator activated receptor alpha	Homo sapiens	110-119
22977252-8	2012	Up-regulation of SHP by metformin-mediated activation of the ATM-AMP-activated protein kinase pathway led to inhibition of GH-mediated induction of hepatic gluconeogenesis, which was abolished by an ATM inhibitor, KU-55933.	Metformin	24-33	growth hormone	Mus musculus	123-125
22977252-10	2012	GH-induced hepatic gluconeogenesis was decreased by either metformin or Ad-SHP, whereas the inhibition by metformin was abolished by SHP knockdown.	Metformin	59-68	growth hormone	Mus musculus	0-2
22751958-1	2012	OBJECTIVE: The C allele at the rs11212617 polymorphism in the ataxia-telangiectasia-mutated (ATM) gene has been associated with greater clinical response to metformin in people with type 2 diabetes.	Metformin	157-166	ATM serine/threonine kinase	Homo sapiens	62-91
22751958-1	2012	OBJECTIVE: The C allele at the rs11212617 polymorphism in the ataxia-telangiectasia-mutated (ATM) gene has been associated with greater clinical response to metformin in people with type 2 diabetes.	Metformin	157-166	ATM serine/threonine kinase	Homo sapiens	93-96
22770998-0	2012	Recommendations for diagnosis and management of metformin-induced vitamin B12 (Cbl) deficiency.	Metformin	48-57	Cbl proto-oncogene	Homo sapiens	79-82
22770998-1	2012	Metformin treatment is a known pharmacological cause of vitamin B12 (Cbl) deficiency with controversial responsible mechanisms.	Metformin	0-9	Cbl proto-oncogene	Homo sapiens	69-72
23130369-0	2012	Replication of the association of gene variant near ATM and response to metformin.	Metformin	72-81	ATM serine/threonine kinase	Homo sapiens	52-55
22950061-7	2012	The hypothalamic phosphorylated signal transducer and activator of transcription 3 (pSTAT3) increased by 3 microg with metformin treatment, but, there was no further increase in pSTAT3 level following increases of metformin dosage.	Metformin	119-128	signal transducer and activator of transcription 3	Rattus norvegicus	32-82
22837425-6	2012	Our current findings suggest for the first time that metformin can function as an antifolate chemotherapeutic agent that induces the ATM/AMPK tumor suppressor axis secondarily following the alteration of the carbon flow through the folate-related one-carbon metabolic pathways.	Metformin	53-62	ATM serine/threonine kinase	Homo sapiens	133-136
22575507-6	2012	Finally, we found that metformin induced the degradation of the oncoproteins PML-RARalpha and c-Myc and activated caspase-3.	Metformin	23-32	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	94-99
22171692-0	2012	The increased dipeptidyl peptidase-4 activity is not counteracted by optimized glucose control in type 2 diabetes, but is lower in metformin-treated patients.	Metformin	131-140	dipeptidyl peptidase 4	Homo sapiens	14-36
22171692-9	2012	In both sets of diabetic patients, the use of metformin was associated with a significantly lower DPP-4 activity, independently of age, sex, body mass index and HbA1c.	Metformin	46-55	dipeptidyl peptidase 4	Homo sapiens	98-103
22171692-11	2012	However, metformin may indirectly reduce DPP-4 activity.	Metformin	9-18	dipeptidyl peptidase 4	Homo sapiens	41-46
21301998-2	2012	Several potential mechanisms have been suggested for the ability of metformin to suppress cancer growth in vitro and vivo: (1) activation of LKB1/AMPK pathway, (2) induction of cell cycle arrest and/or apoptosis, (3) inhibition of protein synthesis, (4) reduction in circulating insulin levels, (5) inhibition of the unfolded protein response (UPR), (6) activation of the immune system, and (7) eradication of cancer stem cells.	Metformin	68-77	serine/threonine kinase 11	Homo sapiens	141-145
22643892-9	2012	Downregulation of c-MYC requires AMP-activated protein kinase-signalling and mir33a upregulation by metformin.	Metformin	100-109	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	18-23
22643892-10	2012	Ectopic expression of c-MYC attenuates the anticancer metabolic effects of metformin.	Metformin	75-84	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	22-27
22643892-11	2012	We suggest that DICER modulation, mir33a upregulation and c-MYC targeting have an important role in the anticancer metabolic effects of metformin.	Metformin	136-145	dicer 1, ribonuclease III	Homo sapiens	16-21
22643892-11	2012	We suggest that DICER modulation, mir33a upregulation and c-MYC targeting have an important role in the anticancer metabolic effects of metformin.	Metformin	136-145	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	58-63
22389381-7	2012	Treatment with metformin was associated with inhibition of mTOR/p70S6K/pS6 signaling and downregulation of pERK in both TT and MZ-CRC-1 cells.	Metformin	15-24	ribosomal protein S6 kinase B1	Homo sapiens	64-70
22389381-7	2012	Treatment with metformin was associated with inhibition of mTOR/p70S6K/pS6 signaling and downregulation of pERK in both TT and MZ-CRC-1 cells.	Metformin	15-24	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	107-111
22349108-4	2012	METHODS: We investigated metformin-mediated SHP production improved insulin resistance through the regulation of an IL-6-dependent pathway (involving signal transducer and activator of transcription 3 [STAT3] and suppressor of cytokine signalling 3 [SOCS3]) in both Shp knockdown and Shp null mice.	Metformin	25-34	suppressor of cytokine signaling 3	Mus musculus	213-248
22349108-4	2012	METHODS: We investigated metformin-mediated SHP production improved insulin resistance through the regulation of an IL-6-dependent pathway (involving signal transducer and activator of transcription 3 [STAT3] and suppressor of cytokine signalling 3 [SOCS3]) in both Shp knockdown and Shp null mice.	Metformin	25-34	suppressor of cytokine signaling 3	Mus musculus	250-255
22349108-5	2012	RESULTS: IL-6-induced STAT3 transactivation and SOCS3 production were significantly repressed by metformin, adenoviral constitutively active AMPK (Ad-CA-AMPK), and adenoviral SHP (Ad-SHP), but not in Shp knockdown, or with the adenoviral dominant negative form of AMPK (Ad-DN-AMPK).	Metformin	97-106	suppressor of cytokine signaling 3	Mus musculus	48-53
22419732-0	2012	Efficacy and tolerability of the DPP-4 inhibitor alogliptin combined with pioglitazone, in metformin-treated patients with type 2 diabetes.	Metformin	91-100	dipeptidyl peptidase 4	Homo sapiens	33-38
22406377-0	2012	Metformin-mediated Bambi expression in hepatic stellate cells induces prosurvival Wnt/beta-catenin signaling.	Metformin	0-9	catenin beta 1	Homo sapiens	86-98
22406377-11	2012	The finding that metformin increases Bambi expression and activates Wnt/beta-catenin signaling provides a possible mechanistic explanation for this observation.	Metformin	17-26	catenin beta 1	Homo sapiens	72-84
22330083-3	2012	We found that pretreatment with metformin significantly decreased serum ALT and AST levels in LPS/D-Gal-exposed mice.	Metformin	32-41	glutamic pyruvic transaminase, soluble	Mus musculus	72-75
22330083-3	2012	We found that pretreatment with metformin significantly decreased serum ALT and AST levels in LPS/D-Gal-exposed mice.	Metformin	32-41	solute carrier family 17 (anion/sugar transporter), member 5	Mus musculus	80-83
20663178-2	2010	The aim of the present study was to evaluate in patients with polycystic ovary syndrome (PCOS) whether metformin administration affects serum and follicular AMH levels, and whether this is related to ovarian response to the treatment.	Metformin	103-112	anti-Mullerian hormone	Homo sapiens	157-160
20663178-11	2010	CONCLUSIONS: Metformin administration in patients with PCOS exerts a differential action on the ovarian AMH levels on the basis of ovulatory response.	Metformin	13-22	anti-Mullerian hormone	Homo sapiens	104-107
20663178-12	2010	Changes in AMH levels in antral follicular fluid during metformin treatment could be involved in the local mechanisms mediating the ovulatory restoration.	Metformin	56-65	anti-Mullerian hormone	Homo sapiens	11-14
21537433-1	2010	The addition of the dipeptidyl peptidase-4 (DDP-4) inhibitor has been reported to achieve greater improvements in glucose metabolism with fewer adverse events compared to increasing the metformin dose in type 2 diabetic patients.	Metformin	186-195	dipeptidyl peptidase 4	Homo sapiens	20-42
21537433-1	2010	The addition of the dipeptidyl peptidase-4 (DDP-4) inhibitor has been reported to achieve greater improvements in glucose metabolism with fewer adverse events compared to increasing the metformin dose in type 2 diabetic patients.	Metformin	186-195	dipeptidyl peptidase 4	Homo sapiens	44-49
20671408-0	2010	Preliminary data on effects of metformin on PED/PEA-15 cellular levels in obese women with polycystic ovary syndrome.	Metformin	31-40	proliferation and apoptosis adaptor protein 15	Homo sapiens	48-54
20671408-2	2010	AIM: To investigate whether metformin (MET) has additive effects on PED/PEA-15 protein levels.	Metformin	28-37	proliferation and apoptosis adaptor protein 15	Homo sapiens	72-78
20371705-0	2010	Metformin, an antidiabetic agent, suppresses the production of tumor necrosis factor and tissue factor by inhibiting early growth response factor-1 expression in human monocytes in vitro.	Metformin	0-9	coagulation factor III, tissue factor	Homo sapiens	89-102
20371705-0	2010	Metformin, an antidiabetic agent, suppresses the production of tumor necrosis factor and tissue factor by inhibiting early growth response factor-1 expression in human monocytes in vitro.	Metformin	0-9	early growth response 1	Homo sapiens	117-147
20371705-5	2010	Metformin significantly inhibited both TNF production and TF expression in isolated human monocytes stimulated with LPS or oxLDL.	Metformin	0-9	coagulation factor III, tissue factor	Homo sapiens	58-60
20371705-6	2010	Metformin also significantly inhibited TNF and TF mRNA in human monocytes stimulated with LPS.	Metformin	0-9	coagulation factor III, tissue factor	Homo sapiens	47-49
20371705-7	2010	Although metformin did not inhibit the activation of either nuclear factor-kappaB or activator protein-1, it inhibited the expression of early growth response factor-1 (Egr-1) and phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2 in monocytes stimulated with LPS or oxLDL.	Metformin	9-18	early growth response 1	Homo sapiens	137-167
20371705-7	2010	Although metformin did not inhibit the activation of either nuclear factor-kappaB or activator protein-1, it inhibited the expression of early growth response factor-1 (Egr-1) and phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2 in monocytes stimulated with LPS or oxLDL.	Metformin	9-18	early growth response 1	Homo sapiens	169-174
20371705-8	2010	These results suggest that metformin may attenuate the inflammatory responses, at least in part, by suppressing the production of both TNF and TF through the inhibition of the ERK1/2-Egr-1 pathway in human monocytes.	Metformin	27-36	coagulation factor III, tissue factor	Homo sapiens	143-145
20371705-8	2010	These results suggest that metformin may attenuate the inflammatory responses, at least in part, by suppressing the production of both TNF and TF through the inhibition of the ERK1/2-Egr-1 pathway in human monocytes.	Metformin	27-36	early growth response 1	Homo sapiens	183-188
20402634-2	2010	Saxagliptin is a nitrile-containing selective, potent, reversible and durable DPP IV inhibitor developed as an alternative second-line adds on to Metformin in place of a sulphonylurea.	Metformin	146-155	dipeptidyl peptidase 4	Homo sapiens	78-84
20564343-13	2010	A Western blot analysis revealed that the phosphorylated mTOR, S6 kinase, and S6 protein levels in the colonic mucosa decreased significantly in mice treated with metformin.	Metformin	163-172	mechanistic target of rapamycin kinase	Mus musculus	57-61
20564343-14	2010	In conclusion, metformin suppresses colonic epithelial proliferation via the inhibition of the mTOR pathway through the activation of AMPK.	Metformin	15-24	mechanistic target of rapamycin kinase	Mus musculus	95-99
20305377-2	2010	In the early 2000s, Anisimov s experiments revealed that chronic treatment of female transgenic HER2-/neu mice with metformin significantly reduced the incidence and size of mammary adenocarcinomas and increased the mean latency of the tumors.	Metformin	116-125	erb-b2 receptor tyrosine kinase 2	Mus musculus	96-100
20305377-6	2010	Our current perception is that metformin may constitute a novel "hybrid anti-cancer pill" physically combining both the long-lasting effects of antibodies -by persistently lowering levels of blood insulin and glucose- and the immediate potency of a cancer cell-targeting molecular agent -by suppressing the pivotal AMPK/mTOR/S6K1 axis and several protein kinases at once, including tyrosine kinase receptors such as HER1 and HER2-.	Metformin	31-40	erb-b2 receptor tyrosine kinase 2	Mus musculus	425-429
20102700-0	2010	Metformin reduces lipid accumulation in macrophages by inhibiting FOXO1-mediated transcription of fatty acid-binding protein 4.	Metformin	0-9	fatty acid binding protein 4	Homo sapiens	98-126
20102700-6	2010	Metformin promoted the expression of carnitine palmitoyltransferase I (CPT-1), while reduced the expression of fatty acid-binding protein 4 (FABP4) which was involved in PA-induced lipid accumulation.	Metformin	0-9	fatty acid binding protein 4	Homo sapiens	111-139
20102700-6	2010	Metformin promoted the expression of carnitine palmitoyltransferase I (CPT-1), while reduced the expression of fatty acid-binding protein 4 (FABP4) which was involved in PA-induced lipid accumulation.	Metformin	0-9	fatty acid binding protein 4	Homo sapiens	141-146
20102700-7	2010	Quantitative real-time PCR showed that metformin regulates FABP4 expression at the transcriptional level.	Metformin	39-48	fatty acid binding protein 4	Homo sapiens	59-64
20102700-11	2010	Metformin reduced FABP4 expression by promoting FOXO1 nuclear exclusion and subsequently inhibiting its activity.	Metformin	0-9	fatty acid binding protein 4	Homo sapiens	18-23
20102700-12	2010	CONCLUSIONS: Taken together, these results suggest that metformin reduces lipid accumulation in macrophages by repressing FOXO1-mediated FABP4 transcription.	Metformin	56-65	fatty acid binding protein 4	Homo sapiens	137-142
20139901-0	2010	SLC22A2 gene 808 G/T variant is related to plasma lactate concentration in Chinese type 2 diabetics treated with metformin.	Metformin	113-122	solute carrier family 22 member 2	Homo sapiens	0-7
20139901-2	2010	METHODS: The SLC22A2 single nucleotide polymorphism (SNP) 808G/T was genotyped in 400 T2DM patients, including a metformin-treated group (n=200) and a non-metformin-treated group (n=200).	Metformin	113-122	solute carrier family 22 member 2	Homo sapiens	13-20
20139901-14	2010	The 808G&gt;T variance in the SLC22A2 gene can affect the plasma lactate level and the incidence of hyperlactacidemia in T2DM patients undergoing metformin therapy.	Metformin	146-155	solute carrier family 22 member 2	Homo sapiens	30-37
20090912-0	2010	Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans Healthspan via AMPK, LKB1, and SKN-1.	Metformin	0-9	BZIP domain-containing protein;Protein skinhead-1	Caenorhabditis elegans	137-142
20090912-6	2010	We also show that the conserved oxidative stress-responsive transcription factor SKN-1/Nrf2 is essential for metformin healthspan benefits in C. elegans, a mechanistic requirement not previously described in mammals.	Metformin	109-118	BZIP domain-containing protein;Protein skinhead-1	Caenorhabditis elegans	81-86
20090912-7	2010	skn-1, which functions in nematode sensory neurons to promote DR longevity benefits and in intestines for oxidative stress resistance lifespan benefits, must be expressed in both neurons and intestines for metformin-promoted healthspan extension, supporting that metformin improves healthy middle-life aging by activating both DR and antioxidant defense longevity pathways.	Metformin	206-215	BZIP domain-containing protein;Protein skinhead-1	Caenorhabditis elegans	0-5
20090912-7	2010	skn-1, which functions in nematode sensory neurons to promote DR longevity benefits and in intestines for oxidative stress resistance lifespan benefits, must be expressed in both neurons and intestines for metformin-promoted healthspan extension, supporting that metformin improves healthy middle-life aging by activating both DR and antioxidant defense longevity pathways.	Metformin	263-272	BZIP domain-containing protein;Protein skinhead-1	Caenorhabditis elegans	0-5
20016287-0	2010	Metformin extends life span of HER-2/neu transgenic mice and in combination with melatonin inhibits growth of transplantable tumors in vivo.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Mus musculus	31-40
20016287-2	2010	In our animal studies, metformin delayed the onset of mammary adenocarcinoma (MAC) in transgenic HER-2/neu mice but not the onset of spontaneous mammary tumors in female SHR mice.	Metformin	23-32	erb-b2 receptor tyrosine kinase 2	Mus musculus	97-102
20016287-2	2010	In our animal studies, metformin delayed the onset of mammary adenocarcinoma (MAC) in transgenic HER-2/neu mice but not the onset of spontaneous mammary tumors in female SHR mice.	Metformin	23-32	erb-b2 receptor tyrosine kinase 2	Mus musculus	103-106
20016287-5	2010	Metformin (0.5 mg/ml in drinking water) increased mean life span by 8% and MAC latency by 13.2% (p &lt; 0.05) in HER2/neu mice.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Mus musculus	113-117
20016287-5	2010	Metformin (0.5 mg/ml in drinking water) increased mean life span by 8% and MAC latency by 13.2% (p &lt; 0.05) in HER2/neu mice.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Mus musculus	118-121
20016287-7	2010	The treatment metformin alone inhibited the growth of transplantable HER2 mammary carcinoma in FVB/N male mice by 46% at the 45(th) day after transplantation (p &lt; 0.001).	Metformin	14-23	erb-b2 receptor tyrosine kinase 2	Mus musculus	69-73
19019358-9	2010	Greater decreases in plasminogen activator inhibitor-1 occurred for the OCP than for metformin (-1.8 +/- 1.6 vs. -0.7 +/- 1.7 U/mL).	Metformin	85-94	serpin family E member 1	Homo sapiens	21-54
20798864-7	2010	Further, metformin increased IkappaBalpha levels in both WG (150%) and RG (67%) of obese rats, indicative of reduced IKKbeta activity (P &lt; .05), and was associated with reduced IRS1-pSer(307) (30%) in the WG of obese rats (P &lt; .02).	Metformin	9-18	NFKB inhibitor alpha	Rattus norvegicus	29-41
20798864-8	2010	From these data we conclude that metformin treatment appears to exert an inhibitory influence on skeletal muscle IKKbeta activity, as evidenced by elevated IkappaBalpha levels and reduced IRS1-Ser(307) phosphorylation in a fiber-type specific manner.	Metformin	33-42	NFKB inhibitor alpha	Rattus norvegicus	156-168
20923527-7	2009	Glucose reduced AMPK activity, while the AMPK activators 5-amino-4-imidazolecarboxamide riboside and metformin increased PPARalpha expression and suppressed the action of glucose.	Metformin	101-110	peroxisome proliferator activated receptor alpha	Rattus norvegicus	121-130
19661063-6	2009	In addition to adiponectin, metformin also induces APPL1-APPL2 dissociation.	Metformin	28-37	adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1	Homo sapiens	51-56
19672815-5	2009	Here we studied the effects of glucose, metformin, and AICAR on the expression of GPCR in INS-1 beta cell.	Metformin	40-49	relaxin family peptide receptor 2	Rattus norvegicus	82-86
19672815-11	2009	These results indicate that glucose, metformin, and AICAR regulated the expressions of incretin receptors and PPARalpha, but not GPR40 in beta cells.	Metformin	37-46	peroxisome proliferator activated receptor alpha	Rattus norvegicus	110-119
19674806-7	2009	Serum MMP-9 levels were decreased in the metformin (-13.5+/-34.8%, p=0.02) and rosiglitazone (-27.2+/-51.0%, p=0.023) groups compared with baseline values, whereas no significant change was seen in serum MCP-1 levels.	Metformin	41-50	C-C motif chemokine ligand 2	Homo sapiens	204-209
19591196-2	2009	Because interindividual variability of OCT expression may affect response to cationic drugs such as metformin, we systematically investigated genetic and nongenetic factors of OCT1/SLC22A1 and OCT3/SLC22A3 expression in human liver.	Metformin	100-109	plexin A2	Homo sapiens	39-42
19591196-14	2009	This indicates consequences for hepatic elimination of and response to OCT substrates such as metformin.	Metformin	94-103	plexin A2	Homo sapiens	71-74
19570550-0	2009	Metformin promotes induction of lipoprotein lipase in skeletal muscle through activation of adenosine monophosphate-activated protein kinase.	Metformin	0-9	lipoprotein lipase	Homo sapiens	32-50
19570550-1	2009	Metformin is known to increase lipoprotein lipase (LPL) mass level in serum.	Metformin	0-9	lipoprotein lipase	Homo sapiens	31-49
19570550-1	2009	Metformin is known to increase lipoprotein lipase (LPL) mass level in serum.	Metformin	0-9	lipoprotein lipase	Homo sapiens	51-54
19570550-3	2009	This study aimed to examine the effect of metformin on LPL production in adipocytes and skeletal muscle cells and to investigate the mechanism by which metformin enhances LPL production.	Metformin	42-51	lipoprotein lipase	Homo sapiens	55-58
19570550-3	2009	This study aimed to examine the effect of metformin on LPL production in adipocytes and skeletal muscle cells and to investigate the mechanism by which metformin enhances LPL production.	Metformin	152-161	lipoprotein lipase	Homo sapiens	171-174
19570550-6	2009	Metformin increased LPL activity only in skeletal muscle cells.	Metformin	0-9	lipoprotein lipase	Homo sapiens	20-23
19570550-9	2009	Like metformin, AICAR increased LPL activity only in skeletal muscle cells.	Metformin	5-14	lipoprotein lipase	Homo sapiens	32-35
19570550-10	2009	Both metformin and AICAR also enhanced LPL protein and LPL mRNA expressions in skeletal muscle cells but not in adipocytes.	Metformin	5-14	lipoprotein lipase	Homo sapiens	39-42
19570550-10	2009	Both metformin and AICAR also enhanced LPL protein and LPL mRNA expressions in skeletal muscle cells but not in adipocytes.	Metformin	5-14	lipoprotein lipase	Homo sapiens	55-58
19570550-12	2009	Lipoprotein lipase activity and LPL expression, which were enhanced by 1 mumol/L metformin, were reduced by AMPKalpha small interfering RNA.	Metformin	81-90	lipoprotein lipase	Homo sapiens	0-18
19570550-12	2009	Lipoprotein lipase activity and LPL expression, which were enhanced by 1 mumol/L metformin, were reduced by AMPKalpha small interfering RNA.	Metformin	81-90	lipoprotein lipase	Homo sapiens	32-35
19756305-0	2009	Zinc-activated C-peptide resistance to the type 2 diabetic erythrocyte is associated with hyperglycemia-induced phosphatidylserine externalization and reversed by metformin.	Metformin	163-172	insulin 2	Rattus norvegicus	15-24
19756305-3	2009	Thus, the aims of this study were to demonstrate that Zn(2+)-activated C-peptide exerts potentially beneficial effects on healthy ERYs and that these same effects on type 2 diabetic ERYs are enhanced in the presence of metformin.	Metformin	219-228	insulin 2	Rattus norvegicus	71-80
19756305-7	2009	Phosphatidylserine (PS) externalization and metformin sensitization of Zn(2+)-activated C-peptide were examined spectrofluorometrically by measuring the binding of FITC-labeled annexin to PS.	Metformin	44-53	insulin 2	Rattus norvegicus	88-97
19756305-9	2009	Summarily, data obtained here demonstrate an apparent resistance to Zn(2+)-activated C-peptide by the ERY that is corrected by metformin.	Metformin	127-136	insulin 2	Rattus norvegicus	85-94
19576170-6	2009	Moreover, metformin strongly decreased mRNA levels of selenophosphate synthetase 2 (SPS-2), an enzyme essential for selenoprotein biosynthesis.	Metformin	10-19	selenophosphate synthetase 2	Rattus norvegicus	54-82
19576170-6	2009	Moreover, metformin strongly decreased mRNA levels of selenophosphate synthetase 2 (SPS-2), an enzyme essential for selenoprotein biosynthesis.	Metformin	10-19	selenophosphate synthetase 2	Rattus norvegicus	84-89
19679549-0	2009	Metformin disrupts crosstalk between G protein-coupled receptor and insulin receptor signaling systems and inhibits pancreatic cancer growth.	Metformin	0-9	C-X-C motif chemokine receptor 6	Homo sapiens	37-63
19679549-4	2009	Here, we determined whether metformin disrupts the crosstalk between insulin receptor and GPCR signaling in pancreatic cancer cells.	Metformin	28-37	C-X-C motif chemokine receptor 6	Homo sapiens	90-94
19679549-8	2009	Low doses of metformin (0.1-0.5 mmol/L) blocked the stimulation of DNA synthesis, and the anchorage-dependent and anchorage-independent growth induced by insulin and GPCR agonists.	Metformin	13-22	C-X-C motif chemokine receptor 6	Homo sapiens	166-170
19520843-2	2009	Here we show that in muscle cells adiponectin and metformin induce AMPK activation by promoting APPL1-dependent LKB1 cytosolic translocation.	Metformin	50-59	adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1	Homo sapiens	96-101
19520843-2	2009	Here we show that in muscle cells adiponectin and metformin induce AMPK activation by promoting APPL1-dependent LKB1 cytosolic translocation.	Metformin	50-59	serine/threonine kinase 11	Homo sapiens	112-116
19528375-7	2009	Metformin treatment also normalized acetylcholine-induced endothelial relaxation and increased the levels of GTPCH I and BH4.	Metformin	0-9	GTP cyclohydrolase 1	Mus musculus	109-114
19483665-0	2009	Effect of genetic variation in the organic cation transporter 2 on the renal elimination of metformin.	Metformin	92-101	solute carrier family 22 member 2	Homo sapiens	35-63
19483665-1	2009	OBJECTIVE: The goal of this study was to determine the effect of a genetic variant in the organic cation transporter 2 (OCT2), OCT2-808G/T, which results in an amino acid change, A270S, on the pharmacokinetics of the antidiabetic drug, metformin.	Metformin	236-245	solute carrier family 22 member 2	Homo sapiens	90-118
19483665-1	2009	OBJECTIVE: The goal of this study was to determine the effect of a genetic variant in the organic cation transporter 2 (OCT2), OCT2-808G/T, which results in an amino acid change, A270S, on the pharmacokinetics of the antidiabetic drug, metformin.	Metformin	236-245	solute carrier family 22 member 2	Homo sapiens	120-124
19483665-1	2009	OBJECTIVE: The goal of this study was to determine the effect of a genetic variant in the organic cation transporter 2 (OCT2), OCT2-808G/T, which results in an amino acid change, A270S, on the pharmacokinetics of the antidiabetic drug, metformin.	Metformin	236-245	solute carrier family 22 member 2	Homo sapiens	127-131
19483665-7	2009	RESULTS: We observed that in HEK-293 stably transfected cells, OCT2-808T had a greater capacity to transport metformin than did the reference OCT2.	Metformin	109-118	solute carrier family 22 member 2	Homo sapiens	63-67
19483665-10	2009	Multivariate analysis revealed that OCT2 genotype was a significant predictor of CL(R) and SrCL(R) of metformin (P&lt;0.01).	Metformin	102-111	solute carrier family 22 member 2	Homo sapiens	36-40
19483665-11	2009	CONCLUSION: We conclude that genetic variation in OCT2 plays an important role in the CL(R) and SrCL(R) of metformin in healthy volunteers.	Metformin	107-116	solute carrier family 22 member 2	Homo sapiens	50-54
18839053-0	2009	The effect of metformin on leptin in obese patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease.	Metformin	14-23	leptin	Homo sapiens	27-33
19538242-0	2009	Investigation of the effect of oral metformin on dipeptidylpeptidase-4 (DPP-4) activity in Type 2 diabetes.	Metformin	36-45	dipeptidyl peptidase 4	Homo sapiens	49-70
19538242-0	2009	Investigation of the effect of oral metformin on dipeptidylpeptidase-4 (DPP-4) activity in Type 2 diabetes.	Metformin	36-45	dipeptidyl peptidase 4	Homo sapiens	72-77
19538242-3	2009	We investigated the acute effects of metformin with and without food on DPP-4 activity in Type 2 diabetes.	Metformin	37-46	dipeptidyl peptidase 4	Homo sapiens	72-77
19538242-8	2009	However, DPP-4 activity was suppressed with metformin following fasting compared with a SMM (n = 6) (AUC(0-4 h) 1578 +/- 4 vs. 1494 +/- 9 micromol/min, P &lt; 0.02).	Metformin	44-53	dipeptidyl peptidase 4	Homo sapiens	9-14
19538242-10	2009	CONCLUSION: Metformin inhibits DPP-4 activity in Type 2 diabetic patients in the fasting state but not when taken with a standard mixed meal.	Metformin	12-21	dipeptidyl peptidase 4	Homo sapiens	31-36
19251820-10	2009	Moreover, out of a set of 27 compounds p.270Ala>Ser OCT2 was significantly less sensitive to inhibition by cimetidine, flurazepam, metformin, mexiletine, propranolol, and verapamil than wild-type OCT2 (e.g., for propranolol: IC(50) wild type versus p.270Ala>Ser 189 versus 895 microM, P < 0.001).	Metformin	131-140	solute carrier family 22 member 2	Homo sapiens	52-56
19251820-10	2009	Moreover, out of a set of 27 compounds p.270Ala>Ser OCT2 was significantly less sensitive to inhibition by cimetidine, flurazepam, metformin, mexiletine, propranolol, and verapamil than wild-type OCT2 (e.g., for propranolol: IC(50) wild type versus p.270Ala>Ser 189 versus 895 microM, P < 0.001).	Metformin	131-140	solute carrier family 22 member 2	Homo sapiens	196-200
18565522-8	2009	Compared with a nonhyperandrogenic control group, the increased CIMT values of PCOS patients decreased to the normal range after treatment with either metformin or Diane(35) Diario.	Metformin	151-160	CIMT	Homo sapiens	64-68
18565522-11	2009	Treatment with either Diane(35) Diario or metformin improved CIMT mean values.	Metformin	42-51	CIMT	Homo sapiens	61-65
19267709-0	2009	Study rationale and design of the CIMT trial: the Copenhagen Insulin and Metformin Therapy trial.	Metformin	73-82	CIMT	Homo sapiens	34-38
19267709-4	2009	OBJECTIVE: The primary objective of this trial is to evaluate the effect of an 18-month treatment with metformin vs. placebo in combination with one of three insulin analogue regimens, the primary outcome measure being carotid intima-media thickness (CIMT) in T2DM patients.	Metformin	103-112	CIMT	Homo sapiens	251-255
19267709-18	2009	CONCLUSION: CIMT is designed to provide evidence as to whether metformin is advantageous even during insulin treatment and to provide evidence regarding which insulin analogue regimen is most advantageous with regard to cardiovascular disease.	Metformin	63-72	CIMT	Homo sapiens	12-16
19221498-6	2009	At the molecular level, metformin treatment was associated with a reduction of cyclin D1 and E2F1 expression with no changes in p27(kip1) or p21(waf1).	Metformin	24-33	E2F transcription factor 1	Homo sapiens	93-97
19418728-0	2009	[Effect of the Gly972Arg, SNP43 and Prol2Ala polymorphisms of the genes IRS1, CAPN10 and PPARG2 on secondary failure to sulphonylurea and metformin in patients with type 2 diabetes in Yucatan, Mexico].	Metformin	138-147	insulin receptor substrate 1	Homo sapiens	72-76
19418728-3	2009	The association of the polymorphisms Gly972Arg, SNP43, and Pro12Ala, of the genes IRS1, CAPN10, PPARG2, with the risk of failure to sulphonylurea and metformin therapies was determinated in patients with DT2 in Yucatan, Mexico.	Metformin	150-159	insulin receptor substrate 1	Homo sapiens	82-86
19055479-0	2009	O-glycoside biomarker of apolipoprotein C3: responsiveness to obesity, bariatric surgery, and therapy with metformin, to chronic or severe liver disease and to mortality in severe sepsis and graft vs host disease.	Metformin	107-116	apolipoprotein C3	Homo sapiens	25-42
19106626-2	2009	Animal studies have shown that metformin suppresses the development of mammary carcinomas in transgenic female mice carrying a HER2 oncogene, but not that of spontaneous tumors.	Metformin	31-40	erb-b2 receptor tyrosine kinase 2	Mus musculus	127-131
18972094-8	2009	CONCLUSIONS/INTERPRETATION: Combined thiazolidinedione-metformin treatment markedly improves sub-maximal and maximal insulin signalling to IR, IRS-1/PI3K, aPKC and PKBbeta in type 2 diabetic muscle.	Metformin	55-64	insulin receptor substrate 1	Homo sapiens	143-148
18972094-8	2009	CONCLUSIONS/INTERPRETATION: Combined thiazolidinedione-metformin treatment markedly improves sub-maximal and maximal insulin signalling to IR, IRS-1/PI3K, aPKC and PKBbeta in type 2 diabetic muscle.	Metformin	55-64	AKT serine/threonine kinase 2	Homo sapiens	164-171
19273354-2	2009	Currently, metformin pharmacogenetics is focussing on drug transport with the recent finding that variation in OCT transporters might affect metformin response.	Metformin	11-20	plexin A2	Homo sapiens	111-114
19273354-2	2009	Currently, metformin pharmacogenetics is focussing on drug transport with the recent finding that variation in OCT transporters might affect metformin response.	Metformin	141-150	plexin A2	Homo sapiens	111-114
19084933-8	2008	The general caspase inhibitor (VAD-fmk) completely abolished metformin-induced PARP cleavage and apoptosis in ASPC-1 BxPc-3 and PANC-1, the caspase-8 specific inhibitor (IETD-fmk) and the caspase-9 specific inhibitor (LEHD-fmk) only partially abrogated metformin-induced apoptosis and PARP cleavage in BxPc-3 and PANC-1 cells.	Metformin	61-70	caspase 9	Homo sapiens	188-197
19046439-0	2008	Cell cycle arrest in Metformin treated breast cancer cells involves activation of AMPK, downregulation of cyclin D1, and requires p27Kip1 or p21Cip1.	Metformin	21-30	cyclin dependent kinase inhibitor 1B	Homo sapiens	130-137
19046439-11	2008	The metformin-resistant cell line MDA-MB-231 expresses significantly lower levels of p27Kip1 and p21Cip1 than the metformin-sensitive cell line, MCF7.	Metformin	4-13	cyclin dependent kinase inhibitor 1B	Homo sapiens	85-92
19046439-12	2008	When p27Kip1 or p21Cip1 were overexpressed in MDA-MB-231, the cells became sensitive to cell cycle arrest in response to metformin.	Metformin	121-130	cyclin dependent kinase inhibitor 1B	Homo sapiens	5-12
18721796-3	2008	Metformin (50 microM) significantly increased collagen-I and osteocalcin mRNA expression, stimulated alkaline phosphatase activity, and enhanced cell mineralization.	Metformin	0-9	bone gamma-carboxyglutamate protein 2	Mus musculus	61-72
18721796-4	2008	Moreover, metformin significantly activated AMPK in dose- and time-dependent manners, and induced endothelial nitric oxide synthase (eNOS) and bone morphogenetic protein-2 (BMP-2) expressions.	Metformin	10-19	nitric oxide synthase 3, endothelial cell	Mus musculus	98-131
18248643-13	2008	Metformin treatment induced a significant decrease in insulin levels (P &lt; 0.01) and the concomitant recovery of NPY secretory capacity in response to ghrelin (AUC-NPY: P &lt; 0.05 vs. baseline) in PCOS women.	Metformin	0-9	neuropeptide Y	Homo sapiens	115-118
18248643-13	2008	Metformin treatment induced a significant decrease in insulin levels (P &lt; 0.01) and the concomitant recovery of NPY secretory capacity in response to ghrelin (AUC-NPY: P &lt; 0.05 vs. baseline) in PCOS women.	Metformin	0-9	neuropeptide Y	Homo sapiens	166-169
18565127-0	2008	The effects of 8 months of metformin on circulating GGT and ALT levels in obese women with polycystic ovarian syndrome.	Metformin	27-36	gamma-glutamyltransferase 2, pseudogene	Homo sapiens	52-55
18565127-2	2008	Small studies have shown reductions in serum alanine aminotransaminase (ALT) and gamma-glutamyltransaminase (GGT) concentrations, both surrogate liver fat markers, and sometimes improvements in liver histology in individuals with NAFLD treated with metformin.	Metformin	249-258	gamma-glutamyltransferase 2, pseudogene	Homo sapiens	81-107
18565127-3	2008	AIMS: We investigated whether metformin reduces serum ALT and GGT concentrations in obese women with PCOS.	Metformin	30-39	gamma-glutamyltransferase 2, pseudogene	Homo sapiens	62-65
18728938-0	2008	Genetic variants of organic cation transporter 2 (OCT2) significantly reduce metformin uptake in oocytes.	Metformin	77-86	solute carrier family 22 member 2	Sus scrofa	20-48
18728938-0	2008	Genetic variants of organic cation transporter 2 (OCT2) significantly reduce metformin uptake in oocytes.	Metformin	77-86	solute carrier family 22 member 2	Sus scrofa	50-54
18728938-7	2008	Metformin uptake was much greater in oocytes expressing OCT2-wild type (OCT2-WT) than OCT1-WT compared with uptake in water-injected oocytes.	Metformin	0-9	solute carrier family 22 member 2	Sus scrofa	56-60
18728938-7	2008	Metformin uptake was much greater in oocytes expressing OCT2-wild type (OCT2-WT) than OCT1-WT compared with uptake in water-injected oocytes.	Metformin	0-9	solute carrier family 22 member 2	Sus scrofa	72-76
18728938-8	2008	Uptake was significantly decreased in oocytes expressing OCT2-T199I, -T201M, and -A270S compared with that in OCT2-WT, suggesting that metformin is a better substrate for OCT2 than for OCT1 and that the amino acid-substituted variants of OCT2 cause a functional decrease in metformin uptake.	Metformin	135-144	solute carrier family 22 member 2	Sus scrofa	57-62
18728938-8	2008	Uptake was significantly decreased in oocytes expressing OCT2-T199I, -T201M, and -A270S compared with that in OCT2-WT, suggesting that metformin is a better substrate for OCT2 than for OCT1 and that the amino acid-substituted variants of OCT2 cause a functional decrease in metformin uptake.	Metformin	135-144	solute carrier family 22 member 2	Sus scrofa	57-61
18728938-8	2008	Uptake was significantly decreased in oocytes expressing OCT2-T199I, -T201M, and -A270S compared with that in OCT2-WT, suggesting that metformin is a better substrate for OCT2 than for OCT1 and that the amino acid-substituted variants of OCT2 cause a functional decrease in metformin uptake.	Metformin	135-144	solute carrier family 22 member 2	Sus scrofa	110-114
18728938-8	2008	Uptake was significantly decreased in oocytes expressing OCT2-T199I, -T201M, and -A270S compared with that in OCT2-WT, suggesting that metformin is a better substrate for OCT2 than for OCT1 and that the amino acid-substituted variants of OCT2 cause a functional decrease in metformin uptake.	Metformin	135-144	solute carrier family 22 member 2	Sus scrofa	110-114
18728938-8	2008	Uptake was significantly decreased in oocytes expressing OCT2-T199I, -T201M, and -A270S compared with that in OCT2-WT, suggesting that metformin is a better substrate for OCT2 than for OCT1 and that the amino acid-substituted variants of OCT2 cause a functional decrease in metformin uptake.	Metformin	274-283	solute carrier family 22 member 2	Sus scrofa	57-62
18728938-8	2008	Uptake was significantly decreased in oocytes expressing OCT2-T199I, -T201M, and -A270S compared with that in OCT2-WT, suggesting that metformin is a better substrate for OCT2 than for OCT1 and that the amino acid-substituted variants of OCT2 cause a functional decrease in metformin uptake.	Metformin	274-283	solute carrier family 22 member 2	Sus scrofa	57-61
18728938-10	2008	In conclusion, the genetic variants of OCT2 (OCT2-T199I, -T201M, and -A270S) decreased the transport activity of metformin and thus may contribute to the inter-individual variation in metformin disposition as OCT2 plays a pivotal role in renal excretion, the major disposition route of metformin.	Metformin	113-122	solute carrier family 22 member 2	Sus scrofa	39-43
18728938-10	2008	In conclusion, the genetic variants of OCT2 (OCT2-T199I, -T201M, and -A270S) decreased the transport activity of metformin and thus may contribute to the inter-individual variation in metformin disposition as OCT2 plays a pivotal role in renal excretion, the major disposition route of metformin.	Metformin	113-122	solute carrier family 22 member 2	Sus scrofa	45-50
18728938-10	2008	In conclusion, the genetic variants of OCT2 (OCT2-T199I, -T201M, and -A270S) decreased the transport activity of metformin and thus may contribute to the inter-individual variation in metformin disposition as OCT2 plays a pivotal role in renal excretion, the major disposition route of metformin.	Metformin	113-122	solute carrier family 22 member 2	Sus scrofa	45-49
18728938-10	2008	In conclusion, the genetic variants of OCT2 (OCT2-T199I, -T201M, and -A270S) decreased the transport activity of metformin and thus may contribute to the inter-individual variation in metformin disposition as OCT2 plays a pivotal role in renal excretion, the major disposition route of metformin.	Metformin	184-193	solute carrier family 22 member 2	Sus scrofa	39-43
18728938-10	2008	In conclusion, the genetic variants of OCT2 (OCT2-T199I, -T201M, and -A270S) decreased the transport activity of metformin and thus may contribute to the inter-individual variation in metformin disposition as OCT2 plays a pivotal role in renal excretion, the major disposition route of metformin.	Metformin	184-193	solute carrier family 22 member 2	Sus scrofa	45-50
18728938-10	2008	In conclusion, the genetic variants of OCT2 (OCT2-T199I, -T201M, and -A270S) decreased the transport activity of metformin and thus may contribute to the inter-individual variation in metformin disposition as OCT2 plays a pivotal role in renal excretion, the major disposition route of metformin.	Metformin	184-193	solute carrier family 22 member 2	Sus scrofa	45-49
18728938-10	2008	In conclusion, the genetic variants of OCT2 (OCT2-T199I, -T201M, and -A270S) decreased the transport activity of metformin and thus may contribute to the inter-individual variation in metformin disposition as OCT2 plays a pivotal role in renal excretion, the major disposition route of metformin.	Metformin	184-193	solute carrier family 22 member 2	Sus scrofa	39-43
18728938-10	2008	In conclusion, the genetic variants of OCT2 (OCT2-T199I, -T201M, and -A270S) decreased the transport activity of metformin and thus may contribute to the inter-individual variation in metformin disposition as OCT2 plays a pivotal role in renal excretion, the major disposition route of metformin.	Metformin	184-193	solute carrier family 22 member 2	Sus scrofa	45-50
18728938-10	2008	In conclusion, the genetic variants of OCT2 (OCT2-T199I, -T201M, and -A270S) decreased the transport activity of metformin and thus may contribute to the inter-individual variation in metformin disposition as OCT2 plays a pivotal role in renal excretion, the major disposition route of metformin.	Metformin	184-193	solute carrier family 22 member 2	Sus scrofa	45-49
18495226-8	2008	Metformin growth inhibition was partly abolished by the AMPK inhibitor, compound C. Western blotting demonstrated that metformin at cytotoxic concentrations, induced AMPK phosphorylation and decreased p70S6K and S6K phosphorylation, suggesting the mechanism for its anti-proliferative action.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	201-207
18495226-8	2008	Metformin growth inhibition was partly abolished by the AMPK inhibitor, compound C. Western blotting demonstrated that metformin at cytotoxic concentrations, induced AMPK phosphorylation and decreased p70S6K and S6K phosphorylation, suggesting the mechanism for its anti-proliferative action.	Metformin	119-128	ribosomal protein S6 kinase B1	Homo sapiens	201-207
18358555-0	2008	The effect of metformin treatment on VEGF and PAI-1 levels in obese type 2 diabetic patients.	Metformin	14-23	serpin family E member 1	Homo sapiens	46-51
18358555-6	2008	After metformin addition, there was a significant decrement in BMI, waist circumference, fat percentage, fasting and postprandial plasma glucose, hemoglobin A1C, plasminogen activator inhibitor-1 (PAI-1), vascular endothelial growth factor (VEGF) and increment in beta cell reserve values of the patients.	Metformin	6-15	serpin family E member 1	Homo sapiens	162-195
18358555-6	2008	After metformin addition, there was a significant decrement in BMI, waist circumference, fat percentage, fasting and postprandial plasma glucose, hemoglobin A1C, plasminogen activator inhibitor-1 (PAI-1), vascular endothelial growth factor (VEGF) and increment in beta cell reserve values of the patients.	Metformin	6-15	serpin family E member 1	Homo sapiens	197-202
18673148-8	2008	We observed that metformin, besides its antihyperglycemic action, induces a significant decrease in TBARS and MDA levels, GPx and GRed activities and a significant increase in GSH levels and MnSOD activity.	Metformin	17-26	glutathione-disulfide reductase	Rattus norvegicus	130-134
17350746-0	2008	Effect of metformin on IGF-1 and IGFBP-1 levels in obese patients with polycystic ovary syndrome.	Metformin	10-19	insulin like growth factor binding protein 1	Homo sapiens	33-40
18194429-6	2008	Treatment with AICAR (5 mM) or metformin (5 mM) for 4 h inhibited GnRH release in the presence or absence of GnRH (10(-8) M).	Metformin	31-40	gonadotropin releasing hormone 1	Mus musculus	66-70
18194429-6	2008	Treatment with AICAR (5 mM) or metformin (5 mM) for 4 h inhibited GnRH release in the presence or absence of GnRH (10(-8) M).	Metformin	31-40	gonadotropin releasing hormone 1	Mus musculus	109-113
18194429-7	2008	Specific AMPK inhibitor compound C completely eliminated the effects of AICAR or metformin on GnRH release.	Metformin	81-90	gonadotropin releasing hormone 1	Mus musculus	94-98
18250273-3	2008	METHODS AND RESULTS: Exposure of human umbilical vein endothelial cells or bovine aortic endothelial cells to metformin significantly increased AMPK activity and the phosphorylation of both AMPK at Thr172 and LKB1 at Ser428, an AMPK kinase, which was paralleled by increased activation of protein kinase C (PKC)-zeta, as evidenced by increased activity, phosphorylation (Thr410/403), and nuclear translocation of PKC-zeta.	Metformin	110-119	serine/threonine kinase 11	Homo sapiens	209-213
18250273-4	2008	Consistently, either pharmacological or genetic inhibition of PKC-zeta ablated metformin-enhanced phosphorylation of both AMPK-Thr172 and LKB1-Ser428, suggesting that PKC-zeta might act as an upstream kinase for LKB1.	Metformin	79-88	serine/threonine kinase 11	Homo sapiens	138-142
18250273-4	2008	Consistently, either pharmacological or genetic inhibition of PKC-zeta ablated metformin-enhanced phosphorylation of both AMPK-Thr172 and LKB1-Ser428, suggesting that PKC-zeta might act as an upstream kinase for LKB1.	Metformin	79-88	serine/threonine kinase 11	Homo sapiens	212-216
18250273-5	2008	Furthermore, adenoviral overexpression of LKB1 kinase-dead mutants abolished but LKB1 wild-type overexpression enhanced the effects of metformin on AMPK in bovine aortic endothelial cells.	Metformin	135-144	serine/threonine kinase 11	Homo sapiens	81-85
18250273-6	2008	In addition, metformin increased the phosphorylation and nuclear export of LKB1 into the cytosols as well as the association of AMPK with LKB1 in bovine aortic endothelial cells.	Metformin	13-22	serine/threonine kinase 11	Homo sapiens	75-79
18250273-6	2008	In addition, metformin increased the phosphorylation and nuclear export of LKB1 into the cytosols as well as the association of AMPK with LKB1 in bovine aortic endothelial cells.	Metformin	13-22	serine/threonine kinase 11	Homo sapiens	138-142
18250273-7	2008	Similarly, overexpression of LKB1 wild-type but not LKB1 S428A mutants (serine replaced by alanine) restored the effects of metformin on AMPK in LKB1-deficient HeLa-S3 cells, suggesting that Ser428 phosphorylation of LKB1 is required for metformin-enhanced AMPK activation.	Metformin	124-133	serine/threonine kinase 11	Homo sapiens	29-33
18250273-7	2008	Similarly, overexpression of LKB1 wild-type but not LKB1 S428A mutants (serine replaced by alanine) restored the effects of metformin on AMPK in LKB1-deficient HeLa-S3 cells, suggesting that Ser428 phosphorylation of LKB1 is required for metformin-enhanced AMPK activation.	Metformin	238-247	serine/threonine kinase 11	Homo sapiens	29-33
18250273-8	2008	Moreover, LKB1 S428A, like kinase-dead LKB1 D194A, abolished metformin-enhanced LKB1 translocation as well as the association of LKB1 with AMPK in HeLa-S3 cells.	Metformin	61-70	serine/threonine kinase 11	Homo sapiens	10-14
18250273-8	2008	Moreover, LKB1 S428A, like kinase-dead LKB1 D194A, abolished metformin-enhanced LKB1 translocation as well as the association of LKB1 with AMPK in HeLa-S3 cells.	Metformin	61-70	serine/threonine kinase 11	Homo sapiens	39-43
18250273-8	2008	Moreover, LKB1 S428A, like kinase-dead LKB1 D194A, abolished metformin-enhanced LKB1 translocation as well as the association of LKB1 with AMPK in HeLa-S3 cells.	Metformin	61-70	serine/threonine kinase 11	Homo sapiens	39-43
18250273-8	2008	Moreover, LKB1 S428A, like kinase-dead LKB1 D194A, abolished metformin-enhanced LKB1 translocation as well as the association of LKB1 with AMPK in HeLa-S3 cells.	Metformin	61-70	serine/threonine kinase 11	Homo sapiens	39-43
18250273-9	2008	Finally, inhibition of PKC-zeta abolished metformin-enhanced coimmunoprecipitation of LKB1 with both AMPKalpha1 and AMPKalpha2.	Metformin	42-51	serine/threonine kinase 11	Homo sapiens	86-90
18220291-10	2008	AMPK activation by AICAR or metformin inhibits HSC proliferation via suppression of ROS production and subsequent inhibition of AKT pathway.	Metformin	28-37	fucosyltransferase 1 (H blood group)	Homo sapiens	47-50
18171434-5	2008	Thus we suggest that DPP-4 inhibitors or long-acting GLP-1 mimetics will be used as either first-line therapy or as an early addition to metformin.	Metformin	137-146	dipeptidyl peptidase 4	Homo sapiens	21-26
18230276-5	2008	This suggests that the saturable components involved in the renal uptake of TEA, cimetidine and metformin are mediated mainly by rOct2.	Metformin	96-105	solute carrier family 22 member 2	Rattus norvegicus	129-134
18445367-3	2008	Metformin was metabolized via hepatic CYP2C11, 2D1, and 3A1/2 in rats.	Metformin	0-9	cytochrome P450, subfamily 2, polypeptide 11	Rattus norvegicus	38-45
18445367-12	2008	CONCLUSIONS: The significantly slower CLNR of metformin in the DMIA rats could be due to the decrease in hepatic CYP2C11 than the controls.	Metformin	46-55	cytochrome P450, subfamily 2, polypeptide 11	Rattus norvegicus	113-120
17657786-1	2007	It was reported that metformin was mainly metabolized via hepatic CYP2C11, 2D1 and 3A1/2 in rats, and in a rat model of dehydration, the expressions of hepatic CYP2C11 and 3A1/2 were not changed.	Metformin	21-30	cytochrome P450, subfamily 2, polypeptide 11	Rattus norvegicus	66-73
17657786-1	2007	It was reported that metformin was mainly metabolized via hepatic CYP2C11, 2D1 and 3A1/2 in rats, and in a rat model of dehydration, the expressions of hepatic CYP2C11 and 3A1/2 were not changed.	Metformin	21-30	cytochrome P450, subfamily 2, polypeptide 11	Rattus norvegicus	160-167
17600084-6	2007	The goal of this study is to investigate whether metformin is a substrate of PMAT and whether PMAT plays a role in the intestinal uptake of metformin.	Metformin	49-58	solute carrier family 29 member 4	Homo sapiens	77-81
17600084-6	2007	The goal of this study is to investigate whether metformin is a substrate of PMAT and whether PMAT plays a role in the intestinal uptake of metformin.	Metformin	140-149	solute carrier family 29 member 4	Homo sapiens	94-98
17600084-7	2007	Using Madin-Darby canine kidney cells stably expressing human PMAT, we showed that metformin is avidly transported by PMAT, with an apparent affinity (K(m) = 1.32 mM) comparable to those reported for hOCT1-2.	Metformin	83-92	solute carrier family 29 member 4	Homo sapiens	62-66
17600084-7	2007	Using Madin-Darby canine kidney cells stably expressing human PMAT, we showed that metformin is avidly transported by PMAT, with an apparent affinity (K(m) = 1.32 mM) comparable to those reported for hOCT1-2.	Metformin	83-92	solute carrier family 29 member 4	Homo sapiens	118-122
17600084-8	2007	Interestingly, the concentration-velocity profile of PMAT-mediated metformin uptake is sigmoidal, with a Hill coefficient of 2.64.	Metformin	67-76	solute carrier family 29 member 4	Homo sapiens	53-57
17600084-9	2007	PMAT-mediated metformin transport is greatly stimulated by acidic pH, with the uptake rate being approximately 4-fold higher at pH 6.6 than at pH 7.4.	Metformin	14-23	solute carrier family 29 member 4	Homo sapiens	0-4
17600084-11	2007	Taken together, our results suggest that PMAT transports metformin, is expressed in human intestine, and may play a role in the intestinal absorption of metformin and possibly other cationic drugs.	Metformin	57-66	solute carrier family 29 member 4	Homo sapiens	41-45
17600084-11	2007	Taken together, our results suggest that PMAT transports metformin, is expressed in human intestine, and may play a role in the intestinal absorption of metformin and possibly other cationic drugs.	Metformin	153-162	solute carrier family 29 member 4	Homo sapiens	41-45
17655515-7	2007	The DPP-IV inhibitors appear to have excellent therapeutic potential in the management of type 2 diabetes as monotherapy or in combination with existing agents, such as metformin.	Metformin	169-178	dipeptidyl peptidase 4	Homo sapiens	4-10
17587390-11	2007	Reductions in PAI-1 and leptin levels indicate that the early effects of metformin involve also the adipose tissue.	Metformin	73-82	serpin family E member 1	Homo sapiens	14-19
17587390-11	2007	Reductions in PAI-1 and leptin levels indicate that the early effects of metformin involve also the adipose tissue.	Metformin	73-82	leptin	Homo sapiens	24-30
17275228-1	2007	It was reported that the hepatic microsomal cytochrome P450 (CYP) 2C11, 2D1, and 3A1 (not via the CYP1A2, 2B1/2, and 2E1) were involved in the metabolism of metformin in rats.	Metformin	157-166	cytochrome P450, subfamily 2, polypeptide 11	Rattus norvegicus	44-70
17387171-7	2007	Leptin and the anti-diabetic drug metformin acutely down-regulated C/EBPbeta expression in hepatocytes, whereas fatty acids up-regulate C/EBPbeta expression.	Metformin	34-43	CCAAT/enhancer binding protein (C/EBP), beta	Mus musculus	67-76
17447005-3	2007	In confluent C6 cultures, on the other hand, metformin caused massive induction of caspase-dependent apoptosis associated with c-Jun N-terminal kinase (JNK) activation, mitochondrial depolarization and oxidative stress.	Metformin	45-54	mitogen-activated protein kinase 8	Rattus norvegicus	127-150
17447005-3	2007	In confluent C6 cultures, on the other hand, metformin caused massive induction of caspase-dependent apoptosis associated with c-Jun N-terminal kinase (JNK) activation, mitochondrial depolarization and oxidative stress.	Metformin	45-54	mitogen-activated protein kinase 8	Rattus norvegicus	152-155
17447005-4	2007	Metformin-triggered apoptosis was completely prevented by agents that block mitochondrial permeability transition (cyclosporin A) and oxygen radical production (N-acetylcisteine), while the inhibitors of JNK activation (SP600125) or glycolysis (sodium fluoride, iodoacetate) provided partial protection.	Metformin	0-9	mitogen-activated protein kinase 8	Rattus norvegicus	204-207
17224152-13	2007	Low-dose metformin therapy improves IR and polycystic ovary morphology, even though levels of T, AMH, and inhibin B remain unchanged.	Metformin	9-18	anti-Mullerian hormone	Homo sapiens	97-100
17292717-0	2007	Metformin reduces endothelial cell expression of both the receptor for advanced glycation end products and lectin-like oxidized receptor 1.	Metformin	0-9	oxidized low density lipoprotein receptor 1	Bos taurus	107-138
17292717-2	2007	We explored whether metformin could modulate the redox-sensible expression of receptor for advanced glycation end products (RAGE) and lectin-like oxidized receptor 1 (LOX-1), 2 endothelial membrane receptors involved in the arterial endothelial dysfunction observed in diabetes.	Metformin	20-29	advanced glycosylation end-product specific receptor	Bos taurus	124-128
17292717-2	2007	We explored whether metformin could modulate the redox-sensible expression of receptor for advanced glycation end products (RAGE) and lectin-like oxidized receptor 1 (LOX-1), 2 endothelial membrane receptors involved in the arterial endothelial dysfunction observed in diabetes.	Metformin	20-29	oxidized low density lipoprotein receptor 1	Bos taurus	134-165
17292717-2	2007	We explored whether metformin could modulate the redox-sensible expression of receptor for advanced glycation end products (RAGE) and lectin-like oxidized receptor 1 (LOX-1), 2 endothelial membrane receptors involved in the arterial endothelial dysfunction observed in diabetes.	Metformin	20-29	oxidized low density lipoprotein receptor 1	Bos taurus	167-172
17292717-7	2007	Taken together, our results suggest that the intracellular antioxidant properties of metformin may result in the inhibition of cell expression of both RAGE and LOX-1, possibly through a modulation of redox-sensible nuclear factors such as nuclear factor kappaB, that were shown to be involved in such receptor cell expression.	Metformin	85-94	advanced glycosylation end-product specific receptor	Bos taurus	151-155
17292717-7	2007	Taken together, our results suggest that the intracellular antioxidant properties of metformin may result in the inhibition of cell expression of both RAGE and LOX-1, possibly through a modulation of redox-sensible nuclear factors such as nuclear factor kappaB, that were shown to be involved in such receptor cell expression.	Metformin	85-94	oxidized low density lipoprotein receptor 1	Bos taurus	160-165
17095593-0	2007	Metformin inhibits adenosine 5"-monophosphate-activated kinase activation and prevents increases in neuropeptide Y expression in cultured hypothalamic neurons.	Metformin	0-9	neuropeptide Y	Homo sapiens	100-114
17095593-8	2007	Taken together, our data demonstrate that metformin can inhibit AMPK activity in hypothalamic neurons, thus modulating the expression of the orexigenic peptide NPY.	Metformin	42-51	neuropeptide Y	Homo sapiens	160-163
17121522-1	2006	OBJECTIVE: This prospective study evaluates the effect of insulin sensitizers, pioglitazone (PGZ) and metformin (MET) on plasma adiponectin and leptin levels in subjects newly diagnosed with type 2 diabetes mellitus (T2DM).	Metformin	102-111	leptin	Homo sapiens	144-150
16945366-0	2006	Inhibition of dipeptidyl peptidase-IV activity by metformin enhances the antidiabetic effects of glucagon-like peptide-1.	Metformin	50-59	dipeptidylpeptidase 4	Mus musculus	14-37
16945366-5	2006	Recent reports indicate that metformin may have the additional property of inhibiting DPP IV activity.	Metformin	29-38	dipeptidylpeptidase 4	Mus musculus	86-92
16945366-6	2006	Here we examine the effects of metformin on plasma DPP IV activity of normal and ob/ob diabetic mice.	Metformin	31-40	dipeptidylpeptidase 4	Mus musculus	51-57
16945366-7	2006	DPP IV activity present in mouse plasma was concentration-dependently inhibited by metformin generating IC(50) values of 38 microM for normal mice and 29 microM for ob/ob mice.	Metformin	83-92	dipeptidylpeptidase 4	Mus musculus	0-6
16945366-8	2006	In vivo metformin lowered plasma DPP IV activity in ob/ob mice, and improved glucose-lowering and insulin-releasing effects of exogenous GLP-1 administration.	Metformin	8-17	dipeptidylpeptidase 4	Mus musculus	33-39
16945366-11	2006	Long-term (12 day) oral metformin administration to ob/ob mice resulted in lower DPP IV activity but had no effect on basal glucose and insulin levels.	Metformin	24-33	dipeptidylpeptidase 4	Mus musculus	81-87
16945366-12	2006	These findings indicate that metformin decreases the plasma DPP IV activity, limiting the inactivation of exogenously administered GLP-1 and improving glycaemic control.	Metformin	29-38	dipeptidylpeptidase 4	Mus musculus	60-66
16940989-0	2006	Effects of enzyme inducers and inhibitors on the pharmacokinetics of metformin in rats: involvement of CYP2C11, 2D1 and 3A1/2 for the metabolism of metformin.	Metformin	148-157	cytochrome P450, subfamily 2, polypeptide 11	Rattus norvegicus	103-110
16940989-9	2006	CONCLUSIONS AND IMPLICATIONS: Our data suggest that metformin was metabolized mainly via CYP2C11, 2D1, and 3A1/2 in rats.	Metformin	52-61	cytochrome P450, subfamily 2, polypeptide 11	Rattus norvegicus	89-96
16940989-10	2006	This result could contribute to understanding of the possible changes in metformin pharmacokinetics in disease models where CYP2C11 and/or 3A1/2 are altered.	Metformin	73-82	cytochrome P450, subfamily 2, polypeptide 11	Rattus norvegicus	124-131
17133785-6	2006	In patients with type 2 diabetes mellitus and metabolic syndrome, the combination of metformin plus thiazolidinediones improved glycaemic control and produced a slight but significant reduction in plasminogen activator inhibitor-1 levels.	Metformin	85-94	serpin family E member 1	Homo sapiens	197-230
16762632-0	2006	Metformin prevents alcohol-induced liver injury in the mouse: Critical role of plasminogen activator inhibitor-1.	Metformin	0-9	serine (or cysteine) peptidase inhibitor, clade E, member 1	Mus musculus	79-112
16762632-6	2006	Instead, the protective effects of metformin correlated with complete prevention of the upregulation of plasminogen activator inhibitor (PAI)-1 caused by ethanol.	Metformin	35-44	serine (or cysteine) peptidase inhibitor, clade E, member 1	Mus musculus	104-143
16636195-6	2006	Furthermore, metformin attenuated the TNF-alpha-induced gene expression of various proinflammatory and cell adhesion molecules, such as vascular cell adhesion molecule-1, E-selectin, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1, in HUVECs.	Metformin	13-22	C-C motif chemokine ligand 2	Homo sapiens	222-256
16505235-6	2006	In an acute study, metformin treatment also increased the anorexic effect of leptin (5 microg), and this was accompanied by an increased level of phosphorylated signal transducer and activator of transcription 3 in the hypothalamus.	Metformin	19-28	signal transducer and activator of transcription 3	Rattus norvegicus	161-211
16505249-5	2006	Repeated treatment with metformin in STZ-induced diabetic rats increased the mRNA and protein levels of GLUT-4 in soleus muscle that was blocked by naloxonazine.	Metformin	24-33	solute carrier family 2 member 4	Rattus norvegicus	104-110
16505249-7	2006	In conclusion, our results provide novel mechanisms for the plasma glucose-lowering action of metformin, via an increase of beta-endorphin secretion from adrenal glands to stimulate opioid mu-receptor linkage, leading to an increase of GLUT-4 gene expression and an attenuation of hepatic PEPCK gene expression in STZ-induced diabetic rats.	Metformin	94-103	solute carrier family 2 member 4	Rattus norvegicus	236-242
16441842-9	2006	Metformin extends the mean and maximum lifespans of female transgenic HER-2/neu mice by 8% and 13.1% in comparison with control mice.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Mus musculus	70-79
16522281-3	2006	Weight loss, metformin, and thiazolidinediones ameliorate insulin resistance and decrease concentrations of PAI-1.	Metformin	13-22	serpin family E member 1	Homo sapiens	108-113
16443786-5	2006	Furthermore, administration of metformin as well as 5-aminoimidazole-4-carboxamide ribonucleoside, an AMPK agonist, significantly increased eNOS Ser1179 phosphorylation, NO bioactivity, and coimmunoprecipitation of eNOS with hsp90 in wild-type C57BL6 mice but not in AMPK-alpha1 knockout mice, suggesting that AMPK is required for metformin-enhanced eNOS activation in vivo.	Metformin	31-40	nitric oxide synthase 3, endothelial cell	Mus musculus	215-219
16443786-6	2006	Finally, incubation of BAECs with clinically relevant concentrations of metformin dramatically attenuated high-glucose (30 mmol/l)-induced reduction in the association of hsp90 with eNOS, which resulted in increased NO bioactivity with a reduction in overexpression of adhesion molecules and endothelial apoptosis caused by high-glucose exposure.	Metformin	72-81	heat shock protein 90 alpha family class A member 1	Homo sapiens	171-176
16443786-7	2006	Taken together, our results indicate that metformin might improve vascular endothelial functions in diabetes by increasing AMPK-dependent, hsp90-mediated eNOS activation.	Metformin	42-51	heat shock protein 90 alpha family class A member 1	Homo sapiens	139-144
16367888-0	2006	Effects of metformin and oleic acid on adipocyte expression of resistin.	Metformin	11-20	resistin	Homo sapiens	63-71
16367888-5	2006	Similar reductions in resistin mRNA were demonstrated with metformin 100 microm (6.2-fold reduction, p &lt; 0.02) and oleic acid 100 microm (3.9-fold reduction, p &lt; 0.03).	Metformin	59-68	resistin	Homo sapiens	22-30
16380496-7	2006	For this reason, we investigated circulating bioactive lipopolysaccharide and the effects of changing insulin action-after treatment with an insulin sensitizer (metformin)-on circulating BPI in subjects with glucose intolerance.	Metformin	161-170	bactericidal permeability increasing protein	Homo sapiens	187-190
16380496-13	2006	In parallel to improved insulin sensitivity, plasma BPI significantly increased in the metformin group but not in the placebo group.	Metformin	87-96	bactericidal permeability increasing protein	Homo sapiens	52-55
16354680-7	2006	Knockdown of Raptor as well as activators of the LKB1/AMPK pathway, such as the widely used antidiabetic compound metformin, suppress IRS-1 Ser636/639 phosphorylation and reverse mTOR-mediated inhibition on PI3-kinase/Akt signaling.	Metformin	114-123	serine/threonine kinase 11	Homo sapiens	49-53
16354680-7	2006	Knockdown of Raptor as well as activators of the LKB1/AMPK pathway, such as the widely used antidiabetic compound metformin, suppress IRS-1 Ser636/639 phosphorylation and reverse mTOR-mediated inhibition on PI3-kinase/Akt signaling.	Metformin	114-123	insulin receptor substrate 1	Homo sapiens	134-139
16169420-1	2005	In women with polycystic ovary syndrome, metformin administration, not laparoscopic ovarian drilling, reduces plasminogen activator inhibitor 1 (PAI-1) activity.	Metformin	41-50	serpin family E member 1	Homo sapiens	110-143
16169420-1	2005	In women with polycystic ovary syndrome, metformin administration, not laparoscopic ovarian drilling, reduces plasminogen activator inhibitor 1 (PAI-1) activity.	Metformin	41-50	serpin family E member 1	Homo sapiens	145-150
16043735-0	2005	Improved meal-related beta-cell function and insulin sensitivity by the dipeptidyl peptidase-IV inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1 year.	Metformin	122-131	dipeptidyl peptidase 4	Homo sapiens	72-95
16043735-11	2005	CONCLUSIONS: This study presents evidence that DPP-4 inhibition by vildagliptin when added to metformin in type 2 diabetes over 52 weeks improves beta-cell function along with improved postmeal insulin sensitivity.	Metformin	94-103	dipeptidyl peptidase 4	Homo sapiens	47-52
16127210-0	2005	Effects of antidiabetic treatment with metformin and insulin on serum and adipose tissue adiponectin levels in db/db mice.	Metformin	39-48	adiponectin, C1Q and collagen domain containing	Mus musculus	89-100
16127210-2	2005	The present study was conducted to examine whether circulating and adipose tissue adiponectin levels are modulated by chronic treatment with metformin and intensive treatment with insulin in murine models of obesity and type 2 diabetes, db/db mice with a C57BL/KsJ genetic background.	Metformin	141-150	adiponectin, C1Q and collagen domain containing	Mus musculus	82-93
16127210-8	2005	Recent studies have shown that adiponectin possibly has the same physiological effects on lipid and glucose metabolism that metformin has.	Metformin	124-133	adiponectin, C1Q and collagen domain containing	Mus musculus	31-42
16127210-9	2005	Therefore, an elevation in blood concentration of metformin following the treatment might lead to suppression in adiponectin synthesis in adipose tissue, independent of inhibition in weight gain and improvement in hyperinsulinemia by metformin treatment.	Metformin	50-59	adiponectin, C1Q and collagen domain containing	Mus musculus	113-124
16125352-5	2005	The chronic treatment of female transgenic HER-2/neu mice with metformin (100 mg/kg in drinking water) slightly decreased the food consumption but failed in reducing the body weight or temperature, slowed down the age-related rise in blood glucose and triglycerides level, as well as the age-related switch-off of estrous function, prolonged the mean life span by 8% (p &lt; 0.05), the mean life span of last 10% survivors by 13.1%, and the maximum life span by 1 month in comparison with control mice.	Metformin	63-72	erb-b2 receptor tyrosine kinase 2	Mus musculus	43-48
16125352-5	2005	The chronic treatment of female transgenic HER-2/neu mice with metformin (100 mg/kg in drinking water) slightly decreased the food consumption but failed in reducing the body weight or temperature, slowed down the age-related rise in blood glucose and triglycerides level, as well as the age-related switch-off of estrous function, prolonged the mean life span by 8% (p &lt; 0.05), the mean life span of last 10% survivors by 13.1%, and the maximum life span by 1 month in comparison with control mice.	Metformin	63-72	erb-b2 receptor tyrosine kinase 2	Mus musculus	49-52
16224592-0	2005	Metformin decelerates aging and development of mammary tumors in HER-2/neu transgenic mice.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Mus musculus	65-70
16224592-0	2005	Metformin decelerates aging and development of mammary tumors in HER-2/neu transgenic mice.	Metformin	0-9	erb-b2 receptor tyrosine kinase 2	Mus musculus	71-74
15853834-1	2005	OBJECTIVE: Treatment with metformin, an insulin-lowering agent, increases serum glycodelin, a progesterone-regulated lipocalin protein of the reproductive axis that may play a role in foeto-maternal defence mechanisms.	Metformin	26-35	progestagen associated endometrial protein	Homo sapiens	80-90
15842525-0	2005	Inhibition of dipeptidyl peptidase IV activity by oral metformin in Type 2 diabetes.	Metformin	55-64	dipeptidyl peptidase 4	Homo sapiens	14-37
15842525-3	2005	We investigated the acute effects of metformin on DPP IV activity in Type 2 diabetes to elucidate inhibition of DPP IV as a possible mechanism of action.	Metformin	37-46	dipeptidyl peptidase 4	Homo sapiens	50-56
15842525-5	2005	RESULTS: Following metformin, DPP IV activity was suppressed compared with placebo (AUC0-6 h 3230+/-373 vs. 5764+/-504 nmol ml/l, respectively, P=0.001).	Metformin	19-28	dipeptidyl peptidase 4	Homo sapiens	30-36
15842525-7	2005	Metformin also concentration-dependently inhibited endogenous DPP IV activity in vitro in plasma from Type 2 diabetic subjects.	Metformin	0-9	dipeptidyl peptidase 4	Homo sapiens	62-68
15842525-8	2005	CONCLUSION: Oral metformin effectively inhibits DPP IV activity in Type 2 diabetic patients, suggesting that the drug may have potential for future combination therapy with incretin hormones.	Metformin	17-26	dipeptidyl peptidase 4	Homo sapiens	48-54
15702236-0	2005	Metformin-induced suppression of glucose-6-phosphatase expression is independent of insulin signaling in rat hepatoma cells.	Metformin	0-9	glucose-6-phosphatase catalytic subunit 1	Rattus norvegicus	33-54
15702236-2	2005	To elucidate the pharmacological action of metformin on hepatic glucose production, we examined its effect on the gene expression of glucose-6-phosphatase (G6Pase), a key enzyme of gluconeogenesis, in H4IIE rat hepatoma cell line by RT-PCR and quantitative real-time PCR.	Metformin	43-52	glucose-6-phosphatase catalytic subunit 1	Rattus norvegicus	133-154
15702236-2	2005	To elucidate the pharmacological action of metformin on hepatic glucose production, we examined its effect on the gene expression of glucose-6-phosphatase (G6Pase), a key enzyme of gluconeogenesis, in H4IIE rat hepatoma cell line by RT-PCR and quantitative real-time PCR.	Metformin	43-52	glucose-6-phosphatase catalytic subunit 1	Rattus norvegicus	156-162
15702236-3	2005	Metformin suppressed dexamethasone/cAMP-induced expression of G6Pase mRNA in a dose dependent manner, its maximum effect being observed at 2 mM (79.3% inhibition, P&lt;0.05).	Metformin	0-9	glucose-6-phosphatase catalytic subunit 1	Rattus norvegicus	62-68
15702236-6	2005	In the present study, we demonstrate that metformin suppresses G6Pase mRNA expression by a mechanism that is independent of the activation of PI3-kinase, Akt, MAP kinase and protein kinase C pathway in hepatocytes.	Metformin	42-51	glucose-6-phosphatase catalytic subunit 1	Rattus norvegicus	63-69
15783073-0	2005	Metformin transport by renal basolateral organic cation transporter hOCT2.	Metformin	0-9	solute carrier family 22 member 2	Homo sapiens	68-73
15783073-2	2005	This study was performed to characterize metformin transport by human organic cation transporter 2 (hOCT2), the most abundant organic cation transporter in the basolateral membranes of the human kidney.	Metformin	41-50	solute carrier family 22 member 2	Homo sapiens	70-98
15783073-2	2005	This study was performed to characterize metformin transport by human organic cation transporter 2 (hOCT2), the most abundant organic cation transporter in the basolateral membranes of the human kidney.	Metformin	41-50	solute carrier family 22 member 2	Homo sapiens	100-105
15783073-3	2005	METHODS: Accumulation of [14C]metformin was assessed by the tracer experiments in the human embryonic kidney (HEK293) cells expressing hOCT2.	Metformin	30-39	solute carrier family 22 member 2	Homo sapiens	135-140
15783073-4	2005	RESULTS: The transport of [14C]metformin was markedly stimulated in hOCT2-expressing cells compared with the vector-transfected cells.	Metformin	31-40	solute carrier family 22 member 2	Homo sapiens	68-73
15783073-6	2005	The apparent Km and Vmax values of [14C]metformin transport by hOCT2-expressing HEK293 cells were 1.38+/-0.21 mM and 11.9+/-1.5 nmol mg protein(-1) min(-1), respectively.	Metformin	40-49	solute carrier family 22 member 2	Homo sapiens	63-68
15783073-7	2005	The order of the potencies of unlabeled biguanides to inhibit [14C]metformin transport by hOCT2 was phenformin &gt; buformin &gt; metformin.	Metformin	67-76	solute carrier family 22 member 2	Homo sapiens	90-95
15783073-7	2005	The order of the potencies of unlabeled biguanides to inhibit [14C]metformin transport by hOCT2 was phenformin &gt; buformin &gt; metformin.	Metformin	130-139	solute carrier family 22 member 2	Homo sapiens	90-95
15783073-9	2005	CONCLUSIONS: Metformin is transported by the basolateral organic cation transporter hOCT2 in the human kidney.	Metformin	13-22	solute carrier family 22 member 2	Homo sapiens	84-89
15783073-10	2005	hOCT2 could play a role in the drug interactions between metformin and some cationic drugs.	Metformin	57-66	solute carrier family 22 member 2	Homo sapiens	0-5
15607575-9	2005	Plasma PAI-1 can be decreased in insulin resistant subjects by improving adipocyte insulin sensitivity (with weight loss and thiazolidinediones), by consuming a very-low-fat diet that minimizes postprandial free fatty acid flux, and by administering activators of AMP-activated kinase (e.g., metformin), which can be expected to lessen tissue DAG synthesis.	Metformin	292-301	serpin family E member 1	Homo sapiens	7-12
15356668-8	2004	Interestingly, pharmacological agents such as thiazolidinediones, metformin and AT(1)-receptor antagonists were found to reduce adipose expression of PAI-1.	Metformin	66-75	serpin family E member 1	Homo sapiens	150-155
15531718-0	2004	Metformin inhibits leptin secretion via a mitogen-activated protein kinase signalling pathway in brown adipocytes.	Metformin	0-9	leptin	Homo sapiens	19-25
15531718-7	2004	Metformin acutely stimulated p44/p42 mitogen-activated protein (MAP) kinase in a dose- (3.2-fold at 1 mmol/l, P&lt; 0.05) as well as time-dependent (3.8-fold at 5 min, P&lt; 0.05) manner.	Metformin	0-9	cyclin dependent kinase 20	Homo sapiens	33-36
15531718-9	2004	Furthermore, chronic metformin treatment for 12 days dose-dependently inhibited leptin secretion by 35% and 75% at 500 mumol/l and 1 mmol/l metformin respectively (P&lt; 0.01).	Metformin	21-30	leptin	Homo sapiens	80-86
15531718-9	2004	Furthermore, chronic metformin treatment for 12 days dose-dependently inhibited leptin secretion by 35% and 75% at 500 mumol/l and 1 mmol/l metformin respectively (P&lt; 0.01).	Metformin	140-149	leptin	Homo sapiens	80-86
15531718-11	2004	Moreover, the impairment in leptin secretion by metformin was reversible within 48 h after removal of the drug.	Metformin	48-57	leptin	Homo sapiens	28-34
15531718-12	2004	Pharmacological inhibition of p44/p42 MAP kinase prevented the metformin-induced negative effect on leptin secretion.	Metformin	63-72	cyclin dependent kinase 20	Homo sapiens	34-37
15531718-12	2004	Pharmacological inhibition of p44/p42 MAP kinase prevented the metformin-induced negative effect on leptin secretion.	Metformin	63-72	leptin	Homo sapiens	100-106
15531718-13	2004	Taken together, our data demonstrate direct acute effects of metformin on adipocyte signalling and endocrine function with robust inhibition of leptin secretion.	Metformin	61-70	leptin	Homo sapiens	144-150
15372361-0	2004	Metformin ameliorates treatment of obese type 2 diabetic patients with mental retardation; its effects on eating behavior and serum leptin levels.	Metformin	0-9	leptin	Homo sapiens	132-138
15068958-2	2004	We recently found that, in cultured cells, the LKB1 tumor suppressor protein kinase activates AMPK in response to the metformin analog phenformin and the AMP mimetic drug 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).	Metformin	118-127	serine/threonine kinase 11	Rattus norvegicus	47-51
15242807-7	2004	As with AICAR, metformin activated c-Jun-N-terminal kinase (JNK) and caspase-3 prior to the appearance of apoptosis.	Metformin	15-24	mitogen-activated protein kinase 8	Rattus norvegicus	35-58
15242807-7	2004	As with AICAR, metformin activated c-Jun-N-terminal kinase (JNK) and caspase-3 prior to the appearance of apoptosis.	Metformin	15-24	mitogen-activated protein kinase 8	Rattus norvegicus	60-63
15334791-9	2004	Both glimepiride and metformin lowered plasminogen activator inhibitor Type 1 (PAI-1) at 12 months and significantly improved levels of glycosylated haemoglobin, fasting plasma glucose and post-prandial plasma glucose after 6 and 12 months.	Metformin	21-30	serpin family E member 1	Homo sapiens	39-77
15334791-9	2004	Both glimepiride and metformin lowered plasminogen activator inhibitor Type 1 (PAI-1) at 12 months and significantly improved levels of glycosylated haemoglobin, fasting plasma glucose and post-prandial plasma glucose after 6 and 12 months.	Metformin	21-30	serpin family E member 1	Homo sapiens	79-84
15063962-2	2004	This study was designed to evaluate effects of metformin therapy on serum levels of IGFBP-1 and IGF-I.	Metformin	47-56	insulin like growth factor binding protein 1	Homo sapiens	84-91
15063962-6	2004	RESULTS: Metformin therapy significantly increased IGFBP-1 concentration by 38% (P = 0.05) but had no demonstrable effect on the total IGF-I levels.	Metformin	9-18	insulin like growth factor binding protein 1	Homo sapiens	51-58
14761669-2	2004	The combined use of TZDs and metformin resulted in maximum tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) at 12.5 microM of TZDs and 100 microM of metformin as compared to the maximum tyrosine phosphorylation of IR and IRS-1 achieved at 50 microM of TZDs or 400 microM of metformin.	Metformin	29-38	insulin receptor substrate 1	Homo sapiens	143-148
14761669-2	2004	The combined use of TZDs and metformin resulted in maximum tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) at 12.5 microM of TZDs and 100 microM of metformin as compared to the maximum tyrosine phosphorylation of IR and IRS-1 achieved at 50 microM of TZDs or 400 microM of metformin.	Metformin	29-38	insulin receptor substrate 1	Homo sapiens	263-268
14761669-2	2004	The combined use of TZDs and metformin resulted in maximum tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) at 12.5 microM of TZDs and 100 microM of metformin as compared to the maximum tyrosine phosphorylation of IR and IRS-1 achieved at 50 microM of TZDs or 400 microM of metformin.	Metformin	191-200	insulin receptor substrate 1	Homo sapiens	143-148
14761669-2	2004	The combined use of TZDs and metformin resulted in maximum tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) at 12.5 microM of TZDs and 100 microM of metformin as compared to the maximum tyrosine phosphorylation of IR and IRS-1 achieved at 50 microM of TZDs or 400 microM of metformin.	Metformin	191-200	insulin receptor substrate 1	Homo sapiens	143-148
14502100-5	2003	Metformin has a weight neutral/weight lowering effect and reduces hypertriglyceridaemia, elevated levels of PAI-1, factor VII and C-reactive protein.	Metformin	0-9	serpin family E member 1	Homo sapiens	108-113
12803833-0	2003	Urinary PC-1 and N-acetyl-beta-D-glucosaminidase activity in patients with type 2 diabetes treated with metformin, gliclazide or glibenclamide.	Metformin	104-113	polycystin 1, transient receptor potential channel interacting	Homo sapiens	8-12
12803833-3	2003	METHODS: Urinary excretion of PC-1 was determined in 45 newly detected, obese diabetic patients treated with metformin (16 patients), gliclazide (14 patients) or glibenclamide (15 patients).	Metformin	109-118	polycystin 1, transient receptor potential channel interacting	Homo sapiens	30-34
12511230-5	2003	Tyrosine phosphorylation of IR?, IRS1, and IRS2 was increased by 2.7 fold (P &lt; 0.01), 6.8 fold (P &lt; 0.01), and 2.3 fold (P &lt;0.01) of chronically insulin-treated cells alone, respectively, after metformin 0.1 mmol/L was added.	Metformin	203-212	insulin receptor substrate 1	Homo sapiens	33-37
12511230-5	2003	Tyrosine phosphorylation of IR?, IRS1, and IRS2 was increased by 2.7 fold (P &lt; 0.01), 6.8 fold (P &lt; 0.01), and 2.3 fold (P &lt;0.01) of chronically insulin-treated cells alone, respectively, after metformin 0.1 mmol/L was added.	Metformin	203-212	insulin receptor substrate 2	Homo sapiens	43-47
12511230-7	2003	In contrast, metformin in pharmacological concentration (1-10 mmol/L) further inhibited tyrosine phosphorylation of IR?, IRS1, IRS2 and the interaction of PI3K with IRS.	Metformin	13-22	insulin receptor substrate 1	Homo sapiens	121-125
12511230-7	2003	In contrast, metformin in pharmacological concentration (1-10 mmol/L) further inhibited tyrosine phosphorylation of IR?, IRS1, IRS2 and the interaction of PI3K with IRS.	Metformin	13-22	insulin receptor substrate 2	Homo sapiens	127-131
12413946-0	2002	Effect of metformin on adipose tissue resistin expression in db/db mice.	Metformin	10-19	resistin	Mus musculus	38-46
12413946-2	2002	To evaluate whether an insulin-sensitizing drug, metformin, regulates adipose tissue resistin expression, murine models of obesity and diabetes, db/db mice, were treated with metformin (metformin group), insulin (insulin group), and vehicle (control group) for 4 weeks, followed by analyzing resistin protein expression in their adipose tissues.	Metformin	49-58	resistin	Mus musculus	85-93
12413946-3	2002	Unexpectedly, resistin protein expression was increased by 66% in the metformin group relative to the control group, while it did not differ between the insulin and control groups.	Metformin	70-79	resistin	Mus musculus	14-22
12413946-6	2002	These data collectively suggest that resistin expression may be suppressed by hyperinsulinemia and that metformin may upregulate resistin expression via the improvement of hyperinsulinemia in obesity.	Metformin	104-113	resistin	Mus musculus	129-137
12412817-5	2002	Metformin, an agent commonly used for non-insulin-dependent diabetes mellitus (NIDDM), appears to favorably decrease PAI-1 production in NIDDM patients but not nondiabetic patients.	Metformin	0-9	serpin family E member 1	Homo sapiens	117-122
12086935-5	2002	Metformin treatment for 10 weeks significantly increased AMPK alpha2 activity in the skeletal muscle, and this was associated with increased phosphorylation of AMPK on Thr172 and decreased acetyl-CoA carboxylase-2 activity.	Metformin	0-9	acetyl-CoA carboxylase beta	Rattus norvegicus	189-213
11912566-0	2002	Short-term treatment with metformin decreases serum leptin concentration without affecting body weight and body fat content in normal-weight healthy men.	Metformin	26-35	leptin	Homo sapiens	52-58
11912566-7	2002	Yet, serum leptin concentration was distinctly reduced after metformin (P &lt;.001).	Metformin	61-70	leptin	Homo sapiens	11-17
11912566-10	2002	Data indicate that metformin decreases the serum leptin concentration even without affecting body weight and body composition in normal-weight men.	Metformin	19-28	leptin	Homo sapiens	49-55
11883961-0	2002	Metformin effects on dipeptidylpeptidase IV degradation of glucagon-like peptide-1.	Metformin	0-9	dipeptidyl peptidase 4	Homo sapiens	21-43
11883961-2	2002	Data indicating that metformin increases the circulating amount of active glucagon-like peptide-1 (GLP-1) in obese nondiabetic subjects have recently been presented, and it was proposed that metformin might act as a DP IV inhibitor.	Metformin	21-30	dipeptidyl peptidase 4	Homo sapiens	216-221
11883961-2	2002	Data indicating that metformin increases the circulating amount of active glucagon-like peptide-1 (GLP-1) in obese nondiabetic subjects have recently been presented, and it was proposed that metformin might act as a DP IV inhibitor.	Metformin	191-200	dipeptidyl peptidase 4	Homo sapiens	216-221
11883961-5	2002	Inhibition of DP IV hydrolysis of the substrate Gly-Pro-pNA by metformin was examined spectrophotometrically.	Metformin	63-72	dipeptidyl peptidase 4	Homo sapiens	14-19
11953071-11	2002	CONCLUSIONS: Metformin may ameliorate the PAI-1, endocrine, metabolic profiles and menstrual abnormalities and improve the ovarian response to CC in CC resistant cases.	Metformin	13-22	serpin family E member 1	Homo sapiens	42-47
11707532-1	2001	OBJECTIVE: The aim of this study was to investigate the effects of combined hypocaloric diet and metformin on circulating testosterone and leptin levels in obese men with or without type 2 diabetes.	Metformin	97-106	leptin	Homo sapiens	139-145
11436194-0	2001	Metformin reduces weight, centripetal obesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30.	Metformin	0-9	leptin	Homo sapiens	56-62
11436194-14	2001	On metformin, there were linear trends in decrements in weight, girth, waist circumference, waist/hip ratio, insulin, and leptin throughout the study period (P &lt;.007).	Metformin	3-12	leptin	Homo sapiens	122-128
11436194-19	2001	The higher the entry serum leptin, the greater its reduction on metformin therapy (partial R(2) = 29%, P =.002).	Metformin	64-73	leptin	Homo sapiens	27-33
11436194-20	2001	The greater the reduction in insulin on metformin, the greater the reduction in leptin (partial R(2) = 8%, P =.03).	Metformin	40-49	leptin	Homo sapiens	80-86
11468878-3	2001	But metformin has fibrinolytic features by means of diminished plasminogen activator inhibitor 1 activity.	Metformin	4-13	serpin family E member 1	Homo sapiens	63-96
11289473-8	2001	In pooled human plasma, metformin (0.1-0.5 microg/ml) significantly inhibited degradation of GLP-1(7-36)amide after a 30-min incubation at 37 degrees C; similar results were obtained in a buffer solution containing DPP-IV.	Metformin	24-33	dipeptidyl peptidase 4	Homo sapiens	215-221
11239532-11	2001	Metformin led to modulation of preovulatory of follicular fluid IGF levels with increases of IGF-I (140 +/- 8 vs. 109 +/- 7ng/mL) and decreased of IGFBP-1 (133 +/- 8 vs.153 +/- 9ng/mL).	Metformin	0-9	insulin like growth factor binding protein 1	Homo sapiens	147-154
11238496-0	2001	Insulin reduction with metformin increases luteal phase serum glycodelin and insulin-like growth factor-binding protein 1 concentrations and enhances uterine vascularity and blood flow in the polycystic ovary syndrome.	Metformin	23-32	progestagen associated endometrial protein	Homo sapiens	62-72
11238496-0	2001	Insulin reduction with metformin increases luteal phase serum glycodelin and insulin-like growth factor-binding protein 1 concentrations and enhances uterine vascularity and blood flow in the polycystic ovary syndrome.	Metformin	23-32	insulin like growth factor binding protein 1	Homo sapiens	77-121
11238496-11	2001	We conclude that insulin reduction with metformin increases follicular and luteal phase serum glycodelin and insulin-like growth factor-binding protein-1 concentrations and enhances luteal phase uterine vascularity and blood flow in the polycystic ovary syndrome.	Metformin	40-49	progestagen associated endometrial protein	Homo sapiens	94-104
11238496-11	2001	We conclude that insulin reduction with metformin increases follicular and luteal phase serum glycodelin and insulin-like growth factor-binding protein-1 concentrations and enhances luteal phase uterine vascularity and blood flow in the polycystic ovary syndrome.	Metformin	40-49	insulin like growth factor binding protein 1	Homo sapiens	109-153
11158071-0	2001	Increased PAI-1 and tPA antigen levels are reduced with metformin therapy in HIV-infected patients with fat redistribution and insulin resistance.	Metformin	56-65	serpin family E member 1	Homo sapiens	10-15
11158071-3	2001	Furthermore, we investigated the effect of treatment with metformin on PAI-1 and tPA antigen levels in patients with HIV-associated fat redistribution.	Metformin	58-67	serpin family E member 1	Homo sapiens	71-76
11158071-9	2001	Similarly, metformin resulted in improvement in PAI-1 levels (-8.7 +/- 2.3 vs +1.7 +/- 2.9 microg/L, P = 0.03).	Metformin	11-20	serpin family E member 1	Homo sapiens	48-53
11158071-12	2001	Metformin reduces PAI-1 and tPA antigen concentrations in these patients and may ultimately improve associated CVD risk.	Metformin	0-9	serpin family E member 1	Homo sapiens	18-23
10927066-10	2000	After she received metformin for 4 months, PAI-Fx normalized (12.4 U/mL), as did insulin (12 microU/mL), androstenedione (185 ng/dL), and testosterone (39 ng/dL); weight fell from 109 to 91.3 kg (16%).	Metformin	19-28	serpin family E member 1	Homo sapiens	43-46
11202216-2	2000	alpha-Glucosidase inhibitors slow carbohydrate absorption, resulting in reduced postprandial hyperglycemia; thiazolidinediones increase insulin sensitivity, especially in muscle and adipocytes; metformin decreases hepatic gluconeogenesis; sulfonylureas result in prolonged increases in insulin secretion; and meglitinide causes rapid, short-lived increases in insulin secretion.	Metformin	194-203	sucrase-isomaltase	Homo sapiens	0-17
10225476-7	1999	Plasma membrane GLUT4 protein content was significantly augmented by a factor of 1.48-fold (p&lt;0.02) in the glibenclamide-treated group and tended to be increased 1.32 times by administration of metformin (p=0.06).	Metformin	197-206	solute carrier family 2 member 4	Rattus norvegicus	16-21
9498621-0	1998	Potentiating effect of metformin on insulin-induced glucose uptake and glycogen metabolism with Xenopus oocytes.	Metformin	23-32	insulin S homeolog	Xenopus laevis	36-43
9498621-1	1998	Xenopus laevis oocytes were chosen as the in vitro model for this study with the aim of reconsidering metformin action on the main insulin-responsive glucose pathway.	Metformin	102-111	insulin S homeolog	Xenopus laevis	131-138
9498621-4	1998	In contrast, when combined with 2 micromol/l insulin, metformin led to a specific rise of both free and stored glucose, by 42.4 and 102.3% respectively.	Metformin	54-63	insulin S homeolog	Xenopus laevis	45-52
9498621-5	1998	Moreover, a short-term preincubation of mature oocytes with metformin, but in the absence of glucose, enhanced significantly the amount of synthase a when stimulated by 50 nmol/l insulin (basal 17.4 +/- 5.7%, metformin 21.3 +/- 4.1%, insulin 31.2 +/- 4.6%, metformin together with insulin 62.7 +/- 4.2%, p &lt; 0.005, n = 5).	Metformin	60-69	insulin S homeolog	Xenopus laevis	179-186
9498621-5	1998	Moreover, a short-term preincubation of mature oocytes with metformin, but in the absence of glucose, enhanced significantly the amount of synthase a when stimulated by 50 nmol/l insulin (basal 17.4 +/- 5.7%, metformin 21.3 +/- 4.1%, insulin 31.2 +/- 4.6%, metformin together with insulin 62.7 +/- 4.2%, p &lt; 0.005, n = 5).	Metformin	60-69	insulin S homeolog	Xenopus laevis	234-241
9498621-5	1998	Moreover, a short-term preincubation of mature oocytes with metformin, but in the absence of glucose, enhanced significantly the amount of synthase a when stimulated by 50 nmol/l insulin (basal 17.4 +/- 5.7%, metformin 21.3 +/- 4.1%, insulin 31.2 +/- 4.6%, metformin together with insulin 62.7 +/- 4.2%, p &lt; 0.005, n = 5).	Metformin	60-69	insulin S homeolog	Xenopus laevis	234-241
9498621-5	1998	Moreover, a short-term preincubation of mature oocytes with metformin, but in the absence of glucose, enhanced significantly the amount of synthase a when stimulated by 50 nmol/l insulin (basal 17.4 +/- 5.7%, metformin 21.3 +/- 4.1%, insulin 31.2 +/- 4.6%, metformin together with insulin 62.7 +/- 4.2%, p &lt; 0.005, n = 5).	Metformin	209-218	insulin S homeolog	Xenopus laevis	179-186
9498621-5	1998	Moreover, a short-term preincubation of mature oocytes with metformin, but in the absence of glucose, enhanced significantly the amount of synthase a when stimulated by 50 nmol/l insulin (basal 17.4 +/- 5.7%, metformin 21.3 +/- 4.1%, insulin 31.2 +/- 4.6%, metformin together with insulin 62.7 +/- 4.2%, p &lt; 0.005, n = 5).	Metformin	209-218	insulin S homeolog	Xenopus laevis	179-186
9109854-5	1997	On metformin, by stepwise multiple regression, the absolute reduction in Izero was a significant determinant of the absolute reduction in PAI-1 (partial R2 = 35%, P = .02), and the percent reduction in Izero was a significant determinant of the percent reduction in PAI-1 (partial R2 = 52%, P = .003).	Metformin	3-12	serpin family E member 1	Homo sapiens	138-143
9109854-5	1997	On metformin, by stepwise multiple regression, the absolute reduction in Izero was a significant determinant of the absolute reduction in PAI-1 (partial R2 = 35%, P = .02), and the percent reduction in Izero was a significant determinant of the percent reduction in PAI-1 (partial R2 = 52%, P = .003).	Metformin	3-12	serpin family E member 1	Homo sapiens	266-271
9109854-6	1997	Metformin decreases Izero in hyperinsulinemic PCOS patients, reverses the hyperinsulinemia-driven endocrinopathy, decreases PAI-1, and decreases Lp(a), and should thus reduce the increased risk of atherothrombosis in PCOS.	Metformin	0-9	serpin family E member 1	Homo sapiens	124-129
8651938-1	1996	The effect of the antihyperglycaemic agent metformin was studied on gene expression of the energy-dependent sodium-hexose cotransporter (SGLT1) and the facilitative hexose transporters GLUT2 and GLUT5 in rat intestine.	Metformin	43-52	solute carrier family 2 member 2	Rattus norvegicus	185-190
7835271-0	1995	Action of metformin on glucose transport and glucose transporter GLUT1 and GLUT4 in heart muscle cells from healthy and diabetic rats.	Metformin	10-19	solute carrier family 2 member 4	Rattus norvegicus	75-80
7835271-6	1995	Like insulin, metformin caused an approximately 1.6-fold increase in the content of both glucose transporter isoforms GLUT1 and GLUT4 in the plasma membrane of cardiac myocytes, with a corresponding decrease in an intracellular membrane fraction.	Metformin	14-23	solute carrier family 2 member 4	Rattus norvegicus	128-133
7818725-0	1994	Reduction of the acute bioavailability of metformin by the alpha-glucosidase inhibitor acarbose in normal man.	Metformin	42-51	sucrase-isomaltase	Homo sapiens	59-76
7818725-1	1994	In a double-blind cross-over study, we investigated a possible influence of the alpha-glucosidase inhibitor acarbose on the bioavailability of the biguanide compound metformin.	Metformin	166-175	sucrase-isomaltase	Homo sapiens	80-97
7930997-0	1994	Internalization of metformin is necessary for its action on potentiating the insulin-induced Xenopus laevis oocyte maturation.	Metformin	19-28	insulin S homeolog	Xenopus laevis	77-84
7930997-1	1994	In this study, metformin (N, N1 dimethylbiguanide) was found to potentiate insulin-induced Xenopus laevis oocyte maturation, a phenomenon of transition from late G2 to M phase of the cell cycle.	Metformin	15-24	insulin S homeolog	Xenopus laevis	75-82
7930997-5	1994	Micro-injection of metformin (120 nmol/oocyte) to oocytes accelerated the insulin-induced maturation, but it was lower than in cells which were incubated with free metformin together with insulin.	Metformin	19-28	insulin S homeolog	Xenopus laevis	74-81
7930997-5	1994	Micro-injection of metformin (120 nmol/oocyte) to oocytes accelerated the insulin-induced maturation, but it was lower than in cells which were incubated with free metformin together with insulin.	Metformin	164-173	insulin S homeolog	Xenopus laevis	74-81
7930997-9	1994	These results suggest that the internalization of metformin is necessary for its action and its effects are specific on insulin activity.	Metformin	50-59	insulin S homeolog	Xenopus laevis	120-127
8325447-0	1993	Metformin blocks downregulation of cell surface GLUT4 caused by chronic insulin treatment of rat adipocytes.	Metformin	0-9	solute carrier family 2 member 4	Rattus norvegicus	48-53
8325447-10	1993	The downregulation of GLUT4 observed after chronic insulin treatment was alleviated by metformin, and the proportion of GLUT4 at the cell surface was maintained at 60% of the total.	Metformin	87-96	solute carrier family 2 member 4	Rattus norvegicus	22-27
8387542-6	1993	The effect of metformin, a dimethyl-substituted biguanide, known to lower plasma insulin and PAI-1 levels in vivo was concomitantly evaluated.	Metformin	14-23	serpin family E member 1	Homo sapiens	93-98
8387542-11	1993	The results indicate that PAI-1 synthesis in presence of insulin is markedly increased in down-regulated cells, and that metformin inhibits this effect by acting at the cellular level.	Metformin	121-130	serpin family E member 1	Homo sapiens	26-31
8462390-12	1993	CONCLUSIONS: These findings indicate that metformin treatment improves glycemic control, and lowers insulin resistance and risk factors for cardiovascular disease, including PAI-1, and may therefore be useful in the long-term management of NIDDM subjects who have a high risk of cardiovascular disease.	Metformin	42-51	serpin family E member 1	Homo sapiens	174-179
33798839-7	2021	Metformin exposure was also associated with decreased levels of the inflammatory cytokines TNFalpha, IL-1a, IL-1b and IL-6 in serum, placenta and omental tissue taken from pregnant women.	Metformin	0-9	interleukin 1 alpha	Homo sapiens	101-106
33798839-8	2021	Metformin significantly decreased the release of anti-angiogenic factors sFlt-1 and sEng from ex-vivo placental and umbilical vein tissue, and increased maternal serum levels of non-phosphorylated IGFBP-1.	Metformin	0-9	insulin like growth factor binding protein 1	Homo sapiens	197-204
33235419-7	2020	Results: After the six month follow-up, there was a significant decrease in the QT interval in patients who were using SGLT2 inhibitors as an add-on therapy to metformin compared to other glucose-lowering agents (373.4 +- 9.9 ms vs. 385.4 +- 12.5 ms, 382.9 +- 11.2 ms; p < 0.001 respectively).	Metformin	160-169	solute carrier family 5 member 2	Homo sapiens	119-124
33235419-9	2020	Conclusions: Our data showed that using SGLT2 inhibitors as an add-on therapy to metformin favorably alters ventricular repolarization indices in patients with type 2 diabetes mellitus.	Metformin	81-90	solute carrier family 5 member 2	Homo sapiens	40-45
25590243-6	2015	We found that metformin was able to restore the increased levels of vascular endothelial growth factor, angiopoietin (ANGPT)1, and ANGPT1/ANGPT2 ratio and the decreased levels of platelet-derived growth factor B and platelet-derived growth factor D observed in the dehydroepiandrosterone-treated rats.	Metformin	14-23	angiopoietin 1	Rattus norvegicus	118-125
25590243-6	2015	We found that metformin was able to restore the increased levels of vascular endothelial growth factor, angiopoietin (ANGPT)1, and ANGPT1/ANGPT2 ratio and the decreased levels of platelet-derived growth factor B and platelet-derived growth factor D observed in the dehydroepiandrosterone-treated rats.	Metformin	14-23	angiopoietin 1	Rattus norvegicus	131-137
25590243-6	2015	We found that metformin was able to restore the increased levels of vascular endothelial growth factor, angiopoietin (ANGPT)1, and ANGPT1/ANGPT2 ratio and the decreased levels of platelet-derived growth factor B and platelet-derived growth factor D observed in the dehydroepiandrosterone-treated rats.	Metformin	14-23	platelet derived growth factor D	Rattus norvegicus	179-248
24047401-6	2013	AMP-activated protein kinase (AMPK) activators such as resveratrol, AICAR and metformin protected endothelial cells against complement-mediated cytotoxicity through the increase in CD55, CD59, haem oxygenase-1 (HO-1) and ferritin heavy chain (ferritin H) genes, all of which were attenuated by AMPKalpha knock-down.	Metformin	78-87	ferritin heavy chain 1	Homo sapiens	221-241
24047401-6	2013	AMP-activated protein kinase (AMPK) activators such as resveratrol, AICAR and metformin protected endothelial cells against complement-mediated cytotoxicity through the increase in CD55, CD59, haem oxygenase-1 (HO-1) and ferritin heavy chain (ferritin H) genes, all of which were attenuated by AMPKalpha knock-down.	Metformin	78-87	ferritin heavy chain 1	Homo sapiens	243-253
20668229-2	2010	We show in our current study that the LKB1/AMPK/TSC tumor suppressor axis is functional in AML and can be activated by the biguanide molecule metformin, resulting in a specific inhibition of mammalian target of rapamycin (mTOR) catalytic activity.	Metformin	142-151	serine/threonine kinase 11	Homo sapiens	38-42
20213998-22	2009	This change may be attributed to chronicity of diabetes or uncontrolled diabetic status or due to effect of metformin on post-prandial DPP IV levels.	Metformin	108-117	dipeptidyl peptidase 4	Homo sapiens	135-141
20357370-0	2010	A single nucleotide polymorphism in STK11 influences insulin sensitivity and metformin efficacy in hyperinsulinemic girls with androgen excess.	Metformin	77-86	serine/threonine kinase 11	Homo sapiens	36-41
20357370-2	2010	We tested the hypothesis that a gene variant in STK11 contributes to variation in insulin sensitivity and metformin efficacy.	Metformin	106-115	serine/threonine kinase 11	Homo sapiens	48-53
20357370-9	2010	The response to metformin differed by STK11 genotype: GG homozygotes (n = 24) had robust metabolic improvements, GC heterozygotes (n = 38) had intermediate responses, and CC homozygotes (n = 23) had almost no response.	Metformin	16-25	serine/threonine kinase 11	Homo sapiens	38-43
20357370-11	2010	CONCLUSIONS: In hyperinsulinemic girls with androgen excess, the STK11 rs8111699 SNP influences insulin sensitivity and metformin efficacy, so that the girls with the least favorable endocrine-metabolic profile improve most with metformin therapy.	Metformin	120-129	serine/threonine kinase 11	Homo sapiens	65-70
20357370-11	2010	CONCLUSIONS: In hyperinsulinemic girls with androgen excess, the STK11 rs8111699 SNP influences insulin sensitivity and metformin efficacy, so that the girls with the least favorable endocrine-metabolic profile improve most with metformin therapy.	Metformin	229-238	serine/threonine kinase 11	Homo sapiens	65-70
34506671-5	2022	In presence of metformin in the resistant induction process to DTIC, (MET-DTIC) cells had increased antioxidant thiols, MDA, nuclear p53, 8-OH-DG, Nrf2 and reducing NF-kB, weakening the DTIC-resistant phenotype.	Metformin	15-24	transformation related protein 53, pseudogene	Mus musculus	133-136
34718940-5	2022	METHODS AND RESULTS: In this context, we created a full-thickness excisional wound model in Wistar albino rats and, investigated NF-kappaB p65 DNA-binding activity and expression levels of RELA (p65), MMP2 and MMP9 in wound samples taken on days 0, 3, 7, and 14 from diabetic/non-diabetic rats treated with metformin and saline.	Metformin	307-316	RELA proto-oncogene, NF-kB subunit	Rattus norvegicus	189-193
34946771-8	2021	Furthermore, Stevioside enhanced glucose uptake (GU) and oxidation in diabetic muscles by augmenting glucose transporter 4 (GLUT 4) synthesis very effectively in a similar way to metformin.	Metformin	179-188	solute carrier family 2 member 4	Rattus norvegicus	101-122
34774192-0	2021	Retraction notice to KLF4/Ch25h axis activated by metformin suppresses EndoMT in human umbilical vein endothelial cells (Biochem.	Metformin	50-59	mannosidase endo-alpha	Homo sapiens	71-77
34944532-1	2021	It has been considered that proline dehydrogenase/proline oxidase (PRODH/POX) is involved in antineoplastic activity of metformin (MET).	Metformin	120-129	proline dehydrogenase 1	Homo sapiens	67-72
34944532-1	2021	It has been considered that proline dehydrogenase/proline oxidase (PRODH/POX) is involved in antineoplastic activity of metformin (MET).	Metformin	120-129	proline dehydrogenase 1	Homo sapiens	73-76
34944532-1	2021	It has been considered that proline dehydrogenase/proline oxidase (PRODH/POX) is involved in antineoplastic activity of metformin (MET).	Metformin	120-129	SAFB like transcription modulator	Homo sapiens	131-134
34910358-0	2022	Metformin regulates macrophage polarization via the Shh signaling pathway to improve pulmonary vascular development in bronchopulmonary dysplasia.	Metformin	0-9	sonic hedgehog	Mus musculus	52-55
34910358-14	2022	In conclusion, metformin regulates macrophage polarization via the Shh signaling pathway to improve pulmonary vascular development in bronchopulmonary dysplasia.	Metformin	15-24	sonic hedgehog	Mus musculus	67-70
34530523-6	2021	Results: The increased malondialdehyde (MDA) levels and myeloperoxidase (MPO) activities and the decreased superoxide dismutase (SOD) activities induced by I/R injury were reduced by treatment with metformin and/or sildenafil.	Metformin	198-207	myeloperoxidase	Rattus norvegicus	56-71
34530523-6	2021	Results: The increased malondialdehyde (MDA) levels and myeloperoxidase (MPO) activities and the decreased superoxide dismutase (SOD) activities induced by I/R injury were reduced by treatment with metformin and/or sildenafil.	Metformin	198-207	myeloperoxidase	Rattus norvegicus	73-76
34530523-7	2021	The I/R group had significantly higher JNK, p38 MAPK, Bax, caspase-3, and NF-kappaB levels, and lower ERK and Bcl-2 levels in the bladder than the sham-operated group; these changes were significantly ameliorated by metformin and/or sildenafil treatment.	Metformin	216-225	mitogen-activated protein kinase 8	Rattus norvegicus	39-42
34530523-7	2021	The I/R group had significantly higher JNK, p38 MAPK, Bax, caspase-3, and NF-kappaB levels, and lower ERK and Bcl-2 levels in the bladder than the sham-operated group; these changes were significantly ameliorated by metformin and/or sildenafil treatment.	Metformin	216-225	BCL2 associated X, apoptosis regulator	Rattus norvegicus	54-57
34850372-9	2022	Although metformin reduced mTORC1 downstream activated P70S6K, it did not significantly alter mTORser2448 activation and even increased BDNF expression.	Metformin	9-18	ribosomal protein S6 kinase B1	Rattus norvegicus	55-61
34881181-9	2021	Animal experiments confirmed that metformin downregulated PD-L1 expression and that combination treatment with metformin and PD-1 inhibitors synergistically enhanced the antitumor response.	Metformin	34-43	CD274 molecule	Homo sapiens	58-63
34881181-9	2021	Animal experiments confirmed that metformin downregulated PD-L1 expression and that combination treatment with metformin and PD-1 inhibitors synergistically enhanced the antitumor response.	Metformin	111-120	CD274 molecule	Homo sapiens	58-63
34881181-10	2021	Conclusions: Metformin downregulated PD-L1 expression by blocking the IL-6/JAK2/STAT3 signaling pathway in ESCC, which enhanced the antitumor immune response.	Metformin	13-22	CD274 molecule	Homo sapiens	37-42
34957500-8	2022	Functional enrichment analysis for cDNA microarrays from kidney samples revealed significant enrichment of several pro-proliferative pathways including beta-catenin, hypoxia-inducible factor-1alpha, protein kinase Calpha and Notch signaling pathways in the metformin-treated mutant mice.	Metformin	257-266	hypoxia inducible factor 1, alpha subunit	Mus musculus	166-197
34957500-11	2022	These results demonstrate that metformin may exacerbate late-stage cyst growth associated with the activation of lactate-related signaling pathways in Pkd1 deficiency.	Metformin	31-40	polycystin 1, transient receptor potential channel interacting	Homo sapiens	151-155
34796169-10	2021	Both hyperglycemic db/ + and high-fat diet-induced GDM mice exhibited a compromised AMPK-GLUT3 axis and suppressed cell viability in the placenta as well as excessive fetal growth, and all of these effects were partially alleviated by metformin.	Metformin	235-244	solute carrier family 2 (facilitated glucose transporter), member 3	Mus musculus	89-94
34595852-10	2021	Tissue AQP2 levels decreased with lithium administration but stabilized with metformin treatment.	Metformin	77-86	aquaporin 2	Rattus norvegicus	7-11
34595852-12	2021	CONCLUSIONS: Metformin may help protect the kidneys from lithium-induced NDI through the AQP2 regulating effect and a reduction in oxidative stress.	Metformin	13-22	aquaporin 2	Rattus norvegicus	89-93
34287770-9	2021	Both metformin and the sulfonylureas had a significant ROR under condition 2 (3.42 (95% CI 3.01-3.89) and 2.07 (95% CI 1.66-2.57) respectively); however, this association was not present under condition 3 as only confounded cases occurred, and a large majority of reported cases had concurrent exposure to a DPP-4 inhibitor.	Metformin	5-14	dipeptidyl peptidase 4	Homo sapiens	308-313
34630670-0	2021	Metformin attenuates H2O2-induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway.	Metformin	0-9	sirtuin 3	Mus musculus	69-74
34630670-13	2021	In addition, experiments with SIRT3 knockdown indicated that metformin reverses H2O2-induced osteoblast apoptosis by upregulating the expression of SIRT3 via the PI3K/AKT pathway.	Metformin	61-70	sirtuin 3	Mus musculus	30-35
34630670-13	2021	In addition, experiments with SIRT3 knockdown indicated that metformin reverses H2O2-induced osteoblast apoptosis by upregulating the expression of SIRT3 via the PI3K/AKT pathway.	Metformin	61-70	sirtuin 3	Mus musculus	148-153
34538531-9	2021	An interaction was observed for expression of Edil3 between diet and metformin treatment (unadjusted p = 0.009).	Metformin	69-78	EGF-like repeats and discoidin I-like domains 3	Mus musculus	46-51
33830437-0	2021	Metformin in non-diabetic patients with metabolic syndrome and diastolic dysfunction: the MET-DIME randomized trial.	Metformin	0-9	SAFB like transcription modulator	Homo sapiens	90-93
33355497-5	2021	Moreover, metformin furtherly promoted autophagy by increasing the protein expression of LC3-II, ATG5, ATG7 and Beclin1, and by involving AMPK pathway during MI.	Metformin	10-19	microtubule-associated protein 1 light chain 3 alpha	Rattus norvegicus	89-95
33355497-5	2021	Moreover, metformin furtherly promoted autophagy by increasing the protein expression of LC3-II, ATG5, ATG7 and Beclin1, and by involving AMPK pathway during MI.	Metformin	10-19	autophagy related 5	Rattus norvegicus	97-101
33355497-5	2021	Moreover, metformin furtherly promoted autophagy by increasing the protein expression of LC3-II, ATG5, ATG7 and Beclin1, and by involving AMPK pathway during MI.	Metformin	10-19	autophagy related 7	Rattus norvegicus	103-107
33355497-9	2021	In addition, metformin augmented the protein level of Bcl-2 and diminished the protein levels of Bax and cleaved caspase-3.	Metformin	13-22	BCL2 associated X, apoptosis regulator	Rattus norvegicus	97-100
31550992-1	2021	BACKGROUND: The American Diabetes Association (ADA) recommends sodium-glucose cotransporter-2 (SGLT2) inhibitors as the second medication to be started, after metformin, for patients with chronic kidney disease (CKD).	Metformin	159-168	solute carrier family 5 member 2	Homo sapiens	63-93
31550992-1	2021	BACKGROUND: The American Diabetes Association (ADA) recommends sodium-glucose cotransporter-2 (SGLT2) inhibitors as the second medication to be started, after metformin, for patients with chronic kidney disease (CKD).	Metformin	159-168	solute carrier family 5 member 2	Homo sapiens	95-100
34041677-0	2021	Augmentation of RBP4/STRA6 signaling leads to insulin resistance and inflammation and the plausible therapeutic role of vildagliptin and metformin.	Metformin	137-146	retinol binding protein 4	Rattus norvegicus	16-20
33965434-13	2021	The survival of hippocampal CA1 neurons was significantly higher in the metformin group as compared to the control group, while the number of TUNEL-positive neurons decreased significantly (p < 0.05).	Metformin	72-81	carbonic anhydrase 1	Rattus norvegicus	28-31
33975892-3	2021	SGLT-2 inhibitors and GLP-1 receptor agonists are traditionally used in people with elevated glucose level after metformin treatment.	Metformin	113-122	solute carrier family 5 member 2	Homo sapiens	0-6
33955025-1	2021	A selective and simple salting out assisted thin layer chromatographic methodology was developed for the simultaneous determination of two oral hypoglycemic drugs; namely dapagliflozin (DAPA) and metformin (MET) in their pure forms, tablets, and spiked human plasma samples.	Metformin	196-205	SAFB like transcription modulator	Homo sapiens	207-210
33856655-2	2021	Recently, clinical guidelines have focussed on patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) and recommend a sodium-glucose co-transporter 2 (SGLT2) inhibitor or a glucagon-like peptide 1 (GLP-1) receptor agonist as second-line treatment after metformin or independently of baseline glycated haemogloblin A1c (HbA1c).	Metformin	279-288	solute carrier family 5 member 2	Homo sapiens	177-182
33933135-9	2021	Serum asprosin was found to be positively related with disease duration, systolic blood pressure, blood urea nitrogen, creatinine, uric acid, ACR, calcium channel blockers, and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker therapy, but negatively related with glomerular filtration rate, metformin, and acarbose therapy.	Metformin	314-323	fibrillin 1	Homo sapiens	6-14
32791889-9	2021	In the murine model of BM, metformin delayed tumor growth in the bone and decreased the numbers of TRAP-positive osteoclasts on the bone surface with reduced RANKL in the bone marrow.	Metformin	27-36	tumor necrosis factor (ligand) superfamily, member 11	Mus musculus	158-163
32791889-10	2021	Furthermore, FRO- or SW1736-CM significantly increased the osteoblastic RANKL productions and activated osteoclast differentiation in whole marrow cultures, which were blocked by metformin treatment.	Metformin	179-188	tumor necrosis factor (ligand) superfamily, member 11	Mus musculus	72-77
33865459-15	2021	Additionally, the expressions of PCK1 and ABAT were raised in HepG2 cells pre-treated with metformin and phenformin.	Metformin	91-100	phosphoenolpyruvate carboxykinase 1	Homo sapiens	33-37
33860870-10	2021	Metformin, metformin and ketamine, triciribine, LY294002, and torin2 reduced Akt and PI3K expression, peribronchial and perivascular inflammation, and increased expression of Foxp3.	Metformin	0-9	forkhead box P3	Mus musculus	175-180
33860870-10	2021	Metformin, metformin and ketamine, triciribine, LY294002, and torin2 reduced Akt and PI3K expression, peribronchial and perivascular inflammation, and increased expression of Foxp3.	Metformin	11-20	forkhead box P3	Mus musculus	175-180
33918222-0	2021	Additional Inhibition of Wnt/beta-Catenin Signaling by Metformin in DAA Treatments as a Novel Therapeutic Strategy for HCV-Infected Patients.	Metformin	55-64	catenin beta 1	Homo sapiens	29-41
33918222-7	2021	Unexpectedly, Wnt/beta-catenin signaling remained activated in chronic HCV-infected cells after HCV eradication by DAA, but metformin reversed it through PKA/GSK-3beta-mediated beta-catenin degradation, inhibited colony-forming ability and proliferation, and increased apoptosis, suggesting that DAA therapy in combination with metformin may be a novel therapy to treat HCV-associated HCC where metformin suppresses Wnt/beta-catenin signaling for HCV-infected patients.	Metformin	124-133	catenin beta 1	Homo sapiens	177-189
33918222-7	2021	Unexpectedly, Wnt/beta-catenin signaling remained activated in chronic HCV-infected cells after HCV eradication by DAA, but metformin reversed it through PKA/GSK-3beta-mediated beta-catenin degradation, inhibited colony-forming ability and proliferation, and increased apoptosis, suggesting that DAA therapy in combination with metformin may be a novel therapy to treat HCV-associated HCC where metformin suppresses Wnt/beta-catenin signaling for HCV-infected patients.	Metformin	124-133	catenin beta 1	Homo sapiens	177-189
33927970-6	2021	Furthermore, anti-diabetic drugs including metformin, thiazolidinediones, and glucagon-like peptide-1 (GLP-1) analogue could modulate IRS-1 phosphorylation, brain IR, PI3K/Akt insulin signaling pathway, and other pathologic processes of AD.	Metformin	43-52	insulin receptor substrate 1	Homo sapiens	134-139
32745279-10	2021	CONCLUSIONS: Dapagliflozin is a cost-saving alternative to DPP-4 inhibitor when added to metformin and sulfonylurea.	Metformin	89-98	dipeptidyl peptidase 4	Homo sapiens	59-64
33838614-13	2021	CONCLUSION: DPP-4 inhibitor use was associated with lower mortality in COVID-19 patients, and the association was weaker in patients who were also taking metformin and/or ACE inhibitors.	Metformin	154-163	dipeptidyl peptidase 4	Homo sapiens	12-17
33685669-3	2021	Metformin (MET) is typically prescribed as first-line therapy, but a second line is often needed, given MET can be insufficient for maintaining long-term glycemic control.	Metformin	0-9	SAFB like transcription modulator	Homo sapiens	11-14
33164274-0	2021	Metformin modulates oncogenic expression of HOTAIR gene via promoter methylation and reverses epithelial-mesenchymal transition in MDA-MB-231 cells.	Metformin	0-9	HOX transcript antisense RNA	Homo sapiens	44-50
33164274-9	2021	Reduction in the expression of vimentin, beta-catenin, and HOTAIR was detected as the result of metformin treatment, but the snail showed a constant expression.	Metformin	96-105	vimentin	Homo sapiens	31-39
33164274-9	2021	Reduction in the expression of vimentin, beta-catenin, and HOTAIR was detected as the result of metformin treatment, but the snail showed a constant expression.	Metformin	96-105	catenin beta 1	Homo sapiens	41-53
33164274-9	2021	Reduction in the expression of vimentin, beta-catenin, and HOTAIR was detected as the result of metformin treatment, but the snail showed a constant expression.	Metformin	96-105	HOX transcript antisense RNA	Homo sapiens	59-65
33164274-11	2021	HOTAIR promoter methylation pattern was also investigated in metformin-exposed cells using bisulfite sequencing PCR which the result showed differences in the methylation profile of CpG islands between the treated and untreated cells.	Metformin	61-70	HOX transcript antisense RNA	Homo sapiens	0-6
33164274-12	2021	In conclusion, metformin modulated oncogenic expression of the HOTAIR gene in the MDA-MB-231 cells.	Metformin	15-24	HOX transcript antisense RNA	Homo sapiens	63-69
33164274-14	2021	Since HOTAIR induces EMT in breast cancer, HOTAIR decline might be one of the mechanisms by which metformin reverses EMT.	Metformin	98-107	HOX transcript antisense RNA	Homo sapiens	6-12
33164274-14	2021	Since HOTAIR induces EMT in breast cancer, HOTAIR decline might be one of the mechanisms by which metformin reverses EMT.	Metformin	98-107	HOX transcript antisense RNA	Homo sapiens	43-49
32989831-4	2021	In vitro, tucatinib inhibited OCT2-, MATE1-, and MATE2-K-mediated transport of metformin, with IC50 values of 14.7, 0.340, and 0.135 microM, respectively.	Metformin	79-88	solute carrier family 22 member 2	Homo sapiens	30-34
32969596-7	2021	Gas6 levels were found to be in proportion to the expression of adiponectin, which has been regarded as closely relevant to improved insulin sensitivity after metformin treatment.	Metformin	159-168	growth arrest specific 6	Mus musculus	0-4
32969596-7	2021	Gas6 levels were found to be in proportion to the expression of adiponectin, which has been regarded as closely relevant to improved insulin sensitivity after metformin treatment.	Metformin	159-168	adiponectin, C1Q and collagen domain containing	Mus musculus	64-75
33642112-11	2021	Metformin alleviated transcription and secretion of IL-1beta, Tumor Necrosis Factor-alpha, and Fibroblast Growth Factor 2, expression and nuclear translocation of C/EBPbeta in this model.	Metformin	0-9	interleukin 1 alpha	Mus musculus	52-60
33915857-11	2021	Moreover, post-stroke treatment with metformin significantly decreases the number of total and activated microglia at 48 h. The anti-inflammatory effect of metformin is associated with increased IL-10 production at 48 h after pMCAO.	Metformin	37-46	interleukin 10	Rattus norvegicus	195-200
33915857-11	2021	Moreover, post-stroke treatment with metformin significantly decreases the number of total and activated microglia at 48 h. The anti-inflammatory effect of metformin is associated with increased IL-10 production at 48 h after pMCAO.	Metformin	156-165	interleukin 10	Rattus norvegicus	195-200
33382900-0	2021	TLR4-associated IRF-7 and NFkB signaling acts as a molecular link between androgen and metformin activities and cytokine synthesis in the PCOS endometrium.	Metformin	87-96	toll like receptor 4	Homo sapiens	0-4
33382900-10	2021	CONCLUSION: Cytokine synthesis and increased endometrial inflammation in PCOS patients is coupled to androgen-induced TLR4/IRF-7/NFkB signaling, which is be inhibited by metformin treatment.	Metformin	170-179	toll like receptor 4	Homo sapiens	118-122
33606884-1	2021	AIMS: To evaluate the effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) on major cardiovascular events (MACE) in metformin-naive patients with type 2 diabetes (T2D).	Metformin	181-190	solute carrier family 5 member 2	Homo sapiens	32-62
33606884-1	2021	AIMS: To evaluate the effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) on major cardiovascular events (MACE) in metformin-naive patients with type 2 diabetes (T2D).	Metformin	181-190	solute carrier family 5 member 2	Homo sapiens	64-70
33746115-13	2021	The contents of CHOP and cleaved ATF6 were decreased in metformin-treated 24 mo.	Metformin	56-65	DNA-damage inducible transcript 3	Mus musculus	16-20
33841656-15	2021	In addition, metformin overcame progestin resistance by down-regulating Nrf2/LASS2 expression.	Metformin	13-22	ceramide synthase 2	Homo sapiens	77-82
33758522-6	2021	T2DM on metformin group had significantly higher Bad, Bax, and caspase-7 expression.	Metformin	8-17	caspase 7	Homo sapiens	63-72
33758522-8	2021	Metformin treatment significantly inhibited the expression of Bcl-10, Bid, and caspase-3 and upregulated Bad/Bax/caspase-7 pathway suggesting the activation of Bad/Bax/caspase-7 apoptotic pathway.	Metformin	0-9	caspase 7	Homo sapiens	113-122
33758522-8	2021	Metformin treatment significantly inhibited the expression of Bcl-10, Bid, and caspase-3 and upregulated Bad/Bax/caspase-7 pathway suggesting the activation of Bad/Bax/caspase-7 apoptotic pathway.	Metformin	0-9	caspase 7	Homo sapiens	168-177
33690729-18	2021	However, further investigations are necessary to confirm the observations and conclusions drawn from the presented data after metformin administration, especially for proteins that were regulated in a favorable way, i.e. AKT3, CCND2, CD63, CD81, GFAP, IL5, IL17A, IRF4, PI3, and VTCN1.	Metformin	126-135	CD63 molecule	Homo sapiens	234-238
33831975-2	2022	Metformin"s effects on men"s related health are reviewed here, focusing on reproductive health under subtitles of erectile dysfunction (ED), steroidogenesis and spermatogenesis; and on prostate-related health under subtitles of prostate specific antigen (PSA), prostatitis, benign prostate hyperplasia (BPH), and prostate cancer (PCa).	Metformin	0-9	kallikrein related peptidase 3	Homo sapiens	228-253
33831975-2	2022	Metformin"s effects on men"s related health are reviewed here, focusing on reproductive health under subtitles of erectile dysfunction (ED), steroidogenesis and spermatogenesis; and on prostate-related health under subtitles of prostate specific antigen (PSA), prostatitis, benign prostate hyperplasia (BPH), and prostate cancer (PCa).	Metformin	0-9	kallikrein related peptidase 3	Homo sapiens	255-258
33831975-4	2022	With regards to prostate-related health, metformin use may be associated with lower levels of PSA in humans, but its clinical implications require more research.	Metformin	41-50	kallikrein related peptidase 3	Homo sapiens	94-97
33747548-2	2021	Sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are second-line options after metformin, while cardiovascular outcome trials have been conducted to establish the cardiovascular safety of these antidiabetic drug classes.	Metformin	178-187	solute carrier family 5 member 2	Homo sapiens	0-31
33522578-0	2021	Metformin induces ferroptosis by targeting miR-324-3p/GPX4 axis in breast cancer.	Metformin	0-9	glutathione peroxidase 4	Homo sapiens	54-58
33522578-10	2021	Our study suggested that metformin promotes ferroptosis of breast cancer by targeting the miR-324-3p/GPX4 axis.	Metformin	25-34	glutathione peroxidase 4	Homo sapiens	101-105
32075509-8	2021	In contrast, increased activity of AMPK with metformin, AICAR, 2DG, or by gene overexpression did not enhance autophagy but had different effects on Abeta secretion: whereas metformin and 2DG diminished the secreted Abeta levels, AICAR and PRKAA1/AMPK gene overexpression increased them.	Metformin	174-183	amyloid beta (A4) precursor protein	Mus musculus	216-221
33434538-7	2021	In addition, the mRNA, protein expression level and activity of the renal organic cation transporter 2 (OCT2) was markedly increased, suggesting that the enhanced renal clearance of metformin in CIA rats may be due to the up-regulated activity of OCT2.	Metformin	182-191	solute carrier family 22 member 2	Rattus norvegicus	74-102
33434538-7	2021	In addition, the mRNA, protein expression level and activity of the renal organic cation transporter 2 (OCT2) was markedly increased, suggesting that the enhanced renal clearance of metformin in CIA rats may be due to the up-regulated activity of OCT2.	Metformin	182-191	solute carrier family 22 member 2	Rattus norvegicus	104-108
33434538-7	2021	In addition, the mRNA, protein expression level and activity of the renal organic cation transporter 2 (OCT2) was markedly increased, suggesting that the enhanced renal clearance of metformin in CIA rats may be due to the up-regulated activity of OCT2.	Metformin	182-191	solute carrier family 22 member 2	Rattus norvegicus	247-251
33434538-8	2021	In conclusion, our study suggested that the reduced bioavailability of metformin in CIA rats is possibly related to the up-regulated function of the renal protein OCT2.	Metformin	71-80	solute carrier family 22 member 2	Rattus norvegicus	163-167
33648513-12	2021	Metformin protects the cells from the increase of LPS-induced binding activity of NF-kappaB on both TNFA and IL1B promoters.	Metformin	0-9	tumor necrosis factor	Bos taurus	100-104
33218786-3	2021	Glucagon-like peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors when added to metformin therapy provide the most CV benefit and should be considered in most patients.	Metformin	93-102	solute carrier family 5 member 2	Homo sapiens	37-67
32462317-10	2021	Restoration of the insulin signaling pathway, IRS/Akt/GLUT4 protein expression, was demonstrated in hesperidin and metformin-treated groups (p < 0.05).	Metformin	115-124	solute carrier family 2 member 4	Rattus norvegicus	54-59
33453674-2	2021	Hence, the study aimed to inspect the ability of the combination therapy of metformin and omega-3 to modulate different signaling pathways and micro RNAs such as (miR-155, miR-146a and miR-34) as new targets in order to mitigate adjuvant-induced arthritis and compare their effect to that of methotrexate.	Metformin	76-85	microRNA 146a	Homo sapiens	172-180
33412215-0	2021	Metformin prevented high glucose-induced endothelial reactive oxygen species via OGG1 in an AMPKalpha-Lin-28 dependent pathway.	Metformin	0-9	8-oxoguanine DNA glycosylase	Homo sapiens	81-85
33412215-6	2021	KEY FINDINGS: Metformin reduced HG-induced endothelial ROS by upregulating OGG1.	Metformin	14-23	8-oxoguanine DNA glycosylase	Homo sapiens	75-79
33412215-9	2021	SIGNIFICANCE: These results suggested that metformin modulated HG-induced endothelial ROS via the AMPKalpha/Lin-28/OGG1 pathway.	Metformin	43-52	8-oxoguanine DNA glycosylase	Homo sapiens	115-119
33047165-10	2021	Metformin significantly attenuated diabetes-related histopathological ocular deteriorations in the cornea, lens, sclera, ciliary body, iris, conjunctiva, retina, and optic nerve partly by restoring serum TNF-alpha, VEGF, claudin-1, and glutathione/malondialdehyde ratios without significantly affecting the fasting blood glucose levels or body weight in these hyperglycemic rats.	Metformin	0-9	vascular endothelial growth factor A	Rattus norvegicus	215-219
33603170-0	2021	Repurposing dextromethorphan and metformin for treating nicotine-induced cancer by directly targeting CHRNA7 to inhibit JAK2/STAT3/SOX2 signaling.	Metformin	33-42	cholinergic receptor nicotinic alpha 7 subunit	Homo sapiens	102-108
33603170-6	2021	Mechanistically, dextromethorphan non-competitively inhibited nicotine binding to CHRNA7 while metformin downregulated CHRNA7 expression by antagonizing nicotine-induced promoter DNA hypomethylation of CHRNA7.	Metformin	95-104	cholinergic receptor, nicotinic, alpha polypeptide 7	Mus musculus	119-125
33603170-6	2021	Mechanistically, dextromethorphan non-competitively inhibited nicotine binding to CHRNA7 while metformin downregulated CHRNA7 expression by antagonizing nicotine-induced promoter DNA hypomethylation of CHRNA7.	Metformin	95-104	cholinergic receptor, nicotinic, alpha polypeptide 7	Mus musculus	119-125
32879144-7	2021	She was treated with metformin and canagliflozin (a sodium glucose co-transporter 2 (SGLT2) inhibitor), which ameliorated overt diurnal hyperglycemia and mild nocturnal hypoglycemia and reduced her blood HbA1c around 7%.	Metformin	21-30	solute carrier family 5 member 2	Homo sapiens	52-83
32879144-7	2021	She was treated with metformin and canagliflozin (a sodium glucose co-transporter 2 (SGLT2) inhibitor), which ameliorated overt diurnal hyperglycemia and mild nocturnal hypoglycemia and reduced her blood HbA1c around 7%.	Metformin	21-30	solute carrier family 5 member 2	Homo sapiens	85-90
33507658-4	2021	Currently, the best classes to add after metformin seem to be SGLT2 inhibitors and GLP-1 receptor agonists, as these molecules showed some cardiovascular and renal beneficial effects in dedicated studies.	Metformin	41-50	solute carrier family 5 member 2	Homo sapiens	62-67
33575255-6	2020	Interestingly, we discovered that the activation of ECE1, ABCA12, BPY2, EEF1A1, RAD9A, and NIPSNAP1 contributed to in vitro resistance to metformin in DU145 and PC3 cell lines.	Metformin	138-147	endothelin converting enzyme 1	Homo sapiens	52-56
33575255-6	2020	Interestingly, we discovered that the activation of ECE1, ABCA12, BPY2, EEF1A1, RAD9A, and NIPSNAP1 contributed to in vitro resistance to metformin in DU145 and PC3 cell lines.	Metformin	138-147	nipsnap homolog 1	Homo sapiens	91-99
33543290-2	2021	Whether metformin, a widely prescribed anti-diabetes agent with mTOR inhibitory effect, could preserve ovarian function against CP toxicity is unknown.	Metformin	8-17	mechanistic target of rapamycin kinase	Mus musculus	64-68
33543290-8	2021	Expression of phospho-mTOR and the number of TUNEL-positive granulosa cells increased after CP treatment and decreased in the CP + metformin groups, suggesting the mTOR inhibitory and anti-apoptotic effects of metformin.	Metformin	131-140	mechanistic target of rapamycin kinase	Mus musculus	22-26
33543290-8	2021	Expression of phospho-mTOR and the number of TUNEL-positive granulosa cells increased after CP treatment and decreased in the CP + metformin groups, suggesting the mTOR inhibitory and anti-apoptotic effects of metformin.	Metformin	131-140	mechanistic target of rapamycin kinase	Mus musculus	164-168
33543290-8	2021	Expression of phospho-mTOR and the number of TUNEL-positive granulosa cells increased after CP treatment and decreased in the CP + metformin groups, suggesting the mTOR inhibitory and anti-apoptotic effects of metformin.	Metformin	210-219	mechanistic target of rapamycin kinase	Mus musculus	164-168
33543290-9	2021	In in-vitro granulosa cell experiments, the anti-apoptotic effect of metformin was blocked after inhibiting p53 or p21 function, and the expression of p53 mRNA was blocked with AMPK inhibitor, suggesting that the anti-apoptotic effect was AMPK/p53/p21-mediated.	Metformin	69-78	transformation related protein 53, pseudogene	Mus musculus	108-111
33157041-8	2021	The beneficial effects of using both the naringenin and metformin along with the lower dose of doxorubicin were evident from the reduced dose-related body weight loss and increase in cytokines (TNF-alpha and IL-1beta) compared to a large dose of doxorubicin alone.	Metformin	56-65	interleukin 1 alpha	Mus musculus	208-216
33197442-0	2021	Metformin ameliorates brain damage caused by cardiopulmonary resuscitation via targeting endoplasmic reticulum stress-related proteins GRP78 and XBP1.	Metformin	0-9	X-box binding protein 1	Rattus norvegicus	145-149
33197442-11	2021	Furthermore, metformin inhibited the mRNA and protein expressions of glucose-regulated protein 78 (GRP78) and X-box binding protein 1 (XBP1) in the CA/CPR rat model.	Metformin	13-22	X-box binding protein 1	Rattus norvegicus	110-133
33197442-11	2021	Furthermore, metformin inhibited the mRNA and protein expressions of glucose-regulated protein 78 (GRP78) and X-box binding protein 1 (XBP1) in the CA/CPR rat model.	Metformin	13-22	X-box binding protein 1	Rattus norvegicus	135-139
33197442-12	2021	We confirmed that CA/CPR can induce ERS-related apoptosis and oxidative stress in the brain; moreover, inhibiting ERS-related proteins GRP78 and XBP1 with metformin might attenuate cerebral injury post CA/CPR.	Metformin	155-164	X-box binding protein 1	Rattus norvegicus	145-149
33220275-0	2021	Metformin reduces proteinuria in spontaneously hypertensive rats by activating the HIF-2alpha-VEGF-A pathway.	Metformin	0-9	vascular endothelial growth factor A	Rattus norvegicus	94-100
33220275-8	2021	Metformin increased the production of vascular endothelial growth factor (VEGF)-A in rat kidneys and cultured rat podocytes.	Metformin	0-9	vascular endothelial growth factor A	Rattus norvegicus	74-78
33220275-9	2021	Metformin activated hypoxia-inducible factor-2alpha (Hif-2alpha) in response to VEGF but did not affect Hif-1alpha in rat kidneys and cultured rat podocytes.	Metformin	0-9	vascular endothelial growth factor A	Rattus norvegicus	80-84
33220275-10	2021	Metformin reduced the proteinuria induced by long-term high blood pressure in vivo and increased the VEGF-A production in rat kidneys and cultured rat podocytes, probably by activating the Hif-2alpha-VEGF signaling pathway.	Metformin	0-9	vascular endothelial growth factor A	Rattus norvegicus	101-107
33220275-10	2021	Metformin reduced the proteinuria induced by long-term high blood pressure in vivo and increased the VEGF-A production in rat kidneys and cultured rat podocytes, probably by activating the Hif-2alpha-VEGF signaling pathway.	Metformin	0-9	vascular endothelial growth factor A	Rattus norvegicus	101-105
32951587-5	2021	In this review, we summarize the chemosensitization effects of metformin and focus primarily on its molecular mechanisms in enhancing the sensitivity of multiple chemotherapeutic drugs, through targeting of mTOR, ERK/P70S6K, NF-kappaB/HIF-1alpha, and mitogenactivated protein kinase (MAPK) signaling pathways, as well as by down-regulating the expression of CSC genes and pyruvate kinase isoenzyme M2 (PKM2).	Metformin	63-72	ribosomal protein S6 kinase B1	Homo sapiens	217-223
32951587-5	2021	In this review, we summarize the chemosensitization effects of metformin and focus primarily on its molecular mechanisms in enhancing the sensitivity of multiple chemotherapeutic drugs, through targeting of mTOR, ERK/P70S6K, NF-kappaB/HIF-1alpha, and mitogenactivated protein kinase (MAPK) signaling pathways, as well as by down-regulating the expression of CSC genes and pyruvate kinase isoenzyme M2 (PKM2).	Metformin	63-72	pyruvate kinase M1/2	Homo sapiens	372-400
32951587-5	2021	In this review, we summarize the chemosensitization effects of metformin and focus primarily on its molecular mechanisms in enhancing the sensitivity of multiple chemotherapeutic drugs, through targeting of mTOR, ERK/P70S6K, NF-kappaB/HIF-1alpha, and mitogenactivated protein kinase (MAPK) signaling pathways, as well as by down-regulating the expression of CSC genes and pyruvate kinase isoenzyme M2 (PKM2).	Metformin	63-72	pyruvate kinase M1/2	Homo sapiens	402-406
33007330-6	2021	In particular, we found that, in addition to AKT and ERK1/2 activation, FGFR1-induced activation of IRS1 and IGF1R, key regulators connecting metabolism and cancer, was associated with metformin resistance.	Metformin	185-194	insulin receptor substrate 1	Homo sapiens	100-104
33007330-7	2021	Targeting IRS with IRS1 KO or IRS inhibitor NT157 significantly sensitized FGFR1 overexpressing cells to metformin.	Metformin	105-114	insulin receptor substrate 1	Homo sapiens	19-23
33007330-10	2021	Our study highlights the significance of FGFR1 status and IRS1 activation in metformin-resistance, which will facilitate the development of strategies targeting FGFR overexpression-associated metformin resistance.	Metformin	77-86	insulin receptor substrate 1	Homo sapiens	58-62
33217690-11	2021	However, metformin co-administration significantly decreased the levels of TNF-alpha, IL-6 and IL-1beta while increased the level of IL-10 in epididymal white adipose tissue compared to olanzapine-treated rats.	Metformin	9-18	interleukin 10	Rattus norvegicus	133-138
32940848-12	2021	CONCLUSIONS: We conclude that the combination of metformin and BMS-754807 is more effective than either drug alone in inhibiting cell proliferation in the majority of TNBC cell lines, and that one important mechanism may be suppression of SCFSkp2 and subsequent stabilization of the cell cycle inhibitor p27Kip1.	Metformin	49-58	cyclin dependent kinase inhibitor 1B	Homo sapiens	304-311
32702185-10	2021	Heat shock protein 70 expression was increased in metformin-treated porcine kidneys.	Metformin	50-59	heat shock protein family A (Hsp70) member 1B	Rattus norvegicus	0-21
31881233-6	2021	Gene expression analysis revealed that metformin could upregulate cat-2 gene expression and GFP-tagged SOD-3 expression.	Metformin	39-48	BH4_AAA_HYDROXYL_2 domain-containing protein;Tyrosine 3-hydroxylase;Tyrosine 3-monooxygenase	Caenorhabditis elegans	66-71
33533444-9	2020	Eventually, we obtained stable simulation of OCT-metformin interaction.	Metformin	49-58	plexin A2	Homo sapiens	45-48
32415700-13	2020	Similarly, VPA-induced increase in acetylcholinesterase activity in the hippocampus and PFC were attenuated by post-natal treatment with metformin.	Metformin	137-146	acetylcholinesterase	Rattus norvegicus	35-55
32878700-7	2020	Use of insulin increased (OR 1.16, 95 % CI 1.06-1.27) whereas use of metformin and DPP-4 inhibitors decreased (metformin: OR 0.80, 95 % CI 0.70-0.90; DPP-4 inhibitors: OR 0.82, 95 % CI 0.73-0.93).	Metformin	111-120	dipeptidyl peptidase 4	Homo sapiens	83-88
33303055-0	2020	Metformin protects chondrocytes against IL-1beta induced injury by regulation of the AMPK/NF-kappa B signaling pathway.	Metformin	0-9	interleukin 1 alpha	Mus musculus	40-48
33303055-6	2020	We found that metformin increased the proliferation of the cells, alleviated IL-1beta-induced ECM metabolic imbalance and proinflammatory cytokine production, and exerted anti-apoptosis activity in ATDC5 cells.	Metformin	14-23	interleukin 1 alpha	Mus musculus	77-85
33303055-7	2020	Furthermore, the results showed that metformin blocked the NF-kappa B pathway in IL-1beta-induced ATDC5 cells via activation of AMP-activated protein kinase (AMPK).	Metformin	37-46	interleukin 1 alpha	Mus musculus	81-89
33303055-8	2020	These results indicated that metformin protected chondrocytes against IL-1beta-induced injury, possibly by regulation of the AMPK/NF-kappa B signaling pathway.	Metformin	29-38	interleukin 1 alpha	Mus musculus	70-78
33425803-1	2020	Sulfonylurea (SU) and dipeptidyl peptidase-4 (DPP-4) inhibitors are most common secondary agents that are added to metformin monotherapy.	Metformin	115-124	dipeptidyl peptidase 4	Homo sapiens	22-44
33425803-1	2020	Sulfonylurea (SU) and dipeptidyl peptidase-4 (DPP-4) inhibitors are most common secondary agents that are added to metformin monotherapy.	Metformin	115-124	dipeptidyl peptidase 4	Homo sapiens	46-51
33189895-1	2021	AIMS: Preliminary data have suggested that metformin might potentiate cardiovascular (CV) protection by dipeptidyl peptidase-4 inhibitors (DPP-4is), but reduce CV protection by sodium-glucose cotransporter type-2 inhibitors (SGLT2is), in patients with type 2 diabetes (T2DM) at high CV-related risk.	Metformin	43-52	dipeptidyl peptidase 4	Homo sapiens	104-126
33189895-1	2021	AIMS: Preliminary data have suggested that metformin might potentiate cardiovascular (CV) protection by dipeptidyl peptidase-4 inhibitors (DPP-4is), but reduce CV protection by sodium-glucose cotransporter type-2 inhibitors (SGLT2is), in patients with type 2 diabetes (T2DM) at high CV-related risk.	Metformin	43-52	dipeptidyl peptidase 4	Homo sapiens	139-144
33189895-1	2021	AIMS: Preliminary data have suggested that metformin might potentiate cardiovascular (CV) protection by dipeptidyl peptidase-4 inhibitors (DPP-4is), but reduce CV protection by sodium-glucose cotransporter type-2 inhibitors (SGLT2is), in patients with type 2 diabetes (T2DM) at high CV-related risk.	Metformin	43-52	solute carrier family 5 member 2	Homo sapiens	225-230
32763300-0	2020	The effect of metformin on carotid intima-media thickness (CIMT): A systematic review and meta-analysis of randomized clinical trials.	Metformin	14-23	CIMT	Homo sapiens	59-63
32763300-1	2020	Metformin administration has been reported to influence the carotid intima-media thickness (CIMT) in humans.	Metformin	0-9	CIMT	Homo sapiens	92-96
32763300-2	2020	However, since previously conducted studies have yielded inconsistent results, the exact effect of metformin on CIMT remains unclear.	Metformin	99-108	CIMT	Homo sapiens	112-116
32763300-4	2020	To address this inconsistency, we conducted a systematic review and meta-analysis to evaluate the influence of metformin on CIMT in human subjects.	Metformin	111-120	CIMT	Homo sapiens	124-128
32763300-7	2020	Combining data from 1087 participants (9 studies), our meta-analysis revealed that the administration of metformin resulted in a significant reduction in CIMT (WMD = -0.049 mm; 95% CI: -0.095, -0.004).	Metformin	105-114	CIMT	Homo sapiens	154-158
32763300-10	2020	The results of the current study confirm that metformin administration is associated with a significant reduction in CIMT.	Metformin	46-55	CIMT	Homo sapiens	117-121
32449077-4	2020	OBJECTIVE: The objective of this study was to provide mechanistic whole-body physiologically based pharmacokinetic models of metformin and cimetidine, built and evaluated to describe the metformin-SLC22A2 808G>T drug-gene interaction, the cimetidine-metformin drug-drug interaction, and the impact of renal impairment on metformin exposure.	Metformin	125-134	solute carrier family 22 member 2	Homo sapiens	197-204
32449077-4	2020	OBJECTIVE: The objective of this study was to provide mechanistic whole-body physiologically based pharmacokinetic models of metformin and cimetidine, built and evaluated to describe the metformin-SLC22A2 808G>T drug-gene interaction, the cimetidine-metformin drug-drug interaction, and the impact of renal impairment on metformin exposure.	Metformin	187-196	solute carrier family 22 member 2	Homo sapiens	197-204
32449077-4	2020	OBJECTIVE: The objective of this study was to provide mechanistic whole-body physiologically based pharmacokinetic models of metformin and cimetidine, built and evaluated to describe the metformin-SLC22A2 808G>T drug-gene interaction, the cimetidine-metformin drug-drug interaction, and the impact of renal impairment on metformin exposure.	Metformin	187-196	solute carrier family 22 member 2	Homo sapiens	197-204
32449077-4	2020	OBJECTIVE: The objective of this study was to provide mechanistic whole-body physiologically based pharmacokinetic models of metformin and cimetidine, built and evaluated to describe the metformin-SLC22A2 808G>T drug-gene interaction, the cimetidine-metformin drug-drug interaction, and the impact of renal impairment on metformin exposure.	Metformin	187-196	solute carrier family 22 member 2	Homo sapiens	197-204
32911202-0	2020	Effect of metformin and insulin combination on monocyte chemoattractant protein-1 and cathepsin-D in type 2 diabetes mellitus.	Metformin	10-19	C-C motif chemokine ligand 2	Homo sapiens	47-81
32911202-7	2020	CONCLUSION: Patients treated with metformin and insulin combination had lower serum MCP-1 and cathepsin-D levels which suggests that this combination may be more effective in reducing the progression of diabetic retinopathy.	Metformin	34-43	C-C motif chemokine ligand 2	Homo sapiens	84-89
33112812-0	2020	Metformin decreases miR-122, miR-223 and miR-29a in women with polycystic ovary syndrome.	Metformin	0-9	microRNA 29a	Homo sapiens	41-48
32870322-0	2020	Metformin improves depressive-like symptoms in mice via inhibition of peripheral and central NF-kappaB-NLRP3 inflammation activation.	Metformin	0-9	NLR family, pyrin domain containing 3	Mus musculus	103-108
32870322-6	2020	We further found that metformin significantly suppressed NLRP3 inflammasome activation, subsequent caspase-1 cleavage, and interleukin-1beta secretion in both peripheral macrophages and central hippocampus.	Metformin	22-31	NLR family, pyrin domain containing 3	Mus musculus	57-62
32870322-7	2020	Our findings reveal that metformin confers an antidepressant effect partly through inhibition of peripheral and central NLRP3 inflammasome activation.	Metformin	25-34	NLR family, pyrin domain containing 3	Mus musculus	120-125
32870322-8	2020	In light of metformin favorable properties, it should be evaluated in the treatment of depression and related neurologic disorders characterized by NLRP3 inflammasome activation.	Metformin	12-21	NLR family, pyrin domain containing 3	Mus musculus	148-153
32239671-6	2020	Western blot analysis of lysates of CRC-derived cells revealed a substantial metformin-induced increase in the level of p120-catenin as well as E-cadherin phosphorylation on Ser838/840 , a modification associated with beta-catenin/E-cadherin interaction.	Metformin	77-86	catenin beta 1	Homo sapiens	218-230
32239671-7	2020	These modifications in E-cadherin, p120-catenin and beta-catenin localization suggest that metformin induces rebuilding of AJs in CRC-derived cells.	Metformin	91-100	catenin beta 1	Homo sapiens	52-64
32679167-13	2020	In sum, we have concluded that progranulin can be a key mediator in epilepsy, and the anti-inflammatory action of metformin in status epilepticus is through increasing the secretion of IL-10 and inhibiting IL-1 beta and astrogliosis.	Metformin	114-123	interleukin 10	Rattus norvegicus	185-190
32785826-7	2020	Furthermore, we propose that the beneficial effects of metformin we observed towards seizure development are related to a normalization of both GLUT-1 and GLUT-3 expression levels.	Metformin	55-64	solute carrier family 2 (facilitated glucose transporter), member 1	Mus musculus	144-150
32785826-7	2020	Furthermore, we propose that the beneficial effects of metformin we observed towards seizure development are related to a normalization of both GLUT-1 and GLUT-3 expression levels.	Metformin	55-64	solute carrier family 2 (facilitated glucose transporter), member 3	Mus musculus	155-161
32934724-4	2020	The direct mechanisms of metformin include inhibition of the LKB1-AMP-activated protein kinase-mTOR, PI3K-Akt and insulin-like growth factor 1-related signaling pathways, which reduces the proliferation and promotes the apoptosis of EC cells.	Metformin	25-34	serine/threonine kinase 11	Homo sapiens	61-65
33482956-0	2020	Evaluation of Dipeptidyl Peptidase-4 Inhibitors versus Thiazolidinediones or Insulin in Patients with Type 2 Diabetes Uncontrolled with Metformin and a Sulfonylurea in a Real-World Setting.	Metformin	136-145	dipeptidyl peptidase 4	Homo sapiens	14-36
33065544-9	2020	The expression of genes related to steroidogenesis such as FSHR, STAR, CYP11A1, HSD3B, and progesterone secretion was significantly decreased in response to metformin treatment in a dose-dependent manner.	Metformin	157-166	cytochrome P450 family 11 subfamily A member 1	Gallus gallus	71-78
33108409-0	2020	Metformin partially reverses the inhibitory effect of co-culture with ER-/PR-/HER2+ breast cancer cells on biomarkers of monocyte antitumor activity.	Metformin	0-9	transmembrane protein 37	Homo sapiens	74-76
33108409-2	2020	Metformin (1,1-dimethylbiguanide hydrochloride, MET), has been shown to decrease tumor cell proliferation, but its effects have yet to be explored with respect to MOs (monocytes) activity during their crosstalk with breast cancer cells.	Metformin	0-9	SAFB like transcription modulator	Homo sapiens	48-51
32930254-1	2020	The combination therapy of cisplatin (CDDP) and metformin (MET) is a clinical strategy to enhance therapeutic outcomes in lung cancer.	Metformin	48-57	SAFB like transcription modulator	Homo sapiens	59-62
32367399-0	2020	Descending Expression of miR320 in Insulin-Resistant Adipocytes Treated with Ascending Concentrations of Metformin.	Metformin	105-114	microRNA 320	Mus musculus	25-31
32367399-3	2020	This study aimed at determining the effect of Metformin on miR320 expression in insulin-resistant (IR) adipocytes.	Metformin	46-55	microRNA 320	Mus musculus	59-65
32367399-6	2020	Compared to the normal adipocytes, IR adipocytes exhibited a significantly higher level of miR320 expression, however, in response to Metformin graded concentrations, IR adipocytes down-regulated miR320 and were almost at normal level.	Metformin	134-143	microRNA 320	Mus musculus	91-97
32367399-6	2020	Compared to the normal adipocytes, IR adipocytes exhibited a significantly higher level of miR320 expression, however, in response to Metformin graded concentrations, IR adipocytes down-regulated miR320 and were almost at normal level.	Metformin	134-143	microRNA 320	Mus musculus	196-202
32367399-8	2020	In IR adipocytes, miR320 expression is over-expressed which can be down-regulated by Metformin treatment.	Metformin	85-94	microRNA 320	Mus musculus	18-24
32800853-5	2020	Herein, we found that metformin enhanced the phosphorylation of tyrosine hydroxylase (TH) which was accompanied by increase in brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and activation of their downstream signaling pathways in the mouse brain and SH-SY5Y cells.	Metformin	22-31	brain derived neurotrophic factor	Mus musculus	127-160
32800853-5	2020	Herein, we found that metformin enhanced the phosphorylation of tyrosine hydroxylase (TH) which was accompanied by increase in brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and activation of their downstream signaling pathways in the mouse brain and SH-SY5Y cells.	Metformin	22-31	brain derived neurotrophic factor	Mus musculus	162-166
32912901-0	2020	AMPK regulation of Raptor and TSC2 mediate metformin effects on transcriptional control of anabolism and inflammation.	Metformin	43-52	TSC complex subunit 2	Mus musculus	30-34
32912901-3	2020	Metformin-dependent activation of AMPK classically inhibits mTORC1 via TSC/RHEB, but several lines of evidence suggest additional mechanisms at play in metformin inhibition of mTORC1.	Metformin	0-9	TSC22 domain family, member 1	Mus musculus	71-74
32912901-5	2020	Metformin treatment of primary hepatocytes and intact murine liver requires AMPK regulation of both RAPTOR and TSC2 to fully inhibit mTORC1, and this regulation is critical for both the translational and transcriptional response to metformin.	Metformin	0-9	TSC complex subunit 2	Mus musculus	111-115
32917052-9	2020	Multifactorial discriminant analysis revealed that irisin and vaspin plasma levels contribute clinically relevant information concerning the effectiveness of metformin treatment in T2D patients.	Metformin	158-167	fibronectin type III domain containing 5	Homo sapiens	51-57
32886218-5	2022	METHODS: We evaluated the hemorheological parameters of 63 patients of whom 38 received metformin with a dipeptidyl peptidase 4 (DPP-4) inhibitor, while 25 received metformin with SGLT-2 inhibitor.	Metformin	88-97	dipeptidyl peptidase 4	Homo sapiens	105-127
32886218-5	2022	METHODS: We evaluated the hemorheological parameters of 63 patients of whom 38 received metformin with a dipeptidyl peptidase 4 (DPP-4) inhibitor, while 25 received metformin with SGLT-2 inhibitor.	Metformin	165-174	solute carrier family 5 member 2	Homo sapiens	180-186
32700188-1	2020	INTRODUCTION: International guidelines recommend treatment with a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist for treatment intensification in type 2 diabetes mellitus (T2DM) patients with progression on metformin.	Metformin	262-271	solute carrier family 5 member 2	Homo sapiens	66-96
32700188-1	2020	INTRODUCTION: International guidelines recommend treatment with a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist for treatment intensification in type 2 diabetes mellitus (T2DM) patients with progression on metformin.	Metformin	262-271	solute carrier family 5 member 2	Homo sapiens	98-104
32680850-9	2020	Importantly, when the dDBT mutants were administrated with Metformin, the aberrances in BCAA levels and motor behavior were ameliorated.	Metformin	59-68	discs overgrown	Drosophila melanogaster	22-26
32841254-8	2020	Lower OPG/RANKL, increased OCN and TRAP expression were observed in hyperglycemic animals, and treatment with metformin partially reversed hyperglycemia on the OPG/RANKL, OPN and TRAP expression in the periodontitis.	Metformin	110-119	TNF receptor superfamily member 11B	Rattus norvegicus	6-9
32841254-8	2020	Lower OPG/RANKL, increased OCN and TRAP expression were observed in hyperglycemic animals, and treatment with metformin partially reversed hyperglycemia on the OPG/RANKL, OPN and TRAP expression in the periodontitis.	Metformin	110-119	TNF receptor superfamily member 11B	Rattus norvegicus	160-163
32841254-12	2020	Treatment of NH with metformin was able to mediate increased levels of TNF-alpha, IL-10 and IL-17, whereas for H an increase of TNF-alpha and IL-17 was detected in the 24- or 48-hour after stimulation with LPS.	Metformin	21-30	interleukin 10	Rattus norvegicus	82-87
32841254-12	2020	Treatment of NH with metformin was able to mediate increased levels of TNF-alpha, IL-10 and IL-17, whereas for H an increase of TNF-alpha and IL-17 was detected in the 24- or 48-hour after stimulation with LPS.	Metformin	21-30	interleukin 17A	Rattus norvegicus	92-97
32841254-13	2020	Ligature was able to induce increased levels of TNF-alpha and IL-17 in both NH and H. This study revealed the negative impact of hyperglycemia and/or treatment with metformin in the bone repair via inhibition of transcription factors associated with osteoblastic differentiation.	Metformin	165-174	interleukin 17A	Rattus norvegicus	62-67
32598218-18	2020	In patients at increased cardiovascular risk receiving metformin-based background therapy, specific GLP-1 RAs and SGLT-2 inhibitors have a favorable effect on certain cardiovascular outcomes.	Metformin	55-64	solute carrier family 5 member 2	Homo sapiens	114-120
32811807-6	2020	Combination treatment of the CDKs inhibitor abemaciclib with metformin profoundly inhibited tumor viability in vitro and in vivo.	Metformin	61-70	cyclin dependent kinase 1	Homo sapiens	29-33
32811807-9	2020	Collectively, our study suggests that the combination of CDKs inhibitor with metformin could be recognized as a potential therapy in future clinical applications.	Metformin	77-86	cyclin dependent kinase 1	Homo sapiens	57-61
32470453-8	2020	As a plausible mechanism to mediate T-cell function, metformin showed enhanced potential to regulate mechanistic targets of rapamycin (mTOR), STAT5 and adenosine-monophosphate-activated protein kinase (AMPK) signalling pathways.	Metformin	53-62	signal transducer and activator of transcription 5A	Homo sapiens	142-147
32641388-5	2020	The effects of metformin + 2-DG on human T cells were accompanied by significant remodeling of activation-induced metabolic transcriptional programs, in part because of suppression of key transcriptional regulators MYC and HIF-1A.	Metformin	15-24	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	215-218
32641388-6	2020	Accordingly, metformin + 2-DG treatment significantly suppressed MYC-dependent metabolic genes and processes, but this effect was found to be independent of mTORC1 signaling.	Metformin	13-22	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	65-68
32690681-0	2020	Metformin inhibits RAN translation through PKR pathway and mitigates disease in C9orf72 ALS/FTD mice.	Metformin	0-9	RAN, member RAS oncogene family	Mus musculus	19-22
32690681-5	2020	p-PKR is elevated in C9orf72 ALS/FTD human and mouse brains, and inhibiting PKR in C9orf72 BAC transgenic mice using AAV-PKR-K296R or the Food and Drug Administration (FDA)-approved drug metformin, decreases RAN proteins, and improves behavior and pathology.	Metformin	187-196	eukaryotic translation initiation factor 2 alpha kinase 2	Homo sapiens	2-5
32515037-6	2020	However, SRB extract was more effective than metformin to increase the levels of GLUT4 and Nrf2 mRNA.	Metformin	45-54	solute carrier family 2 member 4	Rattus norvegicus	81-86
32792943-8	2020	The presence of metformin also sensitized NSCLC cells to celecoxib-induced apoptosis by activating caspase-9, -8, -3, and -7, upregulating the pro-apoptotic proteins Bad and Bax, and downregulating the antiapoptotic proteins Bcl-xl and Bcl-2.	Metformin	16-25	caspase 9	Homo sapiens	99-124
32631421-2	2020	We previously showed that metformin disrupts the sponge effect of long non-coding RNA MALAT1/miR-142-3p to inhibit cervical cancer cell proliferation.	Metformin	26-35	metastasis associated lung adenocarcinoma transcript 1	Homo sapiens	86-92
32631421-9	2020	RESULTS: Metformin inhibited cervical cancer cell proliferation, cervical cancer xenograft growth, expression of PCNA, p-PI3K and p-Akt.	Metformin	9-18	proliferating cell nuclear antigen	Homo sapiens	113-117
32631421-11	2020	In addition, metformin upregulated the expression of DDR-1 and p53 in human cervical cancer cells.	Metformin	13-22	discoidin domain receptor tyrosine kinase 1	Homo sapiens	53-58
32061625-0	2020	Does Metformin Interfere With the Cardiovascular Benefits of SGLT2 Inhibitors?	Metformin	5-14	solute carrier family 5 member 2	Homo sapiens	61-66
32173428-4	2020	Besides, agar/kappa-carrageenan mixed hydrogels were used as carriers for the delivery of metformin hydrochloride (MET).	Metformin	90-113	SAFB like transcription modulator	Homo sapiens	115-118
32537703-0	2020	Metformin and/or low dose radiation reduces cardiotoxicity and apoptosis induced by cyclophosphamide through SIRT-1/SOD and BAX/Bcl-2 pathways in rats.	Metformin	0-9	BCL2 associated X, apoptosis regulator	Rattus norvegicus	124-127
32606605-0	2020	Metformin Decreases Insulin Resistance in Type 1 Diabetes Through Regulating p53 and RAP2A in vitro and in vivo.	Metformin	0-9	RAP2A, member of RAS oncogene family	Homo sapiens	85-90
32606605-8	2020	Metformin could effectively improve insulin resistance and inflammatory response while down-regulating p53 and up-regulating RAP2A.	Metformin	0-9	RAP2A, member of RAS oncogene family	Homo sapiens	125-130
32606605-10	2020	Conclusion: Metformin improves T1D insulin resistance and inflammatory response through p53/RAP2A pathway, and the regulation of p53/RAP2A pathway is conducive to improving the efficacy of metformin in the treatment of insulin resistance.	Metformin	12-21	RAP2A, member of RAS oncogene family	Homo sapiens	92-97
32606605-10	2020	Conclusion: Metformin improves T1D insulin resistance and inflammatory response through p53/RAP2A pathway, and the regulation of p53/RAP2A pathway is conducive to improving the efficacy of metformin in the treatment of insulin resistance.	Metformin	189-198	RAP2A, member of RAS oncogene family	Homo sapiens	133-138
32626781-11	2020	Finally, the levels of IL-1beta, TNF-alpha, Bax, and caspase-3 were also decreased in both treated groups (metformin and green coffee) when compared to the diabetic group.	Metformin	107-116	BCL2 associated X, apoptosis regulator	Rattus norvegicus	44-47
32572457-10	2020	Metformin treatment led to an upregulation of clock regulatory genes such as melanopsin (Opn4) and aralkylamine N-acetyltransferase (Aanat).	Metformin	0-9	arylalkylamine N-acetyltransferase	Mus musculus	99-131
32572457-10	2020	Metformin treatment led to an upregulation of clock regulatory genes such as melanopsin (Opn4) and aralkylamine N-acetyltransferase (Aanat).	Metformin	0-9	arylalkylamine N-acetyltransferase	Mus musculus	133-138
32572457-11	2020	In rMC-1 cells, AMPK activation via AICAR and metformin resulted in increased Kir4.1 and intermediate core clock component Bmal-1 protein expression.	Metformin	46-55	potassium inwardly-rectifying channel, subfamily J, member 10	Rattus norvegicus	78-84
31840936-12	2020	Metformin or AICAR presence decreased spontaneous production of IL-6, IL-8 and MCP-1 in RA synovial explants and SFCs (n=5-7).	Metformin	0-9	C-C motif chemokine ligand 2	Homo sapiens	79-84
32270948-9	2020	In addition, metformin significantly attenuated IL-6, IL-1beta, and TNF-alpha production and increased the expression of active caspase-3 and Bax in the liver (p<0.05).	Metformin	13-22	BCL2 associated X, apoptosis regulator	Rattus norvegicus	142-145
31883148-8	2020	Furthermore, transport of cationic drugs, metformin and paclitaxel in HepG2 cells was blunted by OCT inhibitors, suggesting that hOCT1 and hOCT3 expressed in HepG2 cells exhibit notable impacts on cationic drug actions.	Metformin	42-51	plexin A2	Homo sapiens	97-100
32492904-5	2020	In fully symptomatic RTT mice (12 months old MeCP2-308 heterozygous female mice), systemic treatment with metformin (100 mg/kg ip for 10 days) normalized the reduced mitochondrial ATP production and ATP levels in the whole-brain, reduced brain oxidative damage, and rescued the increased production of reactive oxidizing species in blood.	Metformin	106-115	methyl CpG binding protein 2	Mus musculus	45-50
32399705-0	2020	Histomorphological, VEGF and TGF-beta immunoexpression changes in the diabetic rats" ovary and the potential amelioration following treatment with metformin and insulin.	Metformin	147-156	vascular endothelial growth factor A	Rattus norvegicus	20-24
32050809-4	2020	Among the metformin users, we assessed the titration in its dose or treatment during the 12 month period after initiation at 3 month intervals.Results: Among 20,401 new antidiabetic users, the most frequently used agents during the study period were dipeptidyl peptidase-4 inhibitors (DPP4is; 47.4%), followed by biguanides (18.5%) and sodium glucose cotransporter-2 inhibitors (SGLT2is; 6.7%).	Metformin	10-19	dipeptidyl peptidase 4	Homo sapiens	250-272
32050809-6	2020	Moreover, 27% remained on the same daily dose during the 1 year follow-up, whereas another 29.9% discontinued their antidiabetic treatment altogether.Conclusions: A unique pattern of prescription was observed amongst Japanese patients with T2DM, and DPP4is, rather than metformin, were predominantly used as the first-line treatment.	Metformin	270-279	dipeptidyl peptidase 4	Homo sapiens	250-254
32331584-1	2020	The renal hemodynamic effects of the SGLT2 inhibitor dapagliflozin are caused by post-glomerular vasodilatation rather than pre-glomerular vasoconstriction in metformin-treated patients with type 2 diabetes in the randomized, double-blind RED trial."	Metformin	159-168	solute carrier family 5 member 2	Homo sapiens	37-42
32203160-0	2020	NCOA5 deficiency promotes a unique liver protumorigenic microenvironment through p21WAF1/CIP1 overexpression, which is reversed by metformin.	Metformin	131-140	nuclear receptor coactivator 5	Mus musculus	0-5
32203160-3	2020	Importantly, prophylactic metformin treatment reversed these characteristics including aberrant p21WAF1/CIP1 expression and subsequently reduced HCC incidence in Ncoa5+/- male mice.	Metformin	26-35	nuclear receptor coactivator 5	Mus musculus	162-167
32368014-0	2020	Metformin Inhibits Propofol-Induced Apoptosis of Mouse Hippocampal Neurons HT-22 Through Downregulating Cav-1.	Metformin	0-9	caveolin 1, caveolae protein	Mus musculus	104-109
32368014-8	2020	In addition, Cav-1 level in HT-22 cells was regulated by metformin treatment.	Metformin	57-66	caveolin 1, caveolae protein	Mus musculus	13-18
32368014-9	2020	Notably, metformin reversed propofol-induced apoptosis stimulation and proliferation decline in HT-22 cells via downregulating Cav-1.	Metformin	9-18	caveolin 1, caveolae protein	Mus musculus	127-132
32368014-11	2020	Then, we found that metformin protects propofol-induced neuronal apoptosis via downregulating Cav-1.	Metformin	20-29	caveolin 1, caveolae protein	Mus musculus	94-99
32377293-0	2020	Metformin Ameliorates Abeta Pathology by Insulin-Degrading Enzyme in a Transgenic Mouse Model of Alzheimer"s Disease.	Metformin	0-9	amyloid beta (A4) precursor protein	Mus musculus	22-27
32377293-5	2020	In this study, we tried to figure out whether metformin could activate insulin-degrading enzyme (IDE) to ameliorate Abeta-induced pathology.	Metformin	46-55	amyloid beta (A4) precursor protein	Mus musculus	116-121
32377293-6	2020	Morris water maze and Y-maze results indicated that metformin could improve the learning and memory ability in APPswe/PS1dE9 (APP/PS1) transgenic mice.	Metformin	52-61	presenilin 1	Mus musculus	118-121
32377293-7	2020	18F-FDG PET-CT result showed that metformin could ameliorate the neural dysfunction in APP/PS1 transgenic mice.	Metformin	34-43	presenilin 1	Mus musculus	91-94
32377293-8	2020	PCR analysis showed that metformin could effectively improve the mRNA expression level of nerve and synapse-related genes (Syp, Ngf, and Bdnf) in the brain.	Metformin	25-34	brain derived neurotrophic factor	Mus musculus	137-141
32377293-9	2020	Metformin decreased oxidative stress (malondialdehyde and superoxide dismutase) and neuroinflammation (IL-1beta and IL-6) in APP/PS1 mice.	Metformin	0-9	interleukin 1 alpha	Mus musculus	103-111
32377293-9	2020	Metformin decreased oxidative stress (malondialdehyde and superoxide dismutase) and neuroinflammation (IL-1beta and IL-6) in APP/PS1 mice.	Metformin	0-9	presenilin 1	Mus musculus	129-132
32377293-10	2020	In addition, metformin obviously reduced the Abeta level in the brain of APP/PS1 mice.	Metformin	13-22	amyloid beta (A4) precursor protein	Mus musculus	45-50
32377293-10	2020	In addition, metformin obviously reduced the Abeta level in the brain of APP/PS1 mice.	Metformin	13-22	presenilin 1	Mus musculus	77-80
32377293-13	2020	Metformin increased the protein levels of p-AMPK and IDE in the brain of APP/PS1 mice, which might be the key mechanism of metformin on AD.	Metformin	0-9	presenilin 1	Mus musculus	77-80
32377293-13	2020	Metformin increased the protein levels of p-AMPK and IDE in the brain of APP/PS1 mice, which might be the key mechanism of metformin on AD.	Metformin	123-132	presenilin 1	Mus musculus	77-80
31999406-9	2020	Pre-operative/post-operative AMH decreases were statistically significant in negative direction in the detorsion only group when compared to the metformin+detorsion and control groups (p=0.001).	Metformin	145-154	anti-Mullerian hormone	Rattus norvegicus	29-32
32014718-17	2020	The short-term treatment using low-dose aspirin combined with metformin may provide therapeutic benefits in preventing complications associated with dysregulated Th2 cell responses.	Metformin	62-71	heart and neural crest derivatives expressed 2	Mus musculus	162-165
31789451-0	2020	Persistent whole day meal effects of three dipeptidyl peptidase-4 inhibitors on glycemia and hormonal responses in metformin-treated type 2 diabetes.	Metformin	115-124	dipeptidyl peptidase 4	Homo sapiens	43-65
32235654-1	2020	Metformin is a substrate for plasma membrane monoamine transporters (PMAT) and organic cation transporters (OCTs); therefore, the expression of these transporters and interactions between them may affect the uptake of metformin into tumor cells and its anticancer efficacy.	Metformin	0-9	solute carrier family 29 member 4	Homo sapiens	29-67
32235654-1	2020	Metformin is a substrate for plasma membrane monoamine transporters (PMAT) and organic cation transporters (OCTs); therefore, the expression of these transporters and interactions between them may affect the uptake of metformin into tumor cells and its anticancer efficacy.	Metformin	0-9	solute carrier family 29 member 4	Homo sapiens	69-73
32235654-1	2020	Metformin is a substrate for plasma membrane monoamine transporters (PMAT) and organic cation transporters (OCTs); therefore, the expression of these transporters and interactions between them may affect the uptake of metformin into tumor cells and its anticancer efficacy.	Metformin	218-227	solute carrier family 29 member 4	Homo sapiens	29-67
32235654-1	2020	Metformin is a substrate for plasma membrane monoamine transporters (PMAT) and organic cation transporters (OCTs); therefore, the expression of these transporters and interactions between them may affect the uptake of metformin into tumor cells and its anticancer efficacy.	Metformin	218-227	solute carrier family 29 member 4	Homo sapiens	69-73
32194991-3	2020	Although metformin reportedly inhibits mature IL-1beta secretion via NLRP3 inflammasome in macrophages of T2DM patients, it remains unclear whether it affects skin inflammation in psoriasis.	Metformin	9-18	interleukin 1 alpha	Homo sapiens	46-54
32194991-5	2020	This stimulation induced the upregulation of pro-IL-1beta mRNA and protein levels, and subsequently mature IL-1beta secretion, which was inhibited by metformin treatment.	Metformin	150-159	interleukin 1 alpha	Homo sapiens	49-57
32194991-10	2020	Metformin treatment inhibited upregulation of IL-36gamma, CXCL1, CXCL2, CCL20, S100A7, S100A8 and S100A9 mRNA and protein levels induced by TNF-alpha and IL-17A stimulation.	Metformin	0-9	C-X-C motif chemokine ligand 2	Homo sapiens	65-70
32194991-13	2020	A cytokine profile in the epidermis under metformin treatment showed that IL-1beta, Cxcl1, Cxcl2, S100a7, S100a8 and S100A9 mRNA levels were downregulated compared with control levels.	Metformin	42-51	interleukin 1 alpha	Mus musculus	74-82
32194991-13	2020	A cytokine profile in the epidermis under metformin treatment showed that IL-1beta, Cxcl1, Cxcl2, S100a7, S100a8 and S100A9 mRNA levels were downregulated compared with control levels.	Metformin	42-51	C-X-C motif chemokine ligand 2	Homo sapiens	91-96
31864213-2	2020	Our previous results showed that metformin can destroy the sponge effect of long-chain non-coding RNA MALAT1/miR-142-3p and inhibit the proliferation of cervical cancer cells.	Metformin	33-42	metastasis associated lung adenocarcinoma transcript 1	Homo sapiens	102-108
32031335-0	2020	Metformin alleviates breast cancer through targeting high-mobility group AT-hook 2.	Metformin	0-9	high mobility group AT-hook 2	Homo sapiens	53-82
32031335-4	2020	Western blotting and RT-PCR assays were used to detect the regulation of metformin on the expression of oncogenic HMGA2.	Metformin	73-82	high mobility group AT-hook 2	Homo sapiens	114-119
32031335-6	2020	A luciferase reporter gene assay was performed to analyze the effect of metformin on HMGA2 promoter activity in breast cancer cells.	Metformin	72-81	high mobility group AT-hook 2	Homo sapiens	85-90
32031335-8	2020	The function of metformin-regulated HMGA2 in breast cancer growth was tested using a cell viability assay.	Metformin	16-25	high mobility group AT-hook 2	Homo sapiens	36-41
32031335-10	2020	The level of mRNA and protein of HMGA2 was significantly reduced by metformin in the cells.	Metformin	68-77	high mobility group AT-hook 2	Homo sapiens	33-38
32031335-11	2020	Mechanistically, metformin was able to inactivate the HMGA2 promoter through downregulating transcription factor Sp1 in the cells.	Metformin	17-26	high mobility group AT-hook 2	Homo sapiens	54-59
32031335-12	2020	In terms of function, treatment with metformin suppressed the proliferation of breast cancer cells and overexpressed HMGA2 reversed the inhibition of cell proliferation mediated by metformin.	Metformin	37-46	high mobility group AT-hook 2	Homo sapiens	117-122
32031335-12	2020	In terms of function, treatment with metformin suppressed the proliferation of breast cancer cells and overexpressed HMGA2 reversed the inhibition of cell proliferation mediated by metformin.	Metformin	181-190	high mobility group AT-hook 2	Homo sapiens	117-122
32031335-13	2020	CONCLUSION: Metformin resists the growth of breast cancer through targeting Sp1/HMGA2 signal.	Metformin	12-21	high mobility group AT-hook 2	Homo sapiens	80-85
31926250-6	2020	KEY FINDINGS: We found that metformin could synergistically sensitize AML cells to Ara-C via inhibiting mTORC1/P70S6K pathway.	Metformin	28-37	ribosomal protein S6 kinase B1	Homo sapiens	111-117
31926250-8	2020	SIGNIFICANCE: We firstly found the synergistic anti-tumor effect of Ara-C/metformin in AML through inhibiting mTORC1/P70S6K pathway.	Metformin	74-83	ribosomal protein S6 kinase B1	Homo sapiens	117-123
32051301-2	2020	Sulfonylureas (SU) and the combination of SU and metformin (SU+MET) were the most common monotherapy and combination therapies used in Thailand tertiary care hospitals.	Metformin	49-58	SAFB like transcription modulator	Homo sapiens	63-66
32104542-4	2020	We found that metformin reduced the expression of senescence-associated gene P21 in high-glucose-induced (30 mmol/L) renal tubular epithelial cells and decreased the beta-galactosidase positive staining rate (decreased 16%, p < 0.01).	Metformin	14-23	galactosidase, beta 1	Mus musculus	166-184
31963541-0	2020	Metformin Mitigates Nickel-Elicited Angiopoietin-Like Protein 4 Expression via HIF-1alpha for Lung Tumorigenesis.	Metformin	0-9	angiopoietin like 4	Homo sapiens	36-63
31963541-3	2020	In this study, we assessed the role of ANGPTL4 in lung carcinogenesis under nickel exposure and investigated the effects of the antidiabetic drug metformin on ANGPTL4 expression and lung cancer chemoprevention.	Metformin	146-155	angiopoietin like 4	Homo sapiens	159-166
31963541-5	2020	The expression of ANGPTL4 and HIF-1alpha induced by NiCl2 were significantly repressed after metformin treatment.	Metformin	93-102	angiopoietin like 4	Homo sapiens	18-25
31963541-7	2020	Chromatin immunoprecipitation and the luciferase assay revealed that NiCl2-induced HIF-1alpha hypoxia response element interactions activate ANGPTL4 expression, which is then inhibited by metformin.	Metformin	188-197	angiopoietin like 4	Homo sapiens	141-148
31963541-9	2020	Additionally, metformin has the ability to prevent NiCl2-induced ANGPTL4 through inhibiting HIF-1alpha expression and its binding activity.	Metformin	14-23	angiopoietin like 4	Homo sapiens	65-72
31936169-0	2020	Metformin Inhibits Tumor Metastasis through Suppressing Hsp90alpha Secretion in an AMPKalpha1-PKCgamma Dependent Manner.	Metformin	0-9	heat shock protein 90 alpha family class A member 1	Homo sapiens	56-66
31936169-0	2020	Metformin Inhibits Tumor Metastasis through Suppressing Hsp90alpha Secretion in an AMPKalpha1-PKCgamma Dependent Manner.	Metformin	0-9	protein kinase C gamma	Homo sapiens	94-102
31936169-4	2020	Here we show that metformin inhibits tumor metastasis by suppressing Hsp90alpha (heat shock protein 90alpha) secretion.	Metformin	18-27	heat shock protein 90 alpha family class A member 1	Homo sapiens	69-79
31936169-5	2020	Mass spectrometry (MS) analysis and functional validation identify that eHsp90alpha (extracellular Hsp90alpha) is one of the most important secreted proteins for metformin to inhibit tumor cells migration, invasion and metastasis both in vitro and in vivo.	Metformin	162-171	heat shock protein 90 alpha family class A member 1	Homo sapiens	73-83
31936169-6	2020	Moreover, we find that metformin inhibits Hsp90alpha secretion in an AMPKalpha1 dependent manner.	Metformin	23-32	heat shock protein 90 alpha family class A member 1	Homo sapiens	42-52
31936169-8	2020	Collectively, our results illuminate that metformin inhibits tumor metastasis by suppressing Hsp90alpha secretion in an AMPKalpha1 dependent manner.	Metformin	42-51	heat shock protein 90 alpha family class A member 1	Homo sapiens	93-103
31936070-0	2020	Extended Intake of Mulberry Leaf Extract Delayed Metformin Elimination via Inhibiting the Organic Cation Transporter 2.	Metformin	49-58	solute carrier family 22 member 2	Rattus norvegicus	90-118
31936070-12	2020	Thus, these findings suggest that MLE lowered the elimination of Met via inhibiting the hOCT2.	Metformin	65-68	solute carrier family 22 member 2	Homo sapiens	88-93
31906986-0	2020	Metformin-repressed miR-381-YAP-snail axis activity disrupts NSCLC growth and metastasis.	Metformin	0-9	microRNA 381	Homo sapiens	20-27
31906986-2	2020	Metformin regulates miR-381 stability, which plays a vital role in tumor progression.	Metformin	0-9	microRNA 381	Homo sapiens	20-27
31906986-4	2020	However, the molecular mechanism underpinning how metformin-induced upregulation of miR-381 directly targets YAP or its interactions with the epithelial-mesenchymal transition (EMT) marker protein Snail in NSCLC is still unknown.	Metformin	50-59	microRNA 381	Homo sapiens	84-91
31906986-13	2020	In addition, metformin decreased cell growth, migration, invasion, and EMT via up-regulation of miR-381.	Metformin	13-22	microRNA 381	Homo sapiens	96-103
31906986-16	2020	Furthermore, miR-381, YAP, and Snail constitute the miR-381-YAP-Snail signal axis, which is repressed by metformin, and enhances cancer cell invasiveness by directly regulating EMT.	Metformin	105-114	microRNA 381	Homo sapiens	13-20
31906986-16	2020	Furthermore, miR-381, YAP, and Snail constitute the miR-381-YAP-Snail signal axis, which is repressed by metformin, and enhances cancer cell invasiveness by directly regulating EMT.	Metformin	105-114	microRNA 381	Homo sapiens	52-59
31906986-17	2020	CONCLUSIONS: Metformin-induced repression of miR-381-YAP-Snail axis activity disrupts NSCLC growth and metastasis.	Metformin	13-22	microRNA 381	Homo sapiens	45-52
32324524-5	2020	OBJECTIVE: It is aimed to synthesize Metformin (MET) loaded Solid Lipid Nanoparticles (MET-SLN) and radiolabeled with technetium-99m tricarbonyl core.	Metformin	37-46	sarcolipin	Homo sapiens	91-94
32324524-8	2020	Quality control studies of radiolabeled MET-SLN [ 99mTc(CO)3-MET-SLN] were performed by High-Performance Liquid Radiochromatography (HPLRC) and Thin Layer Radiochromatography(TLRC).	Metformin	40-43	sarcolipin	Homo sapiens	44-47
32324524-8	2020	Quality control studies of radiolabeled MET-SLN [ 99mTc(CO)3-MET-SLN] were performed by High-Performance Liquid Radiochromatography (HPLRC) and Thin Layer Radiochromatography(TLRC).	Metformin	40-43	sarcolipin	Homo sapiens	65-68
31902918-4	2020	In the present study, we found that metformin reduced the production of nitric oxide (NO) and the level of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.	Metformin	36-45	interleukin 1 alpha	Mus musculus	176-198
30663560-4	2020	Regarding antidiabetic medication, metformin, gliclazide, pioglitazone, exenatide and dapagliflozin exert a beneficial effect on Endothelial Function (EF); glimepiride and glibenclamide, dipeptidyl peptidase-4 inhibitors and liraglutide have a neutral effect, while studies examining the effect of insulin analogues, empagliflozin and canagliflozin on EF are limited.	Metformin	35-44	dipeptidyl peptidase 4	Homo sapiens	187-209
31407866-5	2020	The observed improvements in CV and renal outcomes with SGLT-2is in CVOTs suggest a class effect in this patient population and have influenced treatment guidelines for the way add-on therapy to metformin is initiated in patients with T2D and high CV risk.	Metformin	195-204	solute carrier family 5 member 2	Homo sapiens	56-62
31778746-7	2020	In the future early combination therapy of metformin e.g. with SGLT-2 inhibitors should be more often used.	Metformin	43-52	solute carrier family 5 member 2	Homo sapiens	63-69
34005114-9	2020	Importantly, when the dDBT mutants were administrated with Metformin, the aberrances in BCAA levels and motor behavior were ameliorated.	Metformin	59-68	discs overgrown	Drosophila melanogaster	22-26
31892847-5	2020	Further research indicated the induction of apoptosis and autophagy triggered by metformin could remarkably attenuate after the treatment of ROS scavenger NAC and JNK inhibitor SP600125.	Metformin	81-90	synuclein alpha	Homo sapiens	155-158
31892847-6	2020	Additionally, our results showed that NAC-suppressed JNK/c-Jun signaling pathway could have been activated through metformin treatment.	Metformin	115-124	synuclein alpha	Homo sapiens	38-41
31521867-0	2020	Metformin ameliorates stress-induced depression-like behaviors via enhancing the expression of BDNF by activating AMPK/CREB-mediated histone acetylation.	Metformin	0-9	brain derived neurotrophic factor	Mus musculus	95-99
31521867-6	2020	Further RNA sequencing analysis revealed that metformin treatment prevented the transcriptional changes in the medial prefrontal cortex (mPFC) of the animals and Golgi staining indicated favorable morphological changes in the neurite plasticity of CA1 pyramidal neurons, which approximated to those found in unstressed mice.	Metformin	46-55	carbonic anhydrase 1	Mus musculus	248-251
31521867-7	2020	At a molecular level, metformin significantly upregulated the expression of the brain-derived neurotrophic factor (BDNF) by increasing the histone acetylation along with the BDNF promoter, which was attributed to the activation of AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB).	Metformin	22-31	brain derived neurotrophic factor	Mus musculus	80-113
31521867-7	2020	At a molecular level, metformin significantly upregulated the expression of the brain-derived neurotrophic factor (BDNF) by increasing the histone acetylation along with the BDNF promoter, which was attributed to the activation of AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB).	Metformin	22-31	brain derived neurotrophic factor	Mus musculus	115-119
31521867-7	2020	At a molecular level, metformin significantly upregulated the expression of the brain-derived neurotrophic factor (BDNF) by increasing the histone acetylation along with the BDNF promoter, which was attributed to the activation of AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB).	Metformin	22-31	brain derived neurotrophic factor	Mus musculus	174-178
32538851-8	2020	DNLA and metformin treatments decreased amyloid-beta1-42, AbetaPP, PS1, and BACE1, while increasing IDE and neprilysin for Abeta clearance.	Metformin	9-18	presenilin 1	Mus musculus	67-70
32538851-8	2020	DNLA and metformin treatments decreased amyloid-beta1-42, AbetaPP, PS1, and BACE1, while increasing IDE and neprilysin for Abeta clearance.	Metformin	9-18	beta-site APP cleaving enzyme 1	Mus musculus	76-81
32538851-8	2020	DNLA and metformin treatments decreased amyloid-beta1-42, AbetaPP, PS1, and BACE1, while increasing IDE and neprilysin for Abeta clearance.	Metformin	9-18	amyloid beta (A4) precursor protein	Mus musculus	58-63
32538851-9	2020	Furthermore, DNLA and metformin enhanced autophagy activity by increasing LC3-II, Beclin1, and Klotho, and by decreasing p62 in the hippocampus and cortex.	Metformin	22-31	beclin 1, autophagy related	Mus musculus	82-89
33184242-0	2020	High-glucose-induced apoptosis, ROS production and pro-inflammatory response in cardiomyocytes is attenuated by metformin treatment via PP2A activation.	Metformin	112-121	protein phosphatase 2 phosphatase activator	Homo sapiens	136-140
33184242-2	2020	In the present research we investigated whether metformin would reduce cardiomyocyte apoptosis that was induced by high-glucose stimulation in vitro via activation of PP2A.	Metformin	48-57	protein phosphatase 2 phosphatase activator	Homo sapiens	167-171
33184242-15	2020	In conclusion, metformin reduced apoptosis, ROS production and inflammatory response in primary human and rat cardiomyocytes in vitro in a PP2A dependent manner.	Metformin	15-24	protein phosphatase 2 phosphatase activator	Homo sapiens	139-143
31753516-11	2020	More importantly, metformin inhibited LPS-enhanced CCL-2 synthesis through modulation of the iNOS/NO pathway.	Metformin	18-27	C-C motif chemokine ligand 2	Homo sapiens	51-56
32423242-7	2020	Also, a significant (P < .05) reduction in fasting blood glucose, lipid peroxidation, glucose-6-phosphatase, and all anti-inflammatory parameters were observed in diabetic rats administered the extracts and metformin.	Metformin	207-216	glucose-6-phosphatase catalytic subunit 1	Rattus norvegicus	86-107
30820523-2	2020	In mice, when metformin treatment (Met) is added to the mTOR inhibitor rapamycin (Rap), median and maximal life span is extended to a greater degree than with Rap or Met alone.	Metformin	14-23	mechanistic target of rapamycin kinase	Mus musculus	56-60
31791665-0	2020	The renal hemodynamic effects of the SGLT2 inhibitor dapagliflozin are caused by post-glomerular vasodilatation rather than pre-glomerular vasoconstriction in metformin-treated patients with type 2 diabetes in the randomized, double-blind RED trial.	Metformin	159-168	solute carrier family 5 member 2	Homo sapiens	37-42
32224233-5	2020	In diabetic patients, oral antidiabetic drugs (glyburide, metformin or pioglitazone) reduced circulating levels fractalkine and E-selectin (both P < .05), without affecting vascular responses (all P > .05).	Metformin	58-67	selectin E	Homo sapiens	128-138
31626790-11	2019	SIGNIFICANCE: Taken together these data indicate that HIF-1alpha/PFKFB3/PFK1 regulatory axis is a vital determinant of glucose metabolic reprogramming in hepatocellular carcinoma, which gives new insights into the action of metformin in combatting liver cancer.	Metformin	224-233	phosphofructokinase, muscle	Homo sapiens	72-76
31832799-3	2019	This study presents the development and production, by twin-screw melt granulation technology, of a high-dose immediate-release fixed-dose combination (FDC) product of metformin hydrochloride (MET) and sitagliptin phosphate (SIT), with drug loads of 80% w/w and 6% w/w, respectively.	Metformin	168-191	SAFB like transcription modulator	Homo sapiens	193-196
31550733-2	2019	The aim of the work was to study the possibilities of enhancing the therapeutic effect of anti-estrogen drug toremifene by combining it with biguanide, metformin, on the HER2-positive breast cancer model in FVB/N HER-2/neu transgenic mouse.	Metformin	152-161	erb-b2 receptor tyrosine kinase 2	Mus musculus	170-174
31657647-6	2019	Together our data indicate that IPMK participates in the regulation of cell migration and provides a potential link between metformin and wound healing impairment.-Tu-Sekine, B., Padhi, A., Jin, S., Kalyan, S., Singh, K., Apperson, M., Kapania, R., Hur, S. C., Nain, A., Kim, S. F. Inositol polyphosphate multikinase is a metformin target that regulates cell migration.	Metformin	322-331	inositol polyphosphate multikinase	Mus musculus	32-36
31645006-8	2019	Metformin treatment induced AMPK-dependent alleviation of dyslipidemia in a dose and time dependent manner, upregulated p53 (Ser-15), restored tissue architecture and reduced oxidative stress in tissues of AEBN and arecoline treated mice.	Metformin	0-9	transformation related protein 53, pseudogene	Mus musculus	120-123
31806203-3	2019	This meta-analysis was conducted to quantitatively pool the incremental net benefit of SGLT2 inhibitors in T2DM patients who failed metformin monotherapy.	Metformin	132-141	solute carrier family 5 member 2	Homo sapiens	87-92
31788033-10	2019	In the pathways, CPT1a in WAT, CPT1b and CPT2 in BAT were down-regulated by metformin significantly.	Metformin	76-85	carnitine palmitoyltransferase 1a, liver	Mus musculus	17-22
31788033-10	2019	In the pathways, CPT1a in WAT, CPT1b and CPT2 in BAT were down-regulated by metformin significantly.	Metformin	76-85	carnitine palmitoyltransferase 1b, muscle	Mus musculus	31-36
31788033-13	2019	CPT1 might be a potential target of metformin in WAT and BAT.	Metformin	36-45	carnitine palmitoyltransferase 1b, muscle	Mus musculus	0-4
31582211-0	2019	Treatment with metformin prevents pre-eclampsia by suppressing migration of trophoblast cells via modulating the signaling pathway of UCA1/miR-204/MMP-9.	Metformin	15-24	microRNA 204	Homo sapiens	139-146
31886264-7	2019	Metformin phosphorylates extracellular signal-regulated kinase (ERK), stimulates endothelial and inducible nitric oxide synthases (e/iNOS), inhibits the GSK3beta/Wnt/beta-catenin pathway, and promotes osteogenic differentiation of osteoblasts.	Metformin	0-9	catenin beta 1	Homo sapiens	166-178
31814900-0	2019	Metformin attenuates PD-L1 expression through activating Hippo signaling pathway in colorectal cancer cells.	Metformin	0-9	CD274 molecule	Homo sapiens	21-26
31814900-5	2019	Here, we showed that metformin decreases PD-L1 and YAP1 expression in vitro and in vivo.	Metformin	21-30	CD274 molecule	Homo sapiens	41-46
31814900-7	2019	Furthermore, metformin directly phosphorylated YAP1 and restricted YAP1 to entry in the nucleus, so that PD-L1 was reduced via western blot and immunofluorescence assays in SW480 and HCT116 cells.	Metformin	13-22	CD274 molecule	Homo sapiens	105-110
31814900-9	2019	Compared with the control group, PD-L1 and YAP1 expressions in tumor tissues, detected by immunohistochemistry, were reduced in the group of metformin treatment.	Metformin	141-150	CD274 molecule	Homo sapiens	33-38
31814900-10	2019	These findings illuminate a new regulatory mechanism, metformin activates Hippo signaling pathway to regulate PD-L1 expression and suggests that metformin has the possibility to increase the efficacy of immunotherapy in human CRC.	Metformin	54-63	CD274 molecule	Homo sapiens	110-115
31814900-10	2019	These findings illuminate a new regulatory mechanism, metformin activates Hippo signaling pathway to regulate PD-L1 expression and suggests that metformin has the possibility to increase the efficacy of immunotherapy in human CRC.	Metformin	145-154	CD274 molecule	Homo sapiens	110-115
31563650-9	2019	Meanwhile in rats with NAFLD: i) metformin inhibited hepatic total cholesterol and TGF-beta, increased diarrhea frequency, and slightly decreased liver steatosis, and fibrosis; ii) 4-hydroxychalcone decreased IL-6, TNF-alpha and TGF-beta, increased IL-10, and markedly decreased liver steatosis and fibrosis; and iii) co-treatment markedly decreased food intake, total caloric intake, and body weight, increased diarrhea; increased IL-10, showing and intermediate effect on decrease TNF-alpha, TGF-beta, liver steatosis and fibrosis.	Metformin	33-42	interleukin 10	Rattus norvegicus	249-254
31563650-9	2019	Meanwhile in rats with NAFLD: i) metformin inhibited hepatic total cholesterol and TGF-beta, increased diarrhea frequency, and slightly decreased liver steatosis, and fibrosis; ii) 4-hydroxychalcone decreased IL-6, TNF-alpha and TGF-beta, increased IL-10, and markedly decreased liver steatosis and fibrosis; and iii) co-treatment markedly decreased food intake, total caloric intake, and body weight, increased diarrhea; increased IL-10, showing and intermediate effect on decrease TNF-alpha, TGF-beta, liver steatosis and fibrosis.	Metformin	33-42	interleukin 10	Rattus norvegicus	432-437
31070566-0	2019	Effects of TCF7L2 rs7903146 variant on metformin response in patients with type 2 diabetes.	Metformin	39-48	transcription factor 7 like 2	Homo sapiens	11-17
31070566-3	2019	In this study, we explored the effects of the TCF7L2 rs7903146 genotype on metformin response in T2D.	Metformin	75-84	transcription factor 7 like 2	Homo sapiens	46-52
31070566-11	2019	Our results suggest that the TCF7L2 rs7903146 variant affects markers of insulin resistance and glycemic response to metformin in newly diagnosed patients with T2D within the first year of metformin treatment.	Metformin	117-126	transcription factor 7 like 2	Homo sapiens	29-35
31070566-11	2019	Our results suggest that the TCF7L2 rs7903146 variant affects markers of insulin resistance and glycemic response to metformin in newly diagnosed patients with T2D within the first year of metformin treatment.	Metformin	189-198	transcription factor 7 like 2	Homo sapiens	29-35
31686542-0	2022	Metformin reduces lipid accumulation in HepG2 cells via downregulation of miR-33b.	Metformin	0-9	microRNA 33b	Homo sapiens	74-81
31686542-1	2022	Introduction: Here, we aimed to investigate whether the beneficial effects of metformin on lipid accumulation is mediated through regulation of miR-33b.Methods: The expression of the genes and miRNAs and protein levels were evaluated using real-time PCR and western blot, respectively.	Metformin	78-87	microRNA 33b	Homo sapiens	144-151
31686542-2	2022	To investigate the potential role of miR-33b in lipid accumulation, the mimic of the miR-33b was transfected into HepG2 cells.Results: We found that metformin reduces high glucose-induced lipid accumulation in HepG2 cells through inhibiting of SREBP1c and FAS and increasing the expression of CPT1 and CROT.	Metformin	149-158	microRNA 33b	Homo sapiens	37-44
31686542-2	2022	To investigate the potential role of miR-33b in lipid accumulation, the mimic of the miR-33b was transfected into HepG2 cells.Results: We found that metformin reduces high glucose-induced lipid accumulation in HepG2 cells through inhibiting of SREBP1c and FAS and increasing the expression of CPT1 and CROT.	Metformin	149-158	microRNA 33b	Homo sapiens	85-92
31686542-2	2022	To investigate the potential role of miR-33b in lipid accumulation, the mimic of the miR-33b was transfected into HepG2 cells.Results: We found that metformin reduces high glucose-induced lipid accumulation in HepG2 cells through inhibiting of SREBP1c and FAS and increasing the expression of CPT1 and CROT.	Metformin	149-158	sterol regulatory element binding transcription factor 1	Homo sapiens	244-251
31686542-3	2022	Overexpression of miR-33b significantly prevented the decreasing effect of metformin on lipid content and intra and extra triglyceride levels.	Metformin	75-84	microRNA 33b	Homo sapiens	18-25
31686542-4	2022	Importantly, miR-33b mimic inhibited the increasing effects of metformin on the expression of CPT1 and CROT.Conclusion: These findings suggest that metformin attenuates high glucose-induced lipid accumulation in HepG2 cell by downregulating the expression of miR-33b.	Metformin	63-72	microRNA 33b	Homo sapiens	13-20
31518877-0	2019	Metformin inhibited Nod-like receptor protein 3 inflammasomes activation and suppressed diabetes-accelerated atherosclerosis in apoE-/- mice.	Metformin	0-9	NLR family, pyrin domain containing 3	Mus musculus	20-47
31518877-1	2019	AIMS: The present study aimed to investigate the effect of metformin on diabetes-accelerated atherosclerosis and whether Nod-like receptor protein 3 (NLRP3) inflammasome is a target for metformin.	Metformin	186-195	NLR family, pyrin domain containing 3	Mus musculus	121-148
31518877-1	2019	AIMS: The present study aimed to investigate the effect of metformin on diabetes-accelerated atherosclerosis and whether Nod-like receptor protein 3 (NLRP3) inflammasome is a target for metformin.	Metformin	186-195	NLR family, pyrin domain containing 3	Mus musculus	150-155
31518877-7	2019	In vitro experiments showed that high glucose induced the accumulation of reactive oxygen species and activated NLRP3 inflammasomes, which was significantly suppressed by treatment with metformin or antioxidant N-acetyl-L-cysteine.	Metformin	186-195	NLR family, pyrin domain containing 3	Mus musculus	112-117
31518877-8	2019	Moreover, Compound C, an inhibitor of adenosine 5"-monophosphate-activated protein kinase (AMPK), blocked the anti-inflammatory effect of metformin, indicating that metformin inhibited high glucose-induced NLRP3 inflammasomes activation through AMPK activation.	Metformin	138-147	NLR family, pyrin domain containing 3	Mus musculus	206-211
31518877-8	2019	Moreover, Compound C, an inhibitor of adenosine 5"-monophosphate-activated protein kinase (AMPK), blocked the anti-inflammatory effect of metformin, indicating that metformin inhibited high glucose-induced NLRP3 inflammasomes activation through AMPK activation.	Metformin	165-174	NLR family, pyrin domain containing 3	Mus musculus	206-211
31518877-10	2019	CONCLUSIONS: Metformin inhibited NLRP3 inflammasomes activation and suppressed diabetes-accelerated atherosclerosis in apoE-/- mice, which at least partially through activation of AMPK and regulation of thioredoxin-1/thioredoxin-interacting protein.	Metformin	13-22	NLR family, pyrin domain containing 3	Mus musculus	33-38
31612008-0	2019	AGR2 silencing contributes to metformin-dependent sensitization of colorectal cancer cells to chemotherapy.	Metformin	30-39	anterior gradient 2, protein disulphide isomerase family member	Homo sapiens	0-4
31612008-7	2019	In AGR2-knockout cells, markedly higher levels of phosphorylated-AMPK were observed in comparison with control cells transfected with GFP-scrambled guide RNA, which indicated that the presence of AGR2 may interfere with the metformin-dependent activation of AMPK.	Metformin	224-233	anterior gradient 2, protein disulphide isomerase family member	Homo sapiens	3-7
31612008-7	2019	In AGR2-knockout cells, markedly higher levels of phosphorylated-AMPK were observed in comparison with control cells transfected with GFP-scrambled guide RNA, which indicated that the presence of AGR2 may interfere with the metformin-dependent activation of AMPK.	Metformin	224-233	anterior gradient 2, protein disulphide isomerase family member	Homo sapiens	196-200
31359366-4	2019	Regarding overweight patients inadequately controlled with metformin, treatment with a sodium-glucose transport protein 2 inhibitor (SGLT2-I) is preferred over treatment with a dipeptidyl peptidase-4 inhibitor (DPP4-I).	Metformin	59-68	solute carrier family 5 member 2	Homo sapiens	133-138
31410711-9	2019	Furthermore, there is growing evidence to illustrate the overall safety profile of this class of agents and support the benefit-risk profile of SGLT2 inhibitors as a preferred option following metformin monotherapy failure, with respect to both kidney disease progression and heart failure outcomes.	Metformin	193-202	solute carrier family 5 member 2	Homo sapiens	144-149
31440988-3	2019	Given the results from recent studies, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) recommend that patients with T2D and clinical cardiovascular disease (CVD) with inadequate glucose control despite treatment with metformin should receive an SGLT2 inhibitor or GLP-1 receptor agonist.	Metformin	271-280	solute carrier family 5 member 2	Homo sapiens	299-304
31607288-7	2019	Metformin inhibited the expression of GLUT1, LDHA, ALDOA, PDK1, and PGK1 genes of K562 cells (P&lt;0.05) showing a dose-dependent manner(r=0.83,r=0.80,r=0.72,r=0.76,r=0.73,respectively).	Metformin	0-9	phosphoglycerate kinase 1	Homo sapiens	68-72
31319067-0	2019	Metformin suppresses cancer cell growth in endometrial carcinoma by inhibiting PD-L1.	Metformin	0-9	CD274 molecule	Homo sapiens	79-84
31319067-10	2019	Our results showed that metformin treatment on endometrial cancer cells Ishikawa and RL95-2 decreased the expression level of PD-L1 protein.	Metformin	24-33	CD274 molecule	Homo sapiens	126-131
31319067-12	2019	We demonstrated that the inhibition of PD-L1 by metformin is dependent on the AMPK signaling protein, and that metformin promotes direct binding of the AMPK protein to the PD-L1 protein.	Metformin	48-57	CD274 molecule	Homo sapiens	39-44
31319067-12	2019	We demonstrated that the inhibition of PD-L1 by metformin is dependent on the AMPK signaling protein, and that metformin promotes direct binding of the AMPK protein to the PD-L1 protein.	Metformin	111-120	CD274 molecule	Homo sapiens	172-177
31319067-14	2019	The suppression of metformin is relevant to the inhibition of PD-L1 expression and the activation of AMPK signaling protein, providing a novel mechanism in the anti-tumor property of metformin.	Metformin	19-28	CD274 molecule	Homo sapiens	62-67
31319067-14	2019	The suppression of metformin is relevant to the inhibition of PD-L1 expression and the activation of AMPK signaling protein, providing a novel mechanism in the anti-tumor property of metformin.	Metformin	183-192	CD274 molecule	Homo sapiens	62-67
31348945-10	2019	SIGNIFICANCE: Metformin with reduction of ECM component as collagen VI, MMP2 and MMP9, integrin/ERK pathway, necrosis markers as RIPK1, RIPK3 and MLKL, and apoptosis markers including DAP, DAPK1, DAPK3 and SIVA effects on fibrosis in insulin resistant and hypertrophied adipocytes in vitro.	Metformin	14-23	multimerin 1	Homo sapiens	42-45
31348946-7	2019	However, there is a growing understanding that Metformin demonstrates its anti-epileptic effect mainly via ameliorating brain oxidative damage, activation of AMPK, inhibition of mTOR pathway, downregulation of alpha-synuclein, reducing apoptosis, downregulation of BDNF and TrkB level.	Metformin	47-56	synuclein alpha	Homo sapiens	210-225
31330313-4	2019	Drugs used for T2DM treatment from insulin and metformin through dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists may represent a promising approach to fight AD.	Metformin	47-56	dipeptidyl peptidase 4	Homo sapiens	65-87
31346998-0	2019	Effects of Metformin Treatment on Soluble Leptin Receptor Levels in Women with Polycystic Ovary Syndrome.	Metformin	11-20	leptin receptor	Homo sapiens	42-57
31346998-1	2019	The effects of metformin treatment on soluble leptin receptor (sOB-R) levels in women with polycystic ovary syndrome (PCOS) were investigated.	Metformin	15-24	leptin receptor	Homo sapiens	46-61
31108386-0	2019	Combination of metformin with sodium selenite induces a functional phenotypic switch of human GM-CSF monocyte-derived macrophages.	Metformin	15-24	colony stimulating factor 2	Homo sapiens	94-100
31108386-1	2019	OBJECTIVES: We evaluated the effects of metformin (Met, 1,1-dimethylbiguanide hydrochloride) combined or not with sodium selenite (Ss, Na2SeO3) on the functional activities of LPS-activated GM-CSF monocyte-derived macrophages (GM-MDM).	Metformin	56-91	interferon regulatory factor 6	Homo sapiens	176-179
31108386-1	2019	OBJECTIVES: We evaluated the effects of metformin (Met, 1,1-dimethylbiguanide hydrochloride) combined or not with sodium selenite (Ss, Na2SeO3) on the functional activities of LPS-activated GM-CSF monocyte-derived macrophages (GM-MDM).	Metformin	56-91	colony stimulating factor 2	Homo sapiens	190-196
30989716-12	2019	We also discuss the activation of AMP activated protein kinase (AMPK) by the most widely used drug for type 2 diabetes, metformin, which exerts a dual negative regulatory effect on mTOR and BMP signaling, suggesting that metformin is a promising drug treatment for HO.	Metformin	120-129	bone morphogenetic protein 1	Homo sapiens	190-193
30989716-12	2019	We also discuss the activation of AMP activated protein kinase (AMPK) by the most widely used drug for type 2 diabetes, metformin, which exerts a dual negative regulatory effect on mTOR and BMP signaling, suggesting that metformin is a promising drug treatment for HO.	Metformin	221-230	bone morphogenetic protein 1	Homo sapiens	190-193
30759215-10	2019	Metformin-dependent PYY secretion was blocked by inhibitors of the plasma membrane monoamine transporter (PMAT) and the serotonin reuptake transporter (SERT), as well as by an inhibitor of AMP kinase (AMPK).	Metformin	0-9	solute carrier family 29 member 4	Homo sapiens	67-104
30759215-10	2019	Metformin-dependent PYY secretion was blocked by inhibitors of the plasma membrane monoamine transporter (PMAT) and the serotonin reuptake transporter (SERT), as well as by an inhibitor of AMP kinase (AMPK).	Metformin	0-9	solute carrier family 29 member 4	Homo sapiens	106-110
30759215-11	2019	CONCLUSIONS: This is a report of a direct action of metformin on the gut epithelium to trigger PYY secretion in humans, occurring via cell internalization through PMAT and SERT and intracellular activation of AMPK.	Metformin	52-61	solute carrier family 29 member 4	Homo sapiens	163-167
31275246-7	2019	Recently, DPP-4 inhibitors have increasingly replaced sulfonylureas as second line therapy after metformin failure and many metformin/DPP-4 inhibitor fixed dose combinations are available.	Metformin	97-106	dipeptidyl peptidase 4	Homo sapiens	10-15
31275246-7	2019	Recently, DPP-4 inhibitors have increasingly replaced sulfonylureas as second line therapy after metformin failure and many metformin/DPP-4 inhibitor fixed dose combinations are available.	Metformin	124-133	dipeptidyl peptidase 4	Homo sapiens	10-15
31275246-8	2019	In later stages of type 2 diabetes, DPP-4 inhibitors are also recommended in the guidelines in triple therapies with metformin and SGLT-2 inhibitors or with metformin and insulin.	Metformin	117-126	dipeptidyl peptidase 4	Homo sapiens	36-41
31275246-8	2019	In later stages of type 2 diabetes, DPP-4 inhibitors are also recommended in the guidelines in triple therapies with metformin and SGLT-2 inhibitors or with metformin and insulin.	Metformin	157-166	dipeptidyl peptidase 4	Homo sapiens	36-41
31275246-10	2019	DPP-4 inhibitors can be used as monotherapy when metformin is contraindicated or not tolerated.	Metformin	49-58	dipeptidyl peptidase 4	Homo sapiens	0-5
31275246-11	2019	Some studies have shown value of initial metformin-DPP-4 inhibitor combination therapy in special populations.	Metformin	41-50	dipeptidyl peptidase 4	Homo sapiens	51-56
30851273-12	2019	Inhibition of PP2A significantly restored NLRP3 and pro-IL-1beta protein expression level downregulated by metformin in ox-LDL-stimulated macrophages.	Metformin	107-116	protein phosphatase 2 phosphatase activator	Homo sapiens	14-18
30851273-13	2019	PP2A catalytic activity was required for NF-kappaB inhibition and Tristetraprolin activation induced by metformin in ox-LDL-stimulated macrophages.	Metformin	104-113	protein phosphatase 2 phosphatase activator	Homo sapiens	0-4
30851273-14	2019	Our data showed Metformin reduced NLRP3 protein expression and NLRP3 inflammasome activation in ox-LDL-stimulated macrophages through AMPK and PP2A.	Metformin	16-25	protein phosphatase 2 phosphatase activator	Homo sapiens	143-147
30603867-2	2019	The introduction of dipeptidyl peptidase-4 (DPP-4) inhibitors, more than 10 years ago, has provided an alternative to conventional medications for the intensification of glucose-lowering treatment after failure of metformin monotherapy, and therefore, marked an important advance in the management of T2DM.	Metformin	214-223	dipeptidyl peptidase 4	Homo sapiens	20-42
30603867-2	2019	The introduction of dipeptidyl peptidase-4 (DPP-4) inhibitors, more than 10 years ago, has provided an alternative to conventional medications for the intensification of glucose-lowering treatment after failure of metformin monotherapy, and therefore, marked an important advance in the management of T2DM.	Metformin	214-223	dipeptidyl peptidase 4	Homo sapiens	44-49
30767126-16	2019	There is a need to inculcate GLP-1 analogs and SGLT2 inhibitors that reduce major CV events and heart failure hospitalizations (alongside lifestyle management and metformin) in the treatment of patients with diabetes and CV disease.	Metformin	163-172	solute carrier family 5 member 2	Homo sapiens	47-52
31244286-3	2019	Recent studies have found that metformin has a potential anticancer effect mostlythrough reduction of cyclin expression and activation of Activated Adenosine Monophosphate Kinase (AMPK).	Metformin	31-40	proliferating cell nuclear antigen	Homo sapiens	102-108
31244286-15	2019	Other cyclin family members, CDK inhibitors and AMPKsignaling should be further investigated in order to know mechanism of metformin action.	Metformin	123-132	proliferating cell nuclear antigen	Homo sapiens	6-12
31041606-0	2019	Sodium-Glucose Co-Transporter 2 Inhibitors Compared with Sulfonylureas in Patients with Type 2 Diabetes Inadequately Controlled on Metformin: A Meta-Analysis of Randomized Controlled Trials.	Metformin	131-140	solute carrier family 5 member 2	Homo sapiens	0-31
31041606-2	2019	This meta-analysis was to compare the efficacy and safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors with sulfonylureas (SUs) as second-line therapy in patients with T2DM inadequately controlled on metformin.	Metformin	209-218	solute carrier family 5 member 2	Homo sapiens	94-99
31041606-11	2019	CONCLUSIONS: Despite similar glycemic efficacy in a relatively short term, SGLT2 inhibitors are more effective in the longer term than SUs as add-on to metformin.	Metformin	152-161	solute carrier family 5 member 2	Homo sapiens	75-80
30885951-0	2019	Variation in the Plasma Membrane Monoamine Transporter (PMAT) (Encoded by SLC29A4) and Organic Cation Transporter 1 (OCT1) (Encoded by SLC22A1) and Gastrointestinal Intolerance to Metformin in Type 2 Diabetes: An IMI DIRECT Study.	Metformin	180-189	solute carrier family 29 member 4	Homo sapiens	17-54
30885951-0	2019	Variation in the Plasma Membrane Monoamine Transporter (PMAT) (Encoded by SLC29A4) and Organic Cation Transporter 1 (OCT1) (Encoded by SLC22A1) and Gastrointestinal Intolerance to Metformin in Type 2 Diabetes: An IMI DIRECT Study.	Metformin	180-189	solute carrier family 29 member 4	Homo sapiens	56-60
30885951-3	2019	We hypothesized that reduced transport of metformin via the plasma membrane monoamine transporter (PMAT) and organic cation transporter 1 (OCT1) could increase the risk of severe gastrointestinal adverse effects.	Metformin	42-51	solute carrier family 29 member 4	Homo sapiens	60-97
30885951-3	2019	We hypothesized that reduced transport of metformin via the plasma membrane monoamine transporter (PMAT) and organic cation transporter 1 (OCT1) could increase the risk of severe gastrointestinal adverse effects.	Metformin	42-51	solute carrier family 29 member 4	Homo sapiens	99-103
31210335-11	2019	GW9662 treatment resulted in elevated expressions of MCP-1, TNF-alpha and IL-6, which were reversed by metformin treatment.	Metformin	103-112	C-C motif chemokine ligand 2	Rattus norvegicus	53-58
31210335-12	2019	CONCLUSIONS: Metformin can effectively inhibit the mRNA and protein expressions of IL-6, MCP-1, and TNF-alpha in LPS-induced VSMCs.	Metformin	13-22	C-C motif chemokine ligand 2	Rattus norvegicus	89-94
30880174-7	2019	Notably, miR-146a was significantly overexpressed in T2DM patients treated with metformin.	Metformin	80-89	microRNA 146a	Homo sapiens	9-17
31148423-5	2019	These favorable effects place them, like SGLT-2 inhibitors, as a second option in the case of unsatisfactory glycemic control after metformin and dietary and lifestyle measures.	Metformin	132-141	solute carrier family 5 member 2	Homo sapiens	41-47
31137785-9	2019	Disrupting the antioxidant HO-1 activity, especially under low glucose concentration, could be an attractive approach to potentiate metformin antineoplastic effects and could provide a biochemical basis for developing HO-1-targeting drugs against solid tumors.	Metformin	132-141	heme oxygenase 1	Homo sapiens	27-31
31118051-2	2019	Although Metformin has antiproliferative and proapoptotic effects on breast cancer, the heterogenous nature of this disease affects the response to metformin leading to the activation of pro-invasive signalling pathways that are mediated by the focal adhesion kinase PYK2 in pure HER2 phenotype breast cancer.	Metformin	148-157	protein tyrosine kinase 2 beta	Homo sapiens	267-271
31118051-4	2019	The activation of PYK2 by metformin in pure HER2 phenotype (HER2+/ER-/PR-) cell lines was investigated by microarrays, quantitative real time PCR and immunoblotting.	Metformin	26-35	protein tyrosine kinase 2 beta	Homo sapiens	18-22
31118051-11	2019	The role of PYK2 in promoting invasion of metformin resistant HER2 breast cancer cells was confirmed through investigating the effect of PYK2 knockdown and metformin on cell invasion and by proteomic analysis of associated cellular pathways.	Metformin	42-51	protein tyrosine kinase 2 beta	Homo sapiens	12-16
31118051-11	2019	The role of PYK2 in promoting invasion of metformin resistant HER2 breast cancer cells was confirmed through investigating the effect of PYK2 knockdown and metformin on cell invasion and by proteomic analysis of associated cellular pathways.	Metformin	42-51	protein tyrosine kinase 2 beta	Homo sapiens	137-141
31118051-11	2019	The role of PYK2 in promoting invasion of metformin resistant HER2 breast cancer cells was confirmed through investigating the effect of PYK2 knockdown and metformin on cell invasion and by proteomic analysis of associated cellular pathways.	Metformin	156-165	protein tyrosine kinase 2 beta	Homo sapiens	12-16
31118051-15	2019	CONCLUSIONS: We provide evidence of a PYK2-driven pro-invasive potential of metformin in pure HER2 cancer therapy and propose that metformin-based therapy should consider the molecular heterogeneity of breast cancer to prevent complications associated with cancer chemoresistance, invasion and recurrence in treated patients.	Metformin	76-85	protein tyrosine kinase 2 beta	Homo sapiens	38-42
31489252-5	2019	Western blot analysis showed that levels of O-linked N-acetylglucosamine (O-GlcNAc) and O-GlcNAc transferase (OGT) were increased in cervical cancer cells; these effects were reversed by metformin treatment.	Metformin	187-196	O-linked N-acetylglucosamine (GlcNAc) transferase	Homo sapiens	74-82
31489252-5	2019	Western blot analysis showed that levels of O-linked N-acetylglucosamine (O-GlcNAc) and O-GlcNAc transferase (OGT) were increased in cervical cancer cells; these effects were reversed by metformin treatment.	Metformin	187-196	O-linked N-acetylglucosamine (GlcNAc) transferase	Homo sapiens	88-108
31489252-5	2019	Western blot analysis showed that levels of O-linked N-acetylglucosamine (O-GlcNAc) and O-GlcNAc transferase (OGT) were increased in cervical cancer cells; these effects were reversed by metformin treatment.	Metformin	187-196	O-linked N-acetylglucosamine (GlcNAc) transferase	Homo sapiens	110-113
31489252-9	2019	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.	Metformin	23-32	H3 histone pseudogene 16	Homo sapiens	81-84
31489252-9	2019	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.	Metformin	23-32	interferon alpha inducible protein 27	Homo sapiens	89-92
31083566-9	2019	By further analysis, ATP6V1G1, THY1, PRKCA and NDUFB3 were identified as the most promising candidates potentially mediating reprogramming effects of metformin in a maternal high fat diet.	Metformin	150-159	ATPase, H+ transporting, lysosomal V1 subunit G1	Mus musculus	21-29
31083566-9	2019	By further analysis, ATP6V1G1, THY1, PRKCA and NDUFB3 were identified as the most promising candidates potentially mediating reprogramming effects of metformin in a maternal high fat diet.	Metformin	150-159	NADH:ubiquinone oxidoreductase subunit B3	Mus musculus	47-53
31120717-14	2019	CONCLUSIONS: In the United States, sequential addition of SGLT2 inhibitors to DPP-4 inhibitors may be considered cost-effective compared with traditional treatment with generic medications for patients who fail to achieve glycemic goal on metformin.	Metformin	239-248	solute carrier family 5 member 2	Homo sapiens	58-63
30653446-0	2019	Metformin alleviates hyperglycemia-induced endothelial impairment by downregulating autophagy via the Hedgehog pathway.	Metformin	0-9	hedgehog	Drosophila melanogaster	102-110
30849641-0	2019	Metformin sensitizes endometrial cancer cells to progestin by targeting TET1 to downregulate glyoxalase I expression.	Metformin	0-9	tet methylcytosine dioxygenase 1	Homo sapiens	72-76
30849641-0	2019	Metformin sensitizes endometrial cancer cells to progestin by targeting TET1 to downregulate glyoxalase I expression.	Metformin	0-9	glyoxalase I	Homo sapiens	93-105
30849641-3	2019	Our previous studies have demonstrated that metformin reversed progestin resistance through the downregulation of the expression of glyoxalase I (GLOI) in type I endometrial cancer.	Metformin	44-53	glyoxalase I	Homo sapiens	132-144
30849641-3	2019	Our previous studies have demonstrated that metformin reversed progestin resistance through the downregulation of the expression of glyoxalase I (GLOI) in type I endometrial cancer.	Metformin	44-53	glyoxalase I	Homo sapiens	146-150
30849641-9	2019	In current study, we found that metformin effectively sensitized progestin in endometrial cancer cell lines through the down regulation of the expression of TET1 and GLOI.	Metformin	32-41	tet methylcytosine dioxygenase 1	Homo sapiens	157-161
30849641-9	2019	In current study, we found that metformin effectively sensitized progestin in endometrial cancer cell lines through the down regulation of the expression of TET1 and GLOI.	Metformin	32-41	glyoxalase I	Homo sapiens	166-170
30849641-13	2019	Therefore, this finding suggests that metformin sensitized progestin in endometrial cancer through the TET1-5hmC-GLOI signaling pathway.	Metformin	38-47	tet methylcytosine dioxygenase 1	Homo sapiens	103-107
30849641-13	2019	Therefore, this finding suggests that metformin sensitized progestin in endometrial cancer through the TET1-5hmC-GLOI signaling pathway.	Metformin	38-47	glyoxalase I	Homo sapiens	113-117
31086662-0	2019	Frequency of CYP2C9 (*2, *3 and IVS8-109A&gt;T) allelic variants, and their clinical implications, among Mexican patients with diabetes mellitus type 2 undergoing treatment with glibenclamide and metformin.	Metformin	196-205	cytochrome P450 family 2 subfamily C member 9	Homo sapiens	13-19
30968600-5	2019	The Cox method analysis showed that the metformin cohort had an adjusted hazard ratio (aHR) of 0.69 (95% confidence interval [CI] = 0.49-0.96, P = 0.0298) for prostate cancer, compared to the nonmetformin cohort after controlling for age, traditional Chinese medicine (TCM) use, prostate specific antigen, and Charlson comorbidity index.	Metformin	40-49	kallikrein related peptidase 3	Homo sapiens	279-304
30457671-8	2019	Hypoglycemia risk for DPP-4 inhibitors, SGLT2 inhibitors, and thiazolidinediones was generally very low but increased slightly for both GLP-1RAs and metformin.	Metformin	149-158	dipeptidyl peptidase 4	Homo sapiens	22-27
31139382-0	2019	Metformin-induced autophagy and irisin improves INS-1 cell function and survival in high-glucose environment via AMPK/SIRT1/PGC-1alpha signal pathway.	Metformin	0-9	insulin 1	Rattus norvegicus	48-53
30972229-0	2019	Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice.	Metformin	30-39	mechanistic target of rapamycin kinase	Mus musculus	53-57
30972229-1	2019	Objective  This study was aimed to measure the effects of a high-fat diet and metformin on placental mechanistic target of rapamycin (mTOR) signaling in mice.	Metformin	78-87	mechanistic target of rapamycin kinase	Mus musculus	101-132
30972229-1	2019	Objective  This study was aimed to measure the effects of a high-fat diet and metformin on placental mechanistic target of rapamycin (mTOR) signaling in mice.	Metformin	78-87	mechanistic target of rapamycin kinase	Mus musculus	134-138
30972229-11	2019	Conclusion  Increased placental mTOR signaling and metformin inhibition of placental mTOR signaling only occurred in the presence of an HFD exposure.	Metformin	51-60	mechanistic target of rapamycin kinase	Mus musculus	85-89
30972229-12	2019	These findings suggest that metformin may modulate placental mTOR signaling in the presence of metabolic exposures during pregnancy.	Metformin	28-37	mechanistic target of rapamycin kinase	Mus musculus	61-65
31106005-0	2019	Metformin reverses PARP inhibitors-induced epithelial-mesenchymal transition and PD-L1 upregulation in triple-negative breast cancer.	Metformin	0-9	CD274 molecule	Homo sapiens	81-86
31106005-6	2019	Blocking the p-Akt S473 axis by metformin reversed EMT and PD-L1 expression which sensitized PARPi-resistant cells to cytotoxic T cells.	Metformin	32-41	CD274 molecule	Homo sapiens	59-64
31062756-0	2019	Treatment with metformin prevents myocardial ischemia-reperfusion injury via STEAP4 signaling pathway.	Metformin	15-24	STEAP4 metalloreductase	Rattus norvegicus	77-83
31062756-9	2019	RESULTS: We found that metformin decreased infarct size, increased expression of STEAP4, mitigated myocardial apoptosis and increased mitochondrial membrane potential (MMP) when the models were subjected to H/R or I/R injuries.	Metformin	23-32	STEAP4 metalloreductase	Rattus norvegicus	81-87
31062756-10	2019	However, STEAP4 knockdown significantly abrogated the beneficial effect of metformin.	Metformin	75-84	STEAP4 metalloreductase	Rattus norvegicus	9-15
31062756-11	2019	CONCLUSIONS: We further demonstrated the protective effect of metformin on cardiomyocytes, which might be at least partly attributable to upregulation of STEAP4.	Metformin	62-71	STEAP4 metalloreductase	Rattus norvegicus	154-160
30933547-1	2019	INTRODUCTION: Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) are recommended after metformin for a large spectrum of patients with type 2 diabetes, because of a favorable benefit/risk profile despite a variety of adverse events.	Metformin	93-102	solute carrier family 5 member 2	Homo sapiens	62-67
30229901-2	2019	We aimed to investigate the association between different glucose-lowering treatments, including DPP-4 inhibitors and metformin, both with potential NRF2 modulating effects, and new-onset metastatic cancer among type 2 diabetes patients with comorbid incident cancer.	Metformin	118-127	dipeptidyl peptidase 4	Homo sapiens	97-102
30720053-0	2019	Metformin prevents nephrolithiasis formation by inhibiting the expression of OPN and MCP-1 in vitro and in vivo.	Metformin	0-9	C-C motif chemokine ligand 2	Rattus norvegicus	85-90
30720053-7	2019	In vitro, metformin significantly inhibited the production of MCP-1 and OPN induced by oxalate at the mRNA and protein expression levels.	Metformin	10-19	C-C motif chemokine ligand 2	Rattus norvegicus	62-67
30720053-8	2019	In vivo, increased expression levels of MCP-1 and OPN were detected in the EG group compared with the controls, and this upregulation was reversed in the EG + metformin group.	Metformin	159-168	C-C motif chemokine ligand 2	Rattus norvegicus	40-45
30720053-10	2019	Therefore, the results of the study suggest that metformin suppressed urinary crystal deposit formation, possibly by mediating the expression of inflammatory mediators OPN and MCP-1.	Metformin	49-58	C-C motif chemokine ligand 2	Rattus norvegicus	176-181
30720062-5	2019	Western blot analysis demonstrated that treatment with metformin increased the phosphorylation of AMPK, and decreased the phosphorylation of AKT, mTOR and p70S6k.	Metformin	55-64	ribosomal protein S6 kinase B1	Homo sapiens	155-161
30655321-0	2019	SPHK1 Is a Novel Target of Metformin in Ovarian Cancer.	Metformin	27-36	sphingosine kinase 1	Homo sapiens	0-5
30655321-9	2019	In support of this, metformin blocked hypoxia-induced SPHK1, which was associated with inhibited nuclear translocation and transcriptional activity of hypoxia-inducible factors (HIF1alpha and HIF2alpha).	Metformin	20-29	sphingosine kinase 1	Homo sapiens	54-59
30655321-9	2019	In support of this, metformin blocked hypoxia-induced SPHK1, which was associated with inhibited nuclear translocation and transcriptional activity of hypoxia-inducible factors (HIF1alpha and HIF2alpha).	Metformin	20-29	endothelial PAS domain protein 1	Homo sapiens	192-201
30655321-10	2019	Further, ovarian cancer cells with high SPHK1 were found to be highly sensitive to the cytotoxic effects of metformin, whereas ovarian cancer cells with low SPHK1 were resistant.	Metformin	108-117	sphingosine kinase 1	Homo sapiens	40-45
30655321-11	2019	Together, the findings reported here show that hypoxia-induced SPHK1 expression and downstream S1P signaling promote ovarian cancer progression and that tumors with high expression of SPHK1 or S1P levels might have increased sensitivity to the cytotoxic effects of metformin.	Metformin	265-274	sphingosine kinase 1	Homo sapiens	63-68
30655321-11	2019	Together, the findings reported here show that hypoxia-induced SPHK1 expression and downstream S1P signaling promote ovarian cancer progression and that tumors with high expression of SPHK1 or S1P levels might have increased sensitivity to the cytotoxic effects of metformin.	Metformin	265-274	sphingosine kinase 1	Homo sapiens	184-189
30655321-12	2019	IMPLICATIONS: Metformin targets sphingolipid metabolism through inhibiting SPHK1, thereby impeding ovarian cancer cell migration, proliferation, and self-renewal.	Metformin	14-23	sphingosine kinase 1	Homo sapiens	75-80
30710234-9	2019	Our study provided new insights of the anticarcinogenic effects of EGCG and metformin on HCC through their effects on glypican-3 and lncRNA-AF085935.	Metformin	76-85	glypican 3	Homo sapiens	118-128
29934960-13	2019	Pretreatment with metformin suppressed upregulation of MCP-1 and downregulation of BAMBI, as well as phosphorylation of ERK1/2 induced by TGF-beta1.	Metformin	18-27	C-C motif chemokine ligand 2	Rattus norvegicus	55-60
29934960-13	2019	Pretreatment with metformin suppressed upregulation of MCP-1 and downregulation of BAMBI, as well as phosphorylation of ERK1/2 induced by TGF-beta1.	Metformin	18-27	BMP and activin membrane-bound inhibitor	Rattus norvegicus	83-88
29934960-17	2019	CONCLUSION: In rat renal tubular epithelial cells, metformin prevents TGF-beta1-induced MCP-1 expression, in which BAMBI-mediated inhibition of MEK/ERK1/2 might be involved.	Metformin	51-60	C-C motif chemokine ligand 2	Rattus norvegicus	88-93
29934960-17	2019	CONCLUSION: In rat renal tubular epithelial cells, metformin prevents TGF-beta1-induced MCP-1 expression, in which BAMBI-mediated inhibition of MEK/ERK1/2 might be involved.	Metformin	51-60	BMP and activin membrane-bound inhibitor	Rattus norvegicus	115-120
30466344-10	2019	Endoplasmic reticulum stress-related apoptosis proteins (glucose-regulated protein 78, caspase-12, and CCAAT/enhancer binding protein (EBP) homologous protein) were downregulated after metformin treatment.	Metformin	185-194	EBP, cholestenol delta-isomerase	Rattus norvegicus	103-133
30466344-10	2019	Endoplasmic reticulum stress-related apoptosis proteins (glucose-regulated protein 78, caspase-12, and CCAAT/enhancer binding protein (EBP) homologous protein) were downregulated after metformin treatment.	Metformin	185-194	EBP, cholestenol delta-isomerase	Rattus norvegicus	135-138
30984619-0	2019	The C Allele of ATM rs11212617 Associates With Higher Pathological Complete Remission Rate in Breast Cancer Patients Treated With Neoadjuvant Metformin.	Metformin	142-151	ATM serine/threonine kinase	Homo sapiens	16-19
30984619-1	2019	Background: The minor allele (C) of the single-nucleotide polymorphism (SNP) rs11212617, located near the ataxia telangiectasia mutated (ATM) gene, has been associated with an increased likelihood of treatment success with metformin in type 2 diabetes.	Metformin	223-232	ATM serine/threonine kinase	Homo sapiens	106-135
30984619-1	2019	Background: The minor allele (C) of the single-nucleotide polymorphism (SNP) rs11212617, located near the ataxia telangiectasia mutated (ATM) gene, has been associated with an increased likelihood of treatment success with metformin in type 2 diabetes.	Metformin	223-232	ATM serine/threonine kinase	Homo sapiens	137-140
30934600-0	2019	Metformin Pharmacogenetics: Effects of SLC22A1, SLC22A2, and SLC22A3 Polymorphisms on Glycemic Control and HbA1c Levels.	Metformin	0-9	solute carrier family 22 member 2	Homo sapiens	48-55
30934600-3	2019	The objective of this study was to investigate the relationship between twenty-one single nucleotide polymorphisms (SNPs) in the SLC22A1, SLC22A2, and SLC22A3 genes and their effects on metformin pharmacogenetics in Jordanian patients diagnosed with type 2 diabetes mellitus.	Metformin	186-195	solute carrier family 22 member 2	Homo sapiens	138-145
30845774-5	2019	Of note, abdominal fat tissue of obese pre-DM patients treated with metformin therapy presented higher SIRT6 expression and lower NF-kappaB, PPAR-gamma, and SREBP-1 expression levels compared to pre-DM control group.	Metformin	68-77	sterol regulatory element binding transcription factor 1	Homo sapiens	157-164
30530000-10	2019	DSC study showed that metformin in SLN is in an amorphous form.	Metformin	22-31	sarcolipin	Homo sapiens	35-38
30530000-11	2019	FT-IR spectra of Met-SLN showed that the prominent functional groups existed in the formulations which could be an indication of good entrapment of metformin in a lipid matrix.	Metformin	148-157	sarcolipin	Homo sapiens	21-24
30710655-15	2019	INTERPRETATION: These results suggest better safety profile for DPP-4 inhibitors than sulfonylureas for both comparisons, and it is more notable when the treatment regimen includes metformin.	Metformin	181-190	dipeptidyl peptidase 4	Homo sapiens	64-69
30421661-3	2019	It has been shown that treatment of patients with type 2 diabetes with metformin leads to increased GLO1-activity in peripheral-blood-cells.	Metformin	71-80	glyoxalase I	Homo sapiens	100-104
30421661-4	2019	The aim of this study was to evaluate whether metformin treatment increases GLO1-activity in atherosclerotic lesions of patients with type 2 diabetes.	Metformin	46-55	glyoxalase I	Homo sapiens	76-80
30421661-9	2019	GLO1-activity was increased by the factor 1.36 when treated with metformin - however, not significantly (0.86 vs. 0.63 U/mg, p = 0.056).	Metformin	65-74	glyoxalase I	Homo sapiens	0-4
30421661-11	2019	GLO1-activity correlated positively with increasing HbA1c, especially under metformin treatment.	Metformin	76-85	glyoxalase I	Homo sapiens	0-4
30421661-12	2019	CONCLUSIONS: Treatment with metformin in patients with type 2 diabetes is associated with enhanced GLO1-activity in atherosclerotic lesions.	Metformin	28-37	glyoxalase I	Homo sapiens	99-103
30873028-6	2019	Additionally, cardiac expression of brain-like natriuretic peptide (BNP) was significantly reduced in metformin-treated mice after 14 days of cardiac I/R.	Metformin	102-111	natriuretic peptide type B	Mus musculus	36-66
30873028-6	2019	Additionally, cardiac expression of brain-like natriuretic peptide (BNP) was significantly reduced in metformin-treated mice after 14 days of cardiac I/R.	Metformin	102-111	natriuretic peptide type B	Mus musculus	68-71
30853913-0	2019	Metformin Suppresses Hypopharyngeal Cancer Growth by Epigenetically Silencing Long Non-coding RNA SNHG7 in FaDu Cells.	Metformin	0-9	small nucleolar RNA host gene 7	Homo sapiens	98-103
30853913-2	2019	Metformin is associated with reduced cancer risk through promoting global DNA methylation in cancer cells by controlling S-adenosylhomocysteine (SAHH) activity.	Metformin	0-9	adenosylhomocysteinase	Homo sapiens	145-149
30853913-6	2019	LncRNA microarray analysis, QPCR, methylation specific PCR, Western blot and RNA Immunoprecipitation were performed to analyze the molecular mechanism, Here, we report that metformin inhibits FaDu cell proliferation in time- and dose-dependent manner by suppressing lncRNA SNHG7.	Metformin	173-182	small nucleolar RNA host gene 7	Homo sapiens	273-278
30853913-7	2019	Further investigations revealed that SNHG7 interacted with SAHH and metformin decreased SNHG7 expression by activating SAHH activity.	Metformin	68-77	small nucleolar RNA host gene 7	Homo sapiens	37-42
30853913-7	2019	Further investigations revealed that SNHG7 interacted with SAHH and metformin decreased SNHG7 expression by activating SAHH activity.	Metformin	68-77	small nucleolar RNA host gene 7	Homo sapiens	88-93
30853913-7	2019	Further investigations revealed that SNHG7 interacted with SAHH and metformin decreased SNHG7 expression by activating SAHH activity.	Metformin	68-77	adenosylhomocysteinase	Homo sapiens	119-123
30853913-12	2019	Metformin sensitizes FaDu cells to taxol and irradiation through decreasing SNHG7.	Metformin	0-9	small nucleolar RNA host gene 7	Homo sapiens	76-81
30853913-13	2019	In conclusion, our recent study demonstrates that metformin inhibits FaDu cell proliferation by decreasing SNHG7 expression via SAHH-mediated DNA methylation.	Metformin	50-59	small nucleolar RNA host gene 7	Homo sapiens	107-112
30853913-13	2019	In conclusion, our recent study demonstrates that metformin inhibits FaDu cell proliferation by decreasing SNHG7 expression via SAHH-mediated DNA methylation.	Metformin	50-59	adenosylhomocysteinase	Homo sapiens	128-132
30911317-0	2019	Metformin Promotes Neuronal Differentiation via Crosstalk between Cdk5 and Sox6 in Neuroblastoma Cells.	Metformin	0-9	cyclin dependent kinase 5	Homo sapiens	66-70
30911317-7	2019	Further investigation found that metformin significantly decreased Cdk5 but increased Sox6 during cell differentiation.	Metformin	33-42	cyclin dependent kinase 5	Homo sapiens	67-71
30911317-8	2019	Analysis of the mechanism underlying these changes using Cdk5 inhibitor, roscovitine, indicated that expressions of Cdk5 and Sox6 corresponded to metformin treatment.	Metformin	146-155	cyclin dependent kinase 5	Homo sapiens	57-61
30911317-8	2019	Analysis of the mechanism underlying these changes using Cdk5 inhibitor, roscovitine, indicated that expressions of Cdk5 and Sox6 corresponded to metformin treatment.	Metformin	146-155	cyclin dependent kinase 5	Homo sapiens	116-120
30911317-9	2019	These results suggested that metformin produces neuronal differentiation via Cdk5 and Sox6.	Metformin	29-38	cyclin dependent kinase 5	Homo sapiens	77-81
30911317-11	2019	Taken together, these findings suggest that metformin promotes neuronal differentiation via ROS activation through Cdk5/Sox6 crosstalk, relating to Erk1/2 and Akt signaling.	Metformin	44-53	cyclin dependent kinase 5	Homo sapiens	115-119
30779140-3	2019	Herein, we investigated the anti-inflammatory effects of metformin on the NIMA-related kinase 7(Nek7)/NOD-like receptor family pyrin domain containing 3 (NLRP3) pathway both in vivo and in vitro in experimental diabetic periodontitis.	Metformin	57-66	NLR family, pyrin domain containing 3	Mus musculus	154-159
30779140-13	2019	Furthermore, after stimulation with the mTOR inhibitor rapamycin, additional metformin treatment could still downregulate Nek7/NLRP3.	Metformin	77-86	mechanistic target of rapamycin kinase	Mus musculus	40-44
30779140-13	2019	Furthermore, after stimulation with the mTOR inhibitor rapamycin, additional metformin treatment could still downregulate Nek7/NLRP3.	Metformin	77-86	NLR family, pyrin domain containing 3	Mus musculus	127-132
30779140-15	2019	Metformin suppressed the inflammatory state by inhibiting Nek7 expression to decrease NLRP3 inflammasome activity.	Metformin	0-9	NLR family, pyrin domain containing 3	Mus musculus	86-91
30899391-8	2019	Moreover, in the metformin but not the sitagliptin treated group, JAK2/STAT3 activation was associated with having better improved cardiac remolding and reduced myocardial apoptosis.	Metformin	17-26	signal transducer and activator of transcription 3	Rattus norvegicus	71-76
30899391-9	2019	In vitro studies further validated that metformin could activate JAK2/STAT3 pathway and alleviate apoptosis of NRCMs under hyperglycemia incubation.	Metformin	40-49	signal transducer and activator of transcription 3	Rattus norvegicus	70-75
30899391-11	2019	The superior cardio-protective effect of metformin over sitagliptin treatment may partly account for the differences we observed in JAK2/STAT3 activation, indicating that measuring JAK2/STAT3 pathway coupled with metformin treatment may give insight into a more promising DM treatment.	Metformin	41-50	signal transducer and activator of transcription 3	Rattus norvegicus	137-142
30899391-11	2019	The superior cardio-protective effect of metformin over sitagliptin treatment may partly account for the differences we observed in JAK2/STAT3 activation, indicating that measuring JAK2/STAT3 pathway coupled with metformin treatment may give insight into a more promising DM treatment.	Metformin	41-50	signal transducer and activator of transcription 3	Rattus norvegicus	186-191
30625338-0	2019	Metformin delays AKT/c-Met-driven hepatocarcinogenesis by regulating signaling pathways for de novo lipogenesis and ATP generation.	Metformin	0-9	met proto-oncogene	Mus musculus	21-26
30625338-4	2019	Here, we investigate the preventive efficacy of metformin in a rapid AKT/c-Met-triggered HCC mouse model featuring excessive levels of steatosis.	Metformin	48-57	met proto-oncogene	Mus musculus	73-78
30625338-7	2019	The results show that metformin obstructs the malignant transformation of hepatocytes in AKT/c-Met mice.	Metformin	22-31	met proto-oncogene	Mus musculus	93-98
30625338-8	2019	Mechanistically, metformin reduces the expression of phospho-ERK (Thr202/Tyr204) and two forms of proto-oncogenes, Cyclin D1 and c-Myc, in AKT/c-Met mice.	Metformin	17-26	met proto-oncogene	Mus musculus	143-148
30625338-9	2019	Moreover, metformin ameliorates FASN-mediated aberrant lipogenesis and HK2/PKM2-driven ATP generation in vivo.	Metformin	10-19	hexokinase 2	Mus musculus	71-74
30625338-10	2019	Furthermore, metformin represses the expression of FASN and HK-2 by targeting c-Myc in an AMPK-dependent manner in vitro.	Metformin	13-22	hexokinase 2	Mus musculus	60-64
30760281-0	2019	Low glucose and metformin-induced apoptosis of human ovarian cancer cells is connected to ASK1 via mitochondrial and endoplasmic reticulum stress-associated pathways.	Metformin	16-25	mitogen-activated protein kinase kinase kinase 5	Homo sapiens	90-94
30760281-5	2019	This study was designed to investigate the functional significance of ASK1, mitochondria and endoplasmic reticulum and underlying mechanism in low glucose and metformin-induced cell apoptosis.	Metformin	159-168	mitogen-activated protein kinase kinase kinase 5	Homo sapiens	70-74
30760281-13	2019	Utilization of a specific pharmacological inhibitor or ASK1-siRNA identified a potential role for ASK1 as an apoptotic protein in the regulation of low glucose and metformin-induced cell apoptosis via ASK1-mediated mitochondrial damage through the ASK1/Noxa pathway and via ER stress through the ROS/ASK1/JNK pathway.	Metformin	164-173	mitogen-activated protein kinase kinase kinase 5	Homo sapiens	55-59
30760281-13	2019	Utilization of a specific pharmacological inhibitor or ASK1-siRNA identified a potential role for ASK1 as an apoptotic protein in the regulation of low glucose and metformin-induced cell apoptosis via ASK1-mediated mitochondrial damage through the ASK1/Noxa pathway and via ER stress through the ROS/ASK1/JNK pathway.	Metformin	164-173	mitogen-activated protein kinase kinase kinase 5	Homo sapiens	98-102
30760281-13	2019	Utilization of a specific pharmacological inhibitor or ASK1-siRNA identified a potential role for ASK1 as an apoptotic protein in the regulation of low glucose and metformin-induced cell apoptosis via ASK1-mediated mitochondrial damage through the ASK1/Noxa pathway and via ER stress through the ROS/ASK1/JNK pathway.	Metformin	164-173	mitogen-activated protein kinase kinase kinase 5	Homo sapiens	98-102
30760281-13	2019	Utilization of a specific pharmacological inhibitor or ASK1-siRNA identified a potential role for ASK1 as an apoptotic protein in the regulation of low glucose and metformin-induced cell apoptosis via ASK1-mediated mitochondrial damage through the ASK1/Noxa pathway and via ER stress through the ROS/ASK1/JNK pathway.	Metformin	164-173	mitogen-activated protein kinase kinase kinase 5	Homo sapiens	98-102
30760281-13	2019	Utilization of a specific pharmacological inhibitor or ASK1-siRNA identified a potential role for ASK1 as an apoptotic protein in the regulation of low glucose and metformin-induced cell apoptosis via ASK1-mediated mitochondrial damage through the ASK1/Noxa pathway and via ER stress through the ROS/ASK1/JNK pathway.	Metformin	164-173	mitogen-activated protein kinase kinase kinase 5	Homo sapiens	98-102
30760281-14	2019	Moreover, ASK1 inhibition weakened the antitumor activity of metformin in vivo.	Metformin	61-70	mitogen-activated protein kinase kinase kinase 5	Homo sapiens	10-14
30760281-16	2019	CONCLUSIONS: These data suggested that low glucose and metformin induce cell apoptosis via ASK1-mediated mitochondrial damage and ER stress.	Metformin	55-64	mitogen-activated protein kinase kinase kinase 5	Homo sapiens	91-95
30554148-6	2019	Significantly, metformin prevents oxidation of heme in three protein scaffolds, cytochrome c, myoglobin and hemoglobin, with Kd values &lt; 3 mM suggesting a dual oxidation and reduction role in the regulation of heme redox transition.	Metformin	15-24	myoglobin	Homo sapiens	94-103
30733434-4	2019	Thr222 phosphorylation following AMPK activation is required for protein stabilization of Insig-1, inhibition of cleavage and processing of SREBP-1, and lipogenic gene expression in response to metformin or A769662.	Metformin	194-203	sterol regulatory element binding transcription factor 1	Mus musculus	140-147
30717766-10	2019	In addition, the AMPK activator metformin remarkably suppressed the growth of PCK1-knockout PLC/PRF/5 cells and inhibited tumor growth in an orthotropic HCC mouse model.	Metformin	32-41	phosphoenolpyruvate carboxykinase 1	Homo sapiens	78-82
30717766-10	2019	In addition, the AMPK activator metformin remarkably suppressed the growth of PCK1-knockout PLC/PRF/5 cells and inhibited tumor growth in an orthotropic HCC mouse model.	Metformin	32-41	heparan sulfate proteoglycan 2	Homo sapiens	92-95
30717766-11	2019	CONCLUSION: This study revealed that PCK1 negatively regulates cell cycle progression and hepatoma cell proliferation via the AMPK/p27Kip1 axis and supports a potential therapeutic and protective effect of metformin on HCC.	Metformin	206-215	phosphoenolpyruvate carboxykinase 1	Homo sapiens	37-41
30717766-11	2019	CONCLUSION: This study revealed that PCK1 negatively regulates cell cycle progression and hepatoma cell proliferation via the AMPK/p27Kip1 axis and supports a potential therapeutic and protective effect of metformin on HCC.	Metformin	206-215	cyclin dependent kinase inhibitor 1B	Homo sapiens	131-138
30718758-10	2019	Ionizing radiation-induced gamma-H2AX and 53BP1 foci persisted longer in both cell lines in the presence of metformin.	Metformin	108-117	tumor protein p53 binding protein 1	Homo sapiens	42-47
30427219-11	2019	When inner medullary tissue was treated with the PKC activator phorbol dibutyrate (PDBu), the AMPK activator metformin, or both, AQP2 phosphorylation at S261 was decreased with PDBu or metformin alone, but there was no additive effect on phosphorylation with PDBu and metformin together.	Metformin	109-118	aquaporin 2	Rattus norvegicus	129-133
30427219-11	2019	When inner medullary tissue was treated with the PKC activator phorbol dibutyrate (PDBu), the AMPK activator metformin, or both, AQP2 phosphorylation at S261 was decreased with PDBu or metformin alone, but there was no additive effect on phosphorylation with PDBu and metformin together.	Metformin	185-194	aquaporin 2	Rattus norvegicus	129-133
30427219-11	2019	When inner medullary tissue was treated with the PKC activator phorbol dibutyrate (PDBu), the AMPK activator metformin, or both, AQP2 phosphorylation at S261 was decreased with PDBu or metformin alone, but there was no additive effect on phosphorylation with PDBu and metformin together.	Metformin	185-194	aquaporin 2	Rattus norvegicus	129-133
30465181-8	2019	DSPP, ALP, and DMP-1 gene expressions of DPSCs on metformin resin were much higher than DPSCs on control resin without metformin (p &lt; 0.05).	Metformin	50-59	dentin matrix acidic phosphoprotein 1	Homo sapiens	15-20
30321069-0	2019	Metformin increases glucose uptake and acts renoprotectively by reducing SHIP2 activity.	Metformin	0-9	inositol polyphosphate phosphatase like 1	Homo sapiens	73-78
30321069-4	2019	Here, we demonstrate that metformin directly binds to and reduces the catalytic activity of the recombinant SHIP2 phosphatase domain in vitro.	Metformin	26-35	inositol polyphosphate phosphatase like 1	Homo sapiens	108-113
30321069-6	2019	In SHIP2-overexpressing myotubes, metformin ameliorates reduced glucose uptake by slowing down glucose transporter 4 endocytosis.	Metformin	34-43	inositol polyphosphate phosphatase like 1	Homo sapiens	3-8
30321069-7	2019	SHIP2 overexpression reduces Akt activity and enhances podocyte apoptosis, and both are restored to normal levels by metformin.	Metformin	117-126	inositol polyphosphate phosphatase like 1	Homo sapiens	0-5
30321069-8	2019	SHIP2 activity is elevated in glomeruli of patients with T2D receiving nonmetformin medication, but not in patients receiving metformin, compared with people without diabetes.	Metformin	74-83	inositol polyphosphate phosphatase like 1	Homo sapiens	0-5
30804576-1	2019	OBJECTIVE: To determine the frequencies of single nucleotide polymorphisms rs201919874 and rs138244461 in genes SLC22A2 and SLC47A2 respectively in Pakistani diabetes patients in order to characterise the genetic variants and determine their association with the pharmacokinetics of metformin.	Metformin	283-292	solute carrier family 22 member 2	Homo sapiens	112-119
30569135-0	2019	Metformin attenuates cells stemness and epithelial-mesenchymal transition in colorectal cancer cells by inhibiting the Wnt3a/beta-catenin pathway.	Metformin	0-9	catenin beta 1	Homo sapiens	125-137
30569135-3	2019	Additionally, metformin attenuated the EMT process, characterized by a decrease of mesenchymal marker Vimentin and an increase in the expression of an epithelial marker.	Metformin	14-23	vimentin	Homo sapiens	102-110
30569135-4	2019	Mechanistically, metformin inactivated the Wnt3a/beta-catenin signaling pathway, and reactivation of Wnt3a/beta-catenin signaling attenuated the inhibition of metformin on the stemness of HCT116 colorectal cancer cells and EMT.	Metformin	17-26	catenin beta 1	Homo sapiens	49-61
30569135-4	2019	Mechanistically, metformin inactivated the Wnt3a/beta-catenin signaling pathway, and reactivation of Wnt3a/beta-catenin signaling attenuated the inhibition of metformin on the stemness of HCT116 colorectal cancer cells and EMT.	Metformin	159-168	catenin beta 1	Homo sapiens	107-119
30483811-9	2019	The present study also explored the role of metformin in the LKB1 signaling pathway.	Metformin	44-53	serine/threonine kinase 11	Homo sapiens	61-65
30423430-9	2019	Since organic cation transporter 3 (OCT3) transports metformin and is dense in placenta, social preferences of OCT3 knock-out males were measured.	Metformin	53-62	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	6-34
30423430-9	2019	Since organic cation transporter 3 (OCT3) transports metformin and is dense in placenta, social preferences of OCT3 knock-out males were measured.	Metformin	53-62	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	36-40
30385301-8	2019	Protective effect of metformin and berberine against these toxic insults were found to be associated with the mitochondrial SirT3 pathway.	Metformin	21-30	sirtuin 3	Rattus norvegicus	124-129
30312887-10	2019	The method showed excellent linearity over concentration ranges 0.25-10 and 25-2000 ng mL-1 for linagliptin and metformin, respectively.	Metformin	112-121	L1 cell adhesion molecule	Mus musculus	87-91
30693913-0	2019	Metformin Inhibit Lung Cancer Cell Growth and Invasion in Vitro as Well as Tumor Formation in Vivo Partially by Activating PP2A.	Metformin	0-9	protein phosphatase 2 phosphatase activator	Homo sapiens	123-127
30693913-1	2019	BACKGROUND The aim of this study was to investigate whether PP2A activation is involved in the anti-cancer activity of metformin.	Metformin	119-128	protein phosphatase 2 phosphatase activator	Homo sapiens	60-64
30693913-3	2019	Influences of okadaic acid (OA) treatment, O/E alpha4 or sh-PP2Ac on metformin treated cells were investigated by cell viability, proliferation, apoptosis, and Transwell invasion assay in vitro.	Metformin	69-78	protein phosphatase 2 catalytic subunit alpha	Homo sapiens	60-65
30693913-6	2019	RESULTS Metformin treatment significantly reduced A549 or H1651 cell growth and invasive capacity in vitro as well as Ser184 phosphorylation of Bax, Ser62 phosphorylation of Myc, and Ser473 phosphorylation of Akt, all of which could be partially attenuated by OA treatment, O/E alpha4 or sh-PP2Ac.	Metformin	8-17	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	174-177
30693913-6	2019	RESULTS Metformin treatment significantly reduced A549 or H1651 cell growth and invasive capacity in vitro as well as Ser184 phosphorylation of Bax, Ser62 phosphorylation of Myc, and Ser473 phosphorylation of Akt, all of which could be partially attenuated by OA treatment, O/E alpha4 or sh-PP2Ac.	Metformin	8-17	protein phosphatase 2 catalytic subunit alpha	Homo sapiens	291-296
30693913-7	2019	Metformin treatment also significantly reduced tumor formation in vivo as well as protein expression of PCNA, Akt, Myc, and serine phosphorylation of the latter 2, which can be partially blocked by O/E alpha4 or sh-PP2Ac.	Metformin	0-9	proliferating cell nuclear antigen	Homo sapiens	104-108
30693913-7	2019	Metformin treatment also significantly reduced tumor formation in vivo as well as protein expression of PCNA, Akt, Myc, and serine phosphorylation of the latter 2, which can be partially blocked by O/E alpha4 or sh-PP2Ac.	Metformin	0-9	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	115-118
30693913-7	2019	Metformin treatment also significantly reduced tumor formation in vivo as well as protein expression of PCNA, Akt, Myc, and serine phosphorylation of the latter 2, which can be partially blocked by O/E alpha4 or sh-PP2Ac.	Metformin	0-9	protein phosphatase 2 catalytic subunit alpha	Homo sapiens	215-220
30693913-8	2019	CONCLUSIONS Metformin reduced lung cancer cell growth and invasion in vitro as well as tumor formation in vivo partially by activating PP2A.	Metformin	12-21	protein phosphatase 2 phosphatase activator	Homo sapiens	135-139
31016151-15	2019	Dipeptidyl peptidase-4 inhibitors seem to be fast catching up with sulfonylureas as a second-line treatment after metformin.	Metformin	114-123	dipeptidyl peptidase 4	Homo sapiens	0-22
30745848-0	2019	Activation of AMPK by metformin promotes renal cancer cell proliferation under glucose deprivation through its interaction with PKM2.	Metformin	22-31	pyruvate kinase M1/2	Homo sapiens	128-132
30745848-7	2019	Furthermore, depletion of PKM2 or beta-Catenin abrogated the proliferative effects of metformin under GD condition.	Metformin	86-95	pyruvate kinase M1/2	Homo sapiens	26-30
30745848-7	2019	Furthermore, depletion of PKM2 or beta-Catenin abrogated the proliferative effects of metformin under GD condition.	Metformin	86-95	catenin beta 1	Homo sapiens	34-46
30745848-8	2019	And inhibition of PKM2 also re-sensitized the A498 xenograft in response to metformin treatment.	Metformin	76-85	pyruvate kinase M1/2	Homo sapiens	18-22
30880507-4	2019	Both endocannabinoids and metformin may modulate hepatosteatosis; therefore, it was interesting to examine whether metformin may affect lipid accumulation in hepatocytes by acting on cannabinoid receptors, CB1 and CB2, in in vitro study.	Metformin	115-124	cannabinoid receptor 2	Homo sapiens	214-217
30909226-3	2019	There is evidence that metformin acts in a neuroprotective manner via the AMPK/mTOR pathway by inhibiting the tau phosphorylation.	Metformin	23-32	mechanistic target of rapamycin kinase	Mus musculus	79-83
30909226-4	2019	In addition, it is known that metformin upregulates Fgf21, which in turn activates the AMPK/mTOR pathway and mediates neuroprotection.	Metformin	30-39	mechanistic target of rapamycin kinase	Mus musculus	92-96
30909226-5	2019	Thus, metformin-induced Fgf21 release may be involved in AMPK/mTOR activation.	Metformin	6-15	mechanistic target of rapamycin kinase	Mus musculus	62-66
30909226-8	2019	Metformin-treated mice revealed increased expression of lipogenic genes, i.e., lxralpha and srebp1c.	Metformin	0-9	sterol regulatory element binding transcription factor 1	Mus musculus	92-99
30909226-9	2019	In line with this, metformin caused an increase in plasma triglyceride leading to enhanced gliosis as indicated by an increase of GFAP-positive cells.	Metformin	19-28	glial fibrillary acidic protein	Mus musculus	130-134
31450493-0	2019	Resveratrol and Metformin Recover Prefrontal Cortex AMPK Activation in Diet-Induced Obese Mice but Reduce BDNF and Synaptophysin Protein Content.	Metformin	16-25	brain derived neurotrophic factor	Mus musculus	106-110
31450493-0	2019	Resveratrol and Metformin Recover Prefrontal Cortex AMPK Activation in Diet-Induced Obese Mice but Reduce BDNF and Synaptophysin Protein Content.	Metformin	16-25	synaptophysin	Mus musculus	115-128
31939444-10	2019	Metformin attenuated transforming growth factor-beta1 induced decrease of E-cadherin and increase of Vimentin proteins.	Metformin	0-9	vimentin	Homo sapiens	101-109
31804919-4	2019	METHODS: Rosuvastatin, digoxin, and metformin were selected as probe substrates of hepatic transporters OATP1B1, OATP1B3, BCRP, P-gp, and OCT1.	Metformin	36-45	solute carrier organic anion transporter family member 1B1	Homo sapiens	104-111
31804919-4	2019	METHODS: Rosuvastatin, digoxin, and metformin were selected as probe substrates of hepatic transporters OATP1B1, OATP1B3, BCRP, P-gp, and OCT1.	Metformin	36-45	BCR pseudogene 1	Homo sapiens	122-126
31804919-4	2019	METHODS: Rosuvastatin, digoxin, and metformin were selected as probe substrates of hepatic transporters OATP1B1, OATP1B3, BCRP, P-gp, and OCT1.	Metformin	36-45	phosphoglycolate phosphatase	Homo sapiens	128-132
31804919-12	2019	CONCLUSIONS: These data suggest that rosuvastatin and metformin can be administered as a cocktail to evaluate the function of OATP1B1, OATP1B3, BCRP, and OCT1 in SCHH, and that digoxin may not be an ideal component of such a cocktail.	Metformin	54-63	solute carrier organic anion transporter family member 1B1	Homo sapiens	126-133
31804919-12	2019	CONCLUSIONS: These data suggest that rosuvastatin and metformin can be administered as a cocktail to evaluate the function of OATP1B1, OATP1B3, BCRP, and OCT1 in SCHH, and that digoxin may not be an ideal component of such a cocktail.	Metformin	54-63	BCR pseudogene 1	Homo sapiens	144-148
30218721-0	2019	Metformin ameliorates Ox-LDL-induced foam cell formation in raw264.7 cells by promoting ABCG-1 mediated cholesterol efflux.	Metformin	0-9	ATP binding cassette subfamily G member 1	Mus musculus	88-94
30218721-8	2019	KEY FINDINGS: Our results showed that metformin decreased oxidized low-density lipoprotein (Ox-LDL)-induced cholesterol accumulation and foam cell formation by increasing cholesterol efflux to HDL, which was associated with an upregulation of ABC transporter ABCG-1.	Metformin	38-47	ATP binding cassette subfamily G member 1	Mus musculus	259-265
30414431-6	2019	KEY FINDINGS: Metformin improved osteoblast differentiation, reduced apoptosis in hyperglycemic osteoblasts, and inhibited TLR4, MyD88 and NF-kappaB expression in a dose-dependent manner.	Metformin	14-23	MYD88, innate immune signal transduction adaptor	Rattus norvegicus	129-134
30414431-9	2019	Metformin increased ALP and OCN secretion, enhanced BMP-2 expression, improved bone mineral density (BMD), and decreased TLR4, MyD88 and NF-kappaB levels in the femur tissues of diabetic rats.	Metformin	0-9	MYD88, innate immune signal transduction adaptor	Rattus norvegicus	127-132
30414431-10	2019	SIGNIFICANCE: Taken together our experimentation support the hypothesis that metformin may alleviate hyperglycemia-induced apoptosis and differentiation suppression in osteoblasts by inhibiting the TLR4/MyD88/NF-kappaB signaling pathway.	Metformin	77-86	MYD88, innate immune signal transduction adaptor	Rattus norvegicus	203-208
29909574-9	2019	Significant downregulation of mRNA expression of SREBP-1c in the liver, white as well as brown adipose tissues (P &lt; 0.001) and different patterns of mRNA expression of VDR gene in pancreas and white adipose tissue were observed in rats treated with alfacalcidol solely or in combination with metformin.	Metformin	295-304	vitamin D receptor	Rattus norvegicus	171-174
30025915-14	2018	Furthermore, metformin promoted AMP-activated protein kinase (AMPK) phosphorylation but inhibited insulin-like growth factor-1 receptor (IGF-1R) expression, protein kinase B (PKB/AKT) phosphorylation and mammalian target of rapamycin (mTOR) phosphorylation.	Metformin	13-22	protein tyrosine kinase 2 beta	Homo sapiens	157-173
30025915-16	2018	We conclude that metformin inhibits cell proliferation and induces apoptosis in AtT20 cells by activating AMPK/mTOR and inhibiting IGF-1R/AKT/mTOR signaling pathways.	Metformin	17-26	mechanistic target of rapamycin kinase	Mus musculus	111-115
30025915-16	2018	We conclude that metformin inhibits cell proliferation and induces apoptosis in AtT20 cells by activating AMPK/mTOR and inhibiting IGF-1R/AKT/mTOR signaling pathways.	Metformin	17-26	mechanistic target of rapamycin kinase	Mus musculus	142-146
30545422-6	2018	The whole-genome DNA methylation analysis in total revealed 125 differentially methylated CpGs, of which 11 CpGs and their associated genes with the most consistent changes in the DNA methylation profile were selected: POFUT2, CAMKK1, EML3, KIAA1614, UPF1, MUC4, LOC727982, SIX3, ADAM8, SNORD12B, VPS8, and several differentially methylated regions as novel potential epigenetic targets of metformin.	Metformin	390-399	protein O-fucosyltransferase 2	Homo sapiens	219-225
30537987-11	2018	AMPK activation by aspirin and metformin effectively abrogated the statin-induced aberrant upregulation of HMGCR and sensitized these resistant cells to fluvastatin.	Metformin	31-40	3-hydroxy-3-methylglutaryl-CoA reductase	Homo sapiens	107-112
30540938-0	2018	Dual Inhibition of the Lactate Transporters MCT1 and MCT4 Is Synthetic Lethal with Metformin due to NAD+ Depletion in Cancer Cells.	Metformin	83-92	solute carrier family 16 member 3	Homo sapiens	53-57
30651935-0	2018	Metformin alters H2A.Z dynamics and regulates androgen dependent prostate cancer progression.	Metformin	0-9	H2A.Z variant histone 1	Homo sapiens	17-22
30651935-5	2018	We provide data showing that metformin epigenetically targets PCa by altering the levels and gene binding dynamics of histone variant H2A.Z.	Metformin	29-38	H2A.Z variant histone 1	Homo sapiens	134-139
30651935-6	2018	Moreover, we show that the increase in H2A.Z upon metformin treatment occurs preferentially due to H2A.Z.1 isoform.	Metformin	50-59	H2A.Z variant histone 1	Homo sapiens	39-44
30651935-6	2018	Moreover, we show that the increase in H2A.Z upon metformin treatment occurs preferentially due to H2A.Z.1 isoform.	Metformin	50-59	H2A.Z variant histone 1	Homo sapiens	99-106
30651935-7	2018	Chromatin immunoprecipitation (ChIP)-RT PCR analysis indicates that metformin treatment results in an increased H2A.Z occupancy on the androgen receptor (AR) and AR-regulated genes that is more prominent in the androgen dependent AR positive LNCaP cells.	Metformin	68-77	H2A.Z variant histone 1	Homo sapiens	112-117
30651935-9	2018	Based on preliminary data with an EZH2-specific inhibitor, we suggest that the effects of metformin on the early stages of PCa may involve both EZH2 and H2A.Z through the alteration of different molecular pathways.	Metformin	90-99	H2A.Z variant histone 1	Homo sapiens	153-158
30646315-18	2018	Clinicians may consider prescribing GLP-1 receptor agonists, SGLT-2 inhibitors, or DPP-4 inhibitors more routinely after metformin rather than sulfonylureas or basal insulin.	Metformin	121-130	dipeptidyl peptidase 4	Homo sapiens	83-88
30584280-7	2018	Metformin reduced the sterol regulatory element-binding protein-2 (SREBP-2) and its downstream target proteins and increased low-density lipoprotein receptor (LDLR) levels.	Metformin	0-9	low density lipoprotein receptor	Homo sapiens	125-157
30584280-7	2018	Metformin reduced the sterol regulatory element-binding protein-2 (SREBP-2) and its downstream target proteins and increased low-density lipoprotein receptor (LDLR) levels.	Metformin	0-9	low density lipoprotein receptor	Homo sapiens	159-163
30584280-8	2018	Conclusion: Our preliminary results demonstrate that metformin as a first-line and initial medication suppresses the synthesis of SREBP-2 and upregulates LDLR, and consequently decreases cholesterol production via activation of AMPK, at least partly.	Metformin	53-62	low density lipoprotein receptor	Homo sapiens	154-158
30509271-2	2018	Metformin and recent antidiabetic drugs, SGLT2 inhibitors, reduce cardiovascular events.	Metformin	0-9	solute carrier family 5 member 2	Homo sapiens	41-46
30372835-13	2018	Compared to the control, Metformin blunted the expression of VEGF subtypes and directed cells to energy status by induction of PRKAA1, PRKAB2, and PRKAG1 genes (p &lt; 0.05).	Metformin	25-34	protein kinase AMP-activated non-catalytic subunit gamma 1	Homo sapiens	147-153
30088260-10	2018	The oncogenic microRNAs miR-21 and miR-155 were found to be downregulated by metformin, which may be correlated with the suppression of cell proliferation and/or migration.	Metformin	77-86	microRNA 21	Homo sapiens	24-30
30088260-14	2018	Finally, we found that metformin may modulate the pro-apoptotic Bax, anti-apoptotic Bcl-2, MMP-2, MMP-9, miR-21 and miR-155 expression levels.	Metformin	23-32	microRNA 21	Homo sapiens	105-111
30219950-6	2018	Three scenarios were designed for the prescribing pattern for SGLT-2 inhibitors: (1) monotherapy, (2) metformin-based (m-based) drug prescriptions, and (3) metformin and sulfonylurea-based (m-s-based) drug prescriptions.	Metformin	102-111	solute carrier family 5 member 2	Homo sapiens	62-68
30219950-6	2018	Three scenarios were designed for the prescribing pattern for SGLT-2 inhibitors: (1) monotherapy, (2) metformin-based (m-based) drug prescriptions, and (3) metformin and sulfonylurea-based (m-s-based) drug prescriptions.	Metformin	156-165	solute carrier family 5 member 2	Homo sapiens	62-68
29656591-8	2018	The inhibitor of AMPK, compound C, could block the EPO-induced autophagy and beneficial action on SCI, whereas the activator of AMPK, metformin, could mimic the effects of EPO.	Metformin	134-143	erythropoietin	Rattus norvegicus	172-175
30307719-12	2018	Metformin combined with CO-1686 synergistically inhibited the p-IKBalpha, p-IKKalpha/beta, p50, and p65.	Metformin	0-9	inhibitor of nuclear factor kappa B kinase subunit beta	Homo sapiens	76-89
29920623-0	2018	Synergistic Anti-proliferative Effects of Metformin and Silibinin Combination on T47D Breast Cancer Cells via hTERT and Cyclin D1 Inhibition.	Metformin	42-51	telomerase reverse transcriptase	Homo sapiens	110-115
30242842-5	2018	Further, metformin was shown to inhibit FcepsilonR1- and AhR-mediated passive cutaneous anaphylaxis (PCA) in vivo, reversible by a S1P receptor 2 antagonist, JTE-013.	Metformin	9-18	sphingosine-1-phosphate receptor 2	Homo sapiens	131-145
30388519-10	2018	The effects of piperine were mediated by blocking AMPK activation, and the AMPK agonist metformin bypassed the activities of piperine, and resumed pyroptosis as well as the activation on NLRP3 inflammasome.	Metformin	88-97	NLR family, pyrin domain containing 3	Mus musculus	187-192
30733798-0	2018	Interaction of rs316019 variants of SLC22A2 with metformin and other drugs- an in silico analysis.	Metformin	49-58	solute carrier family 22 member 2	Homo sapiens	36-43
30733798-5	2018	The 270S form of SLC22A2 clears metformin from circulation at much reduced level compared to the 270A form.	Metformin	32-41	solute carrier family 22 member 2	Homo sapiens	17-24
30409193-12	2018	CONCLUSIONS: Our results highlight an unexpected adverse effect of metformin-induced MSC apoptosis through AMPK-mediated mTOR suppression, which is attenuated by an AMPK inhibitor.	Metformin	67-76	mechanistic target of rapamycin kinase	Mus musculus	121-125
29902536-10	2018	By contrast, activation of AMPK with metformin and AICAR blocked AldoA function during cardiomyocyte hypertrophy.	Metformin	37-46	aldolase A, fructose-bisphosphate	Mus musculus	65-70
30037614-11	2018	Metformin promotes AMPK-dependent telomerase activation (critical for telomere maintenance) and induces activation of the endonuclease RAG1 (promotes DNA cleavage and transposition) via AMPK.	Metformin	0-9	recombination activating 1	Homo sapiens	135-139
30053447-6	2018	Specifically, metformin showed an anti-pancreatic stellate cells (PSCs) effect via decreasing the expression of sonic hedgehog (SHH) and then sparked some downstream effects, for example, inhibiting the production of vascular endothelial growth factor (VEGF) in the tumor microenvironment, reducing the formation of tumor neovascularization, attenuating the desmoplastic reaction and enhancing the antitumor effect of gemcitabine.	Metformin	14-23	sonic hedgehog	Mus musculus	112-126
30053447-6	2018	Specifically, metformin showed an anti-pancreatic stellate cells (PSCs) effect via decreasing the expression of sonic hedgehog (SHH) and then sparked some downstream effects, for example, inhibiting the production of vascular endothelial growth factor (VEGF) in the tumor microenvironment, reducing the formation of tumor neovascularization, attenuating the desmoplastic reaction and enhancing the antitumor effect of gemcitabine.	Metformin	14-23	sonic hedgehog	Mus musculus	128-131
30171812-0	2018	Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway.	Metformin	23-32	cellular communication network factor 1	Homo sapiens	108-124
30171812-0	2018	Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway.	Metformin	23-32	cellular communication network factor 1	Homo sapiens	126-131
30171812-9	2018	RESULTS Our results indicated that treatment of ovarian cancer cells with metformin caused significant downregulation of Cyr61 protein expression levels ultimately favoring apoptosis.	Metformin	74-83	cellular communication network factor 1	Homo sapiens	121-126
30171812-12	2018	Conversely the extracellular supplementation of recombinant Cyr61 attenuates the cytotoxic properties of metformin in ovarian cancer cells.	Metformin	105-114	cellular communication network factor 1	Homo sapiens	60-65
30171812-13	2018	CONCLUSIONS Taken together, we concluded that metformin exhibits anticancer effects and Cyr61 acts as a direct target for metformin in ovarian cancer cells.	Metformin	122-131	cellular communication network factor 1	Homo sapiens	88-93
30118675-3	2018	(2018) revealed that the anti-diabetic drug metformin induces ERAD of programmed death ligand (PD-L1), which attenuates tumor growth.	Metformin	44-53	CD274 molecule	Homo sapiens	95-100
30118680-0	2018	Metformin Promotes Antitumor Immunity via Endoplasmic-Reticulum-Associated Degradation of PD-L1.	Metformin	0-9	CD274 molecule	Homo sapiens	90-95
30118680-3	2018	Here, we show that metformin increases CTL activity by reducing the stability and membrane localization of programmed death ligand-1 (PD-L1).	Metformin	19-28	CD274 molecule	Homo sapiens	107-132
30118680-3	2018	Here, we show that metformin increases CTL activity by reducing the stability and membrane localization of programmed death ligand-1 (PD-L1).	Metformin	19-28	CD274 molecule	Homo sapiens	134-139
30118680-4	2018	Furthermore, we discover that AMP-activated protein kinase (AMPK) activated by metformin directly phosphorylates S195 of PD-L1.	Metformin	79-88	CD274 molecule	Homo sapiens	121-126
30118680-6	2018	Consistently, tumor tissues from metformin-treated breast cancer patients exhibit reduced PD-L1 levels with AMPK activation.	Metformin	33-42	CD274 molecule	Homo sapiens	90-95
30118680-7	2018	Blocking the inhibitory signal of PD-L1 by metformin enhances CTL activity against cancer cells.	Metformin	43-52	CD274 molecule	Homo sapiens	34-39
30118680-8	2018	Our findings identify a new regulatory mechanism of PD-L1 expression through the ERAD pathway and suggest that the metformin-CTLA4 blockade combination has the potential to increase the efficacy of immunotherapy.	Metformin	115-124	CD274 molecule	Homo sapiens	52-57
30118680-8	2018	Our findings identify a new regulatory mechanism of PD-L1 expression through the ERAD pathway and suggest that the metformin-CTLA4 blockade combination has the potential to increase the efficacy of immunotherapy.	Metformin	115-124	cytotoxic T-lymphocyte associated protein 4	Homo sapiens	125-130
29969038-6	2018	Moreover, metformin alleviated LPS-induced NF-kappaB phosphorylation, promoted Nrf2 nuclear translocation, and increased the expression of the antioxidative genes (HO-1 and NQO-1), leading to reduced intestinal ROS content.	Metformin	10-19	heme oxygenase 1	Homo sapiens	164-168
29658305-5	2018	Metformin administration restored succinate dehydrogenase and lactate dehydrogenase activity and associated ROS production and OMP content to the level of intact rats, with predominant activation of superoxide dismutase (SOD) and glutathione reductase (GR).	Metformin	0-9	olfactory marker protein	Rattus norvegicus	127-130
29658305-5	2018	Metformin administration restored succinate dehydrogenase and lactate dehydrogenase activity and associated ROS production and OMP content to the level of intact rats, with predominant activation of superoxide dismutase (SOD) and glutathione reductase (GR).	Metformin	0-9	glutathione-disulfide reductase	Rattus norvegicus	230-251
29658305-5	2018	Metformin administration restored succinate dehydrogenase and lactate dehydrogenase activity and associated ROS production and OMP content to the level of intact rats, with predominant activation of superoxide dismutase (SOD) and glutathione reductase (GR).	Metformin	0-9	glutathione-disulfide reductase	Rattus norvegicus	253-255
29859833-7	2018	In addition, co-administration of the mTOR activator 3BDO but not the sirtuin 1 inhibitor EX-527 abolished the effects of metformin on IL-6 induction and pulmonary lesions.	Metformin	122-131	mechanistic target of rapamycin kinase	Mus musculus	38-42
29859833-9	2018	These data suggest that metformin might provide anti-inflammatory benefits in endotoxemia-induced inflammatory lung injury via restoring AMPK-dependent suppression of mTOR.	Metformin	24-33	mechanistic target of rapamycin kinase	Mus musculus	167-171
29946054-4	2018	Backward stepwise multiple linear regression analysis identified PCSK9 concentrations as a positive predictor of TRL apoB-48 production rate (standard beta = +0.20, P = 0.007) independent of BMI, age, T2D/metformin use, dietary fat intake during the kinetic study, and fasting concentrations of TGs, insulin, glucose, LDL cholesterol, or C-reactive protein.	Metformin	205-214	proprotein convertase subtilisin/kexin type 9	Homo sapiens	65-70
30258965-11	2018	Moreover, the signal axis of Rarb/Runx3/Col6a1 is pharmaceutically accessible to a widely used antidiabetic substance, metformin, and Rar modulator.	Metformin	119-128	RUNX family transcription factor 3	Homo sapiens	34-39
30258965-11	2018	Moreover, the signal axis of Rarb/Runx3/Col6a1 is pharmaceutically accessible to a widely used antidiabetic substance, metformin, and Rar modulator.	Metformin	119-128	collagen type VI alpha 1 chain	Homo sapiens	40-46
30045688-9	2018	Finally, KDM individuals on metformin treatment exhibited significantly lower levels of MMP-1, - 2, - 3, - 7, - 9 and - 12 at baseline and of MMP-7 post-treatment.	Metformin	28-37	matrix metallopeptidase 1	Homo sapiens	88-122
30045688-9	2018	Finally, KDM individuals on metformin treatment exhibited significantly lower levels of MMP-1, - 2, - 3, - 7, - 9 and - 12 at baseline and of MMP-7 post-treatment.	Metformin	28-37	matrix metallopeptidase 7	Homo sapiens	142-147
30008267-10	2018	Weight loss from baseline was greatest in patients treated with metformin plus either an SGLT-2 inhibitor (-4.2 kg) or a DPP-4 inhibitor (-1.5 kg).	Metformin	64-73	solute carrier family 5 member 2	Homo sapiens	89-95
30008267-12	2018	CONCLUSIONS: In this population-based cohort, all second-line therapies added to metformin monotherapy improved glycaemic control, but the lowest treatment change/discontinuation rate and most sustained weight loss was seen with patients receiving metformin plus an SGLT-2 inhibitor.	Metformin	248-257	solute carrier family 5 member 2	Homo sapiens	266-272
29704494-11	2018	In conclusion, this study provides evidence that metformin can prevent the MALAT1/miR-142-3p sponge from developing anti-neoplastic properties in human cervical cancer cells and cervical cancer cell xenografts in nude mice.	Metformin	49-58	metastasis associated lung adenocarcinoma transcript 1	Homo sapiens	75-81
29853564-4	2018	This study was undertaken to assess the possibility that metformin induces Abcg5 and Abcg8 expression in liver and to elucidate the underlying mechanisms.	Metformin	57-66	ATP binding cassette subfamily G member 8	Mus musculus	85-90
29933869-1	2018	Metformin (MET) has possibilities to be utilized as an adjunct of tuberculosis (TB) therapy for controlling the growth of Mycobacterium tuberculosis (M. tuberculosis).	Metformin	0-9	SAFB like transcription modulator	Homo sapiens	11-14
29984503-5	2018	The cardiovascular benefits of SGLT-2 inhibitors and some glucagon-like peptide-1 receptor agonists suggest that they may be the preferred choice, usually as an add-on to metformin, for patients with type 2 diabetes mellitus at high cardiovascular risk.	Metformin	171-180	solute carrier family 5 member 2	Homo sapiens	31-37
29039022-10	2018	Metformin globally normalized the increased glycogen synthase kinase 3beta activity induced by chronic treatment of L-DOPA in a manner associated with Akt activation in unilaterally 6-OHDA-lesioned mice.	Metformin	0-9	glycogen synthase kinase 3 beta	Mus musculus	44-74
29061071-3	2018	Leukocytes from both groups of T2D patients exhibited increased protein levels of 78-kDa glucose-regulated protein (GRP78) with respect to controls, whereas activating transcription factor 6 (ATF6) was enhanced specifically in nonmetformin-treated T2D, and (s-xbp1) and phosphorylated eukaryotic initiation factor 2alpha (p-eIF2alpha) increased only in the metformin-treated group.	Metformin	230-239	activating transcription factor 6	Homo sapiens	157-190
29061071-3	2018	Leukocytes from both groups of T2D patients exhibited increased protein levels of 78-kDa glucose-regulated protein (GRP78) with respect to controls, whereas activating transcription factor 6 (ATF6) was enhanced specifically in nonmetformin-treated T2D, and (s-xbp1) and phosphorylated eukaryotic initiation factor 2alpha (p-eIF2alpha) increased only in the metformin-treated group.	Metformin	230-239	activating transcription factor 6	Homo sapiens	192-196
29061071-3	2018	Leukocytes from both groups of T2D patients exhibited increased protein levels of 78-kDa glucose-regulated protein (GRP78) with respect to controls, whereas activating transcription factor 6 (ATF6) was enhanced specifically in nonmetformin-treated T2D, and (s-xbp1) and phosphorylated eukaryotic initiation factor 2alpha (p-eIF2alpha) increased only in the metformin-treated group.	Metformin	230-239	X-box binding protein 1	Homo sapiens	260-264
29061071-5	2018	Our observations raise the question of whether metformin treatment could reduce oxidative stress and act as an ER stress modulator in T2D patients by promoting an adaptive unfolded protein response (s-xbp1 and p-eIF2alpha) in their leukocytes; this was in contrast with nonmetformin-treated patients whose response could be driven by the ATF6-dependent pro-apoptotic pathway.	Metformin	47-56	X-box binding protein 1	Homo sapiens	201-205
29061071-5	2018	Our observations raise the question of whether metformin treatment could reduce oxidative stress and act as an ER stress modulator in T2D patients by promoting an adaptive unfolded protein response (s-xbp1 and p-eIF2alpha) in their leukocytes; this was in contrast with nonmetformin-treated patients whose response could be driven by the ATF6-dependent pro-apoptotic pathway.	Metformin	47-56	activating transcription factor 6	Homo sapiens	338-342
29679571-0	2018	Metformin ameliorates TGF-beta1-induced osteoblastic differentiation of human aortic valve interstitial cells by inhibiting beta-catenin signaling.	Metformin	0-9	catenin beta 1	Homo sapiens	124-136
29679571-4	2018	Our results showed that metformin ameliorated TGF-beta1-induced production of osteogenic proteins Runx2 and osteopontin as well as calcium deposition in the cultured human AVICs.	Metformin	24-33	secreted phosphoprotein 1	Homo sapiens	108-119
29679571-6	2018	Moreover, metformin inhibited the TGF-beta1-induced activation of beta-catenin, and beta-catenin siRNA blocked TGF-beta1-induced osteoblastic differentiation of AVICs.	Metformin	10-19	catenin beta 1	Homo sapiens	66-78
29679571-8	2018	In conclusion, our results suggest a beneficial effect of metformin based on the prevention of osteoblastic differentiation of human AVICs via inhibition of beta-catenin, which indicates the therapeutic potential of metformin for CAVD.	Metformin	58-67	catenin beta 1	Homo sapiens	157-169
29679571-8	2018	In conclusion, our results suggest a beneficial effect of metformin based on the prevention of osteoblastic differentiation of human AVICs via inhibition of beta-catenin, which indicates the therapeutic potential of metformin for CAVD.	Metformin	216-225	catenin beta 1	Homo sapiens	157-169
29790415-0	2018	A gene variant near ATM affects the response to metformin and metformin plasma levels: a post hoc analysis of an RCT.	Metformin	48-57	ATM serine/threonine kinase	Homo sapiens	20-23
29790415-0	2018	A gene variant near ATM affects the response to metformin and metformin plasma levels: a post hoc analysis of an RCT.	Metformin	62-71	ATM serine/threonine kinase	Homo sapiens	20-23
29790415-4	2018	RESULTS: rs11212617 (ATM) was associated with an improved Z score and a lower metformin plasma concentration.	Metformin	78-87	ATM serine/threonine kinase	Homo sapiens	21-24
29790415-6	2018	CONCLUSION: The ATM SNP rs11212617 significantly affected the effect of metformin and metformin plasma concentration.	Metformin	72-81	ATM serine/threonine kinase	Homo sapiens	16-19
29790415-6	2018	CONCLUSION: The ATM SNP rs11212617 significantly affected the effect of metformin and metformin plasma concentration.	Metformin	86-95	ATM serine/threonine kinase	Homo sapiens	16-19
30322471-5	2018	Dipeptidyl peptidase-4 inhibitors are considered as second-line drugs (and as first-line drugs if metformin is contraindicated or poorly tolerated).	Metformin	98-107	dipeptidyl peptidase 4	Homo sapiens	0-22
29880175-5	2018	Plasminogen activator inhibitor-1 levels decreased 41.34% in the metformin group.	Metformin	65-74	serpin family E member 1	Homo sapiens	0-33
29795113-8	2018	Our results, for the first time, presents evidence that the miR-570-3p-mediated suppression of LCMR1 and ATG12 is involved in the metformin-induced inhibition of metastasis in osteosarcoma cells.	Metformin	130-139	microRNA 570	Homo sapiens	60-67
29394501-11	2018	Moreover, co-treatment with T317 and metformin improved triglyceride metabolism by inducing expression of adipose triglyceride lipase, hormone-sensitive lipase, PPARalpha and carnitine acetyltransferase and by inhibiting acyl-CoA:diacylglycerol acyltransferase 1 expression.	Metformin	37-46	patatin-like phospholipase domain containing 2	Mus musculus	106-133
29601127-0	2018	LKB1 obliterates Snail stability and inhibits pancreatic cancer metastasis in response to metformin treatment.	Metformin	90-99	serine/threonine kinase 11	Homo sapiens	0-4
29601127-6	2018	Notably, metformin could increase Snail protein ubiquitination via augmenting the location of LKB1 at cytoplasm as well as increasing LKB1 expression.	Metformin	9-18	serine/threonine kinase 11	Homo sapiens	94-98
29601127-6	2018	Notably, metformin could increase Snail protein ubiquitination via augmenting the location of LKB1 at cytoplasm as well as increasing LKB1 expression.	Metformin	9-18	serine/threonine kinase 11	Homo sapiens	134-138
29601127-8	2018	Targeting the LKB1/FBXL14/Snail axis may represent a promising therapeutic strategy and metformin might be beneficial for PC therapy through activating the LKB1-mediated Snail ubiquitination pathway.	Metformin	88-97	serine/threonine kinase 11	Homo sapiens	156-160
29555409-3	2018	We hypothesized that to effectively enhance osteogenic differentiation, and ultimately bone regeneration, metformin must gain access into functional OCT-expressing MSCs.	Metformin	106-115	plexin A2	Homo sapiens	149-152
29555409-8	2018	CONCLUSIONS: Our findings indicate that functional OCT expression in UC-MSCs is a biological prerequisite that facilitates the intracellular uptake of metformin to induce an osteogenic effect.	Metformin	151-160	plexin A2	Homo sapiens	51-54
29535146-4	2018	In vivo and in vitro studies of the effects of metformin on the regulation of the uterine P4 signaling pathway under PCOS conditions showed that metformin directly inhibits the expression of PGR and ER along with the regulation of several genes that are targeted dependently or independently of PGR-mediated uterine implantation.	Metformin	145-154	progesterone receptor	Rattus norvegicus	191-194
29535146-4	2018	In vivo and in vitro studies of the effects of metformin on the regulation of the uterine P4 signaling pathway under PCOS conditions showed that metformin directly inhibits the expression of PGR and ER along with the regulation of several genes that are targeted dependently or independently of PGR-mediated uterine implantation.	Metformin	145-154	progesterone receptor	Rattus norvegicus	295-298
29535146-5	2018	Functionally, metformin treatment corrected the abnormal expression of cell-specific PGR and ER and some PGR-target genes in PCOS-like rats with implantation.	Metformin	14-23	progesterone receptor	Rattus norvegicus	85-88
29535146-5	2018	Functionally, metformin treatment corrected the abnormal expression of cell-specific PGR and ER and some PGR-target genes in PCOS-like rats with implantation.	Metformin	14-23	progesterone receptor	Rattus norvegicus	105-108
29535146-6	2018	Additionally, we documented how metformin contributes to the regulation of the PGR-associated MAPK/ERK/p38 signaling pathway in the PCOS-like rat uterus.	Metformin	32-41	progesterone receptor	Rattus norvegicus	79-82
29512021-11	2018	We also determined that metformin exposure leads to increased production of collagen I-III and decreased activation of NF-kB(p65) activity.	Metformin	24-33	v-rel reticuloendotheliosis viral oncogene homolog A (avian)	Mus musculus	125-128
29512021-12	2018	The data are consistent with the observation that metformin has a protective effect in this in vitro model of aging 3T3 fibroblasts under high glucose conditions inducing cell proliferation, collagen I and III production, protection from apoptosis, and reducing NF-kB(p65) activity.	Metformin	50-59	v-rel reticuloendotheliosis viral oncogene homolog A (avian)	Mus musculus	268-271
30302331-2	2018	BGR-34 provides an effective treatment option for adults with type 2 diabetes who have been inadequately controlled on lifestyle with or without other oral hypoglycemic agents (OHGAs) such as metformin, sulfonylurea, or a glitazones.	Metformin	192-201	C-type lectin domain containing 7A	Homo sapiens	0-3
29549573-10	2018	The rate of HF among AE reports for DPP4is was modestly moderated by the concomitant use of metformin (- 15%) and strongly moderated by the concomitant use of SGLT2 inhibitors (- 63%), even after excluding competing AEs.	Metformin	92-101	dipeptidyl peptidase 4	Homo sapiens	36-40
29460133-6	2018	In the subunit of metformin, along with the suppression of IR, the level of prostatic hyperplasia and the expression of IGF-1 pathway have both decreased (P &lt; 0.05).	Metformin	18-27	insulin-like growth factor 1	Rattus norvegicus	120-125
29460133-9	2018	The application of metformin can suppress the expression of IGF-1 and IGF-1R, thus preventing the promotive effect of IR on prostate tissue in animal model of MetS.	Metformin	19-28	insulin-like growth factor 1	Rattus norvegicus	60-65
29375082-6	2018	Treatment with SGLT2 inhibitors as add-on to metformin and sulfonylurea was also associated with significant reductions in blood pressure and triglycerides and increase in high-density lipoprotein-cholesterol.	Metformin	45-54	solute carrier family 5 member 2	Homo sapiens	15-20
29496445-6	2018	Then, we revealed that metformin inhibits ISC aging phenotypes in Atg6-dependent manner.	Metformin	23-32	Autophagy-related 6	Drosophila melanogaster	66-70
29496445-7	2018	Taken together, our study suggests that Atg6 is required for the inhibitory effect of metformin on ISC aging, providing an intervention mechanism of metformin on adult stem cell aging.	Metformin	86-95	Autophagy-related 6	Drosophila melanogaster	40-44
29496445-7	2018	Taken together, our study suggests that Atg6 is required for the inhibitory effect of metformin on ISC aging, providing an intervention mechanism of metformin on adult stem cell aging.	Metformin	149-158	Autophagy-related 6	Drosophila melanogaster	40-44
28686850-0	2018	The effect of metformin treatment on endoplasmic reticulum (ER) stress induced by status epilepticus (SE) via the PERK-eIF2alpha-CHOP pathway.	Metformin	14-23	DNA-damage inducible transcript 3	Rattus norvegicus	129-133
28686850-4	2018	In this study, we analyzed the effect of metformin on ER stress via the pro-apoptotic protein kinase RNA-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2alpha (eIF2alpha)-C/EBP homologous protein (CHOP) pathway.	Metformin	41-50	DNA-damage inducible transcript 3	Rattus norvegicus	194-218
28686850-4	2018	In this study, we analyzed the effect of metformin on ER stress via the pro-apoptotic protein kinase RNA-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2alpha (eIF2alpha)-C/EBP homologous protein (CHOP) pathway.	Metformin	41-50	DNA-damage inducible transcript 3	Rattus norvegicus	220-224
28686850-11	2018	At 6 hours, CHOP expression was significantly reduced in salubrinal, GSK2656157 and metformin groups versus SE group.	Metformin	84-93	DNA-damage inducible transcript 3	Rattus norvegicus	12-16
28686850-16	2018	Overall, CHOP expression and apoptosis induced by SE in rats were reduced with metformin.	Metformin	79-88	DNA-damage inducible transcript 3	Rattus norvegicus	9-13
29466360-5	2018	OBJECTIVES: We set out to assess whether combining metformin and esomeprazole would additively reduce sFlt-1 and soluble endoglin secretion and reduce endothelial dysfunction (verses drug alone).	Metformin	51-60	endoglin	Homo sapiens	121-129
29467552-10	2018	Metformin decreased the expression of vascular endothelial growth factor (VEGF) in HSCs through inhibition of hypoxia inducible factor (HIF)-1alpha in both PDGF-BB treatment and hypoxic conditions, and it down-regulated VEGF secretion by HSCs and inhibited HSC-based angiogenesis in hypoxic conditions in vitro.	Metformin	0-9	hypoxia inducible factor 1, alpha subunit	Mus musculus	110-147
24504677-3	2014	The biomolecular characteristics of tumors, such as appropriate expression of organic cation transporters or genetic alterations including p53, K-ras, LKB1, and PI3K may impact metformin"s anticancer efficiency.	Metformin	177-186	KRAS proto-oncogene, GTPase	Homo sapiens	144-149
25142987-0	2014	[Effects of metformin therapy on serum CA125 levels and its related factors in type 2 diabetics].	Metformin	12-21	mucin 16, cell surface associated	Homo sapiens	39-44
25142987-1	2014	OBJECTIVE: To explore the effects of metformin therapy on serum carbohydrate antigen 125 (CA125) levels and its related factors in type 2 diabetics with normal liver and kidney function.	Metformin	37-46	mucin 16, cell surface associated	Homo sapiens	90-95
25142987-5	2014	RESULTS: The CA125 level of metformin group was significantly lower than that of non-metformin group (10.51(8.18, 13.80) vs 11.93(9.05, 15.52) U/ml, P &lt; 0.01) .	Metformin	28-37	mucin 16, cell surface associated	Homo sapiens	13-18
25142987-5	2014	RESULTS: The CA125 level of metformin group was significantly lower than that of non-metformin group (10.51(8.18, 13.80) vs 11.93(9.05, 15.52) U/ml, P &lt; 0.01) .	Metformin	85-94	mucin 16, cell surface associated	Homo sapiens	13-18
25142987-6	2014	The CA125 levels of males aged 30-39 and 50-59 as well as females aged over 50 remarkably decreased after metformin dosing (all P &lt; 0.05).	Metformin	106-115	mucin 16, cell surface associated	Homo sapiens	4-9
25142987-7	2014	The difference of CA125 level between metformin and non-metformin groups in patients with normal BMI and obese females reached statistical significance (all P &lt; 0.05).	Metformin	38-47	mucin 16, cell surface associated	Homo sapiens	18-23
25142987-7	2014	The difference of CA125 level between metformin and non-metformin groups in patients with normal BMI and obese females reached statistical significance (all P &lt; 0.05).	Metformin	56-65	mucin 16, cell surface associated	Homo sapiens	18-23
25142987-8	2014	The correlation analysis showed that serum CA125 level was positively associated with gender, HbA1c, glycated serum albumin, triglyceride, total cholesterol (P &lt; 0.05), but negatively with metformin and creatinine (P &lt; 0.01).	Metformin	192-201	mucin 16, cell surface associated	Homo sapiens	43-48
25142987-9	2014	Multiple stepwise regression analysis further revealed that GA, metformin dosing, gender and total glycerides were independent influencing factors of CA125 concentrations (all P &lt; 0.05).	Metformin	64-73	mucin 16, cell surface associated	Homo sapiens	150-155
25142987-10	2014	CONCLUSION: Metformin dosing is an independent associated factor of serum CA125 levels reduction in type 2 diabetics, especially females.	Metformin	12-21	mucin 16, cell surface associated	Homo sapiens	74-79
24428821-6	2014	Metformin also increased PGC-1alpha in human primary hepatocytes; this effect of metformin was abolished by AMPK inhibitor compound C and sirtuin 1 siRNA.	Metformin	0-9	sirtuin 1	Homo sapiens	138-147
24428821-6	2014	Metformin also increased PGC-1alpha in human primary hepatocytes; this effect of metformin was abolished by AMPK inhibitor compound C and sirtuin 1 siRNA.	Metformin	81-90	sirtuin 1	Homo sapiens	138-147
24428821-8	2014	Whereas metformin increased PGC-1alpha, it down-regulated gluconeogenic genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase).	Metformin	8-17	phosphoenolpyruvate carboxykinase 1, cytosolic	Mus musculus	78-111
24428821-8	2014	Whereas metformin increased PGC-1alpha, it down-regulated gluconeogenic genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase).	Metformin	8-17	phosphoenolpyruvate carboxykinase 1, cytosolic	Mus musculus	113-118
24428821-9	2014	Furthermore, metformin attenuated the increase in PEPCK and G6Pase mRNAs induced by PGC-1alpha overexpression, but did not affect PGC-1alpha-mediated induction of mitochondrial genes.	Metformin	13-22	phosphoenolpyruvate carboxykinase 1, cytosolic	Mus musculus	50-55
24530383-3	2014	Both CP and CPC inhibited the uptake of 1-methyl-4-phenylpyridinium (MPP(+)) and metformin, typical substrates of OCT1, in MDCK-hOCT1 cells with low IC50 (0.307-14.0 muM).	Metformin	81-90	solute carrier family 22 member 1	Rattus norvegicus	114-118
24762064-8	2014	We observed that metformin and pioglitazone attenuated ovarian chemerin expression and improved insulin resistance and abnormal steroid production in PCO rats.	Metformin	17-26	retinoic acid receptor responder 2	Rattus norvegicus	63-71
24762064-9	2014	CONCLUSION: Based on data presented here we concluded that alteration of ovarian chemerin expression may has important role in PCO development and manipulation of chemerin expression or signaling by pioglitazone or metformin can be a novel therapeutic mechanism in the treatment of PCO patients by these drugs.	Metformin	215-224	retinoic acid receptor responder 2	Homo sapiens	81-89
24762064-9	2014	CONCLUSION: Based on data presented here we concluded that alteration of ovarian chemerin expression may has important role in PCO development and manipulation of chemerin expression or signaling by pioglitazone or metformin can be a novel therapeutic mechanism in the treatment of PCO patients by these drugs.	Metformin	215-224	retinoic acid receptor responder 2	Homo sapiens	163-171
24520038-0	2014	Repurposing of metformin and aspirin by targeting AMPK-mTOR and inflammation for pancreatic cancer prevention and treatment.	Metformin	15-24	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	50-54
24520038-6	2014	For metformin, the most important mechanism may involve the inhibition of mTOR signaling via AMP-activated protein kinase (AMPK)-dependent and -independent pathways.	Metformin	4-13	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	93-121
24520038-6	2014	For metformin, the most important mechanism may involve the inhibition of mTOR signaling via AMP-activated protein kinase (AMPK)-dependent and -independent pathways.	Metformin	4-13	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	123-127
24437490-0	2014	Metformin inhibits androgen-induced IGF-IR up-regulation in prostate cancer cells by disrupting membrane-initiated androgen signaling.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	36-42
24437490-3	2014	Metformin exerts complex antitumoral functions in various models and may inhibit CREB activation in hepatocytes.	Metformin	0-9	cAMP responsive element binding protein 1	Homo sapiens	81-85
24437490-4	2014	We, therefore, evaluated whether metformin may affect androgen-dependent IGF-IR up-regulation.	Metformin	33-42	insulin like growth factor 1 receptor	Homo sapiens	73-79
24437490-5	2014	In the AR(+) LNCaP prostate cancer cells, we found that metformin inhibits androgen-induced CRE activity and IGF-IR gene transcription.	Metformin	56-65	insulin like growth factor 1 receptor	Homo sapiens	109-115
24437490-7	2014	Metformin inhibited Ser133-CREB phosphorylation and induced nuclear exclusion of CREB cofactor CRTC2, thus dissociating the CREB-CREB binding protein-CRTC2 complex and blocking its transcriptional activity.	Metformin	0-9	cAMP responsive element binding protein 1	Homo sapiens	27-31
24437490-7	2014	Metformin inhibited Ser133-CREB phosphorylation and induced nuclear exclusion of CREB cofactor CRTC2, thus dissociating the CREB-CREB binding protein-CRTC2 complex and blocking its transcriptional activity.	Metformin	0-9	cAMP responsive element binding protein 1	Homo sapiens	81-85
24437490-7	2014	Metformin inhibited Ser133-CREB phosphorylation and induced nuclear exclusion of CREB cofactor CRTC2, thus dissociating the CREB-CREB binding protein-CRTC2 complex and blocking its transcriptional activity.	Metformin	0-9	CREB regulated transcription coactivator 2	Homo sapiens	95-100
24437490-7	2014	Metformin inhibited Ser133-CREB phosphorylation and induced nuclear exclusion of CREB cofactor CRTC2, thus dissociating the CREB-CREB binding protein-CRTC2 complex and blocking its transcriptional activity.	Metformin	0-9	cAMP responsive element binding protein 1	Homo sapiens	81-85
24437490-7	2014	Metformin inhibited Ser133-CREB phosphorylation and induced nuclear exclusion of CREB cofactor CRTC2, thus dissociating the CREB-CREB binding protein-CRTC2 complex and blocking its transcriptional activity.	Metformin	0-9	cAMP responsive element binding protein 1	Homo sapiens	81-85
24437490-7	2014	Metformin inhibited Ser133-CREB phosphorylation and induced nuclear exclusion of CREB cofactor CRTC2, thus dissociating the CREB-CREB binding protein-CRTC2 complex and blocking its transcriptional activity.	Metformin	0-9	CREB regulated transcription coactivator 2	Homo sapiens	150-155
24437490-8	2014	Similarly to metformin action, CRTC2 silencing inhibited IGF-IR promoter activity.	Metformin	13-22	insulin like growth factor 1 receptor	Homo sapiens	57-63
24437490-11	2014	By inhibiting androgen-dependent IGF-IR up-regulation, metformin reduced IGF-I-mediated proliferation of LNCaP cells.	Metformin	55-64	insulin like growth factor 1 receptor	Homo sapiens	33-39
24437490-12	2014	These results indicate that, in prostate cancer cells, metformin inhibits IGF-I-mediated biological effects by disrupting membrane-initiated AR action responsible for IGF-IR up-regulation and suggest that metformin could represent a useful adjunct to the classical antiandrogen therapy.	Metformin	55-64	insulin like growth factor 1 receptor	Homo sapiens	167-173
24675468-8	2014	Metformin, an activator of AMPK (adenosine monophosphate-activated protein kinase), increased whereas Compound C, an inhibitor of AMPK pathway, reduced the ability of osmotin and adiponectin to protect against ethanol-induced apoptosis.	Metformin	0-9	adiponectin, C1Q and collagen domain containing	Rattus norvegicus	179-190
24638078-7	2014	In addition, metformin treatment caused an increase in the phosphorylation of liver AMP-activated protein kinase (AMPK), which was accompanied by an increase in the phosphorylation of liver acetyl-CoA carboxylase and decreases in the phosphorylation of liver c-Jun N-terminal kinase 1 (JNK1) and in the mRNA levels of lipogenic enzymes and proinflammatory cytokines.	Metformin	13-22	mitogen-activated protein kinase 8	Mus musculus	259-284
24638078-7	2014	In addition, metformin treatment caused an increase in the phosphorylation of liver AMP-activated protein kinase (AMPK), which was accompanied by an increase in the phosphorylation of liver acetyl-CoA carboxylase and decreases in the phosphorylation of liver c-Jun N-terminal kinase 1 (JNK1) and in the mRNA levels of lipogenic enzymes and proinflammatory cytokines.	Metformin	13-22	mitogen-activated protein kinase 8	Mus musculus	286-290
24638078-10	2014	Additionally, in bone marrow-derived macrophages, metformin treatment partially blunted the effects of lipopolysaccharide on inducing the phosphorylation of JNK1 and nuclear factor kappa B (NF-kappaB) p65 and on increasing the mRNA levels of proinflammatory cytokines.	Metformin	50-59	mitogen-activated protein kinase 8	Mus musculus	157-161
24361375-10	2014	Collectively, we show that rosiglitazone and metformin inhibit ILK gene expression through PPARgamma- and AMPKalpha-dependent signaling pathways that are involved in the regulation of AP-2alpha and Sp1 protein expressions.	Metformin	45-54	transcription factor AP-2 alpha	Homo sapiens	184-193
24119262-6	2014	RESULTS: PPARgamma stimulation decreased cerebrovascular collateral growth and recovery of hemodynamic reserve capacity (CVRC controls: 12 +- 7%; pio low: -2 +- 9%; pio high: 1 +- 7%; metformin: 9 +- 13%; sitagliptin: 11 +- 12%), counteracted G-CSF-induced therapeutic arteriogenesis and interfered with EC activation, SMC proliferation, monocyte activation and migration.	Metformin	184-193	peroxisome proliferator-activated receptor gamma	Rattus norvegicus	9-18
24269517-4	2014	Metformin use on treatment related outcomes (TTR: time to recurrence; RFS: recurrence free survival; OS: overall survival) were evaluated using univariate and multivariate modeling.	Metformin	0-9	transthyretin	Homo sapiens	45-48
24252946-0	2014	Metformin represses drug-induced expression of CYP2B6 by modulating the constitutive androstane receptor signaling.	Metformin	0-9	nuclear receptor subfamily 1 group I member 3	Homo sapiens	72-104
24252946-4	2014	We show that metformin could suppress drug-induced expression of CYP2B6 (a typical target gene of CAR) by modulating the phosphorylation status of CAR.	Metformin	13-22	nuclear receptor subfamily 1 group I member 3	Homo sapiens	98-101
24252946-4	2014	We show that metformin could suppress drug-induced expression of CYP2B6 (a typical target gene of CAR) by modulating the phosphorylation status of CAR.	Metformin	13-22	nuclear receptor subfamily 1 group I member 3	Homo sapiens	147-150
24252946-5	2014	In human hepatocytes, metformin robustly suppressed the expression of CYP2B6 induced by both indirect (phenobarbital) and direct CITCO [6-(4-chlorophenyl)imidazo[2,1-b]1,3thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime] activators of human CAR.	Metformin	22-31	nuclear receptor subfamily 1 group I member 3	Homo sapiens	244-247
24252946-6	2014	Mechanistic investigation revealed that metformin specifically enhanced the phosphorylation of threonine-38 of CAR, which blocks CAR nuclear translocation and activation.	Metformin	40-49	nuclear receptor subfamily 1 group I member 3	Homo sapiens	111-114
24252946-6	2014	Mechanistic investigation revealed that metformin specifically enhanced the phosphorylation of threonine-38 of CAR, which blocks CAR nuclear translocation and activation.	Metformin	40-49	nuclear receptor subfamily 1 group I member 3	Homo sapiens	129-132
24252946-7	2014	Moreover, we showed that phosphorylation of CAR by metformin was primarily an AMP-activated protein kinase- and extracellular signal-regulated kinase 1/2-dependent event.	Metformin	51-60	nuclear receptor subfamily 1 group I member 3	Homo sapiens	44-47
24252946-8	2014	Additional two-hybrid and coimmunoprecipitation assays demonstrated that metformin could also disrupt CITCO-mediated interaction between CAR and the steroid receptor coactivator 1 or the glucocorticoid receptor-interacting protein 1.	Metformin	73-82	nuclear receptor subfamily 1 group I member 3	Homo sapiens	137-140
24252946-9	2014	Our results suggest that metformin is a potent repressor of drug-induced CYP2B6 expression through specific inhibition of human CAR activation.	Metformin	25-34	nuclear receptor subfamily 1 group I member 3	Homo sapiens	128-131
24233023-6	2014	Metformin stimulated the nuclear translocation of beta-catenin and TOPflash reporter activity, and gene depletion of beta-catenin or enhancement of mutation of transcription factor 7-like 2 binding site offset GLP1.	Metformin	0-9	catenin (cadherin associated protein), beta 1	Mus musculus	50-62
24257750-5	2014	Metformin also suppressed Sepp1 gene expression in the liver of mice.	Metformin	0-9	selenoprotein P	Mus musculus	26-31
24762600-10	2014	Knockdown of SIRT3 (P &lt; 0.05) reversed the metformin-induced decreases in NF-kappaB p65 and JNK1 and the metformin-induced increase in SOD2 (P &lt; 0.05).	Metformin	108-117	superoxide dismutase 2	Rattus norvegicus	138-142
24791887-11	2014	Conlusion Metformin can suppress the expression of NF-kappaB, MCP-1, ICAM-1 and TGF-beta1 of glomerular MCs induced by high glucose via AMPK activation, which may partly contribute to its reno-protection.	Metformin	10-19	intercellular adhesion molecule 1	Rattus norvegicus	69-75
23848354-5	2014	Films of metformin were prepared by solvent casting method using Hydroxypropyl methylcellulose K15 (HPMC).	Metformin	9-18	keratin 15	Rattus norvegicus	95-98
24603137-3	2014	The aim of this study was to evaluate gene and protein expression of an insulin receptor (IR), insulin-like growth factor-1 (IGF1) receptor (IGF1R) and aromatase in granulosa cells treated with metformin and insulin.	Metformin	194-203	insulin like growth factor 1 receptor	Homo sapiens	95-139
24603137-3	2014	The aim of this study was to evaluate gene and protein expression of an insulin receptor (IR), insulin-like growth factor-1 (IGF1) receptor (IGF1R) and aromatase in granulosa cells treated with metformin and insulin.	Metformin	194-203	insulin like growth factor 1 receptor	Homo sapiens	141-146
24603137-6	2014	RESULTS: IR and IGF1R mRNA expression was significantly enhanced by metformin but was not affected by insulin.	Metformin	68-77	insulin like growth factor 1 receptor	Homo sapiens	16-21
24603137-9	2014	CONCLUSION: A direct effect of metformin on the gene expression of IGF1R, IR and aromatase was observed.	Metformin	31-40	insulin like growth factor 1 receptor	Homo sapiens	67-72
26351208-2	2014	Adenosine 5"-monophosphate-activated protein kinase (AMPK) activators such as metformin have similar actions in keeping with the TSC2/1 pathway linking activation of AMPK to inhibition of mTOR.	Metformin	78-87	TSC complex subunit 2	Homo sapiens	129-133
24107633-9	2013	Mechanisms of metformin action at normal vs. high glucose overlapped but were not identical; for example, metformin reduced IGF-1R expression in both the HER2+ SK-BR-3 and TNBC MDA-MB-468 cell lines more significantly at 5, as compared with 10 mmol/L glucose.	Metformin	14-23	insulin like growth factor 1 receptor	Homo sapiens	124-130
24107633-9	2013	Mechanisms of metformin action at normal vs. high glucose overlapped but were not identical; for example, metformin reduced IGF-1R expression in both the HER2+ SK-BR-3 and TNBC MDA-MB-468 cell lines more significantly at 5, as compared with 10 mmol/L glucose.	Metformin	106-115	insulin like growth factor 1 receptor	Homo sapiens	124-130
23803693-2	2013	Several metformin-induced responses and genes are similar to those observed after knockdown of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 by RNA interference, and we hypothesized that the mechanism of action of metformin in pancreatic cancer cells was due, in part, to downregulation of Sp transcription factors.	Metformin	8-17	Sp4 transcription factor	Homo sapiens	155-158
23803693-2	2013	Several metformin-induced responses and genes are similar to those observed after knockdown of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 by RNA interference, and we hypothesized that the mechanism of action of metformin in pancreatic cancer cells was due, in part, to downregulation of Sp transcription factors.	Metformin	232-241	Sp4 transcription factor	Homo sapiens	155-158
23803693-3	2013	Treatment of Panc1, L3.6pL and Panc28 pancreatic cancer cells with metformin downregulated Sp1, Sp3 and Sp4 proteins and several pro-oncogenic Sp-regulated genes including bcl-2, survivin, cyclin D1, vascular endothelial growth factor and its receptor, and fatty acid synthase.	Metformin	67-76	Sp4 transcription factor	Homo sapiens	104-107
23803693-3	2013	Treatment of Panc1, L3.6pL and Panc28 pancreatic cancer cells with metformin downregulated Sp1, Sp3 and Sp4 proteins and several pro-oncogenic Sp-regulated genes including bcl-2, survivin, cyclin D1, vascular endothelial growth factor and its receptor, and fatty acid synthase.	Metformin	67-76	fatty acid synthase	Homo sapiens	200-276
23803693-5	2013	Metformin also inhibited pancreatic tumor growth and downregulated Sp1, Sp3 and Sp4 in tumors in an orthotopic model where L3.6pL cells were injected directly into the pancreas.	Metformin	0-9	Sp4 transcription factor	Homo sapiens	80-83
23993965-5	2013	Metformin also increases the phosphorylation of p21-activated kinase 1 (PAK1), a direct downstream target of Rac1, dependent on AMPK.	Metformin	0-9	p21 (RAC1) activated kinase 1	Mus musculus	48-70
23993965-5	2013	Metformin also increases the phosphorylation of p21-activated kinase 1 (PAK1), a direct downstream target of Rac1, dependent on AMPK.	Metformin	0-9	p21 (RAC1) activated kinase 1	Mus musculus	72-76
23305245-2	2013	The aim of this study was to investigate the effects of trimethoprim on metformin pharmacokinetics and genetic modulation by organic cation transporter 2 (OCT2) and multidrug and toxin extrusion 1 (MATE1) polymorphisms.	Metformin	72-81	solute carrier family 47 member 1	Homo sapiens	198-203
23946431-0	2013	Metformin increases the novel adipokine adipolin/CTRP12: role of the AMPK pathway.	Metformin	0-9	C1q and TNF related 12	Homo sapiens	40-48
23946431-0	2013	Metformin increases the novel adipokine adipolin/CTRP12: role of the AMPK pathway.	Metformin	0-9	C1q and TNF related 12	Homo sapiens	49-55
23946431-6	2013	We also investigated the ex vivo effect of glucose and metformin on adipolin protein production in human subcutaneous adipose tissue explants.	Metformin	55-64	C1q and TNF related 12	Homo sapiens	68-76
23946431-12	2013	Moreover, glucose profoundly reduced and metformin significantly increased adipolin protein production in human adipose tissue explants respectively.	Metformin	41-50	C1q and TNF related 12	Homo sapiens	75-83
23845075-8	2013	Metformin activates 5-adenosine monophosphate-activated protein kinase (AMPK), that has growth inhibition effects on human cancer cell lines via inhibition of its downstream target mammalian target of rapamycin (mTOR), and decreases the expression of Livin, a protein involved in both cell proliferation and survivalexpressed at high level in neoplastic cell.	Metformin	0-9	baculoviral IAP repeat containing 7	Homo sapiens	251-256
23846817-11	2013	Metformin also reduced FSH-induced phosphorylation of CREB and hence CRE activity, which could potentially disrupt the CREB-CREB-binding protein-CRTC2 coactivator complex that binds to CRE in promoter II of the aromatase gene.	Metformin	0-9	cAMP responsive element binding protein 1	Homo sapiens	54-58
23846817-11	2013	Metformin also reduced FSH-induced phosphorylation of CREB and hence CRE activity, which could potentially disrupt the CREB-CREB-binding protein-CRTC2 coactivator complex that binds to CRE in promoter II of the aromatase gene.	Metformin	0-9	cAMP responsive element binding protein 1	Homo sapiens	119-123
23846817-11	2013	Metformin also reduced FSH-induced phosphorylation of CREB and hence CRE activity, which could potentially disrupt the CREB-CREB-binding protein-CRTC2 coactivator complex that binds to CRE in promoter II of the aromatase gene.	Metformin	0-9	cAMP responsive element binding protein 1	Homo sapiens	119-123
23846817-11	2013	Metformin also reduced FSH-induced phosphorylation of CREB and hence CRE activity, which could potentially disrupt the CREB-CREB-binding protein-CRTC2 coactivator complex that binds to CRE in promoter II of the aromatase gene.	Metformin	0-9	CREB regulated transcription coactivator 2	Homo sapiens	145-150
23889981-10	2013	Metformin treatment also resulted in an increase in eNOS phosphorylation at ser1177.	Metformin	0-9	nitric oxide synthase 3	Rattus norvegicus	52-56
23889981-11	2013	CONCLUSIONS: Metformin treatment increased eNOS phosphorylation and improved erectile function in AngII hypertensive rats by reestablishing normal cavernosal smooth muscle tone.	Metformin	13-22	nitric oxide synthase 3	Rattus norvegicus	43-47
24071688-0	2013	[Effect of metformin on the expression of SIRT1 and UCP2 in rat liver of type 2 diabetes mellitus and nonalcoholic fatty liver].	Metformin	11-20	uncoupling protein 2	Rattus norvegicus	52-56
24071688-1	2013	OBJECTIVE: To observe the effect of metformin on the expression of SIRT1 and UCP2 in rat liver of type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD), and discuss the pathogenesis of T2DM with NAFLD, and the treatment with and possible mechanism of metformin.	Metformin	36-45	uncoupling protein 2	Rattus norvegicus	77-81
24071688-10	2013	After the metformin treatment, the expression of SIRT1 was higher than in group MC (P&lt;0.05), and the expression of UCP2 was lower than in group MC (P&lt;0.05).	Metformin	10-19	uncoupling protein 2	Rattus norvegicus	118-122
24071688-13	2013	Metformin can increase the expression of SIRT1 and reduce the expression of UCP2, with negative correlation between the expression of SIRT1 and UCP2.	Metformin	0-9	uncoupling protein 2	Rattus norvegicus	76-80
24071688-13	2013	Metformin can increase the expression of SIRT1 and reduce the expression of UCP2, with negative correlation between the expression of SIRT1 and UCP2.	Metformin	0-9	uncoupling protein 2	Rattus norvegicus	144-148
23709654-9	2013	In vitro data revealed that metformin inhibited cancer cell growth, activated cAMP-inducible protein kinase (5"-AMP-activated protein kinase [AMPK]), and down-regulated p70S6K/pS6.	Metformin	28-37	taste 2 receptor member 63 pseudogene	Homo sapiens	176-179
23709654-14	2013	In vitro data suggest that p70S6K/pS6 is likely a molecular target of metformin in DTC cells.	Metformin	70-79	taste 2 receptor member 63 pseudogene	Homo sapiens	34-37
23936124-9	2013	AMPK activation by metformin completely reversed the inhibitory effect of glucose on Nampt-Sirt1-PGC-1 alpha and Rev-erb alpha.	Metformin	19-28	nuclear receptor subfamily 1, group D, member 1	Mus musculus	113-126
23660683-0	2013	Metformin inhibits glioma cell U251 invasion by downregulation of fibulin-3.	Metformin	0-9	EGF containing fibulin extracellular matrix protein 1	Homo sapiens	66-75
23660683-3	2013	In the present study, we determined the effect of metformin on the expression of fibulin-3 in U251 Human glioma cells.	Metformin	50-59	EGF containing fibulin extracellular matrix protein 1	Homo sapiens	81-90
23660683-5	2013	Metformin inhibited the expression of fibulin-3 at the transcriptional level.	Metformin	0-9	EGF containing fibulin extracellular matrix protein 1	Homo sapiens	38-47
23660683-6	2013	Moreover, metformin abolished the protein expression of fibulin-3 in a concentration-dependent manner.	Metformin	10-19	EGF containing fibulin extracellular matrix protein 1	Homo sapiens	56-65
23660683-8	2013	Taken together, our results suggest that metformin abolishes fibulin-3 expression and subsequently inhibits invasion of glioma cells.	Metformin	41-50	EGF containing fibulin extracellular matrix protein 1	Homo sapiens	61-70
23651427-2	2013	The goal of this study is to determine whether IRIP regulates the activities of OCT1 and MATE1, and hence the disposition in vivo of their substrate metformin, a therapeutic drug for diabetes and other obesity-related syndromes.	Metformin	149-158	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	80-84
23663483-0	2013	Metformin-mediated growth inhibition involves suppression of the IGF-I receptor signalling pathway in human pancreatic cancer cells.	Metformin	0-9	insulin like growth factor 1 receptor	Homo sapiens	65-79
23663483-9	2013	The anti-proliferative actions of metformin were associated with an activation of AMP-activated protein kinase AMPKThr172 together with an inhibition of the insulin/insulin-like growth factor-I (IGF-I) receptor activation and downstream signalling mediators IRS-1 and phosphorylated Akt.	Metformin	34-43	insulin like growth factor 1 receptor	Homo sapiens	195-210
23225247-8	2013	Furthermore, metformin at 0.01 mM completely suppressed the AGEs-induced upregulation of RAGE and VEGF mRNA levels in MCF-7 cells.	Metformin	13-22	long intergenic non-protein coding RNA 914	Homo sapiens	89-93
23225247-9	2013	An inhibitor of AMP-activated protein kinase, compound C significantly blocked the growth-inhibitory and RAGE and VEGF suppressing effects of metformin in AGEs-exposed MCF-7 cells.	Metformin	142-151	long intergenic non-protein coding RNA 914	Homo sapiens	105-109
23225247-10	2013	Our present study suggests that metformin could inhibit the AGEs-induced growth and VEGF expression in MCF-7 breast cancer cells by suppressing RAGE gene expression via AMP-activated protein kinase pathway.	Metformin	32-41	long intergenic non-protein coding RNA 914	Homo sapiens	144-148
23225247-11	2013	Metformin may protect against breast cancer expansion in diabetic patients by blocking the AGEs-RAGE axis.	Metformin	0-9	long intergenic non-protein coding RNA 914	Homo sapiens	96-100
23315983-0	2013	Visfatin is expressed in human granulosa cells: regulation by metformin through AMPK/SIRT1 pathways and its role in steroidogenesis.	Metformin	62-71	sirtuin 1	Homo sapiens	85-90
23223177-4	2013	Conversely, activation of AMPK by metformin stimulated JNK1-Bcl-2 signaling and disrupted the Beclin1-Bcl-2 complex.	Metformin	34-43	mitogen-activated protein kinase 8	Mus musculus	55-59
23223177-7	2013	Finally, chronic administration of metformin in diabetic mice restored cardiac autophagy by activating JNK1-Bcl-2 pathways and dissociating Beclin1 and Bcl-2.	Metformin	35-44	mitogen-activated protein kinase 8	Mus musculus	103-107
23000260-0	2013	Involvement of ferritin heavy chain in the preventive effect of metformin against doxorubicin-induced cardiotoxicity.	Metformin	64-73	ferritin heavy polypeptide 1	Mus musculus	15-35
23000260-5	2013	The addition of metformin to adult mouse cardiomyocytes (HL-1 cell line) induced both gene and protein expression of the ferritin heavy chain (FHC) in a time-dependent manner.	Metformin	16-25	ferritin heavy polypeptide 1	Mus musculus	121-141
23000260-5	2013	The addition of metformin to adult mouse cardiomyocytes (HL-1 cell line) induced both gene and protein expression of the ferritin heavy chain (FHC) in a time-dependent manner.	Metformin	16-25	ferritin heavy polypeptide 1	Mus musculus	143-146
23000260-6	2013	The silencing of FHC expression with siRNAs inhibited the ability of metformin to protect cardiomyocytes from doxorubicin-induced damage, in terms of the percentage of cell viability, the levels of reactive oxygen species, and the activity of antioxidant enzymes (catalase, glutathione peroxidase, and superoxide dismutase).	Metformin	69-78	ferritin heavy polypeptide 1	Mus musculus	17-20
23000260-7	2013	In addition, metformin induced the activation of NF-kappaB in HL-1 cells, whereas preincubation with SN50, an inhibitor of NF-kappaB, blocked the upregulation of the FHC and the protective effect mediated by metformin.	Metformin	208-217	ferritin heavy polypeptide 1	Mus musculus	166-169
23000260-8	2013	Taken together, these results provide new knowledge on the protective actions of metformin against doxorubicin-induced cardiotoxicity by identifying FHC and NF-kappaB as the major mediators of this beneficial effect.	Metformin	81-90	ferritin heavy polypeptide 1	Mus musculus	149-152
23540700-5	2013	Alterations in metformin-induced longevity by mutation of worm methionine synthase (metr-1) and S-adenosylmethionine synthase (sams-1) imply metformin-induced methionine restriction in the host, consistent with action of this drug as a dietary restriction mimetic.	Metformin	15-24	putative S-adenosylmethionine synthase 1	Caenorhabditis elegans	127-133
23540700-5	2013	Alterations in metformin-induced longevity by mutation of worm methionine synthase (metr-1) and S-adenosylmethionine synthase (sams-1) imply metformin-induced methionine restriction in the host, consistent with action of this drug as a dietary restriction mimetic.	Metformin	141-150	putative S-adenosylmethionine synthase 1	Caenorhabditis elegans	127-133
23382195-5	2013	Our results show that AMPK activation with treatment of 5-aminoimidazole-4-carboxamide ribonucleotide, metformin, or pulsatile shear stress induces PARP-1 dissociation from the Bcl-6 intron 1, increases Bcl-6 expression, and inhibits expression of inflammatory mediators.	Metformin	103-112	BCL6 transcription repressor	Homo sapiens	177-182
23267855-0	2013	The effect of novel promoter variants in MATE1 and MATE2 on the pharmacokinetics and pharmacodynamics of metformin.	Metformin	105-114	solute carrier family 47 member 1	Homo sapiens	41-46
23621234-10	2013	In conclusion, expression changes in miRNAs of miR-146a, miR-100, miR-425, miR-193a-3p and, miR-106b in metformin-treated cells may be important.	Metformin	104-113	microRNA 106b	Homo sapiens	92-100
23894862-5	2013	For example, genetic variations of several membrane transporters, including SLC2A1/2 and SLC47A1/2 genes, are implicated in the highly variable glycemic response to metformin, a first-line drug used to treat newly diagnosed T2DM.	Metformin	165-174	solute carrier family 2 member 1	Homo sapiens	76-82
23894862-5	2013	For example, genetic variations of several membrane transporters, including SLC2A1/2 and SLC47A1/2 genes, are implicated in the highly variable glycemic response to metformin, a first-line drug used to treat newly diagnosed T2DM.	Metformin	165-174	solute carrier family 47 member 1	Homo sapiens	89-96
24335168-4	2013	Treatment with metformin was also associated with activation of AMP kinase and inhibition of mTOR/p70S6K/pS6 signaling in both cells.	Metformin	15-24	taste 2 receptor member 63 pseudogene	Homo sapiens	105-108
24335168-6	2013	In addition, we found USP7, a positive regulator of tumor suppressor p53, as a new molecular target of metformin.	Metformin	103-112	ubiquitin specific peptidase 7	Homo sapiens	22-26
24335168-7	2013	Esophagus cancer cells can be protected against metformin-induced growth inhibition by small interfering RNA against USP7.	Metformin	48-57	ubiquitin specific peptidase 7	Homo sapiens	117-121
23135276-11	2012	Furthermore, the promoter activity of CAP was increased by metformin in an AMPK/JNK-dependent fashion.	Metformin	59-68	mitogen-activated protein kinase 8	Mus musculus	80-83
22864903-0	2012	Metformin inhibits advanced glycation end products (AGEs)-induced renal tubular cell injury by suppressing reactive oxygen species generation via reducing receptor for AGEs (RAGE) expression.	Metformin	0-9	advanced glycosylation end-product specific receptor	Homo sapiens	174-178
22864903-4	2012	We examined here whether and how metformin could block the AGEs-RAGE-elicited tubular cell injury in vitro.	Metformin	33-42	advanced glycosylation end-product specific receptor	Homo sapiens	64-68
22864903-9	2012	Compound C, an inhibitor of AMP-activated protein kinase significantly blocked the effects of metformin on RAGE gene expression and ROS generation in AGEs-exposed tubular cells.	Metformin	94-103	advanced glycosylation end-product specific receptor	Homo sapiens	107-111
22864903-11	2012	Our present study suggests that metformin could inhibit the AGEs-induced apoptosis and inflammatory and fibrotic reactions in tubular cells probably by reducing ROS generation via suppression of RAGE expression through AMP-activated protein kinase activation.	Metformin	32-41	advanced glycosylation end-product specific receptor	Homo sapiens	195-199
22864903-12	2012	Metformin may protect against tubular cell injury in diabetic nephropathy by blocking the AGEs-RAGE-ROS axis.	Metformin	0-9	advanced glycosylation end-product specific receptor	Homo sapiens	95-99
22184060-6	2012	Circulating LBP concentration was increased in HFD mice, whereas decreased in glucagon-like peptide 1 receptor knockout mice (significantly more insulin sensitive than wild-type mice) and after metformin administration.	Metformin	194-203	lipopolysaccharide binding protein	Mus musculus	12-15
22977252-8	2012	Up-regulation of SHP by metformin-mediated activation of the ATM-AMP-activated protein kinase pathway led to inhibition of GH-mediated induction of hepatic gluconeogenesis, which was abolished by an ATM inhibitor, KU-55933.	Metformin	24-33	nuclear receptor subfamily 0, group B, member 2	Mus musculus	17-20
22964327-9	2012	Suppression of AMPK by Compound C augmented RANKL expression, and AMPK activation by metformin significantly decreased RANKL expression in hPDL cells.	Metformin	85-94	TNF superfamily member 11	Homo sapiens	119-124
22964327-10	2012	Additionally, metformin down-regulated RANKL expression in hPDL cells exposed to high glucose via AMPK activation.	Metformin	14-23	TNF superfamily member 11	Homo sapiens	39-44
22540890-3	2012	Herein, we report that metformin significantly inhibited human epidermoid A431 tumor xenograft growth in nu/nu mice, which was associated with a significant reduction in proliferative biomarkers PCNA and cyclins D1/B1.	Metformin	23-32	cyclin D1	Mus musculus	204-217
22445233-10	2012	CONCLUSIONS: Metformin treatment decreased the chemerin expression and alleviated the ER stress in the visceral adipose tissue of high-fat diet-induced insulin-resistant rats.	Metformin	13-22	retinoic acid receptor responder 2	Rattus norvegicus	47-55
22770236-3	2012	(2012) demonstrate that the diabetes medication metformin enhances spatial learning in mice by activating the atypical PKC/CBP pathway in adult neural stem cells.	Metformin	48-57	CREB binding protein	Mus musculus	123-126
22442140-1	2012	Focus on "A novel inverse relationship between metformin-triggered AMPK-SIRT1 signaling and p53 protein abundance in high glucose-exposed HepG2 cells".	Metformin	47-56	sirtuin 1	Homo sapiens	72-77
22407892-0	2012	Ablation of both organic cation transporter (OCT)1 and OCT2 alters metformin pharmacokinetics but has no effect on tissue drug exposure and pharmacodynamics.	Metformin	67-76	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	17-50
22407892-1	2012	Organic cation transporter (OCT)1 and OCT2 mediate hepatic uptake and secretory renal clearance of metformin, respectively.	Metformin	99-108	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	0-33
22493491-13	2012	Likewise, metformin decreases PTP-1B activity and improves response to IFNalpha in insulin-resistant obese mice.	Metformin	10-19	interferon alpha	Mus musculus	71-79
22389381-7	2012	Treatment with metformin was associated with inhibition of mTOR/p70S6K/pS6 signaling and downregulation of pERK in both TT and MZ-CRC-1 cells.	Metformin	15-24	taste 2 receptor member 63 pseudogene	Homo sapiens	71-74
22349108-0	2012	Metformin ameliorates IL-6-induced hepatic insulin resistance via induction of orphan nuclear receptor small heterodimer partner (SHP) in mouse models.	Metformin	0-9	nuclear receptor subfamily 0, group B, member 2	Mus musculus	130-133
22349108-2	2012	Metformin is an anti-diabetic drug used for the treatment of type 2 diabetes, and orphan nuclear receptor small heterodimer partner (SHP, also known as NR0B2), a transcriptional co-repressor, plays an important role in maintaining metabolic homeostasis.	Metformin	0-9	nuclear receptor subfamily 0, group B, member 2	Mus musculus	133-136
22349108-2	2012	Metformin is an anti-diabetic drug used for the treatment of type 2 diabetes, and orphan nuclear receptor small heterodimer partner (SHP, also known as NR0B2), a transcriptional co-repressor, plays an important role in maintaining metabolic homeostasis.	Metformin	0-9	nuclear receptor subfamily 0, group B, member 2	Mus musculus	152-157
22349108-3	2012	Here, we demonstrate that metformin-mediated activation of AMP-activated protein kinase (AMPK) increases SHP protein production and regulates IL-6-induced hepatic insulin resistance.	Metformin	26-35	nuclear receptor subfamily 0, group B, member 2	Mus musculus	105-108
22349108-4	2012	METHODS: We investigated metformin-mediated SHP production improved insulin resistance through the regulation of an IL-6-dependent pathway (involving signal transducer and activator of transcription 3 [STAT3] and suppressor of cytokine signalling 3 [SOCS3]) in both Shp knockdown and Shp null mice.	Metformin	25-34	nuclear receptor subfamily 0, group B, member 2	Mus musculus	44-47
22349108-4	2012	METHODS: We investigated metformin-mediated SHP production improved insulin resistance through the regulation of an IL-6-dependent pathway (involving signal transducer and activator of transcription 3 [STAT3] and suppressor of cytokine signalling 3 [SOCS3]) in both Shp knockdown and Shp null mice.	Metformin	25-34	nuclear receptor subfamily 0, group B, member 2	Mus musculus	266-269
22349108-4	2012	METHODS: We investigated metformin-mediated SHP production improved insulin resistance through the regulation of an IL-6-dependent pathway (involving signal transducer and activator of transcription 3 [STAT3] and suppressor of cytokine signalling 3 [SOCS3]) in both Shp knockdown and Shp null mice.	Metformin	25-34	nuclear receptor subfamily 0, group B, member 2	Mus musculus	284-287
22349108-5	2012	RESULTS: IL-6-induced STAT3 transactivation and SOCS3 production were significantly repressed by metformin, adenoviral constitutively active AMPK (Ad-CA-AMPK), and adenoviral SHP (Ad-SHP), but not in Shp knockdown, or with the adenoviral dominant negative form of AMPK (Ad-DN-AMPK).	Metformin	97-106	nuclear receptor subfamily 0, group B, member 2	Mus musculus	175-178
22349108-5	2012	RESULTS: IL-6-induced STAT3 transactivation and SOCS3 production were significantly repressed by metformin, adenoviral constitutively active AMPK (Ad-CA-AMPK), and adenoviral SHP (Ad-SHP), but not in Shp knockdown, or with the adenoviral dominant negative form of AMPK (Ad-DN-AMPK).	Metformin	97-106	nuclear receptor subfamily 0, group B, member 2	Mus musculus	183-186
22349108-5	2012	RESULTS: IL-6-induced STAT3 transactivation and SOCS3 production were significantly repressed by metformin, adenoviral constitutively active AMPK (Ad-CA-AMPK), and adenoviral SHP (Ad-SHP), but not in Shp knockdown, or with the adenoviral dominant negative form of AMPK (Ad-DN-AMPK).	Metformin	97-106	nuclear receptor subfamily 0, group B, member 2	Mus musculus	200-203
22349108-9	2012	CONCLUSIONS/INTERPRETATION: Our results demonstrate that SHP upregulation by metformin may prevent hepatic disorders by regulating the IL-6-dependent pathway, and that this pathway can help to ameliorate the pathogenesis of cytokine-mediated metabolic dysfunction.	Metformin	77-86	nuclear receptor subfamily 0, group B, member 2	Mus musculus	57-60
28157435-5	2010	Furthermore, we showed that metformin inhibits 2DG-induced autophagy, decreases beclin 1 expression and triggers a switch from a survival process to cell death.	Metformin	28-37	beclin 1	Homo sapiens	80-88
20590612-6	2010	In these cells, metformin also suppressed phorbol-12-myristate-13-acetate (PMA)-enhanced levels of matrix metalloproteinases-9 (MMP-9) protein, mRNA and transcription activity through suppression of activator protein-1 (AP-1) activation.	Metformin	16-25	matrix metallopeptidase 9	Homo sapiens	99-126
20590612-6	2010	In these cells, metformin also suppressed phorbol-12-myristate-13-acetate (PMA)-enhanced levels of matrix metalloproteinases-9 (MMP-9) protein, mRNA and transcription activity through suppression of activator protein-1 (AP-1) activation.	Metformin	16-25	matrix metallopeptidase 9	Homo sapiens	128-133
20590612-6	2010	In these cells, metformin also suppressed phorbol-12-myristate-13-acetate (PMA)-enhanced levels of matrix metalloproteinases-9 (MMP-9) protein, mRNA and transcription activity through suppression of activator protein-1 (AP-1) activation.	Metformin	16-25	Jun proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	199-218
20590612-6	2010	In these cells, metformin also suppressed phorbol-12-myristate-13-acetate (PMA)-enhanced levels of matrix metalloproteinases-9 (MMP-9) protein, mRNA and transcription activity through suppression of activator protein-1 (AP-1) activation.	Metformin	16-25	Jun proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	220-224
20590612-10	2010	CONCLUSIONS AND IMPLICATIONS: Metformin inhibited PMA-induced invasion and migration of human fibrosarcoma cells via Ca(2+)-dependent PKCalpha/ERK and JNK/AP-1-signalling pathways.	Metformin	30-39	Jun proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	155-159
20564343-12	2010	The BrdU and PCNA indices decreased in mice treated with metformin.	Metformin	57-66	proliferating cell nuclear antigen	Mus musculus	13-17
22263023-10	2010	The expressions of MMP2 and MMP9 mRNA were both up-regulated after metformin treatment, while in the 8mmol/L Group the genes changes were the most significant.	Metformin	67-76	matrix metallopeptidase 9	Homo sapiens	28-32
22263023-11	2010	CONCLUSIONS: Metformin can increase the migration speed and enhance invasion abilities of A549 cells in vitro, which may be attributed to the up-regulation of MMP2 and MMP9.	Metformin	13-22	matrix metallopeptidase 9	Homo sapiens	168-172
20215500-8	2010	Finally, metformin inhibited 2DG-induced autophagy, decreased beclin 1 expression, and triggered a switch from a survival process to cell death.	Metformin	9-18	beclin 1	Homo sapiens	62-70
19887597-3	2010	In mice, muscle-specific aPKC (PKC-lambda) depletion by conditional gene targeting impaired AICAR-stimulated glucose disposal and stimulatory effects of both AICAR and metformin on 2-deoxyglucose/glucose uptake in muscle in vivo and AICAR stimulation of 2-[(3)H]deoxyglucose uptake in isolated extensor digitorum longus muscle; however, AMPK activation was unimpaired.	Metformin	168-177	protein kinase C, iota	Mus musculus	9-41
20016398-1	2010	Multidrug and toxin extrusions (MATE1/SLC47A1 and MATE2-K/SLC47A2) play important roles in the renal excretion of metformin.	Metformin	114-123	solute carrier family 47 member 1	Homo sapiens	32-37
20016398-1	2010	Multidrug and toxin extrusions (MATE1/SLC47A1 and MATE2-K/SLC47A2) play important roles in the renal excretion of metformin.	Metformin	114-123	solute carrier family 47 member 1	Homo sapiens	38-45
19898263-0	2010	Interaction between polymorphisms in the OCT1 and MATE1 transporter and metformin response.	Metformin	72-81	solute carrier family 47 member 1	Homo sapiens	50-55
19898263-1	2010	OBJECTIVE: Metformin is transported into the hepatocyte by organic cation transporter 1 (OCT1) and out of the hepatocyte by multidrug and toxin extrusion 1 (MATE1).	Metformin	11-20	solute carrier family 47 member 1	Homo sapiens	124-155
19898263-1	2010	OBJECTIVE: Metformin is transported into the hepatocyte by organic cation transporter 1 (OCT1) and out of the hepatocyte by multidrug and toxin extrusion 1 (MATE1).	Metformin	11-20	solute carrier family 47 member 1	Homo sapiens	157-162
19898263-2	2010	Recently, we discovered that polymorphisms rs622342 A&gt;C in the SLC22A1 gene, coding for OCT1, and rs2289669 G&gt;A in the SLC47A1 gene, coding for MATE1, are associated with the degree of glucose lowering by metformin.	Metformin	211-220	solute carrier family 47 member 1	Homo sapiens	125-132
19898263-9	2010	CONCLUSION: The effect of the MATE1 rs2289669 polymorphism on the glucose lowering effect of metformin is larger in incident users with the OCT1 rs622342 CC genotype than in incident users with the AA genotype.	Metformin	93-102	solute carrier family 47 member 1	Homo sapiens	30-35
19672815-9	2009	We demonstrated that the expressions of GLP-1R, GIPR, and PPARalpha were downregulated when INS-1beta cells were treated with glucose, while their expressions were upregulated when treated with metformin or AICAR.	Metformin	194-203	glucagon-like peptide 1 receptor	Rattus norvegicus	40-46
19700143-6	2009	rOct1 but no rOct2 was expressed extensively in osteoblasts and the protein level of rOct1 could be up-regulated by metformin.	Metformin	116-125	solute carrier family 22 member 1	Rattus norvegicus	0-5
19700143-6	2009	rOct1 but no rOct2 was expressed extensively in osteoblasts and the protein level of rOct1 could be up-regulated by metformin.	Metformin	116-125	solute carrier family 22 member 1	Rattus norvegicus	85-90
19700143-8	2009	In conclusion, rat osteoblasts have the ability to transport the metformin intra-cellularly, the uptake of metformin by osteoblasts is a secondary active transportation mediated by rOct1 and high-glucose can improve the uptake of metformin by osteoblasts through phosphorylation of rOct1.	Metformin	65-74	solute carrier family 22 member 1	Rattus norvegicus	282-287
19700143-8	2009	In conclusion, rat osteoblasts have the ability to transport the metformin intra-cellularly, the uptake of metformin by osteoblasts is a secondary active transportation mediated by rOct1 and high-glucose can improve the uptake of metformin by osteoblasts through phosphorylation of rOct1.	Metformin	107-116	solute carrier family 22 member 1	Rattus norvegicus	181-186
19700143-8	2009	In conclusion, rat osteoblasts have the ability to transport the metformin intra-cellularly, the uptake of metformin by osteoblasts is a secondary active transportation mediated by rOct1 and high-glucose can improve the uptake of metformin by osteoblasts through phosphorylation of rOct1.	Metformin	107-116	solute carrier family 22 member 1	Rattus norvegicus	282-287
19700143-8	2009	In conclusion, rat osteoblasts have the ability to transport the metformin intra-cellularly, the uptake of metformin by osteoblasts is a secondary active transportation mediated by rOct1 and high-glucose can improve the uptake of metformin by osteoblasts through phosphorylation of rOct1.	Metformin	107-116	solute carrier family 22 member 1	Rattus norvegicus	181-186
19700143-8	2009	In conclusion, rat osteoblasts have the ability to transport the metformin intra-cellularly, the uptake of metformin by osteoblasts is a secondary active transportation mediated by rOct1 and high-glucose can improve the uptake of metformin by osteoblasts through phosphorylation of rOct1.	Metformin	107-116	solute carrier family 22 member 1	Rattus norvegicus	282-287
19674806-7	2009	Serum MMP-9 levels were decreased in the metformin (-13.5+/-34.8%, p=0.02) and rosiglitazone (-27.2+/-51.0%, p=0.023) groups compared with baseline values, whereas no significant change was seen in serum MCP-1 levels.	Metformin	41-50	matrix metallopeptidase 9	Homo sapiens	6-11
19591196-9	2009	We localized the OCT3 protein to the basolateral hepatocyte membrane and identified metformin as an OCT3 substrate.	Metformin	84-93	solute carrier family 22 member 3	Homo sapiens	100-104
19536068-0	2009	The effects of genetic polymorphisms in the organic cation transporters OCT1, OCT2, and OCT3 on the renal clearance of metformin.	Metformin	119-128	POU class 2 homeobox 2	Homo sapiens	78-82
19536068-0	2009	The effects of genetic polymorphisms in the organic cation transporters OCT1, OCT2, and OCT3 on the renal clearance of metformin.	Metformin	119-128	solute carrier family 22 member 3	Homo sapiens	88-92
19536068-2	2009	We explored metformin pharmacokinetics in relation to genetic variations in OCT1, OCT2, OCT3, OCTN1, and MATE1 in 103 healthy male Caucasians.	Metformin	12-21	POU class 2 homeobox 2	Homo sapiens	82-86
19536068-2	2009	We explored metformin pharmacokinetics in relation to genetic variations in OCT1, OCT2, OCT3, OCTN1, and MATE1 in 103 healthy male Caucasians.	Metformin	12-21	solute carrier family 22 member 3	Homo sapiens	88-92
19490902-2	2009	(2009) shows how metformin circumvents a block between insulin and atypical protein kinase C in obese and diabetic mice to inhibit gluconeogenesis by stimulating the phosphorylation of CBP and the disassembly of the CREB transcriptional complex.	Metformin	17-26	CREB binding protein	Mus musculus	185-188
19367387-12	2009	Metformin ameliorated autophagy alterations in diabetic beta cells and beta cells exposed to NEFA, a process associated with normalisation of LAMP2 expression.	Metformin	0-9	lysosomal associated membrane protein 2	Homo sapiens	142-147
19414638-6	2009	Metformin also promoted phosphorylation of both AMPK and endothelial nitric oxide synthase, increased plasma nitric oxide levels, and improved insulin resistance.	Metformin	0-9	insulin	Canis lupus familiaris	143-150
18597869-7	2009	Pre-treatment with metformin (100-1000 micromol/L) also inhibited TNF-alpha-induced IL-6 production, phosphorylation of IkappaB kinase (IKK) alpha/beta and IkappaB-alpha degradation.	Metformin	19-28	component of inhibitor of nuclear factor kappa B kinase complex	Homo sapiens	120-146
18597869-11	2009	CONCLUSIONS: Metformin had anti-inflammatory effects on endothelial cells and inhibited TNF-alpha-induced IKKalpha/beta phosphorylation, IkappaB-alpha degradation and IL-6 production in HUVEC.	Metformin	13-22	component of inhibitor of nuclear factor kappa B kinase complex	Homo sapiens	106-114
19426682-7	2009	Metformin, which was also an anti-diabetic agent, and creatinine more potently inhibited the uptake of [(14)C]aminoguanidine by hOCT2 than that by hOCT1.	Metformin	0-9	POU class 2 homeobox 2	Homo sapiens	128-133
19237574-8	2009	Finally, inhibition of AMP-activated protein kinase (AMPK) by the pharmacological inhibitor Compound C largely suppresses metformin"s effect on Abeta generation and BACE1 transcription, suggesting an AMPK-dependent mechanism.	Metformin	122-131	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	23-51
19237574-8	2009	Finally, inhibition of AMP-activated protein kinase (AMPK) by the pharmacological inhibitor Compound C largely suppresses metformin"s effect on Abeta generation and BACE1 transcription, suggesting an AMPK-dependent mechanism.	Metformin	122-131	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	53-57
19237574-8	2009	Finally, inhibition of AMP-activated protein kinase (AMPK) by the pharmacological inhibitor Compound C largely suppresses metformin"s effect on Abeta generation and BACE1 transcription, suggesting an AMPK-dependent mechanism.	Metformin	122-131	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	200-204
19228809-0	2009	Genetic variation in the multidrug and toxin extrusion 1 transporter protein influences the glucose-lowering effect of metformin in patients with diabetes: a preliminary study.	Metformin	119-128	solute carrier family 47 member 1	Homo sapiens	25-56
19228809-1	2009	OBJECTIVE: Metformin, an oral glucose-lowering drug, is taken up in hepatocytes by the organic cation transporter (OCT) 1 and in renal epithelium by OCT2.	Metformin	11-20	POU class 2 homeobox 2	Homo sapiens	149-153
19228809-2	2009	In these cells, the multidrug and toxin extrusion (MATE) 1 protein, encoded by the SLC47A1 gene, is responsible for the excretion of metformin into the bile and urine, respectively.	Metformin	133-142	solute carrier family 47 member 1	Homo sapiens	20-29
19228809-2	2009	In these cells, the multidrug and toxin extrusion (MATE) 1 protein, encoded by the SLC47A1 gene, is responsible for the excretion of metformin into the bile and urine, respectively.	Metformin	133-142	solute carrier family 47 member 1	Homo sapiens	51-58
19228809-2	2009	In these cells, the multidrug and toxin extrusion (MATE) 1 protein, encoded by the SLC47A1 gene, is responsible for the excretion of metformin into the bile and urine, respectively.	Metformin	133-142	solute carrier family 47 member 1	Homo sapiens	83-90
19228809-3	2009	We studied the effect of single nucleotide polymorphisms (SNPs) in the SLC47A1 gene on the A1C-lowering effect of metformin.	Metformin	114-123	solute carrier family 47 member 1	Homo sapiens	71-78
19228809-12	2009	These results suggest that the transporter MATE1, encoded by SLC47A1, may have an important role in the pharmacokinetics of metformin, although replication is necessary.	Metformin	124-133	solute carrier family 47 member 1	Homo sapiens	43-48
19228809-12	2009	These results suggest that the transporter MATE1, encoded by SLC47A1, may have an important role in the pharmacokinetics of metformin, although replication is necessary.	Metformin	124-133	solute carrier family 47 member 1	Homo sapiens	61-68
18304542-7	2009	RESULT(S): During metformin pretreatment DHEAS increased, wheres other androgens were unaffected.	Metformin	18-27	sulfotransferase family 2A member 1	Homo sapiens	41-46
18304542-10	2009	CONCLUSION(S): In infertile PCOS women metformin treatment increased DHEAS levels.	Metformin	39-48	sulfotransferase family 2A member 1	Homo sapiens	69-74
18855699-5	2008	In fact, it has been recently reported that drugs used in the treatment of diabetes, such as metformin and thiazolidinediones (TZDs), exert their beneficial effects through the activation of AMPK.	Metformin	93-102	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	191-195
18686197-5	2008	As for hOCT2-mediated uptake, the IC(50) values of quinidine and the I(f) channel inhibitor for metformin uptake were lower than those for MPP uptake.	Metformin	96-105	POU class 2 homeobox 2	Homo sapiens	7-12
18250273-3	2008	METHODS AND RESULTS: Exposure of human umbilical vein endothelial cells or bovine aortic endothelial cells to metformin significantly increased AMPK activity and the phosphorylation of both AMPK at Thr172 and LKB1 at Ser428, an AMPK kinase, which was paralleled by increased activation of protein kinase C (PKC)-zeta, as evidenced by increased activity, phosphorylation (Thr410/403), and nuclear translocation of PKC-zeta.	Metformin	110-119	protein kinase C zeta	Homo sapiens	413-421
18250273-4	2008	Consistently, either pharmacological or genetic inhibition of PKC-zeta ablated metformin-enhanced phosphorylation of both AMPK-Thr172 and LKB1-Ser428, suggesting that PKC-zeta might act as an upstream kinase for LKB1.	Metformin	79-88	protein kinase C zeta	Homo sapiens	62-70
18250273-4	2008	Consistently, either pharmacological or genetic inhibition of PKC-zeta ablated metformin-enhanced phosphorylation of both AMPK-Thr172 and LKB1-Ser428, suggesting that PKC-zeta might act as an upstream kinase for LKB1.	Metformin	79-88	protein kinase C zeta	Homo sapiens	167-175
18250273-9	2008	Finally, inhibition of PKC-zeta abolished metformin-enhanced coimmunoprecipitation of LKB1 with both AMPKalpha1 and AMPKalpha2.	Metformin	42-51	protein kinase C zeta	Homo sapiens	23-31
18019665-0	2007	[Serum level of retinol-binding protein 4 in obese patients with insulin resistance and in patients with type 2 diabetes treated with metformin].	Metformin	134-143	retinol binding protein 4	Homo sapiens	16-41
18019665-2	2007	METHOD: 28 obese individuals with insulin resistance, 11 type 2 diabetes patients treated with metformin and 17 control individuals were examined for serum level of retinol-binding protein 4 using the RIA method.	Metformin	95-104	retinol binding protein 4	Homo sapiens	165-190
18019665-4	2007	OUTCOME: The highest and the lowest RBP4 levels (561.6 +/- 209 ng/ml) were recorded, respectively, for obese individuals with IR (IR HOMA 3.9) and for obese type 2 diabetics treated with metformin (391.1 +/- 133,5 ng/ml) (P &lt; 0.01).	Metformin	187-196	retinol binding protein 4	Homo sapiens	36-40
18019665-5	2007	The RBP4 level of the control group was significantly lower as compared with the obese individuals with IR (452.8 +/- 104.6 ng/ml) (P &lt; 0.05), but insignificantly higher as compared with the obese individuals with DM2T treated with metformin (391,1 +/- 133.5 ng/ml).	Metformin	235-244	retinol binding protein 4	Homo sapiens	4-8
18019665-8	2007	Through its effect on RBP4 expression in adipocytes, metformin may improve total insulin sensitivity in obese individuals including those with MS and delay the onset of manifest DM.	Metformin	53-62	retinol binding protein 4	Homo sapiens	22-26
17509534-5	2007	Kinetic analyses demonstrated the Michaelis-Menten constants for the hMATE1-mediated transport of tetraethylammonium, 1-methyl-4-phenylpyridinium, cimetidine, metformin, guanidine, procainamide, topotecan, estrone sulfate, acycrovir, and ganciclovir to be (in mM) 0.38, 0.10, 0.17, 0.78, 2.10, 1.23, 0.07, 0.47, 2.64, and 5.12, respectively.	Metformin	159-168	solute carrier family 47 member 1	Homo sapiens	69-75
17314235-5	2007	However, metformin treatment decreased visceral fat deposition and restored nNOS and eNOS expression in penile tissue.	Metformin	9-18	nitric oxide synthase 1	Rattus norvegicus	76-80
17476361-0	2007	Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action.	Metformin	74-83	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	35-63
17476361-0	2007	Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action.	Metformin	74-83	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	65-69
17476361-2	2007	Organic cation transporter 1 (OCT1) plays a role in the hepatic uptake of metformin, but its role in the therapeutic effects of the drug, which involve activation of AMP-activated protein kinase (AMPK), is unknown.	Metformin	74-83	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	0-28
17476361-2	2007	Organic cation transporter 1 (OCT1) plays a role in the hepatic uptake of metformin, but its role in the therapeutic effects of the drug, which involve activation of AMP-activated protein kinase (AMPK), is unknown.	Metformin	74-83	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	30-34
17476361-5	2007	In mouse hepatocytes, deletion of Oct1 resulted in a reduction in the effects of metformin on AMPK phosphorylation and gluconeogenesis.	Metformin	81-90	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	34-38
17476361-7	2007	Seven nonsynonymous polymorphisms of OCT1 that exhibited reduced uptake of metformin were identified.	Metformin	75-84	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	37-41
17476361-8	2007	Notably, OCT1-420del (allele frequency of about 20% in white Americans), previously shown to have normal activity for model substrates, had reduced activity for metformin.	Metformin	161-170	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	9-13
17476361-9	2007	In clinical studies, the effects of metformin in glucose tolerance tests were significantly lower in individuals carrying reduced function polymorphisms of OCT1.	Metformin	36-45	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	156-160
17476361-10	2007	Collectively, the data indicate that OCT1 is important for metformin therapeutic action and that genetic variation in OCT1 may contribute to variation in response to the drug.	Metformin	59-68	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	37-41
17018841-9	2007	In diabetic rats, metformin and AICAR increased renal AMPK phosphorylation, reversed mTOR activation, and inhibited renal hypertrophy, without affecting hyperglycemia.	Metformin	18-27	mechanistic target of rapamycin kinase	Rattus norvegicus	85-89
17224000-0	2007	Effects of rosiglitazone and metformin on inflammatory markers and adipokines: decrease in interleukin-18 is an independent factor for the improvement of homeostasis model assessment-beta in type 2 diabetes mellitus.	Metformin	29-38	interleukin 18	Homo sapiens	91-105
17111267-0	2007	Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and therapeutic effects of metformin.	Metformin	95-104	POU class 2 homeobox 2	Homo sapiens	43-47
17111267-2	2007	In this study we analyzed variants of OCT1 and OCT2 genes in 33 patients (24 responders and nine non-responders) based on the hypothesis that polymorphisms in both genes contribute to large inter-patient variability in the clinical efficacy of metformin.	Metformin	244-253	POU class 2 homeobox 2	Homo sapiens	47-51
16489446-4	2006	METHODS: We used reporter gene analysis to examine the effects of rosiglitazone and metformin on the activity of the proinsulin and insulin promoter factor 1 (IPF1) gene promoters in the glucose-responsive mouse beta cell line Min6.	Metformin	84-93	insulin II	Mus musculus	117-127
16505249-7	2006	In conclusion, our results provide novel mechanisms for the plasma glucose-lowering action of metformin, via an increase of beta-endorphin secretion from adrenal glands to stimulate opioid mu-receptor linkage, leading to an increase of GLUT-4 gene expression and an attenuation of hepatic PEPCK gene expression in STZ-induced diabetic rats.	Metformin	94-103	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	289-294
16505254-1	2006	AMP-activated protein kinase (AMPK) is a key molecular regulator of cellular metabolism, and its activity is induced by both metformin and thiazolidinedione antidiabetic medications.	Metformin	125-134	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	0-28
16505254-1	2006	AMP-activated protein kinase (AMPK) is a key molecular regulator of cellular metabolism, and its activity is induced by both metformin and thiazolidinedione antidiabetic medications.	Metformin	125-134	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	30-34
16124352-2	2005	This newer formulation may enhance patient compliance with oral therapy compared to conventional immediate-release metformin (MIR) in T2DM.	Metformin	115-124	membrane associated ring-CH-type finger 8	Homo sapiens	126-129
15039452-11	2004	These results demonstrate that the combination therapy of metformin with DPPIV inhibitor leads to reduced food intake and body weight gain, most likely through the significant increase of plasma GLP-1 level.	Metformin	58-67	glucagon	Rattus norvegicus	195-200
15135305-6	2004	In an indirect stimulation of the insulin receptor, metformin inhibited endogenous tyrosine phosphatases and purified human protein tyrosine phosphatase 1B that dephosphorylate and inhibit the insulin receptor kinase.	Metformin	52-61	protein tyrosine phosphatase non-receptor type 1	Homo sapiens	124-155
15130413-13	2004	CONCLUSIONS: (1) High-fat diet induces insulin resistance in SD rats; this was associated with an increase in visceral fat and a decrease in the level of adiponectin; (2) Metformin treatment improved insulin sensitivity accompanied by a decrease in body weight and TG level; (3) Rosiglitazone treatment ameliorates IR in a greater extent and is accompanied by a reduction of FFA, TG and an increase of adiponectin levels.	Metformin	171-180	adiponectin, C1Q and collagen domain containing	Rattus norvegicus	154-165
15130413-13	2004	CONCLUSIONS: (1) High-fat diet induces insulin resistance in SD rats; this was associated with an increase in visceral fat and a decrease in the level of adiponectin; (2) Metformin treatment improved insulin sensitivity accompanied by a decrease in body weight and TG level; (3) Rosiglitazone treatment ameliorates IR in a greater extent and is accompanied by a reduction of FFA, TG and an increase of adiponectin levels.	Metformin	171-180	adiponectin, C1Q and collagen domain containing	Rattus norvegicus	402-413
15258553-6	2004	RESULTS: After 8 weeks of treatment in subjects on metformin + pioglitazone 30 mg (group MP1), we found a reduction of nocturnal blood pressure values (mean nocturnal systolic BP 128.05+/- 1.23 vs 122.8+/-2.3 mmHg; p&lt;0.02; mean nocturnal diastolic BP 81.2+/-0.99 vs 75.65+/-0.93 mmHg; p&lt;0.005).	Metformin	51-60	pitrilysin metallopeptidase 1	Homo sapiens	89-92
14502105-6	2003	Metformin is a mild inhibitor of respiratory chain complex 1; it activates AMPK in several models, apparently independently of changes in the AMP-to-ATP ratio; it activates G6PDH in a model of high-fat related insulin resistance; and it has antioxidant properties by a mechanism (s), which is (are) not completely elucidated as yet.	Metformin	0-9	glucose-6-phosphate dehydrogenase	Homo sapiens	173-178
12747837-2	2003	Furthermore, metformin and rosiglitazone, frontline drugs used for the treatment of type II diabetes, activate AMPK.	Metformin	13-22	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	111-115
12749511-2	2003	This newer formulation may enhance patient compliance with oral therapy and improve long-term control of diabetes compared with the conventional immediate-release formulation of metformin (MIR).	Metformin	178-187	membrane associated ring-CH-type finger 8	Homo sapiens	189-192
12419322-2	2002	There are two possible mechanisms for this effect: (1) metformin inhibits dipeptidyl peptidase IV (DPPIV), an enzyme degrading GLP-1, and (2) metformin enhances GLP-1 secretion.	Metformin	55-64	glucagon	Rattus norvegicus	127-132
12419322-2	2002	There are two possible mechanisms for this effect: (1) metformin inhibits dipeptidyl peptidase IV (DPPIV), an enzyme degrading GLP-1, and (2) metformin enhances GLP-1 secretion.	Metformin	55-64	glucagon	Rattus norvegicus	161-166
12419322-2	2002	There are two possible mechanisms for this effect: (1) metformin inhibits dipeptidyl peptidase IV (DPPIV), an enzyme degrading GLP-1, and (2) metformin enhances GLP-1 secretion.	Metformin	142-151	glucagon	Rattus norvegicus	161-166
12419322-5	2002	Metformin treatment (30, 100, and 300mg/kg) increased plasma active GLP-1 levels dose-dependently in DPPIV-deficient F344/DuCrj rats (approximately 1.6-fold at 3 and 5h after administration of 300mg/kg).	Metformin	0-9	glucagon	Rattus norvegicus	68-73
12419322-8	2002	In DPPIV-positive F344/Jcl rats, coadministration of metformin (300mg/kg) and valine-pyrrolidide (30mg/kg) resulted in elevation of plasma active GLP-1, but neither metformin nor valine-pyrrolidide treatment alone had any effect.	Metformin	53-62	glucagon	Rattus norvegicus	146-151
12419322-9	2002	These findings suggest that metformin has no direct inhibitory effect on DPPIV activity and that metformin and the other biguanides enhance GLP-1 secretion, without altering glucose metabolism.	Metformin	97-106	glucagon	Rattus norvegicus	140-145
12485530-0	2002	[Effect of metformin on gene expression of phosphoenolpyruvate carboxykinase].	Metformin	11-20	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	43-76
12130709-7	2002	Distribution of metformin to the liver in Oct1(-/-) mice was more than 30 times lower than that in Oct1(+/+) mice, and can be accounted for by the extracellular space.	Metformin	16-25	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	42-46
12130709-9	2002	In conclusion, the present findings suggest that Oct1 is responsible for the hepatic uptake as well as playing a role in the intestinal uptake of metformin, whereas the renal distribution and excretion are mainly governed by other transport mechanism(s).	Metformin	146-155	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	49-53
8651938-0	1996	Effect of metformin on SGLT1, GLUT2, and GLUT5 hexose transporter gene expression in small intestine from rats.	Metformin	10-19	solute carrier family 5 member 1	Rattus norvegicus	23-28
8651938-1	1996	The effect of the antihyperglycaemic agent metformin was studied on gene expression of the energy-dependent sodium-hexose cotransporter (SGLT1) and the facilitative hexose transporters GLUT2 and GLUT5 in rat intestine.	Metformin	43-52	solute carrier family 5 member 1	Rattus norvegicus	137-142
8882631-13	1996	The metformin-induced increase in hexose transport in BSMC treated for 24 h with the drug correlated with increased abundance of GLUT1 protein in the plasma membrane, as determined by Western blot analysis.	Metformin	4-13	solute carrier family 2 member 1	Homo sapiens	129-134
33811249-3	2021	The antidiabetic drug metformin, a well-known activator of AMPK, has improved stroke outcomes in diabetic patients with normal renal function.	Metformin	22-31	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	59-63
33811249-4	2021	We investigated whether chronic metformin pre-conditioning can rescue AMPK activity and prevent stroke damage in non-diabetic mice with CKD.	Metformin	32-41	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	70-74
33808727-11	2021	In chondrocytes from OA patients, metformin reduced catabolic factor gene expression and inflammatory cell death factor expression, increased LC3IIb, p62, and LAMP1 expression, and induced an autophagy-lysosome fusion phenotype.	Metformin	34-43	nucleoporin 62	Homo sapiens	150-153
33807522-7	2021	It is also known that metformin reduces food intake and lowers body weight by increasing circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15).	Metformin	22-31	growth differentiation factor 15	Homo sapiens	131-163
33807522-7	2021	It is also known that metformin reduces food intake and lowers body weight by increasing circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15).	Metformin	22-31	growth differentiation factor 15	Homo sapiens	165-170
33763207-0	2020	Glibenclamide, ATP and metformin increases the expression of human bile salt export pump ABCB11.	Metformin	23-32	ATP binding cassette subfamily B member 11	Homo sapiens	67-88
33763207-0	2020	Glibenclamide, ATP and metformin increases the expression of human bile salt export pump ABCB11.	Metformin	23-32	ATP binding cassette subfamily B member 11	Homo sapiens	89-95
33763207-16	2020	Western blot and real-time PCR analysis confirmed the upregulation of BSEP on the treatment of HepG2 cells with glibenclamide, ATP, and metformin.	Metformin	136-145	ATP binding cassette subfamily B member 11	Homo sapiens	70-74
33763207-18	2020	We have found glibenclamide, ATP, and metformin upregulates BSEP.	Metformin	38-47	ATP binding cassette subfamily B member 11	Homo sapiens	60-64
33768205-2	2020	Therapeutic activation of AMPK by metformin could inhibit cyst enlargement by inhibition of both the mammalian target of rapamycin pathway and fluid secretion via the CFTR chloride channel.	Metformin	34-43	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	26-30
24047401-6	2013	AMP-activated protein kinase (AMPK) activators such as resveratrol, AICAR and metformin protected endothelial cells against complement-mediated cytotoxicity through the increase in CD55, CD59, haem oxygenase-1 (HO-1) and ferritin heavy chain (ferritin H) genes, all of which were attenuated by AMPKalpha knock-down.	Metformin	78-87	CD55 molecule (Cromer blood group)	Homo sapiens	181-185
34718940-5	2022	METHODS AND RESULTS: In this context, we created a full-thickness excisional wound model in Wistar albino rats and, investigated NF-kappaB p65 DNA-binding activity and expression levels of RELA (p65), MMP2 and MMP9 in wound samples taken on days 0, 3, 7, and 14 from diabetic/non-diabetic rats treated with metformin and saline.	Metformin	307-316	matrix metallopeptidase 9	Rattus norvegicus	210-214
34718940-6	2022	As a result of our study, we showed that topically applied metformin accelerates wound healing by suppressing NF-kappaB p65 activity and diminishing the expression of MMP2 and MMP9.	Metformin	59-68	matrix metallopeptidase 9	Rattus norvegicus	176-180
34774192-0	2021	Retraction notice to KLF4/Ch25h axis activated by metformin suppresses EndoMT in human umbilical vein endothelial cells (Biochem.	Metformin	50-59	Kruppel like factor 4	Homo sapiens	21-25
34774192-0	2021	Retraction notice to KLF4/Ch25h axis activated by metformin suppresses EndoMT in human umbilical vein endothelial cells (Biochem.	Metformin	50-59	cholesterol 25-hydroxylase	Homo sapiens	26-31
34910358-13	2022	Purmorphamine reversed the effects of metformin on M2 polarization and VEGF upregulation in RAW264.7 macrophages exposed to hyperoxia.	Metformin	38-47	vascular endothelial growth factor A	Mus musculus	71-75
34883492-6	2022	The biomarkers (HGF, CD133, ALP, beta-catenin and SOX2) associated with the hair-inductive activity of dermal cells were detected in the grafted skin tissues and in cultured 3D aggregates treated with metformin using immunofluorescent staining, quantitative real-time RT-PCR (qRT-PCR), and western blotting.	Metformin	201-210	hepatocyte growth factor	Mus musculus	16-19
34883492-6	2022	The biomarkers (HGF, CD133, ALP, beta-catenin and SOX2) associated with the hair-inductive activity of dermal cells were detected in the grafted skin tissues and in cultured 3D aggregates treated with metformin using immunofluorescent staining, quantitative real-time RT-PCR (qRT-PCR), and western blotting.	Metformin	201-210	catenin (cadherin associated protein), beta 1	Mus musculus	33-45
34883492-8	2022	RESULTS: Metformin directly stimulates the activity of alkaline phosphatase (ALP) of cultured 3D aggregates, upregulates both the protein and mRNA expression levels of molecular markers (HGF, CD133, ALP, beta-catenin and SOX2) and improves the survival rate of reconstituted hair follicles.	Metformin	9-18	hepatocyte growth factor	Mus musculus	187-190
34883492-8	2022	RESULTS: Metformin directly stimulates the activity of alkaline phosphatase (ALP) of cultured 3D aggregates, upregulates both the protein and mRNA expression levels of molecular markers (HGF, CD133, ALP, beta-catenin and SOX2) and improves the survival rate of reconstituted hair follicles.	Metformin	9-18	prominin 1	Mus musculus	192-197
34883492-8	2022	RESULTS: Metformin directly stimulates the activity of alkaline phosphatase (ALP) of cultured 3D aggregates, upregulates both the protein and mRNA expression levels of molecular markers (HGF, CD133, ALP, beta-catenin and SOX2) and improves the survival rate of reconstituted hair follicles.	Metformin	9-18	catenin (cadherin associated protein), beta 1	Mus musculus	204-216
34883492-8	2022	RESULTS: Metformin directly stimulates the activity of alkaline phosphatase (ALP) of cultured 3D aggregates, upregulates both the protein and mRNA expression levels of molecular markers (HGF, CD133, ALP, beta-catenin and SOX2) and improves the survival rate of reconstituted hair follicles.	Metformin	9-18	SRY (sex determining region Y)-box 2	Mus musculus	221-225
34883492-9	2022	Moreover, we also found that metformin increases the expression of CD133 in dermal cells thus maintaining their trichogenic capacity that would normally be lost by serial subculture.	Metformin	29-38	prominin 1	Mus musculus	67-72
34628167-18	2021	These results demonstrate that metformin can improve memory impairments, increase BDNF, DCX and Nrf2 protein expressions and antioxidant capacities, and decrease MDA levels in MTX-treated rats.	Metformin	31-40	brain-derived neurotrophic factor	Rattus norvegicus	82-86
34628167-18	2021	These results demonstrate that metformin can improve memory impairments, increase BDNF, DCX and Nrf2 protein expressions and antioxidant capacities, and decrease MDA levels in MTX-treated rats.	Metformin	31-40	doublecortin	Rattus norvegicus	88-91
34850372-9	2022	Although metformin reduced mTORC1 downstream activated P70S6K, it did not significantly alter mTORser2448 activation and even increased BDNF expression.	Metformin	9-18	brain-derived neurotrophic factor	Rattus norvegicus	136-140
34850372-10	2022	Notably, ketamine, scopolamine, and metformin all exerted significant antidepressant-like actions, as evidenced by increased AMPK phosphorylation and BDNF expression.	Metformin	36-45	brain-derived neurotrophic factor	Rattus norvegicus	150-154
34957500-8	2022	Functional enrichment analysis for cDNA microarrays from kidney samples revealed significant enrichment of several pro-proliferative pathways including beta-catenin, hypoxia-inducible factor-1alpha, protein kinase Calpha and Notch signaling pathways in the metformin-treated mutant mice.	Metformin	257-266	catenin (cadherin associated protein), beta 1	Mus musculus	152-164
34772914-8	2021	Activation of AMPK using metformin reversed the EMT program and impaired the metastatic capacity of FATP5-depleted HCC cells.	Metformin	25-34	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	14-18
6838630-9	1983	Metformin administration to diabetic rats caused a marked decrease in both intestinal HMG-CoA reductase activity (P less than 0.001) and ACAT activity (P less than 0.002).	Metformin	0-9	3-hydroxy-3-methylglutaryl-CoA reductase	Rattus norvegicus	86-103
33838541-4	2021	The use of metformin for chemoprevention has been shown to reduce CRC and adenoma incidence through the upregulation of AMPK, which causes cell cycle arrest in the Gap 1-S (G1-S) phase and inhibits the mTOR pathway, even potentially reversing the epithelial-mesenchymal transition.	Metformin	11-20	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	120-124
33859820-15	2021	The ratio of leptin to adiponectin was increased in obese compared with the lean rats in both the control and metformin treatment groups (P<0.0001).	Metformin	110-119	adiponectin, C1Q and collagen domain containing	Rattus norvegicus	23-34
34043989-10	2021	In suppressing LC progression, anti-tumor compounds including metformin, ginsenosides, casticin and duloxetine dually induce/inhibit AMPK signaling.	Metformin	62-71	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	133-137
33965434-0	2021	Long-Term Administration of Metformin Ameliorates Age-Dependent Oxidative Stress and Cognitive Function in Rats.	Metformin	28-37	renin binding protein	Rattus norvegicus	50-53
33965434-5	2021	This study aimed to evaluate the effects of long-term administration of metformin on age-dependent oxidative stress and cognitive function.	Metformin	72-81	renin binding protein	Rattus norvegicus	85-88
33965434-15	2021	CONCLUSION: It can be concluded that long-term metformin intake, by modulating the oxidant/antioxidant mechanisms, prevents the loss of hippocampal neurons caused by age-dependent oxidative stress and improves memory.	Metformin	47-56	renin binding protein	Rattus norvegicus	166-169
34046440-6	2021	AMPK activators, like metformin, are associated with reduced calcification deposits in certain groups of patients, indicating that AMPK is a potential therapeutic target for VC.	Metformin	22-31	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	0-4
34046440-6	2021	AMPK activators, like metformin, are associated with reduced calcification deposits in certain groups of patients, indicating that AMPK is a potential therapeutic target for VC.	Metformin	22-31	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	131-135
32791889-0	2021	Metformin reduces thyroid cancer tumor growth in the metastatic niche of bone by inhibiting osteoblastic RANKL productions.	Metformin	0-9	TNF superfamily member 11	Homo sapiens	105-110
32791889-14	2021	Metformin also inhibited the FRO- or SW1736-CM-induced osteoclastic differentiation of bone marrow-derived monocyte macrophage (BMM) by RANK/c-Fos/NFATC1 signaling.	Metformin	0-9	Fos proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	141-146
32791889-14	2021	Metformin also inhibited the FRO- or SW1736-CM-induced osteoclastic differentiation of bone marrow-derived monocyte macrophage (BMM) by RANK/c-Fos/NFATC1 signaling.	Metformin	0-9	nuclear factor of activated T cells 1	Homo sapiens	147-153
32791889-15	2021	Conclusions In the microenvironment of BM, metformin effectively reduced ATC tumor growth by inhibiting cancer cell viability, blocking cancer cell induced osteoblastic RANKL production, which further activated osteoclastogenesis, and directly reduced osteoclast differentiation.	Metformin	43-52	TNF superfamily member 11	Homo sapiens	169-174
33439105-8	2021	Metformin increased the phosphorylation of AMPK and decreased the phosphorylation of mammalian target of rapamycin and extracellular signal-regulated kinase and the expression of cystic fibrosis transmembrane conductance regulator, aquaporin I, transforming growth factor-beta and type 1 collagen in the liver.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	43-47
33460803-5	2021	Metformin reportedly occurs in different environmental matrices, as measurable concentrations of metformin are found in sewage (urban and hospital), influent/sludge/effluent from wastewater treatment plants, surface water (rivers, lakes, estuaries, oceans, and non-specific sources), tap/drinking water, and sediment (lake and recipient seawaters).	Metformin	0-9	nuclear RNA export factor 1	Homo sapiens	284-287
33460803-5	2021	Metformin reportedly occurs in different environmental matrices, as measurable concentrations of metformin are found in sewage (urban and hospital), influent/sludge/effluent from wastewater treatment plants, surface water (rivers, lakes, estuaries, oceans, and non-specific sources), tap/drinking water, and sediment (lake and recipient seawaters).	Metformin	97-106	nuclear RNA export factor 1	Homo sapiens	284-287
33504231-0	2021	Metformin alleviates inflammation in oxazolone induced ulcerative colitis in rats: plausible role of sphingosine kinase 1/sphingosine 1 phosphate signaling pathway.	Metformin	0-9	sphingosine kinase 1	Rattus norvegicus	101-145
33504231-1	2021	OBJECTIVES: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is associated with high sphingosine kinase 1(SPHK1) expression in the colon, however its role in pathogenesis of UC is not clearly understood so, the aim of the present study was to clarify the role of SPHK1 and investigate whether the anti-inflammatory effects of metformin in UC is mediated by Sphingosine kinase 1/sphingosine 1 phosphate (S1P) signaling pathway.	Metformin	346-355	sphingosine kinase 1	Rattus norvegicus	105-125
33504231-1	2021	OBJECTIVES: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is associated with high sphingosine kinase 1(SPHK1) expression in the colon, however its role in pathogenesis of UC is not clearly understood so, the aim of the present study was to clarify the role of SPHK1 and investigate whether the anti-inflammatory effects of metformin in UC is mediated by Sphingosine kinase 1/sphingosine 1 phosphate (S1P) signaling pathway.	Metformin	346-355	sphingosine kinase 1	Rattus norvegicus	126-131
33504231-7	2021	Metformin also induced a significant decrease in Plasma SIP, SPHK1 activity, inflammatory, oxidative stress markers, ICAM-1 and Caspase-3 genes expression compared to oxazolone group.	Metformin	0-9	sphingosine kinase 1	Rattus norvegicus	61-66
33504231-7	2021	Metformin also induced a significant decrease in Plasma SIP, SPHK1 activity, inflammatory, oxidative stress markers, ICAM-1 and Caspase-3 genes expression compared to oxazolone group.	Metformin	0-9	intercellular adhesion molecule 1	Rattus norvegicus	117-123
33504231-8	2021	CONCLUSION: It is revealed that metformin alleviated inflammation and underlying mechanism may result from inhibition of SPHK1/S1P signaling pathway.	Metformin	32-41	sphingosine kinase 1	Rattus norvegicus	121-126
33915902-9	2021	In addition, metformin treatment increased the expression of monophosphate (AMP)-activated protein kinase (AMPK) and p53 in both HCT116 xenografts and colorectal cancer cell lines and decreased the expression of the urea cycle enzymes, including carbamoyl phosphate synthase 1 (CPS1), arginase 1 (ARG1), ornithine trans-carbamylase (OTC), and ODC.	Metformin	13-22	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	107-111
33915902-11	2021	These results demonstrate that metformin inhibited CRC cell proliferation via activating AMPK/p53 and that there was an association between metformin, urea cycle inhibition and a reduction in putrescine generation.	Metformin	31-40	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	89-93
33757524-0	2021	Correction to: A combination of herbal compound (SPTC) along with exercise or metformin more efficiently alleviated diabetic complications through down-regulation of stress oxidative pathway upon activating Nrf2-Keap1 axis in AGE rich diet-induced type 2 diabetic mice.	Metformin	78-87	kelch-like ECH-associated protein 1	Mus musculus	212-217
33757860-3	2021	Preclinical studies have shown that metformin downregulates the insulin/IGF-1 signaling pathway, corrects dendritic defects, and improves repetitive behavior in Fmr1 knockout mice.	Metformin	36-45	fragile X messenger ribonucleoprotein 1	Mus musculus	161-165
33686698-6	2021	Our results contrast the BMI lowering effects of an acute increase in GDF15 levels observed after metformin use.	Metformin	98-107	growth differentiation factor 15	Homo sapiens	70-75
33690729-18	2021	However, further investigations are necessary to confirm the observations and conclusions drawn from the presented data after metformin administration, especially for proteins that were regulated in a favorable way, i.e. AKT3, CCND2, CD63, CD81, GFAP, IL5, IL17A, IRF4, PI3, and VTCN1.	Metformin	126-135	AKT serine/threonine kinase 3	Homo sapiens	221-225
33690729-18	2021	However, further investigations are necessary to confirm the observations and conclusions drawn from the presented data after metformin administration, especially for proteins that were regulated in a favorable way, i.e. AKT3, CCND2, CD63, CD81, GFAP, IL5, IL17A, IRF4, PI3, and VTCN1.	Metformin	126-135	glial fibrillary acidic protein	Homo sapiens	246-250
33690729-18	2021	However, further investigations are necessary to confirm the observations and conclusions drawn from the presented data after metformin administration, especially for proteins that were regulated in a favorable way, i.e. AKT3, CCND2, CD63, CD81, GFAP, IL5, IL17A, IRF4, PI3, and VTCN1.	Metformin	126-135	interleukin 17A	Homo sapiens	257-262
33690729-18	2021	However, further investigations are necessary to confirm the observations and conclusions drawn from the presented data after metformin administration, especially for proteins that were regulated in a favorable way, i.e. AKT3, CCND2, CD63, CD81, GFAP, IL5, IL17A, IRF4, PI3, and VTCN1.	Metformin	126-135	V-set domain containing T cell activation inhibitor 1	Homo sapiens	279-284
33522578-0	2021	Metformin induces ferroptosis by targeting miR-324-3p/GPX4 axis in breast cancer.	Metformin	0-9	microRNA 324	Homo sapiens	43-50
33522578-10	2021	Our study suggested that metformin promotes ferroptosis of breast cancer by targeting the miR-324-3p/GPX4 axis.	Metformin	25-34	microRNA 324	Homo sapiens	90-97
33412224-0	2021	Hyaluronic acid engrafted metformin loaded graphene oxide nanoparticle as CD44 targeted anti-cancer therapy for triple negative breast cancer.	Metformin	26-35	CD44 antigen	Mus musculus	74-78
33648513-11	2021	Compared with the LPS group, phosphorylation of p65 and IkappaBalpha in the ML group were decreased and accumulation of NF-kappaB in the nucleus was significantly reduced by pretreatment with metformin.	Metformin	192-201	NFKB inhibitor alpha	Bos taurus	56-68
33666871-9	2021	Compared with the model group, IL-6 and visfatin levels were significantly decreased in the acupuncture and metformin groups (P<0.05).	Metformin	108-117	nicotinamide phosphoribosyltransferase	Rattus norvegicus	40-48
33453674-2	2021	Hence, the study aimed to inspect the ability of the combination therapy of metformin and omega-3 to modulate different signaling pathways and micro RNAs such as (miR-155, miR-146a and miR-34) as new targets in order to mitigate adjuvant-induced arthritis and compare their effect to that of methotrexate.	Metformin	76-85	microRNA 155	Homo sapiens	163-170
33047165-10	2021	Metformin significantly attenuated diabetes-related histopathological ocular deteriorations in the cornea, lens, sclera, ciliary body, iris, conjunctiva, retina, and optic nerve partly by restoring serum TNF-alpha, VEGF, claudin-1, and glutathione/malondialdehyde ratios without significantly affecting the fasting blood glucose levels or body weight in these hyperglycemic rats.	Metformin	0-9	claudin 1	Rattus norvegicus	221-230
33603170-0	2021	Repurposing dextromethorphan and metformin for treating nicotine-induced cancer by directly targeting CHRNA7 to inhibit JAK2/STAT3/SOX2 signaling.	Metformin	33-42	SRY-box transcription factor 2	Homo sapiens	131-135
33575255-6	2020	Interestingly, we discovered that the activation of ECE1, ABCA12, BPY2, EEF1A1, RAD9A, and NIPSNAP1 contributed to in vitro resistance to metformin in DU145 and PC3 cell lines.	Metformin	138-147	basic charge Y-linked 2	Homo sapiens	66-70
33543290-9	2021	In in-vitro granulosa cell experiments, the anti-apoptotic effect of metformin was blocked after inhibiting p53 or p21 function, and the expression of p53 mRNA was blocked with AMPK inhibitor, suggesting that the anti-apoptotic effect was AMPK/p53/p21-mediated.	Metformin	69-78	cyclin-dependent kinase inhibitor 1A (P21)	Mus musculus	115-118
33543290-9	2021	In in-vitro granulosa cell experiments, the anti-apoptotic effect of metformin was blocked after inhibiting p53 or p21 function, and the expression of p53 mRNA was blocked with AMPK inhibitor, suggesting that the anti-apoptotic effect was AMPK/p53/p21-mediated.	Metformin	69-78	cyclin-dependent kinase inhibitor 1A (P21)	Mus musculus	248-251
33681180-0	2020	Metformin Resensitizes Sorafenib-Resistant HCC Cells Through AMPK-Dependent Autophagy Activation.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	61-65
33681180-6	2020	In response to metformin, the AMPK/cAMP-response element binding protein (CREB) pathway contributes to CEBPD activation, which promotes autophagic cell death.	Metformin	15-24	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	30-34
33681180-6	2020	In response to metformin, the AMPK/cAMP-response element binding protein (CREB) pathway contributes to CEBPD activation, which promotes autophagic cell death.	Metformin	15-24	cAMP responsive element binding protein 1	Homo sapiens	74-78
33681180-6	2020	In response to metformin, the AMPK/cAMP-response element binding protein (CREB) pathway contributes to CEBPD activation, which promotes autophagic cell death.	Metformin	15-24	CCAAT enhancer binding protein delta	Homo sapiens	103-108
33681180-7	2020	Moreover, treatment with metformin can increase sorafenib sensitivity through AMPK activation in EGFR-overexpressed liver cancer cells.	Metformin	25-34	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	78-82
33468193-0	2021	A combination of herbal compound (SPTC) along with exercise or metformin more efficiently alleviated diabetic complications through down-regulation of stress oxidative pathway upon activating Nrf2-Keap1 axis in AGE rich diet-induced type 2 diabetic mice.	Metformin	63-72	kelch-like ECH-associated protein 1	Mus musculus	197-202
33197442-0	2021	Metformin ameliorates brain damage caused by cardiopulmonary resuscitation via targeting endoplasmic reticulum stress-related proteins GRP78 and XBP1.	Metformin	0-9	heat shock protein family A (Hsp70) member 5	Rattus norvegicus	135-140
33197442-11	2021	Furthermore, metformin inhibited the mRNA and protein expressions of glucose-regulated protein 78 (GRP78) and X-box binding protein 1 (XBP1) in the CA/CPR rat model.	Metformin	13-22	heat shock protein family A (Hsp70) member 5	Rattus norvegicus	69-97
33197442-11	2021	Furthermore, metformin inhibited the mRNA and protein expressions of glucose-regulated protein 78 (GRP78) and X-box binding protein 1 (XBP1) in the CA/CPR rat model.	Metformin	13-22	heat shock protein family A (Hsp70) member 5	Rattus norvegicus	99-104
33197442-12	2021	We confirmed that CA/CPR can induce ERS-related apoptosis and oxidative stress in the brain; moreover, inhibiting ERS-related proteins GRP78 and XBP1 with metformin might attenuate cerebral injury post CA/CPR.	Metformin	155-164	heat shock protein family A (Hsp70) member 5	Rattus norvegicus	135-140
33220275-0	2021	Metformin reduces proteinuria in spontaneously hypertensive rats by activating the HIF-2alpha-VEGF-A pathway.	Metformin	0-9	endothelial PAS domain protein 1	Rattus norvegicus	83-93
33220275-9	2021	Metformin activated hypoxia-inducible factor-2alpha (Hif-2alpha) in response to VEGF but did not affect Hif-1alpha in rat kidneys and cultured rat podocytes.	Metformin	0-9	endothelial PAS domain protein 1	Rattus norvegicus	20-51
33220275-9	2021	Metformin activated hypoxia-inducible factor-2alpha (Hif-2alpha) in response to VEGF but did not affect Hif-1alpha in rat kidneys and cultured rat podocytes.	Metformin	0-9	endothelial PAS domain protein 1	Rattus norvegicus	53-63
33220275-10	2021	Metformin reduced the proteinuria induced by long-term high blood pressure in vivo and increased the VEGF-A production in rat kidneys and cultured rat podocytes, probably by activating the Hif-2alpha-VEGF signaling pathway.	Metformin	0-9	endothelial PAS domain protein 1	Rattus norvegicus	189-199
33430475-0	2021	Fer and FerT Govern Mitochondrial Susceptibility to Metformin and Hypoxic Stress in Colon and Lung Carcinoma Cells.	Metformin	52-61	FER tyrosine kinase	Homo sapiens	0-3
33430475-5	2021	Fer- and FerT-deficient SW620 and H1299 cells (SW Fer/FerT and H Fer/FerT cells, respectively) become highly sensitive to metformin treatment and to hypoxia under glucose-restrictive conditions.	Metformin	122-131	FER tyrosine kinase	Homo sapiens	0-3
33430475-5	2021	Fer- and FerT-deficient SW620 and H1299 cells (SW Fer/FerT and H Fer/FerT cells, respectively) become highly sensitive to metformin treatment and to hypoxia under glucose-restrictive conditions.	Metformin	122-131	FER tyrosine kinase	Homo sapiens	9-12
33430475-5	2021	Fer- and FerT-deficient SW620 and H1299 cells (SW Fer/FerT and H Fer/FerT cells, respectively) become highly sensitive to metformin treatment and to hypoxia under glucose-restrictive conditions.	Metformin	122-131	FER tyrosine kinase	Homo sapiens	9-12
33430475-6	2021	Metformin impaired mitochondrial functioning that was accompanied by ATP deficiency and robust death in SW Fer/FerT and H Fer/FerT cells compared to the parental SW620 and H1299 cells.	Metformin	0-9	FER tyrosine kinase	Homo sapiens	107-110
33430475-6	2021	Metformin impaired mitochondrial functioning that was accompanied by ATP deficiency and robust death in SW Fer/FerT and H Fer/FerT cells compared to the parental SW620 and H1299 cells.	Metformin	0-9	FER tyrosine kinase	Homo sapiens	111-114
33430475-7	2021	Notably, selective knockout of the fer gene without affecting FerT expression reduced sensitivity to metformin and hypoxia seen in SW Fer/FerT cells.	Metformin	101-110	FER tyrosine kinase	Homo sapiens	35-38
33430475-8	2021	Thus, Fer and FerT modulate the mitochondrial susceptibility of metastatic cancer cells to hypoxia and metformin.	Metformin	103-112	FER tyrosine kinase	Homo sapiens	6-9
33430391-5	2021	While the inhibition of miR-378a-3p was shown to impair metformin"s effect in ATP production, PEPCK activity and the expression of Tfam.	Metformin	56-65	phosphoenolpyruvate carboxykinase 1, cytosolic	Mus musculus	94-99
33007330-6	2021	In particular, we found that, in addition to AKT and ERK1/2 activation, FGFR1-induced activation of IRS1 and IGF1R, key regulators connecting metabolism and cancer, was associated with metformin resistance.	Metformin	185-194	insulin like growth factor 1 receptor	Homo sapiens	109-114
33007330-8	2021	Combination of NT157 with metformin induced enhanced inhibition of p-IGF1R, p-ERK1/2 and p-mTOR.	Metformin	26-35	insulin like growth factor 1 receptor	Homo sapiens	69-74
33578051-5	2021	We found that rapamycin and spermidine were able to decrease the spontaneous mutation rate at the CAN1 locus, whereas dinitrophenol, metformin, and resveratrol were able to protect yeast against CAN1 mutations induced by ethyl methanesulfonate (EMS).	Metformin	133-142	arginine permease CAN1	Saccharomyces cerevisiae S288C	195-199
32880467-0	2021	Combination of metformin and cold atmospheric plasma induces glioma cell death to associate with c-Fos.	Metformin	15-24	Fos proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	97-102
32880467-9	2021	In addition, the transcript and protein levels of c-FOS were robustly increased after co-treated with metformin and CAP.	Metformin	102-111	Fos proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	50-55
33126079-4	2020	In addition, activation of AMPK by metformin inhibited S1P-induced ASMCs proliferation by suppressing STAT3 phosphorylation and therefore suppression of PLK1 and ID2 protein expression.	Metformin	35-44	polo like kinase 1	Homo sapiens	153-157
33126079-4	2020	In addition, activation of AMPK by metformin inhibited S1P-induced ASMCs proliferation by suppressing STAT3 phosphorylation and therefore suppression of PLK1 and ID2 protein expression.	Metformin	35-44	inhibitor of DNA binding 2	Homo sapiens	162-165
32794612-6	2020	Immunohistochemistry showed that the densities of CD3(+) and CD8(+) tumor infiltrating lymphocytes (TILs) in the invasive front area were significantly higher in 40 patients treated with metformin compared with propensity score matched cases without metformin (p<0.05).	Metformin	187-196	CD8a molecule	Homo sapiens	61-64
32748028-0	2020	Evaluating the impact of AMPK activation, a target of metformin, on risk of cardiovascular diseases and cancer in the UK Biobank: a Mendelian randomisation study.	Metformin	54-63	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	25-29
32748028-2	2020	This study evaluated the effect of AMP-activated protein kinase (AMPK), the target of metformin, on risk of cardiovascular disease and cancer.	Metformin	86-95	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	35-63
32748028-2	2020	This study evaluated the effect of AMP-activated protein kinase (AMPK), the target of metformin, on risk of cardiovascular disease and cancer.	Metformin	86-95	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	65-69
32748028-3	2020	METHODS: This is a Mendelian randomisation design, using AMPK, the pharmacological target of metformin, to infer the AMPK pathway-dependent effects of metformin on risk of cardiovascular disease and cancer in participants of white British ancestry in the UK Biobank.	Metformin	93-102	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	57-61
32748028-3	2020	METHODS: This is a Mendelian randomisation design, using AMPK, the pharmacological target of metformin, to infer the AMPK pathway-dependent effects of metformin on risk of cardiovascular disease and cancer in participants of white British ancestry in the UK Biobank.	Metformin	93-102	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	117-121
32748028-3	2020	METHODS: This is a Mendelian randomisation design, using AMPK, the pharmacological target of metformin, to infer the AMPK pathway-dependent effects of metformin on risk of cardiovascular disease and cancer in participants of white British ancestry in the UK Biobank.	Metformin	151-160	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	57-61
32748028-3	2020	METHODS: This is a Mendelian randomisation design, using AMPK, the pharmacological target of metformin, to infer the AMPK pathway-dependent effects of metformin on risk of cardiovascular disease and cancer in participants of white British ancestry in the UK Biobank.	Metformin	151-160	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	117-121
32748028-7	2020	CONCLUSIONS/INTERPRETATION: This study provides some genetic evidence that AMPK activation by metformin may protect against cardiovascular disease and cancer, which needs to be confirmed by randomised controlled trials.	Metformin	94-103	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	75-79
32843330-6	2020	Here we tested this hypothesis for another drug and another transporter, namely OCT1- mediated hepatic distributional CL of metformin.	Metformin	124-133	solute carrier family 22 member 1	Rattus norvegicus	80-84
33112812-0	2020	Metformin decreases miR-122, miR-223 and miR-29a in women with polycystic ovary syndrome.	Metformin	0-9	microRNA 122	Homo sapiens	20-27
32679167-0	2020	The possible role of progranulin on anti-inflammatory effects of metformin in temporal lobe epilepsy.	Metformin	65-74	granulin precursor	Rattus norvegicus	21-32
32679167-9	2020	Our results showed basal levels of GFAP, S100B, and pro-inflammatory cytokine increased in the epileptic rats but were significantly ameliorated after pretreatment with metformin.	Metformin	169-178	glial fibrillary acidic protein	Rattus norvegicus	35-39
32679167-9	2020	Our results showed basal levels of GFAP, S100B, and pro-inflammatory cytokine increased in the epileptic rats but were significantly ameliorated after pretreatment with metformin.	Metformin	169-178	S100 calcium binding protein B	Rattus norvegicus	41-46
32679167-10	2020	However, anti-inflammatory cytokine and progranulin also increased in the pre-treated rats and metformin alone group.	Metformin	95-104	granulin precursor	Rattus norvegicus	40-51
32679167-12	2020	Hence, metformin may exert at least some of its anti-inflammatory effects by increasing progranulin level.	Metformin	7-16	granulin precursor	Rattus norvegicus	88-99
32781368-0	2020	Glucose 6-phosphate dehydrogenase inhibition sensitizes melanoma cells to metformin treatment.	Metformin	74-83	glucose-6-phosphate dehydrogenase	Homo sapiens	0-33
32829010-5	2020	We identified and selected metformin, simvastatin and digoxin (C3) as a novel combination of FDA approved drugs, which were shown to effectively target PDX1 and BIRC5 in human PDAC tumors in mice with no toxicity.	Metformin	27-36	baculoviral IAP repeat containing 5	Homo sapiens	161-166
33126710-4	2020	Although metformin has been demonstrated to benefit several diseases possibly via AMP-activated protein kinase (AMPK) activation, it remains unknown how AMPK affects retinopathy in NaIO3 model.	Metformin	9-18	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	82-110
33126710-4	2020	Although metformin has been demonstrated to benefit several diseases possibly via AMP-activated protein kinase (AMPK) activation, it remains unknown how AMPK affects retinopathy in NaIO3 model.	Metformin	9-18	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	112-116
33268575-18	2020	Metformin effectively reduced H/R-induced apoptosis (P=0.013), mitoSOX release (P<0.001), HIF-1alpha, PGC1alpha and apoptosis-related protein expression, recovered the cell viability (P<0.001), and reduced myocardial infarction (P=0.003).	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	90-100
33268575-20	2020	Metformin can inhibit the accumulation of HIF-1alpha during hypoxia and effectively protect myocardium from ischemia/reperfusion injury.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	42-52
30572719-3	2020	Notably, protein levels of SIRT1, SIRT3, and SIRT4 were higher in patients with DR compared with controls after adjusting for diabetes duration and taking metformin (p = .001 for SIRT1; p = .001 for SIRT3; p = .005 for SIRT4).	Metformin	155-164	sirtuin 1	Homo sapiens	27-32
32800853-6	2020	We further investigated the role of the neurotrophic factors in the activation of TH and observed that both BDNF and GDNF-induction were essential for metformin-induced TH activation.	Metformin	151-160	brain derived neurotrophic factor	Homo sapiens	108-112
32180335-0	2020	Citrus fruit-derived flavonoid naringenin and the expression of hepatic organic cation transporter 1 protein in diabetic rats treated with metformin.	Metformin	139-148	solute carrier family 22 member 1	Rattus norvegicus	72-100
32180335-2	2020	The purpose of this study was to evaluate the role of naringenin on hepatic expression of organic cation transporter 1 (OCT 1) protein and its associated effects on metformin-associated hyperlactataemia in diabetes.	Metformin	165-174	solute carrier family 22 member 1	Rattus norvegicus	90-118
32180335-2	2020	The purpose of this study was to evaluate the role of naringenin on hepatic expression of organic cation transporter 1 (OCT 1) protein and its associated effects on metformin-associated hyperlactataemia in diabetes.	Metformin	165-174	solute carrier family 22 member 1	Rattus norvegicus	120-125
32180335-11	2020	Furthermore, naringenin with or without metformin but not metformin only significantly increased hepatic OCT1 expression in diabetic compared to non-treated diabetic rats.	Metformin	40-49	solute carrier family 22 member 1	Rattus norvegicus	105-109
32180335-12	2020	Contrastingly, metformin only but not naringenin significantly increased hepatic OCT 1 expression in non-diabetic rats compared to controls.	Metformin	15-24	solute carrier family 22 member 1	Rattus norvegicus	81-86
32180335-15	2020	These results suggest that naringenin ameliorated hyperglycaemia-induced reduction in hepatic OCT 1 expression leading to metformin accumulation and increased lactic acid production.	Metformin	122-131	solute carrier family 22 member 1	Rattus norvegicus	94-99
32841254-8	2020	Lower OPG/RANKL, increased OCN and TRAP expression were observed in hyperglycemic animals, and treatment with metformin partially reversed hyperglycemia on the OPG/RANKL, OPN and TRAP expression in the periodontitis.	Metformin	110-119	acid phosphatase 5, tartrate resistant	Rattus norvegicus	35-39
32841254-8	2020	Lower OPG/RANKL, increased OCN and TRAP expression were observed in hyperglycemic animals, and treatment with metformin partially reversed hyperglycemia on the OPG/RANKL, OPN and TRAP expression in the periodontitis.	Metformin	110-119	acid phosphatase 5, tartrate resistant	Rattus norvegicus	179-183
32841254-9	2020	The expression of SOX9 and RunX2 were also decreased by hyperglycemia and metformin treatment.	Metformin	74-83	SRY-box transcription factor 9	Rattus norvegicus	18-22
32904014-0	2020	Erratum: Metformin Promotes Beclin1-Dependent Autophagy to Inhibit the Progression of Gastric Cancer [Corrigendum].	Metformin	9-18	beclin 1	Homo sapiens	28-35
32690681-0	2020	Metformin inhibits RAN translation through PKR pathway and mitigates disease in C9orf72 ALS/FTD mice.	Metformin	0-9	eukaryotic translation initiation factor 2-alpha kinase 2	Mus musculus	43-46
32690681-6	2020	In summary, targeting PKR, including by use of metformin, is a promising therapeutic approach for C9orf72 ALS/FTD and other expansion diseases.	Metformin	47-56	eukaryotic translation initiation factor 2-alpha kinase 2	Mus musculus	22-25
32409919-8	2020	Moreover, treatment of Huh7-IR with 0.5, 1 or 2 mM of metformin by 24 h decreased the biomarkers associated with an insulin-resistant state.	Metformin	54-63	MIR7-3 host gene	Homo sapiens	23-27
32310257-9	2020	Metformin elevates circulating GDF15 chronically in man and the weight loss caused by this drug appears to be dependent on the rise in GDF15.	Metformin	0-9	growth differentiation factor 15	Homo sapiens	31-36
32310257-9	2020	Metformin elevates circulating GDF15 chronically in man and the weight loss caused by this drug appears to be dependent on the rise in GDF15.	Metformin	0-9	growth differentiation factor 15	Homo sapiens	135-140
32742327-0	2020	Metformin attenuates cardiac remodeling in mice through the Nrf2/Keap1 signaling pathway.	Metformin	0-9	kelch-like ECH-associated protein 1	Mus musculus	65-70
32792943-10	2020	In addition, either celecoxib alone or in combination with metformin suppressed NSCLC cell migration and invasion by inhibiting FAK, N-cadherin, and matrix metalloproteinase-9 activities.	Metformin	59-68	cadherin 2	Homo sapiens	133-143
32792943-10	2020	In addition, either celecoxib alone or in combination with metformin suppressed NSCLC cell migration and invasion by inhibiting FAK, N-cadherin, and matrix metalloproteinase-9 activities.	Metformin	59-68	matrix metallopeptidase 9	Homo sapiens	149-175
32631421-12	2020	Furthermore, metformin also regulated the mRNA and protein expression of MICA and HSP70 on the surface of human cervical cancer cells via the PI3K/Akt pathway, enhancing NK cell cytotoxicity.	Metformin	13-22	heat shock protein family A (Hsp70) member 4	Homo sapiens	82-87
32533334-8	2020	(TILs Rs = 0.63, CD4 + Rs = 0.224, CD8 + Rs = 0.42) In the metformin group, TILs increases were confirmed in five (29%) patients, while a decrease was confirmed in two (12%).	Metformin	59-68	CD8a molecule	Homo sapiens	35-38
32222530-6	2020	Moreover, NAC could recover the downregulation of p-PI3K and p-Akt treated with combination of metformin and cisplatin, which subsequently activated the PI3K/Akt signaling pathway.	Metformin	95-104	X-linked Kx blood group	Homo sapiens	10-13
32444490-0	2020	Metformin selectively inhibits metastatic colorectal cancer with the KRAS mutation by intracellular accumulation through silencing MATE1.	Metformin	0-9	KRAS proto-oncogene, GTPase	Homo sapiens	69-73
32444490-0	2020	Metformin selectively inhibits metastatic colorectal cancer with the KRAS mutation by intracellular accumulation through silencing MATE1.	Metformin	0-9	solute carrier family 47 member 1	Homo sapiens	131-136
32444490-2	2020	Inspiringly, the median survival time for KRAS-mutation mCRC patients with diabetes on metformin is 37.8 mo longer than those treated with other hypoglycemic drugs in combination with standard systemic therapy.	Metformin	87-96	KRAS proto-oncogene, GTPase	Homo sapiens	42-46
32444490-3	2020	In contrast, metformin could not improve the survival of mCRC patients with wild-type KRAS Interestingly, metformin is preferentially accumulated in KRAS-mutation mCRC cells, but not wild-type ones, in both primary cell cultures and patient-derived xenografts, which is in agreement with its tremendous effect in KRAS-mutation mCRC.	Metformin	106-115	KRAS proto-oncogene, GTPase	Homo sapiens	149-153
32444490-3	2020	In contrast, metformin could not improve the survival of mCRC patients with wild-type KRAS Interestingly, metformin is preferentially accumulated in KRAS-mutation mCRC cells, but not wild-type ones, in both primary cell cultures and patient-derived xenografts, which is in agreement with its tremendous effect in KRAS-mutation mCRC.	Metformin	106-115	KRAS proto-oncogene, GTPase	Homo sapiens	149-153
32444490-4	2020	Mechanistically, the mutated KRAS oncoprotein hypermethylates and silences the expression of multidrug and toxic compound extrusion 1 (MATE1), a specific pump that expels metformin from the tumor cells by up-regulating DNA methyltransferase 1 (DNMT1).	Metformin	171-180	KRAS proto-oncogene, GTPase	Homo sapiens	29-33
32444490-4	2020	Mechanistically, the mutated KRAS oncoprotein hypermethylates and silences the expression of multidrug and toxic compound extrusion 1 (MATE1), a specific pump that expels metformin from the tumor cells by up-regulating DNA methyltransferase 1 (DNMT1).	Metformin	171-180	solute carrier family 47 member 1	Homo sapiens	135-140
32444490-4	2020	Mechanistically, the mutated KRAS oncoprotein hypermethylates and silences the expression of multidrug and toxic compound extrusion 1 (MATE1), a specific pump that expels metformin from the tumor cells by up-regulating DNA methyltransferase 1 (DNMT1).	Metformin	171-180	DNA methyltransferase 1	Homo sapiens	219-242
32444490-4	2020	Mechanistically, the mutated KRAS oncoprotein hypermethylates and silences the expression of multidrug and toxic compound extrusion 1 (MATE1), a specific pump that expels metformin from the tumor cells by up-regulating DNA methyltransferase 1 (DNMT1).	Metformin	171-180	DNA methyltransferase 1	Homo sapiens	244-249
32444490-5	2020	Our findings provide evidence that KRAS-mutation mCRC patients benefit from metformin treatment and targeting MATE1 may provide a strategy to improve the anticancer response of metformin.	Metformin	76-85	KRAS proto-oncogene, GTPase	Homo sapiens	35-39
32444490-5	2020	Our findings provide evidence that KRAS-mutation mCRC patients benefit from metformin treatment and targeting MATE1 may provide a strategy to improve the anticancer response of metformin.	Metformin	177-186	KRAS proto-oncogene, GTPase	Homo sapiens	35-39
32444490-5	2020	Our findings provide evidence that KRAS-mutation mCRC patients benefit from metformin treatment and targeting MATE1 may provide a strategy to improve the anticancer response of metformin.	Metformin	177-186	solute carrier family 47 member 1	Homo sapiens	110-115
32572457-10	2020	Metformin treatment led to an upregulation of clock regulatory genes such as melanopsin (Opn4) and aralkylamine N-acetyltransferase (Aanat).	Metformin	0-9	opsin 4 (melanopsin)	Mus musculus	77-87
32572457-10	2020	Metformin treatment led to an upregulation of clock regulatory genes such as melanopsin (Opn4) and aralkylamine N-acetyltransferase (Aanat).	Metformin	0-9	opsin 4 (melanopsin)	Mus musculus	89-93
32572457-11	2020	In rMC-1 cells, AMPK activation via AICAR and metformin resulted in increased Kir4.1 and intermediate core clock component Bmal-1 protein expression.	Metformin	46-55	aryl hydrocarbon receptor nuclear translocator-like	Rattus norvegicus	123-129
32017603-0	2020	Metformin regulates TRPM6, a potential explanation for magnesium imbalance in type 2 diabetes patients.	Metformin	0-9	transient receptor potential cation channel subfamily M member 6	Homo sapiens	20-25
32017603-3	2020	Therefore, we aimed to investigate the short- and long-term effects of metformin on TRPM6.	Metformin	71-80	transient receptor potential cation channel subfamily M member 6	Homo sapiens	84-89
32017603-4	2020	Patch clamp recordings and biotinylation assays were performed upon 1h of incubation with metformin in TRPM6-transfected HEK293 cells.	Metformin	90-99	transient receptor potential cation channel subfamily M member 6	Homo sapiens	103-108
32017603-5	2020	Additionally, 24h treatment of mDCT15 kidney and hCaco-2 colon cells with metformin was applied to measure the effects on endogenous TRPM6 expression by RT-qPCR.	Metformin	74-83	transient receptor potential cation channel subfamily M member 6	Homo sapiens	133-138
32017603-6	2020	To assess Mg2+ absorption, 25Mg2+ uptake measurements were performed using ICP-MS. Short-term effects of metformin significantly increased TRPM6 activity and its cell surface trafficking.	Metformin	105-114	transient receptor potential cation channel subfamily M member 6	Homo sapiens	139-144
32017603-8	2020	Metformin lowered TRPM6 mRNA levels independently of insulin- and AMPK-mediated pathways.	Metformin	0-9	transient receptor potential cation channel subfamily M member 6	Homo sapiens	18-23
32017603-10	2020	Thereby, short-term metformin treatment increases TRPM6 activity explained by enhanced cell surface expression.	Metformin	20-29	transient receptor potential cation channel subfamily M member 6	Homo sapiens	50-55
32017603-11	2020	Conversely, long-term metformin treatment results in downregulation of TRPM6 gene expression in intestine and kidney cells.	Metformin	22-31	transient receptor potential cation channel subfamily M member 6	Homo sapiens	71-76
32734128-4	2020	The present study tested the combination therapy of metformin and trametinib by monitoring the alterations of regulatory effector proteins of cell signaling pathways and the effect of the combination on cell viability in NCI-H2087 NSCLC cells with NRAS and BRAF mutations.	Metformin	52-61	NRAS proto-oncogene, GTPase	Homo sapiens	248-252
31883148-8	2020	Furthermore, transport of cationic drugs, metformin and paclitaxel in HepG2 cells was blunted by OCT inhibitors, suggesting that hOCT1 and hOCT3 expressed in HepG2 cells exhibit notable impacts on cationic drug actions.	Metformin	42-51	solute carrier family 22 member 3	Homo sapiens	139-144
32399705-0	2020	Histomorphological, VEGF and TGF-beta immunoexpression changes in the diabetic rats" ovary and the potential amelioration following treatment with metformin and insulin.	Metformin	147-156	transforming growth factor alpha	Rattus norvegicus	29-37
32399705-5	2020	Therefore, the present study investigates the ovarian VEGF and TGF-beta immune-expression and its variations in diabetic, insulin and metformin-treated rats.	Metformin	134-143	transforming growth factor alpha	Rattus norvegicus	63-71
32360359-15	2020	qRT-PCR analyses showed that metformin decreased ACTH induced MC2R expression.	Metformin	29-38	melanocortin 2 receptor	Mus musculus	62-66
32360359-21	2020	In conclusion, we show that metformin acts on MC2R and MC3R signaling directly.	Metformin	28-37	melanocortin 2 receptor	Mus musculus	46-50
32251713-7	2020	Moreover, metformin decreased HSP70, increased Zac1 and AhR expression; these effects were abolished in AIP silenced QGP-1 cells.	Metformin	10-19	PLAG1 like zinc finger 1	Homo sapiens	47-51
32495169-2	2020	Metformin normalized the ratio of adenylyl cyclase effects of beta1/2- and beta3-agonists in the myocardial membranes, that is reduced in DM2, and restored phosphorylation of Akt-kinase by Ser473 and AMPK by Thr172 in the myocardium of diabetic rats.	Metformin	0-9	UDP glucuronosyltransferase family 1 member A6	Rattus norvegicus	62-69
32335799-10	2020	Furthermore, at highest concentration of metformin (500 mug/mL), all the embryos were arrested at compaction stage.	Metformin	41-50	thrombopoietin	Mus musculus	60-62
32203160-0	2020	NCOA5 deficiency promotes a unique liver protumorigenic microenvironment through p21WAF1/CIP1 overexpression, which is reversed by metformin.	Metformin	131-140	cyclin-dependent kinase inhibitor 1A (P21)	Mus musculus	89-93
32203160-3	2020	Importantly, prophylactic metformin treatment reversed these characteristics including aberrant p21WAF1/CIP1 expression and subsequently reduced HCC incidence in Ncoa5+/- male mice.	Metformin	26-35	cyclin-dependent kinase inhibitor 1A (P21)	Mus musculus	104-108
32368014-7	2020	Upregulated Bcl-2 and downregulated Bax were observed in propofol-treated HT-22 cells following metformin administration.	Metformin	96-105	BCL2-associated X protein	Mus musculus	36-39
32377293-8	2020	PCR analysis showed that metformin could effectively improve the mRNA expression level of nerve and synapse-related genes (Syp, Ngf, and Bdnf) in the brain.	Metformin	25-34	nerve growth factor	Mus musculus	128-131
32362869-6	2020	After treatment with metformin and LBP, the pathological changes in the spermatogenic tubules improved significantly, with an increase in the number of spermatogenic cells, upregulation of PCNA, and suppression of apoptosis in the testes.	Metformin	21-30	proliferating cell nuclear antigen	Rattus norvegicus	189-193
32362869-7	2020	The expressions of sirtuin 1 (SIRT1) and hypoxia-inducible factor 1-alpha (HIF-1alpha) in diabetic testes were also upregulated by metformin or LBP treatment.	Metformin	131-140	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	41-73
32362869-7	2020	The expressions of sirtuin 1 (SIRT1) and hypoxia-inducible factor 1-alpha (HIF-1alpha) in diabetic testes were also upregulated by metformin or LBP treatment.	Metformin	131-140	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	75-85
31731885-0	2020	Metformin Reduces CD4 T-Cell Exhaustion in HIV-Infected Adults on Suppressive Antiretroviral Therapy.	Metformin	0-9	CD4 molecule	Sus scrofa	18-21
31731885-5	2020	However, metformin over 24 weeks led to decreases compared to OBS in single PD1+ (percent decrease: -9.6% vs 7.5%, p=0.015), in dual PD1+TIGIT+ (-15.0% vs 10.4%, p=0.002) and in triple PD1+TIGIT+TIM3+ (-24.0% vs 8.1%, p=0.041) CD4 T-cells.	Metformin	9-18	CD4 molecule	Sus scrofa	227-230
31731885-7	2020	CONCLUSIONS: Metformin decreases the frequency of PD1+, PD1+TIGIT+ and PD1+TIGIT+TIM3+ expressing CD4 T-cells.	Metformin	13-22	CD4 molecule	Sus scrofa	98-101
32020647-7	2020	Metformin and ginger reduced the degenerative changes observed in the testes of diabetic rats, significantly reduced (p < .001) caspase-3 immunoexpression, and significantly increased (p < .001) the immune-expression of androgen receptors and proliferating cell nuclear antigen.	Metformin	0-9	proliferating cell nuclear antigen	Rattus norvegicus	243-277
32014566-9	2020	Concomitantly, the hippocampal synaptic density and MAP2 and PSD95 immunoreactivity were significantly reduced by sevoflurane exposure but showed partial recovery in the metformin-pretreated group.	Metformin	170-179	discs large MAGUK scaffold protein 4	Mus musculus	61-66
32207597-0	2021	Study of effect of metformin on expression levels of TNF-alpha and IL-18 in animal models of polycystic ovary syndrome.	Metformin	19-28	interleukin 18	Homo sapiens	67-72
32194991-6	2020	To further reveal the mechanism involved, we examined how metformin treatment affected NLRP3 inflammasome activated by TNF-alpha and IL-17A stimulation.	Metformin	58-67	interleukin 17A	Homo sapiens	133-139
32194991-8	2020	Furthermore, inhibitors of AMPK and SIRT1 abrogated the downregulation of caspase-1 induced by metformin treatment, indicating that AMPK and SIRT1 are essential for the inhibitory effect on NLRP3 inflammasome in NHEKs.	Metformin	95-104	sirtuin 1	Homo sapiens	36-41
32194991-8	2020	Furthermore, inhibitors of AMPK and SIRT1 abrogated the downregulation of caspase-1 induced by metformin treatment, indicating that AMPK and SIRT1 are essential for the inhibitory effect on NLRP3 inflammasome in NHEKs.	Metformin	95-104	sirtuin 1	Homo sapiens	141-146
32194991-10	2020	Metformin treatment inhibited upregulation of IL-36gamma, CXCL1, CXCL2, CCL20, S100A7, S100A8 and S100A9 mRNA and protein levels induced by TNF-alpha and IL-17A stimulation.	Metformin	0-9	C-X-C motif chemokine ligand 1	Homo sapiens	58-63
32194991-10	2020	Metformin treatment inhibited upregulation of IL-36gamma, CXCL1, CXCL2, CCL20, S100A7, S100A8 and S100A9 mRNA and protein levels induced by TNF-alpha and IL-17A stimulation.	Metformin	0-9	interleukin 17A	Homo sapiens	154-160
32194991-13	2020	A cytokine profile in the epidermis under metformin treatment showed that IL-1beta, Cxcl1, Cxcl2, S100a7, S100a8 and S100A9 mRNA levels were downregulated compared with control levels.	Metformin	42-51	C-X-C motif chemokine ligand 1	Homo sapiens	84-89
31815765-7	2020	In addition, metformin reduced the phosphorylation of receptor tyrosine kinases, especially Tie-2, ALK, PYK, EphA4, and EphA10, as well as angiogenesis-related proteins, including RANTES, TGF-beta, and TIMP-1.	Metformin	13-22	ALK receptor tyrosine kinase	Homo sapiens	99-102
31815765-7	2020	In addition, metformin reduced the phosphorylation of receptor tyrosine kinases, especially Tie-2, ALK, PYK, EphA4, and EphA10, as well as angiogenesis-related proteins, including RANTES, TGF-beta, and TIMP-1.	Metformin	13-22	EPH receptor A4	Homo sapiens	109-114
31815765-7	2020	In addition, metformin reduced the phosphorylation of receptor tyrosine kinases, especially Tie-2, ALK, PYK, EphA4, and EphA10, as well as angiogenesis-related proteins, including RANTES, TGF-beta, and TIMP-1.	Metformin	13-22	EPH receptor A10	Homo sapiens	120-126
31815765-7	2020	In addition, metformin reduced the phosphorylation of receptor tyrosine kinases, especially Tie-2, ALK, PYK, EphA4, and EphA10, as well as angiogenesis-related proteins, including RANTES, TGF-beta, and TIMP-1.	Metformin	13-22	C-C motif chemokine ligand 5	Homo sapiens	180-186
31938854-6	2020	Moreover, rapamycin and metformin induced autophagic flux in ARPE-19 cells and increased the LC3-II level in retinal tissues exposed to vital dyes.	Metformin	24-33	microtubule associated protein 1 light chain 3 alpha	Homo sapiens	93-96
31975558-7	2020	Moreover, PINK1 expression displayed a significant positive association with HOMA-beta indices, and TEM studies further confirmed reduced distortions in mitochondrial morphology in the metformin group only.	Metformin	185-194	PTEN induced kinase 1	Homo sapiens	10-15
31653514-12	2020	Metformin reduced plasma TNFalpha levels and decreased tissue expression of COX2 and NOX2 (which were positively correlated), without affecting SOD1 and SOD2.	Metformin	0-9	cytochrome b-245 beta chain	Rattus norvegicus	85-89
32021253-3	2020	Besides, protein levels of p-JNK1 and c-Jun N-terminal kinases (JNK) in metformin-treated TPC-1 cells were detected by Western blot.	Metformin	72-81	Jun proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	38-43
31715372-11	2020	Relative to the diabetic control, treatments with omega-3 or metformin caused significant elevations in hepatic glycogen, total alkaline phosphatase (TALP), osteocalcin, PTH, estradiol, and calcium; however, significant decreases in TRAP and glucose.	Metformin	61-70	acid phosphatase 5, tartrate resistant	Rattus norvegicus	233-237
31955626-8	2020	In addition, combination treatment with ipragliflozin and metformin additively improved these symptoms.Conclusions: These results demonstrate that the SGLT2 selective inhibitor ipragliflozin improves not only hyperglycemia but also NASH in type 2 diabetic mice, suggesting that treatment with ipragliflozin alone and in combination with metformin may be effective for treating type 2 diabetes with NASH.	Metformin	58-67	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	151-156
31955626-8	2020	In addition, combination treatment with ipragliflozin and metformin additively improved these symptoms.Conclusions: These results demonstrate that the SGLT2 selective inhibitor ipragliflozin improves not only hyperglycemia but also NASH in type 2 diabetic mice, suggesting that treatment with ipragliflozin alone and in combination with metformin may be effective for treating type 2 diabetes with NASH.	Metformin	337-346	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	151-156
30474540-5	2020	RESULTS: An in-silico result of current investigation has shown the good interaction of metformin, propranolol, and amitriptyline towards various targets (Beta-lactamase, Penicillin-binding proteins, Staphylokinase protein, Oxidoreductase protein, etc.)	Metformin	88-97	thioredoxin reductase 1	Homo sapiens	224-238
31892847-6	2020	Additionally, our results showed that NAC-suppressed JNK/c-Jun signaling pathway could have been activated through metformin treatment.	Metformin	115-124	Jun proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	57-62
31892847-8	2020	Thus, we propose that metformin could induce cell cycle arrest as well as programmed cell death, including apoptosis and autophagy, through ROS-dependent JNK/c-Jun cascade in human osteosarcoma.	Metformin	22-31	Jun proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	158-163
32538851-9	2020	Furthermore, DNLA and metformin enhanced autophagy activity by increasing LC3-II, Beclin1, and Klotho, and by decreasing p62 in the hippocampus and cortex.	Metformin	22-31	klotho	Mus musculus	95-101
32538851-9	2020	Furthermore, DNLA and metformin enhanced autophagy activity by increasing LC3-II, Beclin1, and Klotho, and by decreasing p62 in the hippocampus and cortex.	Metformin	22-31	nucleoporin 62	Mus musculus	121-124
33184242-11	2020	We found Metformin pre-treatment attenuated human and rat cardiomyocytes apoptosis, HMGB1, TNFalpha and IL-6 release and ROS production that were induced by high-glucose stimulation, and these effects of metformin could be blocked by okadaic acid treatment.	Metformin	9-18	high mobility group box 1	Rattus norvegicus	84-89
32341701-0	2020	The Influence of Metformin to the Transcriptional Activity of the mTOR and FOX3 Genes in Parapancreatic Adipose Tissue of Streptozotocin-Induced Diabetic Rats.	Metformin	17-26	mechanistic target of rapamycin kinase	Rattus norvegicus	66-70
32341701-3	2020	Therefore, the purpose of the study was to determine the mRNA expression levels of mTOR, Foxp3, IL1beta, and IL17A genes in rat parapancreatic adipose tissue with experimental streptozotocin-induced diabetes mellitus, with or without metformin administration.	Metformin	234-243	mechanistic target of rapamycin kinase	Rattus norvegicus	83-87
31654752-2	2020	Metformin is an AMPK inducer that has been used in cancer therapeutic trials.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	16-20
31822720-9	2019	A four-hour treatment of metformin specifically reduced succinate, and the replenishment of succinate inhibited the activation of KDM2A by metformin, but did not inhibit the activation of AMPK.	Metformin	139-148	lysine demethylase 2A	Homo sapiens	130-135
31822720-11	2019	These results indicate that metformin activates AMPK and reduces the intracellular succinate level, both of which are required for the activation of KDM2A to reduce rRNA transcription.	Metformin	28-37	lysine demethylase 2A	Homo sapiens	149-154
31801093-7	2019	Beyond AMPK, metformin activates protein kinase D and MAPKAPK2 in an LKB1-independent manner, revealing additional kinases that may mediate aspects of metformin response.	Metformin	151-160	protein kinase D1	Mus musculus	33-49
31357226-7	2019	Consequently, metformin reduced E-selectin as well ICAM and VCAM-1.	Metformin	14-23	selectin E	Rattus norvegicus	32-42
31357226-7	2019	Consequently, metformin reduced E-selectin as well ICAM and VCAM-1.	Metformin	14-23	intercellular adhesion molecule 1	Rattus norvegicus	51-55
31833226-2	2019	Metformin may exacerbate the energy disturbances observed during exercise leading to enhanced AMPK activation, and these disturbances may provoke early muscular fatigue.	Metformin	0-9	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	94-98
31833226-3	2019	We studied acute (1 day) and short-term (4 days) effects of metformin treatment on AMPK and its downstream signaling network, in healthy human skeletal muscle and adipose tissue at rest and during exercise, by applying a randomized blinded crossover study design in 10 lean men.	Metformin	60-69	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	83-87
31582211-0	2019	Treatment with metformin prevents pre-eclampsia by suppressing migration of trophoblast cells via modulating the signaling pathway of UCA1/miR-204/MMP-9.	Metformin	15-24	matrix metallopeptidase 9	Homo sapiens	147-152
31582211-2	2019	This study aims to investigate the molecular mechanism of how UCA1 interferes with MMP9 expression under the influence of metformin, which contributes to the development of pre-eclampsia.	Metformin	122-131	matrix metallopeptidase 9	Homo sapiens	83-87
31433832-7	2019	Further, we demonstrate that metformin can suppress CD54 expression on CD4+ T cells by inhibiting NF-kappaB/p65 phosphorylation.	Metformin	29-38	intercellular adhesion molecule 1	Homo sapiens	52-56
31220411-3	2019	We found that metformin decreased the cell apoptosis rate and death, ratio of Bcl-2/Bax, and expression of NR2A and NR2B, and increased the expression of LC3 in Abeta25-35 -treated SH-SY5Y cells.	Metformin	14-23	microtubule associated protein 1 light chain 3 alpha	Homo sapiens	154-157
31518877-6	2019	Treatment with metformin alleviated diabetes-induced metabolic disorders and atherosclerosis, as well as NLRP3 inflammasomes activation and dysregulation of thioredoxin-1/thioredoxin-interacting protein.	Metformin	15-24	thioredoxin 1	Mus musculus	157-170
31518877-9	2019	Moreover, high glucose decreased thioredoxin-1 expression and increased thioredoxin-interacting protein expression, which was also reversed by metformin.	Metformin	143-152	thioredoxin 1	Mus musculus	33-46
31518877-10	2019	CONCLUSIONS: Metformin inhibited NLRP3 inflammasomes activation and suppressed diabetes-accelerated atherosclerosis in apoE-/- mice, which at least partially through activation of AMPK and regulation of thioredoxin-1/thioredoxin-interacting protein.	Metformin	13-22	thioredoxin 1	Mus musculus	203-216
31410531-14	2019	ATP and metformin reciprocally change cellular pH homeostasis in liver, causing opposite shifts in liver activity of PTP1B, a key negative regulator of insulin signalling.	Metformin	8-17	protein tyrosine phosphatase, non-receptor type 1	Mus musculus	117-122
31369842-0	2019	Inhibition of neointima hyperplasia by the combined therapy of linagliptin and metformin via AMPK/Nox4 signaling in diabetic rats.	Metformin	79-88	NADPH oxidase 4	Rattus norvegicus	98-102
31369842-11	2019	Linagliptin and metformin were synergistical to target AMPK/Nox4 signal pathway in VSMCs incubated with HG and in the cardia artery of diabetic rats, which was superior to the monotherapy.	Metformin	16-25	NADPH oxidase 4	Rattus norvegicus	60-64
31369842-12	2019	CONCLUSIONS: We demonstrated that the potential protection of the combined use of linagliptin and metformin on VSMC remodeling through AMPK/Nox4 signal pathway, resulting in the improvement of neointima hyperplasia in diabetic rats.	Metformin	98-107	NADPH oxidase 4	Rattus norvegicus	140-144
31486135-10	2019	Finally, we demonstrated that the clinically approved drug metformin sensitizes chemoresistant OVCA cells to CDDP via PDK1-HKII pathway.	Metformin	59-68	pyruvate dehydrogenase kinase 1	Homo sapiens	118-122
31437793-8	2019	Furthermore, an attenuation of antigen-induced IgG2b antibody production by two different doses of metformin was also observed in the AChR-specific recall response.	Metformin	99-108	cholinergic receptor nicotinic alpha 2 subunit	Rattus norvegicus	134-138
31607288-7	2019	Metformin inhibited the expression of GLUT1, LDHA, ALDOA, PDK1, and PGK1 genes of K562 cells (P&lt;0.05) showing a dose-dependent manner(r=0.83,r=0.80,r=0.72,r=0.76,r=0.73,respectively).	Metformin	0-9	solute carrier family 2 member 1	Homo sapiens	38-43
31607288-7	2019	Metformin inhibited the expression of GLUT1, LDHA, ALDOA, PDK1, and PGK1 genes of K562 cells (P&lt;0.05) showing a dose-dependent manner(r=0.83,r=0.80,r=0.72,r=0.76,r=0.73,respectively).	Metformin	0-9	pyruvate dehydrogenase kinase 1	Homo sapiens	58-62
31607288-8	2019	Metformin inhibited the expression of P-Akt, P-S6, GLUT1, LDHA proteins of K562 cells(P&lt;0.05), showing a dose-dependent relationship(r=0.80,r=0.92,r=0.83,r=0.92,respectively).	Metformin	0-9	taste 2 receptor member 63 pseudogene	Homo sapiens	45-49
31607288-8	2019	Metformin inhibited the expression of P-Akt, P-S6, GLUT1, LDHA proteins of K562 cells(P&lt;0.05), showing a dose-dependent relationship(r=0.80,r=0.92,r=0.83,r=0.92,respectively).	Metformin	0-9	solute carrier family 2 member 1	Homo sapiens	51-56
31348945-9	2019	Metformin also reduced collagen VI in both gene and protein expression level, MMP2 and MMP9 in gene expression, and also the expression of apoptosis and necrosis gene.	Metformin	0-9	matrix metallopeptidase 9	Homo sapiens	87-91
31348946-7	2019	However, there is a growing understanding that Metformin demonstrates its anti-epileptic effect mainly via ameliorating brain oxidative damage, activation of AMPK, inhibition of mTOR pathway, downregulation of alpha-synuclein, reducing apoptosis, downregulation of BDNF and TrkB level.	Metformin	47-56	brain derived neurotrophic factor	Homo sapiens	265-269
31001733-14	2019	In addition, we found that metformin not only inhibited CCL15 expression in M2-type TAMs enhanced by hypoxia, but also suppressed CCR1 surface expression in HNSCC cells.	Metformin	27-36	C-C motif chemokine ligand 15	Homo sapiens	56-61
31136032-0	2019	Hyperglycemia induces NF-kappaB activation and MCP-1 expression via downregulating GLP-1R expression in rat mesangial cells: inhibition by metformin.	Metformin	139-148	glucagon-like peptide 1 receptor	Rattus norvegicus	83-89
31136032-7	2019	We further proved that metformin restored high glucose-inhibited GLP-1R mRNA expression and decreased high glucose evoked inflammation in HBZY-1 cells.	Metformin	23-32	glucagon-like peptide 1 receptor	Rattus norvegicus	65-71
31136032-8	2019	On the basis of these findings, we conclude that high glucose lowers GLP-1R expression and leads to inflammatory responses in mesangial cells, which can be reversed by metformin.	Metformin	168-177	glucagon-like peptide 1 receptor	Rattus norvegicus	69-75
31136032-9	2019	These data support the rationale of combinative therapy of metformin with GLP-1R agonists in DN.	Metformin	59-68	glucagon-like peptide 1 receptor	Rattus norvegicus	74-80
30989716-12	2019	We also discuss the activation of AMP activated protein kinase (AMPK) by the most widely used drug for type 2 diabetes, metformin, which exerts a dual negative regulatory effect on mTOR and BMP signaling, suggesting that metformin is a promising drug treatment for HO.	Metformin	120-129	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	34-62
30989716-12	2019	We also discuss the activation of AMP activated protein kinase (AMPK) by the most widely used drug for type 2 diabetes, metformin, which exerts a dual negative regulatory effect on mTOR and BMP signaling, suggesting that metformin is a promising drug treatment for HO.	Metformin	120-129	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	64-68
30989716-12	2019	We also discuss the activation of AMP activated protein kinase (AMPK) by the most widely used drug for type 2 diabetes, metformin, which exerts a dual negative regulatory effect on mTOR and BMP signaling, suggesting that metformin is a promising drug treatment for HO.	Metformin	221-230	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	34-62
30989716-12	2019	We also discuss the activation of AMP activated protein kinase (AMPK) by the most widely used drug for type 2 diabetes, metformin, which exerts a dual negative regulatory effect on mTOR and BMP signaling, suggesting that metformin is a promising drug treatment for HO.	Metformin	221-230	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	64-68
30970232-5	2019	We found that the use of both baicalein and metformin increased the glucose consumption of IR cells, as well as increasing the pyruvate kinase (PK) and glucokinase (GCK) activity.	Metformin	44-53	glucokinase	Homo sapiens	152-163
30970232-5	2019	We found that the use of both baicalein and metformin increased the glucose consumption of IR cells, as well as increasing the pyruvate kinase (PK) and glucokinase (GCK) activity.	Metformin	44-53	glucokinase	Homo sapiens	165-168
31273547-6	2019	DMBG decreases the level of the mTOR protein and reverses the effect of hyperglycaemic stimulation on the activity of MDCK cells.	Metformin	0-4	mechanistic target of rapamycin kinase	Canis lupus familiaris	32-36
31273547-8	2019	Therefore, klotho plays an important role in the mechanism by which DMBG inhibits the mTOR pathway to protect renal function.	Metformin	68-72	mechanistic target of rapamycin kinase	Canis lupus familiaris	86-90
31336028-0	2019	Combination of metformin and luteolin synergistically protects carbon tetrachloride-induced hepatotoxicity: Mechanism involves antioxidant, anti-inflammatory, antiapoptotic, and Nrf2/HO-1 signaling pathway.	Metformin	15-24	heme oxygenase 1	Rattus norvegicus	183-187
30918134-0	2019	Circulating zinc-alpha2-glycoprotein is reduced in women with polycystic ovary syndrome, but can be increased by exenatide or metformin treatment.	Metformin	126-135	alpha-2-glycoprotein 1, zinc-binding	Homo sapiens	12-36
31186373-3	2019	Activation of AMPK with the type 2 diabetes drug metformin (GlucoPhage) also increased mTORC2 signaling in liver in vivo and in primary hepatocytes in an AMPK-dependent manner.	Metformin	49-58	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	14-18
31186373-3	2019	Activation of AMPK with the type 2 diabetes drug metformin (GlucoPhage) also increased mTORC2 signaling in liver in vivo and in primary hepatocytes in an AMPK-dependent manner.	Metformin	49-58	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	154-158
31186373-3	2019	Activation of AMPK with the type 2 diabetes drug metformin (GlucoPhage) also increased mTORC2 signaling in liver in vivo and in primary hepatocytes in an AMPK-dependent manner.	Metformin	60-70	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	14-18
31186373-3	2019	Activation of AMPK with the type 2 diabetes drug metformin (GlucoPhage) also increased mTORC2 signaling in liver in vivo and in primary hepatocytes in an AMPK-dependent manner.	Metformin	60-70	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	154-158
31164151-0	2019	Metformin inhibits metastatic breast cancer progression and improves chemosensitivity by inducing vessel normalization via PDGF-B downregulation.	Metformin	0-9	platelet derived growth factor subunit B	Homo sapiens	123-129
31164151-6	2019	Lentiviral shRNA-PDGF-B transfection was used for observing the contribution of PDGF-B knockdown to metformin"s vascular effects.	Metformin	100-109	platelet derived growth factor subunit B	Homo sapiens	80-86
31164151-11	2019	Further results of genetic screening and in vivo experiments showed that the downregulation of platelet-derived growth factor B (PDGF-B) greatly contributed to the metformin-induced vessel normalization.	Metformin	164-173	platelet derived growth factor subunit B	Homo sapiens	95-127
31164151-11	2019	Further results of genetic screening and in vivo experiments showed that the downregulation of platelet-derived growth factor B (PDGF-B) greatly contributed to the metformin-induced vessel normalization.	Metformin	164-173	platelet derived growth factor subunit B	Homo sapiens	129-135
31020710-8	2019	Enhanced levels of microtubule-associated protein 1 light chain 3 II and Beclin-1 were observed after exposure to tHA plus metformin.	Metformin	123-132	beclin 1	Homo sapiens	73-81
31210335-10	2019	Furthermore, both mRNA and protein levels of PPAR-gamma in VSMCs were downregulated after 500 mug/L LPS induction for 24 h, which were remarkably reversed by the treatment of different concentrations of metformin.	Metformin	203-212	peroxisome proliferator-activated receptor gamma	Rattus norvegicus	45-55
31210335-13	2019	The anti-inflammatory effects of metformin inhibit the inflammatory response through downregulating rely on the downregulation of TLR4 expression and upregulation ofng PPAR-gamma activity.	Metformin	33-42	peroxisome proliferator-activated receptor gamma	Rattus norvegicus	168-178
30903363-4	2019	The major molecular targets of metformin include complex I of the mitochondrial electron transport chain, adenosine monophosphate (AMP)-activated protein kinase (AMPK), and mechanistic target of rapamycin complex 1 (mTORC1), but AMPK-independent effects of metformin have also been described.	Metformin	31-40	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	162-166
30903363-4	2019	The major molecular targets of metformin include complex I of the mitochondrial electron transport chain, adenosine monophosphate (AMP)-activated protein kinase (AMPK), and mechanistic target of rapamycin complex 1 (mTORC1), but AMPK-independent effects of metformin have also been described.	Metformin	31-40	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	229-233
30953641-9	2019	These pharmacodynamic and pharmacokinetic changes were probably due to a decrease in Oct1 expression in the liver, resulting in altered hepatic uptake of metformin in vivo.	Metformin	154-163	solute carrier family 22 member 1	Rattus norvegicus	85-89
30953641-10	2019	SIGNIFICANCE: These results implied that the gut microbiota may play an important role in the pharmacodynamics and pharmacokinetics of metformin and that the changes in these properties are probably due to Oct1 downregulation in the livers of pseudo-germ-free rats.	Metformin	135-144	solute carrier family 22 member 1	Rattus norvegicus	206-210
30653446-8	2019	Furthermore, GLI-family (transcription factors of the Hh pathway) knockdown in HUVECs and retinal vasculature revealed that downregulation of hyperglycemia-activated autophagy by the metformin-mediated Hh pathway activation was GLI1 dependent.	Metformin	183-192	GLI family zinc finger 1	Homo sapiens	13-16
30784939-3	2019	Genistein an isoflavone, is an important polyphenol and has wide range of therapeutic potentials, but its therapeutic effects alone and/or in combination with metformin on GLP-1 secretion have not been investigated yet.	Metformin	159-168	glucagon	Rattus norvegicus	172-177
30784939-4	2019	Hence, we aimed to investigate the stimulatory action of genistein in combination with metformin on GLP-1 via downregulation of inflammatory mediators, hyperlipidemia and hyperglycemia in alloxan-induced diabetic rats.	Metformin	87-96	glucagon	Rattus norvegicus	100-105
30784939-7	2019	We found that genistein alone and/or in combination with metformin significantly increased the serum level (P &lt; 0.01) and tissue content (P &lt; 0.05) of GLP-1 in intestine when compared with that of metformin-treated animals.	Metformin	57-66	glucagon	Rattus norvegicus	157-162
30784939-12	2019	Hence, our work provides new insights on the synergistic effects of genistein and metformin on GLP-1 secretion.	Metformin	82-91	glucagon	Rattus norvegicus	95-100
29934960-12	2019	Metformin inhibited the expression of MCP-1 in NRK-52E cells.	Metformin	0-9	chemokine (C-C motif) ligand 2	Mus musculus	38-43
30466344-10	2019	Endoplasmic reticulum stress-related apoptosis proteins (glucose-regulated protein 78, caspase-12, and CCAAT/enhancer binding protein (EBP) homologous protein) were downregulated after metformin treatment.	Metformin	185-194	caspase 12	Rattus norvegicus	87-97
30926854-8	2019	Promoter analysis and chromatin immunoprecipitation assays of genes that changed expression in response to metformin revealed enrichment of the transcriptional regulator forkhead box O3a (FOXO3a) in normal human fibroblasts, but not of the predicted serum response factor (SRF).	Metformin	107-116	serum response factor	Homo sapiens	250-271
30926854-8	2019	Promoter analysis and chromatin immunoprecipitation assays of genes that changed expression in response to metformin revealed enrichment of the transcriptional regulator forkhead box O3a (FOXO3a) in normal human fibroblasts, but not of the predicted serum response factor (SRF).	Metformin	107-116	serum response factor	Homo sapiens	273-276
30934600-0	2019	Metformin Pharmacogenetics: Effects of SLC22A1, SLC22A2, and SLC22A3 Polymorphisms on Glycemic Control and HbA1c Levels.	Metformin	0-9	solute carrier family 22 member 3	Homo sapiens	61-68
30934600-3	2019	The objective of this study was to investigate the relationship between twenty-one single nucleotide polymorphisms (SNPs) in the SLC22A1, SLC22A2, and SLC22A3 genes and their effects on metformin pharmacogenetics in Jordanian patients diagnosed with type 2 diabetes mellitus.	Metformin	186-195	solute carrier family 22 member 3	Homo sapiens	151-158
30297296-9	2019	mRNA expression of SLC22A3 was significantly reduced in patients taking metformin as compared to other groups.	Metformin	72-81	solute carrier family 22 member 3	Homo sapiens	19-26
30297296-10	2019	CONCLUSIONS: These results suggested that the SLC22A3 rs3088442 at position 2282 A allele may confer metformin clinical responses in patients with type 2 diabetes in the Pakistani population.	Metformin	101-110	solute carrier family 22 member 3	Homo sapiens	46-53
30890498-10	2019	The results of ELISA and qRT-PCR revealed that metformin treatment obviously increased Foxp3 and TGF-beta expressions at both the protein and mRNA levels and significantly decreased the levels of ROR-gammat, IL-17 and TNF-alpha as well as IL-35 level in these patients.	Metformin	47-56	interleukin 17A	Homo sapiens	208-213
30779140-0	2019	Metformin ameliorates experimental diabetic periodontitis independently of mammalian target of rapamycin (mTOR) inhibition by reducing NIMA-related kinase 7(Nek7) expression.	Metformin	0-9	NIMA related kinase 7	Homo sapiens	157-161
30899391-8	2019	Moreover, in the metformin but not the sitagliptin treated group, JAK2/STAT3 activation was associated with having better improved cardiac remolding and reduced myocardial apoptosis.	Metformin	17-26	Janus kinase 2	Rattus norvegicus	66-70
30899391-9	2019	In vitro studies further validated that metformin could activate JAK2/STAT3 pathway and alleviate apoptosis of NRCMs under hyperglycemia incubation.	Metformin	40-49	Janus kinase 2	Rattus norvegicus	65-69
30899391-11	2019	The superior cardio-protective effect of metformin over sitagliptin treatment may partly account for the differences we observed in JAK2/STAT3 activation, indicating that measuring JAK2/STAT3 pathway coupled with metformin treatment may give insight into a more promising DM treatment.	Metformin	41-50	Janus kinase 2	Rattus norvegicus	132-136
30899391-11	2019	The superior cardio-protective effect of metformin over sitagliptin treatment may partly account for the differences we observed in JAK2/STAT3 activation, indicating that measuring JAK2/STAT3 pathway coupled with metformin treatment may give insight into a more promising DM treatment.	Metformin	41-50	Janus kinase 2	Rattus norvegicus	181-185
30625338-8	2019	Mechanistically, metformin reduces the expression of phospho-ERK (Thr202/Tyr204) and two forms of proto-oncogenes, Cyclin D1 and c-Myc, in AKT/c-Met mice.	Metformin	17-26	cyclin D1	Mus musculus	115-124
30614910-5	2019	The number of neuronal nuclei positive neuron was significantly increased and glial fibrillary acidic protein positive astrocyte became obviously declined in the CA1 region in I/R rats treated with metformin.	Metformin	198-207	glial fibrillary acidic protein	Rattus norvegicus	78-109
30718758-9	2019	Furthermore, compared with each treatment alone metformin in combination with cisplatin yielded the lowest level of radiation-induced Rad51 foci, an essential protein of homologous recombination repair.	Metformin	48-57	RAD51 recombinase	Homo sapiens	134-139
30718758-11	2019	Pharmacological inhibition of AMP-activated protein kinase (AMPK) demonstrated that metformin enhances the radiosensitizing effect of cisplatin through an AMPK-dependent pathway only in H460 but not in A549 cells.	Metformin	84-93	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	30-58
30718758-11	2019	Pharmacological inhibition of AMP-activated protein kinase (AMPK) demonstrated that metformin enhances the radiosensitizing effect of cisplatin through an AMPK-dependent pathway only in H460 but not in A549 cells.	Metformin	84-93	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	60-64
30718758-11	2019	Pharmacological inhibition of AMP-activated protein kinase (AMPK) demonstrated that metformin enhances the radiosensitizing effect of cisplatin through an AMPK-dependent pathway only in H460 but not in A549 cells.	Metformin	84-93	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	155-159
30427219-11	2019	When inner medullary tissue was treated with the PKC activator phorbol dibutyrate (PDBu), the AMPK activator metformin, or both, AQP2 phosphorylation at S261 was decreased with PDBu or metformin alone, but there was no additive effect on phosphorylation with PDBu and metformin together.	Metformin	185-194	protein kinase C, gamma	Rattus norvegicus	49-52
30427219-11	2019	When inner medullary tissue was treated with the PKC activator phorbol dibutyrate (PDBu), the AMPK activator metformin, or both, AQP2 phosphorylation at S261 was decreased with PDBu or metformin alone, but there was no additive effect on phosphorylation with PDBu and metformin together.	Metformin	185-194	protein kinase C, gamma	Rattus norvegicus	49-52
29891331-0	2019	Serum Brain-Derived Neurotrophic Factor is Related to Platelet Reactivity and Metformin Treatment in Adult Patients With Type 2 Diabetes Mellitus.	Metformin	78-87	brain derived neurotrophic factor	Homo sapiens	6-39
29891331-6	2019	In univariate linear regression analyses, predictive factors for serum BDNF levels above the median were metformin treatment, current smoking, platelet count, triglyceride concentration, total cholesterol concentration and CADP-CT &gt;74 s. In multivariate backward stepwise analysis CADP-CT &gt;141 s; adiponectin concentration &gt;4.22 microg/mL; total cholesterol and low-density lipoprotein levels were independently associated with serum BDNF levels above the median.	Metformin	105-114	brain derived neurotrophic factor	Homo sapiens	71-75
29891331-7	2019	CONCLUSIONS: Our results suggest that BDNF may be associated with lipid metabolism and that increased production of BDNF may be related to metformin treatment.	Metformin	139-148	brain derived neurotrophic factor	Homo sapiens	116-120
30178545-0	2019	Metformin is the key factor in elevated plasma growth differentiation factor-15 levels in type 2 diabetes: A nested, case-control study.	Metformin	0-9	growth differentiation factor 15	Homo sapiens	47-79
30178545-1	2019	Produced as a tissue defence response to hypoxia and inflammation, growth differentiation factor-15 (GDF-15) is elevated in people receiving metformin treatment.	Metformin	141-150	growth differentiation factor 15	Homo sapiens	67-99
30178545-1	2019	Produced as a tissue defence response to hypoxia and inflammation, growth differentiation factor-15 (GDF-15) is elevated in people receiving metformin treatment.	Metformin	141-150	growth differentiation factor 15	Homo sapiens	101-107
30178545-2	2019	To gain insight into the relationship of GDF-15 with metformin and major cardiovascular risk factors, we analysed the data from the SUMMIT cohort (n = 1438), a four-centre, nested, case-control study aimed at verifying whether biomarkers of atherosclerosis differ according to the presence of type 2 diabetes and cardiovascular disease.	Metformin	53-62	growth differentiation factor 15	Homo sapiens	41-47
30178545-4	2019	In participants with diabetes, metformin treatment was associated with a 40% rise in GDF-15 level, which was independent of the other major factors, and largely explained their elevated GDF-15 levels.	Metformin	31-40	growth differentiation factor 15	Homo sapiens	85-91
30178545-4	2019	In participants with diabetes, metformin treatment was associated with a 40% rise in GDF-15 level, which was independent of the other major factors, and largely explained their elevated GDF-15 levels.	Metformin	31-40	growth differentiation factor 15	Homo sapiens	186-192
30178545-5	2019	The relatively high GDF-15 bioavailability might partly explain the protective cardiovascular effects of metformin.	Metformin	105-114	growth differentiation factor 15	Homo sapiens	20-26
30345618-0	2019	Metformin attenuates renal medullary hypoxia in diabetic nephropathy through inhibition uncoupling protein-2.	Metformin	0-9	uncoupling protein 2	Rattus norvegicus	88-108
30345618-7	2019	Metformin reduced UCP2-dependent LEAK and differentially affected medullary mitochondrial superoxide radical production in control and diabetic rats.	Metformin	0-9	uncoupling protein 2	Rattus norvegicus	18-22
30413829-0	2019	A variant of the glucose transporter gene SLC2A2 modifies the glycaemic response to metformin therapy in recently diagnosed type 2 diabetes.	Metformin	84-93	solute carrier family 2 member 2	Homo sapiens	42-48
30413829-1	2019	AIMS/HYPOTHESIS: The aim of this study was to investigate the modifying effect of the glucose transporter (GLUT2) gene SLC2A2 (rs8192675) variant on the glycaemic response to metformin in individuals recently diagnosed with type 2 diabetes.	Metformin	175-184	solute carrier family 2 member 2	Homo sapiens	107-112
30413829-1	2019	AIMS/HYPOTHESIS: The aim of this study was to investigate the modifying effect of the glucose transporter (GLUT2) gene SLC2A2 (rs8192675) variant on the glycaemic response to metformin in individuals recently diagnosed with type 2 diabetes.	Metformin	175-184	solute carrier family 2 member 2	Homo sapiens	119-125
30413829-8	2019	CONCLUSIONS/INTERPRETATION: The variant rs8192675 in the SLC2A2 gene (C allele) is associated with an improved glucose response to metformin monotherapy during the first year after diagnosis in type 2 diabetes.	Metformin	131-140	solute carrier family 2 member 2	Homo sapiens	57-63
30840303-0	2019	Metformin inhibits proliferation and migration of endometrial cancer cells through regulating PI3K/AKT/MDM2 pathway.	Metformin	0-9	MDM2 proto-oncogene	Homo sapiens	103-107
30840303-10	2019	Western blotting results manifested that the activation of PI3K/AKT/MDM2 signaling pathway was inhibited by metformin (p&lt;0.05).	Metformin	108-117	MDM2 proto-oncogene	Homo sapiens	68-72
30840303-11	2019	CONCLUSIONS: Metformin can inhibit the proliferation and migration of EC cells by inhibiting the activation of PI3K/AKT/MDM2 signaling pathway.	Metformin	13-22	MDM2 proto-oncogene	Homo sapiens	120-124
30680029-0	2019	Metformin protects against sevoflurane-induced neuronal apoptosis through the S1P1 and ERK signaling pathways.	Metformin	0-9	sphingosine-1-phosphate receptor 1	Homo sapiens	78-82
30680029-5	2019	The mechanism of the effect of metformin on sevoflurane-induced neuronal apoptosis was investigated using a sphingosine 1-phosphate receptor 1 (S1P1) antagonist (VPC23019) and mitogen-activated protein kinase kinase inhibitor (U0126).	Metformin	31-40	sphingosine-1-phosphate receptor 1	Homo sapiens	144-148
30680029-7	2019	VPC23019 and U0126 eliminated the neuroprotective effects of metformin on neuronal apoptosis, which suggests that metformin is able to protect against sevoflurane-induced neurotoxicity via activation of the S1P1-dependent ERK1/2 signaling pathway.	Metformin	61-70	sphingosine-1-phosphate receptor 1	Homo sapiens	207-211
30680029-7	2019	VPC23019 and U0126 eliminated the neuroprotective effects of metformin on neuronal apoptosis, which suggests that metformin is able to protect against sevoflurane-induced neurotoxicity via activation of the S1P1-dependent ERK1/2 signaling pathway.	Metformin	114-123	sphingosine-1-phosphate receptor 1	Homo sapiens	207-211
30451370-7	2019	However, metformin enhanced the expression of autophagy markers, while it abrogated the abundance of p62 and ubiquitinated proteins.	Metformin	9-18	nucleoporin 62	Homo sapiens	101-104
31336483-0	2019	Serum chemerin levels in Polycystic Ovary Syndrome after metformin therapy.	Metformin	57-66	retinoic acid receptor responder 2	Homo sapiens	6-14
31336483-1	2019	OBJECTIVES: The aim of this study was to study the effects of metformin therapy on serum chemerin levels in some phenotypes of polycystic ovarian syndrome cases, and to correlate chemerin levels with insulin resistance parameters and with hormonal profile.	Metformin	62-71	retinoic acid receptor responder 2	Homo sapiens	89-97
31336483-6	2019	RESULTS: Before metformin therapy, the serum chemerin were significantly increased in PCOS cases as compared with the control cases.	Metformin	16-25	retinoic acid receptor responder 2	Homo sapiens	45-53
31336483-9	2019	After three months of metformin therapy, the serum chemerin, insulin, and HOMA-IR concentrations were significantly decreased in polycystic ovarian syndrome cases as compared with the levels before therapy.	Metformin	22-31	retinoic acid receptor responder 2	Homo sapiens	51-59
31336483-11	2019	Metformin therapy resulted in a significant decrease in chemerin levels in polycystic ovarian syndrome cases.	Metformin	0-9	retinoic acid receptor responder 2	Homo sapiens	56-64
30745848-0	2019	Activation of AMPK by metformin promotes renal cancer cell proliferation under glucose deprivation through its interaction with PKM2.	Metformin	22-31	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	14-18
30745848-3	2019	In this study, we found that metformin treatment in RCC cells lead to activation of AMPK, which suppressed the cell proliferation under normal condition, but enhanced cell proliferation under glucose deprivation (GD) condition.	Metformin	29-38	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	84-88
30909226-11	2019	Further, metformin-treated mice showed increased tau phosphorylation and reduced numbers of NeuN-and PSD95-positive cells.	Metformin	9-18	discs large MAGUK scaffold protein 4	Mus musculus	101-106
30433870-1	2018	Background This work aimed to evaluate the influence of single nucleotide polymorphisms (SNPs) in the SLC47A1 (922-158G&gt;A; rs2289669) and SLC47A2 (-130G&gt;A; rs12943590) genes on the relative change in HbA1c in type 2 diabetes mellitus (T2DM) patients of South India who are taking metformin as monotherapy.	Metformin	286-295	solute carrier family 47 member 1	Homo sapiens	102-109
30025915-12	2018	The apoptosis induced by metformin was accompanied by increased caspase-3 activity.	Metformin	25-34	caspase 3	Mus musculus	64-73
30025915-13	2018	Meanwhile, metformin down-regulated the anti-apoptotic protein B cell lymphoma 2 (Bcl-2) but up-regulated the pro-apoptotic protein Bcl2-associated X (BAX), which suggests the involvement of the mitochondrial-mediated apoptosis pathway.	Metformin	11-20	BCL2-associated X protein	Mus musculus	132-149
30025915-13	2018	Meanwhile, metformin down-regulated the anti-apoptotic protein B cell lymphoma 2 (Bcl-2) but up-regulated the pro-apoptotic protein Bcl2-associated X (BAX), which suggests the involvement of the mitochondrial-mediated apoptosis pathway.	Metformin	11-20	BCL2-associated X protein	Mus musculus	151-154
30025915-14	2018	Furthermore, metformin promoted AMP-activated protein kinase (AMPK) phosphorylation but inhibited insulin-like growth factor-1 receptor (IGF-1R) expression, protein kinase B (PKB/AKT) phosphorylation and mammalian target of rapamycin (mTOR) phosphorylation.	Metformin	13-22	insulin like growth factor 1 receptor	Homo sapiens	98-135
30025915-14	2018	Furthermore, metformin promoted AMP-activated protein kinase (AMPK) phosphorylation but inhibited insulin-like growth factor-1 receptor (IGF-1R) expression, protein kinase B (PKB/AKT) phosphorylation and mammalian target of rapamycin (mTOR) phosphorylation.	Metformin	13-22	insulin like growth factor 1 receptor	Homo sapiens	137-143
30292140-8	2018	Furthermore, as a direct allosteric AMPK activator, metformin was shown to activate AMPK and significantly reduce C/EBP beta and miR-1a-3p levels compared with those in the control group.	Metformin	52-61	CCAAT/enhancer binding protein beta	Rattus norvegicus	114-124
30292140-9	2018	In conclusion, metformin protects cardiomyocytes against H2O2 damage through the AMPK/C/EBP beta/miR-1a-3p/GRP94 pathway, which indicates that metformin may be applied for the treatment of I/R injury.	Metformin	15-24	CCAAT/enhancer binding protein beta	Rattus norvegicus	86-96
30292140-9	2018	In conclusion, metformin protects cardiomyocytes against H2O2 damage through the AMPK/C/EBP beta/miR-1a-3p/GRP94 pathway, which indicates that metformin may be applied for the treatment of I/R injury.	Metformin	143-152	CCAAT/enhancer binding protein beta	Rattus norvegicus	86-96
30372835-8	2018	CD133+ and VEGFR-2+ cells were detected in blood samples of non-diabetic control, diabetic subjects and diabetics received Metformin.	Metformin	123-132	kinase insert domain receptor	Homo sapiens	11-18
30372835-11	2018	Metformin decreased the angiogenic potential of cells by decreasing VEGFR-2 and Tie-2 expression (p &lt; 0.05).	Metformin	0-9	kinase insert domain receptor	Homo sapiens	68-75
30088260-9	2018	In metastatic MDA-MB-231 cells, migration was found to be suppressed by metformin through deregulation of the matrix metalloproteinases MMP-2 and MMP-9.	Metformin	72-81	matrix metallopeptidase 9	Homo sapiens	146-151
30088260-10	2018	The oncogenic microRNAs miR-21 and miR-155 were found to be downregulated by metformin, which may be correlated with the suppression of cell proliferation and/or migration.	Metformin	77-86	microRNA 155	Homo sapiens	35-42
30088260-14	2018	Finally, we found that metformin may modulate the pro-apoptotic Bax, anti-apoptotic Bcl-2, MMP-2, MMP-9, miR-21 and miR-155 expression levels.	Metformin	23-32	matrix metallopeptidase 9	Homo sapiens	98-103
30088260-14	2018	Finally, we found that metformin may modulate the pro-apoptotic Bax, anti-apoptotic Bcl-2, MMP-2, MMP-9, miR-21 and miR-155 expression levels.	Metformin	23-32	microRNA 155	Homo sapiens	116-123
30343407-9	2018	In skeletal muscle, resveratrol, strength training, cold and Metformin significantly increased the plin5 expression at the gene and protein level (p &lt; 0.05).	Metformin	61-70	perilipin 5	Mus musculus	99-104
29962100-3	2018	We aimed to exploit 8CPT-cAMP, 8CPT-2-Methyl-O-cAMP and NBMPR, which is highly selective for a high-affinity binding-site on ENT1, to investigate the role of ENT1 in the liver-specific glucose-lowering properties of AICAR and metformin.	Metformin	226-235	solute carrier family 29 (nucleoside transporters), member 1	Mus musculus	125-129
30242842-6	2018	Using AhR reporter cells, Huh7-DRE-Luc cells, a human mast cell line, HMC-1, and BMMCs, metformin"s inhibitory effect was mediated through the suppression of FICZ-induced AhR activity, calcium mobilization and ROS generation.	Metformin	88-97	MIR7-3 host gene	Homo sapiens	26-30
30129983-5	2018	Preincubation at high glucose concentration followed by moderate-glucose incubation activated the AMPK pathway, but the activation was abolished with berberine or metformin treatment.	Metformin	163-172	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	98-102
30129983-6	2018	In contrast, alteration from normal glucose to moderate glucose concentration in the medium suppressed AMPK activity, which was activated by berberine or metformin.	Metformin	154-163	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	103-107
30129983-8	2018	In conclusion, AMPK activated by glucose reduction is inhibited by berberine or metformin.	Metformin	80-89	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	15-19
30129983-10	2018	The potent glucose-lowering effects with minimal hypoglycemia of berberine and metformin may be partially due to their bidirectional regulation of the AMPK signaling pathway.	Metformin	79-88	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	151-155
30559718-10	2018	Identification of SIRT1 activators for diabetes has gained wide attention, such as metformin, resveratrol, and resveratrol derivatives.	Metformin	83-92	sirtuin 1	Homo sapiens	18-23
30446679-0	2018	OCT3 promoter haplotype is associated with metformin pharmacokinetics in Koreans.	Metformin	43-52	OCTN3	Homo sapiens	0-4
30446679-1	2018	Organic cation transporter 3 (OCT3) is expressed in various organs in humans and plays an important role in the transport of organic cations and drugs including metformin.	Metformin	161-170	OCTN3	Homo sapiens	0-28
30446679-1	2018	Organic cation transporter 3 (OCT3) is expressed in various organs in humans and plays an important role in the transport of organic cations and drugs including metformin.	Metformin	161-170	OCTN3	Homo sapiens	30-34
30446679-3	2018	Next, the association between the functional haplotype of the OCT3 promoter and pharmacokinetics of metformin was evaluated.	Metformin	100-109	OCTN3	Homo sapiens	62-66
30446679-8	2018	Our study suggests that an OCT3 promoter haplotype affects the pharmacokinetics of metformin in Koreans as well as the OCT3 transcription rate.	Metformin	83-92	OCTN3	Homo sapiens	27-31
30459620-0	2018	Metformin Modulates High Glucose-Incubated Human Umbilical Vein Endothelial Cells Proliferation and Apoptosis Through AMPK/CREB/BDNF Pathway.	Metformin	0-9	cAMP responsive element binding protein 1	Homo sapiens	123-127
30459620-0	2018	Metformin Modulates High Glucose-Incubated Human Umbilical Vein Endothelial Cells Proliferation and Apoptosis Through AMPK/CREB/BDNF Pathway.	Metformin	0-9	brain derived neurotrophic factor	Homo sapiens	128-132
30459620-5	2018	In our study, we demonstrated that high glucose (HG) reduced cell proliferation and induced cell apoptosis via changes in BDNF expression and that metformin reversed the effects of HG injury by upregulating BDNF expression.	Metformin	147-156	brain derived neurotrophic factor	Homo sapiens	207-211
30459620-6	2018	Furthermore, we found that cyclic AMP response element binding (CREB) phosphorylation was reduced in HG-treated human umbilical vein endothelial cells (HUVECs), and this effect was reversed by the metformin treatment.	Metformin	197-206	cAMP responsive element binding protein 1	Homo sapiens	64-68
30459620-7	2018	However, the metformin effect on BDNF levels in HG-incubated HUVECs was blocked by a CREB inhibitor, which indicated that BDNF expression is regulated by metformin through CREB activation.	Metformin	13-22	brain derived neurotrophic factor	Homo sapiens	33-37
30459620-7	2018	However, the metformin effect on BDNF levels in HG-incubated HUVECs was blocked by a CREB inhibitor, which indicated that BDNF expression is regulated by metformin through CREB activation.	Metformin	13-22	cAMP responsive element binding protein 1	Homo sapiens	85-89
30459620-7	2018	However, the metformin effect on BDNF levels in HG-incubated HUVECs was blocked by a CREB inhibitor, which indicated that BDNF expression is regulated by metformin through CREB activation.	Metformin	13-22	brain derived neurotrophic factor	Homo sapiens	122-126
30459620-7	2018	However, the metformin effect on BDNF levels in HG-incubated HUVECs was blocked by a CREB inhibitor, which indicated that BDNF expression is regulated by metformin through CREB activation.	Metformin	13-22	cAMP responsive element binding protein 1	Homo sapiens	172-176
30459620-7	2018	However, the metformin effect on BDNF levels in HG-incubated HUVECs was blocked by a CREB inhibitor, which indicated that BDNF expression is regulated by metformin through CREB activation.	Metformin	154-163	brain derived neurotrophic factor	Homo sapiens	33-37
30459620-7	2018	However, the metformin effect on BDNF levels in HG-incubated HUVECs was blocked by a CREB inhibitor, which indicated that BDNF expression is regulated by metformin through CREB activation.	Metformin	154-163	cAMP responsive element binding protein 1	Homo sapiens	85-89
30459716-0	2018	Metformin Is a Direct SIRT1-Activating Compound: Computational Modeling and Experimental Validation.	Metformin	0-9	sirtuin 1	Homo sapiens	22-27
30459716-1	2018	Metformin has been proposed to operate as an agonist of SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that mimics most of the metabolic responses to calorie restriction.	Metformin	0-9	sirtuin 1	Homo sapiens	56-61
30459716-2	2018	Herein, we present an in silico analysis focusing on the molecular docking and dynamic simulation of the putative interactions between metformin and SIRT1.	Metformin	135-144	sirtuin 1	Homo sapiens	149-154
30459716-3	2018	Using eight different crystal structures of human SIRT1 protein, our computational approach was able to delineate the putative binding modes of metformin to several pockets inside and outside the central deacetylase catalytic domain.	Metformin	144-153	sirtuin 1	Homo sapiens	50-55
30459716-4	2018	First, metformin was predicted to interact with the very same allosteric site occupied by resveratrol and other sirtuin-activating compounds (STATCs) at the amino-terminal activation domain of SIRT1.	Metformin	7-16	sirtuin 1	Homo sapiens	193-198
30459716-6	2018	Third, metformin was predicted to interact with the C-terminal regulatory segment of SIRT1 bound to the NAD+ hydrolysis product ADP-ribose, a "C-pocket"-related mechanism that appears to be essential for mechanism-based activation of SIRT1.	Metformin	7-16	sirtuin 1	Homo sapiens	85-90
30459716-6	2018	Third, metformin was predicted to interact with the C-terminal regulatory segment of SIRT1 bound to the NAD+ hydrolysis product ADP-ribose, a "C-pocket"-related mechanism that appears to be essential for mechanism-based activation of SIRT1.	Metformin	7-16	sirtuin 1	Homo sapiens	234-239
30459716-7	2018	Enzymatic assays confirmed that the net biochemical effect of metformin and other biguanides such as a phenformin was to improve the catalytic efficiency of SIRT1 operating in conditions of low NAD+ in vitro.	Metformin	62-71	sirtuin 1	Homo sapiens	157-162
30459716-8	2018	Forthcoming studies should confirm the mechanistic relevance of our computational insights into how the putative binding modes of metformin to SIRT1 could explain its ability to operate as a direct SIRT1-activating compound.	Metformin	130-139	sirtuin 1	Homo sapiens	143-148
30459716-8	2018	Forthcoming studies should confirm the mechanistic relevance of our computational insights into how the putative binding modes of metformin to SIRT1 could explain its ability to operate as a direct SIRT1-activating compound.	Metformin	130-139	sirtuin 1	Homo sapiens	198-203
30459716-9	2018	These findings might have important implications for understanding how metformin might confer health benefits via maintenance of SIRT1 activity during the aging process when NAD+ levels decline.	Metformin	71-80	sirtuin 1	Homo sapiens	129-134
29908010-8	2018	Importantly, rapamycin and metformin significantly ameliorated IR, relieved disorders of glucose and lipid metabolism, reduced inflammatory level, inhibited mTOR, and promoted autophagy.	Metformin	27-36	mechanistic target of rapamycin kinase	Rattus norvegicus	157-161
30037605-7	2018	Recent evidence has substantiated this hypothesis, with metformin significantly reducing the mRNA and protein levels of both SRSF1 and progerin, activating AMPK, and alleviating pathological defects in HGPS cells.	Metformin	56-65	serine and arginine rich splicing factor 1	Homo sapiens	125-130
30053447-6	2018	Specifically, metformin showed an anti-pancreatic stellate cells (PSCs) effect via decreasing the expression of sonic hedgehog (SHH) and then sparked some downstream effects, for example, inhibiting the production of vascular endothelial growth factor (VEGF) in the tumor microenvironment, reducing the formation of tumor neovascularization, attenuating the desmoplastic reaction and enhancing the antitumor effect of gemcitabine.	Metformin	14-23	vascular endothelial growth factor A	Mus musculus	217-251
30053447-6	2018	Specifically, metformin showed an anti-pancreatic stellate cells (PSCs) effect via decreasing the expression of sonic hedgehog (SHH) and then sparked some downstream effects, for example, inhibiting the production of vascular endothelial growth factor (VEGF) in the tumor microenvironment, reducing the formation of tumor neovascularization, attenuating the desmoplastic reaction and enhancing the antitumor effect of gemcitabine.	Metformin	14-23	vascular endothelial growth factor A	Mus musculus	253-257
29969038-5	2018	We found that metformin improved the expression of intestinal tight junction proteins (ZO1, occludin, and Claudin1) that were reduced by LPS stimulation.	Metformin	14-23	claudin 1	Homo sapiens	106-114
29859833-8	2018	Finally, treatment with metformin suppressed LPS-induced p70S6K1 phosphorylation, which was abolished by the AMPK inhibitor.	Metformin	24-33	ribosomal protein S6 kinase, polypeptide 1	Mus musculus	57-64
30108499-0	2018	Commentary: Metformin reverses TRAP1 mutation-associated alterations in mitochondrial function in Parkinson"s disease.	Metformin	12-21	TNF receptor associated protein 1	Homo sapiens	31-36
29853564-5	2018	APPROACH AND RESULTS: Metformin-treated mouse or human primary hepatocytes showed increased expression of Abcg5/8 and the bile salt export pump, Bsep.	Metformin	22-31	ATP binding cassette subfamily B member 11	Homo sapiens	145-149
29659176-9	2018	A specific AMPK activator metformin increased Wnt3a, beta-catenin, Nrf2 phosphorylation and activation but reduced the levels of IL-6 and IL-8 in NHBE cells and mouse lungs exposed to CSE.	Metformin	26-35	catenin (cadherin associated protein), beta 1	Mus musculus	53-65
29550639-8	2018	In conclusion, short-term exposure to metformin reduces cellular glucose uptake, probably by direct inhibition of GLUT1.	Metformin	38-47	solute carrier family 2 member 1	Homo sapiens	114-119
29480578-4	2018	HCT inhibited human OCT2 and human MATE1-mediated metformin transports in vitro.	Metformin	50-59	solute carrier family 47 member 1	Homo sapiens	35-40
29480578-6	2018	In 28MH rats, rat Oct1-mediated metformin uptake into the liver was enhanced, leading to an improved glucose-lowering effect without hypoglycaemia compared with 28M rats.	Metformin	32-41	solute carrier family 22 member 1	Rattus norvegicus	18-22
29795113-8	2018	Our results, for the first time, presents evidence that the miR-570-3p-mediated suppression of LCMR1 and ATG12 is involved in the metformin-induced inhibition of metastasis in osteosarcoma cells.	Metformin	130-139	mediator complex subunit 19	Homo sapiens	95-100
28230250-0	2018	Metformin attenuates angiotensin II-induced TGFbeta1 expression by targeting hepatocyte nuclear factor-4-alpha.	Metformin	0-9	hepatic nuclear factor 4, alpha	Mus musculus	77-110
28230250-11	2018	Metformin inhibited the AngII-induced increases in HNF4alpha protein expression and binding to the Tgfb1 promoter in CFs.	Metformin	0-9	hepatic nuclear factor 4, alpha	Mus musculus	51-60
28230250-12	2018	In vivo, metformin blocked the AngII-induced increase in cardiac HNF4alpha protein levels in wild-type mice but not in AMPKalpha2-/- mice.	Metformin	9-18	hepatic nuclear factor 4, alpha	Mus musculus	65-74
28230250-15	2018	Metformin inhibits AngII-induced HNF4alpha expression via AMPK activation, thus decreasing TGFbeta1 transcription and cardiac fibrosis.	Metformin	0-9	hepatic nuclear factor 4, alpha	Mus musculus	33-42
29499335-0	2018	Metformin treatment prevents SREBP2-mediated cholesterol uptake and improves lipid homeostasis during oxidative stress-induced atherosclerosis.	Metformin	0-9	sterol regulatory element binding factor 2	Mus musculus	29-35
31938219-5	2018	Metformin prevented high glucose or hyperglycemia-induced MVED by inhibition of HIF-1alpha/PFN1 signaling in cultured HRMECs and in SD rats with DR.	Metformin	0-9	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	80-90
31938219-6	2018	CONCLUSION: Our results indicate that activation of HIF-1alpha/PFN1 by high glucose mediates permeability, apoptosis, and angiogenesis and that metformin alleviates MVED by suppressing HIF-1alpha/PFN1 signaling during DR.	Metformin	144-153	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	185-195
29286156-0	2018	Metformin-induced activation of AMPK inhibits the proliferation and migration of human aortic smooth muscle cells through upregulation of p53 and IFI16.	Metformin	0-9	interferon gamma inducible protein 16	Homo sapiens	146-151
29286156-8	2018	In addition, metformin was able to activate p53, IFI16 and AMPK, in order to inhibit proliferation and migration of HASMCs.	Metformin	13-22	interferon gamma inducible protein 16	Homo sapiens	49-54
29286156-9	2018	Furthermore, siRNA-mediated knockdown of p53 and IFI16 attenuated AMPK activation and reversed the suppressive effects of metformin.	Metformin	122-131	interferon gamma inducible protein 16	Homo sapiens	49-54
29286156-11	2018	These results indicated that metformin-induced activation of AMPK suppresses the proliferation and migration of HASMCs by upregulating p53 and IFI16.	Metformin	29-38	interferon gamma inducible protein 16	Homo sapiens	143-148
28686850-0	2018	The effect of metformin treatment on endoplasmic reticulum (ER) stress induced by status epilepticus (SE) via the PERK-eIF2alpha-CHOP pathway.	Metformin	14-23	eukaryotic translation initiation factor 2A	Rattus norvegicus	119-128
28686850-4	2018	In this study, we analyzed the effect of metformin on ER stress via the pro-apoptotic protein kinase RNA-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2alpha (eIF2alpha)-C/EBP homologous protein (CHOP) pathway.	Metformin	41-50	eukaryotic translation initiation factor 2A	Rattus norvegicus	183-192
28686850-12	2018	eIF2alpha and PERK levels were decreased in metformin compared to SE group.	Metformin	44-53	eukaryotic translation initiation factor 2A	Rattus norvegicus	0-9
29467552-8	2018	Metformin decreased the activation of HSCs, reduced the deposition of ECM, and inhibited angiogenesis in CCl4-treated mice.	Metformin	0-9	chemokine (C-C motif) ligand 4	Mus musculus	105-109
29467552-10	2018	Metformin decreased the expression of vascular endothelial growth factor (VEGF) in HSCs through inhibition of hypoxia inducible factor (HIF)-1alpha in both PDGF-BB treatment and hypoxic conditions, and it down-regulated VEGF secretion by HSCs and inhibited HSC-based angiogenesis in hypoxic conditions in vitro.	Metformin	0-9	vascular endothelial growth factor A	Mus musculus	38-72
29467552-10	2018	Metformin decreased the expression of vascular endothelial growth factor (VEGF) in HSCs through inhibition of hypoxia inducible factor (HIF)-1alpha in both PDGF-BB treatment and hypoxic conditions, and it down-regulated VEGF secretion by HSCs and inhibited HSC-based angiogenesis in hypoxic conditions in vitro.	Metformin	0-9	vascular endothelial growth factor A	Mus musculus	74-78
29467552-10	2018	Metformin decreased the expression of vascular endothelial growth factor (VEGF) in HSCs through inhibition of hypoxia inducible factor (HIF)-1alpha in both PDGF-BB treatment and hypoxic conditions, and it down-regulated VEGF secretion by HSCs and inhibited HSC-based angiogenesis in hypoxic conditions in vitro.	Metformin	0-9	vascular endothelial growth factor A	Mus musculus	220-224